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Qatar Foundation Annual Research Forum Volume 2012 Issue 1
- Conference date: 21-23 Oct 2012
- Location: Qatar National Convention Center (QNCC), Doha, Qatar
- Volume number: 2012
- Published: 01 October 2012
201 - 300 of 469 results
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Gene regulatory network inference using information theoretic methods
Authors: Amina Noor, Erchin Serpedin, Hazem Nounou, Mohamed Nounou, Marwa Qaraqe, Lotfi Chouchane and Nady MohamedBackground & Objectives: Gene regulatory network inference is a problem of prime importance in the budding field of systems biology and bioinformatics. The process which uses the information present in the genes to produce functional gene products is termed gene expression, and it can be measured using the microarray technology. The scope of this work is to propose a series of information theoretic algorithms which utilize the gene expression data to reverse engineer gene regulatory networks. Methods: Using information theoretic tools, this work proposes several algorithms to indicate how the genes are interacting with each other in a biological system. One of the advantages associated with these information theoretic algorithms is that they work with minimum assumptions. The concept of mutual information is a fundamental quantity in information theory that is used extensively in this work to measure the degree of dependency between genes. There are situations when two genes are interacting but only via an intermediate gene. By employing data processing inequality and condition mutual information, this work shows the possibility to identify such indirect interactions. Results: The computer simulations illustrate that the proposed information theoretic methods provide some of the most robust algorithms for inferring the topology of gene regulatory networks. While estimating the genetic interactions, it is necessary to put a constraint on the complexity of the network so as to avoid over-fitting the network. To this end, minimum description length principle and Bayesian information criterion are used for model selection. Results performed on both synthetic and realistic gene regulatory networks attest the superior performance of the proposed algorithms. Conclusions: This work describes different information theoretic approaches for determining the possible interactions between genes using gene expression data. The performance metrics used to assess these algorithms are also discussed. It is concluded that information theoretic methods represent powerful tools for inference of gene regulatory networks.
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Molecular epidemiology of human papillomavirus among Arab women in Qatar
Authors: Asha Elmi, Devendra Bansal, Asma Al-Thani, Afaf Al-Ansari, Nady Mohamed and Ali SultanObjectives: Human papillomavirus (HPV) is the most commonly known sexually transmitted agent. To date, few reports are available on the distribution of most prevalent and variant types of HPV in Arab women. Therefore, the aim of this study is to determine the age-specific distribution of HPV types among Arab women being subjected to routine pap smear tests in the State of Qatar. Methods: 1100 pap smears have been collected in ThinPrep vials (BD SurePath™) from Arab women seeking routine gynecological care at the Women's Hospital, Hamad Medical Corporation (HMC) in Doha, Qatar. All the samples were transported to the laboratory in an icebox container. Viral DNA from ThinPrep samples was extracted by QIAamp MinElute virus spin kit according to manufacturer's instructions and was screened for HPV DNA by real-time PCR using L1 HPV specific (GP5+/6+) primers. The type-specific distribution of the viruses was determined by HPV high and low risk typing RT-PCR kits (Sacace Biotechnology, Italy) and PCR-based sequencing. Real-time PCR amplification was carried out in ABI 7500 real-time PCR (Applied Biosystems). Results: Based on the collected data, HPV DNA was detected in 125 women (11.36%), and 15 different HPV genotypes were detected, comprising high-risk and low-risk genotypes. The prevalence of HPV infection was seen in 54.5% Qatari and 45.5% non-Qatari women. With regard to age, 33.5% of all HPVs were found in women 30-39 years of age, 24.8% in women 40-49 years of age, 15.8% in women 50-59 years of age, 5.5% in women over 60 years and 20.4% in women less than 30 years old. Implications and Impact: The study shows that the prevalence of HPV infection in Arab women in Qatar is among the highest in the Arab world compared with previous reports. However, more extensive population-based studies should be undertaken before implementing HPV vaccination.
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Non-acute responses of hematological and molecular markers to intermittent hypoxic exposure and physical exercise in hot environment
Background & Objectives: Both exercise and hypoxia acutely elicit changes in systemic growth factors and cytokines that mediate increases in erythropoiesis, angiogenesis and, perhaps, arteriogenesis. To what extent the down-stream responses to these interventions are inter-related is, as yet, unclear. A role for circulating micro RNAs (cmiRNAs) in the regulation of these processes is a novel prospect. Thus the aims of this study are to investigate the effect of hypoxia and exercise training on relevant growth factors and cmiRNAs in a healthy human cohort. Methods: 18 healthy, Caucasian, male, elite athletes participated in this study. The project was designed as a parallel, two-groups, matched, randomized, longitudinal (pre-, mid-, post-test), two week intervention. One group was exposed to hypoxia (15 hours/day) the other stayed in a normoxic environment. Both groups performed physical exercise in a 10°C hotter environment than usual. The exercise was standardized for both groups and the daily work load was monitored. Blood was sampled under fasting conditions in the morning, to avoid any effects of acute exercise. Hemoglobin (Hb), reticulocytes, erythropoietin, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), cmiRNAs 144, 146a, 221, 222 were tested in blood and sera. Results: In the normoxic group decreases from pre- to mid- and post-test were found for Hb (p=0.011, p=0.002) and IL-6 (p=0.028, p=0.008). However, in the hypoxic group several changes were apparent. In this group Hb changed at the pre- to mid-test (p=0.013), reticulocytes also increased from pre- to mid-test (p=0.066), erythropoietin increased from pre- to mid- and post-test (p=0.008, p=0.008). VEGF also showed a tendency to increase from pre- to mid-test (p=0.085) and increased from pre- to post-test (p=0.011). The 2-ΔΔCT values for cmiRNAs 221 and 222 showed an increasing trend at the post-test time point but did not reach statistical significance. Conclusions: Hypoxia stimulated several cytokines and growth factors mediating erythropoiesis and angiogenesis, which might have counteracted the plasma volume related decrease in Hb in the normoxic group. While there were changes in cmiRNAs (221 and 222) these were not statistically significant, perhaps due the small study cohort, which is currently being expanded to confirm these results.
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Fetal and perinatal determinants of neonatal mortality in the State of Qatar: A PEARL study analysis
Background and Objective: The State of Qatar has achieved maternal, neonatal and perinatal survival rates which are comparable to many high income countries, both from the West and East. Our study aims to analyze fetal and perinatal determinants of Qatar's neonatal mortality rate (NMR) during 2011. Methodology: A PEARL Study (Perinatal Neonatal Outcomes Research Study in the Arabian Gulf), a joint collaborative research project between Hamad Medical Corporation (HMC) Qatar and University of Gloucestershire United Kingdom, is Qatar's prospective national perinatal epidemiological Study funded by Qatar National Research Fund. The study is quantifying maternal, neonatal and perinatal mortality, morbidities and their correlates by establishing a national neonatal perinatal registry for Qatar called Q-Peri-Reg. Data on live births and neonatal mortality were collected from all public and private maternity facilities in Qatar during 2011. Data on fetal and perinatal determinants was ascertained from maternal obstetric and delivery room record on predesigned performas. Univariate and multivariate regression analysis was done using Epi Info and SPSS-20. Results: Qatar's NMR during 2011 was 4.9. The incidence of low birth weight in Qatar is 11% and the incidence of preterm deliveries 10.7%. 10% of the babies required delivery room resuscitation. The relative risk of neonatal mortality was higher and statistically significant with fetal growth (p<0.001), fetal weight at birth (p<0.001), fetal gestation at birth (p<0.001), APGAR score at 1 and 5 minute (p<0.001) and the need for delivery room resuscitation (p<0.001). The RR of neonatal mortality increased (Table 1) with decreasing birth weight (p<0.001) and gestational age (p<0.001). Conclusion: Further improvement in Qatar's neonatal mortality is possible by addressing the high incidence of low birth weight and preterm deliveries. Better maternal nutrition, improved antenatal care, birth spacing and best obstetric and neonatal practices at delivery are likely to be most helpful.
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Evaluation of glycemic abnormalities in patients with Beta Thalassemia major using continous glucose monitoring system (CGMS) and oral glucose tolerance test (OGTT): A pilot study
Authors: Mohamed Abdeldaem Yassin, Ashraf Tawfiq Soliman and Ahmed Said AlawwaIntroduction: Both insulin deficiency and insulin resistance are reported in patients with β thalassemia major (BTM). The use of CGMS among the different methods for early detection of glycaemic abnormalities has not been studied thorough. The aims of this study are: 1. to detect glycemic abnormalities in young adults with BTM using fasting blood glucose (FBG), (OGTT), 72-h continuous glucose concentration by CGMS, and serum insulin and C-peptide concentrations; 2. To compare the results of these two methods in detecting glycemic abnormalities in these patients; and 3. To calculate (HOMA), and (QUICKI) in these patients. In order to evaluate whether glycemic abnormalities are due to insulin deficiency and/or resistance. Materials and methods: Randomly selected young adults (n = 14) with BTM . All patients were investigated using (OGTT) 75 gram of glucose and 72-h by CGMS. Fasting serum insulin and C-peptide concentrations were measured and HOMA-B, HOMA-IR were calculated accordingly. Results: Using OGTT, 5 patients had impaired fasting glucose (IFG) (Fasting BG from 5.6 to 6.9 mmol/L). Two of them had impaired glucose tolerance IGT (BG from 7.8 and < 11.1 mmol/L) and one had BG = 16.2 mmol/L after 2-hrs (diabetic). Using CGMS in addition to the glucose data measured by glucometer (3-5 times/ day), 6 patients had IFG. The maximum (postprandial) BG recorded exceeded 11.1 mmol/L in 4 patients (28.5%) (Diabetics) and was > 7.8 but < 11.1 mmol/L in 8 patients (57%) (IGT). The mean values of HOMA and QUICKI in patients with BTM were < 2.6 (1.6± 0.8) and > 0.33 (0.36±0.03) respectively ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B%) on the one hand and the fasting and the 2-h BG (r= -0.6, and - 0.48, P< 0.01 respectively) on the other hand. Ferritin concentrations were negatively correlated with the β-cell function (r= -0.41, P< 0.01). Conclusion: CGMS has proved to be superior to OGTT for the diagnosis of glycemic abnormalities in adult patients with BTM. In our patients, defective β-cell function rather than insulin resistance appeared to be the cause for these abnormalities.
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Ethnic and gender differences in skin auto-fluorescence
Background: The AGE reader is a non-invasive device that measures tissue accumulation of advanced glycation endproducts (AGEs) through skin auto-fluorescence (AF) and gives prediction of cardiovascular risk. For the risk prediction, the AGE reader uses a single reference curve, for both females and males, obtained from Caucasian subjects. Based on these reference curves, clinical cut-offs for a low, medium and high AF have been made. This study examines whether these reference values can be used for ethnic populations seen in Qatar. Furthermore, we assess whether gender and smoking affect skin AF in this particular population. Methods: Skin AF was measured in 200 Arabs, 99 South Asians and 35 Filipinos. Using multivariate linear regression analysis and adjusting for the covariates age and the presence of type 2 diabetes, we assessed whether ethnicity, smoking and gender were associated with skin AF. Results: The Arabs and the Filipinos had a significant higher skin AF then the South Asian population (0.272 (95% CI: 0.138, 0.406), p <0.001 and 0.354 (95% CI: 0.147- 0.561), p=0.001 respectively). This is equivalent to a horizontal shift of 14.6% and 19.0%, respectively. Also, skin AF was significantly higher in women compared to men (0.432 (95% CI: 0.307, 0.558), p <0.001). Smoking was positively associated with skin AF (0.21 (95% CI: -0.01, 0.41), p=0.056), with an increasing effect of number of pack-years smoked on AF (p=0.024). Conclusions: The results of this study suggest that the existing reference values should be expanded for ethnicity, gender and smoking. These results also indicate that the use of the AGE reader in clinical settings should be used with caution, since the clinical cut-off points are dependent on various factors such as ethnicity that still need to be studied in greater detail.
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Endothelial dysfunction in morbidily obese young Qataris
Background & objectives: The prevalence of metabolic syndrome (MetS), including obesity, dyslipidemia, hyperglycemia and hypertension, associated with an increased predisposition to cardiovascular disease (CVD), is especially high in the Middle East, primarily amongst young Qataris. Both insulin resistance and endothelial dysfunction have been proposed to contribute to the pathogenesis of CVD in obese patients. Recent reports have shown that abdominal adipose tissue depot-specific differences impact on endothelial vasomotor function, with the visceral/omental environment considered more pathogenic. It is, however, unclear how severe the effect would be on a relatively young obese population. This study investigated endothelium-dependent relaxation of small arteries embedded in two adipose tissue depots, the sub-cutaneous and the omental. Methods: Arteries were isolated from omental (OM) and subcutaneous (SC) adipose tissues collected from consented Qatari patients undergoing bariatric surgery for weight reduction. The arteries (ID ~251 µM for SC and ~ 262 µM for OM) were cut into segments (~2 mm) and mounted on a dual wire Myograph (510A) for measurement of isometric tension. Cumulative concentration-response curves were constructed for acetylcholine (1- 10000 nM, the classical endothelium-dependent relaxant) in the absence or presence of Nω-Nitro-L-arginine methyl ester (L-NAME,100 µM, nitric oxide synthase inhibitor) on initial tone generated with noradrenaline (5 µM). Relaxation to sodium nitroprusside (SNP) and prostaglandin E2 were also recorded. Results: The mean age of the patients was 32 years, their blood glucose 5.6 mmol/L, Insulin 19.3 µU/ml , the index of insulin sensitivity/resistance (HOMA) 5.5 and body mass index 43.4 Kg/m2. Relaxation to Ach was significantly attenuated in OM vessels (Emax 51±9 %) compared with SC vessels (Emax 79±6 %, p<0.05) from same patients. The Ach response was further reduced in the presence of L-NAME. In contrast, the relaxation to SNP and PGE2 were greater in OM vessels compared with the SC vessels. Conclusions: These results demonstrate adipose tissue depot-specific differences in the impact of obesity on endothelial function in morbidly obese, insulin resistant, young Qataris, with a marked reduction in endothelium NO-dependent relaxation in the OM compared with SC vessels. The reversibility of this lesion by weight loss are yet to be ascertained.
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Effect of social and environmental factors on the prevalence of autism in Qatar
More LessAutism spectrum disorders (ASD) are a group of neuro-developmental disabilities common in childhood characterized by impairments in social interaction, communication skills, and patterns of activities. Background: The symptoms of ASDs typically are present before age 3 years and often are accompanied by abnormalities in cognitive functioning, learning, attention, and sensory processing. A formal diagnosis is generally not made until the age of five. The vast majority of cases of autism are idiopathic, the best scientific evidence available to us today points toward a potential for various combinations of factors, namely multiple genetic components and certain environmental and socio-economic factors. Timing of exposure during the child's development (before, during or after birth) may also play a role in the development or final presentation of the disorder. Objectives: To estimate the effect of certain socio-economic and other risk factors on the prevalence of autism in Qatar. Methods: The target population for this study are children diagnosed with autism attending the Shafallah Center for children with special needs. Clinical evaluation is conducted by a developmental psychologist, and/or pediatrician, it includes a medical, developmental, and behavioral history; a standard physical and neurological examination, In addition, the Autism Diagnostic Interview (ADI-R), and Autism Diagnostic Observation Schedule-G (ADOS-G) will be administered. Results: Preliminary analysis of 171 subjects showed the highest prevalence among age group 7-14 years (61%). Male/female ratio was 82%/18%, which is around 5/1. Other factors like consanguinity, education, and family income found to have an effect on the prevalence of the disease in Qatar. Conclusions: Obtaining a reliable estimate is important in planning for providing the best health care and educational services needed to improve the overall outcome of autism in Qatar.
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Early detection of peripheral neuropathy by examining virtual perception of lower extremity join position
Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes that affects nerve functions and may occur in 25% of patients with 10 or more years of diabetes and up to 50% with 20 years of diabetes. Patients with DPN experience a high incidence of injuries while walking and have a low level of perceived safety. In certain cases the impaired judgment - mainly due to impaired proprioceptive feedback - can cause obstacle collision leading to falls and injuries. The subtle early findings that are indicative of postural instability are difficult to accurately assess from a clinical examination, and gait laboratory assessment is not currently available or practical. Thus, unfortunately, many patients that are "at risk for falls" are undiagnosed. Objectives: An innovative virtual obstacle crossing (VOC) paradigm using wearable sensors was developed in attempts to detect lower extremity nerve damage due to DPN. Methods: Sixty-eight participants including diabetes with no, moderate and severe neuropathy and aged-matched healthy controls were recruited. Severity of neuropathy was quantified using vibratory perception threshold (VPT) values. The ability of perception of lower extremity was quantified by measuring the rate of obstacle crossing success (OCS), reaction time (TR), and foot position while crossing a series of virtual obstacles with various heights. Results: Results suggest VOC test allows separating between groups. All proposed parameters were significantly deteriorated by increasing neuropath severity (p<0.05). Results also suggest a significant correlation between TR and VPT values (r=0.5, p<10-5). Finally, results suggest a significant deterioration in balance due to diabetes, irrespective of neuropath severity (p<0.05). Conclusions: The results proposed the benefit of virtual obstacle crossing as an objective method for detecting peripheral neuropathy at an early stage. This is based on the reasoning that lower extremity proprioception decreases with increasing nerve damage. The increased reaction time, decreased OCS, and increased sway of the DPN patients in this study suggests their decreased proprioception, and, therefore, increased peripheral nerve damage. Further studies should be addressed to compare VOC with other standard methods to confirm whether VOC can detect DPN earlier than current methods.
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Endothelial cells provide a niche for placental hematopoietic stem cell expansion
Authors: Christophe Raynaud and Arash RafiiUmbilical cord blood (UCB) is an attractive source of hematopoietic stem cells (HSCs). However, the number of HSCs in UBC remains limited and the attempts to amplify them in-vitro remain of poor efficiency. Several publications document amplification of HSC/progenitors with endothelial or mesenchymal cells, but the lack of homogeneity in culture conditions or HSC qualification impairs direct comparison of these results. Therefore, we compared the possible HSCs amplification using placental mesenchymal progenitors and Akt-activated umbilical vein endothelial cells. After HSCs isolation from UCB (defined as Lin-CD45-CD34+CD38-CD90+) on confluent feeder layer, the number of total cells and HSCs were monitored over 21 days. We demonstrate important cellular expansion on both niches. Most of the expanded cells were differentiated when characterized by flow cytometry. Only endothelial cells could trigger HSCs amplification with a pick at 14 days. Those amplified HSCs were able to differentiate in all cell lineages as attested by colony forming assays. Mesenchymal progenitors mainly triggered the amplification of CD38+ cells previously defined as precursors. A competitive assay demonstrated that HSCs had an in-vitro preference to interact with endothelial cells. Cytokines and transcriptomic analysis of our feeders indicate the mechanisms involved in HSC amplification and differentiation in both cases.
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Dietary composition and postprandial inflammation: Implications for human health
Authors: Amanda Brown, Ken Olson and Mohammad KhaledInflammation, in general, has been found to be associated with many human health complications. Postprandial inflammation, provoked soon after ingesting a meal, is transient in duration, but with dreadful consequences on human health over a period of time depending on the compositions of the meal. However, many populations, particularly in the Western countries, are in a constant postprandial state, which is likely to initiate insulin resistance (IR) resulting in type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Postprandial inflammation is dependent on the food quality and quantity, mostly in terms of its energy/calorie content and its nutritional value. Micronutrients, such as minerals and vitamins, constitute the nutritional value of a food, while macronutrients, such as carbohydrate, protein and fat/lipid, are basically the sources of its energy/calorie content. Since energy content varies significantly between carbohydrates (4 kcal/g) and fats (9 kcal/g), the objective is, therefore, to assess postprandial inflammation of an isocaloric, isonitrogenous high carbohydrate (66%) and low fat (20%) diet (HC) versus a high fat (56%) and low carbohydrate (30%) diet (HF), by measuring diet-induced postprandial thermogenesis (DIPT). Healthy, never-obese, postmenopausal, Caucasian female subjects (n=12) participated in this study for 3 weeks each in a crossover design. Fat-free mass (FFM) and fat mass (FM) were measured by under-water weighing before and after each diet. Resting metabolic rate (RMR) was assessed fasting and for five 40-minute periods over a 6 hours DIPT after ingesting 14.3 kg/FFM of either HC or HF diet. A low respiratory quotient (RQ), during the measurement of DIPT, is usually indicative of lipid peroxidation, an important index of inflammation. RQ after ingesting HC diet was significantly higher in this study, while it was significantly lower for HF diet, thus indicating a higher inflammatory response due to fat. A significant elevation of free fatty acid (FFA) was also observed after ingesting HF diet, which is well-known to be associated in the pathophysiology of T2DM, a significant risk factor for CVD. Further studies are necessary to understand the role of postprandial inflammation in human health.
