Miracle-dz/UniFAR-FTUs huggingface dataset:
Clathrin-mediated post-fusion membrane retrieval influences the exocytic mode of endothelial Weibel-Palade bodies

ABSTRACT Weibel-Palade bodies (WPBs), the storage organelles of endothelial cells, are essential to normal haemostatic and inflammatory responses. Their major constituent protein is von Willebrand factor (VWF) which, following stimulation with secretagogues, is released into the blood vessel lumen as large platelet-catching strings. This exocytosis changes the protein composition of the cell surface and also results in a net increase in the amount of plasma membrane. Compensatory endocytosis is thought to limit changes in cell size and retrieve fusion machinery and other misplaced integral membrane proteins following exocytosis; however, little is known about the extent, timing, mechanism and precise function of compensatory endocytosis in endothelial cells. Using biochemical assays, live-cell imaging and correlative spinning-disk microscopy and transmission electron microscopy assays we provide the first in-depth high-resolution characterisation of this process. We provide a model of compensatory endocytosis based on rapid clathrin- and dynamin-mediated retrieval. Inhibition of this process results in a change of exocytic mode: WPBs then fuse with previously fused WPBs rather than the plasma membrane, leading, in turn, to the formation of structurally impaired tangled VWF strings. This article has an associated First Person interview with the first authors of the paper. Summary: Compensatory endocytosis plays key roles in Weibel-Palade body exocytosis. Inhibition of this process results in a change of exocytic mode and the release of von Willebrand factor as tangled strings.
Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis.

BACKGROUND Prospective studies on fiber and magnesium intake and risk of type 2 diabetes mellitus were inconsistent. We examined associations between fiber and magnesium intake and risk of type 2 diabetes and summarized existing prospective studies by meta-analysis. METHODS We conducted a prospective cohort study of 9702 men and 15 365 women aged 35 to 65 years who were observed for incident diabetes from 1994 to 2005. Dietary intake of fiber and magnesium were measured with a validated food-frequency questionnaire. We estimated the relative risk (RR) by means of Cox proportional hazards analysis. We searched PubMed through May 2006 for prospective cohort studies of fiber and magnesium intake and risk of type 2 diabetes. We identified 9 cohort studies of fiber and 8 studies of magnesium intake and calculated summary RRs by means of a random-effects model. RESULTS During 176 117 person-years of follow-up, we observed 844 incident cases of type 2 diabetes in the European Prospective Investigation Into Cancer and Nutrition-Potsdam. Higher cereal fiber intake was inversely associated with diabetes risk (RR for extreme quintiles, 0.72 [95% confidence interval [CI], 0.56-0.93]), while fruit fiber (0.89 [95% CI, 0.70-1.13]) and vegetable fiber (0.93 [95% CI, 0.74-1.17]) were not significantly associated. Meta-analyses showed a reduced diabetes risk with higher cereal fiber intake (RR for extreme categories, 0.67 [95% CI, 0.62-0.72]), but no significant associations for fruit (0.96 [95% CI, 0.88-1.04]) and vegetable fiber (1.04 [95% CI, 0.94-1.15]). Magnesium intake was not related to diabetes risk in the European Prospective Investigation Into Cancer and Nutrition-Potsdam (RR for extreme quintiles, 0.99 [95% CI, 0.78-1.26]); however, meta-analysis showed a significant inverse association (RR for extreme categories, 0.77 [95% CI, 0.72-0.84]). CONCLUSION Higher cereal fiber and magnesium intakes may decrease diabetes risk.
Analysis of Right Ventricular Myocardial Stiffness and Relaxation Components in Children and Adolescents With Pulmonary Arterial Hypertension

