Miracle-dz/UniFAR-FTUs huggingface dataset:
The Magnitude of TCR Engagement Is a Critical Predictor of T Cell Anergy or Activation1

Fast dissociation rate of peptide-MHC complexes from TCR has commonly been accepted to cause T cell anergy. In this study, we present evidence that peptides that form transient complexes with HLA-DR1 induce anergy in T cell clones in vitro and specific memory T cells in vivo. We demonstrate that similar to the low densities of long-lived agonist peptide-MHC, short-lived peptide-MHC ligands induce anergy by engagement of ∼1000 TCR and activation of a similar pattern of intracellular signaling events. These data strongly suggest that short-lived peptides induce anergy by presentation of low densities of peptide-MHC complexes. Moreover, they suggest that the traditional antagonist peptides might also trigger anergy by a similar molecular mechanism. The use of short-lived peptides to induce T cells anergy is a potential strategy for the prevention or treatment of autoimmune diseases.
Cell cycle arrest and apoptosis induced by enteroaggregative Escherichia coli in cultured human intestinal epithelial cells

Purpose. Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen causing diarrhoeal diseases in multiple epidemiological and clinical settings. However, understanding of the pathogenesis of the disease caused by this organism is still suboptimal. Studies have indicated that enteric bacteria induced cell cycle arrest and apoptosis in host intestinal epithelial cells might play a vital role in the pathogenesis caused by these organisms. In this study an attempt was made to assess EAEC‐induced apoptosis and cell cycle modulation in human intestinal epithelial cell lines. Methodology. INT‐407 and HCT‐15 cells were infected with EAEC‐T8 (clinical isolate) as well as plasmid cured variant of EAEC‐T8 (EAEC‐pT8). Propidium iodide staining was done to select the time of infection and the incubation period of the infected culture. Apoptosis was further assessed in EAEC infected both the cell lines by annexin‐V‐FLUOS & propidium iodide, cell death detection ELISA, DNA strand breaks and microscopic analysis. Further, the DNA content of the EAEC‐infected cells at different phases of cell cycle was also monitored. Results. We have found that EAEC could induce apoptosis in human small intestinal as well as colonic epithelial cell lines, which was assessed by the expression of phosphatidylserine on host cell surface, internucleosomal cleavage of host cell DNA and microscopic analysis of the characteristic apoptotic features of these cells. EAEC was also found to arrest cells at S phase and G2‐M phase of the cell cycle. Conclusions. EAEC‐T8 could induce maximum apoptosis and cell cycle modulation in both small intestinal and colonic epithelial cells. Further, we have observed that the plasmid of this organism had maximum contribution to these processes. The outcome of this study has undoubtedly led to a better understanding of the basic mechanism of pathogenesis caused by EAEC.
Narcolepsy, cataplexy, hypocretin and co-existing other health complaints: A review

Abstract The presence of cataplexy in people with narcolepsy has a well-documented tight association with very low or non-detectable levels of the central nervous system neuropeptide, hypocretin (also termed orexin) while levels of hypocretin are normal in people with narcolepsy without cataplexy. There is evidence to suggest that hypocretin may have an association with pain, migraines and headaches in people with narcolepsy. However, these studies have not compared findings across narcolepsy with and without cataplexy. Currently, there are no studies published to determine whether pain, migraines and headaches are just common symptoms experienced by all people with narcolepsy or whether the presence of the cataplexy symptom (and thus assumed low levels of hypocretin) exacerbates these symptoms. Also, it is unclear whether general health and wellbeing (including psychological wellbeing) is similarly affected by hypocretin levels, or may be confounded by different levels of other health symptoms, such as pain. This review poses a number of research questions that need to be explored about whether the presence or absence of cataplexy is differentially associated with different types, severity and location of chronic pain; frequency, location and types of migraines and headaches; and general health and wellbeing among people with narcolepsy. A greater understanding of the role of hypocretin in these health complaints could aid in the development of more appropriate treatments for pain, migraines and headaches amongst people with and without narcolepsy.
[Knowledge, practices and attitudes toward volunteer work in an influenza pandemic: cross-sectional study with Peruvian medical students].

