Qatar Foundation Annual Research Forum Volume 2010 Issue 1

Primary ciliary dyskinesia is a heterogeneous autosomal recessive genetic disorder that leads to ultrastructural and functional defects of cilia. This leads to recurrent and persistent respiratory infections, sinusitis, otitis media, and male infertility. In a fraction of patients situs inversus is present. Primary ciliary dyskinesia can result from mutation in at least nine different genes. However, these mutations are responsible for the disease in 40 percent of patients. These genes provide instructions for making proteins that form the inner structure of cilia and produce the force needed for motility.

We identified two large inbred Qatari families with multiple individuals affected by primary ciliary dyskinesia. As a first step we excluded all known genes associated with the disorder. We then performed whole genome genotyping using 200K SNP chips on an Illumina platform followed by homozygosity mapping. In one family two significant homozygous regions were identified, a 35 Mb region on the long arm of chromosome 3 and a 46 Mb region on the long arm of chromosome 5. In the second family single homozygous regions was identified on the short arm of chromosome 5 spanning 3.2Mb. Candidate genes were prioritized based on conservation through evolution and expression in cilia. Examination of candidate genes by resequencing is currently being performed.

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism due to deficiency in the phenylalanine hydroxylase gene (PAH). This study describes the distribution of PAH mutations in nine probands from Libya with the diagnosis of phenylketonuria and hyperphenylalaninemia. Molecular genetics screening was done at the Shafallah Medical Genetics Center laboratory by resequencing and analysis of the entire coding sequences, exon flanking regions and splice sites of PAH. Genomic DNA was isolated from dry blood spots (n=9) by organic extraction technique and purified using centrifugal column filter device. The 13 exons , exon-intron boundaries and splice sites of the PAH were amplified by polymerase chain reaction using in-house designed primers and optimized conditions. The DNA sequencing reactions were carried out by automated sequencer using BigDye Terminator chemistry. Two homologous PAH mutations were found in 7/9 probands and were c.838G>A/p.E280K (missense) and c.1055delG (frame shift). The frame shift mutation produces a truncated protein of 399 amino acid length. Two Probands were homozygous for the missense mutation, three were homozygous for the frame shift mutation and two were compound heterozygous for both mutations. This initial study should be followed by an analysis of phenotype – genotype correlation pattern to better understand the disease process.

Rett syndrome is a neurodevelopmental disorder that leads to regression in language and motor skills. In most cases, it is caused by genetic mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett Syndrome occurs almost exclusively in girls and may be easily misdiagnosed, because its spectrum of clinical characteristics is overlapping with characteristics of other disorders such as autism, ataxic cerebral palsy, atypical Angelman's syndrome, spinocerebellar degeneration, etc. A 16-year-old girl with behavior within the autistic spectrum disorder, moderate to severe intellectual delay and subtle dysmorphic features enrolled in the Shafallah Center for children with special needs, School Unit 1. She is shy, with no sustained eye contact and has secondary seizures. She can use her hands in eating, drinking, painting in the class and she can hold a pencil between the index finger and thumb to do lines and circles, her history shows no regression. The clinical characteristics are closer to the autistic spectrum disorders than to the Rett syndrome.

In order to avoid misdiagnosis between Autism and Rett syndrome, a genetic testing of the MECP2 was realized in the Shafallah Medical Genetics Center, by sequencing and Multilocus Ligation Probe Amplification (MLPA). The sequencing analysis showed no variations in both directions, while the MLPA analysis detected a deletion of 0.6-2 kb in exon 4 of MECP2. The tests were repeated twice and the result was confirmed.

The molecular testing result supports a Rett syndrome diagnosis, while the clinical characteristics of the patient are not the typical Rett syndrome features. The case demonstrates that the spectrum of the clinical characteristics of the Rett syndrome is broader than is generally considered. This fact makes the diagnosis of Rett syndrome difficult by relying only in the clinical manifestations. Cases like this enforce the role of the molecular testing as a strong diagnostic tool.

