Qatar Foundation Annual Research Conference Proceedings Volume 2016 Issue 1

The Conversion of natural gas into synthetic liquid fuel carried out through a catalytic conversion process, known as the gas-to-liquid (GTL) technology, had a great impact since its discovery. The process utilizes the Fischer-Tropsch synthesis (FTS) chemistry that was first developed in 1925. Gas-to-liquid (GTL) fuels are synthetic fuels that are intrinsically cleaner than conventional fuels.[1] They are environmentally benign due to the absence of sulfur content and the extremely low aromatic content. Gas-to-liquid (GTL) diesel fuel, being one of the most important GTL products, is therefore classified as ultra-clean fuel with lower emissions of carbon monoxide and particulates upon combustion. Nevertheless, the lack of sulfur and aromatic in the diesel fuels negatively impacts certain important physical characteristics such as lubricity and density. This fact makes these fuels improper for use in existing diesel engines. The lubricity issue is significant for GTL diesel fuels, as it not match the standards required by regulations in the United States, Europe and elsewhere. Lubricity is defined as “a qualitative term describing the ability of a fluid to affect friction between, and wear to, surfaces in relative motion under load.” [2]

The aim of this research project is to design new generation ultra clean diesel fuels, from the GTL process, that are environmentally friendly, have less emissions upon combustion but also practicable and compliant with global standards. The focus of this study is to develop a comprehensive knowledge and data to observe the possibility of stretching and tailoring the GTL diesel properties such that they meet the standards needed to be used in existing engines. The enhancement of lubricity, which serves as the major disadvantage, is to be carried out while maintaining all other physical properties within the range needed for existing engines and ASTM D975 and D7467 standards.

Fatty acid methyl and ethyl esters are biodiesels that can provide significant improvements in the lubricity of diesel fuel. Previous studies on the effects of fatty acid methyl esters on diesel fuel lubricity have shown an increase in lubricity associated with the addition of these esters [3]. Addition of these esters in GTL diesel was found to be the best fit for lubricity enhancement. Our campaign, unlike other studies on diesel lubricity, does not only focus on certain physical properties of diesel but provide a comprehensive study showing all changes in other properties that accompany the change of the targeted property, being diesel in this case.

For this study, four lubricity enhancement additives were selected. The selection covers a wide range of biodiesel characteristics and would thus allow deeper understanding of other factors such as saturation and chain length of esters on diesel lubricity and properties enhancement. The four esters that proved to have significant impact are Methyl Oleate (C19H36O2), Methyl Stearate (C19H38O2), Ethyl Oleate (C20H38O2) and Ethyl Stearate (C20H40O2). Both methyl and ethyl esters were found to affect the lubricity. However, other studies showed variation on which serves as a better lubricity enhancement additive. Our research will validate these findings and widen the study to experiment the effect of mixing different additives on all other diesel fuel properties. The concentrations of additives were selected to be in the range of 5%–20% by volume. For this purpose 28 blends were prepared for conducting the research.

Subsequently blends were tested for fuel characteristics and physical properties. The tests nclude vapor pressure, viscosity, flash point, pour point, cloud point, distillation performance, heat content and lubricity. Current results show an increase in density, viscosity, flash point and vapor pressure with increasing additive concentrations of biodiesel. In contrast, the increase in additive concentration decreased the pour point, cloud point, recovery by distillation and calculated cetane number. All the changes lie well within American Society of Testing and Materials (ASTM) standards.

The work will be further continued to validate experimental results with industry partners, testing of lubricity characteristics using advanced microscopy and conducting a thorough result analysis and representation statistical methods and visualization techniques.

This work will suggest ideal mixtures of GTL diesel and biodiesel additives that will best enhance the GTL diesel fuel. Such findings can be used in blending commercial GTL diesel fuel with suggested biodiesel to produce practicable, engine compliant and ASTM standard compliant GTL diesel. Since Qatar has the largest GTL plant in the world, this research is essentially significant and relevant. It also enriches Qatar's scientific research culture and serves the world by creating cleaner fuels for a cleaner environment.

References

[1] Elmalik, E.E., Raza, B., Warrag, S., Ramadhan, H., Alborzi, E., Elbashir, N.O. (2014). Role of Hydrocarbon Building Blocks on Gas-to-Liquid Derived Synthetic Jet Fuel Characteristics. Industrial & Engineering Chemistry Research, 53, 1856–1865.

[2] Crown, L., Warfield, L., Hockert, C. (2013). Handbook 130 (2013)- Uniform Laws and Regulations in the areas of legal metrology and engine fuel quality.

[3] Geller, D. P., & Goodrum, J. W. (2004). Effects of specific fatty acid methyl esters on diesel fuel lubricity. Fuel, 83(17-18), 2351–2356.

Abstract Introduction: Of the various devastating diseases triggered by necrotrophic fungi, the diseases caused by following fungi Fusarium oxysporum, Fusarium solani and Rhizectonia solani are of particular economic significance in date palm (Phoenix dactylifera L.) growing countries. Undoubtedly date palm is the most important fruit tree cultivated in Arabian Peninsula. Unfortunately date palm cultivation encounter many challenges, such as fungal diseases. It has been reported that Fusarium oxysporum, Fusarium solani and Rhizectonia solani are the major causative of various diseases in Date palm.

For successful colonization of host, necrotrophic pathogens secrete an arsenal of effector proteins that facilitates infection by manipulating host cell structure and function. Thus secretory proteins (SPs) are critical for both short and long range intercellular signaling during infection and colonization.

The present study is conducted on three date palm pathogens, which causing diseases like bayoud disease and other necrotrophic diseases including root rot. This study focused on molecular genetics of necrotrophic pathogenicity in date palm by following an in silico approach to mine putative secreted elicitors from publically available Fusarium oxysporum, Fusarium solani and Rhizectonia solani ESTs. Methodology: Methodology involved mining of 25213 Fusarium oxysporum ESTs, 12433, Fusarium solani ESTs and 22324 Rhizectonia solani ESTs for protein sequence based features characteristic of SPs (signal peptides). All the ESTs were collected from NCBI. With using ORF predictor (http://proteomics.ysu.edu/tools/OrfPredictor.html) algorithm, found out all the six frame ORF. Predisi (http://www.predisi.de/) and SignalP (http://www.cbs.dtu.dk/services/SignalP/) algorithms was exploited to infer signal peptide within the ORF. Followed by scanning of transmembrane domain performed with TMHMM (http://www.cbs.dtu.dk/services/TMHMM/) to discard the transmembrane sequences. 0 TM/1TM proteins were selected for further CD (conserved domain) search.