INTRODUCTION Reductions in health personnel during disasters or epidemics such as an influenza pandemic may need to include volunteer students. OBJECTIVE The aim of this article is to determine knowledge and practices about pandemic influenza and the attitudes towards volunteer work in Peruvian medical students. METHODS We performed a cross-sectional analytic study by simple sampling using a survey regarding "knowledge and practices" about pandemic influenza and the attitudes to volunteer work. RESULTS From the group of 865 students who were surveyed, 848 accepted to participate in the investigation (54% were male and their mean age was 22.1 ± 3.0). Ninety-seven percent correctly identified the spread routes of influenza and 81% knew its treatment. Regarding preventive measures, covering the mouth when coughing/sneezing and hand-washing were the most commonly recognized options (95% y 92%, respectively), and vaccination was the less recognized one (54%). The most common practice, readily acknowledged as preventive, was covering when coughing/sneezing (86%). Regarding volunteer works, students answered that it is a moral/ethical/professional obligation (77%); that a contingency university service needs to be established (88%), that it does not have to substitute for the lack of workers (49%), and that its role should be related to hospital work (83%). Coming from a public university was more associated to the concept that volunteer work was a moral obligation and that the student should be punished if he/she refuses to be a volunteer, whereas being from a private university was more related to a history of been involved in volunteering programs. CONCLUSIONS In general, medical students have good knowledge and practices toward influenza. There is a good disposition to volunteer their work and skills, recognizing it as a moral/ethical/professional obligation.
Physician virtual community and medical decision making: Mediating role of knowledge sharing

– Healthcare (HC) utilizes informatics to provide its services through information technology (IT) where social network is a promising initiative to aid medical decision-making (DM) quality. Even though HC is a globally expensive investment and a complex service-oriented industry, it still suffers from quality due to frequently occurring medical errors. In order to reduce medical errors, medical DM needs to be improved. This research has participated in this effort by exploring social capital theory (SCT) within a virtual community of practice (VCoP), HC knowledge management (KM) process – knowledge sharing quality and medical DM quality. , – Traditional and up-to-date HC-related and non-HC-related theoretical, empirical and case study-based literature review has been thoroughly analyzed to hence support the inter-relationships between the theoretical constructs being: SCT, knowledge sharing quality and medical DM quality presented as a conceptual framework. This conceptual framework is based on propositions derived from thorough literature review theory to relate between each of the constructs. , – SCT has the potential to facilitate medical DM within a VCoP, as well as, knowledge sharing quality plays a mediating and facilitating role between SCT and medical DM quality. , – The study has significantly focussed on SCT, which is actually part of the social sciences and anthropology discipline. In parallel, this research also analyzed the literature that pertained to the value of a VCoP to improve medical DM quality. , – The study's focus on SCT, knowledge sharing and medical DM; hence promotes future empirical research findings to be compared within a particular HC VC; from a case study point of view. , – The paper adds value to the large body of intellectual knowledge by enhancing the conception of medical DM quality to improve HC quality. Medical DM is a soft area of research. This research has introduced a new avenue on which HC quality can be improved by reducing medical errors, from the perspective of social computing and medical DM quality and the mediating role of knowledge sharing quality.
Understanding and controlling low-temperature aging of nanocrystalline materials.

