A novel role for NFATC1 gene in patients with both congenital heart diseases and eye defects -

Thesis. M.S. American University of Beirut. Department of Biology, 2014. T:6050Advisor : Dr. Elias Baydoun, Professor, Biology ; Members of Committee : Dr. George Nemer, Associate Professor, Biochemistry and Molecular Genetics ; Dr. Fadi Bitar, Professor, Pediatrics and Adolescent Medicine ; Dr. Zakaria Kambris, Assistant Professor, Biology.Includes bibliographical references (leaves 76-82)Valvulogenesis and eye development are among the most intriguing events during development. Complex signaling hierarchies of transcription and growth factors orchestrate such developmental processes. Among these modulators, NFATC1 (Nuclear Factor of Activated T-cells), VEGF (Vascular Endothelial Growth Factor), TBX5 (T- box transcription factor), and calcineurin are known to be key players implicated in development. Investigating the role of NFATC1 and unveiling its downstream targets and co-operators, are crucial in order to understand the pathological context of valvuloseptal and congenital eye defects. We have recently shown two novel missense (P66L, I701L) mutations in the NFATC1 gene in one patient with tricuspid atresia. Functional analyses did show a defect in its cellular localization, transcriptional activities and DNA binding activity of the protein. Moreover, previous data form our lab have correlated a defective valvular and septal phenotype of aortic stenosis and atrial septal defect to a heterozygous mutation in the TBX5 gene. Our preliminary data suggests also that the interaction between NFATC1-TBX5 and TBX5-calcineurin boosts the transcriptional activity of VEGF promoter. We screened for mutations in the coding region of NFATC1 in a family with septal and valve defects in addition to severe eye defects and found a previously documented polymorphism (rs62096875) leading to a missense mutation (V210M). Our results unravel a novel pathway implicating an interaction with Tbx5, probably responsible for the underlying phenotype. We can confidently suggest that NFATC1 plays a major role in congenital valvular diseases and eye defects. We hypothesize according to our result that the vascular endothelial growth factor (VEGF) is a downstream target for both NFATC1 and Tbx5 and is implicated both in heart and eye development

Coherence in Translation

Coherence is the trait that makes the text easily understandable to a reader. One can help create coherence in his text by creating logical and verbal bridges. Coherence is a product of many different factors, which combine to make every paragraph, sentence, and phrase contribute to the meaning of the whole piece. Coherence in translation is much more difficult to sustain than coherence in the original language simply because translators have less clues to inform them if their message is as clear as it was originally intended or not. Therefore, translators must make their patterns of coherence much more explicit and carefully planned. Coherence itself is the product of two factors – paragraph unity and sentence cohesion. Keywords: Translation, coherence, connection, transition

Essays in international finance

This thesis contributes to the extant research on international finance by presenting a collection of three separate essays. The first essay tests the validity of long-run Purchasing Power Parity (PPP) in two panels of real exchange rates for 13 OECD countries (1989:07-2012:11, 1989:07-2006:12). Three panel unit root tests are applied, one that assumes cross-sectional independence, one that accounts for cross-sectional dependence using a single factor approach, and one that controls for cross-sectional dependence through a multi-factor approach. The main difference in the results is attributed to ignoring or allowing for cross-sectional dependence. The second essay also examines long-run PPP, but uses a panel cointegration test which allows for (i) heterogeneous and multiple structural breaks and (ii) crosssectional dependence. Based on a panel of 53 economies (1992:01-2014:05 ) no evidence of PPP can be found using two types of models that can be equipped/illequipped to handle the potential presence of structural breaks in the data. The third essay employs a factor approach to analyse exchange rate prediction at multiple horizons, from 1 month to two years for a panel of 10 OECD economies spanning the period 1999:01-2013:04. Two new models are proposed, that are based on the separate use of forward rates and interest rate differentials to be added in conjunction with the extracted factors. Factor-based exchange rate models were found to beat the random walk model for long horizons over the latter parts of our forecasting sample

Performance Comparison of Field-oriented Control, Direct Torque Control, and Model-predictive Control for SynRMs

Simulation studies of three synchronous reluctance motor (SynRM) control strategies are presented: field-oriented control (FOC), direct torque control (DTC), and finite-set model-predictive control (FS-MPC). FOC uses linear controllers and pulse-width modulation to control the fundamental components of the load voltages vectors. In contrast, DTC and FS-MPC are nonlinear strategies wherein the voltage vectors are directly generated in the absence of a modulator. Theoretical operating principles and control structures of these control strategies are presented. Moreover, a comparative analysis of the static and dynamic performance of the control strategies is conducted using Matlab/Simulink to identify their advantages and limitations. It is confirmed that each of the control strategies has merits and that all three of them satisfy the requirements of modern high-performance drives.info:eu-repo/semantics/publishedVersio

Predictive Stator Flux and Load Angle Control of Synchronous Reluctance Motor Drives Operating in a Wide Speed Range

This paper presents a new simplified finitecontrol- set model predictive control strategy for synchronous reluctance motors operating in the entire speed range. It is a predictive control scheme that regulates the stator flux and the load angle of the synchronous reluctance motor, incorporating the ability to operate the drive in the field-weakening region and respecting the motor voltage and current limits as well as the load angle limitation needed to operate this type of motor in the maximum torque per voltage region. The proposed control strategy possesses some attractive features, such as no need for controller calibration, no weighting factors in the cost function, good robustness against parameter mismatch, and smaller computational cost compared to more traditional finite-control-set model predictive control algorithms. Simulation and experimental results obtained using a high-efficiency synchronous reluctance motor demonstrate the effectiveness of the proposed control scheme.info:eu-repo/semantics/publishedVersio

