1,480 research outputs found

    DiGeorge syndrome gene tbx1 functions through wnt11r to regulate heart morphology and function

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    DiGeorge syndrome (DGS) is the most common microdeletion syndrome, and is characterized by congenital cardiac, craniofacial and immune system abnormalities. The cardiac defects in DGS patients include conotruncal and ventricular septal defects. Although the etiology of DGS is critically regulated by TBX1 gene, the molecular pathways underpinning TBX1's role in heart development are not fully understood. In this study, we characterized heart defects and downstream signaling in the zebrafish tbx1^(−/−) mutant, which has craniofacial and immune defects similar to DGS patients. We show that tbx1^(−/−) mutants have defective heart looping, morphology and function. Defective heart looping is accompanied by failure of cardiomyocytes to differentiate normally and failure to change shape from isotropic to anisotropic morphology in the outer curvatures of the heart. This is the first demonstration of tbx1's role in regulating heart looping, cardiomyocyte shape and differentiation, and may explain how Tbx1 regulates conotruncal development in humans. Next we elucidated tbx1's molecular signaling pathway guided by the cardiac phenotype of tbx1^(−/−) mutants. We show for the first time that wnt11r (wnt11 related), a member of the non-canonical Wnt pathway, and its downstream effector gene alcama (activated leukocyte cell adhesion molecule a) regulate heart looping and differentiation similarly to tbx1. Expression of both wnt11r and alcama are downregulated in tbx1^(−/−) mutants. In addition, both wnt11r^(−/−) mutants and alcama morphants have heart looping and differentiation defects similar to tbx1^(−/−) mutants. Strikingly, heart looping and differentiation in tbx1^(−/−) mutants can be partially rescued by ectopic expression of wnt11r or alcama, supporting a model whereby heart looping and differentiation are regulated by tbx1 in a linear pathway through wnt11r and alcama. This is the first study linking tbx1 and non-canonical Wnt signaling and extends our understanding of DGS and heart development

    Hepatitis B, C and D viral markers in multitransfused thalassemic children: long term complications and present management

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    Forecasting the Daily Dynamic Hedge Ratios in Emerging European Stock Futures Markets: Evidence from GARCH models

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    This paper empirically estimates and forecasts the hedge ratios of three emerging European and one developed stock futures markets by means of seven different versions of GARCH model. The seven GARCH models applied are bivariate GARCH, GARCH-ECM, BEKK GARCH, GARCH-DCC, GARCH-X, GARCH-GJR and GARCH-JUMP. Daily data during January 2000-July 2014 from Greece, Hungary, Poland and the UK are applied. Forecast errors based on these four stock futures portfolio return forecasts (based on forecasted hedge ratios) are employed to evaluate out-of-sample forecasting ability of the seven GARCH models. The comparison is done by means of Model Confidence Set (MCS) and modified Diebold-Mariano tests. Forecasts are conducted over two nonoverlapping out-of-sample periods, a two-year period and a one-year period. MCS results indicate that the GARCH model provides the most accurate forecasts in five cases, while each of the GARCH-ECM, GARCH-X and GARCH-GJR models constitutes model confidence set in four cases at a reasonable confidence level. Models selection based on modified Diebold-Mariano tests further corroborate results of the MCS tests. Differences between the portfolio returns also indicate the high forecasting ability of GARCH-BEKK and GARCH-GJR models

    Challenges in compression testing of 3D angle-interlocked woven-glass fabric-reinforced polymeric composites.

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    This paper describes the challenges in using testing standards such as D6641/D6641M-14, for determination of compressive strength of 3D angle interlocked glass fabric reinforced polymeric composites (3D-FRPC). It makes use of both experimental investigation and finite element analysis. The experimental investigation involved testing both 2D and 3D-FRPC using ASTM D6641/D6641M-14 and subsequent scanning electron microscopic imaging of failed specimens to reveal the stress state at failure. This was further evaluated using laminate level finite element (FE) analysis. The FE analysis required input of effective orthotropic elastic material properties of 3D-FRPC, which were determined by customizing a recently developed micro-mechanical model. The paper sheds new light on compressive failure of 3D angle interlocked glass fabric composites, as only scarce data is available in literature about this class of materials. It showed that although the tests produce acceptable strength values the internal failure mechanisms change significantly and the standard deviation (SD) and coefficient of variance (COV) of 3D-FRPC comes out to be much higher than that of 2D-FRPC. Moreover, while reporting and using the test data some additional information about the 3D-fabric architecture, such as the direction of angle interlocking fabric needs to be specified. This was because, for 3D angle interlocking of fabric along warp direction, the strength values obtained in the warp and weft direction were significantly different from each other. The study also highlights that due to complex weave architecture it is not possible to achieve comparable volume fractions with 2D and 3D fabric reinforced composites using similar manufacturing parameters for the vacuum assisted resin infusion process. Thus, the normalized compressive strength values (normalized with respect to volume fraction) are the highest for 3D-FRPC when measured along the warp direction, they are at an intermediate level for 2D-FRPC and the lowest for 3D-FRPC, when measured in the weft direction.DelPHE 780 Project grant (DFID UK