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Congenital and genetic disorders in the Sultanate of Oman: Genetic service needs assessment
By Anna RajabBackground and Objectives: In the past 40 years Oman has witnessed remarkable social and economic growth, which is best reflected in the well-organized and efficient healthcare system. It has been anticipated that a change in disease pattern would be brought about by improvement in the quality of life, comprehensive healthcare facilities and successful control of communicable diseases. Although genetic and congenital disorders are increasingly observed in medical practice, there were no convincing available data to support these observations. The study was performed over the years 2010-2012 in order to assess the population needs for genetic services. Methods: A population-based study was conducted with detailed assessment and interviews of more than 3000 Omani mothers. Randomization was performed by counting the number of nationals in each geographical area and places of residence, and interviewing one mother per 600 Omani nationals in all geographic locations throughout the country. The collected data were verified with available hospital records and reports and analyzed. Results and Conclusions The population-based study revealed that 10% of Omani mothers reported congenital and genetic disorders causing morbidity in their offspring. Congenital disorders with mental disability accounted for over half of the reported morbidity, and a third of these reports had familiar recurrence. Morbidity and mortality from congenital and genetic causes that have been derived from this study reflect the situation in traditional Muslim community with high rate of inbreeding where communicable diseases were successfully controlled, and prevention measures are still in a preparatory phase. The current study confirmed that congenital and genetic conditions are the major contributors to childhood morbidity and mortality, and handicap prevalence in the Sultanate of Oman, indicating the need to prioritize future healthcare and planning, in view of their significant financial, social and research relevance.
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Cloning, overexpression and molecular characterization of human mast cell carboxypeptidase A
Authors: Sayed Kamel Goda, Aref Kyyaly, Asia Al-Jabiry, Andrew Walls and Muhammad Al SayrafiBackground: Mast cell proteases represent major protein components of secretory granules. The proteases are classified into a chymases, tryptases and carboxypeptidase (hMC-CPA). Little is known about the function of human lung carboxypeptidase A (hMC-CP) except for its ability to cleave angiotensin I. This suggests that the human mast cell carboxypeptidase A may play a role in the hypertension disease. Objectives: 1) Making human lung cDNA library and isolating the human lung carboxypeptidase A; 2) Cloning and expressing the full length PCR products into the overexpression vector pET28a and into pYES2; 3) Molecular characterization of the recombinant proteins. Methods: Human lung cDNA was prepared and PCR was carried out using DNA primers of the carboxypeptidase A (hMC-CPA).The isolated gene fragment was subcloned into the overexpression vector pET28a and transformed into E. coli DE3 for expression. The gene was also subcloned into the pYES2 vector for expression in yeast. The expression in E. coli has been validated by Western Blot analysis using four different antibodies. The purification was carried out using Ni²+ column chromatography. The recombinant protein was further characterized using MS and peptide amino acid sequencing. Results: We cloned and overexpressed the gene in E.coli using the His-tag vector pET28a. The protein expression in E. coli has been validated by Western blot analysis using four different carboxypeptidase A antibodies. The protein however, has been expressed in the form of inclusion bodies. Despite the fact that we could obtain soluble CPA at lower IPTG concentration and lower induction temperature we decide to subclone and express the gene in Saccharomyces cerevisiae. We successfully managed to subclone the gene in pYES2 vector and to produce a soluble form of the CPA in Saccharomyces cerevisiae. The hrMC-CPA expressed in Saccharomyces cerevisiae in frame with six His-tags. The protein therefore was purified by one step purification using Ni column. Conclusion: The cloning and overexpression of the CPA in soluble form will pave the way for molecular characterization studies of this enzyme and to shed more light on its biological function.
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Genome-wide association study of prostate cancer in Arab populations: Identification of three genomic regions with multiple consecutive prostate cancer susceptibility loci
Background: Prostate cancer is the most common malignancy in many industrialized countries and the second cause of cancer-related death in Europe and the United States. The incidence of the disease has been increasing in Arab populations. Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied. Genetic susceptibility to prostate cancer differs significantly across ethnicities. It would be of interest to identify the common alleles associated with prostate cancer risk in Arab population. Methods: With Affymetrix Genome-Wide Human SNP Array 6.0, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in a Tunisian cohort of 92 cases with prostate cancer and 131 age-matched controls. Then we extended the study to evaluate promising associations of 11 SNPs, identified by GWAS, in a cohort of individuals of Arab ancestry living in Qatar and Saudi Arabia (155 cases and 182 controls) using TaqMan® SNP Genotyping Assays. Results: We identified 3 consecutive regions significantly associated with prostate cancer risk on chromosome 9, 17 and 22, including 18 SNPs (P=8.52×10-5 to P=2.18×10-6) in the Tunisian population. Three previous reported common loci associated with prostate cancer at 17q21 containing STAT3 gene in the Caucasian population were confirmed. Two novel chromosomal regions associated with prostate cancer contain candidate susceptibility genes: SMARCA2, LOC646851and SUN2 were revealed. Conclusion: Our findings, identifying novel GWAS prostate cancer susceptibilty loci, indicate that prostate cancer genetic risk factors could be ethnic specific.
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Chest injury among young population in Qatar
Background: Traumatic chest injury (TCI) constitutes quarter of trauma-related deaths worldwide. Objective: To identify the pattern and outcome of TCI in Qatar in relation to age. Methods: Data were collected from all patients who sustained TCI between January 2008 and December 2010 in Qatar. Patients were classified and analyzed in 3 age groups (group 1 <18, group 2 between 18 and 45 and group 3 above 45 years). The multivariate regression analysis was performed for the predictors of mortality. Results: Of 5118 cases admitted to the section of trauma, 1355 (26.5%) had TCI (10%, 71% and 19% in group 1, 2 and 3 respectively). Children (<18 years) had more traffic-related injury, intubation (42%), high ISS (25%), head injury (44.3%), and liver injury (16%) in comparison to other groups. The overall mortality rate was 13% (28.5 %, 11.3% and 12% in group 1, 2 and 3 respectively). Traffic-related death was 13% while fall-related death was 7%. In comparison to survival, no survival was associated with higher rate of head injury (73% vs 33%), intubation (81% vs 19%) and high ISS (64% vs 14%), P=0.001. Independent predictors for mortality included age (OR 0.98; 95% CI: 0.97-0.99) ISS (OR 1.05; 95% CI: 1.03-1.07) and intubation (OR 9.5; 95% CI: 6.09-14.29). Conclusion: TCI is an alarming problem in Qatar with a high mortality. Young males are the most exposed population that deserves more emphasis on injury prevention. Regulatory efforts by the government at working sites and in the strict enforcement of traffic laws would likely reduce morbidity and mortality.
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Application of PCC and M-FISH assays to detect biomarkers-and stage specificity-of cancer of different origins and to improve cancer therapy regimens
Authors: Firouz Darroudi and Michael LongBackground: Cytogenetics of solid tumors in general is negatively affected by culturing artifacts such as preferential clonal expansion and introduction of chromosomal rearrangements, thus making it difficult to discriminate between primary changes and secondary events. Considering that chromosomal instability is a hallmark of cancer even at the precursor cancer level, it is of a great importance to devise a method of comprehensive chromosome analysis of cancer and cancer precursor cells that can bypass culturing problems as much as possible and that can provide informative karyograms of primary tumors at non-mitosis stages of the cell cycle. Consequently, we have developed a novel approach using chemically induced premature chromosome condensation (PCC) method and combined it with the technique of whole genome chromosome painting assay (M-FISH), in which chromosomal constitution of cancer cells could be detected independent of mitosis and without culture artifact within just three hours after receiving the biopsies. Objectives: 1. To perform karyotype analysis; 2. To define stage specificity; 3. To detect hall-mark(s) of cancer of different origins; 4. To improve therapy regimen by elucidating sensitivity of tumors and patients' lymphocytes to radiation and/or cytostatic drugs. Methods: Chemically-induced PCC method was applied on primary tumors (such as, cervical-, head and neck-, breast- and prostate-cancer) to generate metaphases. Afterwards, these preparations underwent M-FISH. Results: This unique/novel combined assay can give for the first time the possibility to assess genetic instability by detecting spontaneously occurring chromosomal instability (structural and numerical) in different types of primary tumors, as well as adjacent normal cells. It may open up the possibility to detect biomarker(s) for specific type of tumors, that can be used as screening tests. Furthermore, the sensitivity of specific types of tumors as well as patient's normal lymphocytes to cytostatic drugs and/or radiation can be determined. Conclusion: The unique combined state of the art assay we developed can lead to detect biomarker(s) for specific type of cancer. Moreover, for the first time therapy regimen can be individually designed based upon detecting tumors as well as patient's lymphocytes sensitivity.
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Cultural aspect of pedestrian injuries amongst expat workers in Qatar: An opportunity for an injury prevention program
Background: In the State of Qatar, the majority of workers are expatriates from different ethnicity and culture. Most of them are liable to pedestrian motor vehicle crashes (MVC). We sought to understand the anatomy, time and date of injuries amongst expat workers in relation to their country of origin, culture and traditions. Methods: Retrospective analysis of prospectively collected data obtained from trauma registry was done. Analysis includes all traffic related pedestrian injuries admitted to the trauma surgery service at Hamad General Hospital, the only level I trauma center in Qatar, between January 2009 and December 2011. Demographics, time and season of injuries, ISS, type of injuries, anatomical body parts injured, ethanol intake, hospital length of stay, length of ICU stay, and mortality were analyzed. Results: Of the 4997 injured patients admitted to the section of trauma, 603 (12.1%) were pedestrians [(non-Arab (75%), Arabs (17%) and nationals (8%)]. The mean age was 31.8±17 years with 93% males. The mean ISS was higher in those who were injured on Friday and Saturday (16±10 and 15±10; p=0.32) in comparison to the week days. Moreover, mean ISS was also relatively high in those who got injured during the winter season (15.2±11) compared to other months (13.5±10). Head injury (45%) was the most common injury followed by injury of the lower limbs (37%), upper limbs (24%), ribs (22%), pelvic area (20%), lung (17%), spleen (10%), liver (7%) and kidney (4%). Alcohol intake was highest amongst expatriate workers from Nepal and Sri Lanka. The median hospital length of stay was 7 (range 1-312) days, TICU stay was 4 (range 1-150) days and ventilator days was 2 (range 1-36) days. The overall mortality was 11.6 % (83% non-Arabs, 9% Arab non-Qataris and 8% Qataris; p=0.08). Conclusion: Majority of the pedestrian injuries involved expatriate workers with poor socio-economic status and cultural barrier in communication. Injury severity was higher in winter season particularly during weekends. These injuries pose economic burden to the healthcare system of the country and thus need urgent injury prevention measures such as education and awareness campaigns among expat workers in Qatar.
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Acute effects of blood transfusion on pituitary gonadal axis and sperm parameters in young males with sickle cell disease (SCD): A pilot study
Objective: To evaluate semen parameters and measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) concentrations before and 7 days after packed red cell transfusion (PCTx) in adults with sickle cell disease (SCD). Methods: This prospective study investigated 18 young adults with transfusion-dependent SCD, aged 20.7 +/- 2.88 years, with full pubertal development (Tanner's stage 5) (euogonadal), and capacity to ejaculate. Their serum ferritin levels were 1488 +/- 557ng/ml. Basal serum concentrations of FSH, LH, T and IGF-I were evaluated before and 7 days after packed red cell transfusion (PCTx). We studied the effect of PCTx on semen parameters and the endocrine functions in these 18 patients with SCD. Results: Following PCTx, a significant increase of Hb from 8.5 +/- 1.17 g/dl to 10.5 +/- 0.4 g/dl was associated with increased testosterone (12.3 +/- 1.24 nmol/L to 14.23 +/- 1.22nmol/L and gonadotropin concentrations. Total sperm count increased significantly from 87.4 +/- 24.6 million/ml to 146.2 +/- 51.25 million/ml total progressive sperm motility (TPM) from 40.8 +/- 11.1 million/ml to 93.4 +/- 38.3 million/ml, and rapid progressive sperm motility progressive motility (RPM) increased from 29.26 +/- 8.75 million/ml to 67.4 +/- 29 million/ml. After PCTx the total sperm count, TPM and RPM were significantly higher in the ETx group versus the TTx group. Before and after PCTx, testosterone concentrations were correlated significantly with sperm total count, volume, TPM and RPM (r= 0.53, 0.55, 0.42 and 0.38 respectively, p= 0.01). Before and after PCTx, hemoglobin concentrations were correlated significantly with sperm count, TPM, RPM and percentage of sperms with normal morphology (r= 0.60, 0.69, 0.66 and 0.86 respectively, p <0.001) Conclusion: Our study suggests that in males with SCD, blood transfusion associated with significant acute enhancement of sperm parameters and with an increased concentration of testosterone, LH and FSH. Improvements of sperm parameters were significantly higher in the exchange transfusion (ETx) group versus the top-up (TTx) group. These 'acute' effects on spermatogenesis are reached with an unknown mechanism(s) and suggest a number of pathways that need further human and/or experimental studies.
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Prognosis of neurogenic dysphagia by neuromuscular electric stimulation (NMSE) therapy versus NMSE coupled with conventional swallowing training in subacute cases in Qatar
Authors: Amal Idres Ahmad and Mohmad Sajed HusainTo study the effects of VitalStim therapy coupled with conventional swallowing training on recovery of neurogenic dysphagia, a total of 30 dysphagia patients were randomly selected among subacute post-traumatic brain injury and cerebrovascular accident cases. The cases were evenly divided into two groups: neuromuscular electric stimulation (NMSE) group, and NMSE plus conventional swallowing therapy group. Before and after the treatment, swallowing function was evaluated by using fiberoptic endoscopic evaluation of swallowing (FEES) test and swallowing ability function evaluation (SAFE). Outcomes were analyzed for changes in oral and pharyngeal phase dysphagia severity, diet consistency and improvement from non-oral to oral intake. There were significant differences in the SAFE score in each group before and after treatment. After 8-week treatment, the SAFE score was significantly greater in the NMSE therapy plus conventional swallowing training group than in the NMSE therapy group. It was concluded that VitalStim therapy coupled with conventional swallowing training was conducive to recovery of post-stroke dysphagia.
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Investigating poly (ADP-ribose) polymerase-1 (PARP-1) activation in obesity associated DNA damage and pro-inflammatory senescence
Authors: Houari Boumediene Abdesselem, Aisha Madani and Nayef MazloumObesity has increased at an alarming rate over the past three decades. It is likely to be caused by increased caloric intake combined with genetic predisposing factors and is a major risk factor for type 2 diabetes (T2D) and cardiovascular disorders. Obesity is linked to chronic inflammation, which was proposed as a cause for insulin resistance and T2D. However, the molecular mechanism of obesity driven T2D still lacks knowledge and thus is inaccessible to therapeutic intervention. In our research, we are exploring the molecular mechanism underpinning this association and aims to identify novel therapeutic targets for the rapidly growing population of obese individuals living with diabetes. The obese state creates a microenvironment within the adipose tissue that is susceptible to the accumulation of reactive oxygen species (ROS). Accumulated ROS causes oxidation of macromolecules such as DNA. Oxidative DNA damage encompasses a variety of DNA lesions such as DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) including non-telomeric and telomeric DSBs. Broken or dysfunctional telomeres have been hypothesized as a cause of cellular senescence, a state of irreversible cell cycle arrest observed in aging illnesses and even in obesity with accumulation of senescent adipocytes. A major player in detecting and defending against accumulation of oxidative DNA damage is PARP-1. PARP-1 activation has been shown to be associated to diabetes and obesity. We are exploring the role of PARP-1 in ROS-induced senescent and inflamed adipocytes by using a combination of biochemical, molecular and cell biological assays in primary human and mice adipocytes treated with hydrogen peroxide (H₂O₂) as a source of ROS.
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Public attitudes towards participation in Biobank Qatar
Authors: Eman Nasrella and Brian ClarkBackground and Objectives: Biobank Qatar is a research enabling infrastructure requiring members of the Qatari public to donate health and lifestyle information coupled to biological samples to enable research towards better prevention, diagnosis and treatment of diseases common in Qatar. Building a biobank depends on the willing participation of the public. Recruitment of participants requires insight into public knowledge of biobanking, public willingness and an understanding of motivators and the barriers. This study reports public opinion in Qatar and aids the communication campaign that facilitates recruitment. Methods: A qualitative survey was undertaken, by means of recorded structured interviews, with 100 members of the Qatari public including Qatari nationals and long-term expatriate residents (resident for more than 5 years). Results: Qatari nationals believe that Biobank Qatar raises Qatar's international profile. Volunteering is seen as a charitable act, compatible with Islam, to help future generations. Long term residents buy-in less to the benefits to Qatar. Qatari nationals assume confidentiality due to trust in their government. Long-term residents fear their information might be used against them (e.g. in the work place). Fear of infection through contaminated equipment was raised. There is lack of understanding on the process of donating blood. Questions arose over the biobank location, proximity to workplaces and how accessible it would be. Participants suggested commitments with families and employers as potential barriers. The public favor communication using a range of media. Participants particularly suggested raising awareness through gatherings and social events. Some participants volunteered to "spread the message" amongst social groups by acting as "biobank champions". Conclusions: Although limited by scale, scope and composition of the sample, this study provides a way-finder for public opinion related to biobanking for biomedical research. The public support Biobank Qatar, even with limited knowledge of our work. Qatari nationals were particularly supportive and are motivated by national pride, progress and making personal contributions to a healthier future for future generations. This study is useful in guiding our communications and recruitment plans and will be the basis for further sociological studies of the Qatari public and their support for biomedical research.
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STIM1 phosphorylation in Xenopus oocytes during meiosis
Authors: Maya Dib and Khaled MachacaStromal interaction molecule 1 (STIM1), the ER calcium sensor, couples to Orai1, the calcium channel, and mediates store-operated calcium entry (SOCE). STIM1 localizes to the ER membrane. Following Ca²+ store depletion, STIM1 forms puncta that localize to the cortical ER and binds Orai1 to allow Ca²+ influx. The egg's competency to activate at fertilization is dependent on its ability to generate a fertilization-specific Ca2+ transient. This is achieved through remodeling of its calcium signaling machinery during oocyte maturation. Oocyte maturation is driven by kinase cascade including MOS- mitogen-activated protein kinase (MAPK) - maturation promoting factor (MPF). Coordinately, SOCE inactivates during maturation. This inactivation is due to internalizing of Orai1 and the inability of STIM1 to form puncta. Here we show that MPF phosphorylates STIM1. Through molecular and pharmacological manipulation we are able to differentially activate the kinases along the kinase cascade that drives oocyte maturation. STIM1 phosphorylation in these studies was monitored through a mobility shift on SDS-PAGE. When MPF is activated a mobility shift is observed. However, this is not the case when only Mos or the MAPK cascade were active. Our next step is to determine the role of MPF phosphorylation of STIM1, because previous studies have argued that phosphorylation does not inhibit STIM1 clustering during meiosis. Our data argue that MPF is the primary kinase that phosphorylates STIM1 during meiosis.
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Photodynamic therapy for hair removal
Authors: Mohamed Ali, Amr Zaher, Carmen Ali and Khalid A. Al-SaadBackground: Unwanted hair is one of the most common medical problems affecting women of reproductive age inducing a lot of psychological stress and threatening their femininity and self-esteem. Old methods of removing unwanted hair include shaving, waxing, chemical epilation, and electrolysis, all of which have temporary results. However laser-assisted hair removal is the most efficient method of long-term hair removal currently available. It is desirable to develop a reduced-cost photodynamic therapy (PDT) system whose properties should include high efficiency and low side-effects. Objectives: The aim is to develop an adequate PDT system including helium-neon (He-Ne) laser and its effect on the photodynamic activity of methylene blue (Figs. 1 and 2) in biological experiments. Method: Mice skin tissues were used in this study and divided into the following six groups: controls (Fig.3), free methylene blue (MB) incubation, liposomal MB incubation, laser without MB, free MB for 3 and 4 hrs and laser, liposome MB for 3 hrs and laser. MB was applied to wax epilated areas. The areas were irradiated with CW He-Ne laser system that emits orange-red light with wavelength 632.8 nm and 10 mW at energy density of 5 J/cm2 for 10 minutes. The UV-visible spectrum was collected by Cary spectrophotometer. Results: MB is selectively absorbed by actively growing hair follicles due to its cationic property (Fig.4). MB untreated sections showed that hair follicles and sebaceous glands are intact and there is no change due to the laser exposure (Fig.5). Free MB sections incubated for 3 hrs showed that He:Ne laser induced destruction in hair follicles, leaving an intact epidermis (Fig. 6). Treated section with free MB for 4 hrs showed degeneration and necrosis in hair follicles, leaving an intact epidermis (Fig. 7). Liposomal MB sections incubated for 3 hrs showed He:Ne laser induced destruction in hair follicles with intradermal leukocytic infiltration (Fig. 8). Conclusion: Low power He:Ne laser and MB offers a successful PDT system in selectively damaging hair follicles, leaving an intact epidermis. The current PDT system provides better outcome than hair destruction through laser heat transfer procedures and laser-mediated hair removal, due to complete destruction of hair follicles.
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PCA3 molecular urine test: Development of an easy and cheap assay of a potential use in the diagnosis of prostate cancer.