An encoderless high-performance synchronous reluctance motor drive

This paper presents an encoderless high-performance synchronous reluctance motor drive for traction applications. The control system is based on the active flux concept and a hybrid rotor position estimation algorithm is used, being this algorithm based on the injection of high-frequency signals at low speeds and on the position of the active flux vector for medium and high-speeds. A smooth transition algorithm between the two rotor position estimation methods is provided. Moreover, in order to improve the efficiency of the overall drive system, a loss minimization algorithm is proposed in order to reduce the motor copper losses when operating in steady-state. Experimental results obtained in the laboratory confirm the validity and adequacy of the proposed algorithms for the developed drive system.info:eu-repo/semantics/publishedVersio

Therapeutic prospects of extracellular vesicles in cancer treatment

Extracellular vesicles (EVs) are released by all cells within the tumor microenvironment, such as endothelial cells, tumor-associated fibroblasts, pericytes and immune system cells. The EVs carry the cargo of parental cells formed of proteins and nucleic acids, which can convey cell-to-cell communication influencing the maintenance and spread of the malignant neoplasm, for example promoting angiogenesis, tumor cell invasion and immune escape. However, EVs can also suppress tumor progression, either by the direct influence of the protein and nucleic acid cargo of the EVs or via antigen presentation to immune cells as tumor derived EVs carry on their surface some of the same antigens as the donor cells. Moreover, dendritic cell-derived EVs carry MHC class I and class II/peptide complexes and are able to prime other immune system cell types and activate an anti-tumor immune response. Given the relative longevity of vesicles within the circulation and their ability to cross blood-brain barriers, modification of these unique organelles offers the potential to create new biological-tools for cancer therapy. This review examines how modification of the EV cargo has the potential to target specific tumor mechanisms responsible for tumor formation and progression to develop new therapeutic strategies and to increase the efficacy of antitumor therapies

Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools

Simple SummaryExtracellular vesicles (EVs) are secreted continuously from different cell types. The composition of EVs, like proteins, nucleic acids and lipids is linked with the cells of origin and they are involved in cell-cell communication. The presence of EVs in the majority of the body fluids makes them attractive to investigate and define their role in physiological and in pathological processes. This review is focused on EVs with dimensions between 30 and 150 nm like exosomes (EEVs). We described the biogenesis of EEVs, methods for isolation and their role in cancer as innovative diagnostic tools and new drug delivery systems.Nanosized extracellular vesicles (EVs) with dimensions ranging from 100 to 1000 nm are continuously secreted from different cells in their extracellular environment. They are able to encapsulate and transfer various biomolecules, such as nucleic acids, proteins, and lipids, that play an essential role in cell-cell communication, reflecting a novel method of extracellular cross-talk. Since EVs are present in large amounts in most bodily fluids, challengeable hypotheses are analyzed to unlock their potential roles. Here, we review EVs by discussing their specific characteristics (structure, formation, composition, and isolation methods), focusing on their key role in cell biology. Furthermore, this review will summarize the biomedical applications of EVs, in particular those between 30 and 150 nm (like exosomes), as next-generation diagnostic tools in liquid biopsy for cancer and as novel drug delivery vehicles

Determination of sulfur in biological samples using high-resolution molecular absorption spectrometry in a graphite furnace with direct solid sampling

The determination of sulfur in biological materials using high-resolution continuum source molecular absorption spectrometry and electrothermal vaporization of the carbon monosulfide (CS) molecule has been investigated in detail using direct solid sampling. Best results have been obtained coating the platform with tungsten as a permanent modifier, adding 40 mg Pd in solution as a chemical modifier, and the only sulfur compound that showed sufficient sensitivity and thermal stability to be used for calibration purposes under the conditions established for biological materials was thiourea. A pyrolysis temperature of at least 900 C could be used and the optimum vaporization temperature was 2500 C. Under optimized conditions a limit of detection of 0.015 mg S absolute or 0.03 mg g À1 S in the solid sample, based on a sample mass of 0.5 mg could be obtained; the characteristic mass was m 0 ¼ 18 ng. Five certified biological reference materials have been analyzed using direct solid sampling and calibration against aqueous standards; the results were in agreement with the certified values on a 95% confidence interval

Results from the Lebanese 2022 report card on physical activity for children and youth

Objective: The Lebanese Active Healthy Kids Work Group (LAHKWG) synthesized literature published on physical activity (PA) indicators among ages 5- to 17- year-olds, using a recommended harmonized process by the Active Healthy Kids Global Alliance (AHKGA), to explore Lebanon's performance since its previous report card publication. Methods: Peer reviewed literature, national surveys, and gray literature published since 2017, on 10 common AHKGA and two LAHKWG recommended indicators were examined. Common indicators included overall PA, organized sport and PA, active play, active transportation, community and environment, sedentary behaviors, physical fitness, family and peers, school, and government. LAHKWG recommended indicators were sleep and weight status. LAHKWG members reviewed 764 records, of which 28 were selected for full review. A grade was assigned for each indicator using AHKGA's grading rubric and established benchmarks on data from nationally representative samples for children and youth. Results: Data from one nationally representative sample were available for ages 13–17 years (i.e., no data <13 years). Five indicators received “Incomplete” (organized sport and PA; active Play; physical fitness; family and peers; community and environment); overall PA received a D-; active transportation and sleep received a D+; school and government received a D; sedentary behaviors received a C; and weight status received a B-. Conclusion: The LAHKWG strongly encourages stakeholders to take concrete actions towards prioritizing PA promotion at a national level especially in the education sector. Offering more quality PA opportunities for Lebanese children and youth will be beneficial for their physical and mental health in any context. © 2022 The Society of Chinese Scholars on Exercise Physiology and Fitnes