Egypt has the highest prevalence of antibodies to hepatitis C virus (HCV) in the world, estimated nationally at 14.7%. An estimated 9.8% are chronically infected. Numerous HCV prevalence studies in Egypt have published various estimates from different Egyptian communities, suggesting that Egypt, relative to the other nations of the world, might be experiencing intense ongoing HCV transmission. More importantly, a new national study provided an opportunity to apply established epidemiologic models to estimate incidence. Validated mathematical models for estimating incidence from age-specific prevalence were used. All previous prevalence studies of HCV in Egypt were reviewed and used to estimate incidence provided that there was sufficient age-specific data required by the models. All reports of anti-HCV antibody prevalence were much higher than any other single national estimate. Age was the strongest and most consistently associated factor to HCV prevalence and HCV RNA positivity.It was not possible to establish a prior reference point for HCV prevalence or incidence to compare with the 2009 incidence estimates. The modeled incidence from the national study and collectively from the modeled incidence from the previous community studies was 6.9/1,000 [95% confidence interval (CI), 5.5–7.4] per person per year and 6.6/1,000 (95% CI, 5.1–7.0) per person per year, respectively. Projected to the age structure of the Egyptian population, more than 500,000 new HCV infections per year were estimated. Iatrogenic transmission is the most likely, underlining exposure to the ongoing transmission. The study demonstrates the urgency to reduce HCV transmission in Egypt.

In the past decade, biodegradable elastomeric polymers have gained considerable attention due to the renewed interest in their applications in the fields of biomedical tissue engineering and implantable drug delivery systems. Elastomers can be regarded as one of the best biomaterials for such applications because their mechanical properties can be manipulated in a manner that makes them as soft as body tissues, they have the ability to recover and withstand the mechanical challenges upon implantation in a mobile part of the body and they have also proven to be well suited to drug controlled drug delivery applications.

Our lab has recently reported on the successful preparation and characterization of a novel family of poly (diol-co-tricarballylate) elastomers, using visible light photo initiated polymerization. This new patented family of elastomers possess many structural, mechanical and physicochemical properties that make them superior to the currently available biodegradable elastomers.

The purpose of this presentation is to shed light on the preparation, characterization and in vivo animal biocompatibility studies conducted on these new elastomers. In addition, a short illustration on their application in controlled drug delivery and tissue engineering and the current and future scope of work planned utilizing the latest Qatar National Research Fund – National Priorities Research Program 3rd cycle support received will also to be presented.

Oligopeptidase B (opdB, EC 3.4.21.83) is a member of the prolyl oligopeptidase family of serine peptidases and unrelated to the trypsin and subtilisin families. It is a potential processing enzyme of prokaryotes to produce biologically active products, being very specific for the basic amino acid pairs of polypeptides. Bacterial oligopeptidase B cleaves globular proteins, albeit in a highly restricted fashion. While most members of this peptidase family hydrolyse peptide bonds at the C-terminal side of proline residues, oligopeptidase B exhibits a trypsin-like substrate specificity, cleaving peptides after basic residues (arginine or lysine). Oligopeptidase B was first cloned and characterized from Escherichia coli, and has also been described in other prokaryotes. Similar enzymes have been found in plants and some other higher organisms. We report the isolation of two different new oligopeptidase B bacterial strains producers. We identified the two genes, designated opdB1 and opB2. The opdB genes encodes a 703-residue peptide with high homology to the oligopeptidase B family in prokaryotes. The isolated opdBs gave the highest similarity score to oligopeptidase B of Stenotrophomonas maltophilia strain K279a (GenBank AM743169). To reveal the structural and kinetic properties of oligopeptidase B in more detail, we have cloned, expressed, and purified the enzymes to produce sufficient material to help in physical investigations, including NMR and x-ray crystallographic measurements. We also carried out a molecular characterization study of the two enzymes.

The thrombospondin type 1 repeat (TSR) is an ancient extracellular protein domain that is commonly found in invertebrate and vertebrate proteins. The ADAMTSL4 protein, also known as TSRC1, belongs to the TSR superfamily and has multiple thrombospondin repeats, most of which are clustered at the C-terminus.

It has been reported that some TSP1 domain-containing proteins, e.g. thrombospondin 1 and thrombospondin 2, could induce apoptosis of endothelial cells but it is not clear how these proteins operate in death pathways.

Our recent work shows that mutations in ADAMTSL4 are responsible for autosomal-recessive isolated ectopia lentis, i.e. abnormal positioning of the lens of the eye and affect the development of the zonular fiber. However, little is known about the function of ADAMTSL4. To shed more light on the function of the ADMTSL4 and its roles in different tissues we extended our work to carry out molecular characterization of this gene and its variants.

