Qatar Foundation Annual Research Conference Proceedings Volume 2014 Issue 1
- تاريخ المؤتمر: 18-19 Nov 2014
- الموقع: Qatar National Convention Center (QNCC), Doha, Qatar
- رقم المجلد: 2014
- المنشور: ١٨ نوفمبر ٢٠١٤
121 - 140 of 480 نتائج
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Synthesizing New Anodes From Qatalum's 1st Cut Spl
المؤلفون: Abdullah Hani Holozadah, Aboubakr Abdullah, Mufeed Odeh and Chris Devadas,Aluminum industry produces hundreds of tons of spent pot lining (SPL) waste every year. SPL is classified into two types: 1st cut and 2nd cut. The 1st cut SPL which is the material under study in this work is mainly composed of graphite (~ 60%), ceramic material and Al metal (~ 10%). On contrary with the 2nd Cut SPL, there is a consensus that the 1st cut SPL is a hazardous material and must be treated before dumping it in a landfill. Recycling it will be more beneficial if possible. The aim of this study is using the extracted graphite material from the 1st Cut SPL to produce new carbonaceous anodes for the Al molten electrolytic cells. The idea is to mix the extracted graphitic material with new binder materials e.g. o-phenylenediamine (C6H4(NH2)2), polyaniline or phosphorous (also a mixture of two or all of them) to increase the thermal and chemical stability and electrical conductivity of these new anodes compared to the currently used anodes in Qatalum (Qatalum uses 70% petroleum coke + 30% Coal Tar Pitch (CTP) as a binder). This might result in extending the life time of the carbon anodes and decrease the number of carbon dioxide kilograms that are released per a ton of produced Al metal. For comparison, the anodes were synthesized using the extracted graphite material from the 1st cut SPL, a commercial one and a petroleum coke (PC). The thermal properties were characterized using thermal gravimetric analysis. Also, the electrical conductivity of the new produced anodes was measured. In addition, the impedance spectra for the new anodes were measured at different temperatures and compared to the currently used anodes at Qatalum. Results have shown that anodes prepared from 50% of the extracted graphite with 10% of the commercial graphite and 40% coal tar pitch have impedance of one order of magnitude lower than the currently used anodes in Qatalum.
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The Use Of Wireless Sensor Networks In Agricultute A Tool For A Sustainable Food Supply In The Arab World
المؤلفون: Mustafa Ibrahim AliTHE USE OF WIRELESS SENSOR NETWORKS IN AGRICULTUTE A TOOL FOR A SUSTAINABLE FOOD SUPPLY IN THE ARAB WORLD In this paper some ideas of how to apply the technological advancement of the wireless sensor networks (WSN) in agriculture as a tool for food security is discussed. This will include some examples where the technology can be applied, what changes can this technology brings to the traditional farming, which can help within the solution of the Arab World food security problems. This will help the region to develop and be part of the global strategy for the World food security. WSN features of having a low power consummation nature with different options of using different energy sources will make it as the just technology suitable in a remote and less or without infrastructural bases environment for many countries within the region. The applications of WSN which are suitable for the purpose will be discussed. Keywords: WSN, Food Security, Agriculture in Arab region, WSN Farmer Kits Tool, Energy Sources. Introduction Arabic countries are naturally rich, many countries within the region have a wide virgin land. But unfortunately some of these countries have been a focus in term of food shortages for long time which cause by many factors like land degradation, water crisis, land deals, climate change, agricultural disease, governing system, wars, population growth, land use change, living style change, high prices and lack of technology. As technology has rational parts in solving the most difficult problems for today's society, WSN can be applied in agriculture to reduce or solve this problem. Use of WSN in Agriculture as a solution As traditional farming is the lead in the region, people use their own human sense to perceive the surrounding to investigate the soil and predict the weather. But the remote sensing of the WSN as an activity of recording, observing, perceiving objects or events, wirelessly these happenings are processes and analyzed in a real time. The idea of applying this technology is to be adopted in different applications shortly can be said here. *Soil Investigation by using the specialized soil test sensor detectors to determine the fertility of soil nutrient deficiencies, elements like Nitrogen is very important for plants. *Weather Prediction by using a web data from WSN can be transmitted enabling a remote online interactive retrieval access, and then these data can be shared with the farmers. *Detection of ground water using WSN the level and the amount of sufficient water can be detected before planting. *Using the WSN the water and the area can be controlled during irrigation which will help in reducing the energy consumption. *Food storage system will be advanced by the use of WSN in knowing usage validity time and the space of storing. *Knowing where how and when to deliver what kind of product by using WSN will help in the logistical distribution of crops. *Farming Dissemination by using an integrated WSN tool kit messages can be disseminated.