Background The rate of left ventricular pressure decrease during isovolumic relaxation is traditionally assessed algebraically via 2 empirical indices: the monoexponential and logistic time constants (τE and τL). Since the pattern of right ventricular (RV) pressure decrease is quite different from that of the left ventricular, we hypothesized that novel kinematic model parameters are more appropriate and useful to evaluate RV diastolic dysfunction. Methods and Results Eight patients with pulmonary arterial hypertension (age 12.5±4.8 years) and 20 normal subjects (control group; age 12.3±4.4 years) were enrolled. The kinematic model was parametrized by stiffness/restoring Ek and damping/relaxation μ. The model predicts isovolumic relaxation pressure as a function of time as the solution of d2P/dt2+(1/μ)dP/dt+EkP=0, based on the theory that the pressure decay is determined by the interplay of inertial, stiffness/restoring, and damping/relaxation forces. In the assessment of RV diastolic function, τE and τL did not show significant differences between the pulmonary arterial hypertension and control groups (46.8±15.5 ms versus 32.5±14.6 ms, and 19.6±5.9 ms versus 14.5±7.2 ms, respectively). The pulmonary arterial hypertension group had a significantly higher Ek than the control group (915.9±84.2 s−2 versus 487.0±99.6 s−2, P<0.0001) and a significantly lower μ than the control group (16.5±4.3 ms versus 41.1±10.4 ms, P<0.0001). These results show that the RV has higher stiffness/elastic recoil and lower cross‐bridge relaxation in pulmonary arterial hypertension. Conclusions The present findings indicate the feasibility and utility of kinematic model parameters for assessing RV diastolic function.
Electrostatic contribution to the binding stability of protein–protein complexes

To investigate roles of electrostatic interactions in protein binding stability, electrostatic calculations were carried out on a set of 64 mutations over six protein–protein complexes. These mutations alter polar interactions across the interface and were selected for putative dominance of electrostatic contributions to the binding stability. Three protocols of implementing the Poisson‐Boltzmann model were tested. In vdW4 the dielectric boundary between the protein low dielectric and the solvent high dielectric is defined as the protein van der Waals surface and the protein dielectric constant is set to 4. In SE4 and SE20, the dielectric boundary is defined as the surface of the protein interior inaccessible to a 1.4‐Å solvent probe, and the protein dielectric constant is set to 4 and 20, respectively. In line with earlier studies on the barnase–barstar complex, the vdW4 results on the large set of mutations showed the closest agreement with experimental data. The agreement between vdW4 and experiment supports the contention of dominant electrostatic contributions for the mutations, but their differences also suggest van der Waals and hydrophobic contributions. The results presented here will serve as a guide for future refinement in electrostatic calculation and inclusion of nonelectrostatic effects. Proteins 2006. © 2006 Wiley‐Liss, Inc.
AC and AG dinucleotide repeats in the PAX6 P1 promoter are associated with high myopia

Purpose The PAX6 gene, located at the reported myopia locus MYP7 on chromosome 11p13, was postulated to be associated with myopia development. This study investigated the association of PAX6 with high myopia in 379 high myopia patients and 349 controls. Methods High myopia patients had refractive errors of –6.00 diopters or greater and axial length longer than 26 mm. Control subjects had refractive errors less than –1.00 diopter and axial length shorter than 24 mm. The P1 promoter, all coding sequences, and adjacent splice-site regions of the PAX6 gene were screened in all study subjects by polymerase chain reaction and direct sequencing. PAX6 P1 promoter-luciferase constructs with variable AC and AG repeat lengths were prepared and transfected into human ARPE-19 cells prior to assaying for their transcriptional activities. Results No sequence alterations in the coding or splicing regions showed an association with high myopia. Two dinucleotide repeats, (AC)m and (AG)n, in the P1 promoter region were found to be highly polymorphic and significantly associated with high myopia. Higher repeat numbers were observed in high myopia patients for both (AC)m (empirical p = 0.013) and (AG)n (empirical p = 0.012) dinucleotide polymorphisms, with a 1.327-fold increased risk associated with the (AG)n repeat (empirical p = 0.016; 95% confidence interval: 1.059–1.663). Luciferase-reporter analysis showed elevated transcription activity with increasing individual (AC)m and (AG)n and combined (AC)m(AG)n repeat lengths. Conclusions Our results revealed an association between high myopia and AC and AG dinucleotide repeat lengths in the PAX6 P1 promoter, indicating the involvement of PAX6 in the pathogenesis of high myopia.
Heterogeneous organization and connectivity of the chicken auditory thalamus (Gallus gallus)

