Spatial Dynamics and the Mechanoresponse in CD4+ T Cell Activation

The activation of naïve CD4+ T cells by antigen presenting cells is a critical step in the response of the immune system to foreign pathogens and in its acclimation to host tissues. Activation of naïve T cells proceeds through TCR engagement and is further augmented by CD28 costimulation: ensuring T cell survival and conferring numerous functional capabilities. The work in this dissertation highlights the spatial and temporal dynamics that regulate the initial coupling of CD28 with TCR signaling and also dissects the mechanical properties conferred by downstream effectors that are required to relay CD28 costimulation. A reaction-diffusion model that describes the spatial regulation of costimulation in activating human T cells is developed. The Src kinase Lck, though predominantly cytosolic, is an ideal candidate for the coupling of the TCR and CD28 pathways. Membrane associations bring Lck in contact with these receptors, where mediation of its active state by kinase activity and regulation of its spatial dynamics dictate its capacity to integrate early TCR and CD28 signaling. This developed reaction-diffusion model focusing on Lck is then extrapolated to mouse cells that do not share similar sensitivity to segregation of TCR and CD28 triggering: indicating that while Lck is essential for costimulation, it does not confer spatial sensitivity in activating mouse T cells. A comparison of human and mouse cells demonstrate underlying differences in the diffusivity of Lck across the membrane and the enrichment of the cytoskeleton at the interface. The role of the cytoskeleton in generating TCR-driven contractile forces is then investigated through use of micropillar arrays. This approach also enables the quantification of forces generated by T cells during cellular activation. The impact of CD28 costimulation on TCR-driven force generation is assessed and noted to increase cellular forces by 80% beyond what is induced through TCR triggering. By manipulating the presentation of CD28 activation, CD28 is determined to be a mechanoresponsive receptor that is not directly responsible for mechanosensitivty. Rather, CD28 mediates a change in cellular forces through PI3 kinase, whose inhibition normalizes force generation in T cells activated by TCR and those costimulated with TCR and CD28. Downstream of PI3 kinase, PDK1 is identified as being essential in both TCR and CD28 costimulatory force generation; inhibition of PDK1 fully abrogates cellular forces. Lastly, we qualitatively characterize T cell activation on micropillar arrays, where their complex topology reveals a multiphasic behavior during activation. Whereas T cells activated on planar surfaces are relatively stationary, T cells activated on micropillars slowly migrate towards the base of the array. Forces exerted during this migration are substantially greater than those previously measured, and the slow migration leads to the characterization of multiple phases and the relocalization of key cellular proteins

A qualitative study exploring barriers to adequate uptake of antenatal care in pre-conflict Syria: low cost interventions are needed to address disparities in antenatal care.

Syria has made progress in reducing maternal mortality and morbidity before the conflict in 2011. Despite the improvement in antenatal care (ANC) coverage and patterns of use, analyses of national surveys demonstrated wide regional variations in uptake, timing and number of visits even after controlling for women's socio-demographic characteristics. This study compares two governorates: Latakia, where uptake of ANC was high and Aleppo, where uptake of ANC was low to highlight the barriers to women's adequate uptake of ANC that existed in Syria pre-conflict. This qualitative study carried out 30 semi-structured interviews with (18-45-year-old) pregnant women from Aleppo and Latakia (recruited purposively from different types of health facilities in rural and urban areas), and 15 observation sessions at health facilities. Transcripts and fieldnotes were analyzed using the Framework Method with attention to the dimensions of availability, accessibility and acceptability of services. Inadequate uptake of ANC in Aleppo included not attending ANC, seeking care with providers who are not trained to provide ANC or discontinuing care. Three themes explained the regional disparities in the uptake of ANC in Aleppo and Latakia: women's assessment of their health status and reasoning of causes of ill health in pregnancy; women's evaluation of the risks of seeking ANC; and women's appraisal of the value of different types of service providers. Poor experiences at public health facilities were reported by women in Aleppo but not by women in Latakia. Evaluations of ANC services were connected with the availability, accessibility (geographical and financial) and acceptability of ANC services, however, women's views were shaped by the knowledge and prevailing opinions in their families and community. Findings are utilized to discuss low-cost interventions addressing the disparities in ANC uptake. Interventions should aim to enable vulnerable women to make informed decisions focusing on regions of low uptake. Women's groups that foster education and empowerment, which have been effective in other low resource settings, could be of value in Syria. Increased use of mobile phones and social media platforms suggests mobile health technologies (mHealth) may present efficient platforms to deliver these interventions

Alginate-pomegranate peels' polyphenols beads: effects of formulation parameters on loading efficiency