Background: The use of the serum prostate-specific antigen (PSA) test for prostate cancer screening has resulted in a diagnostic dilemma: PSA is not prostate cancer specific and could be found in the normal prostate at equal or higher levels than is found in prostate cancer. Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA with a median 66-fold up-regulation compared to adjacent benign tissue. In contrast, PSA gene expression is similar in cancerous and benign cells; PSA mRNA levels may therefore be used to normalize for the amount of prostate-specific ribonucleic acid (RNA) in molecular test samples. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine. Methods: First-catch urine specimens were collected after digital rectal examination. The total RNA was isolated with Trizol, amplified, and quantified by use of a real-time PCR method. PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. PCA3 score is calculated by one thousand times of PCA3/PSA mRNA ratio. ROC curve analysis is applied to determine the cutoff value of PCA3 score according to prostate biopsy results. Results: We have collected urine samples of 163 patients from uro-oncology clinic at Hamad Hospital. Due to the mixture of the blood cells and prostate cells in the urine, we failed to obtain RNA with proper quality for 29 samples. The specimen informative rate (fraction of specimens yielding proper RNA for analysis) was 82.2%. From ROC curve with the known diagnostic data, the cut off of PCA3 score is 1232 with a sensitivity of 70% and specificity of 68%. Conclusion: The established PCA3 assay could increase specificity to the current prostate cancer diagnosis. Comparing to the commercial kit, it provides equivalently useful information and it is much cheaper and faster. The challenge is to avoid the interference from the blood cells in the urine.
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Determination of titanium and copper by ICP-MS in rat tissues after oral administration of nanoparticles
Authors: Mohamed A. Amr and Najat AljufairiIn this study, the high sensitive ICP-MS was employed to detect the contents of titanium and copper in liver, lung, spleen, kidney, heart, testis, brain and blood after administering an acute dose of different nano particle sizes of titanium and copper to rats by a syringe via gastrointestinal tract. In coupling with pathological examinations, the target organs of nano- and micro-copper were successfully determined. Biodistribution experiment showed that TiO2 mainly retained in the liver, spleen, kidneys, and lung tissues, which indicated that TiO2 particles could be transported to other tissues and organs after uptake by gastrointestinal tract. Moreover, the target organs of copper nano particles of different sizes after administrating a dose of 100 mg/kg were kidney, liver and blood. Liver is the main damaged organ.
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An innovative thermometric "Stress Test" for early diagnosis of acute charcot
Background & Objectives: Charcot neuroarthropathy (CN) is a devastating complication of diabetes. It has two-fold higher rate of major amputation compared to those without CN. Unfortunately, to date, there is no pathological marker or diagnostic criterion for it and diagnosis relies on pattern recognition and clinical intuition. Not surprisingly, the diagnosis can be missed up to 95% of the time and the average diagnostic delay has been estimated at almost 7 months. Recent studies reported asymmetric plantar temperature differences secondary to inflammation as a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. Methods: Fifteen individuals with acute CN and 17 age-matched non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The plantar temperature (PT) response as a function of number of steps was examined using a validated wearable sensor technology. A custom image processing toolbox was designed to characterize the plantar temperature response to activity. Results: During initial activity, the PT was reduced in all participants, but the temperature drop for the non-affected foot was 1.9 times greater than the affected side in CN group (p=0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps. Conclusions: The observed differential thermal response to walking initiation between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between activity dosing and thermal response. It may also lead to a valuable insight into identifying an "inflammatory trigger" that may ultimately provide an early warning sign or increased sensitivity for subsequent unilateral or bilateral CN development or clinical expression of foot ulcer. These results also support that managing modulating duration of continuous steps and or prolonged standing during daily activity could be helpful for reducing the trauma in patients with CN or patients at risk of diabetic foot ulcer.
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Association between obesity, cardiometabolic disease biomarkers and innate immunity-related inflammation: Relevance of vitamin D.
Background and Objectives: Obesity is associated with a state of chronic inflammation and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese subjects. Methods: Subjects (n = 1,805, aged 18 to 79 years) from Canada were examined for associations between BMI, cardiometabolic markers [apolipoprotein (Apo) A1, ApoB, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, total:HDL-C ratio, triglycerides, and glycosylated hemoglobin (HbA1c)], inflammatory factors [C-reactive protein (CRP), fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in adults. Results: All biomarkers were significantly associated with BMI (P≤0.001). ApoA1 (β= 0.31, P<0.0001), HDL-C (β=-0.61, P<0.0001), and 25(OH)D (β=-0.25, P<0.0001) were all inversely associated with BMI, while all other biomarkers showed positive linear associations. Different patterns of significant associations were noted for all biomarkers among normal weight, overweight, and obese groups, excluding CRP which was consistently correlated with BMI and showed a significant positive association in the overall population (β=2.80, P<0.0001) and in the normal weight (β=3.20, P=0.02), overweight (β=3.53, P=0.002) and obese (β=2.22, P=0.0002) groups. Interestingly, plasma vitamin D levels were significantly inversely correlated with BMI (β=-0.25±0.06, P<0.0001). Conclusions: There is a distinctive profile of cardiometabolic and inflammatory biomarkers that emerges with obesity as BMI increases from normal weight to obesity. Elucidating these profiles may permit developing an effective approach for early risk prediction of cardiometabolic disease and its prevention based on modulating the corresponding metabolic phenotype in each BMI stage., e.g., by micronutrients such as vitamin D.
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Cellular senescence as a tumor suppressor mechanism is mediated by sequential activation of the p53 and RB pathways
Authors: Naima Al Mulla, Zafar Nawaz and Raya SaabBackground and Objectives: Oncogene induced senescence is a tumor suppressor mechanism that limits progression of pre-malignant lesions. Identifying the molecular mechanisms by which cells can escape senescence may provide novel cancer therapeutic and preventive targets. Two tumor suppressors, p53 and Rb, are involved in senescence, but their specific roles are still unclear. Our aim is to investigate the role of the Rb and p53 pathways in cellular senescence, to identify mechanisms of cellular escape from senescence, and to evaluate human tumor samples for disruption of the identified pathways. Methods: We are using a transgenic mouse with pineal-cell specific cyclin D1 expression (Irbp-Cyclin D1 mouse). These mice develop premalignant pineal hyperplasia with features of cellular senescence, and tumors progress only when the p53 or the RB pathway is disrupted. Results: We found that p53 was activated early in the senescence response, and led to cell cycle exit. RB activation occurred days later, and coincided with the senescence phenotype that included formation of heterochromatin foci. Disruption of either pathway alone was sufficient for pineal tumor progression. Using genetically engineered mice with regulatable expression of p53, we are now investigating the specific role of p53 in the induction versus maintenance of cell cycle exit. In addition, we are using primary cultures of Irbp-Cyclin D1 pineal cells to examine the effects of turning the p53 and RB pathways "on" and "off" during cellular senescence, to dissect their roles during induction and maintenance of senescence. We are also analyzing premalignant versus malignant tumors from these transgenic mice, to identify recurring genetic lesions that may be important targets for tumor prevention. Finally, we are evaluating human tumor samples for genetic lesions that overlap with the identified pathways. Conclusion: Our preliminary results suggest that the p53 and RB pathways have distinct and complementary effects in the senescence response, where the p53 pathway is important for induction of senescence, while the RB pathway may be responsible for its maintenance. Studies are currently ongoing to verify these observations. These findings will have direct implications on novel approaches to cancer therapy and prevention, by activating cellular senescence and tumor suppression.
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"Ca2+ funneling": Functional coupling between SOCE, SERCA and IP3 receptors enhances Ca2+ signaling efficiency in activating the Ca2+-activated Cl channels as downstream effectors.
Authors: Raphael Courjaret and Khaled MACHACAStore-operated calcium entry (SOCE) is a ubiquitous Ca2+ influx pathway leading to a sustained, low amplitude Ca2+ signal that activates multiple physiological process including gene transcription and secretion, and contributes to store refilling. We here describe a novel mechanism, that we call "Ca2+ funneling", which allows efficient activation by SOCE of Calcium-activated chloride channels (CaCl2) in the xenopus oocyte to regulate the cell's membrane potential. When intracellular Ca2+ stores were emptied using ionomycin, a small CaCl2 current is observed. Conversely, when the stores were depleted following injection of IP3 there was a significantly larger CaCl2 activation than with ionomycin (2.5 ± 0.5 nA, n=14 vs 0.08 ± 0.02 nA, n=20). Surprisingly the size of the SOCE current was similar in both conditions, indicating that an equivalent calcium influx was leading to different CaCl2 activation. Ca2+ injection experiments ruled out any change in the CaCl2 sensitivity to Ca2+. The CaCl2 activated by IP3 could be inhibited by La3+, BTP-2, 2-APB and heparin showing its dependence on both store-operated channels as well as IP3 receptor activation. The same mechanism could also be induced when IP3 production was stimulated by lysophosphatidic acid (LPA). Moreover, we could show that the sustained phase of the biphasic depolarization induced by LPA required SOCE activation. Analysis of the cellular localization of the xenopus TMEM16a (CaCl2) and of the ER calcium sensor STIM1 revealed a tendency of the two proteins to exclude each other following store depletion. We therefore propose the existence of a functional coupling between SOCE, SERCA and IP3 receptors to effectively activate CaCl2 in response to an agonist-induced store depletion. We refer to this coupling as "Ca2+ funneling" where calcium entering the cell through SOCE is rapidly taken up into the ER by SERCAs and released through open IP3 receptors close to its target, the Ca2+-activated Cl channels.
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A pilot study of diagnosed and undiagnosed type 2 diabetic patients in Qatar
Background and Objectives: The prevalence of type 2 diabetes (T2D) in Qatar is the highest in the world. It is estimated that about one quarter of the T2D patients in Qatar are still undiagnosed. We set out to examine determinants of pre-diabetes (PD) or undiagnosed T2D (UT2D). Furthermore, we examined risk factors for glucose regulation in patients with known T2D. Methods: We examined 178 patients with known T2D and 196 controls. Anthropometrics and HbA1c were measured. Socio-demographic (age, gender, ethnicity and educational level) and health information were assessed through questionnaires. Results: Twenty-six (13.3%) and twelve (6.1%) participants in the control group were PD and UT2D, respectively. Control participants from South Asian descent were at a greater risk of being PD or UT2D than Arab controls (Odds Ratio: 5.27 (95% confidence interval: 2.10, 13.22). Being obese was also associated with an increased risk of PD or UT2D (Odds Ratio: 2.94 (95% confidence interval: 1.31, 6.59). Of control participants from South Asian descent, 38% were actually PD or UT2D. In patients with known T2D, insulin use and a longer duration of T2D were both related to higher HbA1c levels (both p<0.0001). No socio-demographic factors were associated with glucose control in T2D. Conclusions: In a nation with a large South Asian immigrant population, we found a strong increased risk of being PD or UT2D in these subjects. Focus should be on the prevention and early identification in South Asian individuals. Larger studies are necessary to further examine the determinants of T2D and glucose regulation in Qatar.
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Metformin regulates hyperglycemia-induced vascular senescence through SIRT1
Authors: Gnanapragasam Arunachalam, Samson M Samuel, Isra Marei, Hong Ding and Chris R TriggleBackground and Objective: Vascular aging is associated with changes in the structure and function of the vascular system and such changes contribute to the risk for the development of diabetes and associated cardiovascular diseases. Vascular senescence reflects the limited ability of vascular cells to divide and proliferate and is accompanied by specific phenotypic changes in morphology, gene expression and function. In endothelial cells, these changes result in a phenotype that is pro-inflammatory and pro-atherosclerotic. The early onset of vascular senescence is also an indicator of premature aging. Recent studies have shown that hyperglycemia-induced vascular senescence is an important contributing factor to promote the development of aging-associated cardiovascular events. Sirtuin 1 (SIRT1) is highly expressed in the vasculature and has recently been identified as an important regulator of endothelial cell senescence-like growth arrest. Metformin is the most frequently prescribed first-line oral hypoglycemic agent for the treatment of type 2 diabetes. Recent studies have demonstrated that the beneficial effects of metformin may be associated, directly or indirectly, with the activation of SIRT1. Methods: In this study, we investigated the molecular mechanisms and protective effects of metformin against high glucose (HG) induced endothelial cell senescence and the contribution of SIRT1-dependent mechanisms. Mouse microvascular endothelial cells (MMECs) were maintained in culture under either normoglycemic (11mM glucose) or hyperglycemic (HG, 40 mM) conditions and Western Immunoblot techniques were used to determine changes in protein expression. Results: Immunoblot analysis reveals that MMECs exposed to HG results in a significant reduction in SIRT1 expression, but an increase in FoxO1 and p53 acetylation. HG exposure also results in a significant up regulation of p21 expression and a decrease in anti-apoptotic Bcl-2 expression. The percentage of senescence-associated β-galactosidase activity is increased with exposure to HG. The presence of metformin reduces the negative effect of HG on SIRT1 expression and protects endothelial cells from HG-induced senescence. Conclusion: These data suggest that HG-induced down-regulation of SIRT1 plays a crucial role in diabetes-associated endothelial cell senescence and, furthermore, that the protective effect of metformin against HG-induced endothelial dysfunction is, at least in part, due to its effects on SIRT1 expression/activity.
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Tunneling nanotubes mediate preferential transfer of mitochondria from endothelial to cancer cells and confer chemoresistance
Many tumors are regulated by complex interactions with cellular components of the microenvironment including mesenchymal stem cells (MSC) or endothelial cells (ECs). While the role of receptor-ligand interaction at the cell surface is well documented, direct cell-to-cell contact has not been clearly established. Recently, tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfer of organelles, various plasma membrane components and cytoplasmic molecules in several cell lines. We thus investigated the formation of TnTs between stromal cells and cancer cells supported by them. We demonstrate that TnTs occur between different cancer and stromal cell lines. TnTs formation seemed to be dependent of large membrane adhesion. We show that intercellular transfers of cytoplasmic content can occur by TnTs. However, we demonstrate that the exchange of mitochondria occurs preferentially between endothelial cells and cancer cells and contributes to chemoresistance. Our results point out the role of direct endothelial to cancer cell exchange, which emphasize our hypothesis that this angiogenesis-independent role of the endothelium plays a role in the constitution of the metastatic niche.
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Biobank Qatar: Implementation and initial results
Authors: Elio Riboli and Paul ElliottBiobank Qatar aims to establish a large national bioresource that will support the development of cutting edge medical research during the next decades. While the design of Biobank Qatar has similarities with other large-scale population-based prospective cohort studies established in other parts of the world, it is unique in the region and excels for its highly innovative scientific and technological features. Biobank Qatar will include up to 80,000 healthy volunteers, who will be followed up during the next decades to investigate the major behavioral, genetic and environmental causes of the chronic diseases most prevalent in the Qatari population. At the initial baseline visit the study participants will provide detailed information on lifestyle and medical history, a number of medical measurements will be made including ECG, spirometry, retinal image, pulse-wave velocity, anthropometric measurements, iDXA etc. Blood, urine and saliva samples will be collected, aliquoted and stored frozen for future investigations. A set of established clinical chemistry analyses (e.g. haematology, lipids, inflammation markers, hormones, nutrients) will be measured at baseline. During 2011-2012, activities focused on the establishment of protocols, clinical and IT facilities. A unique feature of Biobank Qatar is the comprehensive, real-time IT integration of all the baseline measurements. An initial test of the study protocol and clinical measurements was conducted December 2011 to May 2012 when 100 participants attended the biobank facilities at Hamad Medical City. Cooperation of the study participants was excellent. This initial sample provided helpful insights on some lifestyle and medical conditions. For example: - Sedentary lifestyle is highly prevalent. - High prevalence of participants having gained weight in a year. - Diabetics have higher body mass index and larger waist circumference than non-diabetics. - Short sleeping hours are associated with higher blood pressure. - Physical activity, even at modest levels, is associated with lower blood pressure and smaller waist circumference. These initial findings indicate feasibility of high quality data collection, and confirm well-known associations between lifestyle and metabolic features in the Qatari population. The initial test provides strong rationale for the extension of the Biobank to include large numbers of participants as planned.
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Epidemiology of football injuries in Asia: A prospective study in Qatar
Authors: Cristiano Eirale, Abdulaziz Farooq, Faten Smiley, Johannes Tol and Hakim ChalabiObjectives: To investigate the incidence, characteristics and patterns of football injuries at club level in Qatar. Design: Prospective cohort study. Methods: Data were prospectively collected from the first division football league clubs in Qatar, in accordance with the international consensus statement on football injury epidemiology. An injury was defined as any physical complaint sustained during football activity resulting in the inability to participate fully in the next training or match. Individual injuries and exposure of each player were recorded by the medical staff of each team over one season. Results: A total of 217 injuries were recorded, with an injury rate during matches of 14.5/1000 h (95% CI: 11.6-18.0) compared with 4.4/1000 h during training sessions (95% CI: 3.7-5.2). More than one third of all injuries were muscle strains (36.4%). Hamstring strains (54.4% of all muscle strains) exhibited a higher incidence than all other injury types (p < 0.001). The thigh was the most frequent injury location (41.9%, p < 0.001). Re-injuries (15% of total injuries) were mainly comprised of muscle strains associated with a higher severity compared with new injuries. Conclusions: Despite the different environmental, social and cultural setting, our findings are comparable with previous data from a European club football, confirming the previous finding at national team level that there are no regional peculiarities of football injuries in this part of the Asiatic continent. The relatively high overuse injury incidence rate and the high recurrence rate for (severe) thigh muscle strains, especially during games, warrants prevention strategies.
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Evidence for a cell fate refinement mechanism in sensory neurons
Authors: Ishmail Abdus-Saboor and Benjamin ShykindThe olfactory receptors (ORs), which are G-protein coupled receptors, number more than 1,000 and comprise the largest gene family in the mammalian genome. ORs are expressed both monogenically and monoallelically in olfactory sensory neurons (OSNs) and the mechanism that controls their regulation is largely unknown. ORs reside in constitutive heterochromatin and selection of one OR and from one allele occurs stochastically. To ensure singular monoallelic OR expression, a negative feedback mechanism is elicited by the first selected OR to suppress non-selected ORs in a given neuron. Here we describe results for mice with a 'monoclonal' nose that express one OR, M71,in 95% of all mature OSNs. The M71 transgene suppresses expression of endogenous ORs, and remaining endogenous expression is mostly restricted to immature neurons in the olfactory epithelium. We show that the endogenous OR repertoire are expressed prior to suppression by M71 transgene expression, contrary to current models. When we introduced a second transgene into M71 mice that expressed another OR in most mature OSNs, OSNs uncharacteristically expressed both of the ORs. We hypothesize that unresolved OR competition compromised the neuron's ability to express only one receptor. We further show that suppression of endogenous ORs by M71 is not reversible, and that M71 does not need to be continuously expressed for endogenous ORs to remain suppressed. In these experiments, we have engineered OSNs to express more than one OR in an OSN at a time, which is normally a low probability event. We believe that these experiments reveal the existence of a backup pathway that ensures only one OR will be expressed per neuron. It is possible that mammals have evolved similar mechanisms in other examples of stochastic, monoallelic gene expression, such as in random X-chromosome inactivation or lymphocyte receptor expression.
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Bioinformatic parallel processing tools development for mutation identification from whole exome data following homozygosity mapping for autosomal recessive disorders
Authors: Yasser Al-Sarraj, Adel Abouzehry, Hatem El-Shanti and Marios KambourisEight consanguineous Arab families with novel autosomal recessive disorders were mapped with illumina 700K SNP. All relevant positional candidate genes were screened for pathogenic mutations. None were identified. Multiple homozygosity intervals were obtained for each family since no significant LOD scores were possible. Whole exome sequencing was on ABI SOLiD4 for 1 affected individual from each family. Mapping and annotation was on LifeScope software. Data validation was done manually for each linkage interval, by visual inspection of read depth and bead number coverage. On average 30,000 sequence variations were detected in each sample including novel variants, known polymorphisms & exome sequencing errors. For each chromosome with a linkage interval, data was isolated and filtered by exportation to Excel spreadsheets and visual inspection to exclude non-linkage interval data. The number of variants in the linkage intervals for each family was between 400 and 1300. Homozygous sequence variations within the linkage intervals were between 50 and 300 with 15-30 novel variants. Determination if a variant was homozygous or heterozygous, novel or annotated was done manually upon visual inspection of data on Excel spreadsheets. For each novel variant it was manually determined if it were exonic, splice site specific or intronic. For each annotated variation it was manually determined if it is associated to a disease phenotype relevant to the family disease. Minor genotype frequency was investigated for annotated variants if they represent disease states. All novel exonic variants were tested in silico with PolyPhen and Sift Protein Modeling software to access the effect on protein function. All damaging variants (novel or annotated exonic, and splice site) were validated by Sanger sequencing and tested for co-segregation to disease. An identical approach is essential to access pathogenic effects of insertion/deletion variants within each linkage interval. This approach is tedious, involves a tremendous amount of manual work and is prone to oversight errors. Software tools development for automating next-generation sequencing data analysis is essential to eliminate manual work and identify pathogenic mutations among the plethora of existing variants. Such automation is applicable in cases without linkage intervals to limit the number of variants under consideration.