Before going to the mining experiment, the pathogenicity of soil isolated (from northern part of Qatar) fungal pathogen on Date palm was confirmed with detached leaf inoculation method. All the three fungi, Fusarium oxysporum, Fusarium solani and Rhizectonia solani showed necrosis in date palm leaf after three days of infection. Result and conclusion: Out of 25213 Fusarium oxysporum ESTs 24890 have ORF. 12176 ORF found in Fusarium solani ESTs. Above 60% of all the three fungal ESTs had signal peptide. Number of sequences narrowed down by transmembrane topology search and the sequence doesn't containing transmembrane domain were selected for conserved domain identification.

Subsequent to our searches with sequences lacking transmembrane domains, we could catalog candidate effector sequences based on conserved features common to characterized fungal effectors. In Fusarium oxysporum following protein found to be extracellular secretory protein, this include cellulose binding protein, which possibly involved in in host cell adhesion, qaq like polyprotein: a virulent associated protein, lysin motif: an effector protein, extracellular peptidase, cell wall hydrolase, 150 amino acid cerato platanin sequence (elicitor), alpha amylase, beta 1,3 glucanase and 165 amino acid necrosis inducing protein. These effector proteins have the ability to degrade plant derived compound, this suggest the role of the effectors in pathogenicity.

In addition to these high amount of lipid targeting enzymes and glycoside hydrolase found in all the three phyto pathogenic ESTs. Presents of secretory protease detected in Fusarium solani. Peptidase like superfamily domain found in Rhizectonia solani.

To date, none of these effectors have been cloned and thus we propose that the catalogued effectors will in future be useful for isolation and characterization of these identified proteins. Expression studies are already underway and we expect that the results will provide insights into mechanisms underlying host-Pythium interactions and thereby help in generating new strategies for effective date palm disease control.

The Compact Muon Solenoid (CMS) experiment in the Large Hadron Collider (LHC) at CERN has been the tool to performing ground-breaking research in high energy physics. The CMS detector has been built over the last two decades by an international collaboration of scientists from all over the world. Two years after its operation, the two experiments ATLAS and CMS have announced in 2012 the discovery of the Higgs boson, a long awaited particle responsible to give elementary particles their respective masses.

After the first 3 years of operation at moderate luminosity, the LHC is entering a new phase of high luminosity and energy regimes, which will put stringent requirements on the detectors.

The CMS experiment has planned a rigorous plan of upgrade of its different components to cope with the harsh conditions imposed by the new regime. One of the subsystem of CMS detector that will require upgrade is the muon system. This latter detects muon particles, which are the signature of most of the interesting physics channels we are looking for at the LHC.

The Qatar team, together with an international team of scientists, has proposed the Gas Electron Multiplier (GEM) as the future detecting element of the upgrade of the muon system.

We have conducted an extensive simulation program to assess the GEM detector and optimize it for the future upgrade.

During this project, various simulations have been conducted to predict the efficiency and time resolution of the GEM. The simulations, which have been conducted using ANSYS, computational fluid dynamics software, focus on producing the electric field maps inside the detector. In addition, the resulting electron avalanche was simulated based on the solution of the Boltzmann equation. A signal was then generated to study the gain, resolution, and other parameters. During this work, several conditions were simulated in order to reach the optimum conditions under which the GEM would be most effective. These simulations had to be conducted using a supercomputing facility since their range surpasses the regular computing powers of personal computers. Using Raad, the cluster at Texas A&M University at Qatar, helped widen the scope of the simulations to approach a realistic situation that would occur within the CMS.

Furthermore, as part of its next upgrade, a novel detector, the Fast Timing Micropattern (FTM) detector is being considered as a possible beneficial addition to the CMS. Initial investigations of the FTM detector have shown a considerable improvement in the time resolution that is proportional to the number of layers. In addition, the use of resistive WELL techniques solves the problem of spark occurrences and discharges that such detectors experience with high electric fields. It also differs from the GEM in the sense that the gain is extracted at every multiplication stage rather than at the very last level of the detector where the readout plane exists. The FTM detector could be cost-efficient in its assembly process. Simulations are being further extended in order to evaluate the FTM's performance and optimize its gain and other resulting parameters.

Abstract Purpose: The invention relates to the oil industry, inorganic chemistry, in particular, to the methods of complex processing of formation water, using flare gas of oil and gas field as fuel for producing enriched concentrates of iodine, bromine, magnesium and valuable trace elements, as well as desalinated water (technical and drinking water). The technology includes pre-cleaning of formation water from mechanical impurities and oil using adsorbents, followed by evaporation of water under vacuum, condensing water vapor in the barometric condenser, using of condensed water vapor as the coolant, using of saline water as a coolant of hot water coming out of the barometric condenser to 15–20 °C. The novelty of the design?: The novelty of the design is to get a comprehensive treatment of formation water, using flare gas of oil and gas field as fuel for obtaining enriched concentrates of iodine, bromine, magnesium and valuable trace elements, as well as desalinated water (technical and drinking water). Recycling of formation water with this method considers new directions. Worldwide the patents were received for constructing chemical plants for producing cheap food salt, killing fluid for oil wells, iodine, bromine, hydrochloric acid, caustic soda, sodium sulfate, sodium chloride, potassium bromide, sodium bromide, borax, boric acid, phosphoric acid, lithium carbonate, lithium phosphate, borax, boric acid, ammonia and carbonate products, potassium chloride, bromide and products LiCl, alkali rare elements, uranium, etc.

Hundreds of plants are engaged in the processing of brines in the world, but due to the large content variety of raw materials for each company developed its own individual process steps, depending on the climate or nearby sources of cheap heat. This is due to the fact that for concentrating and isolating the salts removal of a large mass of water required. Therefore, all businesses usually do not produce a particular product, but try to all the useful chemical elements alongside with secondary products - metals, chlorine, bromine, etc. All plants use successive allocation scheme of used salts may vary greatly from each other depending on the primary composition of the brine.