Pérolas de alginato de cálcio, contendo polifenóis de extrato de casca de romã, foram encapsuladas pelo método de gelificação iônica. Os efeitos de vários fatores de formulação (concentração de alginato de sódio, concentração de cloreto de cálcio, cloreto de cálcio, o tempo de exposição, o tempo de manutenção do banho de gelificação e a concentração do extrato) sobre a eficiência de carga do extrato foram investigados. A formulação que contém 1 g extrato de casca de romã em 100 mL de água destilada, encapsulado com 3% de alginato de sódio curada em 0,05 M de cloreto de cálcio durante 20 minutos e mantido em banho de gelificação por 15 min foi escolhida como a melhor em relação à eficiência de carga. Estas condições otimizadas permitem o encapsulamento de 43,90% do total de polifenóis extraídos e de 46,34% do total de proantocianidinas extraídas. A microencapsulação de extrato de cascas de romã em esferas de alginato de cálcio é uma técnica promissora para a suplementação farmacêutica e de alimentos com antioxidantes naturais.Calcium alginate beads containing pomegranate peels' polyphenol extract were encapsulated by ionic gelation method. The effects of various formulation factors (sodium alginate concentration, calcium chloride concentration, calcium chloride exposure time, gelling bath time maintaining, and extract concentration) on the efficiency of extract loading were investigated. The formulation containing an extract of 1 g pomegranate peels in 100 mL distilled water encapsulated with 3 % of sodium alginate cured in 0.05 M calcium chloride for 20 minutes and kept in a gelling bath for 15 minutes was chosen as the best formula regarding the loading efficiency. These optimized conditions allowed the encapsulation of 43.90% of total extracted polyphenols and 46.34 % of total extracted proanthocyanidins. Microencapsulation of pomegranate peels' extract in calcium alginate beads is a promising technique for pharmaceutical and food supplementation with natural antioxidants

Diagnostic value of chest X-ray and echocardiography for cardiac tamponade in post cardiac surgery patients

Objective: To investigate the effectiveness of X-ray and echocardiography (ECHO) as a diagnostic tool for cardiac tamponade in adult cardiac surgery patients.Methods: Thirty five coronary artery bypass and graft surgery patients who developed cardiac tamponade at Cleveland clinic foundation, were included in this study. Their diagnosis was confirmed at the time of re-exploration in the operating room. These patients were followed retrospectively for demographics, X-ray and echocardiography findings. Abnormal and enlarged cardiac silhouette which was different from first postoperative X-ray was used as radiological criteria for tamponade while echocardiographic diagnosis was left to the discretion of cardiologist.Results: Twenty four males (69%) and 11 (31%) females with an average age of 60.7 +/- 15.2 years were included in this study. Only 7 (20%) patients met our criteria for radiological diagnosis of tamponade. All 35 patients showed pericardial effusion on ECHO while cardiac tamponade was present in 30 (86%) patients. Tamponade developed on an average on 4th postoperative day.CONCLUSION: Radiological diagnosis of cardiac tamponade based on changes in cardiac silhouette provide limited information while ECHO is a reliable diagnostic tool when combined with clinical findings

High Voltage Optical Fibre Sensor for Use in Wire Relay Electrical Protection Systems

The last few decades have a wide spread use of optical fibre sensors in many applications. Optical fibre sensors have significant benefits over existing conventional sensors such as; high immunity to electromagnetic interference, the ability to transmit signal over long distance at high bandwidth, high resolution, usage in hazardous environments and no need for isolation when working at high voltages. The measurement of high voltages is essential for electrical power systems as it is used as a source of electrical information for Relay Protection Systems (RPS) and load management systems. Electrical Power Systems need to be protected from faults. Faults can range from short circuits, voltage dips, surges, transients etc. The Optical High Voltage sensor developed is based on the principle that the Lead Zirconate Titanate (PZT) electrostriction displacement changes when a voltage is applied to it. The displacement causes the fibre (FBG) which is bonded to the PZT material to have a resultant change in the wavelength. An optical fibre sensor prototype has been developed and evaluated that measures up to 250 V DC. Simulation using ANSYS software has been used to demonstrate the operational capability of the sensor up to 300kV AC. This sensor overcomes some of the challenges of conventional sensors issues like electromagnetic interference, signal transmission, resolution etc. R BASHOUR 2 A novel optical fibre high voltage based on the Kerr effect has been demonstrated. The The Kerr effect was determined using Optsim (R-Soft) software and Maxwell software was used to model an optical Kerr Cell. Maxwell software is an electromagnetic/electric field software used for simulating, analysing, designing 2D and 3D electromagnetic materials and devices. It uses highly accurate Finite Element techniques to solve time varying, static, frequency domain electric and electromagnetic fields. A Relay Protection System on electrical networks was discussed in detail. Keywords: Fibre Bragg Grating, Fibre Optics Sensors, Piezoelectricity, Kerr effect, Relay Protection Systems.N/