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Source Term Modeling Of Cryogenic Liquid Vapor Formation By Experimental Investigation - Evaporation Regime And Convection Effect
المؤلفون: Asma Sadia, Waqas Nawaz, Tomasz Olewski and Luc VechotSafe handling, storage and transportation of Liquefied Natural Gas (LNG) has been the root concern in the process industry due to the growing demand for ecological and clean alternative energy namely natural gas. Due to economic advantages in transportation, natural gas is transported in the liquid form. This calls for a thorough research in LNG safety due to its hazardous flammability properties. The study of consequence of loss of containment of LNG is critical to the risk assessment for LNG facilities. This is especially important for Qatar since it is the largest exporter of LNG accounting for about 32 % of the global LNG exports as of 2013. It is important to conduct fundamental and applied research to enrich the knowledge of LNG related safe operations. It is necessary to be able to model consequences of accidental LNG spill to assure sustainability of its production. The loss of containment of LNG leads to the generation of flammable vapor that gets dispersed in the atmosphere. This phenomenon is the same for any cryogenic liquid and is usually split into two stages: vapor formation (source term) and atmospheric dispersion. The vapor formation rate will be determined by its storage conditions (temperature and pressure) and the condition of the release (geometry and location of the dike/bund and the release point, ground temperature and weather data). During the dispersion stage, the behavior of the fluid is controlled by the atmospheric conditions (atmosphere stability class, wind speed, air temperature). The division of the phenomenon into two stages is a convenient approach from modeling perspective. Historically, less attention has been given to source term modeling. Simultaneously, the output of source term is the input into dispersion modeling, and thus, if the former is not accurately estimated the latter cannot be. Moreover, source term modeling is very complex and it cannot be well defined and validated since there is a lack of useful experimental data. This work aims at filling the gap and improving the experimental database. The scope of this part of project includes study of the convective heat flux to the cryogenic liquid pool, which is a part of source term model and study of evaporation regime. It also looks at different scales (small and medium) of experiments and the effect of spilled liquid composition. Currently, experimental results are available for spill of liquid nitrogen at small (0.001 m3) and medium scale (0.023 m3). The aim is to study the transition to evaporation regime and to validate existing evaporation models. It was determined that at the small scale five of the six models were valid but at the medium scale only one model gave close prediction. The deviation increase with scale up, which could be expected as most of the existing models were developed utilizing small scale experimental data. In near future, more investigations will be carried out at the large scale for better understanding of the phenomena.
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Role Of Aromatics In Synthetic Fuels
المؤلفون: Muaz Selam, Wajdi Ahmed, Moiz Bohra, Hafis Mohamed, Rehan Hussain and Nimir ElbashirThis paper describes our investigation into the effects of adding aromatic compounds to synthetic aviation fuels on the performance of these fuels. The work was done as an undergraduate research (UREP) project and was an extension to our group's previous studies which were aimed at characterizing blends of conventional and synthetic aviation fuels [1] and identifying optimum paraffinic building blocks for SPK [2]. Aromatics play a key role in aviation fuels as they enhance the density and elastomer swelling properties of these fuels. However, they are absent from synthetic gas-to-liquids (GTL) derived aviation fuels such as synthetic paraffinic kerosene (SPK) and thus must be added in from another source. In the first part of this study, standard analytical tests were conducted on blends of SPK and aromatic additives (styrene and Shell A150) in different concentrations from 0 to 25 % to measure certain fuel properties (i.e. density, flash point, freezing point, heat content and viscosity) using relevant ASTM procedures. The measured properties were then compared with the desired values for certification according to the ASTM D-1655 and D-7566 standards for conventional and hybrid (i.e. mixtures of oil-derived and synthetic fuels obtained from either natural gas or coal) jet fuels, respectively. In particular, ASTM D-7566 specifies the use of the 50-50 synthetic fuel blend with jet A-1; our group's efforts are aimed at increasing the workable synthetic ratio in the fuel. The experimental work was conducted in the Fuel Characterization Lab at Texas A&M University at Qatar. The data generated from these experiments was used to identify correlations between blend compositions and properties. In the second part of this study, small amounts (i.e. 1 vol %) of specialty aromatic compounds (such as benzaldehyde) were added to the blends from the first part of the study, specifically to enhance the elastomer swelling characteristics of these blends. This is a crucial property of aviation fuels as it ensures a tight seal in fuel tanks, thus preventing potentially catastrophic leakages. The added aromatic compounds were identified based on a Hansen solubility parameter analysis, and it was found that their addition favorably increased both the density and elastomer swelling characteristics of the SPK. Notably, three of the blends tested outperformed the elastomer swelling characteristics of conventional Jet A-1 by about a factor of 2. With respect to freezing point, viscosity, heat content, and flash point, the performance of all of the blends tested were in agreement with ASTM standards. These experimental results demonstrate the favorability our approach to synthetic fuel design i.e. the focused introduction of additives to improve the performance of synthetic fuels to standards at par with or, in some cases, surpassing those of conventional jet fuel.
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Fiberglass Casing And Tubing In Highly Corrosive Environments
المؤلفون: Ahmed Abdul RaufThe UER formation in the Dukhan Field, Qatar has an aquifer associated with it. The formation water and sour crude associated with the formation and aquifer lead to many corrosion-related problems, and casings are being replaced at an almost bi-annual rate. Our research proposal was to replace these with fiberglass casing and tubing. Any tubing and casing that is replaced would need to withstand similar pressures and temperatures as the original steel and fulfill the same functions. Despite plenty of mechanical testing data available on fiberglass as a material, there is very little existing research on fiberglass tubing and casing. This was essential as the manufacturing and therefore composition of fiberglass varies greatly depending on the application. Therefore field-specific, quantative and mechanical research on fiberglass casing and tubing is required. Before conducting physical research, we compiled industrial advantages of fiberglass through fiberglass manufacturer guarentees and product ratings. In the laboratory, we re-established the high resistance to corrosion of fiberglass, and demonstrated comparable resistances to compressive pressure and shear of fiberglass piping to that of steel. In some cases, the fiberglass even proved to perform better and failed at a higher pressure than steel. Latex cement was used to cement the casing and tubing models together, this cement is oil wet and bonds to the inner surface of the fiberglass piping. The cement bonded very well and held even after until the piping had failed under compression. Piping made of fiberglass would not only be cheaper to transport and install, but also more resistant to corrosion, lighter to handle and easier to push into deviated or horizontal wells. (Williams 1987). Overtime, there will be a lower cost of corrosion-control and remediation. Indeed, fiberglass casing and tubing can be employed in the place of steel not only in the UER formation, but in a large number of highly corrosive environments, both down hole and on surface. The use of fiberglass instead of steel casings will not only reduce the affect on the environment due to pollutants, but also contribute to material safety and cost savings.
