Qatar Foundation Annual Research Conference Proceedings Volume 2014 Issue 1

The main two challenges hindering the deployment of solar cells in large scale are the high cost and low efficiency. One of the strategies to reduce the cost is by using thin film materials with enhanced solar cell conversion efficiency. However, thin film materials suffer from weak absorption and the presence of defects, which act as recombination canters for charge carriers. Various studies were conducted to improve absorption in thin film solar cells. However, those approaches are not optimized yet for high efficiency solar cells. In this study, we focus on enhancing light absorption of thin film silicon solar cells by using Zinc Oxide (ZnO) nanostructures.

BACKGROUND & OBJECTIVES: Improving materials properties is one of the biggest scientific issues of all the times. When it becomes impossible to further manipulate the raw material, one feasible way to push its properties beyond the theoretical limits is to modify the properties of the surface. That is where advanced surface coatings come in. From a manufacturing point of view, tools for machining are of particular interest. These tools are usually made of hard steels and cemented carbide (WC-Co). For specialized applications, such as aluminium machining, diamond or polycrystalline cubic boron nitride are also used. The main problem with steel, is that it exhibits a relatively low hardness (below 10 GPa) which strongly decreases upon annealing above about 600 K. Thus, the majority of modern tools are nowadays coated with hard coatings, in order to: (i) increase the hardness, (ii) decrease the coefficient of friction, and (iii) protect the tools against oxidation. A similar approach has been recently used to obtain a longer duration of the dies for aluminium die-casting. Multi-component and nanostructured materials represent a promising class of protective hard coatings due to their enhanced mechanical and thermal oxidation properties. METHODS: Three different thin hard nitrogen-rich coatings were mechanically, microstructurally, and thermally characterized: (i) a 2.5 micron-thick nano-layered CrN-NbN, (ii) a 11.7 micron-thick monolayer TiAlN, and (iii) a 2.92 micron-thick multilayer AlTiCrxNy. The main feature of the CrN-NbN coating is the fabrication by the alternate deposition of 4 nm thick-nanolayer of NewChrome (new type of CrN, with strong adhesion and low coating temperature). All the three coatings can reach values of hardness and elastic modulus exceeding 20 and 250 GPa, respectively. Their main applications include stainless steel drawing, plastic materials forming and extrusion, and aluminum alloys die-casting. The here studied TiAlN (SBN, super booster nitride) is one of the latest evolution of TiAlN coatings for cutting applications, where maximum resistance to wear and oxidation are required. The AlTiCrxNy combines the very high wear resistance of the Cr-coatings with peculiarities of the Al-containing coatings, such as high thermal stability and high-temperature hardness. All the coatings were deposited on a S600 tool steel. The coatings were subjected to two different thermal cycling tests: (i) 100 thermal cycles consisting of 60 s dwelling time, respectively at the high- (573 to 1173 K) and at the room-temperature, and (ii) 100 thermal cycles consisting of 115 s dwelling time, at same temperatures of the first test, followed by 5 s dwelling at room-temperature. The temperature induced hardness and elastic modulus coating variations were measured by nanoindentation. RESULTS: During thermal cycling, the TiAlN monolayer coating and the AlTiCrxNy multilayer coating showed a high oxidation resistance even at high temperature, while the CrN-NbN nano-layer coating undergoes a oxidation phenomena, for temperatures above 873 K. CONCLUSIONS: The investigated coatings showed a sufficient-to-optimal thermal response either in terms of mechanical stability, such hardness and elastic modulus, and in terms of oxidation degradation.

The development of artificial photosynthesis is one of the greatest scientific challenges of our times, not only to protect the environment but also to ensure global economic security. To mimic the natural photosynthesis process, a complete understanding of the natural photosynthesis process at the molecular level is essential to enable the production of inexpensive, lightweight, and high-energy-density fuels. Artificial photosynthesis may involve photo/electrocatalytic H2 generation by water splitting or the use of H2 in combination with atmospheric/industrially sourced CO2 conversion products to provide a continuous supply of high-energy carrier fuels at small/medium scales. Recently, Cu2O has received considerable attention in various energy-conversion applications, including photo/electrochemical hydrogen production and the photo/electrochemical conversion of carbon dioxide (CO2) to energy-carrier fuels. The Cu(I) state, with its d10 electronic configuration, is required for cuprous oxides to exhibit photo/electrochemical and chemical catalytic activity. For electrochemical CO2 reduction, Cu(I) sites are proposed to stabilize reaction intermediates such as CO, carbonates (CO23−), formates (HCOO−), and methoxy (H3CO−) adsorbates, as expected from their high heats of adsorption. Although the Cu(I) state makes these materials attractive, the stability of Cu(I) species toward redox reactions remains an issue to be solved. In this study, we report the novel design of multi-metal based electrocatalysts which may introduce different (other than Cu) active species due to effect of the hetro-atoms on the Cu surface. As a result the reaction intermediates on the surface may be stabilized generating CO exclusively as a reaction product of electrochemical reduction of aqueous CO2 while suppressing the competitive H2 generation. The higher selectivity towards CO generation may be attributed to perturbing the d-band metal center or the geometric effects caused by the second metal center around Cu.

Disinfection of drinking water is one of the extreme public health activities in Qatar. Chlorination, ozonation, ultra-violet, chloramination, and others are the most important treatment processes used and they can cause the formation of toxic by-products. The existence of bromide (Br-), for example, in water sources might cause in formation of brominated toxic by-products. Up-to-date drinking water treatment methodologies are challenged to successfully eliminate Br- before final consumption. Remediation onto activated carbons has a number of restrictions. Date pits are suitable as raw remediating adsorbent for preparing various modified adsorbents, because particular surface functional groups and the micro-pore structures can be attained by active modifications. The overall objective of this study was to develop an economical and environmentally acceptable process to safely eliminate the levels of Br- from desalinated water. Roasted date pits (RODPs) and activated charcoal (AC) (used as a control) were crushed and sieved with four different particles size ranges. The percentage of Br- removal was also studied under different experimental conditions such as pH, sorbent mass and initial concentration. In addition, surface characterization was also investigated. Experimental date analyses were investigated using different isotherm and kinetic sorption models. The modification of the date pits surface enhanced the Br- removal capacity at high initial concentration of bromide (200 ppm) by 27%. Using scanning electron microscope (SEM), the date pits surface images showed a different in pore sizes upon modification. Removal capacity of RODPs reached 39% at pH 4. In this study the heterogeneity of adsorbing mechanisms and the fitting with pseudo second order model and inter particulate diffusion models were concluded, and more than 35% of Br- removal efficiency was achieved within the RODPs at the first hour of contact time. The adsorption Br- onto RODPs was not fitted well with the pseudo-first order model. It was found that the kinetics of Br- adsorption was followed the pseudo-second order. It was also observed fluctuations in the removal efficiency for smaller particle sizes; indicating heterogeneity of adsorption/desorption and potential chemical bindings, this particular behaviour was not observed and investigated elsewhere in the literature (Figure below). The surface of RODPs contains oxygen functional groups such hydroxyl; hence the presence of such functional groups on the surface of date pits considerably influences on the adsorption mechanism of organic and inorganic compounds on the RODP. Economically RODPs are successfully used to remove Br-, comparing to AC. However, both adsorbents have nearly the same removal efficiency after one hour contact time. Apparently, the removal efficiency of both systems was quite significant. This may cover the way for the cheap and widely available date pits to be used as an adsorbent in water purification process.

Many hydrocarbon reservoirs - in Qatar and worldwide - are constituted of dolomite. For this reason, the origin of this Ca-Mg carbonate mineral has been extensively studied by generations of geologists, with the goal of exploiting gas and oil from rock reservoirs in the most efficient way. However, despite more than two centuries of research, several fundamental questions regarding the origin of sedimentary dolomite remain without a convincing answer. Recent research conducted in the field of geobiology suggests that dolomite formation may be the result of a microbial process, that is, organic molecules that in natural environments are produced by microorganisms seem to play a key role for dolomite nucleation at low temperatures in many geological settings. However, this innovative hypothesis is far from being unanimously accepted by the scientific community, and many details on the exact mechanism through which microorganisms mediate dolomite formation are still to be fully understood. The aim of this contribution is to summarize the most recent scientific studies that support the microbial model for dolomite formation, providing examples from culture experiments conducted in the laboratory using artificial growth solutions and from modern dolomite forming environments, such as the hypersaline lagoons located in the State of Rio de Janeiro (Brazil), the sabkhas of Abu Dhabi (UAE), and the sabkhas of Dohat Faishakh and Khor Al-Adaid (Qatar). Furthermore, we will elaborate on why we consider the coastal sabkhas of Qatar to be among the most ideal places on Earth where it is possible to study microbe-mineral interactions in evaporitic environments. In fact, thanks to the distinctive geology that characterizes this region, it is possible to obtain samples documenting the progressive transformation of the living microbial mats that mediate dolomite formation and other authigenic minerals into a fully lithified sediment, which is analogous to dolomite formations constituting economically important gas/oil reservoir rocks. This approach will provide key insights to test whether dolomite present in ancient evaporitic sequences can be interpreted as a fully biological product associated with early diagenesis or whether most of the dolomite forms during later stage metamorphic/replacement events that are controlled by purely abiotic processes. Finally, considering not only the scientific importance but also the aesthetic beauty of the Qatari evaporitic environments, we will discuss the idea and the challenges of transforming selected areas of the modern sabkhas into geoparks - protected natural reserves that would be of interest for the local Qatari population, as well as for tourists visiting Qatar.

