Miracle-dz/UniFAR-FTUs huggingface dataset:
Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin

Edema stemming from leaky blood vessels is common in eye diseases such as age-related macular degeneration and diabetic retinopathy. Whereas therapies targeting vascular endothelial growth factor A (VEGFA) can suppress leakage, side-effects include vascular rarefaction and geographic atrophy. By challenging mouse models representing different steps in VEGFA/VEGF receptor 2 (VEGFR2)-induced vascular permeability, we show that targeting signaling downstream of VEGFR2 pY949 limits vascular permeability in retinopathy induced by high oxygen or by laser-wounding. Although suppressed permeability is accompanied by reduced pathological neoangiogenesis in oxygen-induced retinopathy, similarly sized lesions leak less in mutant mice, separating regulation of permeability from angiogenesis. Strikingly, vascular endothelial (VE)-cadherin phosphorylation at the Y685, but not Y658, residue is reduced when VEGFR2 pY949 signaling is impaired. These findings support a mechanism whereby VE-cadherin Y685 phosphorylation is selectively associated with excessive vascular leakage. Therapeutically, targeting VEGFR2-regulated VE-cadherin phosphorylation could suppress edema while leaving other VEGFR2-dependent functions intact.
Status of anthelmintic resistance in gastrointestinal nematodes of sheep in Rajasthan

A study was conducted to assess the status of anthelmintic resistance in gastrointestinal nematodes (predominantly Haemonchus contortus) of sheep maintained at organized farms and farmer’s field in Rajasthan through in-vivo faecal egg count reduction test and in-vitro egg hatch assay. The magnitude of reduction in the faecal egg counts by fenbendazole (@ 5.0 mg kg -1 body weight) revealed emergence of benzimidazole resistance in H. contortus of sheep from all the farm and field flocks except in field flocks from north-eastern Rajasthan where 66.7% flocks possessed benzimidazoleresistant H. contortus. With tetramisole (@ 15 mg kg-1 body weight) resistance in H. contortus was observed in farm flock of north-eastern region whereas among field flocks it ranged from 33.33% (north region) to 83.33% (eastern region). On egg hatch assay, strains of worms were found susceptible to benzimidazole in farm flocks of northern region while in field flocks prevalence of benzimidazole resistance strongyle worms was 100% in eastern and northern region and 83.33% in north-eastern region. A high agreement (86.4%) with poor linear correlation (r = 0.087) was observed between results of both faecal egg count reduction test and egg hatch assay for benzimidazole resistance.
Evaluation of the sensitivity of pulmonary arterial pressure to elevation using a reaction norm model in Angus Cattle.

Pulmonary arterial pressure (PAP) is a diagnostic measure used to determine an individual's susceptibility to developing high altitude disease (HAD). The importance of PAP measures collected at elevations lower than the intended breeding elevation of the bulls (i.e., ≥ 1,520 m) is unknown. Therefore, the objective of this study was to determine the genetic relationship between PAP measures collected in a range of elevations using reaction norm models. A total of 9,177 PAP and elevation observations on purebred Angus cattle, which averaged 43.49 ± 11.32 mmHg and 1,878.6 ± 296.8 m, respectively, were used in the evaluation. The average age of the individuals in the evaluation was 434.04 ± 115.9 d. A random regression model containing the effects of sex, a linear covariate of age, a quadratic fixed covariate of elevation, and random effects consisting of contemporary group and a linear regression of PAP on elevation were used for the evaluation of PAP. Two forms of PAP were evaluated with this model. First, to address the non-normality of the data, PAP was raised to the power of -2.6 (ptPAP) based on the results of a Box-Cox analysis. Second, raw PAP (rPAP) phenotypes were evaluated to compare the results to those obtained from the transformed data. For ptPAP, heritability ranged from 0.25 to 0.37 corresponding to elevations of 1,900 m and 1,215 m, respectively. For rPAP, heritability ranged from 0.22 to 0.41 corresponding to elevations of 1,700 m and 2,495 m, respectively. Generally, lower elevations corresponded to decreased heritabilities while higher elevations corresponded to increased heritability estimates. For ptPAP, genetic correlations ranged from 0.18 (elevation: 1,215 m and 2,495 m) to 1.00. For rPAP, genetic correlations ranged from 0.08 (elevation: 1,215 m and 2,495 m) to 1.00. In general, the closer the elevations in which PAP was measured, the greater the genetic relationship. The greater the difference in elevation between PAP measures resulted in lower genetic correlations. The rank correlation between expected progeny differences for 1,215 m and 2,495 m) was 0.65 and 0.49 for the ptPAP and rPAP, respectively. These results suggested that PAP measures collected in lower elevations may be used as an indicator of high-altitude adaptability. In the estimation of EPD to rank sires for their suitability for use in high elevation production systems, it is important to account for the relationships among varied altitudes.
Caractérisation de la RNase E et du dégradosome d'ARN de la bactérie marine adaptée au froid Pseudoalteromonas haloplanktis