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Investigating New Imaging Modality: Magnetic Particle Imaging
المؤلفون: Ahmed El Ghamrawy and Steven M. WrightMagnetic Particle Imaging (MPI) is a newly found imaging modality. It utilizes superparamagnetic materials as tracers in the blood stream to obtain very high resolutions. MPI promises to have high sensitivity, high spatial resolution and no radiation compared to other imaging modalities. Most commercially available MRI tracers (used for MPI for now) are all non-harmful when compared to Iodine (used for CT scan) and Gadolinium (used for MRI). MPI research is divided into three categories: MPI scanner development, superparamagnetic materials development, and image reconstruction techniques. In this project a small scale LabView-based system will be developed for use on small lab created phantoms, using 25 nm superparamagnetic iron oxide (SPIO) particles. At first a relaxometer will be developed, the imager will come as the next step. Transmitting and receiving signals will be implemented using LabView and a National Instruments PXI-1033 Chassis. Lab-built coils will be used to send the excitation signal and receive the signal induced by those SPIO's. The objective of this project is to be introduced to a new imaging modality that can have various applications and at the same time considered safe. The system being built is considered inexpensive and shows most of the aspects of how magnetic particle imaging works, starting with the physical phenomena, superparamagnetic nanoparticle properties and relaxation, signal generation and acquisition, and an introduction to the hardware of MPI. The system can be used to introduce engineers and engineering students to the MPI physical phenomena.
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Screening Of Some Qatari Plant Extracts For Anti Fungal Activities Of Plant Pathogenic Fungi
المؤلفون: Ibtihal Mohamed and Talaat AhmadThe present study aimed to evaluate the antifungal activity of three desert plants extracts grown naturally in Qatar: (Al-rayhan) Ocimum basilicum, Shafallah (Capparis spinosa) and Qwaif(Prosopis juliflora)to study their inhibitory effect against three pathogenic fungi: Aspergillus niger, Fusarium oxysporum and Giberella baccata. Samples were collected from Qatar University farm. Filter disk method was used for antagonistic study and four chemical solvents: distilled water, n-butanol, ethyle acetate and chloroform were used to extract the plant materials. The fungi were diluted by DMSO and then treated by 0,5, 10 and 20 mg/ml concentration of extracts in addition to the control group. The study revealed thatCapparis spinosa and Prosopis juliflora extracts had the highest inhibitory effect against Aspergillus niger, Fusarium oxysporum and Giberella baccata while Osmium basilicum of n-butanol and chloroform extracts showed no significant effecton Gibberella baccata. Distilled water and ethyl acetate extracts of Osmium basilicumat 20% concentration showed high inhibition against Gibberella baccata. The study revealed that ethyl acetate at 20% concentration significantly reduced Aspergillus niger growth when treated with Prosopis juliflora and Capparis spinosa extracts (0.88 and 0.93 cm), respectively. Ocimum basilicumalsosignificantly minimizedthe growth ofFusariumoxysporum (0.92 cm) using the same solvent concentration. It could be concluded that the studied plants are promising in the treatment of pathogenic fungi when treated using the appropriate solvents and concentration.
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Dna Barcoding Of Lizards (reptilia, Squamata) Of Qatar
Recent rapid development in Qatar has brought awareness and recognition of the importance to catalogue, describe and preserve its biodiversity. Traditional methods of using morphological characteristics for species identification, although important, requires years of experience and is in need of complete specimens before identity is certain. Recent worldwide endeavor of DNA barcoding by using a segment of the mitochondrial gene cytochrome oxidase c 1 (CO1) to describe all species in the world, has gained recognition and popularity. In this student-centered research supported by Undergraduate Research Experience Program (UREP) of Qatar National Research Fund (QNRF), the objective is to sequence the barcoding gene CO1 of the lizards in Qatar and to compare the sequence among closely related species to facilitate future identification. The final results of this study will make available the barcode sequences of CO1 to be included in the GenBank database. Lizard species were collected across Qatar and photographs were taken for appropriated morphological identification. About 0.5 cm3 of muscle tissues were obtained from each specimen for DNA extraction. Currently between 8 to 12 different primer pairs suggested in literature and primer pair combinations were used for 7 species and a variety of programs of polymerase chain reaction (PCR) were employed in order to amplify the segment of gene of about 650 bp. Among the successfully amplified sequences from the 7 species currently analyzed, three species, Trachylepis septemtaeniata, Mesalina brevirostris, and Uromastyx aegyptia produced PCR products. To eliminate the presence of multiple sequences in the PCR product, PCR fragments were ligated to cloning vector in order to amplify one single sequence for each species. The current total success rate (<43%) based on the primer sequences obtained from publish results and from internal primers developed in this study further supports that the universal primers for reptiles are difficult to develop due to deep phylogenetic divergence. Future studies seeking universal primers should focus on candidate genes that evolve more slowly than CO1 gene to ensure higher homology of sequences among the reptilian species.