Management of production from gas reservoirs can be a challenging process. The challenge gets bigger when the reservoir is characterized by having a small pore size, such as the tight carbonate reservoirs which are prominent in this part of the world. In such conditions, condensate blockage becomes a real threat to productivity. Carbon dioxide can be injected into the reservoir to combat this threat. We built a reservoir model to conduct a simulation study with the goal of finding the most feasible method for overcoming the negative impact of condensate formation. We have attempted to simulate huff-n-puff enhanced gas recovery in the same reservoir model, but this method did not achieve much success in alleviating the damage caused by condensate blockage. As a result, according to the model and data we collected, using huff-n-puff is not efficient since it failed to maintain the average reservoir pressure as well as CO2 did, therefore peripheral CO2 injection have been tested. The minimum requirement again is to achieve gas plateau production, while also maximizing the condensate recovery and minimizing the CO2 breakthrough into the wells. It was decided that seven CO2 injector wells were to be placed at strategic locations (injectors have been planned to be drilled away from the reservoir and producing wells) across the field in order to enhance the sweeping of condensate as well as minimize CO2 breakthrough. In other words, the injectors had to be at a distance where it can achieve all our simulation objectives. We ended up understanding the effect of the CO2 injection on condensate formation. As a result, it could be notice how the saturation of oil is high near the producing end of the core, this kind of saturation can completely nullify the relative permeability of gas, whereas after using CO2 flooding, the saturation is decreased significantly and the amount of condensate throughout the core is also much less.

Qatar and the region are experiencing transformative growth over relatively very short periods of time, due primarily to hydrocarbon based energy resources. As the country pushes to meet growing global demand for its finite fossil fuel reserves, it is looking also to capitalize on renewable energy sources including solar power generation. However, the high ambient humidity, high annual average surface temperature, high atmospheric aerosols including haze, secondary organic aerosols and dust particulates, all negatively impact the efficiency of solar power generation technology. We will present over ten years of Aerosol Optical Thickness (AOT) measurements from both ground and satellite based remote sensing data from NASA's Aerosol Robotic Network (AERONET) and Multi-angle Imaging SpectroRadiometer (MISR) instrument onboard the TERRA satellite. AOT is a measure of the atmosphere's ability to attenuate incoming solar radiation. As AOT increases, surface insolation decreases which in-turn decreases the theoretical limit for solar power generation. The data shows a net positive trend in AOT of >1% per annum over most of the Arabian Peninsula, including Qatar. The positive trend is associated with increased intensity of dust events, but not necessarily in the frequency of the events. The trend is observed over the operational spectral range of Photovoltaic (PV) cells (340-1020 nm.) The AOT trend is positive for all months of the year, except November, but exhibits a strong seasonal signature that indicates the dusty months are becoming dustier (March through July) and less productive for solar power generation. Trends in the angstrom parameter, an indicator of the size of the atmospheric aerosols, during the less dusty winter months, indicate an increase in the average size of the atmospheric aerosols, i.e. the winter months too are becoming dustier. Work continues on quantifying the net impact of the observed trend on solar power generation.

Power monitoring is needed in most electrical systems, and is crucial for ensuring reliability in everything from industrial and telecom applications, to automotive and consumer electronics. Power monitoring of integrated circuits (ICs) is also essential, as today ICs exist in most electrical and electronic systems, in a vast range of applications. Many ICs have functional blocks across the chip that are used for different purposes. Power ICs also have multiple circuit blocks, each performing their own function. Measuring circuit block currents in both analog and digital ICs is important in a wide range of applications, including power management as well as IC testing and fault detection and analysis. For example, the presence of different kinds of faults in IC circuit blocks during IC fabrication causes the currents flowing through these circuit blocks to change from the expected values. There has been general interest in monitoring currents through different circuit blocks in an attempt to identify the location and type of the faults. Previous works on nonintrusive load monitoring as well as on power-line communications (PLCs) provide motivation for the work presented here. The techniques are extended and used to develop a new method for power monitoring in ICs. Most solutions to the challenge of measuring currents in different circuit blocks of the IC involve adding circuitry that is both costly and power consuming. In this work, a new method is proposed to enable individual measurement of current consumed in each circuit block within an IC while adding negligible area and power overhead. This method works by encoding the individual current signatures in the main supply current of the IC, which can then be sensed and sampled off-chip, and then disaggregated through signal processing. A demonstration of this power monitoring scheme is given on a modular discrete platform that is implemented based on the UC3842 current-mode controller IC, which can also be used for educational purposes.

Solution combustion synthesis (SCS) is a widely used technique for synthesizing variety of high purity oxide nanoparticles. Two basic modes for combustion synthesis are the self-propagating high temperature synthesis (SHS) and Volume Combustion Synthesis (VCS). The first method is based on the reaction that is locally ignited by an external source (laser, tungsten coil etc) which ends up with an exothermic redox reaction in a self-sustained manner without requiring any further energy for the combustion. Second method is the uniform heating of the entire sample in a controlled manner using a constant heat until the reaction occurs simultaneously throughout the volume. SCS typically involved a self-sustained reaction in a homogeneous solution of oxidizer (metal precursor) and oxygen containing fuels (urea, glycine, hydrazine etc). The selection of fuel is based on the reactive groups such as amino, hydroxyl and carboxyl bonded to a hydrocarbon chain. In our total work, we used two modes of synthesis: VCS and ILCS (impregnated layer combustion synthesis) to synthesize transition metal nanoparticles. The precursors used in this work were Nickel nitrate hexahydrate, Ni(NO3)2.6H2O, Copper nitrate hexahydrate, Cu(NO3)23H2O, Cobalt nitrate hexahydrate, Co(NO3)2. 6H2O and Glycine CH2NH2COOH. The ratio of metal nitrates and glycine were optimized to give pure metals of high surface area. The precursors were thermally analyzed using TGA/DTA to understand the metal phase development with increasing temperature. Phase Composition and average particle size were analyzed using XRD and the specific surface area of the synthesized particle was calculated using BET method, while its morphology was analyzed by SEM. The objective of our work is to synthesize nanoparticle with high surface area, selectivity and reactivity, which will be more suitable to be act as catalysts for electrochemical reaction in the conversion of CO2 to valuable products The XRD calculations indicated crystallite size to be in the range of 8nm - 15 nm indicating small nanoparticles with high surface area suitable of catalytic applications. The XRD profile of Copper-Nickel in glycine for different stiochiometric ratios shows the presence of pure alloy of Copper Nickel at its higher value of ?, say it as 1.75. The multiple peaks in XRD for its lower stiochiometric ratio indicates the presence of oxide. The objective of our work is to synthesize nanoparticle with high surface area, selectivity and reactivity, which will be more suitable to be act as catalysts for electrochemical reaction in the conversion of CO2 to valuable products The large surface area for Copper Nanoparticles were synthesized first which having large surface active sites, they become excellent catalysts in metallurgical and petrochemical Investigation has been done based on the basic mechanism to describe the phase transformation in the combustion front. The SEM analysis pointed a remarkable change in the particle distribution, grain size, porosity and its microstructure by changing the oxidizer/ fuel ratio These nanoparticles are currently being investigated for catalytic reduction of CO2 to valuable chemicals.

Spent Pot Lining (SPL) is produced in thousands of tons annually as a waste from the aluminum industry. SPL is classified into two types, 1st and 2nd Cut SPL. The 1st cut, which is the material under investigation in this study, is a contaminated graphite/ceramics material (50 - 60% of graphite) that is used in lining the electrolytic cell within which aluminum is produced by the reduction of molten Al2O3. 1st Cut SPL is considered as a hazardous material since it contains many other contaminants such as fluorides, cyanides, lead and chromium in addition to its production of flammable gases when it comes in contact with water e.g. ammonia, phosphine, hydrogen and methane. The aim of this study is threefold: (i) fully characterize the 1st Cut SPL produced by Qatalum in Qatar to help in creating the materials safety data sheet (MSDS), (ii) chemically treat this 1st Cut SPL in order to extract the graphite component to use it in other applications in addition to the Cryolite and finally (iii) use the extracted graphite in removing heavy metal ions from aqueous solutions. In this work, the first treatment for 1st Cut SPL was washing it with deionized water. The produced gases were collected in gas bags and characterized using GC-MS which confirmed the evolution of H2 gas when the 1st Cut SPL comes in contact of water. The second step was washing the 1st Cut SPL powder several times with organic solvents to dissolve the existing organic compounds and characterize the eluent using HPLC-MS technique to identify the dissolved organics. A thermal treatment to get rid of the undissolved organic materials was done. Next, surface characterization was carried out for the dried powder which confirmed the absence of any organic materials. Later, the powder was treated with cycles of different concentrations of NaOH, HNO3 and deionized water to remove the remaining inorganic contaminants. The eluents, resulted from the chemical treatment and washing processes, were collected and analyzed using HPLC-MS and ICP. The purity of the produced graphite powder was characterized using XRD to check its purity. The produced graphite powder was functionalized through boiling in 1:1 of H2SO4 : HNO3, washing with deionized water, hot NaOH and finally with deionized water to increase the carboxylate groups on the graphite surface which increases the negative charge on the graphite's surface once mixed with water. The functionalized graphite was proved to Cu ions from aqueous solutions at different pH values with efficiency close to 100 % at pH 10.

THE 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.

This 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.

Magnetic 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.

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.

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

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.

Traditional 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.

Background: 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.

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.

Noncoding 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.