La degradation des ARNm est l'un des processus biologiques essentiels qui implique chez les bacteries, l'intervention d'un complexe multiproteique appele « degradosome d'ARN ». Chez E. Coli, la formation de ce complexe necessite l'endoribonuclease essentielle « RNase E », qui porte dans sa region non conservee, des ilots de 15 a 40 acides amines appeles « microdomaines ». Ces microdomaines sont responsables des interactions entre la RNase E et trois proteines : l'helicase a ARN RhlB, l'enzyme de la glycolyse enolase et l'exoribonuclease PNPase. Chez d'autres bacteries, plusieurs de��gradosomes d’ARN assembles sur la RNase E ont ete identifies et ils presentent une composition proteique differente du degradosome d'E. Coli. Il y a ainsi une plasticite des interactions RNase E-proteines qui serait due a la divergence de la sequence des microdomaines et leur evolution. Cependant, au debut de ce travail de these, seuls les microdomaines de la RNase E d'E. Coli ont ete caracterises. Les travaux de these presentes dans ce manuscrit se sont focalises sur la bacterie marine adaptee au froid et relativement distante d'E. Coli, Pseudoalteromonas haloplanktis, pour caracteriser le degradosome d'ARN et les microdomaines responsables des interactions RNase E-proteines. Le degradosome d'ARN adapte au froid de P. Haloplanktis est compose de la RNase E, de l'exoribonuclease PNPase et de l'helicase a ARN RhlB. Chez E. Coli, la RNase E de P. Haloplanktis est capable de restaurer la viabilite d'E. Coli depourvue de RNase E sans conferer un avantage de croissance a E. Coli a basse temperature. De plus, la RNase E de P. Haloplanktis est capable d'interagir avec la proteine RhlB d'E. Coli. Les microdomaines d'interaction entre la RNase E et les proteines RhlB et PNPase ont ete caracterises ce qui a permis de mieux comprendre la conservation de ces deux types d'interaction retrouves au sein du degradosome d'ARN d'E. Coli, malgre la distance evolutive separant P. Haloplanktis et E. Coli. L'interaction RNase E-PNPase de P. Haloplanktis implique un microdomaine de sequence non conservee en comparaison avec celui de l'interaction RNase E-PNPase d'E. Coli. Ceci suggere une conservation structurale de l'interaction RNase E-PNPase. Quant a l'interaction RNase E-RhlB, le microdomaine d'interaction presente des acides amines conserves et similaires au microdomaine d'interaction RNase E-RhlB d'E. Coli. L'analyse de ces microdomaines est elargie de maniere in silico a d'autres RNase E des gamma-proteobacteries pour avoir une vue d'ensemble de leur distribution. Enfin, une etude phylogenetique de la proteine RhlB a ete initiee dans le but de voir une correlation potentielle entre la presence du microdomaine de fixation de RhlB et la presence de RhlB chez les gamma-proteobacteries
Implementing Dietary and Physical Activity Guidelines in a College Health Center

iii ACKNOWLEDGEMENTS . iv TABLE OF CONTENTS . v CHAPTER I . 1 Problem Statement . 3 Purpose Statement . 3 CHAPTER II . 4 Literature Review. 4 Summary . 9 Needs Assessment . 10 Population Identification . 10 Key Stakeholders . 10 Description and Scope of the Project . 11 Mission . 11 Goals and Objectives . 11 CHAPTER III . 13 Theoretical Underpinnings. 13 Health Belief Model . 13 CHAPTER IV . 15 Project Plan . 15 Population of Interest . 15 Measures and Activities . 15
Rapid pacing and high‐frequency jet ventilation additively improve catheter stability during atrial fibrillation ablation