An important advantage of groundwater as a raw material source of rare elements are: the low cost of the product, because groundwater is a grade raw material, some of its geochemical types have relatively high adaptability, besides exploitation of rare elements water deposits does not require expensive mining. So in most countries (United States, Italy, Israel, Japan, New Zealand, Iceland, Australia, etc.) technological research to develop methods for extracting these elements from specific geochemical types of natural waters are constantly and systematically conducted. Cleaning the reservoir water: The technology includes pre-cleaning of formation water from mechanical impurities and oil using adsorbents. Cleaning is carried out in order to separate the unnecessary substances (organic substances) for a concentrate. Organic substances with high concentration cause by negative effects under using a concentrate and are considered to be hazardous substances in fresh water. Getting technical and drinking water and concentrate?: This technology helps to solve issues on providing facilities and public by technical water and are urgently needed, especially in those areas where there are sufficient amounts of formation waters and flare gases resources. The authors of the project developed a way for using flare gas and reservoir water for drinking water treatment and concentrates for medicine. The advantages of this technology?: Thanks to Tashkent State Technical University scientists an improved vacuum evaporation plant, was developed to split reservoir water 2 fractions - for distillate and concentrate. The advantage of this plant is that it works at lower boiling temperatures. This fact has a positive effect on the process of evaporation. Process takes place with low fuel consumption and lack of scale on the inner surfaces of the plant, since it is operated at temperatures not exceeding the limit scaling. Moreover, a significant part of the energy consumed in this process, is formed during combustion of existing flare gas, which leads to cheaper cost of the products. Using the results of this project, the production of a concentrate rich in iodine, bromine, magnesium and other minerals, as well as technical and drinking water will be ensured.

Recycling formation water and separating necessary useful from its structure we can get low cost products, as well as improve the environmental situation. In addition, solving problems with providing with of water is urgently, especially in those areas where there is sufficient amounts of formation water and flare gases resources. Water scarcity is felt in more than 40 countries (estimated at the beginning of the 21st century will reach 120–150 √ 109 m³ per year). Nearly a billion people in the world suffer from a lack of clean drinking water. This deficit can be covered by desalination of saline (salt content of more than 10 g/l) and saline (2–10 g/l) of ocean, sea and groundwater reserves totaling 98% of all water on earth.

Currently, one of the areas of energy is an efficient search of alternative methods to the traditional technologies of desalination of saline and brackish water that is the development of desalination methods of electro- spray nozzles and with subsequent evaporation and condensation. The authors of the project developed a way to use flare gas and reservoir water for drinking water treatment and concentrates.

Another advantage of the technology is solving environmental issues. These environmental problems exist in the areas where flare gases is burnt more million tons per day. Flare gas contains sulfur compounds. Sulfur compounds influences negatively on man and nature. Before the use, flare gas is purify led from compounds of sulfur, moreover, a boiler used in the technology helps complete combustion of flare gases. As a result, of flare gas, full burning decreases a rate of waste gases in the atmosphere. Technical and economic advantages of technology: The developed technology has several technical and economic advantages extraction formation water does not require much cost to obtaining it, produced water gets oil and condensates, and separated from them as by water, oil and gas fields also present flare gases of low pressure. Flare gases can be used as a source of thermal energy concentration - the result of the evaporation process of saline salty water. In addition, the next to the field “South Kemachi” there is a pond of salt water (lake “Devhona”). In the technology it is used as a coolant. In this region, there is the scarcity of fresh water. It should be noted that obtaining a concentrate rich in trace elements, from mineral water from underground using this technology is considered to be cheap raw materials and of low cost.

Lack of technologies that allow effectively utilize APG (gases rich in heavy hydrocarbons, that complicates their pumping through pipelines). Remoteness of potential markets from oil locations. Construction of pipelines to transport the petroleum to plants requires much capital investments, 1 km of the pipeline will cost more than $ 1.0 million to transport APG gas to processing enterprises from remote fields increase the cost of associated gas.

Associated petroleum gas can be used by the subsoil user as fuel in order to heat and electricity in the manner prescribed by the legislation in the field of gas and electricity and in compliance with applicable statutory rules of industrial and environmental safety.

The feature of the field “South Kemachi” is the high content of hydrogen sulfide in oil and associated petroleum gas (APG). As part of APG volume fraction of hydrogen sulfide it is about 2%. Without prior purification of hydrogen sulfide is not possible to use APG for production needs of the field and in this case the only acceptable way of dealing with it is APG flaring. Consumption of crude APG production on the deposit site is not possible. Gas contaminated with hydrogen sulfide when it is used as fuel for the boiler with prolonged exposure can lead to hydrogen embrittlement, cracking sulfide stress and/or cracking under stress corrosion in iron alloys, in other words, to a rapid deterioration of equipment.

In this project the authors consider purification associated gas from hydrogen sulfide in order to use APG purified for use as fuel for a iodine-bromine-magnesium concentrate and desalinated water and gas condensate of the field of formation water, significantly reducing the pollutants and greenhouse gases (GHG) into the atmosphere.

Reduction GHG emission achieved by the volume of natural gas, as well as in a much more complete oxidation of methane using APG as fuel compared to flaring. Flares of the deposits provide a so-called smoke spot flaring characterized by a high coefficient of unburnt gas, which leads to the release of a significant amount of methane in to the atmosphere.

Purification of hydrogen sulfide chemicals is costly.

Boiler for of desulfurization. It makes sense to include this boiler in the project due to the fact that APG is burned with total oxidation. Therefore, due to the work of the boiler methane emissions are reduced compared to flaring.

In the technology barometric condenser is used to create the vacuum that receives the amount of vapor generated by concentrating the solution and evaporation of cooling water. Certain part of the barometric condenser condensate is brought refrigerator X -1 which is the bottom of the lake “Devhona.” cooling fresh water from the cooler X-1 is brought to the barometric condenser. These regions, are short of fresh water for cooling. It is required to develop new methods for cooling.