In Egypt, β-thalassemia is the most common hereditary hemolytic anemia. Cardiac dysfunction, secondary to iron overload with formation of oxygen free radicals, is the most common cause of death in β-thalassemia patients. This study was designed to determine whether the allelic genotype of apolipoprotein E (Apo E), which exhibits antioxidant properties, could represent a genetic risk factor for the development of left ventricular (LV) dysfunction in β-thalassemia major. Fifty Egyptian β-thalassemia major patients were subjected to echocardiography to assess LV function. Apo E genotyping by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was done for all patients in addition to 50 age and sex matched healthy control subjects. Patients were classified into three groups. Group I and II were clinically asymptomatic. Group II subjects had evidence of LV dilatation, while Group III patients had clinical and echocardiographic findings of LV failure. Apo E4 allele was significantly higher among Group II and III than in controls. In conclusion, Apo E4 allele can be considered as a genetic risk factor for LV dysfunctions in β-thalassemic patients. It could be used as predictive indicator for additional risk of LV failure, particularly in asymptomatic patients with LV dilatation, requiring a closer follow-up, to prevent further disease progression

Environment Gene Interaction in Parkinson's disease (EGI-PD) Mohamed M. Salama1, Thomas W. Rösler2, Ali Shalash3, Abdelhaleem Tantawy4, , Günter U. Höglinger2,5 1Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt 2Department for Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany 3. Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt 4. Department of Neurology, Faculty of Medicine, Mansoura University, Mansoura, Egypt 3 Department of Neurology, Technical University, Munich, Germany Introduction: The prevalence of PD is increased in Egypt compared to reports in other countries. Both genetic and environmental causes might be responsible. E.g. a high rate of LRRK2 mutations has been reported in other North African countries, but has not been systematically studied in Egypt. Also, several epidemiologic studies have supported the hypothesis that broadly defined pesticide exposure may increase the risk of PD. A high degree of pesticide use occurs in Egypt due to the limited availability of agricultural areas in the country. Moreover, lack of precautionary measures on applying pesticides leads to increased pesticide exposures. We aimed to study the link between genes encoding detoxifying enzymes and PD-risk genes on one hand and exposure to pesticides on the other hand in the etiology of PD in Egypt. Methods: This work is undertaken in collaboration between the Technische Universtität München, Germany and a network of 16 Egyptian Universities leaded by Mansoura University (Egyptian Network of Neurodegenerative Diseases [ENND]). PD cases from all over Egypt are recruited. Half of the cases were chosen in areas of low pesticide exposure, the other half with high pesticides exposure (farmers 50 years of age or older). Similar numbers of non-PD controls are chosen from two sources; first, patients arriving to outpatient clinic who are not suffering from any other neurodegenerative disorder; secondly, persons accompanying participating PD patients. Controls are further stratified into low pesticides and high pesticides controls, as described for the PD cases. Patients are assessed with a standardized questionnaire to evaluate past exposure to pesticides or other Parkinson-related environmental factors, a standardized clinical neurological examination to verify presence of PD (UK brain bank criteria) and to quantify disease severity (Hoehn & Yahr stage, UPDRS motor part) and genotyping for presence or absence of risk-carrying alleles in detoxification and Parkinson's associated genes. Results: We were able to establish ENND which is the first collaborative network of this type in Egypt. Moreover, we established a functional Standard Operation Procedure to collect and ship clinical data and blood for analysis to the German cooperation partner at TUM. So far, we collected blood and epidemiological data from 70 cases and 80 controls. Preliminary data on the analysis of gene-environment interaction analysis will be presented. Conclusion: This work will provide further insights into the mechanisms of gene environment interplay in the etiology of PD and hopefully insights which allow the establishment of primary preventive measures. Funding: DAAD-funded Al-Tawasul project EGI-PD

Objective: We hypothesized that nebulized magnesium sulfate added to combined bronchodilator and systemic steroid therapy would shorten time to discharge without undue risk. Study design: Patients aged 2 to 14 y with moderate and severe asthma (PRAM severity score >4) admitted to infirmary care were randomized double-blind to 800 mg nebulized isotonic magnesium sulfate or normal saline placebo via Aeroneb Pro and Idehaler, after intensive therapy with combined albuterol-ipratropium and intravenous methylprednisolone. Time to medical readiness for discharge was the primary outcome. Improvement over time in PRAM severity score and other secondary outcomes were compared for the overall group and severe asthma subset. Results: 191 magnesium sulfate and 174 placebo patients met criteria for analysis. The groups were similar with mean baseline PRAM scores>7. Blinded active therapy significantly increased blood magnesium level 2 h post-treatment 0.85 (SD 0.07) vs 0.82 (SD 0.06) mmol/L, p=0.001). There were no important adverse effects. Accelerated failure time analysis showed a non-significantly relatively shortened time to medical readiness for discharge of 14% favoring the magnesium sulfate group, OR=1.14, 95% CI 0.93 to 1.40, p=0.20, with an absolute prolonged time at 24 h of 2.1 h, p=0.5 . Mean times until readiness for discharge were 14.6 h [SD 9.7] vs 15.6 h [SD 11.3] for the investigational and placebo groups, respectively, p=0.9. Conclusions: Adding nebulized magnesium sulfate to combined nebulized bronchodilator and systemic steroid therapy is either very weakly or very rarely effective, or futile for benefitting pediatric patients with moderate or severe asthma.

OBJECTIVE: Differentiation capacity of human preadipocytes exhibits depot specific variation and is influenced by local cytokine production. The effect of obesity-induced insulin resistance on preadipocyte differentiation and its relation to proinflammatory cytokine release was investigated. RESEARCH DESIGN AND METHODS: Differentiation of preadipocytes obtained from subcutaneous & omental tissue biopsies isolated from obese patients undergoing weight reduction surgery and their cytokines release were compared between insulin sensitive and insulin resistant subjects. RESULTS: Compared to subcutaneous-derived cells, omental cells expanded from the same patients showed diminished differentiation, marked by increased proinflammatory cytokines secretion. When subjects were dichotomized into insulin sensitive & insulin resistant depending on their HOMA-IR, preadipocytes derived from insulin sensitive subjects exhibited a greater ability to differentiate into larger adipocytes with more lipid droplets, marked by a lower expression and secretion of IL-6 and TNFα. Addition of these cytokines inhibited preadipocyte differentiation in insulin sensitive-derived cultures, suggesting that proinflammatory cytokines may underlie inhibition of differentiation seen in insulin resistant patients-derived cultures. CONCLUSIONS: These findings suggest that insulin-resistance is associated with impaired preadipocyte differentiation and increased proinflammatory cytokines release. Understanding mechanisms underlying impaired preadipocyte differentiation associated with insulin resistance may help future treatment strategies.

Previous studies have shown that low intensity pulsed ultrasound (LIPUS) can prevent orthodontically induced teeth root resorption (OITRR) in human. Also, stem cells have been used to treat different types of bone defects. Severe OITRR is still untreatable problem in orthodontics. The aim of this study was to evaluate the effect of local injection of osteogenically induced gingival stem cells (OIGSCs) and LIPUS on periodontal ligament (PDL) during tooth movement that induces OITRR in beagle dogs. We hypothesized that local injection of OIGSCs and LIPUS can enhance PDL metabolism and hence enhances the reparative effect of OITRR. Seven adolescent beagle dogs were used and their third and fourth premolars were moved orthodontically. Gingival stem cells were isolated, characterized by flowcytometry and were differentiated into osteoblast -like cells using osteogenic medium to produce osteogenically induced gingival cells (OIGCs). OIGSCs were then re-injected into the alveolar bone in the proximity of the roots of the orthodontically moved teeth. Premolars were randomly divided into five groups. 1) Negative control (OITRR only); 2) Local injection of BMP; 3) OIGSCs; 4) LIPUS and 5) LIPUS +OIGSCs. In LIPUS groups, premolars were treated for four weeks. Animals were then euthanized and tissue blocks were processed for histological and histomorphometric analysis. Cementum thickness, PDL thickness and PDL cell number were counted using Metamorph software. Measurements were made at three levels of the tested roots. Level 1 is the coronal level 9towards the crown); level 2 (middle level of the root) and level 3 (apical, towards the apex of the roots). Variables were compared between groups by Wilcoxon Signed Ranks Test using SPSS statistical package. Results showed that LIPUS, BMP2 and LIPUS+OIGCs significantly increased cementum thickness compared to control group in the apical area of the teeth roots (P<0.05). There was statistically significant increases in PDL thickness and PDL cell count in all groups compared to control group (P<0.05). The combined LIPUS+OIGCs showed the highest cell count between al the groups. Conclusion: LIPUS + OIGCs showed the highest PDL regeneration potential and may be used in clinical cases with severe OITRR.

Cdc25C is a member of the dual specific protein phosphatase family capable of dephosphorylating both phospho-Tyr and phospho-Ser/Thr residues. In vertebrates, there are three isoforms of the Cdc25 enzyme (Cdc25A, Cdc25B and Cdc25C). The N-terminal (regulatory domain) region of these three enzymes is highly divergent (~20-25% identity) while the C-terminal (catalytic domain) region is more conserved (~60% identity). The Cdc25C isoform is of particular importance because it dephosphorylates Cdc2, which is part of the Cdc2/Cyclin B complex, allowing the cell to transition into mitosis. We want to gain further insight into how Cdc25C interacts with its substrate Cdc2. One way to do this is to utilize the ability of E. coli to heterologously express recombinant Cdc25c. This will allow us to obtain large amounts of the protein for in vitro characterization. First, several E. coli cell lines were tested (each with unique properties; e.g. expression of toxic protein, expression of disulfide rich proteins) for their ability to overexpress Cdc25C. The cell line and expression condition having the highest yield of full-length protein was chosen and purified using a single immobilized metal affinity chromatography (IMAC) column that will bind a 6xHis affinity tag fused to the N-terminus of Cdc25C or a tandem approach that utilizes two affinity tags (an N-terminal 6xHis affinity tag and a C-terminal StrepII tag). The pure protein will then be subjected to a variety of chromatography techniques such as UV-Vis spectroscopy and circular dichrosim (CD) to characterize structural changes the protein undergoes when binding to its zinc cofactor. Site directed mutagenesis will be used to create mutations in the zinc binding region of Cdc25C and these proteins will also be characterized for their ability to bind or not to bind the zinc cofactor.