The auditory ascending system contains parallel pathways in vertebrate brains. In chickens (Gallus gallus), three pathways arise from nucleus laminaris (NL), nucleus angularis (NA), and regio intermedius (RI) in the brainstem, innervating three subdivisions of the nucleus mesencephalicus lateralis pars dorsalis (MLd) in the midbrain. The current study reveals the segregation of these pathways in their subsequent projections to the nucleus ovoidalis (Ov) in the thalamus. Based on cytoarchitecture and myelin distribution, we identified seven Ov subregions, including five neuronal clusters within the Ov proper, the nucleus semilunaris parovoidalis (SPO), and the circum‐ovoidalis (cOv). Immunocytochemistry further revealed that a ventromedial cluster of the Ov proper (Ovvm) contains unique cell types expressing α8 subunit nicotinic acetylcholine receptor, while SPO and cOv are characterized with expression of calcitonin‐gene‐related peptide and cholecystokinin. Tract tracing studies demonstrated that Ovvm is a major target of the NL‐recipient zone of MLd, while the RI‐recipient zone of MLd predominantly projects to a ventrolateral cluster of the Ov proper. Afferent inputs to the remaining regions of the Ov proper mostly arise from the NA‐recipient zone of MLd. SPO and cOv receive a projection from the surrounding areas of MLd, named the nucleus intercollicularis. Importantly, the Ov proper, SPO and cOv all project to the Field L2 in the forebrain, the avian auditory cortex. Taken together, these results demonstrate that the avian auditory thalamus is a structurally and functionally heterogeneous structure, implicating an important role in generating novel representations for specific acoustic features.
Towards fine-grained radio-based indoor location

Location systems are key to a rich experience for mobile users. When they roam outdoors, mobiles can usually count on a clear GPS signal for an accurate location, but indoors, GPS usually fades, and so up until recently, mobiles have had to rely mainly on rather coarse-grained signal strength readings for location. What has changed this status quo is the recent trend of dramatically increasing numbers of antennas at the indoor AP, mainly to bolster capacity and coverage with multiple-input, multiple-output (MIMO) techniques. In the near future, the number of antennas at the access point will increase several-fold, to meet increasing demands for wireless capacity with MIMO links, spatial division multiplexing, and interference management. We thus observe an opportunity to revisit the important problem of localization with a fresh perspective. This paper presents the design and experimental evaluation of ArrayTrack, an indoor location system that uses MIMO-based techniques to track wireless clients in real time as they roam about a building. We prototype ArrayTrack on a WARP platform, emulating the capabilities of an inexpensive 802.11 wireless access point. Our results show that ArrayTrack can pinpoint 33 clients spread out over an indoor office environment to within a 36 cm location accuracy.
Performing Strategy : Analogical Reasoning as a Strategic Practice Working Paper 67 September 2005 DR

Imagination Lab Foundation researchers communicate their findings to interested readers through the Working Paper publication series. This paper should be considered preliminary in nature and subject to subsequent revision. ABSTRACT Analogical reasoning refers to the successful transfer of structural similarities from a source to a target domain. In strategic management research, this concept has materialized in approaches such as strategic mapping. Yet, the concept and its application seem to have emphasized primarily the cognitive aspects of analogical reasoning. Bourdieu's concept of practice allows us to explore analogical reasoning in a more integral manner, i.e., by presenting embodied aspects of analogical reasoning as complementary, equally relevant for such processes. Thus, we conceptualize analogical reasoning as a practice of strategy and illustrate this concept with an empirical case.
Hypoxic preconditioning protects against ischemic brain injury

SummaryAnimals exposed to brief periods of moderate hypoxia (8% to 10% oxygen for 3 hours) are protected against cerebral and cardiac ischemia between 1 and 2 days later. This hypoxia preconditioning requires new RNA and protein synthesis. The mechanism of this hypoxia-induced tolerance correlates with the induction of the hypoxia-inducible factor (HIF), a transcription factor heterodimeric complex composed of inducible HIF-1α and constitutive HIF-1β proteins that bind to the hypoxia response elements in a number of HIF target genes. Our recent studies show that HIF-1α correlates with hypoxia induced tolerance in neonatal rat brain. HIF target genes, also induced following hypoxia-induced tolerance, include vascular endothelial growth factor, erythropoietin, glucose transporters, glycolytic enzymes, and many other genes. Some or all of these genes may contribute to hypoxia-induced protection against ischemia. HIF induction of the glycolytic enzymes accounts in part for the Pasteur effect in brain and other tissues. Hypoxia-induced tolerance is not likely to be equivalent to treatment with a single HIF target gene protein since other transcription factors including Egr-1 (NGFI-A) have been implicated in hypoxia regulation of gene expression. Understanding the mechanisms and genes involved in hypoxic tolerance may provide new therapeutic targets to treat ischemic injury and enhance recovery.
A genome-by-environment interaction classifier for precision medicine: personal transcriptome response to rhinovirus identifies children prone to asthma exacerbations