Reservoir coolers were designed and constructed at Smolensk, Kursk, Chernobyl, South Ukrainian, Khmelnitsky, Kostroma NPP, and Surgut GRES Berezovsky; a cooling reservoir on the basis of natural lakes and depressions is in: Kalinin NPP.

A the construction of such facilities in areas where there is a lack of cooling water is very important. Recently, the amount of industrial cooling water has been increased significantly, so penetrate existing and develop new cooling methods.

Lake water have different temperatures at different depths (10 to 25 °C on the surface of 30 to 40 °C at a depth of 1 m and from 40 to 60 °C at a depth of 1.5 m). In deeper layers, the temperature is lowered at a depth of 10 m up to 18–20 °C.

In the salt lakes several types of vertical thermal structure are observed. Salt lake is a reservoir with a capacity of warm water layer between two layers of colder. In some lakes may be two “hot” zone. Often “hot” area is located in the bottom layer and in this case the vertical thermal structure of the lake consists of an upper “cold” zone and the lower “hot” as it was observed in the lake. Vanda (Antarctica), Solarium Lake Elat (Israel), in some lakes Kulunda steppe, on the Crimean peninsula, the Karakum (Dzens-Litovsk, 1957) and on the lake. Sassykkul the Eastern Pamirs (Egorov, 1991).

By stepwise refinement on multiple data, the method increases the accuracy of 3D models gradually and effectively. In addition, the mechanisms used in the method for organizing and manipulating information can have an equally important impact upon geologists’ thought, the interpretation of geological data, and 3D modeling methodology. A concrete example of using the method to Huai Bei fault and fold belt shows that the method can be applied to broad and complex geological areas. The technology of 3D geological modeling will bring about great changes in the methods of acquiring, storing, processing and displaying geological data. The 3D modeling methods frequently used are mainly based on plenty of 2D/3D seismic data or borehole data with cross sections between boreholes. Outlined a prospective 3D model construction method that depends on a 2.5D geological mapping anddata extraction technique. An open CORBA-based system architecture was presented that connects two existing geoscientific software tools—the geological 3D modeling and visualization tool (GOCAD) and a geophysical 3D modeling tool (IGMAS)––via a 3D Geo-database kernel. We propose a stepwise refinement method with multi-source data integration and present a comprehensive yet convenient 3D modeling system. The method can naturally simulate geological structures no matter whether the available geological data is sufficient or not. By stepwise refinement on multiple data, the method increases the accuracy of 3D modeling gradually and effectively. In addition, the mechanisms used in the method for organizing and manipulating information. 3D subsurface visualization system (SVS) has been developed. The SVS implemented in Visual C++ 6.0 and OpenGL graphics library and being able to run on the PC platform, provides a comprehensive yet convenient environment, which makes it possible for the user to build 3D models in oil exploration where there is enough available data, as well as in geological survey and mineral extraction where the geological data is insufficient. The method/SVS can be applied to broad and complex geological areas. The proposed method builds 3D models from multisource data in a stepwise manner and involves six steps: (1) integration of 2D/2.5D data, (2) supplement of cross sections, (3) Simulation of faults, (4) definition of a template, (5) construction of horizons, and (6) representation of solids. Data of different types and qualities are first merged into a 3D geologic model by data conversion interfaces. The diverse data are classified into three types: direct data, indirect data, or assistant data, depending on the type and the purpose of the information and application.

• 1-Direct data, such as borehole data and property data, is original sampling data obtained by direct observation and survey, and is highly accurate.

• 2-Indirect data, being original too, has different precision with different resolutions of graphs, such as boundaries, faults, folds and DEM derived from geological maps, topographic maps and structural geology maps, as well as 2D/3D seismic-reflection data, exploring data, etc. This type of data should be stored as files after being digitized. However, this kind of data cannot be used as direct input data for the 3D modeling system.

• 3-Assistant data will be used in the process of 3D modeling as icons like 2D/3D primitives, and texture maps including satellite or aerial imagery, scanned maps, etc. The research in the past has focused on generating 3D models from borehole and cross-section data. This has limitations, however, since these data are lacking in many areas. In this section, we emphasize on how to use data of different types and qualities, as well as various mathematical methods to gradually refine 3D models to a desired accuracy.

Solar thermal energy research and utilization is progressing rapidly since it is clean energy and can achieve carbon credits in developed and developing countries. The energy conversion efficiency of most of the solar collectors is low, as much of the energy absorbed by collectors is lost due to transient atmospheric conditions. Reduction of losses and improving the performance of collectors by providing economical solutions has been the greatest challenge that scientists are facing even today. Material technology has achieved highest boundaries in all the applied fields ranging from medical to space. According to literature, the use of nanofluids in thermal devices improves the performance thereby further increasing the thermal conversion efficiency of solar collectors. The work here aims at numerically and experimentally studying the heat transfer enhancement obtained as a result of introducing grooved tube collector and using ZnO nanofluid as the working media in a solar flat plate collector. Helical grooves of different pitch are made in collector tubes that generate a spin flow which would increases the heat transfer rate at the expense of increased pressure drop. The convection heat transfer is enhanced as a result of flow through these grooved tubes which is the reason for the absorption efficiency increase. Heat transfer augmentation increase in grooved and plain tubes is compared here. Heat transfer augmentation is expected to increase when compared to a plain tube and a comparative analysis is carried out on the basis of the heat transfer coefficient, wall shear stress at constant Reynolds number and constant mass flow rate condition. The improvement in absorption efficiency at two different groove depth (e/d =  .023, .0175) and varying flow velocity is also studied. The use of nanofluid has been a recent technological advancement as the metal/metal oxides dispersed in a base medium improved the absorptive solar energy by up to 95% which further increasing the thermal conversion efficiency. ZnO nanofluids are prepared by economical methods at different volume concentrations. The particle concentration is one determining parameter and on increasing the concentration the heat transfer properties show a rise up to a maximum value and beyond which it decreases. The numerical analysis here is done for ZnO nanofluid with particle concentration varying from .5%–2%. The synergic effect of the two improvements in the heat transfer and fluid flow characteristic is studied experimentally and numerically in the transition and turbulent flow regimes.