Abstract Nanobiotechnology has been recently widely applied in multidisciplinary fields including pharmaceutical applications. The last decade has witnessed an increase research interests focused on the biosynthesis of metal nanoparticles from fungi as a natural sources and as bionanofactories. However, silver nanoparticles (AgNPs) are of great importance particularly in medical therapy applications and can be used as antimicrobial agent. The objective of this study was to biosynthesize silver nanoparticles from the soil fungus Curvularia tuberculata and to examine their efficacy against five strains of pathogenic bacteria namely; Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi and Staphylococcus aureus using agar well diffusion technique. The synergistic efficacy of biosynthesized silver nanoparticles in a combination with commercially used antibiotic Gentamycin against the selected bacteria was also examined. The biosynthesized silver nanoparticles from fungal free-cell filtrate were characterized by using UV-Vis spectrophotometer analysis, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). UV-Vis spectrophotometer analysis revealed a peak at 420 nm indicating the synthesis of silver nanoparticles. FTIR analysis verified the detection of protein capping of silver nanoparticles while SEM micrographs showed that the synthesized silver nanoparticles are dispersed and mostly having spherical shape within the size range between 10-50 nm. The biosynthesized silver nanoparticles possessed a varied growth inhibition activity ranged between 12- 28 mm diam inhibition zones at different concentrations against the tested pathogenic bacterial strains. A remarkable increase of bacterial growth inhibition (25.5-35.5 mm diam) was detected when a combination of silver nanoparticles and Gentamycin was used. A significant increase in fold area of antibacterial efficacy was observed when AgNPs in combination with Gentamycin was applied as compared with the efficacy of Gentamycin alone. The biosynthesized AgNPs did not show any toxicity against human blood. The synthesized silver nanoparticles by the fungus C.tuberculata is promising to be used as an antimicrobial agent in medical therapy due to their broad spectrum efficacy against pathogenic bacteria. Nevertheless, further studies are needed to investigate the activity of silver nanoparticles as antibacterial agent in vivo.

Worldwide 1.24 million deaths occur annually due to road traffic injuries. Additionally, 20-50 million are injured or disabled. Similarly, within the Gulf Cooperation Council countries injury and mortality due to road traffic injury are high. In the State of Qatar, for example, the road traffic fatality rate for the year 2010 is estimated to be 14 per 100,000. Young adult males are disproportionately affected. Road safety risk factor laws namely, seat belt use, driving under the influence of alcohol, helmet use and speed management exist in Qatar but enforcement is lax. An additional new risk factor causing distraction while driving and causing road traffic injury and fatalities is the use of mobile phone whilst driving a vehicle. Currently, in Qatar baseline national data pertaining to seat belt and mobile phone use among drivers is not available. We have thus conducted an observational study to estimate the prevalence of these two variables among vehicle drivers in Doha. Additionally, we will examine and present the associations between phone and seat belt use, and variables such as the gender of the driver, type of vehicle and the time of the day during which the observations were made. Furthermore, policy implications of the study findings will be discussed. Acknowledgement: This work is supported by the Biomedical Research Program at Weill Cornell Medical College in Qatar, a program funded by Qatar Foundation.

One of the key objectives of the surveillance of communicable disease (CDs) is the identification of areas for research and healthcare system improvement. In a recent paper published in Qatar Medical Journal (http://dx.doi.org/10.5339/qmj.2014.9) is shown the delay in diagnosis of CDs of cases reported at The Cuban Hospital (TCH) during 2012 and 2013. Examples of delay in diagnosis was for tuberculosis 61.7 days, acute hepatitis 18.5 days, typhoid fever 17 days, food poisoning 9.5 days, measles 8.0 days and meningitis 3.8 days. These are diseases that require immediate reporting because of their public health importance and some of them are highly transmissible (e.g. tuberculosis and measles). Additional evaluation of patients with tuberculosis admitted at The Cuban Hospital (many reported in Hamad General Hospital and referred to TCH because of bed crisis) from January 2013 to June 2014 (105 patients) show diagnosis delay of 49.5 days (standard deviation 51.9 years) with a maximum figure of 365 days. In patients with positive smear (highly infectious) the delay was 49.7 days (SD 53.5 days) (minimum 2 days, maximum 365 days). The delay was superior in cases with pulmonary tuberculosis (51.3 days (SD 52 days)) than in non pulmonary (36.1 days (SD 51.9 days). Delay in diagnosis of CDs is significant with regard to not only disease prognosis at the individual level but also transmission within the community. The delay could be divided in ¨patient delay and system delay¨. Patient delay refers to the time between onset of symptom and the first contact with a healthcare professional. The system delay refers to the time between this first contact to the diagnosis or confirmation of the disease. The knowledge of the two components of the delay is essential to identify actions to minimize the delay and reduce the probability of disease transmission at the community. In summary data from the surveillance of CDs suggest the need of research to identify the causes of diagnostic delay and subsequently implement actions its reduction, which will contribute to the prevention and control of CDs in Qatar.

Human endogenous retroviruses (HERVs) have been classified into three different classes I, II, III. Betaretrovirus-like sequences, including HERV-K, belong to the class II and contains ten groups, termed HML1-10. It has been reported that an HML-10 sequence, termed HERV-K(C4), is inserted within the gene coding for the human complement C4 in an antisense orientation (Tassabehij et al. 1994). The expression of the HERV-K(C4) RNA has been hypothesized to possibly modulate C4 expression as well as to act as a possible mechanism of defense against retroviral infections (Schneider et al 2001). Recently, it has been demonstrated that low HERV-K(C4) copy number is associated with type 1 diabetes, raising the possibility that this retroviral element contributes to functional protection against this autoimmune disease (Mason et al. 2014). Given the correlation between lower HERV-K(C4) copy number and expression, it has also been proposed that HERV-K(C4) may influence C4 RNA processing and/or have an impact on other endogenous retroviral sequences (Mason et al. 2014). To have more insights into this hypothesis, we identified, lassified and characterized the HML-10 sequences that are present in the human genome GRCh37/hg19 assembly. We used the model-based software Retrotector (Sperberg et al 2007) to search HML-10 sequences in the human genome assembly GRCh37/hg19 and identified 10 HML-10 proviruses in chromosomes 1, 6, 16, 19 and Y. These proviruses were confirmed to belong to the HERV-K (HML-10) group and shown to have the Rec sequence. Out of the 10 identified HML-10s, 5 sequences have both LTRs, 4 have only 3'-LTR and 1 sequence is without LTRs. Age estimation analysis performed on the 5 sequences with both LTRs indicated that they inserted into the human genome >25 Mya ago. Five sequences conserved the primer binding site (PBS) region, all recognizing the Lys tRNA. Translational analysis showed that all proviral sequences have multiple stop codons that preclude their production of functional proteins. Phylogenetic analyses were performed with complete DNA sequences as well as with the Pol amino acid sequences and will be presented. Overall, we have identified and characterized 10 HML-10 sequences in the human genome GRCh37/hg19 assembly. Precise knowledge of all HML-10 sequences will allow further investigation of their physiological and pathological role in autoimmune diseases (Yu & Whitacre 2004), particularly their possible involvement in type 1 diabetes, giving new insights into their understanding. References 1. Tassabehij et al. NAR 22, 5211-17 (1994). 2. Mason et al. Diabetes 63, 1789-95 (2014). 3. Sperber et al. NAR 35, 4964-76 (2007). 4. Yu & Whitacre Trends in immunology 25, 694-99 (2004).

Abstract Introduction Bleeding is a common complication after cardiac surgery. However, lower gastrointestinal bleeding is not usually associated with this type of surgery. Case presentation A 50-year-old man with a history of aortic regurgitation underwent elective mechanical valve replacement under cardiopulmonary bypass. He experienced a complicated intraoperative course involving unexplained cardiac arrest following induction of anesthesia. He also developed two episodes of massive lower gastrointestinal bleeding secondary to mucosal ischemia while convalescing in the cardiothoracic surgery intensive care unit. After unsuccessful attempts to control the bleeding, exhaustion of blood products, and consideration of the high risk of mortality associated with surgery and the possibility of early- and long-term surgical complications, the decision was made to administer two successive doses of recombinant activated factor VII at 60 mcg/kg. Hemostasis was achieved without adverse systemic or valvular effects. Conclusions A favorable outcome was achieved after administration of recombinant activated factor VII, which controlled the patient's severe lower gastrointestinal bleeding. This outcome suggests the need to raise awareness about the use of this drug in dire circumstances when other conventional measures fail or are unsuitable.

Introduction: Intractable bleeding is one of common adverse events after cardiac surgeries. Recombinant activated factor VII (rVIIa) showed efficiency in controlling postoperative intractable bleeding (1). Its usage after cardiac surgeries should be more investigated. Patients and methods: - All patients received rVIIa post cardiac surgeries over a period of two years were included in a retrospective descriptive study. All patients were evaluated for base line laboratory results and comorbidities, operative details, dose of rVIIa received, total chest drains pre and post rVIIa administration, total blood and blood products given pre and post rVIIa, post rVIIa laboratory results, complications of rVIIa, length of stay in intensive care unit. Results: -. We recruited 19 patients with a mean age of 49±18 years who received RVIIa in a dose of 90 mcg/kg. Packed red blood cells transfusion post rVIIa administration was decreased from mean of 10±6 units to 3.7±1.7 units P<0.0001. Chest drains post rVIIa administration were decreased from median of 2000 ml and IQR of 1200 to median of 500 ml and IQR of 500 P<0.1 .No complications related to rVIIa administration were observed. Discussion: - The study highlight the following findings: Efficiency and safety of rVIIa in the control of intractable bleeding post cardiac surgeries. Usage of rVIIa saves blood bank resources, decreases the need of surgical reopening and decreases morbidity. More studies needed to elaborate clinical guidelines for the usage of rVIIa in the management of intractable bleeding post cardiac surgeries. Conclusion: - There is increase need for clinical guidelines for the usage of rVIIa post cardiac surgeries. In our experience at Qatar heart hospital recombinant activated factor VII is safe and efficient treatment to control intractable bleeding post cardiac surgeries. Reference: - (1) Conrad V. Bishop, William E.P. Renwick, Chris Hogan, Michael Haeusler, Annabel Tuckfield and James Tatoulis: Recombinant Activated Factor VII: Treating Postoperative Hemorrhage in Cardiac Surgery. Ann Thorac Surg 2006; 81:875-879.