Catheter stability during atrial fibrillation ablation is associated with higher ablation success rates. Rapid cardiac pacing and high‐frequency jet ventilation (HFJV) independently improve catheter stability. Simultaneous modulation of cardiac and respiratory motion has not been previously studied. The objective of this study was to determine the effect of simultaneous heart rate and respiratory rate modulation on catheter stability.
Evaluation of correlation between myocardial performance index and left ventricular ejection fraction in patients with acute ST-elevation myocardial infarction

Background: In the diagnosis of patients with ST-elevation myocardial infarction (STEMI), prediction of left ventricular systolic function is one of the vital elements. Traditionally, assessment of left ventricular function is focused on measurement of left ventricular ejection fraction (LVEF). But it is load dependent and sensitive to the alterations in preload and after-load. However, myocardial performance index (MPI) demonstrates supremacy over older established indexes. Hence, the purpose of the study is to estimate the correlation between MPI and LVEF in patients with acute STEMI.Methods: A total of 105 consecutive patients underwent conventional estimation of ejection fraction and LV end-systolic volume by a Teichholz method. All patients received 325mg dispersible aspirin, 300mg clopidogrel at the time of admission and streptokinase. Doppler echocardiographic evaluations were performed at presentation, immediately after thrombolysis (90 minutes) and before discharge on 3rd to 5th days.Results: The mean patient age was 56.36years and 89 (84.76%) patients were male. A low LVEF of <40%, significantly correlated with higher (worse) MPI at the time of presentation (P= 0.04). LVEF showed improvement after thrombolysis, moreover it was significantly higher at 0' (P= <0.03) and 3rd day (P= 0.05) in patients with MPI <0.5. Conclusions: A significant correlation was found between left ventricular ejection fraction and myocardial performance index; lesser the left ventricular ejection fraction, higher the myocardial performance index. However, myocardial performance index could not predict adverse cardiac events during the hospital stay.
Modifications on the heterocyclic base of ganciclovir, penciclovir, acyclovir - syntheses and antiviral properties

АBSTRACT Esters of the antiherpetic drugs ganciclovir, penciclovir with the bile acids (cholic, chenodeoxycholic and deoxycholic) and amino acid esters of acyclovir were generated and evaluated for their in vitro antiviral activity against herpes simplex viruses type 1 and type 2 (HSV-1, HSV-2). The antiviral assays demonstrated that modified analogs of ACV and PCV are less active compared to the initial substances against HSV-1and HSV-2. CC50 for ganciclovir-deoxycholate corresponded to the CC50 of the other analogs and its activity is lower than ganciclovir. Obtained results show that tested modification do not improve bioavailability of nucleoside analogs in cells.
The Impact of Cholecystectomy on Long-Term Disease Outcomes and Quality of Life in Patients with Crohn's Disease.

BACKGROUND Cholecystectomy (CCY) is one of the most frequently performed abdominal surgeries. However, the impact of CCY in clinical settings with altered gastrointestinal physiology and anatomy, such as Crohn's disease (CD), has not been fully characterized. We sought to investigate clinical outcomes, disease severity, and quality of life of CD patients after CCY. METHODS We utilized a prospective, longitudinal registry of consented CD patients followed at a tertiary center. Crohn's disease patients that had or had not undergone CCY formed the 2 study groups. The absence or presence of gallbladder was confirmed with abdominal CT scans obtained during routine care. Multiyear clinical, biochemical, and histologic data were collected and analyzed. RESULTS Among 834 CD patients, 151 (18%) had undergone CCY. History of CCY was associated with higher disease activity (median Harvey-Bradshaw index; P < 0.001), more years with anemia (P = 0.048), lower albumin (P = 0.001), worse quality of life (mean Short Inflammatory Bowel Disease Questionnaire; P < 0.001), chronic abdominal pain (P < 0.001), higher risk for incident colonic dysplasia (P = 0.011), higher rates of annual hospital admissions (P = 0.004), and opioid use (P < 0.001). In multivariate analysis, CCY remained associated with higher disease activity (P < 0.001), lower albumin (P = 0.008), lower quality of life (P < 0.001), and more hospital admissions (P = 0.008), whereas CD patients with diseased ileum had higher risk for colonic dysplasia (P = 0.031). CONCLUSIONS CCY in CD patients was associated with multiple markers of disease activity and worse quality of life during multiyear follow up. This data suggests that CCY in CD patients may adversely impact the long-term clinical course.
High resolution crystal structure of a KRAS promoter G-quadruplex reveals a dimer with extensive poly-A π-stacking interactions for small-molecule recognition