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Novel pyridinium-based cationic lipids as gene delivery vectors
Background: For the past two decades, cationic lipids have remained one of the most widely used non-viral gene delivery vectors due in large to their safety and ease of use despite having low efficiency. We and others believe that the key to improving the effectiveness of non-viral agents is unlocking the still unsolved mechanism behind lipid gene delivery. Our objective is the rational design, synthesis and evaluation of the DNA complexation and in vitro delivery efficiency of novel lipid vectors in an effort to gain structure-function data which may give insight towards the non-viral mechanism. Objectives: Here we report preliminary data on two novel pyridinium-based cationic lipid vectors, designated as TFSA (saturated acyclic structure) and TFUA (unsaturated acyclic structure), both possessing a pyridinium headgroup with a delocalized positive charge, and two saturated (TFSA) or monounsaturated (TFUA) C15 hydrophobic alkyl chains. In the case of the unsaturated analogue, the double bonds are located at the terminal ends of the alkyl chains. Methods: Liposomes were prepared from these novel pyridinium-based cationic lipids in combination with a commercial vector, EPC, together with a co-lipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol. Lipid-DNA complexes (lipoplexes) were then formulated by incubating the liposomes with plasmid DNA. Lipoplexes were characterized by gel retardation, DNAse I degradation, as well as biocompatibility and β-galactosidase (β-gal) transfection assays using Chinese Hamster Ovarian (CHO-K1) cells. Fluorescent GFP-plasmid DNA was used to track DNA inside cells using epifluorescence microscopy. Results: The novel lipid formulations were shown to effectively complex DNA and protect it from DNAse I degradation. They were biocompatible with CHO-K1 cells, and performed better when they were formulated with cholesterol over DOPE as co-lipid. Furthermore, the formulation containing the unsaturated compound (TFUA/EPC/DOPE) revealed transfection efficiencies far above TFSA/EPC/DOPE, and superior to the commercial transfection agent EPC formulated alone with DOPE. Results from the GFP-plasmid tracking experiments were consistent with the relative β-gal expressions observed in the transfection assay. Conclusions: These preliminary results suggest that our novel pyridinium-based cationic lipid vectors are effective gene transfer agents, suitable for further investigations into the mechanism of non-viral gene delivery.
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Adipokines as mediators of components of metabolic syndrome in a Qatari population
Background and Objectives: There is a high prevalence of obesity and its co-morbidities within the Arab population, especially in Qatar. Furthermore, the younger age of onset of obesity and its preponderance amongst females have seen an increase in type 2 diabetes and cardiovascular disease in this cohort. Adipose tissue dysfunction preceding frank obesity may underlie the increased risk of metabolic syndrome (MeS). Therefore aims of this study were to characterize the relationship between components of MeS and adipokines in a Qatari population. Methods: Non-diabetic subjects were recruited from the general Qatari population and patients awaiting weight reduction surgery (Al-Emadi Hospital). Lipid profiling and liver function were determined by conventional techniques (HMC). Insulin resistance was measured by HOMA. Adipokines were measured by ELISA. Results: In the whole study population (n=56, 13 males/43 females, 30.5+/-7.5 years old, BMI of 37.5+/-11kg/m-2) significant positive correlations between plasma leptin and BMI were confirmed. However, after controlling for BMI, partial correlations showed that leptin was associated negatively with all measures of blood pressure (all p≤0.01), triglycerides, total- and LDL-cholesterol (all p≤0.01), with liver enzymes (SGPT, AST and Billirubin, p=0.009, p≤0.01 and p=0.02 respectively), and positively with HDL cholesterol (p=0.05). Furthermore, leptin, was also negatively correlated with fasting blood glucose and HOMA (p=0.03 and p=0.01 respectively). In order to investigate this further, the population was dichotomized into age-matched normal weight (n=14) and obese (n=42) sub-groups. The obese group had significantly higher SBP (p=0.006), triglycerides (p=0.03), leptin (p≤0.001) and lower HDL (p≤0.001). Obesity was also associated with deteriorating liver functions manifested as elevation in SGPT (p =0.02), ALP (p= 0.01) and AST (p =0.02). Conclusions: Leptin was elevated in obesity. After correcting for BMI, an inverse relationship between leptin and risk factors for MeS was apparent, suggesting a protective role for leptin in this population, perhaps through its vasodilatory capability. However, when dichotomized into lean and obese groups, chronic elevation in leptin appeared to be associated with increased risk of MeS and deterioration of liver function, as previously described. These novel data are currently being confirmed in a larger ethnicity matched cohort.
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Akt-activated endothelial cells enhance self-renewal, stemness, resistance to therapy, and metastasis in breast cancer
Authors: Pegah Ghiabi, Jennifer Pasquier, Bella Guerrouahen and Arash Rafii TabriziRecently, the role of tumor microenvironment (niche) in regulating cancer progression has been indicated. Tumor microenvironments consists of tumor vasculature, bone marrow mesenchymal stem cells, immune cells and the components of the extracellular matrix. It is believed that the phenotypic advantages acquired by tumor cells are partly the outcome of their interaction with their niche. Endothelial cells are the building blocks of tumor vasculature and have lately been shown to have additional benefits than merely a conduit for supplying oxygen and nutrients. Here, we intend to demonstrate the critical role of the Akt-activated endothelial (E4ORF1) cells on breast cancer development, survival and spreading. The effect of E4ORF1 cells on breast cancer (BC) and breast cancer stem cells (BCSC) self-renewal was assessed by co-cultivating E4ORF1 with MDA-MB231 and MCF-7 BC cells under adherent and suspension conditions. BCSC enrichment by E4ORF1 cells was measured by analyzing the CD44+/CD24Low/- population of BC cells by flow cytometry as well as by evaluating the expression of pluripotency markers by RT-PCR. BCSCs resistance to treatment was investigated by addition of metformin and determining BCSC proliferation with/out E4ORF1. The role of E4ORF1 on BC cell metastasis was shown by migration and adhesion potential of BC cells with/out E4ORF1 cells. Our results demonstrated a 5-fold increase in the self-renewal capacity of BC cells and BCSCs in the presence of E4ORF1. Also, E4ORF1 was able to promote stemness in BC cells as was shown by significant increase in CD44+/CD24Low/- BCSC population and the up-regulation of pluripotency markers. Moreover, BCSCs survived drug treatment by 2.5 folds in the presence of E4ORF1. Besides, BC cells showed enhanced invasion/adhesion property when exposed to E4ORF1 cells. Our data suggest a major role for E4ORFl cells in BC progression, stemness, resistance and metastasis. This characteristic of E4ORF1 cells in maintaining BC cells can be exploited in developing novel anti-cancer therapy to combat BC in a more effective way.
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Identification of molecular pathways implicated in the metastasis process in a mouse model of lung adenocarcinoma
Authors: Mouaadh Abdelkarim, Supria Gerardine, Rufayda Marmar, Omar Kallas, Hamid Massaeli and Nasrin MesaeliA global survey of cancer has shown that lung cancer is the most common cause of the new cancer cases and cancer deaths in both men and women worldiwide. In Qatar a recent retrospective study based on a cohort of patient registry of Al Amal Cancer Hospital from 1991-2006, showed that lung cancer and lumph node cancer are the major cancers in men (5.9%, incident rate per 100,000) while in women breast cancer had the highest incidence. To study the mechanisms of lung cancer development we recently developed a transgenic mouse model overexpressing CRT under the control of Tie2-promotor. The main phenotype of these mice is the development of metastatic lung adenocarcinoma similar to human patients. The objectives of the current study was to identify the molecular pathways involved in the metastatic behavior of lung adenocarcinoma. To examine our objectives we used anchorage independent and adherent culture of lung adenocarcinoma cells isolated from mouse and human cell lines. Using microarray and bioinformatic analysis we have identified several pathways and genes that are altered in mouse cells. The microarray analysis demonstrates that 90 genes are up-regulated and 66 genes are down regulated under anchorage-independent condition compared to adherent conditions. The bioinformatic analyses demonstrate that the up-regulated genes are implicated in cellular development, cellular growth and proliferation pathways. These pathways include: VEGF signaling, bladder cancer signaling, VEGF family ligand-receptor interaction and Ephrin-receptor signaling. The bioinformatic analyses also demonstrate that the downregulated genes were implicated in cell cycle regulation and cell-to-cell signaling and interaction. The analysis of these genes by canonical pathawy demonstrate that these genes are involved in the regulation of very relevant pathaway implicated in cancer essentially : Hematopoeisis from multipotent stem cells, TGF-β signaling and tight junction signaling. We are currently examining these pathways in human adenocarcinoma cell line. In conclusion, our data illustrate that although calreticulin is an endoplasmic reticulum calcium binding chaperone, it is involved in the process of tumor development and metastasis. Further work is needed to decipher the molecular mechanism of involvement of calreticulin in tumor development. This research was funded by QNRF grants UREP09-084-3-016 and NPRP4-043-3-016.
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Epigenetic changes in beta cells related to high glucose
Background & Objectives: Epigenetic changes include two types of changes DNA methylation and Histone modifications. These modifications are influenced by the change in various environmental factors resulting in a stable form of gene expression changes. Type II Diabetes incidence keeps rising with so little understanding of the actual cause at gene expression level despite the massive amount of research around the subject. Which is why we chose to capture a closer image of what happens at the genome level when environmental factors such as high glucose intake can influence healthy cells into change their gene expression to adapt and how is that related to Diabetes. Methods: Mouse Beta cells are grown for several generations at various glucose concentrations in two groups, each group consisting of three biological replicates, each replica of glucose concentration (High vs. Normal) is devoted for one histone modification marker (H3K4me2, H3K27me2). The treated cells are further processed by chromatin-immuoprecipitation followed by next generation Sequencing (ChIP-Seq). Results: Data analysis was performed to identify enriched affected pathways. Significant differences in gene expression between high levels of glucose versus normal glucose were found using ChIP-Seq and confirming what was previously obtained by ChIP on Chip. Conclusion: The results of this experiment shed some light on the matter of surrounding environment effect on gene expression. Evidence of environmental elements affecting blood glucose levels was seen predecting difference in gene expression, e.g. type II diabetes risk factors. Genes involved in several pathways showing evidence of cardiac muscle diseases, kidney damage and changes in the calcium channel signaling were observed, all of which are related to type II diabetes complications.
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The relative risk of road mortality (RRRM) in Qatar
Authors: Rafael Consunji, Ruben Rosario Peralta, Hassan Al Thani and Rifat LatifiBackground and Objectives: The epidemiology of road deaths in Qatar has not been fully described. This study will analyze and compare the age-specific death rates from motor vehicle crashes (MVC's) and make recommendations for targeted injury prevention programs for road safety in Qatar. Method: Data from the Qatar Statistic Authority (QSA), for the year 2010 was collected and analyzed. All deaths classified as "motor- or nonmotor-vehicle accident, type of vehicle unspecified" were included. Age group populations were computed from age-specific crude death rates. Results: There were 247 MVC deaths in Qatar in 2010. An overall death rate was computed at 14.2 deaths per 100,000 population. The RRRM varied over ten times amongst different populations with Qatari males (QM) having an increased RRRM from 10 years of age. The QM's aged 20-29 had the highest RRRM of 10.2. The lowest RRRM was for Qatari females who did not have a single road fatality in 2010. Other populations with elevated RRRM (i.e. RRRM >1.0) were non-Qatari males ages 10 to 19 and older than 50 years. Conclusions: Qatari males have an elevated RRRM from the age of 10 onward, definite programs must be implemented to reduce these unnecessary deaths amongst the populations at the highest risk. Multidisciplinary approaches must be implemented and their efficacy evaluated.
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Inhibition of NFκB signaling in calreticulin deficient cells
Calreticulin (CRT) is an endoplasmic reticulum (ER) Ca²+ binding chaperone, which regulates many of cellular processes. Previous work from our lab showed loss of CRT leads to increased resistance to apoptosis. We also showed loss of CRT leads to increased AKT phosphorylation and activation of the proteosome activity. Thus we hypothesized that in the absence of CRT function, NFκB signaling is activated leading to enhanced resistance to apoptosis of these cells. Wild type and CRT knockout mouse embryonic fibroblast were used to examine changes in the NFκB signaling pathway. Reporter gene assays showed a significant reduction in the basal NFκB transcriptional activity. Activation of NFκB with lipopolysaccharide increased the transcriptional activity of NFκB in both the cells, however, the transcriptional activity of NFκB was still significantly lower in the CRT deficient cells as compared to the wild type cells. Our immunocytochemical staining showed a delay in the translocation of NFκB p65 to the nucleus of CRT deficient cells after lipopolysaccharide treatment. We also observed an increase in the level of IκB and phospho-IκB accumulation in CRT deficient cells after lipopolysaccharide treatment. We conclude that in the absence of CRT NFκB signaling is inhibited due to decreased IκB degradation and decreased NFκB p65 nuclear translocation.
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SID-MRM-MS enabled verification of biomarkers of type 2 diabetes in a Qatari population
Authors: Prabhjit Kaur, Nasser M Rizk, Noura Younes, Mahmoud Zirie and Amrita K CheemaBackground and Objectives: Recent technological advancements in liquid chromatography coupled with high resolution mass spectrometry have facilitated clinical biomarker discovery, verification and validation. Targeted metabolic profiling refers to the precise quantitative measurements of metabolites for validation of markers identified via untargeted metabolomics. Specifically, multiple reaction monitoring mass spectrometry has enabled the reliable quantification of biomarkers in hundreds of samples, in a multiplexed manner. Methods: In this clinical study we have employed SID-MRM-MS (stable isotope dilution - multiple reaction monitoring - mass spectrometry) to quantify different classes of endogenous metabolites including intermediates of TCA cycle and lipids, on a triple quadrupole mass spectrometer. NPRP funded project enabled us to recruit a total of 169 controls and T2DM (type 2 diabetes mellitus) patients at the Hamad Medical Corporation in Doha, Qatar. Based on the discovery mode metabolomics profiling experiments, ten target molecules were chosen for biomarker validation using a cohort of 72 (control and diabetic) urine and plasma samples spiked with a known concentration of stable isotope labeled standard for each metabolite. The normalized peak area ratios were used to calculate the levels of deregulated metabolites in the T2DM cohort. We also performed extensive quality control experiments to check for retention time variation, matrix effects and metabolite degradation during sample processing. Statistical analysis was performed using GraphPad Prism (v5.0). ROC curves and interactive plots with a stringency cut-off of P ≤0.05 were plotted to test biomarker specificity and sensitivity. The cut-off values were selected to maximize the Youden index. Results: Statistically significant downregulation of succinate, xanthurenic acid, α-ketoglutaric acid and kynurenic acid were observed in the T2DM group while the concentrations of serotonin, PG (18:0/18:1), PC, sphingosine-1-phosphate and pyruvate were determined to be significantly higher in the diabetic group. The OPLS-DA model for the target metabolites had two orthogonal components and the R2 and Q2 were 0.88 and 0.87 respectively. Conclusions Our results underscore the clinical and translational utility of the MRM-MS approach. Further validation and characterization with larger cohorts, is likely to provide valuable insights into clinical potential of these markers and their correlation with T2DM associated complications.
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Fuzzy-QFD approach to quality assurance in pediatric services in public and private hospitals in Qatar
Authors: Hana Yousef Al-Shouli and Mohd Nishat FaisalBackground and objectives: This study was conducted to understand the dimensions important for quality assurance in pediatric services of public and private hospitals in Qatar. Method: The study employed Fuzzy- Quality Function Development (Fuzzy-QFD) approach to translate the patients expectations into appropriate service specifications and to perform assessments of the existing processes. The importance of this tool lies in its ability to improve customer satisfaction levels since its major role is the alignment of technical requirements on the basis of customer demands. In this study, patients who visited pediatric services were surveyed about their expectations from pediatric hospitals to develop the "WHAT" part of the Fuzzy-QFD model. Then a focus group consisting of three doctors, a nurse and one healthcare researcher was formed to identify appropriate service specifications and the existing processes available in pediatric hospitals in Qatar. The input from this group was used to develop the correlation matrix, which was an important step in the Fuzzy-QFD process. The matrix showing the relationship between the "WHAT's" and the "HOW's" seeks to match patients' expectations with the technical specifications of the services adopted by the hospitals. Results and conclusions: The final weight and ranking concluded that management should give prime importance to 1) continual survey of patients to assess their needs, 2) patients and family rights, 3) the quality of policy and procedures documentation, 4) in-service continuous education and training, 5) the management of nursing operations, 6) the Service Quality Program (quality and patient safety), and 7) the waiting and distribution systems.
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Targeting microRNAs offers a new therapeutic approach for the treatment of diabetes-related cardiovascular disease
Authors: Hala Omar, Isra Marei, Gnanapragasam Arunachalam, Samson M. Samuel, Christopher Triggle and Hong DingBackground and Objectives: The World Health Organization states that cardiovascular disease is the leading cause of death worldwide. The increasing prevalence of obesity and diabetes indicate that cardiovascular disease will remain a major health concerns for decades to come. The Gulf States including Qatar, the Middle East and the North African (MENA) region as whole, but also elsewhere in the world, face a pandemic of obesity and diabetes. Hyperglycaemia is the common denominator of both type-1 and type-2 diabetes and results in "glucose toxicity" that is closely linked to the high cardiovascular morbidity and mortality associated with diabetes. A reduction in the generation of NO -an important contributor to the endothelium regulation of blood flow and coagulation- in response to hyperglycaemia, is an early indicator of the onset of vascular disease. NO bioavailability is determined through the balance of its generation by eNOS and its quenching by reactive oxygen species, ROS. In response to hyperglycaemia and a variety of metabolic perturbations, eNOS produces predominately superoxide anions rather than NO and there is therefore an increase in oxidative stress and reduced bioactivity of NO. MicroRNAs (miRs) are small non-coding RNAs that inhibit gene expression and have also been implicated in the regulation of endothelial cell biology. A number of miRs including 221 & 222 have been implicated in endothelial cell function. They are involved in post-transcriptional control of major regulatory pathways. Methods: Mouse microvascular endothelial cells (MMECs) were cultured in normal (11mM) or high glucose (HG, 40mM) media and the ratio of coupled (dimeric) to uncoupled (monomeric) eNOS determined by immunoblot. ROS, NO and the expression of miR-221/miR-222 were also measured. Results: HG enhanced ROS, reduced the eNOS dimer/monomer ratio and reduced the generation of NO. Our data indicate that HG-induced ROS generation can be reversed in the presence of inhibitors of miR-221/miR-222. Conclusion: Hyperglycemia is associated with increased oxidative stress and decreased NO bioavailability. miR-221 and miR-222 play an important role in high glucose-induced increased oxidative stress and endothelial dysfunction.
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Relationships between anthropometric factors and repeated-sprint ability in the Qatar national soccer team
Background & Objectives: Muscle mass is a major determinant of power development during maximal sprinting. The ability to recover and subsequently reproduce high-intensity efforts (termed repeated-sprint ability, RSA) is closely related to match-performance in soccer. The aim of this study is to assess any relationship between anthropometric parameters and RSA performance in a national soccer team in the Middle East. Method: Sixteen members of the senior male Qatar national soccer team performed six 35-m maximal running sprints on grass departing every 10-second. Sprint times, acceleration (Accbest and Accmean), velocity and peak (PP) and mean (MP) power were calculated. Power results were also adjusted to body mass. To assess RSA, total time and sprint decrement (Sdec) score were calculated. Anthropometric measures (e.g. breadths, girths, skinfolds) and derived factors (e.g. body composition, proportionality) were assessed according to the standard of the International Society for the Advancement of Kinanthropometry. Pearson's product-moment correlations were conducted. Results: Significant (p<0.05) relationships occurred between muscle-to-bone ratio and all RSA variables (r < -0.53 for sprint times and all r > 0.51 for Accmean, velocity and power scores) with the exception of Accbest and Sdec. Muscle index, cross-sectional area for mid-thigh and calf muscle groups were only correlated (p<0.05) with PP (r = 0.70, 0.73 and 0.60, respectively) and MP (r = 0.63, 0.73 and 0.62 respectively). The sum of 6 skinfolds and adipose index were positively correlated with Sdec (r = 0.68 and 0.55, respectively; p < 0.05). Conclusion: In the Qatar national soccer team players' RSA is associated with a high muscular profile and a low adiposity. Such observation would be of benefit with the purpose of providing training and nutritional recommendations to improve match-related performance in soccer.
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Point prevalence survey of antibiotic utilization in oncology patients
Authors: Sara Hayder Ahmed, Arwa Hammuda, Emily Kathleen Black and Shereen ElAzzazyBackground & Objectives Point Prevalence Surveys (PPS) are used internationally for identifying antibiotic prescribing practices and evaluating antibiotic stewardship programs. The objectives of this study are to develop a PPS tool to be used in Qatar, to determine prevalence of antibiotic consumption in the National Center for Cancer Care and Research (NCCCR) inpatient population, and to characterize antibiotic prescribing practices. The secondary goal is to identify targets for antibiotic stewardship programs to improve prescribing practices. Methods A chart audit tool was designed based on the available literature and piloted for face validity. All adult inpatients receiving active systemic antibiotic prescriptions at 8:00AM on each audit day were surveyed. Data were collected on 3 separate days over a two week period from 26 April through 3 May 2012 at NCCCR. Collected data obtained from electronic and paper-based charts included: diagnosis, type, dose and frequency of antibiotics, route of administration, and duration of therapy. Further information such as compliance to the available local guidelines and microbiology results were also assessed. Results The overall prevalence of antibiotic use during the audit was 43% (25/58). A total of 33 antibiotics were prescribed to the 25 patients receiving systemic antibiotic therapy. An indication for antibiotic prescribing was documented in 80% (20/25) of patient charts, however, only 20% (5/25) reported duration of antibiotic therapy. The most frequently used antibiotics were Penicillin/β-lactamase inhibitor combinations 40% (13/33), followed by carbapenems 15% (5/33). In 2 out of 6 febrile neutropenic patients, local febrile neutropenia guideline was accurately implemented. Sixty one percent (20/33) of prescriptions complied with local antibiotic restriction guideline. Pre-therapy cultures were performed for 96% (24/25) of patients and all antibiotic choices matched results of available sensitivity tests performed for these patients. Conclusions The findings of this study demonstrate frequent antibiotic consumption in the immunocompromised population highlighting the importance of development, implementation, and expansion of antibiotic stewardship programs at NCCCR.