We have obtained cDNA clones encoding the full ADAMTSL4 protein and its truncated isoform. Both are subcloned into the pET28a vector for expression in E. coli. In anticipation of possible expression challenges in this host, e.g. formation of inclusion bodies or lack of expression, we subcloned each fragment into the yeast vector, pYES2. The gene in both cases has been fused in frame with a region encoding an N-terminal His-Tag to facilitate the purification of the recombinant protein. DNA analysis indicates that each fragment has been correctly cloned into the pYES2 vector. Each construct was transformed into Saccharomyces cerevisiae for protein expression. Our preliminary analysis indicates that one of the genes is expressed in S. cerevisiae but at a very low level. Work to optimize the expression of ADAMTSL4 in yeast as well as in E. coli is in progress.

We also extracted the seven domains of the ADAMTSL4 using PCR. Each domain was subcloned into the E. coli overexpression vector, pET28a. Expression studies of all the constructs have shown that the seven domains have been successfully overexpressed in E. coli. The overexpression was confirmed using Western blot techniques. The recombinant protein of each domain is purified for NMR and x-ray studies.

Metal toxicity is a global health concern. We summarize the evidence for metal interactions with the nervous system with an emphasis on synaptic transmission. The appropriate functioning of synaptic transmission is crucial for the information transfer in any neural network.

Presynaptically, metal ions modulate transmitter release through their interaction with neurotransmitter (NT) synthesis, fusion of synaptic vesicles, signaling cascades and ion channels. Ca²⁺ entry through voltage-gated channels is impaired by Pb²⁺, Cd²⁺ or Zn²⁺, therefore all processes which depend on Ca²⁺, including NT release, will be affected. Furthermore, some metals interact with intracellular pathways e.g. Pb²⁺ inhibits PKC enzymes through its catalytic domains, and Ni²⁺ causes a decline in the transcription of two isoforms of PKC (prkcc and prkz) and two regulatory binding proteins (prkcbp1 and prkcdb) affecting most functions of PKC. Cd and Hg inhibit adenylate cyclase activity, while the extent of inhibition depends on exposure time and brain area. Exocytosis is impaired by Pb²⁺ and Cu²⁺, which interact with Synaptotagmin I.

Postsynaptically, processes associated with binding of NT to their receptors, activation of the channels and degradation of NT are changed by metal. Zn²⁺, Pb²⁺, Cu²⁺, Cd²⁺, Ni²⁺, Co²⁺, Li³⁺, Hg⁺ and methylmercury modulate NMDA, AMPA/Kainate and/or GABA receptor's activity. These effects are more or less specific e.g. Zn²⁺ and Cu²⁺ modulate all three types of receptors, while Zn²⁺ is more potent (IC50= 0.77μM) compared to Cu²⁺ (IC50=15μM) at NMDA-Rs, but both have similar potencies at GABA-R. For the most part, metal interactions depend on the subunit composition of the NMDA-R, while less data are available for other targets, possibly underestimating their importance.

These modulations change the synaptic efficiency and therefore impair long-term potentiation (LTP). Consequently, metals such as Al, Pb or Cd result in various cognitive deficits. In addition the generation and maintenance of LTP is reduced by metal actions on phosphorylation of transcription factors like CREB as well as by reduction of nitric oxide synthase (NOS) that change retrograde signaling.

Overall, there are multiple effects of metals based on the forms of the metals, their concentrations and the types of neurons involved.