Abstract Aberrant KRAS signaling is a driver of many cancers and yet remains an elusive target for drug therapy. The nuclease hypersensitive element of the KRAS promoter has been reported to form secondary DNA structures called G-quadruplexes (G4s) which may play important roles in regulating KRAS expression, and has spurred interest in structural elucidation studies of the KRAS G-quadruplexes. Here, we report the first high-resolution crystal structure (1.6 Å) of a KRAS G-quadruplex as a 5′-head-to-head dimer with extensive poly-A π-stacking interactions observed across the dimer. Molecular dynamics simulations confirmed that the poly-A π-stacking interactions are also maintained in the G4 monomers. Docking and molecular dynamics simulations with two G4 ligands that display high stabilization of the KRAS G4 indicated the poly-A loop was a binding site for these ligands in addition to the 5′-G-tetrad. Given sequence and structural variability in the loop regions provide the opportunity for small-molecule targeting of specific G4s, we envisage this high-resolution crystal structure for the KRAS G-quadruplex will aid in the rational design of ligands to selectively target KRAS.
Influence of nanoscale surface topography and chemistry on the functional behaviour of an adsorbed model macromolecule

The functional behaviour of a model macromolecule (fibrinogen) adsorbed at the nanofabricated solid-liquid interface was found to be strongly influenced by the local topographic structure of the interface. Protein molecules bound at topographically structured surfaces (either chemically homogeneous or heterogeneous 40-nm diameter and 10-nm deep pits) were found to bind platelets significantly faster than uncoated substrates whereas proteins bound to flat (Ra 1 nm) substrates were not. During the initial interaction, the chemistry of the underlying substrate apparently does not affect the macromolecules' functional behaviour.
A Comparison of Four Approaches to Evaluate the Sit-to-Stand Movement

The sit-to-stand test (STS) is a simple test of function in older people that can identify people at risk of falls. The aim of this study was to develop two novel methods of evaluating performance in the STS using a low-cost RGB camera and another an instrumented chair containing load cells in the seat of the chair to detect center of pressure movements and ground reaction forces. The two systems were compared to a Kinect and a force plate. Twenty-one younger subjects were tested when performing two 5STS movements at self-selected slow and normal speeds while 16 older fallers were tested when performing one 5STS at a self-selected pace. All methods had acceptable limits of agreement with an expert for total STS time for younger subjects and older fallers, with smaller errors observed for the chair (−0.18 ± 0.17 s) and force plate (−0.19 ± 0.79 s) than for the RGB camera (−0.30 ± 0.51 s) and the Kinect (−0.38 ± 0.50 s) for older fallers. The chair had the smallest limits of agreement compared to the expert for both younger and older participants. The new device was also able to estimate movement velocity, which could be used to estimate muscle power during the STS movement. Subsequent studies will test the device against opto-electronic systems, incorporate additional sensors, and then develop predictive equations for measures of physical function.
Squalene epoxidase‐induced cholesteryl ester accumulation promotes nasopharyngeal carcinoma development by activating PI3K/AKT signaling

Nasopharyngeal carcinoma (NPC) is a common malignant tumor and a major cause of mortality and morbidity in southern China. However, the mechanism is still elusive. Here, we focused on studying the role of squalene epoxidase (SQLE), a key enzyme of cholesterol biosynthesis, in the progression of NPC. Clinical study revealed that SQLE expression was significantly upregulated in NPC tissues compared to normal tissues from mRNA level and patients with high expression of SQLE showed a poor prognosis. In vitro experiments showed that SQLE overexpression led to a significant proliferation of cells whereas SQLE knockdown showed an opposite result. In vivo studies also showed that SQLE promoted tumor growth in nude mice. Further study revealed that SQLE promoted NPC proliferation by cholesteryl ester accumulation instead of cholesterol. Mechanism studies indicated that cholesteryl ester promoted NPC cell proliferation by activating the PI3K/AKT pathway and inhibition of this pathway in SQLE‐overexpressed or cholesteryl ester‐treated cells resulted in a significant reduction of NPC cell proliferation. These results indicate that the oncogenic effect of SQLE in NPC mainly resulted from cholesteryl ester accumulation and PI3K/AKT is a promising target for NPC with SQLE overexpression.
Etude in vitro et in vivo de la régulation de la mort radioinduite des cellules endothéliales par la Sphingosine-1-Phosphate