Background: Small RNAs play an essential role in fundamental biological processes such as differentiation, proliferation, apoptosis and homeostasis. Evidence suggests that small RNAs may also play function in Cancer progression. The conventional in-vitro two-dimensional (2D) monolayer cell culture models are not sufficient to explain the exact mechanism behind tumor invasion and metastasis. The objective of this study is to analyze the role of small RNAs in tumor invasion and metastasis using in vitro 2D and anchorage independent (3D) models in ovarian cancer cell lines. Methods: Total RNA samples were isolated from several 2D and 3D ovarian cancer cell lines. Small RNA libraries were prepared and sequenced using Next-Generation Sequencing. Results: Gene expression levels of 3D culture differ from 2D culture, especially in epithelial and mesenchymal target genes. We were able to identify the predominant pathways that small RNAs regulate in 3D cultures. These pathways were involved in cellular invasion, migration, metastasis, proliferation, and tumor growth. Conclusion: The Results from this experiment suggest that small RNAs play a crucial role in controlling tumor invasion and metastasis in the studied phenotypes. Therefore, small RNAs may offer a critical target for the development of anti-cancer drugs.

Background and Objective: In the Middle East and North Africa, hepatitis C virus (HCV) infection distribution appears to present a wide range of prevalence. The scale and nature of HCV infection exposure in Yemen is poorly known. The objective of this study was to establish the national population-level HCV prevalence in Yemen and to characterize the epidemiology of this infection in the Yemeni population. Methods: We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Sources of data included PubMed and Embase databases. Our analysis included all primary studies reporting HCV antibody prevalence or incidence measures in Yemen. Extracted measures were then classified and analyzed on the basis of the study population's risk of acquiring HCV. Meta-analyses were conducted incorporating inverse variance weighting and using a random-effects model to pool summary estimates of HCV prevalence among general population groups. Results: We identified 28 studies providing a total of 46 measures on HCV prevalence and none on incidence in Yemen. Pooled HCV prevalence in the general population was 1.8% (95% confidence interval (CI): 1.05-2.75). Among blood donors the prevalence ranged from 0.2 to 3.0% depending on governorate of origin. The highest prevalence within the general population groups was reported among pregnant women in one study (8.5%) followed by a study of African migrant community living in a Shanty town in Sana'a (5.2%). Among high risk populations, HCV prevalence among hemodialysis patients was 40.0% in 1999 and 62.7% in 2007. Among patients with acute and chronic liver disease it was 74.1%. Conclusions: National-level HCV prevalence in Yemen is slightly higher than that in developed countries, but comparable to several other countries in the Middle East and North Africa. The high prevalence found among high risk groups may indicate limitations in implementation of infection control and blood screening protocols, or possibly dates back to exposures before these measures were expanded. These findings are of particular relevance for resource allocation and HCV public health programming in Yemen. HCV prevention policy in Yemen should focus mainly on prevention and infection control in settings of exposure such as in medical care and among people who inject drugs.

Background It is widely perceived that little is known about the epidemiology of HIV infection among people who inject drugs (PWID) in the Middle East and North Africa (MENA). The primary objective of this study was to assess the status of the HIV epidemic among PWID in MENA by describing HIV prevalence and incidence. Secondary objectives were to describe the risk behavior environment and the HIV epidemic potential among PWID, and to estimate the prevalence of injecting drug use in MENA. Methods This was a systematic review following the PRISMA guidelines and covering 23 MENA countries. PubMed, Embase, regional and international databases, as well as country-level reports were searched up to December 16, 2013. Primary studies reporting 1) the prevalence/incidence of HIV, other sexually transmitted infections, or hepatitis C virus (HCV) among PWIDs; or 2) the prevalence of injecting or sexual risk behaviors, or HIV knowledge among PWID; or 3) the number/proportion of PWID in MENA countries, were eligible for inclusion. The quality, quantity, and geographic coverage of the data were assessed at country level. After multiple level screening, 192 eligible reports were included in the review. There were 197 HIV prevalence measures on a total of 58,241 PWID extracted from reports, and an additional 226 HIV prevalence measures extracted from the databases. Findings We estimated that there are 626,000 PWID in MENA (range: 335,000-1,635,000, prevalence of 0.24 per 100 adults). We found evidence of HIV epidemics among PWID in at least one-third of MENA countries, most of which are emerging concentrated epidemics and with HIV prevalence overall in the range of 10-15%. Some of the epidemics have however already reached considerable levels including some of the highest HIV prevalence among PWID globally (87.1% in Tripoli, Libya). The relatively high prevalence of sharing needles/syringes (18-28% in the last injection), the low levels of condom use (20-54% ever condom use), the high levels of having sex with sex workers and with men who have sex with men (15-30% and 2-10% in the last year, respectively), and of selling sex (5-29% in the last year), indicate a high injecting and sexual risk environment. The prevalence of HCV (31-64%) and of sexually transmitted infections suggest high levels of risk behavior indicative of the potential for more and larger HIV epidemics. Conclusions Our study identified a large volume of HIV-related biological and behavioral data among PWID in the MENA region. The coverage and quality of the data varied between countries. There is robust evidence for HIV epidemics among PWID in multiple countries, most of which have emerged within the last decade and continue to grow. The lack of sufficient evidence in some MENA countries does not preclude the possibility of hidden epidemics among PWID in these settings. With the HIV epidemic among PWID in overall a relatively early phase, there is a window of opportunity for prevention that should not be missed through the provision of comprehensive programs, including scale-up of harm reduction services and expansion of surveillance systems.

Background: Type II Diabetes Mellitus (DM) is one of the leading chronic diseases in Qatar as well as worldwide. However, the risk factors for DM in Qatar and their prevalence are not well understood. We conducted a case-control study with the specific aim of estimating, based on data from outpatients with DM in Qatar (cases) and inpatient/outpatient controls, the association between demographic/lifestyle factors and DM. We also estimated the contribution of these factors to the occurrence of DM cases among Qatari nationals and non-Qatari expatriate population. Methods: A total of 459 patients with DM from Hamad Medical Corporation Hospital (HMC) outpatient adult diabetes clinics and 342 control patients from various outpatient clinics and inpatient departments at HMC were identified using rigorous sampling methodologies and recruited between the years 2006 and 2008. The association between risk factors and DM was evaluated using bivariate and multivariate logistic regression analyses, and for the population at large and for only Qatari nationals. In addition to odds ratios (OR) and 95% confidence intervals (95% CI), we calculated the population attributable risk fractions for demographic and lifestyle factors in relation to DM. Results: Qatari nationality was the strongest risk factor for DM (adjusted OR=5.5; 95% CI=3.5-8.6), followed by higher monthly income (defined as ≥ 3000 riyals, OR=5.1; 95% CI=3.0-8.7), age > 65 years (OR=3.3; 95% CI=0.9-11.4), male gender (OR=2.9; 95% CI=1.8-4.8), obesity (body mass index ≥ 30, OR=2.2; 95% CI=1.5-3.2), no college education (OR=1.7; 95% CI=1.2-2.6), and no daily vigorous/moderate activity (OR=1.5; 95% CI=0.9-2.3). Among Qatari nationals, obesity was revealed as the main risk factor for DM (unadjusted OR=3.0; 95% CI=1.6-5.6) followed by no college education (OR=2.7; 95% CI=1.5-5.1), while consanguinity did not appear to play a major role in predicting DM (OR=1.5; 95% CI=0.8-2.8). Our findings further suggested that eliminating obesity and improving access to education could reduce DM cases by up to one third in the population at large (31.7% and 26.8%, respectively) and up to half (46.9% and 49.3%, respectively) among only Qatari nationals. Promoting physical activity may as well reduce the burden of DM by up to 9.4% in the population at large and up to 17.3% among Qatari nationals. Conclusions: Demographic and lifestyle factors were revealed as the main risk factors for the high DM levels observed in Qatar, with a contribution that appears to outweigh that of genetic risk factors. While further evaluation of these factors among the Qatari population (as opposed to the population at large) is important and of interest, these findings highlight the need to focus short-term DM interventions on addressing demographic and lifestyle risk factors to achieve substantial and timely declines in DM levels.

Background: Negative Pressure Wound Therapy (NPWT) is well-established in the management of infected surgical wounds. However, it is a relatively new modality of treatment for the protection of clean surgical sites. This study was aimed at developing guidelines for the use of negative pressure incision management to prevent surgical wound complications after heart surgery. Methods: In this prospective study, we included 134 patients at high risk for sternotomy wound complications from September 2011 to June 2014. Selection criteria included: obesity, diabetes, smoking and COPD, fragile sternum, bilateral mammary arteries, delayed primary closure and repeated operations. We applied negative pressure of - 125 mm Hg on the wounds of 67 patients immediately following skin closure, the dressing was removed after 5 to 7 days. The results were compared to a control group with matching criteria (n=67) who had standard dressings. The primary end point of the study was the development of wound complications including surgical site infection, hematoma formation and sternal dehiscence within 30 days. Results: 2 of the 67 patients who underwent negative pressure incision management developed superficial surgical site infection within the 30 days postoperative period (2.99%). The wound infection of the two patients settled with regular dressings and oral antibiotics. While in the control group with conventional wound dressings (n=67), 5 patients developed superficial surgical site infection and one patient suffered a deep sternal wound infection (total 6 out of 67 patients, 8.96%). Based on our experience, we have proposed some selection criteria for the use of negative pressure incision management following heart surgery (table1). Conclusions: Negative pressure is potentially beneficial in the reduction of wound complications. There are no published criteria so far for the application of negative pressure on clean surgical sites post cardiac surgery. Therefore, we proposed some guidelines for the use of negative pressure incision management to protect high risk sternotomy wounds.