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The effect of graded hypoxia on the development of neuromuscular fatigue during maximal intermittent dynamic leg extensions
Authors: Ryan Christian, Olivier Girard, Francois Billaut and David BishopHypoxia has been shown to exacerbate the performance loss during Maximal Intensity Intermittent Exercise (MIIE). However, the effect of hypoxia on the development of central and peripheral mechanisms of fatigue during MIIE is unknown. The aim of the study is to explore the development of both central and peripheral fatigue during multiple bouts of MIIE under varying severity levels of hypoxia. On separate days, 14 healthy men performed four bouts of 6 x 5 maximal intensity, isokinetic leg extensions at 300°/s (15 s passive rest separating reps, 100 s separating sets) under normoxia (simulated altitude/fraction of inspired 02: 0m/0.21%), moderate (3000m/14.4%), and severe hypoxia (5400m/10.1%). Neuromuscular assessments which included electromyography and measurements of voluntary and evoked contractions of the knee extensors were conducted immediately pre and post each bout of exercise. Performance loss was dependent on the severity of hypoxia with a main effect of condition on the mean peak power during each bout of exercise (p<.005) and the percent decrement in mean peak power across each bout (normoxia; 2.9 ± 1.3 %, moderate hypoxia; 5.2 ± 1.5 %, severe hypoxia; 10.3 ± 2.0 %, p=<.01). Despite a main effect of time, the reduction in RMS activity was not different between conditions (-10.4% all conditions compounded). Maximal voluntary contraction force, % voluntary activation and potential twitch force (Q,tw,pot) all decreased across time (p=<.05), with the end exercise percent reduction in Q,tw,pot being greater in severe hypoxia compared to normoxia (41.3 ± 3.0 % v 28.0 ± 3.2 % p=<.05). In conclusion, performance decrements during maximal intermittent dynamic leg extensions are exacerbated by hypoxia and result from both central and peripheral adjustments. However, central adjustments do not appear to limit excessive development of peripheral fatigue below a critical threshold.
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Effects of lipotoxicity and diabetes on hepatocyte function
Authors: Alhasan Sedeeq, Mohamed Al Hajri, Mennatallah Omar, Isra Marei, Christopher Triggle and Hong DingBackground and Objectives: Obesity is a major risk factor for the development of liver disease and diabetes and there is currently a pandemic of diabetes that is associated with a very high incidence of non-alcoholic fatty liver disease and consequent deregulation of liver function. The overall objective of this project is to determine whether non-alcoholic fatty liver disease and hyperglycemia affect calcium homeostasis via altering the expression of the plasma membrane calcium release-activated calcium channel protein, Orai1, the endoplasmic reticulum calcium sensor protein, STIM1, and store-operated Ca2+ entry, SOCE, in rat hepatocytes. Methods: Rat H4IIE liver cells exposed to amiodarone were used as a cell culture model of steatosis and Western Blot, RT-PCR and fura-2 techniques were used to assess protein, mRNA and changes in Ca2+ homeostasis, respectively. Rat H4IIE liver cells were grown either in normal glucose (5.5 mM) or high glucose (25 mM) for 24 hours, then each group was treated with either vehicle (methanol), amiodarone for 24 hours, or amiodarone for 24 hours followed by normal glucose for another 24 hours. Intracellular calcium [Ca2+]i was measured using fura-2am. Results: Expression of both STIM1 and Oai1 increases after treating with amiodarone for 24 hours in both normal and high glucose, but decreases after treating with amiodarone for 24 hours when followed by normal glucose treatment. In addition high glucose enhances SOCE whereas amiodarone treatment suppresses SOCE. Conclusion: Changes in the concentration of intracellular Ca2+ in hepatocytes play a central role in mediating the actions of insulin, glucagon, catecholamines and other hormones and growth factors on carbohydrate, lipid and protein metabolism in the liver. Both hyperglycemia and steatosis result in alterations in Ca2+ homeostasis suggesting that such changes may be contributing factors by which hyperglycemia, obesity and fatty liver result in insulin resistance in the liver. The results from this UREP project may lead to a better understanding of the mechanisms whereby diabetes, obesity and fatty liver disease result in liver malfunction.
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Screening for the Arab allele mutation in LDLR using molecular techniques among Bahrainis with hypercholesterolemia
Authors: Ameena Ali, Ameena Muhammed Ali, Said Shawar, Aishah Latiff and Muhammad AlsayrafiBackground: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by defects in LDLR and leads to the elevation of blood cholesterol levels. The worldwide prevalence of the disease is 1:500 and 1 in a million for heterozygous and homozygous respectively. Recently, the Arab allele has emerged as a potential founder mutation. Objectives: The aims of this study are to develop a rapid diagnostic assay to screen for the Arab allele. Methods: Using RFLP, ARMS-PCR, and High Resolution Melt (HRM) 150 hypercholesterolemic (HC) patients from Salmaniya Medical Complex (Bahrain) were screened for the presence of the Arab allele mutation in their genomic DNA. Positive and negative controls were always run along with the samples. Results: No mutations were found among the screened volunteers and the Arab allele was not detected in the samples screened using any of the techniques described. Conclusion: Feasibility of screening using RFLP, ARMS-PCR, and HRM as a rapid diagnostic assay for the Arab allele detection was demonstrated. These assays are cost-effective in comparison to sequencing of whole LDLR gene (18 exons and 17 introns) and should be considered as a priority for any screening protocol. Ultimately, screening for FH requires the construction of all known Arab-specific mutations in a chip.
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Effect Of beta-catenin inhibition on liver cancer stem cell profile
More LessHepatocellular carcinoma (HCC) is the most common liver cancer and one of the commonest solid malignancies. High mortality rates and poor prognosis of the disease are mainly due to late diagnosis, underlying cirrhosis and resistance to chemotherapy. The risk factors of HCC include infections with hepatitis B and C viruses, along with other conditions that cause cirrhosis like: alcoholism and non-alcoholic steatohepatisis. Wnt/ß catenin signaling pathway plays a vital role in regulating the cell fate during embryogenesis and cell proliferation in adult tissues. In the absence of the Wnt ligand, beta-catenin is phosphorylated through interaction with GSK-3b, APC, axin and subsequently degraded by the ubiquitin-proteasome system. However, when the Wnt ligand binds to the receptor complex of the pathway, the destruction complex is inactivated leading to the accumulation of beta-catenin in the cytoplasm and its translocation to the nucleus where it forms complexes with TCF/LEF family that causes transcriptional activation of target genes. Recent studies suggest that cancer stem cells play a key role in liver carcinogenesis. Mutations in beta-catenin and activation of Wnt/ß-catenin signaling pathway is likely to cause abnormal proliferation and enhanced self-renewal of hepatic progenitor cells resulting in their transformation into cancer stem cells. Thus understanding the characteristics and function of liver cancer stem cells and their response to beta-catenin inhibitors is crucial to the development of novel, more effective drugs and improving patient survival. In this study we have used various drugs to target Wnt/beta-catenin signaling pathway in hepatic carcinoma cell lines. We assessed the effect of the inhibitors of beta-catenin on the expression of stem cell markers in these cell lines and will present the results of the study.
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Assessment of service quality in public and private pediatric healthcare in Qatar
Authors: Hana Yousef Al-Shouli and Mohd Nishat FaisalObjective: The purpose of this study is to assess the quality of pediatric services in public and private hospitals in Qatar. Methods: The objectives were achieved using a modified SERVQUAL scale. Data from 179 participants who visit public/private hospitals in Qatar were analyzed to find the gaps between expectations and perceptions. Results: The findings revealed that customers' expectations exceeded their perceptions, meaning that they were dissatisfied with the level of healthcare services rendered by public and private healthcare settings. The results indicated that there was a negative quality gap on each service quality scale dimension. Responsiveness and empathy variables had their highest service gaps score in public hospitals; reliability and assurance received their highest negative scores in private hospitals. Conclusions: The managers in these hospitals should work towards improving the quality of their services particularly the responsiveness and empathy dimensions.
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Using lean principles and process analysis techniques to reduce congestion in out patient departments
Authors: Fatih Mutlu, Shaligram Pokharel, Noura Gamal, Fatima Almadhoun, Dima Diab, Zina Fadel and Lama Al-SarrajBackground and Objectives: Congestion in outpatient departments (OPD) in Qatar's public hospital system is a major problem due to the demographics of the country. Despite the congestion in the general registration and assessment areas, the utilization of doctors' time is considerably low. This paradigm is propagated by (i) the inefficiencies in the appointment system, (ii) the allocation of the resources in the service design, and (iii) behavior patterns of the patients. Methods: We investigated the problem through a case study in a public hospital. First, through a careful walk-through of the patients' flow process, we identified the disruptions in the patient flows using lean principles. Simultaneously, through extensive data collection, we measured the patient flow times and resource utilization, and classified the value added- and non-value added times for the patients. Based on the observations and data collected, we propose changes for the appointment systems, patients' flow process, and allocation of resources. We benchmark the impact of our suggestions through simulation. Results: The improved solutions reduce the patient flow times by 30%. Conclusions: The patients' flow experience in public hospitals' OPDs can be significantly improved through better design of the appointment system and by eliminating wasted time in the patient flow process without investing in more resources.
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Tuberculosis beliefs, meanings, and stigmas through the eyes of Qatar's migrant workers: Survey analysis and narratives
Authors: Autumn Watts, Marwa Saleh, Rahima Sanya, Maryam Ayaz, Abhyudaya Joshi, Ali Sultan and Ziad MahfoudBackground: Tuberculosis (TB) kills nearly 3 million people and incurs at least 9 million new cases each year. While developing countries are most affected by this epidemic, migration contributes substantially to the spread of the disease. Qatar employs a vast migrant laborer workforce from TB epidemic countries, who live in high-density labor camps. Workers are grouped in the same camp rooms, and often work side by side. This puts workers at risk of developing MDR TB, with re-activation of their old TB strain or acquiring new TB infections. Objectives & Methods: This project proposed two major phases using quantitative and qualitative research methods to examine TB understandings in the migrant worker population: 1. Surveying worker perceptions of tuberculosis through widely distributed questionnaires 2. Collecting illness narratives through interviews with TB infected patients receiving treatment at the TB National Program in-patient clinic. Understanding these patients' journey with TB from the time of infection to the time of diagnosis, to life during treatment and afterward, will offer physicians, nurses and other TB personnel a better understanding of workers who are infected, or face infection, with TB. Results: -1-Survey Data Analysis Demographic and socio-economic variables of 231 participants (such as age, gender, marital status…etc) were summarized using frequency distributions. The majority of participants were between 20-29 years old and male. Almost half were Nepalese. The majority of participants said that TB is not so common or rare in their countries. Blood in cough, blood in sputum and cough were the most frequent symptoms known to participants. The majority reported the cause of bacteria was smoking. A large proportion of participants indicated that TB is preventable and treatable and it has a vaccine. -2- Three illness narratives are presented. Conclusions: Still about 1 in 4 workers have never heard about TB. Of these, most have heard about it from their own countries. Alarmingly, participants' knowledge about symptoms, causes and modes of human-to-human transmission are less than optimal. The interviews revealed several recurring themes, mainly a reluctance on the part of the patient to ask questions of the physician and health staff due to perceived social, educational, and linguistic barriers.
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The association of adiponectin gene polymorphism with gestational diabetes mellitus: The role of rs1501299 and rs2241766 variants
More LessBackground: Previous studies indicated changes of adiponectin levels during gestation. The adiponectin gene ADIPOQ is located on chromosome 3q27. The association of two single nucleotide polymorphisms (SNPs) (rs1501299 and rs2241766) in ADIPOQ gene with risk of gestational diabetes mellitus (GDM) was investigated among Arab pregnant women residing in Qatar. Methods: A case-control association study was performed on 115 pregnant women with GDM and 130 controls from Qatar. Genotypes were determined using TaqMan real time PCR assay. Fasting serum c-peptide, leptin and adiponectin levels were determined using Multiplex ELISA technique. Results: All SNPs were within the Hardy-Weinberg Equilibrium (HWE). The frequency distribution of the genotype 276 G-T (rs1501299) revealed that (40.9%), (45.6%), had GG and (53.0%), (44.0%) had GT, and (6.1%), (10.4%) had TT between GDM and control, respectively with P value= 0.261. The frequency distribution of the genotype 45T-G (rs2241766) revealed that (20.8%), (16.1%), had TT and (69.6%), (65.4%) had TG, and (9.6%), (18.5%) had GG between GDM and control, respectively with P value= 0.117. T and G alleles were the minor alleles for 276 G-T and 45T-G with a frequency of (0.11) and (0.22), respectively. Using recessive genetic model, the logistic regression analysis reveled that the Odds ratio and 95% CI was 2.14 (1.01-4.95), p=0.04 for 45T-G and was 1.79 (0.69-4.65), p=0.22 for 276 G-T. Serum c-peptide (ng/ml), and leptin (ng/ml) was significantly lower in subjects having GG versus TT+TG alleles of 45T-G with mean and SEM (7.6±1.8 Vs. 17.3 ±1.2, p= 0.002), and (21.5± 2.5 Vs. 42.1± 2.8, p=0.035). Similar significant findings were observed for TT versus TG+GG genotypes for SNP 276G-T. Adiponectin levels (µg/ml) were not significantly different in subjects having GG versus TG+TT genotypes for 45T-G and for TT versus TG+GG genotypes for 276G-T with mean and SEM (17.1± 1.8 vs. 17.2±2.3, p=0.892 and 16.5±3.24 Vs. 19.8 ±1.8, p= 0.478), respectively. Conclusion: GG carriers of 45T-G may increase the odds of getting GDM among Arab residents in Qatar. Decreased pancreatic secretory function (C-peptide) with increased adiposity (leptin) among GG carriers of 45T-G and TT carriers of 276GT may explain its roles in the development of GDM.
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Fibroblast growth factor 21 (FGF21) and diabetes-induced vascular disease
Authors: Tariq Chukir, Isra Marei, Zahra Naqvi, Navid Iqbal, Christopher Triggle and Hong DingBackground: Studying diabetes and obesity is a priority for Qatar and for the entire world. Fibroblast growth factor 21 (FGF21) is a member of the FGF superfamily that has important endocrine functions in the regulation of glucose metabolism. Elevated plasma levels of FGF21 are seen in humans with type 2 diabetes and mouse models where FGF21-resistance is associated with a reduced response to the blood glucose and insulin sensitizing actions of FGF21. There is, however, a lack of data on the effects of FGF21 on the vasculature. The objective of this study is to determine whether FGF21 and/or the FGFR1 receptor is present in endothelial cells and to determine whether FGF21 protects endothelial cells against hyperglycaemia-induced oxidative stress and uncoupling of eNOS. Methodology: RT-PCR and Western Blot techniques were used to determine the presence of FGF21/FGFR1 mRNA and protein in mouse microvascular endothelial (MMEC) and human umbilical vein endothelial (HUVEC) cell cultures. Endothelial cell cultures were treated with FGF21 to investigate the physiologic role of FGF21 in vascular tissue and to determine whether FGF21 protects the endothelial cell against glucose-induced toxicity. Western blot techniques and the dimeric/monomeric ratio were used to determine eNOS uncoupling. CM-H2DCFDA, an indicator for superoxide, was used to assess oxidative stress. Results: FGFR1 and FGF21 proteins are both expressed in MMECs exposed to high (HG) and normal (NG) glucose levels. FGFR1 levels were not changed in MMECs exposed to HG and treated with FGF21 (p=0.9; N=3) or in NG (p=0.4; N=3). For CM-H2DCFDA staining, FGF21 treated cells showed a decrease in oxidative stress (N=4). However, the eNOS dimer/monomer ratio was not affected by FGF21 in HG or NG (p=0.3; p=0.6 respectively, N=4). In HUVECs, FGFR1 is expressed in cells exposed to HG or NG (p=0.23; N3). FGF21 treatment did not affect the levels of FGFR1 in HG or NG (p=0.99; p=0.8 respectively, N=3). The eNOS dimer/monomer ratio decreased in cells exposed to HG, but was corrected following FGF21 treatment (p=0.1; N=3). Conclusion: FGF21 reduces glucose-induced oxidative stress and may , in addition to its metabolic actions, have an endothelial-vascular protective action. Supported by UREP10-034-3-009.
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Enhancing the efficiency of direct reprogramming into cardiac myocytes by defined transcription factors
Authors: Ayman Al Jurdi, Will Schachterle and Shahin RafiiAn efficient method to generate cardiac tissue from other tissues has great therapeutic potential for patients suffering from cardiovascular disease. Pluripotent stem cells, such as embryonic stem (ES) cells, and so-called induced pluripotent stem (iPS) cells can be differentiated into multiple cell types, including cardiac myocytes. However, therapeutic use of these cells has several important risks, including cancer as well as loss of differentiated cell identity and function or "drift." Transdifferentiation, the generation of cell types from other differentiated cell types, is an attractive alternative because it poses little risk of cancer and may give rise to cells whose identity is locked in. However, the direct reprogramming of adult fibroblasts into cardiac myocytes is inefficient and the transcription factors that drive this process are unknown. To circumvent these hurdles we hypothesized that fetal derived cells may be more amenable to reprogramming into cardiac myocytes with defined transcription factors. To this end, fetal derived fibroblasts and mesenchymal cells were transduced with transcription factors that have been shown to play a role in myocyte specification and maintenance, including GATA4, Mef2c, Tbx5 and Nkx2.5. To test this hypothesis, the transcription factors were cloned into lentiviral vectors, which were used to infect fibroblasts and mesenchymal cells. Infected cells were then cultured in different media. To assess the efficiency of the reprogramming, RNA was extracted from infected and uninfected cells, and quantitative RT-PCR was used to evaluate the expression levels of the transcription factors and known cardiac genes. We expected to observe higher levels of the transcription factors and cardiac markers in the infected cells relative to the uninfected cells. The results showed that the infected cells expressed higher levels of the transcription factors and a few cardiac markers relative to the uninfected cells. However, due to the small increase in the levels of only a few cardiac markers, the reprogramming was concluded to be inefficient. To make the reprogramming more efficient, other as yet unrecognized transcription factors possibly in the GATA family of transcription factors and culture conditions are currently being considered.
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Development of an expert system to automate gait data interpretation
Authors: Myriam Abi Hayla, Mohammad Khalil, John Watts and David EwinsGait analysis (GA) is often defined as the study of human walking; typically involving computerized and instrumented measurement of the movement patterns that make up walking. GA can reveal the timing and pattern of activation of muscles and joints, of body segment motions, and the forces that act on them. It can facilitate objective comparison of pathological versus normal gait and monitoring of progress in rehabilitation. However, although raw results can be printed in minutes, the clinical team may spend hours in interpreting the data. The success of this approach is limited mainly by the ability of clinicians to handle large sets of data, their expertise with respect to the biomechanics of gait, and their individual experience with the characteristics of a particular population. In addition, it is recognized that the interpretation of data varies from clinician to clinician and institution to institution which have its impact on clinical decision-making. Also, the techniques used in the interpretation of gait data often do not provide information about possible causes for gait abnormalities. Improving the efficiency of patient testing will greatly enhance the productivity of gait laboratories and improve patient care. For this reason, the focus in this project is on developing a technique for the analysis of gait data to aid clinical interpretation. A software package, also called expert system, is developed based on automating the Rancho Observational Gait Analysis Approach used to denote gait deviations. Causes related to deviations are listed and the result of additional tests that may help prove or refute any cause is also included. A report is then generated that includes all the above. The software is tested with data from a group of cerebral palsy patients to check its efficiency. Results showed that the expert system was capable in denoting deviations and overcoming a number of major challenges in gait data interpretation. However, many limitations are still present such as the need to test it on other pathologies and consider more parameters, e.g. kinetics and EMG data.