Proteger la vascularisation de la mort radioinduite est d’un interet majeur en radioprotection tissulaire. En developpant un modele d’etude de la radiosensibilite des cellules endotheliales, nous avons prouve que les cellules HMEC-1 subissent 2 voies de mort apres une irradiation a 15 Gy: une apoptose premitotique precoce induite par la generation du ceramide, et une mort mitotique tardive induite par les dommages de l’ADN. La Sphingosine-1-Phosphate (S1P), un metabolite du ceramide, protege les HMEC-1 seulement de la mort precoce, mais pas de la mort mitotique. Nous avons confirme in vivo que la S1P protege de l’apoptose radioinduite due a la generation du ceramide. Cette radioprotection est partiellement dependante de l’activation des recepteurs S1Ps. La distinction entre ces 2 types de mort pourrait permettre de definir de nouveaux radioprotecteurs specifiques des tissus sains dont l’endothelium est quiescent, mais pas des cellules endotheliales tumorales qui sont pro-angiogeniques.
Impulsive Synchronization of Unbounded Delayed Inertial Neural Networks With Actuator Saturation and Sampled-Data Control and its Application to Image Encryption

The article considers the impulsive synchronization for inertial neural networks with unbounded delay and actuator saturation via sampled-data control. Based on an impulsive differential inequality, the difficulties caused by unbounded delay and impulsive effect may be effectively avoid. By applying polytopic representation technique, the actuator saturation term is first considered into the design of impulsive controller, and less conservative linear matrix inequality (LMI) criteria that guarantee asymptotical synchronization for the considered model via hybrid control are given. As special cases, the asymptotical synchronization of the considered model via sampled-data control and saturating impulsive control are also studied, respectively. Numerical simulations are presented to claim the effectiveness of theoretical analysis. A new image encryption algorithm is proposed to utilize the synchronization theory of hybrid control. The validity of image encryption algorithm can be obtained by experiments.
Synchronization for Quantized Semi-Markov Switching Neural Networks in a Finite Time

Finite-time synchronization (FTS) is discussed for delayed semi-Markov switching neural networks (S-MSNNs) with quantized measurement, in which a logarithmic quantizer is employed. The stochastic phenomena of structural and parametrical changes are modeled by a semi-Markov process whose transition rates are time-varying to depend on the sojourn time. Practical systems subject to unpredictable structural changes, such as quadruple-tank process systems, are described by delayed S-MSNNs. A key issue under the consideration is how to design a feedback controller to guarantee the FTS between the master system and the slave system. For this purpose, by using the weak infinitesimal operator, sufficient conditions are constructed to realize FTS of the resulting error system over a finite-time interval. Then, the solvability conditions for the desired finite-time controller can be determined under a linear matrix inequality framework. Finally, the theoretical findings are illustrated by the quadruple-tank process model.
Factors to be considered in designing a faculty development program for medical education: local experience from the Western region of Saudi Arabia

Background Among the different aims of medical education, the provision of society with skilled, professional, and knowledgeable healthcare workers who maintain and develop their expertise over a lifetime career is important. The achievement of this goal is linked with the professional development of both faculty members and healthcare workers. This study aims to measure the perception of faculty members regarding their views about the goals of faculty development programs, practices and activities, and factors that determine their achievement. Methods A cross-sectional survey was conducted in multiple universities in the Western region of Saudi Arabia. The participants were given a pre-designed self-administered questionnaire generated from literature. The survey questionnaire consisted of three sections that were designed to assess the faculty members’ perception on the faculty development program. Results A total of 210 faculty members participated in the study. The most important perceived goal was to motivate teachers to become better teachers. The most important perceived practice was establishing a positive climate for teaching and learning. The most important perceived factor was skilled and dedicated staff support. Conclusion The results of this study demonstrate that faculty members have positive perceptions regarding all aspects of faculty development programs. This study will raise awareness regarding the importance of faculty development programs in sustaining educational vitality. We recommend the implementation and maintenance of comprehensive faculty development programs in Saudi universities.