Calreticulin is a conserved Ca²⁺ binding chaperone protein that is localized to the lumen of the endoplasmic reticulum (ER). The protein is implicated in many cellular functions such as the regulation of intracellular Ca²⁺ homeostasis, the regulation of gene expression, the folding of the newly synthesized proteins, cell adhesion, cancer and auto-immunity. The role of calreticulin in Ca²⁺ homeostasis regulation through Ca2+ storage and signaling might be the key to explaining the involvement of the protein in many biological functions inside and outside the ER. In this study, we examined whether calreticulin is responsible for regulating store-operated channels (SOC) on the plasma membrane by assessing changes in Ca²⁺ levels and SOC activity in mouse embryonic fibroblasts that are deficient in calreticulin. Wild type and calreticulin deficient fibroblasts were loaded with fura2-AM and the release of Ca²⁺ from the ER stores was induced using Thapsigargin or Ionomycin, and Ca²⁺ levels were measured using InC lm2 computer program. Calreticulin-defiecint fibroblasts showed a marked decrease in Ca²⁺ influx through SOC compared to wild type. To investigate the mechanism that underlines this decrease in SOC activity we performed western blots using antibodies for ORAI (Calcium release-activated calcium channel protein) and STIM (stromal interacting molecule). Our data showed a significant decrease in the expression of ORAI in the calreticulin-deficient fibroblasts compared to wild type while STIM expression in calreticulin-defiecint fibroblasts did not significantly differ from wild type. We concluded from our data that calreticulin controls SOC activity and this seems to be through regulating the expression of ORAI on the plasma membrane.

The Cohen's lab research focuses mainly on the regulation of mammalian meiosis in mouse models, which include several induced mutants that have helped in broadening our knowledge of meiotic recombination and the gametogenesis. The lab also studies several DNA mismatch repair (MMR) proteins and their subsequent effects on meiotic recombination. Thus, our research serves two major purposes; first, to understand the genetics of re-combination and thereby to understand how such events can fail in human gametogenesis and secondly, to further elucidate the mechanisms of DNA repair and genome stability in an important in vivo system.

Extending from these aims, one of these genes is the MLH3 gene, evolutionarily conserved in many species such as mice, humans, and worms and which can solve the infertility problems in MLH3 mutant mice.

The focus of our project is to investigate the functions of several genes involved in meiotic prophase, using the technique of chromosome spreading. This method allows us to visualize the different stages of prophase I, and see the staining pattern of several antibodies that are specific to meiotic proteins. Using a battery of specific antibodies, we set out to understand the meiotic roles of a number of poorly characterized proteins involved in DNA repair and ubiquitination pathways. These antibodies of interest are those that are involved in the ubiquitination pathway of the sex chromosomes such as antibodies raised against Rnf 8, Rad 18, and Rnf 168, all of which are involved in ubiquitination pathways, as well as other antibodies involved in ubiquitination/deubiquitinatio. A group of other antibodies that include mdc λ, HR9B, MRαB, USP2B, and UBQ 2 is also being studied. Our goal was to first characterize the accumulation of these proteins on meiotic chromosomes in order to identify which, if any of these proteins might be functionally relevant for meiotic recombination and prophase | progression.

The project started with studying the staining pattern of the antibodies listed above in adult male wild type mice, then younger male wild type mice to see both the early and late stages of meiosis. The project is progressing to studying the staining pattern in the MLH3 and Ago 4 mutant mice to see any possible co-localizations between MMR genes and the antibodies considered by this study

Cancer accounts for the death of thousands of people each year and brings pain and suffering to thousands more. Among cancers that specifically affect women, ovarian cancer has the highest fatality rate as 7 out of 10 women die within 5 years of surgery. As highlighted in numerous recent publications, the role of the microenvironment in the development and progression of cancer is critical, albeit not entirely understood and should therefore be a focal point for further inquiry. The goal of our study was to define the metastatic properties enhanced by the interaction between ovarian cancer cells and mesenchymal stem cells. We studied the interaction between ovarian cancer cells and mesenchymal stem cells (MSC) using two different ovarian cancer cell lines (OVCAR3 and SKOV3) as well as different MSC cell lines derived from specific tissue. We studied using cytokine array as well as kinase array the modifications of the MSC upon their interaction with ovarian cancer cells. We demonstrated increased expression of cytokines that might be implicated in ovarian cancer metastasis (IL6 and IL8). Moreover MSC helped the ovarian cancer cells to grow in a tri-dimensional cell culture system. Finally we were able to define transcriptomic modification in the MSC and ovarian cancer cells upon their interaction.