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Characterization of insulin signaling pathway in calnexin knockout cells
Authors: Samah Musa, Aleksandra Liberska, Hamid Massaeli and Nasrin MesaeliBackground: Calnexin is a lectin-like chaperone in the endoplasmic reticulum (ER) lumen, which along with calreticulin are involved in folding, maturation and trafficking of many glycoproteins. Insulin receptor and glucose transporters are among some of the proteins which are synthesized and folded in the ER. Previously, calreticulin was reported to play a role in the folding of GLUT-4 transporter as well as its stability. Furthermore, our lab reported that loss of calreticulin function results in increased insulin receptor synthesis, increased phosphorylation of Akt upon stimulation by insulin and increased glucose uptake. To date no data are available on the changes in insulin receptor pathway upon loss of calnexin chaperone. Objectives: The aim of this study is to examine changes in insulin receptor expression and insulin-mediated phosphorylation of Akt upon loss of calnexin function. Methods: Mouse embryonic fibroblast cells were serum starved overnight, then stimulated with insulin for 10 mins at 37°C. Cell lysate were prepared and Western blots with antibodies of different proteins in insulin signaling pathways were performed. Results: Our results showed a significant increase in insulin receptor expression in calnexin deficient cells. Furthermore, we observed a significant increase in the phosphorylation of Akt illustrating activation of insulin receptor pathway upon loss of calnexin function. Conclusions: In conclusion our data illustrates that loss of either of lectin like chaperones (calreticulin and calnexin) results in the activation of insulin receptor pathways via release of a negative suppressor of insulin receptor gene expression. Further research is needed to decipher the mechanism of this regulation.
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Non-invasive multiple camera calibration in highly crowded environments
Authors: Emanuel Aldea, Khurom Kiyani and Maria PetrouBackground: Very dense crowds that exceed three people per square metre present many challenges in computer vision for efficiently measuring quantities such as density and pedestrian trajectories. An accurate characterisation of such dense crowds can improve existing models and help to develop better strategies for mitigating crowd disasters. Pedestrian models used for tracking are often based on assumptions which are no longer valid in highly dense crowds, e.g. absence of occlusions. Recently, multiple camera systems with partially overlapping fields of view have been shown to offer critical advantages over other non-overlapping schemes. Objectives: We focus on overcoming the non-invasive aspect of the camera calibration, imposed by real crowded environments needed in order to accurately segment individuals. We will also underline the interdisciplinary challenges related to computer vision and real-time processing. Methods: Although there is an important amount of work devoted to multiple camera calibration, the automation of the process in specific environments remains challenging. In dense crowds, such as in Mecca, access to the site for calibration purposes or for adding support visual features is impossible. Moreover, the supervising role of the user for calibration scenarios is very important, and cumbersome for large camera networks. We investigate a light solution based on a coarse-to-fine estimation of the camera positions using both static and dynamic features. This highlights the necessary tradeoff between the crowd coverage, the purpose of the experiment, and the static feature distribution which is required to register the camera system properly. A more practical aspect that we underline is related to the importance of accurate time synchronization within the system in the presence of a dynamic scene. Results: We present a pilot study of the above scheme conducted at Regents Park Mosque in London on Friday when the mosque is particularly crowded. We have set up a distributed system of accurately synchronized Firewire cameras, acquiring high-resolution data at 8Hz. We will also aim to present some preliminary single camera studies of crowd flow using real-world data from the Muslim Hajj pilgrimage from 2011.
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A flexible and concurrent MapReduce programming model for shared-data applications
Authors: Fan Zhang and Qutaibah M MalluhiThe rapid growth of large data processing has meant the implementation of the MapReduce programming model as a widely accepted solution. The simple map and reduce stages have introduced convenience to programmers in order that they may quickly compose and design complex solutions for large-scale problems. Due to the ever-increasing complexity of execution logic in real-life applications, more and more MapReduce applications involve multiple correlated jobs encapsulated and executed according to a defined order. For example, a PageRank job involves two iterative MapReduce sub-jobs; the first job joins the rank and linkage table and the second one calculates the aggregated rank of each URL. Two non-iterative MapReduce sub-jobs for counting out-going URLs and assigning initial ranks are also included in the PageRank job. Besides this, MapReduce programming model lacks built-in support and optimization when the input data are shared. The performance will benefit when the shared and frequently accessed files are read from local instead of from distributed file system. This paper presents Concurrent MapReduce; a new programming model built on top of MapReduce while maintaining optimization and scheduling for big data applications that are composed of large number of shared data items. Concurrent MapReduce has three major characteristics: (1) Unlike traditional homogeneous map and reduce functions, it provides a flexible framework, which supports and manages multiple yet heterogeneous map and reduce functions. In other words, programmers are able to write many different map and reduce functions in a MapReduce job. (2) It launches multiple jobs in a task-level concurrency and a job-level concurrency manner. For job-level concurrency, the framework manages the shared data by replicating them from HDFS to the local file system to ensure data locality. For task-level concurrency, it is the programmers' responsibility to define the data to be shared. (3) We have evaluated the framework using two benchmarks: Single Source Shortest Path and String Matching. Results have demonstrated up to 4X performance speedup compared to traditional non-concurrent MapReduce.
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Track me to track us: Leveraging short range wireless technologies for enabling energy efficient Wi-Fi-based localization
Authors: Mohamed Abdellatif, Abderrahmen Mtibaa and Khaled HarrasGiven the success of outdoor tracking via GPS and the rise of real-time context-aware services, users will soon rely on applications that require higher granularity indoor localization. This need is further manifested in countries like Qatar, where various social and business activities occur indoors. Wi-Fi-based indoor localization is one of the most researched techniques due to its ubiquitous deployment and acceptable accuracy for a wide range of applications. However, we do not witness such techniques widely deployed mainly due to their high demand on energy, which is a precious commodity in mobile devices. We propose an energy-efficient indoor localization system that leverages peoples' typical group mobility patterns and short-range wireless technologies available on their devices. Our system architecture, shown in the figure, is designed to be easily integrated with existing Wi-Fi localization engines. We first utilize low-energy wireless technologies, such as Bluetooth, to detect and cluster individuals moving together. Our system then assigns a group representative to act as a designated cluster head that would be constantly tracked. The location of other group members can be inferred so long as they remain within proximity of the cluster heads. Afterwards, cluster heads continue to send the periodic received signal strength indicator (RSSI) updates, while the remaining members turn off their Wi-Fi interface relying on the cluster head to be localized. Our system is responsible for dynamically handling the merger or splitting of clusters as a result of mobility. We implement a prototype of the system, and evaluate it at scale using the QualNet simulator. Our results show that we can achieve up to 55% energy reduction with a relatively small degradation in localization accuracy averaging 2 meters. This accuracy reduction is non-impactful given the typical applications expected to leverage our system.
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Non-destructive visual pipe mapping for inspection
Authors: Peter Hansen, Brett Browning, Peter Rander and Hatem AlismailPipe inspection is a critical process in many industries, including oil and gas. Conventional practice relies on a range of Non-Destructive Testing (NDT) approaches such as ultrasonic and magnetic flux leakage methods. While these approaches can provide high accuracy wall thickness measurements, which can be used to monitor corrosion, they provide poor visualizations, and are typically unable to provide full pipe coverage. Moreover, they cannot be used to localize where in the pipe a defect is without expensive and possibly restricted sensors such as Inertial Navigation Systems. We have developed an automated vision-based approach that builds high-resolution 3D appearance maps of pipes and provides vehicle localization. These maps include both structure and appearance information, and can be used for direct metric measurement of pipe wall thickness, or as input to automatic corrosion detection algorithms. They may also be imported into 3D rendering engines to provide effective visualization of a pipe network. Our most recent system uses a wide angle of view fisheye camera which enables full pipe coverage and is sufficiently compact for practical applications. Our approach to mapping and localization builds from state-of-the-art visual odometry methods and extends them to deal with (visually) feature poor engineered environments. We present the results of this work using image datasets collected within our constructed pipe network. A range of empirical results are presented to validate the approach.
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Computational and statistical challenges with high dimensionality: A new method and efficient algorithm for feature selection in knowledge discovery
Authors: Mohammed El Anbari and Halima BensmailQatar is currently building one of the largest research infrastructures in the Middle East. In this orientation, Qatar foundation has constructed a number of universities and institutes composed of highly qualified researchers. In particular, QCRI institute is forming a scientific computing multidisciplinary group with a special interest in machine learning, data mining and bioinformatics. We are now able to address the computational and statistical needs of a variety of researchers with a vital set of services contributing to the development of Qatar. The availability of massive amounts of data and challenges from frontiers of research and development have reshaped statistical thinking, data analysis and theoretical studies. There is little doubt that high-dimensional data analysis will be the most important research topic in statistics in the 21st century. Indeed, the challenges of high-dimensionality arise in diverse fields of sciences, engineering, and humanities, ranging from genomics and health sciences to economics, finance, and machine learning and data mining. For example, in biomedical studies, huge numbers of magnetic resonance images (MRI) and functional MRI data are collected for each subject with hundreds of subjects involved. Satellite imagery has been used in natural resource discovery and agriculture, collecting thousands of high resolution images. Other examples of these kinds are plentiful in computational biology, climatology, geology and neurology among others. In all of these fields, variable selection and feature extraction are crucial for knowledge discovery. In this paper, we propose a computationally intensive method for regularization and variable selection in linear models. The method is based on penalized least squares with a penalty function that is a combination of the minimum concave penalty (MCP) and an L2 penalty on successive differences between coefficients. We call it the SF-MCP method. Extensive simulation studies and applications to large biomedical datasets (leukemia and glioblastoma cancers, diabetes, proteomics and metabolomics data sets) show that our approach outperforms its competitors in terms of prediction of errors and identification of relevant genes that are responsible of some lethal diseases.
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Hybrid pronunciation modeling for Arabic large vocabulary speech recognition
Authors: Mohamed Elmahdy, Mark Hasegawa-Johnson and Eiman MustafawiArabic is a morphologically rich language. This morphological complexity results in a high out-of-vocabulary rate. That is why a lookup table for pronunciation modeling is not efficient for large vocabulary tasks. In previous research, graphemic modeling was proposed by approximating pronunciation modeling to be graphemes rather than actual phonemes. In this research, we have proposed a hybrid acoustic and pronunciation modeling approach for Arabic large vocabulary speech recognition tasks. The proposed approach benefits from both phonemic and graphemic modeling techniques, where two acoustic models are fused together. The hybrid approach also benefits from both vocalized and non-vocalized Arabic resources, which is useful because the amount of non-vocalized resources is always higher than vocalized ones. Two speech recognition baseline systems were built: phonemic and graphemic. The two baseline acoustic models were combined after two independent trainings to create a hybrid model. Pronunciation modeling was also hybrid by generating graphemic variants in addition to phonemic variants. Three techniques are proposed for pronunciation modeling: Hybrid-Or, Hybrid-And, and Hybrid-Top(n). In Hybrid-Or, either graphemic or phonemic modeling is applied for any given word. In Hybrid-And, a graphemic pronunciation is always generated in addition to existing phonemic pronunciations. Hybrid-Top(n) is a mixture of Hybrid-Or and Hybrid-And by applying Hybrid-Or on the top n high frequency words. Experiments were conducted in the large vocabulary news broadcast speech domain with a vocabulary size of 250K. The proposed hybrid approach has shown a relative reduction in WER of 8.8% to 12.6% depending on pronunciation modeling settings and the supervision in the baseline systems. In large vocabulary speech domains, acoustic and pronunciation modeling is a common problem among all Arabic colloquial varieties. Thus, for future work, the proposed approach is currently being extended and evaluated with different Arabic colloquial varieties (e.g. Qatari, Egyptian, Levantine, etc.). Moreover, the proposed technique can be applied with other morphologically rich languages like Turkish, Finnish, Korean, etc. This work was funded by a grant from the Qatar National Research Fund under its National Priorities Research Program (NPRP) award number NPRP 09-410-1-069. Reported experimental work was performed at Qatar University in collaboration with University of Illinois.
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Aircraft scheduling on multiple runways
Background: Scheduling aircrafts on single or multiple runways is an important and difficult problem. This problem involves how aircrafts are sequenced on a runway and how they are assigned to runways has a significant impact on the utilization of the runways as well as on meeting the landing and departure target times. Most of the literature focuses on landing operations on a single runway as it is an easier problem to solve. Objective: This project was funded by Qatar Foundation to address the scheduling problem of both landing and departing aircrafts on multiple runways as they attempt to meet aircraft target times. The problem is further complicated when considering sequence-dependent separation times on each runway to avoid wake-vortex effects. Methods: This research project is based on a two-pronged approach. First, mathematical optimization models were developed to find optimal runway assignments and aircraft sequences on each runway. Due to the significant computational complexity of the problem, a second approach was developed to find near-optimal solution through the development of local search algorithms and metaheuristics, especially for larger problems. Results: Several optimization models were developed and the most effective one was selected to find solutions to the problem. The solution effectiveness was enhanced by developing valid inequalities to the mathematical program, which significantly reduced the computational time necessary to solve the problem. Optimal solutions were obtained for problem instances much more difficult than any accounted for in data of available literature. A scheduling index, local search algorithms and metaheuristics (Simulated Annealing and Metaheuristic for Randomized Priority Search-MetaRaPS) were also developed to solve the problem. The results show that optimal or near optimal solutions were obtained for all instances, and the value of the proposed approximate algorithms becomes more evident as the problem size increases. Conclusions: The research done in this project demonstrates that there is added value in assigning aircrafts to runways and sequencing them using more optimized methods than the most commonly used approach of first-come-first-served. This research has the potential to change how airports schedule aircrafts in order to increase the runway utilization and better meet the landing and departing target times.
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A novel and efficient relaying scheme for next generation mobile broadband communication systems
Authors: Mohammad Obaidah Shaqfeh and Hussein AlnuweiriRelaying technologies have been designated as major new enabling technologies for next generation wireless broadband systems, such as 3GPP LTE-Advanced. The practical deployment of decode-and-forward (DF) relaying technologies as supported by the current standard is based on repetition coding, meaning that the relay regenerates the same codeword generated by the source node. This scheme is suboptimal. Nevertheless, it is preferred in practice due to its simple implementation. The optimal relaying schemes called cooperative coding are difficult to construct in practice and require heavy computation load at the receiver. Therefore, they are rarely implemented despite their prospected performance gains. As a simple and practical alternative, we propose a novel relaying scheme that provides a superior performance similar to the advanced cooperative coding techniques, but it is less complex to implement. Our novel scheme is called "decode-partial-forward" (DPF) because its fundamental concept of operation is based on making the relay forwards one part of the source message such that the receiver at the destination node can rely on the direct channel with the source to obtain the other part of the message. The DPF scheme is based favorably on repetition coding and maximal ratio combining techniques, which are standardized techniques with low-complexity and low computation load. Nevertheless, our novel scheme performs very close to the optimal bounds for the supported rates over relaying links. More specifically, the increase in the supported reliable transmission rates (bits/sec) using the proposed DPF scheme may exceed 30% of the supported rates using the conventional repetition coding DF scheme. Another major advantage of our proposed scheme is that it is easy to adapt flexibly based on the channel conditions of the three links of the relay channel (source-destination, source-relay, relay-destination), by adjusting the power and rate allocation at the source and relay using simple closed-form analytic formulas. Therefore, we believe that the DPF relaying scheme is an excellent option for practical deployment in the telecommunication standards due to its simplicity, adaptability and high spectral efficiency gains.
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Adaptive multi-channel downlink assignment for overloaded spectrum-shared multi-antenna overlaid cellular networks
Authors: Redha Mahmoud Radaydeh, Mohmed-Slim Alouini and Khalid QaraqeOverlaid cellular technology has been considered as a promising candidate to enhance the capacity and extend the coverage of cellular networks, particularly indoors. The deployment of small cells (e.g. femtocells and/or picocells) in an overlaid setup is expected to reduce the operational power and to function satisfactorily with the existing cellular architecture. Among the possible deployments of small-cell access points is to manage many of them to serve specific spatial locations, while reusing the available spectrum universally. This contribution considers the aforementioned scenario with the objective to serve as many active users as possible when the available downlink spectrum is overloaded. The case study is motivated by the importance of realizing universal resource sharing in overlaid networks, while reducing the load of distributing available resources, satisfying downlink multi-channel assignment, controlling the aggregate level of interference, and maintaining desired design/operation requirements. These objectives need to be achieved in distributed manner in each spatial space with as low processing load as possible when the feedback links are capacity-limited, multiple small-cell access points can be shared, and data exchange between access points can not be coordinated. This contribution is summarized as follows. An adaptive downlink multi-channel assignment scheme when multiple co-channel and shared small-cell access points are allocated to serve active users is proposed. It is assumed that the deployed access points employ isotropic antenna arrays of arbitrary sizes, operate using the open-access strategy, and transmit on shared physical channels simultaneously. Moreover, each active user can be served by a single transmit channel per each access point at a time, and can sense the concurrent interference level associated with each transmit antenna channel non-coherently. The proposed scheme aims to identify a suitable subset of transmit channels in operating access points such that certain limits on the aggregate interference or number of serving access points are satisfied, while reducing the load of processing. The applicability of the results for some scenarios, including the identification of interference-free channels in operating access points is explained. Numerical and simulations results are shown to clarify achieved gains with the use of the proposed scheme under various operating conditions.
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OPERETTA: An optimal deployable energy efficient bandwidth aggregation system
Authors: Karim Habak, Khaled Harras and Moustafa YoussefThe widespread deployment of varying networking technologies, coupled with the exponential increase in end-user data demand has led to the proliferation of multi-interface enabled devices. To date, these interfaces are mainly utilized independently based on network availability, cost, and user choice. While researchers have focused on simultaneously leveraging these interfaces by aggregating their bandwidths, these solutions however, have faced a steep deployment barrier and only focused on maximizing throughput while overlooking the energy awareness which is critical for mobile devices. We therefore developed OPERETTA, shown in Figure1, an optimal deployable energy efficient bandwidth aggregation system for mobile users. Our system does not require modifications to applications, legacy servers, network infrastructure, or client kernel. If legacy servers choose to adopt our system, however, OPERETTA dynamically leverages this to achieve higher performance gains. OPERETTA is built as a middle-ware that is responsible for scheduling various connections and/or packets to different interfaces. This middleware estimates application and network interface characteristics and utilizes these estimates to take the most appropriate scheduling decisions. We formulate our scheduling problem as a mixed integer programming problem that has a special structure allowing it to be efficiently solved. This formulation allows users to achieve a desired throughput with minimal energy consumed. We evaluate OPERETTA via prototype implementation on the Windows OS, as well as via simulation, and compare the results to the optimal achievable throughput and energy consumption. Our results show that, with no changes to the current legacy servers, OPERETTA can achieve up to 150% enhancement in throughput as compared to the current operating systems, with no increase in energy consumption. In addition, with only 25% of the servers being OPERETTA-enabled, the system performance reaches the throughput upper-bound. We ultimately demonstrate that OPERETTA achieves the goals of being optimal, energy-efficient, as well as easily and incrementally deployable.
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CopITS: The first connected car standard-compliant platform in Qatar and the region
Authors: Fethi Filali, Hamid Menouar and Adnan Abu-DayyaGiven the clear impact that mobility has on economical and social development, the continuous increase in the number of vehicles coupled with the increase in mobility behavior of people are creating new problems and challenges that need to be holistically addressed to ensure safe, sustainable, efficient and environmentally friendly mobility systems. Cooperative Intelligent Transportations Systems (ITS) allow the transportation infrastructure, vehicles and people to be connected wirelessly (through WiFi-like technology, 3G, etc) and contribute to solve these new challenges. QMIC implemented a Connected Car (CopITS) platform that allows vehicles and road infrastructure to exchange, wirelessly, data packets enabling new cooperative applications for road safety (e.g. accident avoidance application), traffic efficiency (e.g. green light optimization application), and infotainment (e.g. media and data downloading). This platform implements the latest draft of the architecture developed within IEEE and ETSI and incorporates new enhancements in terms of communication protocols and mechanisms, which outperform existing ones by enhancing data transfer for vehicle-to-vehicle (V2V) and vehicle-to-infrastructure scenarios as well as the overall performance of the system. Simulation studies using an integrated communication/traffic simulator have been conducted to investigate important metrics like scalability, efficiency, and resilience of these mechanisms Implemented system and applications have been successfully tested in-lab and demonstrated during several events in Qatar using a real car (on-board unit) and a traffic light (roadside unit). Moreover, QMIC's Connected Car platform has been successfully tested in 2011 and 2012 Cooperative Mobility Services Interoperability tests by running all mandatory test cases, which demonstrated its interoperability with the implementations of other vendors and its conformance with the standards. We believe that QMIC's Connected Car platform is an important contribution towards putting Qatar on the world map of the "best connected countries" and being ready to host global events like the football FIFA World Cup 2022.
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Distributed load balancing through a biomimetic self organisation framework
Authors: Ali Imran, Elias Yaacoub and Adnan Abu-DayyaIn wireless cellular systems, uneven traffic load among the cells increases call blocking rates in some cells and causes low resource utilisation in others and thus degrades user satisfaction and overall performance of the cellular system. Various centralised or semi-centralised Load Balancing (LB) schemes have been proposed to cope with this time persistent problem, however, a fully distributed Self Organising (SO) LB solution is still needed for the future cellular networks. To this end, we present a novel distributed LB solution based on an analytical framework developed on the principles of nature-inspired SO systems. A novel concept of super-cell is proposed to decompose the problem of "system-wide blocking minimization" into the local sub-problems in order to enable a SO distributed solution. Performance of the proposed solution is evaluated through system level simulations for both macro cell and femto cell based systems. Numerical results show that the proposed solution can reduce the blocking in the system close to an Ideal Central Control (ICC) based LB solution. The added advantage of the proposed solution is that it does not require heavy signalling overheads.
