The role of Tumour Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) in Pulmonary Arterial Hypertension.

Background Pulmonary arterial hypertension (PAH) is an obliterative vasculopathy characterized by endothelial and smooth muscle cell proliferation affecting small arterioles resulting in progressive elevation of pressure within the lungs. This poses significant load on the right heart which can lead to heart failure. It is a devastating and life threatening disease as patients are frequently diagnosed at an advanced stage. Existing drug therapies augmenting pulmonary vasodilatation have significantly improved patient morbidity but insufficiently modify vascular remodeling and consequently have modestly improved survival. Halting or reversing vascular remodeling could revolutionise human therapy but has yet to come to fruition. To improve disease prognosis, identifying key disease pathways is a priority for developing newer therapies. A role for Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in regulating endothelial cell and smooth muscle cell physiology has been reported in the systemic vasculature but hitherto unexplored in the pulmonary circulation. I hypothesised that TRAIL is an essential mediator in the pathogenesis of PAH. Methods: Expression of TRAIL in human and rodent PAH and the mitogenic effects of TRAIL on pulmonary artery smooth muscle cells (PASMCs) were characterised. The pathogenic role of TRAIL in three independent rodent models of disease was determined and the efficacy of inhibiting TRAIL in halting or regressing established disease was tested. Phenotyping included cardiac catheterisation, echocardiography, and pulmonary vascular immunohistochemistry. Findings Gene and protein expression of TRAIL ligand and receptors were upregulated in PASMCs from patients with PAH. In-vitro TRAIL was a mitogen for PASMCs. TRAIL-deficient mice were protected from both hypoxia and diet-induced PAH. Antibody blockade prevented rats from developing MCT induced PAH. Bone marrow transplantation in chimeric mice supported a role for tissue derived TRAIL. In mice and rats with established disease, an anti-TRAIL antibody improved pulmonary haemodynamics, reversed pulmonary vascular remodeling, reduced proliferation and increased apoptosis in vascular lesions and significantly improved survival. Conclusion: My preclinical studies are the first to determine the importance of TRAIL in the pathogenesis of experimental pulmonary arterial hypertension and highlight its potential as a novel therapeutic target for directing future therapies

Jurisprudence Islamic Selling Contracts and Their Role in Islamic Banks Activities

This research related with Shareah contracts that applied by Islamic banks. it dealt with some jurisprudence aspects briefly. then moved to the application of them by these banks. It displayed some problems that accompanied with the application, making it difficult to these banks to fulfill these contracts as they elaborated in the shareah, this may force these banks or their clients to search about stratagems which leads to mistakes in applying the contracts from the point of view of shareah, or to make many difficulties for these banks to play the role of financial intermediation efficiently, although the research agree that these contracts represent the available way to Islamic banks now to act accordance with shareah, but agree also that this is not the end of the way, because of two reasons, First: the problems we referred to just above, Second: These contracts are not obligatory to Islamic banks (except Sarf contract - Exchange contract-.). The field was opened for them and for Islamic jurists, economists, and Islamic bankers to search about more suitable ways to act. On just one condition that is they must be in line with sharia. The research ended with some recommendations and conclusions. Keywords: Islamic banking, jurisprudence, shariah, Islamic, selling contract

The Impact of Sequencing Human Genome on Drug Design to Treat Oral Cancer

Of all the known cancers, oral cancer is the most preventable and it is the second most deadly cancer after the breast cancer. Out of 609,640 deaths of overall cancers, 13,500 died of oral cancer. In spite of this enormous increase in loss of life, there are no useful drugs to treat oral cancer. Sequencing human genome identifies with precision and accuracy the specific mutations responsible for causing oral cancer. In this chapter, a novel approach to design drugs to attack mutated genes in squamous cell carcinoma responsible for causing oral cancer is proposed. Alkylating aziridines attack single-stranded DNA shutting off genes. Using dinitrobenzamide dye as a carrier for aziridine, we successfully made a novel class of drugs (CB 1954) which shuts off gene of a solid tumor, Walker Carcinoma 256, in rats. We translated the animal work in humans by using quinone as a carrier for aziridines making AZQ (US Patent 4,146,622) for attacking glioblastoma for treating brain cancer in humans. We propose to search for a carrier for aziridines to attack squamous cell carcinomas to treat oral cancer. Ethical issues are discussed. Since tobacco smoking causes oral cancer, it is the most preventable disease

Studies on nucleotides and related compounds

The chemistry of polynucleotides is reviewed. Polydeoxyribonucleotides containing thyuddylate and deoxyadenylate residues were synthesised using aqueous solutions and either l-cyclohexyl-3 (2-morpholinoethyl) carbodiimide metho-p-toluenesulphonate (water-soluble carbodiimide) or ethoxyacetylene as a polymerising agent. In each polymerisation, one of the mononucleotides was labelled with 32P so that nearest neighbour base-sequence analysis could be carried out on the polymeric products. The results of these analyses show that the base-sequence is essentially random, but that thymidylic acid is incorporated some 39 to 44 times more efficiently than deoxyadenylic acid. The reasons for this predominance have been suggested. The polydeoxyribonucleotides were also synthesised in the presence of a primer (polyuridylic acid) under the same conditions as those employed for the above-mentioned syntheses. The results showed a significant increase in the total amount of polymer and in the relative incorporation of deoxyadenylic acid into the polymer; the latter increasing by a factor of 8 to 9. On the basis of these findings it is therefore, suggested that in the absence of primer, the copolymerisation of a mixture of nucleotides is controlled by kinetic factors whereas. in the presence of a suitable primer. the base-pairing due to hydrogen hooding can