Background: a 30 year old gentleman was referred to our in thoracic surgery clinic with an incidental finding of an abnormal shadow around the apical region of the heart on the chest radiograph. He was asymptomatic and non smoker and he had no chronic medical illness in the past. He had no specific findings on physical examination. Echocardiogram revealed rounded cyst in the pericardium around the hear apex measuring 5.9 by 4.1cm. Chest CT Angiography revealed no evidence of coronary artery disease. Magnetic Resonance Imaging (MRI) showed a well defined round pericardial cyst close to the left ventricular apex but there was no evidence of infiltration the left ventricle or wall abnormal enhancement. Procedure and Findings: He underwent robotic excision of the cardiac apical cyst. An inflamed 5 by 6cm cystic mass was found densely adherent to the apical pericardium. There were no adhesions or pleural effusion and the lungs and pleural surfaces were looking normal. The cyst was excised and the cavity was irrigated with hypertonic saline. A chest drain was left in the left pleural cavity. Postoperatively the patient had no complications.Bethadine diluted in normal saline was instilled into the pleural space via the chest drain for washing any remains of the infection. The drain was removed after 48hrs and the patient was discharged from the hospital on antiparasitic treatment (Albendazole tablets). Results: the patient had an uneventful recovery from surgery; he was reviewed in the clinic and had no evidence of recurrence of the disease. Histopathology report revealed laminated membranes with few protoscolices consistent with hydatid cyst (Eccinococcal infection). Conclusion : this is an unusual presentation of cystic echinococcosis (hydatid disease) which was excised robotically. Cystic Echinococcosis is a parasitic disease caused by infection with the larval stage of a tiny tapeworms of Echinococcus granulosus which usually grows in dogs (definitive host), sheep, cattle, goats, and pigs (intermediate hosts). Although most infections in humans are asymptomatic, hydatid disease can lead to the development of harmful, slowly enlarging cysts mainly in the liver and lungs. However, it might rarely affect other organs but it often remains unnoticed and neglected for years.

Rational: Heart failure is a common, costly, and frequently fatal disease. One in three cases of heart failure is due to dilated cardiomyopathy. NHE1 expression and activity are increased in this cardiac defect. We have previously shown that elevated activity of NHE1 in the cardiomyocytes induced cardiac hypertrophy in transgenic mice. However, it protected the myocardium following ischemia/reperfusion. This overexpression of active NHE1 elicited modulation of gene expression in cardiomyocytes including an up regulation of myocardial osteopontin (OPN) expression and a decrease of peroxisome proliferator-activated receptor (PPAR)γ. Since transgenic mice phenotype is very often influenced by the integration position of the transgene, we decide to create new transgenic mice to ascertain our previous data and to test the role of modulated genes. Method and results: We have created 5 new mouse lines overexpressing a constitutively active form of NHE1 specifically in cardiomyocytes (KNHE1+). We have evaluated by echocardiography the cardiac phenotypes and function of two of these new mouse lines. Then heart were harvested and submitted to histological, immunohistological and QRT-PCR analysis. Our data showed that in the both KNHE1 studied lines, a number of mice demonstrated heart remodeling identified by a significant decrease in diastolic interventricular septal (IVSd) and diastolic left ventricular posterior wall (LVPW) thickness and an increased diastolic left ventricular internal dimension (LVIDd) (see table 1). Moreover these hearts demonstrated impaired function with a decreased fraction shortening (<21 % vs 31% in wild type mouse) and ejection fraction. However, the proportion of 12 weeks old mice demonstrating this defect is different in both lines 13% (3/24) in line #4 and 58% (11/19) in line#1 vs 0% (0/37). ANP and BNP up regulation in line #1 confirmed heart suffering. Current experiment is designed to perform a longitudinal study examining evolution of these proportions with the age of the animals. Conclusions: We have developed an interesting comparative model of active NHE1 transgenic mouse lines with low and high rate dilated cardiomyopathy identifying evidence of early and late mechanisms. Further studies will be conducted to evaluate the phenotypes of the other mouse lines and the mechanism by which these changes are occuring.

The endoplasmic reticulum (ER) functions as a storehouse for intracellular calcium. STIM1, a calcium sensor, localizes mostly to the ER membrane. Following Ca2+ store depletion, STIM1 forms puncta that localize to the cortical ER and bind Orai1, a plasma membrane Ca2+ channel, to allow Ca2+ influx. This is the predominant pathway for Ca2+ influx in non-excitable cells and is referred to as Store-Operated Calcium Entry (SOCE). Mutations in STIM1 and Orai1 cause severe combined immunodeficiencies and are linked to several forms of cancers. Tight regulation of the levels of STIM1 and Orai1 is crucial for maintaining the subcellular levels of Ca2+ required for its numerous functions. We are interested in mechanisms of post-transcriptional regulation of STIM1. We have developed a system that allows us to test miRNA-mediated regulation by transfecting different cell types using a GFP and a 3'UTR transcriptional fusion and GFP with no 3'UTR as a control. mCherry expressed from the same vector is used as an internal control of transfection efficiency. The stoichiometry of GFP and mCherry levels in the experimental conditions for Stim1 3' UTR was found to be significantly different from those in the control. Knockdown of Ago2, an important mediator of the miRNA pathway, by siRNA restored GFP expression from these constructs suggesting miRNA-mediated regulation. We have identified a miRNA that regulates Stim1 expression in HEK 293 (embryonic kidney), MCF7 (non-metastatic breast cancer) but not in MDA-MB231 (metastatic breast cancer) cell lines. The mechanisms by which this occurs will be discussed.

Background: Breakdown of blood-retinal barrier (BRB) and subsequent hyperpermeability is a cardinal feature of early diabetic retinopathy (DR) and leading cause of blindness. Fatty acid metabolism is implicated in several biological functions via multiple signaling pathways including the synthesis of bioactive metabolites. Our previous studies established 12/15-lipoxygenase (12/15-LOX)-derived 12- and 15- hydroxyeicosatetraenoic acids or HETEs as proangiogenic mediators during DR via disrupting the retinal levels of vascular endothelial growth factor and pigment epithelium derived factor (PEDF). Purpose: 1) To screen the impact of high glucose (HG) treatment on the levels of bioactive lipids including 12/15-LOX metabolites in cultured human retinal endothelial cells (HREC), 2) To test the impact of 12/15-LOX deletion on BRB function and explore the underlying mechanism in particular the role of NADPH oxidase as a major source of oxidative stress during DR. Material and Methods: Liquid chromatography-mass spectrometry (LC/MS) was used in a comprehensive lipidomic screen of HRECs treated with or without HG (30mM D-glucose). Effect of 12- or 15-HETE (0.1 M) on leukostasis and angiogenesis (tube formation) was examined in HRECs transfected with siRNA against the catalytic subunit of NADPH oxidase (NOX2) or the scrambled siRNA or treated with or without the NADPH oxidase inhibitor (apocynin, 30°M). Human leukocytes (PMNs) labeled with lipophilic fluorescent probe were used for leukostasis assay. Migration assay was performed using the Electrical Cell Impedance Sensor (ECIS). Retinal vascular changes were examined by fluorescein angiogram (FA) and Optical Coherence tomogram (OCT) in streptozotocin-induced diabetic wild type (WT) or 12/15-LOX-knockout mice and in mice received intraocular injection with 12-HETE or 12-HETE with PEDF. Western blotting, immunofluorescence and multiplex system were used to test the changes in the levels of inflammatory markers. Results: Out of 126 bioactive lipids screened, 70 were undetected, 47 un-significantly changed, and 9 metabolites were significantly up-regulated by HG compared to osmotic control (5mM D-glucose+25 mM L-glucose). Intriguingly, six metabolites among the 9-increased are the products of 12/15-LOX pathway (15-HETE, 11-HETE, 8, 15-DiHETE, 12-HETE, 17-HDoHE, and 13-HODE). Of these 15-HETE has the highest fold increase (p value= 0.004). Thereafter, we pursued to determine whether the altered metabolites of 12/15 LOX play a role in BRB dysfunction during diabetes. Retinal vascular leakage was significantly reduced in diabetic mice deficient in 12/15-LOX as evidence by FA and less albumin leakage compared with diabetic wild-type littermates. Furthermore, intravitreal injection of 12-HETE per se in normal WT mice resulted in a marked increases in the vascular leakage and expression of inflammatory markers such as ICAM-1, VCAM-1, CD45 as well as the NOX2 compared to vehicle-injected control or to mice received both 12-HETE and PEDF. In vitro, 12/15-HETEs induced HREC leukostasis, migration, and tube formation. These effects were inhibited by the concomitant use of apocynin and by silencing NOX2. Conclusion: Retinal endothelial 12/15-LOX is activated by hyperglycemia causing overproduction of 12- and 15-HETEs. These metabolites are implicated in the pro-angiogenic, -oxidative and -inflammatory effects of hyperglycemia in HREC. Thus, targeting this signaling system represents an attractive therapeutic strategy to prevent and treat DR.