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Bacteriophage Diversity In The Ecology Of Qatar
المؤلفون: Umm-kulthum Ismail Umlai and Annette VincentThe Science Education Alliance (SEA) Phage Hunters Advancing Genomics and Evolutionary Science, or PHAGES, is a national initiative in the United States, funded by the Howard Hughes Medical Institute (HHMI) and led by Professor Graham Hatfull from the University of Pittsburgh. This project is built around the discovery and analysis of mycobacteriophages in the biodiversity of the United States. For the first time, this research is being done in Qatar at Carnegie Mellon University to discover the possible existence of bacteriophages within the soil and sand of this Gulf State. The aim was to isolate and purify the phages present within the local ecology to be used as subjects of phage related medicinal therapy. Mycobacterium smegmatis (M.smeg) was used as the host bacteria strain in order to identify the presence of its phages within the sand and soil. This host was chosen due to its non pathogenic nature, fast growing ability and for being a universal host. M.Smeg also has physiological similarities with pathogenic species from the same family; M.tuberculosis causes tuberculosis, and M.leprae causes leprosy. Such efforts are intended to allow us to better understand the mechanisms by which to treat such bacterial diseases using phage therapy as opposed to using increasingly ineffective drugs. Although M.smeg failed to act as a host for the isolated phages from local environmental samples, future works to identify the suitability of other bacterial hosts such as Arthrobacter sp. for these phages will be carried out. Furthermore, analysis of the microbial composition of environmental samples will be conducted to identify specific bacteria hosts that exist in Qatar's ecology.
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New Hereditary Hearing Loss (hhl) Genes/mutations Identified By High Throughput Technologies In The Qatari Population
Objectives: Hereditary Hearing Loss (HHL) is a common genetic disorder accounting for at least 60% of prelingual deafness in children. The long tradition of consanguinity, which is widespread among populations of Arabian Peninsula, increases the prevalence of HHL. It is one of the most frequent causes for school failure in Qatar. GJB2 gene plays a worldwide major role in HHL recessive forms while in Qatar it has a minor role thus strongly suggesting the presence of additional causative genes. To overcome the remarkable genetic heterogeneity of HHL in Qatar population, an extremely powerful 2 steps "gene-identification strategy" was designed (Figure 1). STEP1 consists in a screening of 96 HHL genes by targeted re-sequencing (TS). Positive cases contribute to define an accurate molecular epidemiology picture while negative ones undergo STEP2, a combination of linkage studies and whole exome sequencing (WES) or directly to WES (depending on pedigree size). Methods: Ion Torrent (Life Technologies) (400X of mean target coverage and 581.000 Kb of targets size) was used for STEP1 and Illumina genotyping and Ion Proton (Life Technologies) (90X of mean coverage and 60Mb of target size) were used for STEP2. Sequencing variants were annotated/filtered according to standard pipelines. This strategy was applied to a first series of Qatari families. Results: STEP1 characterized 53% of Qatari families with HHL leading to the identification of 20 novel alleles in known HHL genes (i.e. GJB2, P2RX2, TECTA, TMPRSS3, LOXHD1, MYO15A, TMC1, TRIOBP, WFS1). STEP2 had already led to the discovery of 1 new gene (BDP1). The p*2625Gluext*11 mutation resulting in an elongation of 11 residues of the BDP1 protein was identified in a Qatari recessive family and its expression in the inner ear was confirmed by immunohistochemistry. Conclusion: This combined and powerful strategy proved to be very successful by explaining several HHL unsolved cases and by defining an accurate molecular epidemiology picture of Qatari genes/mutations. Moreover, this approach will be used for developing a "Qatari tailored" molecular diagnostic assay opening new important diagnostic perspectives for a such heterogeneous disorder as well as for defining targets for new possible therapeutic interventions
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Metformin Reverses Glucose Starvation Induced Endoplasmic Reticulum Stress And Autophagy In The Microvascular Endothelium
المؤلفون: Suparna Ghosh, Samson Mathews Samuel, Hong Ding and Christopher TriggleBackground and Objective: Diabetes Mellitus is associated with a higher incidence of myocardial infarction (MI) and poor prognosis in affected individuals; however, treatment with the oral hypoglycemic drug, metformin, is associated with a reduction in cardiovascular morbidity and mortality. A MI reduces oxygen delivery and results in nutrient/glucose starvation (GS) with micro-vascular endothelial cells (MECs) receiving the initial impact, the effect being more profound in a diabetic individual as glucose levels drop from hyperglycemia to GS. It is, however, not known whether GS triggers endoplasmic reticulum (ER) stress and autophagy in MECs and whether metformin has any effect on GS associated ER stress and autophagy. Thus, protocols were designed to determine whether GS-induced ER stress and autophagic events could be rescued. Methods— Mouse Microvasuclar Endothelial Cells (MMECs) were subjected to GS for 24h in the presence and absence of sodium-4-phenylbutyrate (chemical chaperone, 4PBA, 10mM) or metformin (50µM and 2mM) and western blot analysis was performed to assess the induction of ER stress and autophagy. Immunofluorescence staining was also done to assess LC3B punctae staining in cells, indicating autophagy. Results- GS caused ER stress as evidenced by significant increase in the levels of ER stress markers such as GRP78, ATF4 and CHOP. Significant increases in the levels of LC3A-II and LC3B-II and an increase in the level of LC3B punctae staining in glucose starved cells confirmed autophagic activation. Treatment with 10mM 4PBA significantly reversed GS induced ER stress and subsequent autophagy. The effects of varying concentrations of metformin (10µM-2mM) were studied. Metformin (2mM) significantly reversed ER stress and autophagy in glucose starved endothelial cells while lower concentrations that were in the therapeutic range had no effect. Markedly decreased LC3B punctae staining in metformin treated glucose deprived cells also ascertained the reversal of autophagy. Conclusions— This study demonstrates for the first time that GS induced ER stress and autophagy in the microvascular endothelium can be reversed by metformin, albeit only at mM concentrations. This work has been supported by QNRF grants JSREP- 3- 016-3-009 and NPRP 4-910-3-244.