Nanocrystalline copper lms were created by both repetitive high-energy pulsed power, to produce material without internal nanotwins; and pulsed laser deposition, to produce nan- otwins. Samples of these lms were indented at ambient (298K) and cryogenic temperatures by immersion in liquid nitrogen (77K) and helium (4K). The indented samples were sectioned through the indented regions and imaged in a scanning electron microscope. Extensive grain growth was observed in the lms that contained nanotwins and were indented cryogenically. The lms that either lacked twins, or were indented under ambient conditions, were found to exhibit no substantial grain growth by visual inspection. Precession transmission elec- tron microscopy was used to con rm these ndings quantitatively, and show that 3 and 7 boundaries proliferate during grain growth, implying that these interface types play a key role in governing the extensive grain growth observed here. Molecular dynamics sim- ulations of the motion of individual grain boundaries demonstrate that speci c classes of boundaries - notably 3 and 7 - exhibit anti- or a-thermal migration, meaning that their mobilities either increase or do not change signi cantly with decreasing temperature. An in-situ cryogenic indentation capability was developed and implemented in a transmission electron microscope. Preliminarymore » results do not show extensive cryogenic grain growth in indented copper lms. This discrepancy could arise from the signi cant di erences in con g- uration and loading of the specimen between the two approaches, and further research and development of this capability is needed. « less
[Non-suicidal self-injury and comorbid mental disorders: a review].

BACKGROUND Non-suicidal self-injury (NSSI) is described as deliberate destruction of one's body without suicidal intent. It is a fact that the phenomenon is associated with several mental disorders. Even so, a systematic review is lacking. The aim of this article is to compile which psychiatric disorders occur most frequently with NSSI. METHODS From a literature search, 21 of 1298 studies fulfilled the inclusion criteria. RESULTS Mood disorders, especially a recurrent major depression disorder, and personality disorders, particularly the borderline syndrome, are closely connected with NSSI in adolescence and adulthood. Self-injury is also present in anxiety and substance use disorders. In adolescence, externalising disorders are related to NSSI, too. CONCLUSIONS Depressive disorders and the borderline personality disorders are robustly associated with NSSI. It is still unknown whether or not the occurrence of NSSI with particular disorders can be explained by comorbidity with the borderline syndrome.
An exact time domain evaluation for radiated fields from a Hertz dipole

This paper provides an exact derivation of the radiated fields of a Hertz dipole in time domain. The usual derivation of the frequency domain dipole fields involves neglecting the phase variation across the dipole and hence, it is not exact. The time domain derivations presented here do not involve any approximations. The relations between time domain and frequency domain fields of an infinitesimal dipole are studied by taking the limit of the exact field expressions as the dipole length goes to zero.
Inferring the past from the present phylogeographic structure of North American forest trees : seeing the forest for the genes

The study of past historical events that have led to ecological changes is a recurrent topic in many disciplines. Given that many of these events have left a large and long-lasting evolutionary imprint on the extant population genetic structure of species, phylogeographic studies on modern taxa have been largely used to infer the impacts of these events and to complement previous paleoecological and paleobotanical surveys. In spite of the geographical and geological complexity of North America, converging patterns can be observed when comparing the available genetic data for forest trees. Such patterns include the co-location of genetic discontinuities among species and their coincidence with mountain ranges (e.g., the Appalachians, the Rocky Mountains, the Sierra Nevada, or the Transverse Volcanic Belt) and with previously inferred glacial refugia. Using examples drawn from the available literature, we illustrate such shared features and present the contrasting phylogeographic patterns observed among the.
GABAergic depolarization during early cortical development and implications for anticonvulsive therapy in neonates

Epileptic seizures rank among the most frequent neurologic symptoms during the neonatal period. Accumulating data from experimental animal studies and clinical trials in humans suggest that neonatal seizures could adversely affect normal brain development and result in long‐term neurologic sequelae. Unfortunately, currently used anticonvulsive drugs are often ineffective in the neonatal period. One particularity of the immature neuronal network during neonatal development is that the neurotransmitter γ‐aminobutyric acid (GABA) is mainly depolarizing, rather than hyperpolarizing as commonly observed in adults. This might, in part, explain not only the higher seizure propensity of the immature neuronal network, but also the limited anticonvulsive efficacy of GABA‐enhancing drugs during early postnatal life. Accordingly, pharmacologic attenuation of GABAergic depolarization has been proposed as a strategy for neonatal seizure control. However, the underlying conjecture of a depolarizing mode of GABA action has been seriously challenged recently. In the present review, we will summarize the state of knowledge regarding GABAergic depolarization in early life and discuss how these data might impact a currently tested anticonvulsive strategy.
Tranexamic acid given into the wound reduces postoperative blood loss by half in major orthopaedic surgery.