Keywords: Flat plate collector, grooved tube, Heat transfer coefficient, Reynolds number, ZnO nanofluid

Background: Obesity (BMI ≥  30 kg/m²) is associated with T2 diabetes (40-fold relative risk) and cardiovascular complications. Bariatric surgery is becoming a treatment of choice in obese individuals because of the multiple benefits associated with significant weight loss leading to an improved quality of life and decreased morbidity and mortality, which far out weighs the cost of surgery. A major metabolic benefit is the remission from T2 diabetes as a consequence of alterations in gut hormone signaling and weight loss. Indeed cost-effectiveness analyses have led NICE to recommend that all patients with a BMI ≥  35 kg/m² with T2 diabetes should be considered for bariatric surgery. In relation to the impact on macro vascular complications there is a significant reduction in MI and stroke in long term follow up studies, which translates to reduced mortality. For the microvascular complications of diabetes, studies are limited but have primarily focused on retinopathy and nephropathy after bariatric surgery. Despite the fact that neuropathy (nerve damage) can lead to pain and foot ulceration with amputation together with increased mortality from autonomic neuropathy, few studies have objectively assessed the impact of bariatric surgery on neuropathy. However, there are concerns that neuropathy could worsen following bariatric surgery due to nutritional deficiencies [1] and indeed there are case-reports of acute Guillain-Barre like demyelinating [2] and motor axonal [3, 4] neuropathy following bariatric surgery. The term post bariatric surgery neuropathic pain has also been coined with a reported prevalence of 33% following bariatric surgery [5]. However, a more recent study has shown complete resolution of neuropathic symptoms with an improvement in the neuropathy disability score [6]. Whereas a recent case-control study has showed no improvement in nerve conduction velocity [7]. Given the potential benefits and indeed harm following bariatric surgery there is a need for a systematic quantitative assessment of neuropathy to define true rates of remission or worsening. Aims: Systematically define the baseline prevalence of neuropathic pain and neuropathy and the outcomes following bariatric surgery on neuropathic pain and objective markers of somatic and autonomic neuropathy in obese subjects with and without T2 diabetes, 6 and 12 months after surgery. Methods: This is a prospective, randomized, single center trial assessing the effect of gastric bypass surgery. The subjects in the study were recruited from Salford Royal NHS Foundation Trust, UK and the study was performed at the Wellcome Trust Clinical Research Facility/NIHR, Manchester, UK from 3 September 2013 until 30 July 2015. We estimated that the minimum sample required to detect a significant difference in peripheral autonomic (Neuropad response) and sensory nerve morphology using the novel imaging technique of corneal confocal microscopy (CCM) to quantify corneal nerve fibre length (CNFL) over 12 months was 52 and 46 subjects, respectively with a power of 80%. Exclusion criteria included history of neuropathy due to non-diabetic cause and corneal trauma or surgery. Painful neuropathy was defined using a composite score of the McGill questionnaire with either a positive neuropathic symptom profile (NSP) or diabetic neuropathy symptom (DNS). The objective end-points for remission from neuropathy were: 1) >15 nerve branches/mm² in corneal nerve branch density (CNBD) and >15 mm/mm² in corneal nerve fibre length (CNFL), 2) for autonomic neuropathy >90% on the Neuropad response, and 3) for sensory neuropathy, < 2 on the neuropathic disability score (NDS) and < 15 Volts for vibration perception threshold (VPT). The Local Research Ethics committee approved this study and all subjects gave informed consent to take part in the study. The research adhered to the tenets of the declaration of Helsinki. Results: Of 106 subjects recruited, 40 refused and 23 are awaiting follow-up assessments. We have analysed 43 subjects with an average age of 52.2 ±  2.1 years. Baseline BMI was 50.6 ±  2.8 kg/m² and was significantly reduced to 38.2 ±  1.4 kg/m² (P < 0.0001) and 35.8 ±  1.7 kg/m² (P < 0.0001) at 6 and 12 months, respectively. 26/43 (60%) of subjects had T2 diabetes before surgery. Based on normalization of HbA1c the remission rate from diabetes was 81% 12 months after surgery. Baseline HbA1c in 26 subjects with T2 diabetes was 7.4 ±  0.3% and was significantly reduced to 5.9 ±  0.2% (P = 0.0007) and 5.6 ±  0.1% (P < 0.0001) at 6 and 12 months, respectively. Hypertension (Systolic BP >120 mmHg) was identified in 37/43 (86%) of subjects pre-surgery. The remission rate from hypertension was 57%, 12 months after bariatric surgery. The average starting systolic blood pressure in these subjects was 130.3 ±  2.7 mmHg and was significantly reduced to 120.8 ±  3.13 (P = 0.03) and 114.4 ±  5.49 (P = 0.008) at 6 and 12 months, respectively. The prevalence of sensory neuropathy assessed using the Neuropathy Disability Score (NDS) in 41 subjects was 34% pre-surgery and the remission rate was 50%, 12 months after surgery. Baseline NDS was 2.0 ±  0.4, indicative of minimal neuropathy but was significantly improved to 0.89 ±  0.4 (P =  0.05) at 12 months. Vibration perception threshold was 13.6 ±  1.25 V and showed no improvement (12.6 ±  1.46 V, P =  0.58) 12 months after surgery. The prevalence of neuropathic pain in 36 subjects was 39% pre-surgery and a complete recovery was observed in 71% and 93% of patients at 6 and 12 months, respectively. Likewise, 45% of the 22 subjects with T2 diabetes had neuropathic pain at baseline and 70% and 90% had no painful neuropathy at 6 and 12 months, respectively. The prevalence of peripheral autonomic dysfunction assessed using Neuropad in 24 subjects was 57% pre-surgery and the remission rate was 69% 12 months after surgery. The Neuropad response at baseline was 77.95 ±  5.1% and improved significantly (91.3 ±  3.86%, P =  0.04) 12 months after surgery. Corneal confocal microscopy showed a significant increase in corneal nerve fibre length in the 26 subjects with diabetes from a mean of 14.2 ±  0.7 mm/mm² to 16.7 ±  1.04 mm/mm² (P =  0.049) and an increase in corneal nerve branch density (32.8 ±  3.35 no./mm² to 43.2 ±  4.49 no./mm² (P =  0.068). However, there was no change in corneal nerve fibre length or branch density in 17 subjects without T2 diabetes 12 months after surgery. Conclusion: Our study shows a high prevalence of diabetes; hypertension, neuropathic pain and neuropathy assessed using objective measures of somatic and autonomic neuropathy in obese people. Bariatric surgery results in significant weight loss, and improved glycemic control and blood pressure, with a reduction in the prevalence of painful neuropathy and improvement in autonomic and in particular small fibre neuropathy assessed using corneal confocal microscopy. Morbid obesity is common (-30%) in the Qatari population and bariatric surgery is an increasingly performed procedure. Contrary to previous data showing a worsening of both neuropathic symptoms and deficits, our data show significant weight loss with an improvement in glycaemic control and blood pressure which improves neuropathy and therefore provide a strong rationale for undertaking bariatric surgery and reducing disabilities to reach the goals of VISION 2020-Qatar.