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Exercise Induced Changes In Erythrocyte Membrane Proteome
More than 30 years ago people have learned that exercise promotes oxidative damage in human tissues. Since then, our knowledge on exercise-induced free radical production and their effect has advanced markedly. In the beginning research has mainly focused on detrimental effects of exercise-induced free radical production (e.g. oxidation of macromolecules); however today a new era of redox biology exist that centers on the cell-signaling effects of exercise-induced free radicals, such as reactive oxygen species (ROS) that were shown to play a crucial role in muscle adaptation to exercise. Erythrocytes are rich in membrane polyunsaturated free fatty acid content and have high cellular concentrations of oxygen and haemoglobin that makes them susceptible to ROS induced damage. However, mild oxidative stress has beneficial effect by increasing endogenous antioxidant mechanisms. Thus, in the present work we have used sensitive mass spectrometry techniques to assess the potentially beneficial oxidative modifications of erythrocyte membrane proteins in response to exercise. We have recruited 3 healthy volunteers and their blood was drawn before exercise, immediately after and few hours after exercise. Erythrocyte membranes ("ghosts") were prepared and membrane proteins isolated. Proteins were then separated by 1-D gel electrophoresis, digested with trypsin and peptides analyzed by Orbitrap ELITE coupled with the Easy n-LC II for nano LC-MS/MS. The acquired data was searched with Proteome Discoverer 1.4 against Homo sapiens database to reveal the changes in the erythrocyte membrane proteome. Furthermore, data acquired was also searched through the database using the comprehensive workflow that included several dynamic modifications of peptides, including N-terminal carboxymethyl, C-terminal oxidation and terminal independent oxidation and trioxidation of peptides. The results obtained revealed several proteins that have translocated from the cytoplasm into the membrane following exercise. Moreover, numerous proteins showed exercise dependent modifications and up/down regulation. Exercise induced proteome changes were demonstrated to play an important role in several signaling pathways related to healthy living and lifestyle.
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The Immune-related Role Of Braf In Melanoma
BACKGROUND. The existence of a dichotomy between immunologically active and quiescent phenotypes has been recently recognized in several types of cancer. The activation of a Th1 type of immune signature has been shown to confer better prognosis and likelihood to respond to immunotherapy. However, whether such dichotomy depends on the genetic make-up of individual cancers is not known yet. In melanoma, BRAF and NRAS mutations are frequently acquired during development. We recently proposed a genetic classification of melanoma metastases based on copy number variation and consistency of genes expressed in vivo and in vitro. We found that genes consistently expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) were critical for oncogenesis and their respective copy number influenced their expression. Most importantly, these genes were able to categorize melanoma metastases into two divergent phenotypes (TARA class: transcriptional adjustments related to amplification/deletions): one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A) and the other one with prevalent expression of genes associated with melanoma signaling and with a Th1 immune phenotype (Class B). An intermediate third class (Class C) was further identified. Here, we tested whether these phenotypes might be at least in part explained by BRAF and NRAS mutations in melanoma. METHODS. One-hundred-thirteen melanoma metastases were processed for microarray analysis and BRAF and NRAS sequencing. Allele-specific PCR (AS-PCR) was also performed to exclude low-frequency mutations. RESULTS. Comparison between BRAF and NRAS mutant versus wild type samples identified mostly constituents or regulators of MAPK and related pathways. When testing gene lists discriminative of BRAF, NRAS and MAPK alterations, we found that 112 BRAF-specific transcripts (p<0.01) were able to distinguish the two immune-related phenotypes already described in melanoma, with the poor phenotype associated mostly with BRAF mutation. Noteworthy, such association resulted stronger in samples displaying low BRAF mRNA expression. When testing NRAS mutation and expression, we could not find the same association. Class comparison between BRAF mutant samples displaying high levels of BRAF mRNA expression and wild type samples revealed that there is much more similarity between the two than with the low expressing BRAF mutant samples. To gain further insights concerning this surprising finding we performed functional interpretation analysis of the 6296 genes differentially expressed between BRAF mutants with high and low expression of the same gene; deregulated pathways included IL-2 and JAK/Stat signaling pathways, supporting the immunoregulatory role of BRAF. CONCLUSION. This study suggests that BRAF mutation-related specific transcripts associate with a poor phenotype in melanoma and provide a nest for further investigation.