Over 14,000 babies are born in Qatar each year, and it is the State's intention to provide each with a health screen at birth for the timely diagnosis of inborn errors of metabolism. And since the population is characterized by a high consanguinity (estimates vary between 25–70%) from first-cousin marriages, congenital and genetic disorders are responsible for a major proportion of infant mortality, morbidity, and handicap birth defects and are relatively common among the population. Accurate and reliable quantification of amino acid (AA), generally in a plasma sample, allows early diagnosis of disorders such as phenylketonuria, tyrosinemia, maple syrup urinary disease, hyperornithinemia and citrullinemia. A deficiency of cystathionine B-synthase (CBS) can cause an autosomal recessive disorder of methionine and homocysteine (Hcy) metabolism known as homocystinuria which results in elevated concentrations of Hcy in plasma and urine. Clinical symptoms in untreated patients include progressive myopia and lens dislocation, thromboembolism, epilepsy, and mental retardation. Hcy is implicated as a wide variety of natal and other disorders – including Alzheimer's. The aim of this study is to develop novel screens for AA levels – and in particular Hcy - in the blood using novel approaches in capillary zone electrophoresis (CZE). In order to quantify relevant amino acids it is necessary to deplete proteins from a complex biological sample such as plasma. In this investigation two protein depletion protocols were investigated on human plasma containing Hcy by label-free intrinsic imaging in the UV using CZE. As with a majority of amino acids, Hcy has very little or no UV absorption and for this reason analysis of samples were performed on an advanced high performance capillary electrophoresis (HPCE) platform, by multiple-pixel multiple-imaging indirect UV measurements. Two complementary analysis workflows were deployed to take advantage of the time-development of the AAs in the analysis allowing accurate quantification and minimum inherent bias.

Studies have been made with pure AAs and also with samples spiked in known quantities in blood which offer real clinical advantages. We have also developed methodologies for the simultaneous detection of several amino acids in plasma samples and limits of detection (LOD) and limits of quantification (LOQ) will be presented. These have been shown to be greatly improved with a pre-concentration technique known as ‘stacking’. Work has been undertaken in our labs in Qatar Science & Technology Park and in collaboration with Hamad Medical Center.

Epithelial ovarian carcinoma (EOC) is the sixth most common malignancy in women and the leading cause of death from gynecological cancer in the world. One of the main differences between ovarian cancers and other neoplasm is burden of local extension. Hence the majority of mortality in ovarian cancer is due to extensive peritoneal disease, with a high rate of mortality and an overall survival rate ranging from 20% to 30% five years after surgery according to various studies. As for any metastatic process, the tumor cells have to go through the steps of detaching from the primary tumor, adhering to the peritoneal surface and then invading the peritoneum. Each of these steps might be critical in the development of a metastatic lesion. Therefore it is essential to understand the molecular background of peritoneal adhesion and invasion in order to define new therapeutic targets. It may be that classic 2-dimensional cultures do not represent an ideal model for the initiation of metastasis, and therefore studies using only 2-dimensional cell cultures might not replicate the reality of ovarian cancer physiology. The goal of our study was to define new 3-dimensional culture models that will mimic the peritoneal tissue. The constraints were; to use an easily accessible tissue, in relevant quantities, as close as possible to the peritoneum, with great manipulability. We demonstrated that we could keep the amniotic membrane in culture and mimic adhesion and the early invasion of ovarian cancer cell aggregates. We were then able to follow the invasive process within the membrane and determine different cell behavior.

Developing reproducible 3-dimensional models of ovarian cancer aggregates and early adhesion and invasion will help us gain a more accurate understanding of the molecular mechanisms involved in the ovarian cancer metastatic process and define potential new therapeutic targets hindered by the use of classic 2-dimensional models.