Abstract Objective To introduce a disease prognosis framework enabled by a robust classification scheme derived from patient-specific transcriptomic response to stimulation. Materials and Methods Within an illustrative case study to predict asthma exacerbation, we designed a stimulation assay that reveals individualized transcriptomic response to human rhinovirus. Gene expression from peripheral blood mononuclear cells was quantified from 23 pediatric asthmatic patients and stimulated in vitro with human rhinovirus. Responses were obtained via the single-subject gene set testing methodology “N-of-1-pathways. ” The classifier was trained on a related independent training dataset (n = 19). Novel visualizations of personal transcriptomic responses are provided. Results Of the 23 pediatric asthmatic patients, 12 experienced recurrent exacerbations. Our classifier, using individualized responses and trained on an independent dataset, obtained 74% accuracy (area under the receiver operating curve of 71%; 2-sided P = .039). Conventional classifiers using messenger RNA (mRNA) expression within the viral-exposed samples were unsuccessful (all patients predicted to have recurrent exacerbations; accuracy of 52%). Discussion Prognosis based on single time point, static mRNA expression alone neglects the importance of dynamic genome-by-environment interplay in phenotypic presentation. Individualized transcriptomic response quantified at the pathway (gene sets) level reveals interpretable signals related to clinical outcomes. Conclusion The proposed framework provides an innovative approach to precision medicine. We show that quantifying personal pathway–level transcriptomic response to a disease-relevant environmental challenge predicts disease progression. This genome-by-environment interaction assay offers a noninvasive opportunity to translate omics data to clinical practice by improving the ability to predict disease exacerbation and increasing the potential to produce more effective treatment decisions.
Analysis of GNB Species and Pattern of Resistance Responsible for LRTI in Patients with Cancer

Lower respiratory tract infection (LRTI) is the most lethal infection remains among patients undergoing treatment for cancer. Most of the previous studies with cancer patients have focus on blood stream infections. For that reason the aim of our study was to examine the spectrum and recent trends in antimicrobial resistance of Gram negative bacteria (GNB) recovered from cancer patient having LRTI in Egypt. In addition our objective was to investigate the prevalence and distribution of Legionella pneumophila among cancer patients with LRTI. Sputum specimens were collected from 285 cancer patients suspecting of having LRTI. The conventional methods and Microscan Negative Identification panel Type 2 were used for identification of GNB. Susceptibility was assessed for 20 antibiotics in bacterial isolates using agar diffusion method. All the sputum specimens were tested by culture and genus specific PCR for the detection of Legionella pneumophila. A total of 130 GNB were isolated. Among these, Klebsiella pneumoniae was the most common (35.4 %). We isolated and identified a number of less frequent GNB (17%), whereas no Legionella pneumophila was detected. Amikacin was found to be the most effective antimicrobial against GNB. We reported very high percentage of multi-drug resistance GNB (96%). This study reported the development of multidrug resistance Gram negative bacilli in Egypt. Continuous updating of data on antimicrobial susceptibility proﬁles is required to ensure the efﬁcacy of antimicrobial agents against GNB due to continuous development of antimicrobial resistance patterns among these pathogens.
Optimization of mooseer (A. hirtifolium Boiss.) dehydration under infrared conditions.