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Prevalence Of Conventional Versus Non-conventional Cardiovascular Risk Factors In Patients Following Percutaneous Coronary Intervention For Acute Coronary Syndrome
المؤلفون: R. Jay Widmer, Mohamed Gomaa, Martin Reriani, Timothy Morgenthaler, Jassim Al Suwaidi and Amir LermanTraditional risk factors often fail to correlate with event incidence, thus there is a need for novel risk assessment in order to predict events and guide therapy in patients with acute coronary syndromes (ACS) following percutaneous coronary intervention (PCI). Peripheral endothelial dysfunction (PED) and obstructive sleep apnea (OSA) can both predict cardiovascular events, yet the prevalence of PED and OSA in patients hospitalized for ACS following PCI is unknown. Patients in the USA (n=65) and Qatar (n=352) were consented, enrolled following PCI for ACS, and underwent endothelial function testing (EndoPAT) on day 5 and home OSA testing (WatchPAT) following PCI. Baseline demographics at the time of patient admission showed only a modest prevalence of traditional CVD risk factors (Figure 1). The prevalence of PED (defined by EndoPAT<2.0) in this cohort was 73% (mean EndoPAT score of 1.8+0.5), and that of OSA 82% (Apnea Hypopnea Index>5; Figure 1). These functional, non-traditional risk factors were significantly more prevalent (p<0.0001) in this population than traditional risk factors, such as prior MI (6%), hypertension (52%), hyperlipidemia (47%), BMI>30 (43%), diabetes (36%), smoking (30%), CHF (1%), or family history of CVD (37%). Prevalence of both PED and OSA was present in 57% of participants. The current study demonstrated a higher prevalence of PED and OSA following ACS than the traditional CVD risk factors, underscoring their potential value for patient management. Detection and treatment of these functional risk factors may predict events and guide therapy in patients with ACS.
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Infection Rates And Phylogenetic Analysis Of Hepatitis G Virus (hgv)/gb Virus C (gbv-c) Among Qatari Blood Donors
Background: A new immerging nonpathogenic single stranded human RNA virus known as GBV-C/HGV was discovered in 1995. Both GBV-C virus and HCV have similar genome, but they replicate in different cell types. The incidence of GBV-C infection has been studied worldwide, however, to our knowledge; no previous studies were conducted in Qatar, thus the objectives of this study are: (i) to determine the rate of GBV-C infection in Qatar among healthy blood donors and liver-diseased patient and (ii) to determine the most predominant GBV-C genotype in Qatar. Methods: 755 blood plasma samples from blood bank (593) and virology section (162) at HMC were collected. RNA was extracted, reversed transcribed, and then subjected for GBV-C detection by nested PCR using primers targeting a 205 bp of the 5' hypervariable untranslated region (5'-UTR) of the GBV-C/HGV. For genotyping, the 5'-UTR PCR product were T/A cloned into pDrive plasmid. The plasmids were transformed into DH5α™, and then plasmids were purified and digested by EcoRI to detect the positive clones. Plasmid were then purified and sequenced. Phylogenetic analysis was conducted by analyzing the 5'-UTR sequence from randomly picked positive clones. The resulted sequences were assembled and analyzed using CLC and MEGA5 software. Results: we found that HGV infection rate among healthy blood donors was 13.5 %, while in liver-diseased patient was 8.6 %. Moreover, there was no significant difference in the GBV-C infection rate among Qatari (13.3%) and Non-Qatari (14.4%) healthy donors. Sequence analysis of 25 5'-UTR PCR amplicons yielded the European genotype (genotype 2) as the most predominant in Qatar. Conclusion: Our results indicate that there is no correlation between GVC- infection rate and other liver-infecting viruses such as HB&CV. Not surprising, genotype 2 was also reported to be dominant in countries surrounding Qatar such as UAE and Kuwait. Finally, we think our results should benefit epidemiologists in the region and may have an impact on the blood screening policy in blood banks.