Dietary fat intake is associated with hepatobiliary cancers which carry a poor prognosis causing over 20,000 deaths per year in the US alone. We hypothesized that excess lipid accumulation in the liver promotes hepatic cancer through inflammation and oxidative DNA damage. In order for eukaryotic cells to protect genomic integrity, the protein kinase ataxia telangiectasia mutated (ATM) responds to oxidative DNA damage and DNA strand breaks. Failure to activate ATM following damage leads to defective cell cycle control and impaired DNA repair. In this study, ATM knockout mice were used as a sensitized background to assess the effects of oxidative stress and DNA damage associated with hepatosteatosis. ATM-deficient and control mice were fed a high fat diet for eight weeks, and then liver tissue was analyzed for apoptosis. It was expected that more apoptotic cells would be found in ATM-deficient mice fed the high fat diet than in control mice due to DNA break repair deficiencies. Liver tissues were sectioned and stained by TUNEL assay, a method for detecting DNA fragmentation that occurs during apoptosis. The TUNEL immunohistochemistry protocol was first optimized for hepatocytes. Positive cells were counted in multiple 40X fields from each tissue section. Statistical differences between groups were determined by comparison of the fraction of positive cells. There were more apoptotic cells in livers from mice fed a high fat diet relative to those fed the normal diet. Interestingly, among mice fed the high fat diet there was a slight decrease in apoptosis in ATM deficient mice relative to controls. Although this difference did not reach statistical significance, this may indicate that ATM is required for inducing hepatic apoptosis in response to stresses associated with increased dietary fat consumption. Additional staining for cell proliferation as well as DNA damage response activation will be performed in the future. This study will begin to elucidate the interaction between lipid metabolism, oxidative stress, DNA damage and hepatobiliary oncogenesis and will establish a new mouse model that will provide a powerful tool for future mechanistic and translation studies of hepatobiliary disease.

Social interaction has drastically evolved over time. Moving away from face-to-face based interactions, telephone networks made the first step towards remote social interaction. The internet, further enhanced with the tremendous increase in lightweight mobile devices, has taken social interaction to new frontiers. Users can already email, chat, call, and video conference with others from around the world without necessarily being attached to any fixed location. The final frontier has been to exploit this technology to completely virtualize social interaction via online social networking services such as facebook, orkut, MySpace, or LinkedIn, etc. These applications create a virtual world where users build social networks of their acquaintances and allow people belonging to these social networks or communities to freely interact regardless of the boundaries of time and location. At this point, we pose a simple question, is this truly the final frontier with respect to social interaction?

When people with similar interests or common acquaintances are a short distance from one another, like the same street, train, or mall, these people have no mechanism to identify this potential social interaction. Current research in geolocalization applications running on mobile devices provide some solutions to such problems, however, they face numerous challenges including network coverage, cost, and energy consumption concerns. We ultimately need context aware, adaptive, and agile solutions that can seamlessly extend peoples senses beyond their physical boundaries in order to exploit potentially rewarding social interactions.

Our work, targeted towards fulfilling this need, takes advantage of physical context merged with online social relationships to ultimately improve the physical social interaction experience of people. We will discuss how current research thrusts such as delay and disruption tolerant networks (DTNs) and mobile opportunistic networking, can exploit social relationships between people in order to efficiently disseminate messages through such challenged networks. We believe that these types of networks better model and reflect human mobility pattern and limitations, and so are more naturally suited as a platform for tackling the problems mentioned above.

Currently in Qatar, and to the best of our knowledge in most Gulf state countries, there is a lack of reliable information about traffic conditions and congestion. This information, especially if ubiquitous and near real time, is highly desirable to support consumer, enterprise, and government centric applications. Since no universal solution exists, a great deal of innovative research is needed. This research work aims at designing and developing an integrated intelligent platform for real time monitoring of road traffic, based on advanced data processing and filtering algorithms. Four sophisticated blocks compose the platform. The Data Sources block is responsible for generating raw traffic data, for example from road sensors. The Platform Core block is where the Platform Engine and Platform Services are implemented. It processes raw traffic data and translates it into meaningful real time information, which is then delivered to user applications in different formats and via various fixed and mobile end‐user devices either in real time or playback mode. The User Applications block contains the set of applications interacting with the platform. Finally, the whole platform is configured and controlled via the fourth block: the Platform Administration and Management block. Given the importance and complexity of the addressed problem, a great deal of research and development effort has been conducted to create a robust, efficient, and rich intelligence platform supporting a large number of services and applications. The research efforts focused on geographical data preparation, communication protocols with remote data sources, speed and travel‐time estimation and prediction, raw data filtering and fusion, map matching, and shortest and fastest routes computation. It is well accepted that reducing mobility time means reducing people stress and enhancing produced results qualitatively and quantitatively. We believe that the platform's services will contribute in reaching this objective in Qatar and in the region.

Transmission Control Protocol (TCP)'s proven stability and scalability has made it the most widely used transport layer protocol for more than twenty years. However, as multimedia applications become ubiquitous over the internet, TCP has been found incapable of meeting their requirements, which place more emphasis on timeliness than on reliability. Because of that, many multimedia applications turn to UDP as their underlying transport protocol. However, the majority of video on demand and live broadcast applications predominantly use TCP over UDP (User Datagram Protocol), due to UDP's unresponsiveness to network conditions and problems with firewalls and NATs (Network Address Translations).