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Performance analysis of switch-based multiuser scheduling schemes with adaptive modulation in spectrum sharing systems
Authors: Marwa Khalid Qaraqe, Mohamed Abdallah, Erchin Serpedin and Mohamed-Slim AlouiniBackground and Objective: Reliable high-speed data communication that supports multimedia application for both indoor and outdoor mobile users is a fundamental requirement for next generation wireless networks and requires a dense deployment of physically coexisting network architectures. Due to the limited spectrum availability, a novel interference-aware spectrum sharing concept is introduced where networks that suffer from congested spectrums (secondary-networks) are allowed to share the spectrum with other networks with available spectrum (primary-networks) under the condition that limited interference occurs to primary networks. The main objective is the development of multiuser access schemes for spectrum sharing systems whereby secondary users that are randomly positioned over the coverage area are allowed to share the spectrum with primary users under the condition that the interference observed at the primary receiver is below a predetermined threshold. Methods: Two scheduling schemes are proposed for selecting a user among those that satisfy the interference constraint and achieve an acceptable signal-to-noise ratio level. The first scheme selects the user that reports the best channel quality while the second is based on the concept of switched diversity where the base station scans the users in a sequential manner until an acceptable user is found. The proposed schemes operate under two power-adaptive settings that are based on the amount of interference available at the secondary transmitter. In the On/Off power setting, users transmit based on whether the interference constraint is met or not, while in the full power adaptive setting, users vary their transmission power to satisfy the interference constraint. Results: Monte Carlo simulations were used to verify the analytical results for the multiuser secondary system in terms of average spectral efficiency, system delay, and feedback. Conclusion: It is shown that scheduling users based on highest channel quality increases the average spectral efficiency, but is associated with a high feedback load. However, the switched scheduling scheme significantly decreased the feedback load but at the expense of a lower average spectral efficiency. Furthermore, it is shown that transmit power techniques increase the performance of spectrum sharing systems in terms of ASE as well as decrease system delay and feedback.
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Human centric system for oil and gas quality and pipeline infrastructure monitoring in Qatar
Authors: Adnan Nasir, Ali Riza Ekti, Khalid A Qaraqe and Erchin SerpedinBackground and Objectives: Radio frequency identification (RFID) has paved the way for a plethora of monitoring applications in the field of oil and gas. Degradation in liquefied petroleum gas (LPG)/ liquefied natural gas (LNG) quality and pipe infrastructure can be a nuisance for the oil and gas industry in Qatar. Hence, a human centric cyber-physical-system (CPS) utilizing hybrid wireless technologies including RFIDs and other sensor motes can detect and prevent such hazards. CPS technique can be used for the oil and gas sector in Qatar with customized framework architecture, event detection and decision algorithms. The objective of this research is to allow maintainers and administrators to perceive and decide on top of the monitoring system to increase the performance and efficiency of the whole monitoring application. Methods: The sensors collect the data and send it to the base station through collaborating wireless technologies. At the base station the data is processed and algorithms were run to detect an event such as presence of moisture, abnormal pressure, temperature and defects in a pipe's infrastructure health. Human interaction will help to further refine the data for possible false alarms. Mobile applications can be used by the users/administrators to send details of a perceived event directly to the base station. Results: Experiments were performed on the moisture detection in Wireless Research Laboratory in Texas A&M University at Qatar. On the similar note, other sensors can also be associated with the RFIDs and their data can be relayed to the server. A framework architecture was proposed for the human centric approach of the detection and monitoring system. Conclusion: We propose a system where these RFID active tags with the sensors such as pressure, temperature, flow, strain etc., in collaboration with other wireless technologies, are able to send information regarding the gas quality and pipe's infrastructure health. The collaboration of RFIDs and other technologies helps us to create a smart human centric monitoring system. This will enhance maintenance and event detection such as the presence of moisture or strain on pipe's structure. It will additionally assist in the automatic adjustment of the valve's and pump's properties according to the detected events.
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Identifying, implementing and recognizing Arabic accents in facial expressions for a cross-cultural robot
Authors: Amna Alzeyara, Majd Sakr and Micheline ZiadeeIn this work we attempt to understand the visual accents in Arabic facial expressions and create culture-specific facial expressions for a female multi-lingual, cross-cultural robot. This study will enable the investigation of the effect of creating such expressions on the quality of the human-robot interaction. Our work is twofold: we first identify the existence of accent variation in facial expressions across cultures, then we validate human recognition of these accents. Facial expressions embody culture and are crucial for effective communication; hence they play an important role in multi-lingual, cross-cultural human-robot interaction. Elfenbein and Ambady found that there are different accents in facial expressions, which are culture-specific, and that the differences in expressions between cultures can create misunderstandings [Elfenbein and Ambady, 2003]. Several studies compared American expressions with expressions from other cultures but none of them included Arabic facial expressions. There is no existing database for Arabic facial expressions. Consequently, we recorded videos of young Arab women narrating stories that express six emotions: happiness, sadness, surprise, fear, disgust, and disappointment. These videos were analyzed to extract Arabic accents in facial expressions. The expressions were then implemented on a 3D face model using the Facial Action Coding System (FACS). To evaluate the expressions we conducted a web-based, human-subject experiment directed at students and staff at Carnegie Mellon University in Qatar. Thirty-four participants were asked to choose the appropriate emotion for each expression and rate, on a ten-level Likert scale, the accuracy with which the expression represents the emotion. The cultural affiliation of the participants was recorded. Preliminary results show that Arabs are more likely to recognize the Arabic facial expressions over non-Arabs. To further support this conclusion the survey will be redistributed to a larger number of subjects from different cultural backgrounds and from different geographical areas.
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Extending the reach of social-based context-aware ubiquitous systems
Authors: Dania Abed Rabbou, Abderrahmen Mtibaa and Khaled HarrasThe proliferation of mobile devices equipped with communication technologies such as WiFi, 3G, and 4G, coupled with the exponential growth of online social networking, have increased the demand for social-context-aware systems. These systems leverage social information provided by users with contextual awareness, particularly location, to provide real-time personalized services. With Euromonitor International indicating a 37.7 % growth in mobile phone penetration in the past five years--ICTQatar recently reporting that each household owns 3.9 devices on average--Qatar is positioned as a strong candidate not only for the consumption of such services, but also for researching, building, and testing solutions related to context-aware system challenges. We address some of these challenges and propose pragmatic solutions. Our contributions fall into the following two categories: (i) We design and implement SCOUT, a context-aware, ubiquitous system that enables real-time mobile services by providing contextually relevant information. This information can either be generated reactively based on user request, or proactively created and disseminated to potentially interested users. Our SCOUT prototype consists of an android-based mobile client interfacing with facebook's API and a load-balancing profile-matching server that interacts with a localization engine. (ii) Since mobile users may not all experience reliable mobile-to-core connectivity due to contention, cost, or lack of connectivity, we therefore extend the reach of context-aware services to disconnected mobile users by proposing a novel communication paradigm that leverages opportunistic communication. We first send the intended information to the smallest subset of connected users deemed sufficient to reach the disconnected destinations. This subset then selectively forwards, based on social profiles, this information to nodes that are more likely to meet the destinations. Our evaluation, via simulation, shows that our algorithm achieves an improvement of 25% to 80% compared to current communication paradigms, while reducing overhead by as much as 50%. With SCOUT currently operational, and based on the simulation results, our ongoing work includes integrating our communication paradigm into the real system. We are also working on integrating real-time group recommender systems that identify groups based on user location coupled with social information to provide real-time contextual group recommendations.
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Technology intervention for the preservation of intangible cultural heritage with motion detecting technologies
By Muqeem KhanBackground: This trans-disciplinary study presents the initial outcomes of a key study undertaken to explore the role of augmented reality and motion detecting technologies in the context of Intangible Cultural Heritage (ICH) for museums-related environments. Initial prototypes are in the form of an interactive infrared camera based application for children to engage with an Aboriginal puppet, and Arabic calligraphic writings without touching any input devices. This study is unique as it tries to combine two extremes: the curation of historical intangible artifacts and their preservation through digital intervention. Objectives: This project aims to produce the following outcomes: *create a proof-of-concept ICH intelligent kinesthetic learning space; *evaluate and explore knowledge transfer opportunities of ICH afforded by peripheral games technology. The central research questions are: 1.Design: What do motion-capture and associated gaming technology experiences that are suitable for knowledge transfer of ICH in a museum situation look like? 2.Exemplified/perceived effectiveness: What is the contribution of this augmenting technology in terms of the perception of authentic and engaging learning environments? 3.Sustainability, scalability and interoperability: How can museums ensure ICH content is reusable and transferable? Methods and Results: The data will be collected and analyzed according to the differences in visitors' interactions and engagements. The data will be examined using (2 x 3 x 4) matrix triangulation strategy. The qualitative data will then be analyzed using quantitative methods such as Chi Square test and Analysis of Variance (ANOVA). The analysis will culminate the visitors' behaviors and further development of the motion-detecting prototype. It is anticipated that the results will clarify the visitors' frequency of interaction with ICH content and their length and quality of engagement with the prototype. Conclusions: Heritage-related intangible content is always restricted because of its non-physical nature and has never been fully embedded in an environment like museums and related exhibitions. The study explores alternative opportunities for knowledge transfer of ICH content that manifest with playfulness in order to elicit a deeper understanding of such intangible cultural artifacts. This study complements multiple disciplines, including heritage preservation, museum technologies and emerging interaction design.
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Interference management for multi-user cooperative relaying networks
Authors: Aymen Omri and MAZEN HASNABackground & Objectives: As the electromagnetic spectrum resource is becoming highly scarce, improving spectral efficiency is becoming extremely important for the development of future wireless communication systems. Integrating cooperative relaying techniques into wireless communication systems sheds new light on better spectral efficiency. By taking advantage of the broadcast nature of wireless communications, cooperative transmission can be used in improving communication reliability, and enhancing power and spectrum efficiency. Moreover, comparing to other emerging techniques that could achieve similar performance advantages, such as multiple-input multiple-output (MIMO) technique, cooperative communication is superior in hardware feasibility and deployment flexibility. The important advantages of cooperative communication make it one of the promising techniques for future wireless communication systems. Recently, many cooperative communication schemes have been included in different cellular standards, such as WiMAX and LTE-Advanced. However, the promised throughput and diversity gain may be lost in the presence of interferences, and hence, interference management is very important for exploiting the benefits of cooperation. This requires the need to find proper methods to prevent the interference problems, which is the main target of our current research. Methods: In this study we introduce an efficient cooperative communications scheme which maximizes the received signal-to-noise ratio (SNR) while keeping the interference levels below a certain threshold. The introduced scheme is based on two relay selection methods: max (link 2) which is based on maximizing the SNR of the second hop, and max (e2e) which aims to maximize the end-to-end SNR of the relayed link. In this method, the perfect decoding-and-forward (DF) relaying protocol is used by the relays, and the maximum ratio combining (MRC) receiver is used to combine the direct and the best selected relay links. We derive exact closed form expressions for the probability density function (PDF) of the SNR, outage probability, average capacity, and average bit error probability for the introduced cooperative schemes. Results & Conclusion: Simulations are used to validate the analytical results and an agreement is observed. The results confirm the advantage of the introduced cooperation schemes in enhancing the wireless communication system and in interference management.
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A novel wavelet-based multimodal compression scheme for joint image-signal compression
Authors: Larbi Boubchir, Tahar Brahimi, Régis Fournier and Amine Naït-AliBackground: Nowadays, by considering the important advances in multimedia and networks including telemedicine applications, the amount of information to store and/or transmit has dramatically increased over time. To overcome the limitations of transmission channels or storage systems, data compression is considered a useful tool. In general, data compression addresses the problem of reducing the amount of data required to represent any digital data including images and signals. This can be achieved by removing redundant information where the main challenge is to reduce the bit-rate while preserving a high quality of the information. Objective: This work aims to propose a new multimodal compression methodology allowing compression of jointly various data, not necessary of the same type, using only one codec. Method: The proposed joint signal-image compression methodology consists of inserting the wavelet coefficients of a decomposed signal in the details region of a wavelet transformed image at the finest scale (i.e., the highest frequency sub-bands: horizontal details, vertical details, or diagonal details) according to a spiral way. The mixture is afterwards compressed using the well-known SPIHT algorithm (Set Partitioning In Hierarchical Trees). This process is inverted by decoding the mixture, then separating the signal from the image using a separation function applied to the insertion detail sub-band area. Next, the signal and image are reconstructed using inverse wavelet transformation followed by a dequantization step. Figure 1 illustrates the corresponding compression scheme. Results: The proposed method was evaluated on medical images with biomedical signals. The experimental results obtained show that this method provides better performance compared to the basic version based on inserting the signal samples in the spatial domain of the image to the encoding phase. This is confirmed by an important obtained improvement in terms of PSNR (Peak Signal to Noise Ratio) and PRD% (Mean Square Difference).
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Geographic Information Systems as a promising area of Education and Scientific research in Qatar
More LessGeographic information systems (GIS) (also known as Geospatial information systems or Geotechnology) are computer software and hardware systems designed to capture, store and manipulate all types of geographical data, as well as analyze, manage, and display geographic information for informing decision making. Users of GIS range from communities, research institutions, environmental scientists, health organisations, land use planners, businesses, and government agencies at all levels. Numerous examples of applications of GIS are available in many different journals and are frequent topics of presentations at conferences in the natural and social sciences. For a long time, GIS has been a well-established and independent discipline throughout American and European Universities; however, there is no single University in the Arab World or even in the Middle East--as far as the author knows--that offers an undergraduate program for this important discipline. Qatar can be the pioneer in this field in the region by offering such a program through Qatar University or any higher education institute in the state. The benefits of opening such a program are numerous to be calculated. Qualified human resources in the field of GIS are in high demand not only in the region but at international level as well. The U.S. Department of Labor has designated Geotechnology (GIS) as one of the three "mega-technologies" of the 21st century—right up there with Nanotechnology and Biotechnology. Opening GIS undergraduate program in Qatar will make the state The "Kaaba" of this science in the region and will attract students from different states, which will generate scientific and financial revenue. Moreover, the host institute of this suggested program can establish an international research centre for GIS to carry out studies for the benefit of the region and beyond. Implementing such a proposal will have great impact on the Computing and Information Technology Research discipline, which is one of Qatar's core research areas.
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RFID distributed antenna systems for intelligent airport applications
Authors: Abdelmoula Bekkali and Abdullah KadriRecent developments in radio frequency identification (RFID) technology have enabled the aviation industry to benefit from its huge potential to solve issues related to baggage mishandling and to improve passenger journeys. The International Air Transport Association (IATA) estimates that more than $733 million savings by airlines alone can be realized through RFID adoption when fully implemented in the top 200 airports. Despite the obvious benefits of RFID technology in airport industry service applications, potential implementation obstacles and technical deployment challenges have to be overcome for effective, low cost and reliable passive RFID-based baggage handling and passenger asset monitoring systems. In the existing RFID system, where the RFID readers are usually placed on the conveyors, the reliable read range is often limited to a few meters. Location is then inferred from the last portal a tag is read at. In addition, the RFID tags reading accuracy varies from 97-99% in most implemented systems. This work aims at improving airport efficiency and security through real-time locating and tracking of both passengers and baggage within airport facilities. We propose to apply the concept of optical distributed antenna systems (DAS) to RFID, to develop an intelligent, adaptive, and self-organizing passive RFID real-time locating system (RTLS), suitable for deployment in airports. This system can provide reliable coverage over a wide area using only few RFID antennas. Our system will have the following characteristics and advantages. Firstly, the RFID DAS system will allow users to rapidly identify all tags and collect information with a reading tag accuracy of 100% compared to ~90-99% for the existing implemented RFID system. And thus, it can eliminate the error of manual operation. Secondly, the interrogation area or the reader coverage is greatly expanded up to 20 meters compared to 3 meters range of the existing system. Thirdly, in addition to baggage handling, the system can also track passengers and airport staff and devices. Finally, this system will provide a glimpse of the great potential returns that will support the smart airport vision.
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Everything happens somewhere: The role of geospatial analyses in government, environmental planning and research
Authors: Robert Arden Ross, Jurgen Foeken, Jeremy Jameson, Christian Strohmenger and Eric FebboWith expansion in the fields of urbanization, technical development and industrialization, Qatar faces the challenge of advancing urban and industrial development while ensuring effective safety and environmental management. Whether assessing environmental quality, the impact of a metro system, or emergency response planning, decision making relies on the integration of disparate sources of data. Geospatial referencing provides a unifying framework from which civil engineering, public policy and research decisions can be made within a web-based environment. The foundation of a geospatial reference system should be the surface geology of the country and its marine habitats. In addition to bedrock geology, the database should include features such as lineaments, drainages, land movement studies, karst features and soil types. Marine data include biota, sediment types, water quality, hydrodynamic data, and ecological sensitivity. In an arid climate, where water resources are key considerations, it is important to have a consistent geological framework for both surface and near surface geology. Accordingly, the near surface, aquifers should have a sequence stratigraphic analysis. Within a web-based infrastructure, geospatial data can be accessible to many users with access controls set by data owners and can be appropriated to user needs. Such a geodatabase mapping tool may combine 3 functions: 1) database/resource-a query tool for government, industry and the public, 2) an evaluation tool allowing the end user forward modeling/impact assessment and cause/effect analysis capability, 3) a communication tool for decision making--where results from a query may be circulated to a linked forum of specialists for consideration. The emergence of web-based, spatial referencing GIS tools shows great promise in many key aspects of public policy and research, including data storage, data analysis, and decision making. The vision is the implementation of integrated diverse multi-scale, multi-disciplinary spatial data from geological rock samples to cutting edge multi-spectral satellite imagery for use in solving complex geological, geophysical, geotechnical and environmental problems.
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Dynamic Health Level Seven Packetizer for on-the-fly integrated healthcare enterprises in disaster zones
Authors: Uvais Qidwai, Junaid Chaudhry and Malrey LeeThe advent of standards such as IEEE 11073 for device connectivity, Health Level Seven (HL7) etc., provide an assimilating platform for medical devices and seamless dataflow among modern health information systems (HIS). However, to date, these standards are either not widely accepted or lack the support of 'on-the-fly' formation of HIS in a disaster zone. In a situation where hybrid medical (standard compliant and the otherwise) devices are in operation, incomplete and ambiguous data can lead to fatal misconduct on the part of technology. In order to eliminate this problem, we propose a HL7 compliant policy engine in support of HL7 Reference Information Model (RIM). The policy engine is used for rich policy expression, vivid XML policies for HL7 compliant devices, and performance enhancement. Due to the dynamic nature of on-the-fly HIS in a disaster zone, it is very costly to manage the change and keep track of authentic HIS devices. We use Java language to extend the HL7 RIM in order to create/modify policies instead of scripting languages to overcome the complexity and interoperability.
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Distributed rendering of computer-generated images on commodity compute clusters
Authors: Othmane Bouhali and Ali SheharyarRendering of computer-generated imagery (CGI) is a very compute-intensive process. Rendering time of individual frames may vary from a few seconds to several hours depending on the scene complexity, output resolution and quality. For example, a short animation project may be about two minutes in length. It comprises 3600 frames at 30 frames per second (fps). An average rendering time for a fairly simple frame can be approximately 2 minutes, resulting in a total of 120 hours to render a simple 2-minute animation. Fortunately, animation rendering is a highly parallelizable activity as frames can be computed independently of each other. A typical animation studio has a render farm, a sophisticated cluster of special computers (nodes) used to render 3D graphics. By spreading the rendering of individual frames across hundreds of machines, the overall render time is reduced significantly. Researchers and students in a university do not usually have a render farm available. Some universities have general-purpose compute clusters but these are used mainly for running complex numerical simulations. Although rendering on these clusters is doable but it usually involves using generic queue manager (e.g. Condor, Portable Batch System PBS) rather than specialized render queue manager (e.g. DrQueue, Qube!), due to which rendering workflow becomes tedious. This paper presents a solution to create a render frame-like environment using compute-cluster resources and most importantly by using the existing render queue manager. This way, researchers and students can be presented with a rendering environment similar to any animation studio. Several benchmarking results will be presented to prove the potential benefit of this method in terms of execution time, simplicity and portability.
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A new generic approach for information extraction
Authors: Samir Elloumi, Ali Jaoua, Fethi Ferjani, Nasredine Semmar, Jihad Al-Jaam and Helmi HammamiAutomatic Information Extraction (IE) is a challenging task because it involves experts' skills and requires well developed Natural Language Processing (NLP) algorithms. Moreover, IE is domain dependent and context sensitive. In this research, we present a general learning approach that may be applied for different types of events. As a matter of fact, we observed that even if a natural language text containing a target event is apparently unstructured, it may contain a segment that we can map automatically into a structured form. Segments representing the same kind of events have a similar structure or pattern. Each pattern is composed of an ordered sequence of named entities, keywords and articulation words. Some generic named entities like organizations, persons, locations, dates, and grammatical annotations are generated by an automatic part of speech identification tool. During the learning step, each relevant segment is manually annotated with respect to the targeted entities (roles) structuring an event of the ontology. IE is processed by associating a role with a specific entity. By alignment of generic entities to specific entities, some strings of a text are automatically annotated. The alignment between patterns and a new text is not often guaranteed because of the writing styles diversity that may be detected in the news. For that reason, we have proposed soft matching between reduced formats with the objective of maximal utilization of pattern expressiveness. In several cases, this reduced format successfully allows the assignment of the same role to similar entities cited in the same side, with respect to some keywords or cue words. The experiment results are very promising since we've obtained 76.90 % as an average recognition rate.