    A review of advancements in synthesis, manufacturing and properties of environment friendly biobased Polyfurfuryl Alcohol Resin and its Composites

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    The quest for environmentally friendly and sustainable materials in the production of fibre reinforced composite materials has led to the use of biobased materials, which are easily accessible and renewable. Biomass-derived chemicals, their derivatives, and their applications have become increasingly prevalent in various industries and processes, greatly contributing to the goal of ecological sustainability. The biobased Polyfurfuryl Alcohol (PFA) resin is one of such polymeric materials that is gaining attention for composite applications due to its endearing Fire Smoke and Toxicity properties. Derived from agricultural by products such as sugar cane bagasse, it has been known for applications within the foundry, coating, and wood industries. However, there has been a growing interest in its use for fibre reinforced composite applications. For this reason, this work intends to provide a comprehensive review of the PFA resin in relationship to fibre reinforced composites applications. The work provides an in-depth discussion on the synthesis, curing process, manufacturing, and properties of the PFA resin as well as its composites

    Off-Axis and On-Axis Performance of Novel Acrylic Thermoplastic (Elium®) 3D Fibre-Reinforced Composites under Flexure Load

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    The flexure response of novel thermoplastic (Elium®) 3D fibre-reinforced composites (FRC) was evaluated and compared with a conventional thermoset (Epolam®)-based 3D-FRC. Ten different types of sample 3D-FRC were prepared by varying fibre orientations, i.e., 0°, 30°, 45°, 60° and 90°, and resin system, i.e., thermoplastic and thermoset. The bending characteristics and failure mechanisms were determined by conducting a three-point bend test. Results elucidate that The flexure response of novel thermoplastic (Elium®) 3D fibre-reinforced composites (FRC) was evaluated and compared with a conventional thermoset (Epolam®)-based 3D-FRC. Ten different types of sample 3D-FRC were prepared by varying fibre orientations, i.e., 0°, 30°, 45°, 60° and 90°, and resin system, i.e., thermoplastic and thermoset. The bending characteristics and failure mechanisms were determined by conducting a three-point bend test. Results elucidate that the on-axis specimens show linear response and brittle failure; in contrast, the off-axis specimens depicted highly The flexure response of novel thermoplastic (Elium®) 3D fibre-reinforced composites (FRC) was evaluated and compared with a conventional thermoset (Epolam®)-based 3D-FRC. Ten different types of sample 3D-FRC were prepared by varying fibre orientations, i.e., 0°, 30°, 45°, 60° and 90°, and resin system, i.e., thermoplastic and thermoset. The bending characteristics and failure mechanisms were determined by conducting a three-point bend test. Results elucidate that the on-axis specimens show linear response and brittle failure; in contrast, the off-axis specimens depicted highly nonlinear response and ductile failure. The thermoplastic on-axis specimen exhibited almost similar flexure strength; in comparison, the off-axis specimens show ~17% lower flexure strength compared to thermoset 3D-FRC. Thermoplastic 3D-FRC shows ~40% higher energy absorption, ~23% lower flexure modulus and ~27% higher flexure strains as compared to its thermoset counterpart