Isolation of Peroxidase Isozymes from Two Flax Genotypes by Column Chromatography

Isolation of the four major peroxidase isozymes (isozymes 1, 2, 3, and 4) of two flax genotypes was achieved by modifying the procedure used by Shannon et al. (1966) for the isolation of horseradish peroxidase isozymes. The net positive and net negative charges of isozymes 1, 2, and 4 were different. Isozyme 3 resembled isozyme 4 in charge but differed in apparent molecular weight. The chromatographic elution profiles of both genotypes were the same. Anionic gel electrophoresis demonstrated that after isolation and repurification, relative mobility differences existed between the corresponding isozymes of the two genotypes for all four isozymes

A mixed methods analysis of factors affecting antenatal care content: A Syrian case study

Background Maternity care services provide critical interventions aimed at improving maternal and newborn health. In this study, we examined determinants of antenatal care (ANC) content in Syria, together with changes over time. Methods We analysed two national surveys conducted by the Central Bureau of Statistics in Damascus (PAPFAM 2001 and MICS 2006). Findings of this initial analysis led to a qualitative study on adequacy of antenatal care content in two Syrian governorates, Aleppo and Latakia in 2010, which in turn informed further quantitative analysis. The perspectives and practices of doctors, women, midwives and health officials were explored using in-depth interviews. A framework approach was used to analyse the data. Results The quantitative analysis demonstrated that women’s education level, the type of health facility they attended and whether they had experienced health complications were important determinants of adequacy of ANC content received. The qualitative study revealed that additional factors related to supply side and demand side factors (e.g. organization of health services, doctors’ selective prescription of ANC tests and women’s selective uptake of those tests), influenced the quality of ANC and explained some regional differences between Aleppo and Latakia. Conclusions The percentage of women who received adequate ANC content was probably higher in Latakia than in Aleppo because women in Latakia were more educated, and because services were more available, accessible, and acceptable to them

Classificiation of Atrial Fibrillation Prone Patients Using Electrocardiographic Parameters in Neuro-Fuzzy Modeling,

Atrial Fibrillation (AF) is a significant clinical problem and the complications of cardiovascular postoperative AF often lead to longer hospital stays and higher heath care costs. The literature showed that AF may be preceded by changes in electrocardiogram (ECG) characteristics such as premature atrial activity, heart rate variability (HRV), and P-wave morphology. We hypothesize that the limitations of statistics-based attempts to predict AF occurrence may be overcome using a hybrid neuro-fuzzy prediction model that is better capable of uncovering complex, non-linear interactions between ECG parameters. We created a neuro-fuzzy network that was able to classify the patients into the control and AF groups with the performances: 99.42% sensitivity, 99.89% specificity, and 99.74% accuracy for 30 minutes just before AF onset

The Intrinsic Dimensionality of Attractiveness: A Study in Face Profiles

The study of human attractiveness with pattern analysis techniques is an emerging research field. One still largely unresolved problem is which are the facial features relevant to attractiveness, how they combine together, and the number of independent parameters required for describing and identifying harmonious faces. In this paper, we present a first study about this problem, applied to face profiles. First, according to several empirical results, we hypothesize the existence of two well separated manifolds of attractive and unattractive face profiles. Then, we analyze with manifold learning techniques their intrinsic dimensionality. Finally, we show that the profile data can be reduced, with various techniques, to the intrinsic dimensions, largely without loosing their ability to discriminate between attractive and unattractive face

Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inhibitor Discontinuation.

Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center. Methods: Using an IRB-approved protocol, 4 patients previously enrolled on CDK4/6i trials were analyzed for outcomes after discontinuing study drug. These patients were treated on a randomized trial of first-line endocrine therapy +/- a CDK4/6i. Rapid disease progression was defined as progression occurring within 4 months of CDK4/6i discontinuation. Results: In total, 4 patients developed rapid disease progression and died; 2 of whom died within 6 months of CDK4/6i discontinuation. Conclusion: This case series suggests a potential for rapid disease progression following CDK4/6i discontinuation. However, the clinical course following progression must be validated in large CDK4/6i clinical trials and standard-of-care cohorts. If confirmed, such observations may alter the algorithm for subsequent therapy in patients with disease progression on CDK4/6i. Nevertheless, the need remains to define a mechanistic basis for this rapid progression and formulate alternative therapeutic strategies