BACKGROUND In recent years, infrared drying has gained popularity as an alternative drying method for a va- riety of agricultural products. The use of infrared radiation technology in drying agricultural products has several advantages. These may include decreased drying time, high energy efficiency, high-quality finished products and uniform temperature in the product. With intermittent infrared and convection heating of a thick porous material, the drying time can be reduced compared to convection alone, while keeping good food quality and high energy efficiency. METHODS Response surface methodology (RSM) was employed to optimize the drying con- ditions of mooseer under infrared-convective drying. Experiments were performed at air temperatures of 40, 55 and 70°C, infrared powers of 500, 1000 and 1500 W, air velocities of 0.5, 1.5 and 2.5 m/s and slice thicknesses of 2, 4, and 6 mm. In this study, effective moisture diffusivity (Deff), shrinkage, color changes and specific energy consumption (SEC) were investigated. The central composite design (CCD) was selected for the design and optimization of the process. RESULTS Deff was obtained between 1.4×10 and 3.57×10 m /s. With increasing air temperature and slice –10 –9 2 thickness, Deff also increased. The level of shrinkage rose as slice thickness increased. The highest and lowest values of color changes were calculated at air temperatures of 70°C (52.3%) and 40°C (5.65%), respectively. Increasing air velocity led to an increase in SEC. CONCLUSIONS Optimum conditions for mooseer drying were achieved at air temperature of 70°C, infrared power of 867.46, air velocity of 0.59 m/s and slice thickness of 2 mm. At this point, Deff, shrinkage, color changes and SEC was obtained as 1.32×10–9 m2/s, 29.58%, 17.62% and 4.64 MJ/kg, respectively. The desir- ability value of 0.689 was achieved for the drying process.
Factors influencing cardiac auscultation proficiency in physician trainees.

INTRODUCTION We assessed the accuracy of physician trainees in identifying different cardiac sounds and examined the factors influencing their cardiac auscultation proficiency. METHODS A total of 106 physicians in the Family Medicine Training Programme were asked to identify 10 cardiac sounds played sequentially on the Littmann electronic stethoscope, which functioned as a surrogate patient. Their auscultation accuracy was scored numerically out of a maximum of 10. Demographical data of the physicians was collected prospectively. RESULTS The mean (+/-SD) auscultation proficiency score of the study population was 4.0 +/- 1.7. Physicians who graduated in 1994 or earlier fared significantly poorer than those who obtained their Bachelor of Medicine and Bachelor of Surgery degrees between 1995 and 2000 (p-value equals 0.02). Auscultation proficiency was not related to current practice, previous years of primary care, cardiology, internal medicine or paediatric medicine postings, or cumulative years of postings. Normal heart sounds were most accurately identified. Prosthetic cardiac sounds were better identified than other extra-cardiac sounds while systolic murmurs were more accurately identified than diastolic murmurs. Tachycardia had the lowest identification rate. CONCLUSION Our data suggest that cardiac auscultation skill declined with time, being significantly impaired eight years after graduation. We suggest that there is a need for retraining in the form of continuing medical education to address not only new knowledge and skills, but also basic skill competency.
Face Recognition Using Nonlinear Feature Parameter and Artificial Neural Network

The paper reports a study of nonlinear nature of face image. A novel feature extraction method using state space feature parameter for the recognition of face images is studied. The results of simulation experiments performed on the standard AT & T face database using both Artificial Neural Network and K-Nearest Neighbour recognition algorithms based on Nonlinear Feature Parameter (NLFP) is also presented. Overall recognition accuracy obtained is better for ANN algorithm and is 98.5%.
A Multicity Analysis of the Short-Term Effects of Air Pollution on the Chronic Obstructive Pulmonary Disease Hospital Admissions in Shandong, China

Although there is growing evidence linking chronic obstructive pulmonary disease (COPD) hospital admissions to the exposure to ambient air pollution, the effect can vary depending on the local geography, pollution type, and pollution level. The number of large-scale multicity studies remains limited in China. This study aims to assess the short-term effects of ambient air pollution (PM2.5, PM10, SO2, NO2) on chronic obstructive pulmonary disease hospital admissions from 2015 to 2016, with a total of 216,159 records collected from 207 hospitals in 17 cities all over the Shandong province, east China. Generalized additive models and penalized splines were applied to study the data whilst controlling for confounding meteorological factors and long-term trends. The air pollution was analyzed with 0–6 day lag effects and the percentage change of hospital admissions was assessed for a 10-μg/m3 increase in the air pollution levels. We also examined the percentage changes for different age groups and gender, respectively. The results showed that air pollution was significantly associated with adverse health outcomes and stronger effects were observed for females. The air pollution health effects were also impacted by geographical factors such that the air pollution had weaker health effects in coastal cities.