References

1. Thaisetthawatkul, P., et al., A controlled study of peripheral neuropathy after bariatric surgery. Neurology, 2004. 63(8): p. 1462-70.

2. Ishaque, N., et al., Guillain-Barre syndrome (demyelinating) six weeks after bariatric surgery: A case report and literature review. Obes Res Clin Pract, 2015. 9(4): p. 416-9.

3. Landais, A., Neurological complications of bariatric surgery. Obes Surg, 2014. 24(10): p. 1800-7.

4. Landais, A.F., Rare neurologic complication of bariatric surgery: acute motor axonal neuropathy (AMAN), a severe motor axonal form of the Guillain Barre syndrome. Surg Obes Relat Dis, 2014. 10(6): p. e85-7.

5. Kattalai Kailasam, V., et al., Postbariatric surgery neuropathic pain (PBSNP): case report, literature review, and treatment options. Pain Med, 2015. 16(2): p. 374-82.

6. Muller-Stich, B.P., et al., Gastric bypass leads to improvement of diabetic neuropathy independent of glucose normalization-results of a prospective cohort study (DiaSurg 1 study). Ann Surg, 2013. 258(5): p. 760-5; discussion 765-6.

7. Miras, A.D., et al., Type 2 diabetes mellitus and microvascular complications 1 year after Roux-en-Y gastric bypass: a case-control study. Diabetologia, 2015. 58(7): p. 1443-7.

Developing effective treatments for neurodegenerative diseases is one of the greatest medical challenges of the 21st century. Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are very common neurological disorders of the elderly (Jankovic et al., 2008). Although many of these clinical entities have been recognized for more than a hundred years, it is only during the past fifteen years that the molecular events that precipitate the diseases have begun to be understood. Mutations in the α-synuclein gene cause early-onset PD, often associated with dementia, and one an α-synuclein mutation segregated with pure DLB (with no Alzheimer's pathology). Neuropathologically these diseases are characterized by the presence of Lewy bodies, intraneuronal inclusions mostly composed of α-synuclein protein fibrils, cementing the notion that this protein has a central role in Lewy body diseases (LBD). Despite the progress that has been made in understanding the underlying disease mechanisms of LBD, there remains an urgent need to develop methods for use in diagnosis. The development of reliable surrogate markers for the presence and abundance of α-synuclein lesions (Lewy bodies) in the brain would naturally facilitate a more streamlined work-up during the early care of PD and DLB patients, and importantly, allow for the biologically guided evaluation of future drug trials aimed at neuroprotection in the synucleinopathies. Recently, we generated new antibodies specific for different forms of α-synuclein such as oligomeric-α-synuclein (o-α-synuclein), phosphorylated-α-synuclein at serine 129 (p-S129-α-synuclein) or total-α-synuclein (t-α-synuclein), to develop highly specific and sensitive ELISA systems to assess the levels of these species in biological fluids. Next, we utilized our assays to explore the potential use of α-synuclein species as biomarkers for PD in cerebrospinal fluid (CSF) samples from a cross-sectional cohort of 46 PD patients and 48 age-matched healthy controls. Thereafter, we validated our results in large longitudinal DATATOP cohort (n = 242) over two-year follow-up period). In our study we also investigated the potential predictive role of CSF Alzheimer's disease (AD) core biomarkers (Aβ42, total tau, p-tau). In our study we also investigated the added predictive value of CSF AD core biomarkers (Aβ42, total tau, p-tau) to CSF α-synuclein species. Interestingly, a strong positive correlation between the changes in CSF t- and o-α-synuclein levels was noted. Such a strong correlation clearly suggests that the increase of CSF t-α-synuclein levels at the early stages of the disease lead to the formation and accumulation of the pathogenic species of o-α-synuclein in the brain that cause neuronal cell death. It has been shown that soluble o-α-synuclein are elevated in brain homogenates from PD and DLB compared to normal brains (Sharon, et al., 2003; Paleologou, et al., 2009). Together with the results from our previous studies, we provide strong evidence for the important role of o-α-synuclein in the pathogenesis of PD and other synucleinopathies (El-Agnaf et al., 2003). Consistent with our recent study (Parnetti, et al., 2014), we also found that the change in CSF Aβ42 levels correlated with the change in UPDRS-mental scores, suggesting that CSF Aβ42 may aid in predicting cognitive decline in PD patients. It's worth mentioning that one of the many important features that distinguished the DATATOP study from other studies is that the untreated PD subjects enrolled in the DATATOP study were at a very early stage of the disease; a stage estimated to be earlier than most of the other clinical trials. At baseline, PD patients presented with minimal disability and were followed until just prior to the initiation of the dopamine replacement therapy, and this is reflected in the low H&Y scores registered for these patients. This limited motor disability may explain the lack of an association between the baseline or follow-up CSF biomarkers and disease severity. However, the significant changes of CSF α-synuclein levels we observed in the DATATOP cohort over approximately two years of disease progression, suggest that a correlation between CSF α-synuclein levels and clinical parameters will become apparent with longer follow-up. However, our findings still need to be further validated in large-scale, prospective and well-controlled studies, especially those that include subjects with neuroimaging-supported definite PD and healthy controls such as the on-going Parkinson's Progression Markers Initiative. Synucleinopathies and tauopathies show significant clinical and pathological overlap, making the early diagnosis of PD more challenging. This overlap necessitates a combination of measurements of CSF α-synuclein species with AD key biomarkers to improve diagnostic accuracy. Our cross-sectional analyses revealed a positive correlation between CSF t-α-synuclein and t-tau and p-tau in the PD group. Our findings confirm and extend the observations by Toledo and his colleagues who reported a positive correlation between CSF t-α-synuclein and tau levels in PD, AD and controls (Toledo et al., 2013). These data suggest that the elevation of CSF tau and t-α-synuclein reflect synaptic degeneration and axonal loss. To our knowledge, this is the first study that combines measurements of different species of α-synuclein, along with AD biomarkers, and showed significant changes of CSF α-synuclein species in large longitudinal study at the early stages of PD. Taken together, these data suggest that the levels of t-, o- and p-S129-α-synuclein species change over the natural course of the disease, and thus might aid in monitoring disease progression and severity. This supports our hypothesis that changes in CSF α-synuclein species are a more direct measure of the formation of LBs and Lewy neurites, which are the hallmarks of PD pathology. Our findings study demonstrated that quantification of α-synuclein species in CSF has strong potential value as a tool not only for PD diagnosis but also for presymptomatic screening of high-risk individuals who are good candidates for neuroprotective treatment.