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A fairness-based preemption algorithm for LTE-Advanced
Authors: Mehdi Khabazian, Osama Kubbar and Hossam HassaneinOne of the radio resource management (RRM) functionalities in LTE systems, call admission control (CAC) is employed to control the number of LTE bearer requests in order to maintain the quality of service (QoS) of the admitted bearers. However, no quality guarantee can be provided due to the inherently dynamic nature of wireless communication. For example, during congestion periods when several communications experience poor channel quality or high mobility, it is highly possible that the network cannot maintain its bearers' QoS requirements. Thus, preemption schemes may be employed to alleviate the situation. As a result, resource preemption mechanism and its fairness are prominent issues as they may directly affect applications' QoS in the higher layers, as well as other network attributes such as generated revenue. In general, preemption is unavoidable in two circumstances, namely, to manage the resources among bearers when the network is overloaded as a congestion control mechanism, or, to allocate a high-priority bearer request while sufficient resources are not available. In this study, we propose a preemption technique by which each an established bearer may be preempted according to its priority as well as the amount of extra allocated resources compared to its basic data rate. We define the contribution of each bearer in the preemption through a contribution metric with tuning parameters which is presented in the form of Cobb-Douglas production function. We compare the fairness of the proposed scheme with a traditional preemption scheme by means of two well-known fairness indices, i.e. Jain's index and min-max index. We also discuss its effect on bearers' blocking and dropping probability and the total generated revenue. Through a simulation approach, we conclude substantial improvements in preemption fairness when compared to the traditional approach. We discuss that the proposed scheme does not affect the main performance measurements of the network, i.e. the bearers' blocking and dropping probabilities due to congestion. We also show that the preemption contribution metric can be effectively used by the service providers to vary the total generated revenue.
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Using information extraction to dynamically create multimedia tutorials
Authors: Amal Dandashi, Jihad Mohamad Aljaam, Massoud Mwinyi, Sami Elzeiny and Ali M. JaouaBackground and Objectives: Multimedia tutorials are often useful for children with disabilities as they are better able to understand new concepts with the use of lessons that engage their senses. These tutorials should include images, sounds and videos. We propose a system to dynamically generate multimedia tutorials that can easily be customized by the instructor, with the use of domain specific information extraction. Methods: Text processing is performed with a stemming algorithm, after which formal concepts analysis is used to extract pre-specified keywords. A formal concept is represented as a hierarchical lattice structure and in this study is applied to the animal kingdom domain. Ontology-based information extraction is then performed, where multimedia elements are extracted online and mapped, by querying the Google image database. Results: The proposed system allows for automated, speedy and efficient dynamic generation of multimedia customized tutorials. Conclusions: This system automates the tutorial generation process and gives disabled children the opportunity to learn with tutorials designed to suit their intellectual needs.
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Information aspects of quantum systems
More LessInformation dynamics of different quantum systems under influence of both a phonon bath in contact with the resonator and irreversible decay of the qubits is considered. The focus of our analysis is devoted to multilevel atoms and the effects arising from the coupling to the reservoir. Even in the presence of the reservoirs, the inherent entanglement is found to be rather robust. Due to this fact, together with control of system parameters, the system may therefore be especially suited for quantum information processing. Information entropy, entropy squeezing and wehrl entropy are discussed as indicators of entanglement. Our findings also shed light on the evolution of open quantum many-body systems.
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Interference-aware random beam selection schemes for spectrum sharing systems
Authors: Mohamed Abdallah, Khalid Qaraqe and Mohamed-Slim AlouiniSpectrum sharing systems have been recently introduced to alleviate the problem of spectrum scarcity by allowing secondary unlicensed networks to share the spectrum with primary licensed networks under acceptable interference levels to the primary users. In this work, we develop interference-aware random beam selection schemes that provide enhanced performance for the secondary network under the condition that the interference observed by the receivers of the primary network is below a predetermined/acceptable value. We consider a secondary link composed of a transmitter equipped with multiple antennas and a single-antenna receiver sharing the same spectrum with a primary link composed of a single-antenna transmitter and a single-antenna receiver. The proposed schemes select a beam, among a set of power-optimized random beams, that maximizes the signal-to-interference-plus-noise ratio (SINR) of the secondary link while satisfying the primary interference constraint for different levels of feedback information describing the interference level at the primary receiver. For the proposed schemes, we develop a statistical analysis for the SINR statistics as well as the capacity and bit error rate (BER) of the secondary link.
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Implementation and evaluation of binary interval consensus on the TinyOS and TOSSIM simulator
Authors: Abderrazak Abdaoui, Tarek mohamed El-Fouly and Moez DraiefThis work considers the deployment of the binary consensus algorithm in wireless sensor networks (WSN). This algorithm is applied for the evaluation of the average measurement with the presence of a faulty/attacked node. As this algorithm has been tested theoretically, we deploy it in real life, including its distributed and routing features. In this paper, we propose the development, under simulation environment, of a distributed binary consensus algorithm. We formulate the algorithm into nesC derived from C language and running over the tiny operating system (TinyOS). The implementation was tested on sensor nodes using the TinyOSSimulator (Tossim) for a large number of nodes N and a testbed with a limited number of nodes. In performance evaluation, we considered the analysis of the average convergence time for node states to a consensus value. As in analytical results, in the simulations we applied the distributed algorithm for fully connected, paths, cycles Erdos Reny random, and starr-shaped graph topologies. Our achieved results of simulation and hardware implementations are consistent with theory.
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A neural network based lexical stress pattern classifier
Authors: Mostafa Shahin, Beena Ahmed and Kirrie BallardBackground and Objectives: In dysprosodic speech, the prosody does not match the expected intonation pattern and can result in robotic-like speech, with each syllable produced with equal stress. These errors are manifested through inconsistent lexical stress as measured by perceptual judgments and/or acoustic variables. Lexical stress is produced through variations in syllable duration, peak intensity and fundamental frequency. The presented technique automatically evaluates the unequal lexical stress patterns Strong-Weak (SW) and Week-Strong (WS) in American English continuous speech production based upon a multi-layer feed forward neural network with seven acoustic features chosen to target the lexical stress variability between two consecutive syllables. Methods: The speech corpus used in this work is the PTDB-TUG. Five females and three males were chosen to form a training set and one female and one male for testing. The CMU pronouncing dictionary with lexical stress levels marked was used to assign stress levels to each syllable in all words in the speech corpus. Lexical stress is phonetically realized through the manipulation of signal intensity, the fundamental frequency (F0) and its dynamics and the syllable/vowel duration. The nucleus duration, syllable duration, mean pitch, maximum pitch over nucleus, the peak-to-peak amplitude integral over syllable nucleus, energy mean and maximum energy over nucleus were calculated for each syllable in the collected speech. As lexical stress errors are identified by evaluating the variability between consecutive syllables in a word, we computed the pairwise variability index ("PVI") for each acoustic measure. The PVI for any acoustic feature f_i is given by: PVI_i= (f_i1-f_i2)/(( f_i1+f_i2)/2)(1), where f_i1,f_i2 are the acoustic features of the first and second syllables consecutively. A multi-layer feed forward neural network which consisted of input, hidden and output layers was used to classify the stress patterns in the words in the database. Results: The presented system had an overall accuracy of 87.6%. It correctly classified 92.4% of the SW stress patterns and 76.5% of the WS stress pattern. Conclusions: A feed-forward neural network was used to classify between the SW and WS stress patterns in American English continuous speech with overall accuracy around 87 percent.
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Accessibility research efforts needed in Qatar
Authors: David Banes and Erik ZetterströmBackground and Objectives: Mada, Qatar's Center for Assistive Technology, is a non-profit organization that strives to empower and enable people with disabilities through ICT. During late 2011 and early 2012, Mada conducted research to identify barriers to accessibility in Qatar Methods: In the survey, the key groups of respondents were identified including disabled people themselves. A combination of quantitative and qualitative methods were applied. The results were validated through the Assistive Technology Research Forum formed by Mada, which analyzed the survey results and gave additional input. These were further validated in discussions with disabled people's organizations as part of the input to the Mada future strategy. Results: The survey indicated the following major results: *People with visual impairment had both a high awareness and usage rate. *People with physical and hearing disabilities were very aware of available assistive technology but the usage rate was still low. *People with learning disabilities were not aware of available assistive technology and hence the usage rate was unsurprisingly low. Based on these findings, the AT Research Forum identified the following priority areas, which could potentially have a very high impact on barriers to accessibility in Qatar: *Arabic crowd sourced free symbol set *Improved statistical source on needs and a registry for easy user communication *Development of a free Arabic text to speech. *Wayfinding technologies for the blind incorporating enhanced technologies in emergency situations *Research into enhanced literacy amongst the deaf community when provided with text based communication solutions In addition, it was possible to highlight some crucial issues that which impeded uptake of technology, including: *The lack of accessible Arabic digital content *The limitations of current OCR technologies *The lack of useful Arabic continuous speech *Arabic word prediction and the lack of a significant available corpus Conclusions: The areas identified are fundamental projects with a very high impact in Qatar. They would best be addressed through collaboration and funding. Such collaborations bridge the private and academic sectors with specialist input from an organization supporting disabled people such as Mada.
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Energy saving mechanism in multiantenna LTE systems
Authors: Reema Imran, Zorba Nizar, Osama Kubbar and Christos VerikoukisLong Term Evolution (LTE) supports closed-loop MIMO techniques to improve its performance; however, in order to exploit the multiuser MIMO channel capabilities, the design of an efficient MAC scheme that supports MU-MIMO is essential and is still an open issue in the literature. This work proposes a novel, energy-efficient MAC scheme for LTE, which aims to achieve simultaneous downlink transmissions to multiple users through the deployment of a low-complexity beamforming technique at the physical layer. Our proposed scheme benefits from the multiuser gain of the MIMO channel and the multiplexing gain of the Multibeam Opportunistic Beamforming (MOB) technique, not only to improve the system throughput but also to provide an energy efficient wireless network. We show that our proposed scheme can provide good energy saving performance at the eNB, where the mathematical expressions for performance evaluation in terms of throughput and saved energy are also presented.
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RAFNI: Robust analysis of functional neuroimages with non-normal alpha-stable errors
Authors: Mohammed El Anbari, Halima Bensmail, Samreen Anjum and Othamne BouhaliOne of the most ambitious goals of Qatar in the next few years is to become a country based on scientific and technical researches instead of being dependent on hydrocarbons. To this end, Qatar Foundation has established a number of high caliber universities and institutes. In particular, Qatar Computing Research Institue (QCRI) is forming a scientific computing multidisciplinary group with a focus on data mining machine learning, statistical modeling and bioinformatics. We now are able to satisfy the computational statistics needs of a variety of fields, especially of biomedical researchers in Qatar. Functional magnetic resonance imaging (fMRI) is a noninvasive neuroimaging method that is widely used in cognitive neuroscience. It relies on the measurement of changes in the blood oxygenation level resulting from neural activity. The technique is widely used in cognitive neuroscience. fMRI is known to be contaminated by artifacts. Artifacts are known to have fat tailed distributions and are often skewed therefore modeling the error using a Gaussian distribution is not enough. In this paper we introduce RAFNI, an extension of AFNI, which is an fMRI open source software for the analysis of functional neuroimages. We are model the error introduced by artifacts using alpha-stable distribution. We demonstrate the applicability and efficiency of stable distributions on real fMRI. We show that the alpha-stable estimator gives better results than the OLS-based estimators.
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Model-free fuzzy intervention in biological phenomena
Authors: Hazem Nounou, Mohamed Numan Nounou, Nader Meskin and Aniruddha DattaAn important objective of modeling biological phenomena is to develop therapeutic intervention strategies to move an undesirable state of a diseased network towards a more desirable one. Such transitions can be achieved by the use of drugs to act on some genes/metabolites that affect the undesirable behavior. Biological phenomena are complex processes with nonlinear dynamics that cannot be perfectly described by a mathematical model due to several challenges such as the scarcity of biological data. Therefore, the need for model-free nonlinear intervention strategies that are capable of guiding the target variables to their desired values often arises. Addressing such a need is the main focus of this work. In many applications, fuzzy systems have been found to be very useful for parameter estimation, model development and control design of nonlinear processes. In this work, a model-free fuzzy intervention strategy (that does not require a mathematical model of the biological phenomenon) is proposed to guide the target variables of biological systems to their desired values. The proposed fuzzy intervention strategy is applied to two biological models: a glycolytic-glycogenolytic pathway model and a purine metabolism pathway model. The simulation results of the two case studies show that the fuzzy intervention schemes are able to guide the target variables to their desired values. Moreover, sensitivity analyses are conducted to study the robustness of the fuzzy intervention algorithm to variations in model parameters, and contamination due to measurement noise, in the two case studies, respectively.
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Multiscale denoising of biological data: A comparative analysis
Authors: Mohamed Nounou, Hazem Nounou, Nader Meskin and Aniruddha DattaWith the advancements in computing and sensing technologies, large amounts of data are collected from various biological systems. These data are a rich source of information about the biological systems they represent. For example, time-series metabolic data can be used to construct dynamic genetic regulatory network models, which can be used not only to better understand the interactions among different genes inside a cell, but also to design intervention strategies that can cure or manage major diseases. Also, copy number data can be used to determine the locations and extent of aberrations in chromosome sequences which are associated with many diseases such as cancer. Unfortunately, measured biological data are usually contaminated with errors that mask the important features in the data. Therefore, noisy biological measurements need to be filtered to enhance their usefulness in practice. Conventional linear low-pass filtering techniques are widely used because they are computationally efficient and can be implemented online. However, they are not effective because they operate on a single scale, meaning that they define a specific frequency, above which all features are considered noise. Real biological data possesses multiscale characteristics, i.e., may contain important features having high frequencies (such as sharp changes) or noise occurring at low frequencies (such as correlated or colored noise). Filtering such data requires multiscale filtering techniques that can account for the multiscale nature of the data. In this work, different batch as well as online multiscale filtering techniques are used to denoise biological data. These techniques include standard multiscale (SMS) filtering, online multiscale (OLMS) filtering, translation invariant (TI) filtering, and boundary corrected TI (BCTI) filtering. The performances of these techniques are demonstrated and compared to those of some conventional low-pass filters (such as the mean filter and the exponentially weighted moving average filter) using two case studies. The first case study uses simulated dynamic metabolic data, while the second case study uses real copy number data. Simulation results show that significant improvement can be achieved using multiscale filtering over conventional filtering techniques.
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A hybrid word alignment approach to build bilingual lexicons for English-Arabic machine translation
In this paper we propose a hybrid approach to align single words, compound words and idiomatic expressions from English-Arabic parallel corpora. The objective is to develop, improve and maintain automatically translation lexicons. This approach combines linguistic and statistical information in order to improve word alignment results. The linguistic improvements taken into account refer to the use of an existing bilingual lexicon, named entity recognition, grammatical tag matching and detection of syntactic dependency relation between words. Statistical information refers to the number of occurrences of repeated words, their positions in the parallel corpus and their lengths in terms of number of characters. Single-word alignment uses an existing bilingual lexicon, named entities and cognate detection and grammatical tag matching. Compound word alignment consists of establishing correspondences between the compound words of the source sentence and the compound words of the target sentences. A syntactic analysis is applied to the source and target sentences in order to extract dependency relations between words and to recognize compound words. Idiomatic expression alignment starts with a monolingual term extraction for each of the source and target languages, which provides a list of sequences of repeated words and a list of potential translations. These sequences are represented with vectors which indicate their number of occurrences and the number of segments in which they appear. Then, translation relations between the source and target expressions are evaluated with a distance metric. We have evaluated the single and multiword expression aligners using two methods: A manual evaluation of the alignment quality on 1000 pairs of English-Arabic sentences and an evaluation of the impact of this alignment on the translation quality of a machine translation system. The obtained results showed that these aligners, on the one hand, generate a translation lexicon with around 85% precision, and on the other hand, report a gain in BLEU score of 0.20 for the translation quality.
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Feature-based method for offline writer identification
Authors: Somaya Al-Maadeed and Abdelaali HassaineWriter identification consists of identifying the writer of a certain handwritten document and is of high importance in forensic document examination. Indeed, numerous cases over the years have dealt with evidence provided by handwritten documents such as wills and ransom notes. Automatic methods for writer identification can be divided into codebook-based and feature-based approaches. In codebook-based approaches, the writer is assumed to act as a stochastic generator of graphemes. The probability distribution of grapheme usage is used to distinguish between writers. Feature-based approaches compare the handwritings according to some geometrical, structural or textural features. Feature-based approaches prove to be efficient and are generally preferred when there is a limited amount of available handwriting. Therefore, we are more interested in this study in this category of approaches. Writer identification is performed by comparing a query document to a set of known documents and assigning it to the closest document in term of similarity of handwriting. This is done by extracting characterizing features from the documents including: directions, curvatures, tortuosities (or smoothness), chain codes distributions and edge based directional features. These features correspond to probability distribution functions (PDF) extracted from the handwriting images to characterize writer individuality. When matching a query document against any other document, the ¬χ2 distance between their corresponding features is computed. The smaller the distance, the more likely the two documents are written by the same writer. Therefore, the identified writer is the one of the document with the smallest distance to the query document. The writer is said to be correctly identified when the identified writer corresponds to the actual writer of the query document. The performance has been evaluated on the IAM handwriting dataset, with chain code based features generally outperforming the other features reaching 71% correct identification rate. The combination of all the features lead to 76% correct identification rate. The proposed system also won the music scores writer identification contest reaching 77% identification rate. The proposed method automatically extracts features used by forensic experts in order to identify writers of handwritten document. The results show that the method is efficient and language-independent.
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e-Security: Methodologies and approaches for the United Arab Emirates Online Business
By Fahim AkhterBackground and Objectives As e-commerce functions in a more perplex and conjoint environment than traditional businesses, a higher degree of trust is required between the users and online businesses. Uncertainties inherent to the current e-commerce environment give rise to a lack of trust and reliability in e-commerce partnerships, thereby reducing confidence and creating barriers to trade. The reason why most users and businesses in United Arab Emirates (U.A.E) are still skeptical about e-commerce involves perceived security risks associated with conducting online business. Online users consciously or subconsciously analyze the provided level of security based on their experience in order to decide whether to conduct business with the specific company or else to move on to the next company. There is a need for a better understanding of hostile environments fueled by financially-motivated, targeted cyber threats that affect consumer's decision-making behavior. The purpose of the study is to identify the factors that support the implementation and acceptance of security in e-commerce among corporations in throughout the United Arab Emirates. The study will explored the common cyber attacks that threaten the U.A.E. online businesses and will describe methodologies and approaches that can be developed to respond to those threats. Methods: A descriptive web-based survey will be adopted as an appropriate method to collect initial data from users due to its cost effectiveness, rapid turnaround, high response volume, and ability to cover a large geographical area. The combination of questions both close- and open-ended will be selected. The URL of the survey will be electronically distributed among participant using mailing lists from the Dubai chamber of commerce. Results and Conclusions: Statistics of participants from seven states of the U.A.E will be accessed and discussed here. Complete responses will be chosen out of anonymous responses for further analysis. Quantitative data will be fed into a statistical framework for researchers to understand and analyze the relationship among different responses.
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Detecting forgeries and disguised signatures in online signature verification
Authors: Abdelaali Hassaine and Somaya Al-MaadeedOnline signatures are acquired using a digital tablet which provides all the trajectories of the signature, as well as the variation in pressure with respect to time. Therefore, online signature verification achieves higher recognition rates than offline signature verification. Nowadays, forensic document examiners distinguish between forgeries, in which an impostor tries to imitate a given signature of another person and disguised signatures, in which the authentic author deliberately tries to hide his/her identity with the purpose of denial at a later stage. The disguised signatures play an important role in real forensic cases but are not considered in recent literature. In this study, we used online signatures acquired using a WACOM Intuos4 digitizing tablet with a sampling rate of 200Hz, a resolution of 2000 lines/cm and a precision of 0.25mm. The pressure information is available in 1024 levels. Online signatures contain a set of samples, each sample corresponds to the point coordinates on the digitizing tablet along with the corresponding pressure (Xt; Yt; Pt) where t corresponds to time. From those three basic signals, four other are extracted: distances, angles, speeds and angular speed. In order to compare the questioned signature with the reference signature, the differences between their corresponding features are computed at both the signal level and the histogram level. This study has been evaluated on ICDAR2009 signature verification competition dataset and a new dataset of online signatures collected at Qatar University (QU-dataset). This dataset contains signatures of genuine signatures, forgeries and disguised of 194 persons. To the extent of our knowledge, this dataset is the only one that contains disguised online signatures. The best individual performing feature for the ICDAR2009 dataset is the pressure histogram difference which reaches 8% equal error rate (EER). The pressure signal difference is the best individual performing feature for the QU-dataset (29% EER). The combination of features led to 7% EER on the ICDAR2009 dataset and 22% EER on the QU-dataset. This online signature verification system deals with both forgeries and disguised signatures. Several features have been proposed and combined using different classifiers reaching promising performance for disguised signatures detection.
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