Prioritizing and Achieving Quality Services in Gas Stations using Analytical Hierarchy Process and Quality Function Deployment

53-55Identifying customer requirement and modifying the services as per expectation of customer in service sector leads to achieve the profit of organization and sustain in the market. The customer expectations towards the service organization dramatically increased in recent years, in order to sustain in the market, the organization should identify the customer requirements, adopting the system, process, services as per expectation of customer in the organization. This article highlights the expectation of customer in gas stations located at Jeddah, Saudi Arabia. The data collection done at various gas stations, a questioner-based survey conducted to identify the customer requirements from 10 gas stations, 250 responds collected from different category of customer based on the driving vehicle such as four wheelers and heavy vehicle. The data collection validated by SPSS software and Analytical Hierarchy process used for prioritizing the customer requirements and House of quality constructed as per requirement of customer, the quality function deployment introduced to enhance the services in gas stations. The article concludes that, the following requirements were highly expected from gas stations, the requirements were need space between one pump to another pump, payment by credit card also to be considered, services for cleaning car windows, quick wash, availably of rest room and the proper maintenance of gas stations (calibration of air machine, cleaning of work station frequently, introducing 5S Concept and displaying in and exit board). The article suggests the function modification required in gas stations for achieving customer requirement

A Statistical Framework for Automating Resonance Detection: Modelling Pion Proton Collision Activity

In this paper, we analyze π− − p elastic collision data from the Particle Data Group (PDG), by creating a general framework to study resonance activity: automating peak detection, extrapolating, parametrizing thresholds, filtering resonances and further comparing and extracting characteristics, to identify Delta (Δ) baryons. We then analyse experimental Energy vs Phase-Shift (δ) data for the collision π+ +π− → π− +π+, model the T matrix from a curve fitted polynomial representation of the K−1 matrix, simulate its Riemann sheets and analyse it to identify the characteristics of ρ0(770) meson, as well as estimate their uncertainties. These methodologies offer a foundation for similar analyses in different systems and events

Adoption process of information technology (IT) innovations in organizations

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Several models have been developed for understanding and predicting innovation adoption in organizations and literature has identified several factors that impact the adoption and implementation of Information Technology (IT). This research examines the process of adoption of IT innovations in organizations. The study explores the processes involved in the adoption of IT and verifies the key factors that influence IT innovation adoption in organizations. Using a systematic literature review, the study developed a conceptual model of IT innovation adoption in organizations. The model is a theoretical combination of Diffusion of Innovation (DOI) theory, Theory of Reasoned Action (TRA), Technology Acceptance Model (TAM), Theory of Planned Behaviour (TPB) and a framework which contains characteristics of innovation, organization, environment, chief executive officer (CEO) and user acceptance. The model represents IT innovation adoption as a stage-based process, progressing from initiation to adoption-decision to implementation. The study aggregated findings of past research on IT adoption to identify key factors that influences IT adoption in organizations. The study performed a meta-analysis of innovation, organization, environment, CEOs and user acceptance determinants to assess the magnitude and the strength of these factors on IT innovation adoption. Results confirmed that relative advantage, compatibility, cost, observability and trialability are strong determinants of IT innovation adoption. In terms of organizational context, IS department size, top management support, organizational size, IT expertise, product champion, IS infrastructure, information intensity, resources and specialization was found influential in the adoption of IT. As for environmental characteristics, the meta-analysis verified the significance of external pressure, government support and competitive pressure. Meta-analysis results verified that CEO‟s innovativeness, attitude and IT knowledge as key determinants. The findings confirmed the importance of perceived usefulness, perceived ease of use, subjective norm and facilitating conditions for the user acceptance of IT in organizations

Adsorption of Cd(II) and Pb(II) Ions from Aqueous Solution byActivated Carbon

Heavy metal consider as major environmental pollutants. Many of industrial wastewater effluents contain a wide range of these heavy metals. The adsorption of Cd2+ and Pb2+ metal ions from aqueous solution by activated carbon was studied. The results showed that maximum adsorption capacity occurred at 486.9×10-3 mg/kg for Pb2+ ion and 548.8×10-3 mg/kg for Cd2+ ion. The adsorption in a mixture of the metal ions had a balancing effect on the adsorption capacity of the activated carbon. The adsorption capacity of each metal ion was affected by the presence of other metal ions rather than its presence individually. The study showed the presence of other heavy metals attribute to the reduction in the activated carbon capacity, and the adsorption process was found to obeys the Freundlich isotherm for both ions