References

El-Agnaf OM, Walsh DM, Allsop D. Soluble oligomers for the diagnosis of neurodegenerative diseases. Lancet Neurol 2003;2:461–462.

Jankovic, J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008;79:368–376, doi:10.1136/jnnp.2007.131045.

Kordower, J. H. et al. Disease duration and the integrity of the nigrostriatal system in Parkinson's disease. Brain 2013;136:2419–2431, doi:10.1093/brain/awt192.

Paleologou, K. E. et al. Detection of elevated levels of soluble alpha-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies. Brain 2009;132, doi:10.1093/brain/awn349.

Parnetti, L. et al. Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease. Front Aging Neurosci 2014;6:53, doi:10.3389/fnagi.2014.00053.

Sharon, R. et al. The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron 2003;37:583–595.

Toledo, J. B., Korff, A., Shaw, L. M., Trojanowski, J. Q. & Zhang, J. CSF α-synuclein improves diagnostic and prognostic performance of CSF tau and Aβ in Alzheimer's disease. Acta Neuropathol 2013;126:683–697, doi:10.1007/s00401-013-1148-z.

The liver is the largest internal organ in the human body and performs a broad range of functions. Hepatocytes are the primary cells of liver. They perform many functions, an endocrine function, secretion of most proteins found in the blood plasma including albumin, exocrine functions and secretion of bile into the digestive tract. They are also involved in carbohydrate and lipid metabolism, drug detoxification and storage of glycogen. In addition, the liver has a unique capability of regeneration as the liver can fully regenerate itself following severe damage which leaves one-third of the cells uninjured (Michalopoulos, 1997; Taub, 2004). Liver disease and progressive loss of liver function is a major clinical challenge. Liver disease is the fifth highest cause of early mortality in the UK and the only cause of death that is increasing every year (Office for National Statics., 2008). With changes in lifestyle, new diseases such-as non-alcoholic fatty liver disease and steatohepatitis, a lack of hepatitis C vaccination and risk of hepatocellular carcinoma in hepatitis patients with increasing age are further compounding the problem of liver disease in the UK (Bosch et al., 2004; Kim et al., 2002) Currently liver transplantation is the only treatment available for end stage liver disease and a few liver based metabolic defects (Sze et al., 2009). Split liver transplantations is available and makes more transplants possible but ultimately is not sufficient to fulfill the growing need. Cell-based therapy involving the transplantation of primary hepatocytes could greatly expand the number of patients provided with effective treatment. However, primary hepatocytes are difficult to obtain in sufficient number. Indeed, they can only be obtained from organs suitable for transplantation as they cannot be expanded in vitro. These limitations can be overcome by using human Embryonic stem cells (hESCs) or induced pluripotent stem cells to differentiate into hepatocytes. Stem cells have great potential because of their self-renewable capacity differentiation potential including differentiation into hepatocytes (Hannan et al., 2013; Si-Tayeb et al., 2010; Sullivan et al., 2010). In our lab Hannan et al. have previously published an efficient and robust protocol to differentiate human stem cells to hepatocyte-like cells in a stepwise manner using defined factors. Human pluripotent stem cells (hPSCs) hold several clinical promises including the potential to produce large quantity of cells necessary for cell based therapy approaches. Hence, hPSCs provide an advantageous alternative since they can be differentiated into hepatocyte-like cells which display functional characteristics of their in vivo counterparts. However, there are two major limitations that must be overcome before this approach can go to clinical trials. Firstly current protocols are not GMP (Good Manufacturing Practice) grade. Secondly, hepatocytes-like cells derived in-vitro lack a several characteristics of adult hepatocytes and express fetal markers indicating that they are not fully functional. Here, I aim to develop a method to generate hepatocyte-like cells from hPSCs in conditions compatible with clinical applications. For that, I have developed a culture system to generate hepatocyte-like cells using culture conditions compatible with GMP. The resulting cells display characteristics of their in vivo counterpart and represent a first step toward the development of cell based therapy for liver diseases. In my study, as far as we know I am the first to have translated differentiation of hepatocytes-like cells into GMP-compliant conditions. Here, I report a method to translate our previously published efficient and promising step-wise hPSCs directed research grade differentiation protocol for the generation of hepatocytes-like cells under GMP-compliance conditions, demonstrating that this can be attained and hepatocytes-like cells can be produced at a standard suitable for clinical trail purposes. In general, the employment of cell-based products in clinical studies needs formal approval from the respective regulatory body (British Standards Institution, London, UK). According to the current national regulations this approval requires manufacturing, processing and testing of cellular products (Bailey et al, 2014). The manufacturing of cell product requires use of safe and pure components and materials in order to fulfil the regulatory standards. It is essential to use stable and clinical grade hESCs cell lines that first generated and preserved in GMP banks which provided effective, safe cell source as starting material. If possible, licensed and GMP-grade materials must be used, in case of no alternatives, highly purified xeno-free or animal-free research grade reagent should be used, with additional in-house testing to ensure safety and quality. The translated protocol fulfills all the above criteria. Depending on the availability in the market the translated protocol has GMP compliant materials wherever possible. When no GMP grade material was available I used preclinical, xeno-free reagents from reputed suppliers. I tested 9 cell lines: two control cell lines derived in research grade (H9 and BBHX8) and 8 fully GMP grade (mShef3, mShef4, mShef7, mShef8, mShef10, mShef11, Val9). The matrixes used for maintenance and differentiation and hESC lines are fully GMP grade. The growth factors and supplements used are GMP grade apart from OncostatinM and HGF, which are soon-to-be GMP grade as promised by the manufacturer and are currently under preclinical version. The media used are GMP grade apart from hepatozyme, which is a serum free medium. Small molecules used are all GMP grade apart from LY294002, which is highly purified HPLC grade. In Addition, freezing medium, reconstitution reagents, splitting reagents, PBS, water etc. are all GMP grade. Both GMP grade and RG HPSCs cell lines maintained their pluripotency in GMP maintenance conditions and were karyotypically normal when karyotyped every 10 passages for 40 passages. Expression of all pluripotent markers was observed. These finding showed that the GMP maintenance conditions are robust, effective and good enough that cell grown in RG condition can also be transferred and maintained. I was able to generate hepatocytes-like cells expressing hepatic markers from mshef3, mShef7, mShef11, H9 and BBHX8. When compared to H9 GMP compliant derived hepatocytes-like cells these differentiated cell lines showed similar protein and gene expression, mShef3 being an exceptionally good cell line having 10 fold increase in Cyp3A4 and tyrosine aminotransferase (TAT). When analysed for the functionality mSef7, BBHX8 showed similar level of Cyp3A4 activity while mShef3 was 7 folds higher expressed. Here, I report successful translation of HPSCs differentiation protocol in hepatocytes-like cells into GMP-compliant conditions by using HPSCs derived in a fully GMP manner and changing into defined feeder and serum free differentiation media and supplements to GMP- compliant conditions.