TCP's poor performance in delivering real-time media is due to the following reasons: 1) TCP's emphasis on reliable in-order delivery causes frame jitter that interrupt media play out. 2) TCP's coarse-grained retransmission timeout (RTO) and its back-off mechanism is detrimental to any real-time based application.

In this study, we propose a new variant of TCP with an early retransmission scheme as an enhancement to make it more suitable for streaming media. We call this new protocol TCP-ER. We performed extensive NS-2 simulations to show that: 1) the early retransmission scheme can reduce the number of retransmission timeouts in a variety of network environments, which results in a considerable decrease in number of retransmission timeouts and packet delay jitter. 2) Under same network conditions, constrained streaming over TCP-ER has a considerably lower number of late packets than its normal TCP counterpart. 3) TCP-ER has a higher throughput in severely congested network conditions, whereas it stays relatively fair with typical TCP implementations (specifically TCP-SACK) as congestion gets alleviated.

In 2009, Carnegie Mellon Qatar, Qatar University, Texas A&M Qatar and IBM launched a joint research project on cloud computing. Cloud computing is a computing paradigm in which the computing resources, the software and the data are made available to the users as a service through the internet. In this paradigm, the software is no longer a standalone application installed on the user's platform, but resides on one or several servers. For instance, Google Docs is an office suite (word processor, spreadsheet and presentation) that can be used through a web browser. This new kind of application is a radical shift in the way we design, implement and deploy software. In this context, ensuring security becomes critical since a vulnerability in a cloud-based application may exposed data of all users using the service. Yet, developing secure cloud applications is complex because programmers are required to reason about distributed computation and to write code using heterogeneous languages, often not originally designed with distributed computing in mind. Testing is the common way to catch bugs and vulnerabilities as current technologies provide limited support. There are doubts this can scale up to meet the expectations of more sophisticated cloud-based applications. In this project, we have designed a type-safe programming language called “Qwesst”. We used it to express interaction patterns commonly found in distributed applications that go beyond current technologies. This language prevents the programmer from writing unsafe code that can lead to a cross site scripting attack, also called XSS attacks. An XSS attack enables an attacker to inject JavaScript code into a webpage. This is a severe vulnerability that has become the most widespread security breach in web-based applications. In the future, we plan to extend the language with new security features that will allow the programmer to control data dissemination and information flow.

It is official. The automotive world is ramping up capabilities in simulation. Applications range from motorsports (optimization of vehicle dynamics, race track familiarization, car engineering), to driver-assistance systems (development of vehicle dynamics controllers), utilizing software in the loop (SIL) and hardware in the loop (HIL) validation in e.g. electronic control units (ECU). Another major emerging market is driver safety and training, e.g. emergency services and driver training centers.

Using HIL, simulation helps develop increasingly complex embedded systems, connect them to car hardware, test and ensure correct functionality and integration. Time-consuming manual testing has been replaced by automated simulation. When done in a pre-production phase, time-to-market and expensive recalls are considerably minimized.

Using driver in the loop (DIL), simulation provides a consistent and safe driving environment for drivers to gain or improve skills. In motorsports this saves track-time related costs and helps gain a competitive advantage; in the commercial world drivers become more successful dealing with hazards, while interacting with in-car functions, thus minimizing the risk of accidents or fatal injuries.

The Williams Technology Centre is engaged in developing driving simulators in the three key areas of motorsports, entertainment and road safety & training. We benefit from years of F1 simulator experience, with excellent understanding of vehicle dynamics and driver training needs. Our capabilities in automotive SIL, HIL and DIL are extensive. By combining in-house developed software, real-car hardware, and outstanding audio & visual graphics, our simulators are incredibly high-fidelity.

Current efforts concentrate on developing a DIL motorsport simulator incorporating real electro-mechanical car parts, and running on advanced software. Following extensive research into the human sensory system, we are pioneering an innovative visual environment to enhance driver immersion.

Research & development endeavors from 2011 will focus on further advancing high-fidelity control loading steering systems, growing our HIL capability, and sophisticated motion-cueing development. Artificial intelligence and scenarios will equally be at the heart of further expansion.