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"whole Exome Sequencing Of A Family With 3 Sibling Affected By Bicuspid Aortic Valve Disease"
المؤلفون: Cornelia Carr, Despina Sanoudou, M. Dilawar, S. Helmi, Emmeleia Nana, Kholoud Al-shafai, Paul Barton, A. Al Khulaifi and Magdi YacoubBackground: Bicuspid aortic valve (BAV) is the most common cardiac malformation affecting 1-2% people worldwide. Despite its high prevalence, the pathogenesis of BAV is largely undetermined, although gene mutations leading to alterations in cell migration and signal transduction, in conjunction with non-genetic factors such as blood flow during valvulogenesis, may contribute to its formation prenatally. Objective: The determination of genetic factors contributing to the presentation of BAV in a family with three affected daughters. Methods: We applied next generation whole exome sequencing (>3Gigabases per individual) to high quality DNA from the blood samples of the three affected daughters and their unaffected parents. The >36.000.000 reads of each of the 5 individuals were analyzed with the bioinformatics tools Burrow-Wheeler Aligner, SOAPsnp, Sam tools, Varscan, and GATK to identify single nucleotide polymorphisms and insertions/deletions. Results: We identified over 38,000 SNPs and 3,400 Indels in each individual, of which >1,000 and >580, respectively, were novel. Forty one SNPs were detected in at least two of the affected siblings but neither parent, and only 3 of those were detected in all three BAV patients: HFM1 (ATP dependent DNA helicase), TSPAN2 (tetraspanin family member) and TTF2 (transcription termination factor, RNA polymerase II - pre-mRNA splicing regulator). All 3 genes carried exonic, non-synonymous SNVs, with highly significant pathogenicity prediction scores (SIFT, PhyloP, MutationTaster, LRT). Eight Indels were detected in at least two of the siblings, and only one of them was common across all three siblings: CCNL2 (cyclin L2). CCLN2 is a regulator of the pre-mRNA splicing process, as well as inducer of apoptosis, by modulating the expression of apoptotic and antiapoptotic proteins. In our patients it was found to carry a four base deletion affecting a splice site. None of the previously reported BAV-related genes were found to carry a common mutation across all, and unique to the BAV patients of this family. Conclusion: We have detected 4 genetic variants, shared by all three BAV patients but neither parent. These genes have not been associated with BAV to date. Of particular interest is the novel variant in TSPAN2, a gene of largely unexplored function, belonging to a transmembrane protein family known to mediate signal transduction events that play a role in the regulation of cell development, activation, growth, adhesion and motility.
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Alterations Of The Tumor Microenvironment By Her-2-neu-induced Creb Activation And Localization And Hypoxia
Cancer incidence is rising fast in Qatar, including in particular breast cancer. The expression of the oncogenic protein HER-2/neu is associated with an aggressive phenotype, and agents targeting this molecule have been successful in prolonging survival of breast cancer patients. Despite treatment progresses, metastatic breast cancer is still a fatal condition, and mechanisms of HER-2/neu regulation/resistance are not fully explained. Therefore a better knowledge of the dynamic of HER-2/neu regulation would enable to define new generation targeted therapy agents. The cAMP responsive element-binding protein (CREB) is involved in tumor initiation as well as tumor progression, but a link between HER-2/neu-induced transformation, CREB activation and alterations of the tumor micromilieu including hypoxia-mediated increased angiogenesis has not yet been established. Therefore, the effect of CREB activation on angiogenesis and its modulation by hypoxia was analysed in CREBhigh and CREBlow HER-2/neu+ murine fibroblasts in vitro as well as in vivo. Human tumor cells transfected with HER-2/neu or a mutant deficient in HER-2/neu signalling served as controls. By determination the number and density of blood vessels, necrosis and hypoxic areas a decreased tumorigenicity coupled with a reduced angiogenesis, but increased necrotic cells and hypoxic areas was found upon injection of CREBlow vs. CREBhigh HER-2/neu-transformed cells. In vitro, a time-dependent increase of pCREBSer133, but not of pCREBSer121 in the presence of hypoxia was detected, which was dependent on HER-2/neu signalling and accompanied by an upregulation of HIF-1α, GLUT1 and VEGF as well as of cell migration and invasion mediated by an increased expression of metalloproteinases. Under normoxic conditions, CREBhigh, but not CREBlow HER-2/neu+ cells showed a low intracellular pH, which was restored by CREB silencing. This was at least partially increased in the presence of hypoxia and correlated with an upregulation of lactate in the cellular supernatant of all cells. Furthermore, a hypoxia-mediated post-transcriptional modification due to an increased ubiquitination of CREB and altered cellular distribution of CREB was found. Under hypoxia CREB was translocated into mitochondria, which was accompanied by an altered expression of mitochondrial genes and enhanced apoptosis sensitivity. Thus, HER-2/neu-mediated CREB activation and localization is modulated by the hypoxic and acidic tumor microenvironment, thereby affecting the tumorigenic phenotype. In conclusion a link between HER-2/neu-mediated CREB activation and changes in the microenvironment and CREB localization was found, which contributes to the pathogenesis of HER-2/neu-expressing tumors, including mammary carcinoma. HER-2/neu-mediated CREB activation stimulates angiogenesis and hypoxia and is increased during hypoxia thereby causing translocation of CREB to the mitochondria, which enhances the malignant phenotype. Thus, targeting molecules downstream of HER-2/neu, like CREB, appear to be promising targets for the development of novel innovative therapies of HER-2/neu overexpressing tumors.