    Assessment of depression and anxiety in adult cancer outpatients: a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>The prevalence of anxiety and depressive disorders in cancer patients and its associated factors in Pakistan is not known. There is a need to develop an evidence base to help introduce interventions as untreated depression and anxiety can lead to significant morbidity. We assessed the prevalence of depression and anxiety among adult outpatients with and without cancer as well as the effect of various demographic, clinical and behavioral factors on levels of depression and anxiety in cancer patients.</p> <p>Methods</p> <p>This cross-sectional study was carried out in outpatient departments of Multan Institute of Nuclear Medicine and Radiotherapy and Nishtar Medical College Hospital, Multan. Aga Khan University Anxiety and Depression Scale (AKUADS) was used to define the presence of depression and anxiety in study participants. The sample consisted of 150 diagnosed cancer patients and 268 participants without cancer (control group).</p> <p>Results</p> <p>The mean age of cancer patients was 40.85 years (SD = 16.46) and median illness duration was 5.5 months, while the mean age of the control group was 39.58 years (SD = 11.74). Overall, 66.0% of the cancer patients were found to have depression and anxiety using a cutoff score of 20 on AKUADS. Among the control group, 109 subjects (40.7%) had depression and anxiety. Cancer patients were significantly more likely to suffer from distress compared to the control group (OR = 2.83, 95% CI = 1.89-4.25, P = 0.0001). Performing logistic regression analysis showed that age up to 40 years significantly influenced the prevalence of depression and anxiety in cancer patients. There was no statistically significant difference between gender, marital status, locality, education, income, occupation, physical activity, smoking, cancer site, illness duration and mode of treatment, surgery related to cancer and presence of depression and anxiety. Cancers highly associated with depression and anxiety were gastrointestinal malignancies, chest tumors and breast cancer.</p> <p>Conclusions</p> <p>This study highlights high prevalence rates of depression and anxiety in cancer patients. Younger age was associated with a higher likelihood of meeting criteria for psychological morbidity. The findings support screening patients for symptoms of depression and anxiety as part of standard cancer care and referring those at a higher risk of developing psychological morbidity for appropriate care.</p

    Bearing performance and damage characteristics of rein-infused thermoplastic 3D woven composites bolted joints

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    This paper presents a comprehensive study on the single-bolt single-shear (SBSS) and double-bolt single shear (DBSS) lap joint performance of resin-infused thermoplastic 3D fibre-reinforced composite (FRC) in on-axis (0°and 90°) and off-axis (45°) configurations. The bearing performance and failure mechanisms are compared with thermoset 3D-FRC. The resin-infused thermoplastic 3D-FRC bolted joint shows improved bearing performance in terms of higher ultimate bearing strength, stiffness loss strength, and reduced damage severity than its thermoset counterpart. Additionally, this paper presents a detailed study on the intermediate and final failure mechanisms, obtained from scanning electron microscopy of the interrupted and ultimate bearing tests, to understand damage progression in SBSS and BDSS lap joints at the submicron level. The major damage characteristics of a thermoplastic 3D-FRC bolted joint include plastic deformation and plastic kinking at the hole front tip, which improve the bearing capacity and reduce stress concentration, damage severity, and its deleterious effects

    Diffusion of the Cu monomer and dimer on Ag(111): Molecular dynamics simulations and density functional theory calculations

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    We present results of molecular dynamics (MD) simulations and density functional theory (DFT) calculations of the diffusion of Cu adatom and dimer on Ag(111). We have used potentials generated by the embedded-atom method for the MD simulations and pseudopotentials derived from the projected-augmented-wave method for the DFT calculations. The MD simulations (at three different temperatures: 300, 500, and 700 K) show that the diffusivity has an Arrhenius behavior. The effective energy barriers obtained from the Arrhenius plots are in excellent agreement with those extracted from scanning tunneling microscopy experiments. While the diffusion barrier for Cu monomers on Ag(111) is higher than that reported (both in experiment and theory) for Cu(111), the reverse holds for dimers [which, for Cu(111), has so far only been theoretically assessed]. In comparing our MD result with those for Cu islets on Cu(111), we conclude that the higher barriers for Cu monomers on Ag(111) results from the comparatively large Ag-Ag bond length, whereas for Cu dimers on Ag(111) the diffusivity is taken over and boosted by the competition in optimization of the Cu-Cu dimer bond and the five nearest-neighbor Cu-Ag bonds. Our DFT calculations confirm the relatively large barriers for the Cu monomer on Ag(111)-69 and 75 meV-compared to those on Cu(111) and hint a rationale for them. In the case of the Cu dimer, the relatively long Ag-Ag bond length makes available a diffusion route whose highest relevant energy barrier is only 72 meV and which is not favorable on Cu(111). This process, together with another involving an energy barrier of 83 meV, establishes the possibility of low-barrier intercell diffusion by purely zigzag mechanisms
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