Objective: To explore the perceptions and attitudes about clinical research participation prevalent amongst the general public in State of Qatar. Background: Recruitment into research trials is a major challenge and an ongoing problem for biomedical researchers.¹ A recent report indicates that only 6% of eligible subjects actually participate in a clinical trial.² Costs of low recruitment rates are high. This includes not just loss of investment made in conducting the research but a more detrimental damage of investigator and institutional reputation as a result of a failed study.³ Surveys of attitudes to research participation have rarely been done.⁴ There is an urgent need to study and address recruitment shortfalls to ensure that trials meet their recruitment target.¹

PERCEPTIONS Study (Perceptions about Enrollment and Recruitment in Clinical Research Prevalent In State of Qatar)

PERCEPTIONS Study is an elaborate, three phased, mixed design research project. Phase 1 was conducted to explore the existing attitudes and behaviours prevalent in the population in Qatar. With the dynamic National Vision 2030, Qatar is set to become world leader in health care research. Diabetes, hypertension, cancer and personalized medicine are some of the projected research goals therefore it is essential to gain an insight about the thoughts, beliefs and concerns of people that this research is meant to thrive with and eventually benefit. Methods: A survey was conducted at two large-scale public events held within the State of Qatar. Residents of Qatar who were 18 years of age or older were surveyed following a verbal consent. Those visiting/touring Qatar or under 18 years were excluded from the survey. Filled surveys were entered in Microsoft Excel and analyzed on SPSS version 23. Results: Total of 2517 surveys were conducted of which 2379 valid forms were analyzed. According to the data 5.6% respondents (n = 137) had previously been approached to participate in a clinical study. Of these 74.6% (n = 86) agreed to participate while 37.3% (n = 51) declined. Remaining 88.7% (n = 2114) of the surveyed population had never been approached to participate in a clinical study. Data was missing for 5.5% (n = 131) respondents. Main reasons for declined consent included: time constraint (50%, n = 11), ‘fear’ (13.6%, n = 3), lack of awareness about clinical research (9.1%, n = 2) and lack of interest in research (9.1%, n = 2). Maximum participation was reported in studies related to diabetes (n = 19) followed by heart diseases (n = 4). ‘To help others’ (n = 24) and ‘thought it might improve my access to health care’ (n = 21) were the prime motivators for participation. Maximum respondents (up to 50%) agreed that their research experience was associated with positive outcomes for self and others, research conduct was ethical and opportunities for participation were and will be welcomed. There was also significant disagreement that research had strong emotional repercussions or that the procedures were ‘too long’, ‘boring’ or ‘inconvenient’. Conclusion: Rate of clinical research participation in Qatar needs improvement. Out- reach to potentially eligible subjects is poor where an overwhelming majority is not approached for consent. Time constraints, lack of trust in and poor state of awareness about clinical research are main barriers to participation. Altruism, monetary benefits, improved health access are prime motivators. Length of stay in Qatar is a statistically significant determinant of recruitment in research (p <  0.002). Deeper insight into the factors affecting clinical research participation is needed to devise evidence based policies for improvement in recruitment strategies and the future of evidence based medical care.

Keywords: Attitudes, Barriers, Motivators, Clinical Research, State of Qatar

References: 1. Trauth JM, Musa D, Siminoff L, Jewell IK, Ricci E. Public attitudes regarding willingness to participate in medical research studies. J Health Soc Policy 2000;12(2):23–43.

2. Nair SC, Ibrahim H, Celentano DD. Clinical trials in the Middle East and North Africa (MENA) Region: grandstanding or grandeur? Contemp Clin Trials 2013 Nov;36(2):704–710.

3. McCullagh MC, Sanon MA, Cohen MA. Strategies to enhance participant recruitment and retention in research involving a community-based population. Appl Nurs Res 2014 Nov;27(4):249–253.

4. Teschke K, Marino S, Chu R, Tsui JK, Harris MA, Marion SA. Public opinions about participating in health research. Can J Public Health 2010 Mar-Apr;101(2):159–164.