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Effects Of Rituximab On The Response To Influenza Vaccine In Complete Remission Lymphoma Patients
Hematological Malignancies (e.g., leukemia and lymphoma) are among the top 5 causes of cancer death in the Middle Eastern Countries, including Qatar, Kuwait and Saudi Arabia. The monoclonal antibody rituximab, directed at the CD20 antigen, has become an essential drug for the treatment of Non Hodgkin Lymphoma (NHL). Although transient B cells depletion frequently occurs after rituximab treatment, it usually resolves after 6-9 months. Nevertheless, high frequency of non-neutropenic infections and persistent hypogammaglobulinaemia during follow-up period have been recently reported. However, impaired humoral response to the recall and primary antigens was found in NHL patients during (or few months after), rituximab treatment. Influenza vaccination is generally recommended in lymphoma patients, but few data are available about the activity of this vaccine after rituximab-containing regimens (RCR). It is presently unclear whether patients treated with RCR regain normal immunocompetence after achievement of complete remission. We present integrated data of 3 sequential studies conduced at our Institutions assessing the humoral response to seasonal influenza vaccination (2008/2009, 2009/2010 and 2011/2012 seasons; RIT-01, RIT-02, and RIT-03 studies, respectively) in NHL patients in complete remission (CR) for at least 6 months after treatment with rituximab-containing regimens (RCR). Overall, we found that patients treated with RCR have a significant lack of humoral response to both recall and naive influenza antigens as compared with HV and with cancer patients treated with chemotherapy not containing rituximab. This weakness was associated with depletion of CD27+ memory b cells. To determine early transcriptional changes predictive of immunoresponsiveness and to determine differences in innate immunity activation among patients treated with RCR, HV, and patients treated with chemotherapy without rituximab, PBMC were collected just before and 1 day after vaccination (RIT-03 study). Whole-genome gene expression analysis of these samples using microarray analysis reveals that the intradermal vaccination was associated with dramatic transcriptomic changes in PBMC, already detectable 24 hours after vaccination. These changes underlie modulation of innate response (eg, interferon stimulated genes, NK-releted transcripts) and differs according to the treatment administered (eg chemotherapy with or without rituximab). In conclusions: a) patients previously treated with RCR should be strictly monitored during influenza epidemic season; b) anti-neoplastic treatments containing rituximab result in prolonged and specific immune alterations.
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Lifetime Prevalence Of Common Mental Disorders In Qatar: Using Who Composite International Diagnostic Interview (who-cidi)
Background: Mental Disorders, particularly Depression, are recognised as one of the biggest burden of disease worldwide. Two of the top three burdens of disease in Qatar are mental health related. Yet, there is scarcity of lifetime prevalence data available to understand the impact in this country. Aim: This study uses the WHO Composite International Diagnostic Interview (WHO-CIDI), to measure the lifetime prevalence of the most presenting mental disorders in the adult Qatari population, aged 18-65, and examine their symptom patterns and co-morbidity. Design: This is a cross sectional study conducted during the period from April 2010 to October 2011. Setting: Five Primary Health Care (PHC) Centres distributed around the country. Subjects: A total of 1,500 Qatari subjects aged 18 to 65 years were approached; 1,063 (70.8%) gave consent and participated in this study. Methods: Four field supervisors from Qatar were trained and certified as trainers by IDRAAC, the education and training centre responsible for the Arabic translation and validation of CIDI. Variations in Arabic dialect were reported to IDRAAC for verification and approval. In line with the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative, a nationally representative psychiatric epidemiological survey was carried out in Qatar. Prevalence and severity of ICD-10 disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI, Version 3.0). Results: Of the studied 1063 subjects, 50.1% were males and 49.9% were females. Most of the respondents were in the age group 18-34 years (46.1%), followed by 35-49 years (34.1%), then 50-65 years (19.8%). The most common ICD-10 disorders were specific generalized anxiety disorders (20.4)%, and major depression (19.1%), with a higher prevalence in women. 20.6% of the sample had chronic physical conditions. There were high levels of statistically significant differences between age groups and gender regarding Generalized Anxiety Disorders, Social phobia, specific phobia, major depression, and personality disorders screen. Women performed significantly worse as assessed by the 30 day functioning screen (p < 0.001). Conclusion: The findings of this study in lifetime prevalence of mental disorders in Qatar are comparable with international figures. Women were more likely than men to have mental illness. Overall, Generalized Anxiety Disorders; Social phobia, specific phobia, major depression, and personality disorders were the commonest disorders.
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Characterization Of Circular Rnas In Ovarian Cancer
المؤلفون: Ikhlak Ahmed, Thasni K. A. Azis, Eman K. Al-azwani, Yasmin Ali Mohamoud, Arash Rafii and Joel MalekNoncoding RNAs such as ribosomal RNAs (rRNA), transfer RNAs (tRNA) micro RNAs (miRNA), small interfering RNAs (siRNA) and long noncoding RNAs (lncRNA) are the dominant products of eukaryotic transcription and collectively represent more than 95% of total RNA of the cell. In addition to contributing as the core components of the translational machinery (rRNAs and tRNAs), these noncoding RNAs have been shown to be involved in a myriad of biological processes such as gene expression regulation and genome defence. Recently, a novel class of endogenously encoded species of RNA called circular RNAs (circRNA) has been shown to regulate gene expression in mammals by competing with miRNA targets under diverse scenarios. To investigate the role and regulatory potency of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of 9 ovarian cancer samples from three patients at primary and metastatic stages and developed an in-house computational pipeline to identify and characterize the circRNA candidates. Our results show that circRNAs are widely expressed in ovarian cancer and oncogenic factors in cancer-associated pathways are particularly enriched for circRNAs. We also show that isoform diversity of circRNAs is comparable to that of the linear counterparts and a significant fraction of exons are preferentially expressed as circular forms compared to the canonical linear RNA form. Further, these candidate circRNAs are particularly enriched for miRNA seed matches and the hybridization energies of interaction favourably predicts formation of stable structural dimers between circRNAs and miRNA mature sequences. A large number of candidate circRNAs are also differentially expressed between primary and metastatic stages of ovarian cancer and show co-expression with their gene targets, implying a role for circRNAs in regulating expression of oncogenic factors. Taken together this study adds an important new dimension to the role of miRNAs vis-à-vis circRNAs in fine-tuning of gene expression and disease progression in ovarian cancer.
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