Spectrum sensing is one of the most important tasks of cognitive radios (CRs) in future wireless systems and of user equipment (UE) in next generation wireless networks (NGWNs). Therefore, deciding whether a specific portion of radio frequency (RF) spectrum is occupied or not is of paramount importance for all sorts of future wireless communications systems. In this study, a spectrum sensing method that employs a second–order statistical approach is proposed for detecting fast fading signals in spatially correlated shadowing environments. Analysis and performance results are presented along with the discussion related to the performance comparison of the energy detection method.

SrTiO3 (STO) is a complex oxide perovskite of great technological interest for its superconductivity, blue-light emission and photovoltaic effect. In normal conditions, SrTiO3 crystallizes in the cubic Perovskite structure and undergoes a second-order phase transition to a tetragonal structure known as the antiferrodistortive (AFD) phase of STO at the critical temperature Tc = 105 K. The AFD phase of STO can appear near the interfaces at much higher temperatures if STO is used as a substrate for the growth of thin films or superlattices with other perovskites. In the last decades, both phases of STO have been extensively studied with different schemes of ab initio calculations, but none of the previously published work has been able to give, at the same time, an accurate estimate of the structural and electronic properties of the cubic and AFD phases of STO. In this work, we use Gaussian 09 to fully explain the reason behind this failure using a large spectrum of functionals ranging from pure DFT functionals like LDA and GGA to more modern and complex hybrid functional like HISS and HSE06. We also show how the quality of the basis set compete with the functional effect in predicting the properties of STO, the strongest competition being observed for the AFD phase. In fact, basis sets of low quality tend to seriously inhibit the tetragonality of the AFD phase and sometimes even suppress it. On the other hand, pure DFT functionals tend to overestimate the tetragonality of the AFD phase in agreement with previously reported results in the literature using basis sets of comparable quality. Hybrid functionals predict the structural properties of the cubic and AFD phase in very good agreement with experimental results, especially if used with high quality basis sets. Thus, we present the most reliable combination of functional and Gaussian basis set for STO currently computationally tractable. This combination gave the best agreement with the experimental structural and electronic properties for the cubic and the AFD phases of STO. It is accurate enough to enable us to understand the changes in the band structure during the cubic to AFD phase transition, predict the carrier densities, find the activation barriers for the formation and mobility of defects and the magnetic ordering.

In nanoparticle image velocimentry (nPIV), evanescent wave illumination is used to measure near-wall velocity fields with an out-of-plane resolution of less than 200nm. Similar methodology can be extended for temperature measurements using Brownian motion characteristics of the sub-micron tracer particles in this region. Temperature change affects Brownian motion of tracer particles through a change in Brownian diffusion coefficient and a change in viscosity. The present study tries to numerically investigate the possibilities of utilizing this effect in near-wall thermometry. Synthetic nPIV images of the illuminated particle tracer of 100nm diameter are initially generated. The spatial distribution of the particles takes in to account near wall forces such as buoyancy, electrostatic repulsion and Van Der Waals attraction, in addition to the hindered Brownian motion. Validation studies are carried out using stationary liquids at constant temperatures. It is believed that this observation would help in explaining the anomalous heat transfer characteristics of nanofluids.

The senses of vision and touch are vital modalities used in the discrimination of objects. Recent advances in human-computer interface technologies have produced various haptic force feedback devices for the industries of rehabilitation, information technology, entertainment, and more. In this research effort, an inexpensive stylus-type haptic device is used to determine thresholds of concave curvature discrimination in visual-haptic experiments. Discrimination thresholds are found for each sense independently as well as for combinations of these with and without the presence of conflicting information.

Results indicate that on average, the visual sense is about three times more sensitive than the haptic sense in discriminating curvature in virtual environments. It is also noticed that subjects seem to rely more heavily on the sense that contains the most informative cues rather than on any one particular sense, in agreement with the sensory integration model proposed by other researchers. The authors believe that the resulting thresholds may serve as relative comparisons between perceptual performance and this study may be further expanded to audio and texture senses supported by the Undergraduate Research Enhancement Program (UREP) of the Qatar National Research Fund. It is also noted that these preliminary studies will constitute a valuable asset to the medical virtual training research and development.