Neuroblastoma is a solid malignant embryonic tumor. It is usually diagnosed in the infancy and rarely found after the age of 10 years. In the current treatment options, CDDP and TOPO are included. Methods: Neuroblastoma (SH SY-5Y) cell death was investigated after treatment with CDDP and TOPO (0.1nM-1μM) using Trypan Blue Cytotoxicity Test and Total Cytotoxicity and Apoptosis Detection Kit (FACS). These data are compared to the drug triggered increase of the intracellular calcium ([Ca2+]i) concentration using live calcium imaging with the calcium sensitive dye Fluo-4 AM. Furthermore, we analyzed changes of gene expression of selected [Ca2+]i signaling related genes such as the calcium binding protein S100A6, IP3 receptors, Ryanodine Receptors, Calmodulin (CALM) and the Calmoduling Binding Transcriptor Activator (CAMTA1). Results: With increasing concentration of either of the two substances the amount of viable cells was reduced after 24h of application. The tests revealed a higher cytotoxicity of TOPO (about 25% cell survival at 0.1μM) compared to CDDP (more than 80% survival). With increasing concentrations the percentage of cells which were in the “late apoptosis” stage increased for both drugs but were more pronounced for TOPO. A similar observation was made when the incubation time for the two drugs was prolonged to 48h or 72h when the amount of viable cells was further reduced. Individual (but not all) neuroblastoma cells increased their [Ca2+]i after the application of either CDDP or TOPO (both 1 μM). Over the period of three to four hours the fluorescence increased about 40%. The increase was time and concentration dependent for CDDP and TOPO, while a concentration of 0.01μM was most efficient to increase [Ca2+]i. CDDP and TOPO influence the gene expression of SHSY-5Y cells, targeting specific calcium signaling related genes. In this context, a concentration and time dependent increase in the expression of S100A6 was observed in the cells treated with CDDP. TOPO showed a more pronounced effect than CDDP in increasing the mRNA expression of S100A6. The expression of ITPR1 and ITPR3 genes encoding the type 1 and 3 of the IP3R were found deregulated in the neuroblastoma cells treated to CDDP and TOPO. The 1μM CDDP exposure for 72h was responsible of ITPR1 and ITPR3 down regulation however; the same concentration applied for 24h transiently increased the mRNA expression of ITPR3. The application of TOPO did diminished concentration and time dependently the mRNA expression of ITPR1 after 24h and 72h exposure and of ITPR3 after 72h exposure, however 24h exposure to TOPO did transiently increased the mRNA expression of ITPR3 for the lower concentrations tested. The expression of Ryanodine Receptor genes RYR1 and RYR3 was found deregulated in the neuroblastoma cells treated to CDDP and TOPO. Conclusion: Time and concentration dependently, the treatment of SHSY-5Y cells with TOPO and CDDP increased the cell death, at clinical relevant concentration. That correlates with increased [Ca2+]i levels and with the deregulation in gene expression of calcium signaling related genes suggesting that [Ca2+]i regulation is involved in the anticancer effects of TOPO and CDDP.

Biocompatible Graphene Oxide with Anchored Zwitterionic Moiety - Synthesis, Characterization and Application Markéta Ilčíková1, Zuzana Kroneková2, Anna Záhoranová2 and Peter Kasák1* 1 Center for Advanced Materials, Qatar University, P.O.Box 2713 Doha, Qatar 2 Polymer Institute, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, Slovakia *Corresponding author: [email protected] The novel biocompatible graphene oxide (GO) bearing zwitterionic moiety was synthesized and characterized. The zwitterionic structures have recently gained attention in biomedical applications as materials for development of ultra-low fouling surfaces. Generally, zwitterions contain both negative and positive charge in their structures; however the overall charge is neutral. That impart them highly hydrophilic performance; the adsorbed water then prevent the cells or bacteria to interact with surface. Graphene is two dimensional filler interesting predominantly due to high electrical conductivity. In oxidized form the electrical conductivity is compromised due to presence of hydroxyl, epoxy and carboxyl functional groups. In this work, the hydroxyl groups were utilized for anchoring the zwitterionic moiety onto the GO surface. The reaction was performed in two steps. First the silanization with (3-mercaptopropyl)trimethoxysilane was preformed to introduce the thiol functionality onto the GO surface that was reacted with sulfobetaine monomer (3-((2-methacrylamidoethyl)dimethylammonio)propane-1-sulfonate) through thiolene click reaction in the following step. The successful modification was confirmed by FTIR and TGA. Compared to neat graphene, the presence of sulfobetaine improved the graphene biotolerability for fibroblasts and pancreatic beta cells. Modification of GO surface with zwitterionic moiety prevents its negative effect on cell viability. Thus the adsorption of cells on the surface and the cell - GO surface interaction is effected. The modified GO will be used for modification of electrode at biochips construction, and the electrorheological response will be discussed as well. Acknowledgement: This publication was made possible by NPRP grant # NPRP-6-381-1- 078 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.

One goal in the field of soft tissue biomechanics is to understand and to model the properties of collagen-fibers in biological tissues such as blood vessels, brain tissues, and skin which undergo growth and remodeling processes. Experimental studies of Bhole et al.\ [1] suggest that the mechanical properties of fibers in biological tissues depend not only on the current state of the deformation but also on the deformation history. Demirkoparan et al.\ [2] developed a hyperelasticity based framework taking this effect into account. The framework developed in [2] uses an additive hyperelastic material model for the strain energy density, $W = W_m + W_f$. The matrix contribution $W_m$ does not take time-dependent changes of the material properties into account yet the fiber contribution $W_f$ changes over time as it is modeled in terms of a constant creation rate and a deformation dependent dissolution rate of the fibers. Then Topol et al.\ [3] have investigated the predictions of such a model by studying the effect of fiber deformation state at the time of their creation on the overall mechanical properties of the material. This research investigates the relation between the change in the fiber density, the Cauchy stress development, and the deformation of the material.

Diabetic retinopathy (DR) is a leading cause of blindness among working diabetic patients worldwide. The current therapeutic strategies are limited by several side effects. Thus, it is important to investigate novel approaches for therapeutic intervention. Early inflammatory response and late neovascularization (NV) are cardinal clinical signs of the DR. We have previously demonstrated the involvement of bioactive lipids especially the products of omega-6 polyunsaturated fatty acids (PUFAs) such as arachidonic acids in the development of retinal hyperpermeability and NV during DR. Hyperglycemia is a major risk factor for endothelial cell activation and development of microvascular dysfunction during DR. Overwhelming evidences suggest that omega-3 PUFAs like DHA (C22:6n-3) are protective in proliferative DR. In the present study, we investigate the effect of exogenous supplementation of DHA on human retinal microvascular endothelial cells (HREC) under hyperglycemic conditions. Cells were treated with or without high glucose (HG, 25 mM) for 36 hrs in the presence or absence of the DHA (30 µM). To study the early inflammatory response, cells were analyzed for cell barrier function by measuring the changes in transcellular electrical resistance (TER) using the Electrical Cell-substrate Impedance Sensing (ECIS). Hyperglycemia resulted in a significant decline in TER while it was significantly improved by DHA. Furthermore, to investigate the effect of DHA on the proangiogenc properties of hyperglycemia in HREC a scratch-wound repair assay was carried out in cultured HREC cells treated with or without HG in the presence or absence of DHA. The migration and proliferation of cells induced by HG was reduced on supplementation of cells with DHA. Levels of apoptosis and oxidative stress were also monitored under the effect of hyperglycemia. While HG treatment did not result in any change in level of apoptosis, it resulted in sharp induction of oxidative stress in cells, which however was ameliorated under the effect of DHA treatment to hyperglycemic cells. Real-time PCR revealed significantly enhanced transcripts for the vascular endothelial growth factor (vegf) in hyperglycemic cells while reduced expression of the pigment epithelium derived factor (pedf) and the peroxisome proliferator activated receptor gamma (PPAR) was observed. These changes were prevented by DHA. Anti-inflammatory properties of DHA were further evinced by monitoring the levels of several inflammatory cytokines and angiogenic factors by multiplex enzyme-linked immunosorbent assay. Glucose treatment resulted in upregulation of various pro-angiogenic factors like angiogenin, angiopoietin, pdgf, pigf and this effect of HG was prevented by DHA treatment. Similarly, inflammatory cytokines like TNF-alpha and MCP1, which are involved in promotion of angiogenesis and inflammation were induced by HG and was attenuated in the presence of DHA. Interestingly, anti-inflammatory cytokines like IL-1 beta and IL-6 were markedly increased by DHA as compared to HG alone. These results suggest that DHA protects HREC against the pro-angiogenic, -inflammatory and -oxidative effects of HG and thus it can be proposed as alternative or supplementary treatment to the current therapeutic strategies of DR.

General consensus exists that biomedical research is a key determinant of innovation, health, and economic wellbeing. However, the answer to the question how do we determine and quantify the value and the impact of research is apparently simple, while a thoughtful and analytical answer quickly becomes very probing and difficult to address. Qatar has dedicated itself to transitioning from a resource-based to a knowledge-based economy and Sidra Medical and Research Center is envisioned to become a beacon of learning and a world-class institution of its kind in the MENA region. A unique opportunity exists at Sidra for the development of a comprehensive system to capture the return on investment (ROI) for research on knowledge, the economy, and on health outcomes. This would enable Sidra to establish itself as a leader in the field of impact assessment, ahead of many other countries also grappling with this thorny problem. In fact, Sidra's status as a startup creates a rare situation where measurement and analysis of ROI can be initiated from a baseline. Work can then be done prospectively rather than trying to gather information retroactively, a difficult obstacle that institutions that have attempted to implement similar systems have had to try to overcome. In order to take advantage of this opportunity at Sidra, we propose creating a core system consisting of a smart, web-based, auto-populated "Sidra Biosketch". This system will interact with internal enterprise resource planning, grants and proposal management systems, as well as external publication, patent, startup and commercial license databases (e.g., PubMed). This system takes into consideration two critical factors. First, it minimizes the administrative burden on investigators and administrators. Second, it does not solely measure stochastically by counting numbers of publications, citations, etc. Rather, it focuses and relies heavily on content and contextual assessment to enable Sidra to fully understand exactly what research is being done, where it is being done, by whom, and with what collaborators. The impact on knowledge, economic and health outcomes can then be mapped through dynamic network analyses, natural language processing, and topic modeling approaches. This approach to measuring the impact of Sidra research will maximize efficiency of input and analysis as well as the quality of outputs and results. Meanwhile, this system will also enable Sidra to make decisions that will enhance resource allocation and allow for better assessment of its contribution to progress in science, the economy, and health outcomes in Qatar and worldwide.