OBJECTIVE To evaluate the effect of locally applied tranexamic acid on postoperative blood loss and measures of fibrinolysis in drained blood. DESIGN Prospective study. SETTING University hospital, Norway. PATIENTS 30 patients operated on for low back pain by screw fixation of the lumbar spine, 16 of who were randomised to be given topical tranexamic acid. MAIN OUTCOME MEASURES Postoperative blood loss after 18 hours. Concentrations of plasmin/alpha2-antiplasmin (PAP) and D-dimer in arterial and drained blood at the time of wound closure and in drained blood after 1 hour. RESULTS In the tranexamic group median (interquartile) blood loss was reduced by half from 525 (325-750) ml to 252 (127-465) ml, p = 0.02. In drained blood after one hour the increase in the concentration of PAP was 150 (109-170)% and D-dimer 150 (107-272)% in the tranexamic group compared with the control group where the increase in PAP was 320 (140-540)% and D-dimer 260 (161-670)%. CONCLUSION Tranexamic acid applied in the wound inhibits blood loss by up to a half in major orthopaedic surgery probably because it prevents excessive fibrinolysis.
Immunosuppression and donor age with respect to severity of HCV recurrence after liver transplantation

In HCV cirrhotic patients after liver transplantation, survival and recurrence of HCV appears to be worsening in recent years. Donor age has been suggested as a cause. However, it is not clear if early and/or late mortality is affected and whether donor age is a key factor, as opposed to changes in immunosuppression. The aim of this study was to assess impact of donor age and other factors with respect to the severity of HCV recurrence posttransplant. A consecutive series of 193 HCV cirrhotic patients were transplanted with cadaveric donors, median age 41.5 years (13–73) and median follow‐up of 38 months (1–155). Donor age and other factors were examined in a univariate/multivariate model for early/late survival, as well as fibrosis (grade 4 or more, Ishak score) with regular biopsies, 370 in total, from 1 year onwards. Results of the study indicated that donor age influenced only short‐term (3 months) survival, with no significant effect on survival after 3 months. Known HCC independently adversely affected survival, as did the absence of maintenance azathioprine. Severe fibrosis (stage ≥ 4) in 51 patients was related to neither donor age nor year of transplantation, but it was independently associated with combined biochemical/histological hepatitis flare (OR 2.9, 95% CI 1.76‐4.9) whereas maintenance steroids were protective (OR 0.4, 95% CI 0.23‐0.83). In conclusion, in this cohort donor age did not influence late mortality in HCV transplanted cirrhotic patients or development of severe fibrosis, which was related to absence of maintenance steroids and a hepatitis flare. Maintenance azathioprine gave survival advantage. (Liver Transpl 2005;11:386–395.)
Sleep disorders and aging: understanding the causes.

A many as 40% of the elderly population complain L about sleep problems. Studies sampling from a wide variety of populations have consistently demonstrated that older people are disproportionately dissatisfied with their sleep; these studies have also noted disproportionate use of sedative medications among the aged (e.g., 1,2,3). Significant sleep disturbance can lead to daytime sleepiness and fatigue and impaired daytime function; it can seriously compromise the quality of life of many elderly individuals and cause them to seek professional health care. The sleep disturbances of elderly people arise from a multitude of causes and create a complex problem. There are three major considerations regarding sleep disorders and aging: (a) the recognition of the multifactorial nature of sleep disorders in the elderly; (b) the need to, wherever possible, treat the primary problem rather than the symptom of sleep disturbance; and (c) the importance of taking a very conservative approach to prescription of hypnotics for sleep complaints.
Mutational analysis of the Pseudomonas syringae pv. tomato hrpA gene encoding Hrp pilus subunit