Nonlinear continuum mechanics is commonly used to study the response of highly de- formable materials. Nowadays, the proposed material models often include internal ma- terial variables in order to capture realistic engineering behavior. The theoretical back- ground is mature and its implementation in the frame of nite element method is well established. Solely, these material constitutive models are expressed in terms of defor- mation gradient F, its derived quantities, and various multiplicative decompositions such as F = ^F F (1) This multiplicative decomposition serves to pertain particular portions of F to specic parts of the material response. The usual scheme is then that ^F models elastic response and it is associated to the rules of variational calculus. The F portion then models inelastic response, usually by means of a time dependent evolution law. Recently, the arguments of variational calculus have been applied to both portions of the deformation gradient decomposition for incompressible hyperelastic material [1]. The decomposition itself is then determined by an additional internal balance equation that is generated by such a variational treatment. The internally balanced compressible hyperelastic material response is presented in [2]. Fundamental studies of this type are key to better physics-based modeling of complex biomechanical processes in soft tissue, including long time scale processes of growth, and short time scale processes of wound healing. The FE formulation of this internal balance multiplicative decomposition is naturally achieved by linearizing the weak form that is obtained by the variation with respect to both portions of the multiplicative decomposition. In this work, we would like to present the Updated Lagrange Formulation. This formulation will be implemented into com- mercial nite element package FEAP that will facilitate in future studying engineering application in the eld of biomechanics. The correctness of implementation will be ex- amined by simulating homogeneous deformations such as uniaxial loading, dilatation and simple shear. References [1] H. Demirkoparan, T. J. Pence, and H. Tsai. Hyperelastic internal balance by multi- plicative decomposition of the deformation gradient. Archive for Rational Mechanics and Analysis, 2014. DOI: 10.1007/s00205-014-0770-9. [2] A. Hadoush, H. Demirkoparan, and T.J. Pence. Modeling of soft materials via mul- tiplicative decomposition of deformation gradient. In USNCTAM, 2014.

Background Islet cell death is a common feature of type 1 diabetes (T1D), including after islet cell transplantation, as well as of type 2 diabetes (T2D). As of today, we lack tools to quantitatively detect islet cell loss prior to the clinical onset of diabetes, or to predict the progression of established diabetes. Our preliminary data demonstrates that a signature of 20 different non-coding (nc) RNAs (including microRNAs) reflects beta cell death (RAPID: RNA-based Analysis for Prediction of Islet Death signature). Objectives 1)To identify a high-throughput platform for detection of ncRNAs/microRNAs 2)To validate the RAPID signature of 20 ncRNAs using this high-throughput platform 3)To test the suitability of these ncRNA biomarkers in predicting the progression to T1D Method Next Generation Sequencing (NGS) studies on developing human pancreas have led to the identification of specific ncRNAs that are found to be expressed specifically in the human pancreatic islets. We use combined FISH and immunostaining to confirm the localization of each miRNA in human islets. TaqMan-based real-time PCR on plasma from at-risk diabetic individuals and age/gender matched controls in a longitudinal study, is used to measure the abundance of specific ncRNAs in plasma-EDTA samples of individuals at risk of T1D. I will discuss the comparison of 2 different ultra-high-throughput TaqMan real-time PCR platforms that we use to analyze these samples and present the data demonstrating the suitability of these RNA-based biomarkers in predicting the progression to T1D. Results Present study has allowed us to validate a microRNA-based signature of islet cell death in diabetes. Using a cohort of kids at risk of T1D, we demonstrate the suitability and advantages of these ncRNA biomarkers over traditional / conventional antibody- and glucose-based detection. The development of an assay for early detection of islet injury and death has direct applications in clinical medicine. Hopefully, this study results will inform medical researchers as to how to predict the development of Type 1 diabetes, monitor response to interventions such as islet transplantation, vaccines and drugs that aim to retard beta cell loss or promote beta cell regeneration.

Over the last two decades the prevalence of obesity has reached epidemic levels worldwide. Secondary major health risks, such as hypertension, insulin resistance, type 2 diabetes and cardiovascular diseases, can be summarized as the metabolic syndrome and are highly associated with obesity. In cases in which energy intake e.g. through high caloric food intake exceeds energy expenditure the overall energy homeostasis is imbalanced. White adipose tissue depots mainly act as the body's main energy storage and additionally act as an endocrine organ by releasing adipokines and cytokines into the body. Additionally, functional brown adipose tissue (BAT) has been discovered through radiological detection in the last years in substantial amount in adults. Formerly overlooked BAT, which was thought to be absent in the human adult, has therefore recently become an interesting anti‐obesity target due to its ability to dissipate energy in form of heat. We extensively characterized human brown PAZ6 adipocytes in comparison with a white adipose cell line SW872. In addition, human SGBS adipocytes were included in the analysis. Brown and white adipocyte markers were tested by quantitative Real-time PCR. Fluorescent and Oil‐Red staining assessed the quantity and quality of the differentiation process. Next generation RNA sequencing of undifferentiated and mature SGBS and PAZ6 cells was performed in order to elucidate pathways distinctly activated in white vs. brown human adipocytes. Functional assessment of oxidative rates of each cell line was conducted using the Seahorse technology. Whereas PAZ6 and SW872 cells showed classical molecular and phenotypic markers of brown and white adipocytes, respectively, SGBS cells presented a versatile phenotype of adipocyte. 14 days after initiating the differentiation process the expression of classical brown marker such as UCP‐1 and PPARγ peaked and declined until day 28. The white adipocyte marker Tcf21 however, showed reciprocal behavior. Interestingly, Leptin levels peaked at day 28 whereas the highest adiponectin mRNA levels were monitored at day 14. Phenotypic analysis of the abundance and shape of lipid droplets were consistent with the molecular patterns. On day 14, SGBS cells showed multiple small droplets, however the number of droplets decreased and the size increased until day 28 as expected for a white adipocyte phenotype. Lastly, functional metabolic analysis showed the highest oxidative rate of mature SGBS cells on Day 14, which remained consistent or slightly decreased until day 28. SGBS cells are widely used as a model for white adipocytes. Our data suggest that the cell line harbors a versatile phenotype, which changes throughout their mature stage. Many reports suggest recently that the traditional classification of adipocytes is not exclusive and the existence of beige/brite adipocytes has been shown. We are presenting data derived from a human cell line model, which harbors characteristics of both distinct phenotypes. This knowledge will be of importance for studies aimed to increase brown fat depots in order to increase energy expenditure in obese subjects with the ultimate goal of weight reduction.

Background: Polycythemia Vera (PV), Essential Thrombocytosis (ET) & Primary Myelofibrosis (PMF) are Philadelphia negative Myeloproliferative Neoplasms (MPNs) characterized by overproduction of one or more myeloid cell lineages. MPNs are associated with the presence JAK2 V617F mutation in 95% of PV & 50% of ET & PMF patients. Several molecular methods such as RQ-PCR, HRM & Sequencing are currently used to detect common mutations. However, there are still significant numbers of MPNs are negative to the most common genetic anomalies. The advent of Next Generation Sequencing (NGS) gives the opportunity to study relevant mutations in several genes. Aim: Utilizing NGS to identify potential genetic anomalies causing familial MPNs patients in Qatar. Methods: 6 MPNs patients from consanguineous families & 5 healthy individuals were consented into the study gDNA was extracted & used for multiplex amplification of amplicons targeting cancer associated mutations in 28 key genes using the Ion AmpliSeq Kit. NGS was performed via the Ion Torrent using the 318 chip & data was analyzed with the Torrent Suite. The confirmation of NGS data was done by RQ-PCR or Sequencing. Results: NGS identified novel deleterious mutations in MPNs patients. Out of 6 familial cases, 5 patients (P1- P5) were ET & 1 patient (P6) was PV. P1 had JAK2 V617F, ASXL1 T600P, CBFB G180S, THPO S184R & ITGA2 R76Q, P2 had JAK2 V617F, MPL A554G & ATM F582L, the other three Patients (P3, P4 & P5) had CLAR K385fs*47 & one PV patient (P6) had TYK2 E1163G, ASXL1 P808H, PDGFRB P4L TERT G300fs. In patients & healthy individuals, mutations/SNVs such as MPL P106L, K553N, SH2B3 L476F, ATM F1036F KIT N564S & TET2 T730R were also found Discussion & conclusion: In this study, several deleterious somatic/germ-line mutations/SNVs were identified using Targeted Exome Sequencing approach. A complex combination of mutations occurred in ET patients & coexistence of several oncogenic events occurred in PV patient. This finding may also suggest that the MPNs phenotype may depend on presence of other mutations. It is worth to mention that the presence of ATM variant in P2 is associated with increased risk of CLL. Somatic CALR type-2 mutation was identified in 3 ET (nonmutated JAK2 or MPL) patients. This mutation is 5-bp TTGTC insertion in exon 9 that generates a mutant protein with a novel C-terminal (p.K385fs*47). In patients & healthy individuals, a heterozygous germ-line mutation in exon 3 of the MPL gene (MPL P106L) has been observed and previously described as a rare autosomal-dominant disorder. However, this mutation is considered to be frequent in Arabic populations also several unreported variants of uncertain significance were identified. Our finding suggested that familial MPNs patients in Qatari tribes have several potential disease- associated variants/mutations which represent a unique interest for the scientific community worldwide and present an unprecedented opportunity for local and international collaborations to carry out WES in society with its unique coherence and genetic pool (founder effect), this would offer invaluable resources to unravel the genetic etiology and pathogenesis, delineate the mechanisms behind MPNs phenotypic diversity.