Plant pathogenic Pseudomonas syringae strains harbour a type III secretion pathway suggested to be involved in the delivery of effector proteins from the bacteria into plant cells. During plant interaction, the bacteria apparently produce surface appendages, termed Hrp pili, that are indispensable for the secretion process. We have created an insertion mutation library, as well as deletion mutations to hrpA, the structural gene encoding Hrp pilin. Analysis of the mutants revealed gene regions important for hrpA expression, pilus assembly and pilus‐dependent autoagglutination of the bacteria. The majority of insertions in the amino‐terminal half of the pilin were tolerated without bacterial interaction with plants being affected, while the carboxy‐terminus appeared to be needed for pilus assembly. Insertions in the 5′ non‐translated region and the first codons within the open reading frame affected mRNA production or stability and abolished protein production.
Effect of Slot-and-Pole Combination on the Leakage Inductance and the Performance of Tooth-Coil Permanent-Magnet Synchronous Machines

The influence of slot-and-pole-number combinations on the leakage inductance of double-layer fractional-slot concentrated nonoverlapping winding (i.e., tooth-coil winding) permanent-magnet synchronous machines is studied. A Fourier-analysis-based method for calculating the harmonic air-gap leakage inductance applied to the current-linkage waveform (winding function) in the air gap is suggested. Different slot-and-pole combinations are considered, and their influence, in particular, on the air-gap leakage inductance is indicated. In tooth-coil machines, the air-gap harmonic leakage can have a surprisingly large impact on the machine performance.
Hypoxia‐inducible factor‐3α promotes angiogenic activity of pulmonary endothelial cells by repressing the expression of the VE‐cadherin gene

The variants of the hypoxia‐inducible factor‐3α gene HIF‐3α and NEPAS are known to repress the transcriptional activities driven by HIF‐1α and HIF‐2α. Although NEPAS has been shown to play an important role in vascular remodeling during lung development, little is known about the roles of HIF‐3α in adult lung function. Here, we examined pulmonary endothelial cells (ECs) isolated from wild‐type (WT) and HIF‐3α functional knockout (KO) mice. The expression levels of angiogenic factors (Flk1, Ang2 and Tie2) were significantly greater in the HIF‐3α KO ECs than those in the WT ECs irrespective of oxygen tension. However, the HIF‐3α KO ECs showed impaired proliferative and angiogenic activities. The impaired EC function was likely due to the excess vascular endothelial (VE)‐cadherin, an inhibitor of Flk1/PI3 kinase/Akt signaling, as treatment of the cells to a neutralizing antibody partly restored the phenotype of the HIF‐3α KO ECs. Importantly, we found that the mRNA levels of HIF‐2α and Ets‐1 were significantly increased by HIF‐3α ablation. Given that both factors are known to activate the VE‐cadherin gene, the transcriptional repression of these factors by HIF‐3α might be important for silencing the irrelevant expression of the VE‐cadherin gene. Collectively, these data show novel and unique roles of HIF‐3α for angiogenic gene regulation in pulmonary ECs.
Ignoring Is a Bliss: Learning with Large Noise Through Reweighting-Minimization

We consider learning in the presence of arbitrary noise that can overwhelm the signal in terms of magnitude on a fraction of data points observed (aka outliers). Standard approaches based on minimizing empirical loss can fail miserably and lead to arbitrary bad solutions in this setting. We propose an approach that iterates between finding a solution with minimal empirical loss and reweighting the data, reinforcing data points where the previous solution works well. We show that our approach can handle arbitrarily large noise, is robust as having a non-trivial breakdown point, and converges linearly under certain conditions. The intuitive idea of our approach is to automatically exclude “difficult” data points from model fitting. More importantly (and perhaps surprisingly), we validate this intuition by establishing guarantees for generalization and iteration complexity that essentially ignore the presence of outliers.