Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of GCSB-5, a Herbal Formulation, on Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Therapeutic effects of GCSB-5 on osteoarthritis were measured by the amount of glycosaminoglycan in rabbit articular cartilage explants in vitro, in experimental osteoarthritis induced by intra-articular injection of monoiodoacetate in rats in vivo. GCSB-5 was orally administered for 28 days. In vitro, GCSB-5 inhibited proteoglycan degradation. GCSB-5 significantly suppressed the histological changes in monoiodoacetate-induced osteoarthritis. Matrix metalloproteinase (MMP) activity, as well as, the levels of serum tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase protein, and mRNA expressions were attenuated by GCSB-5, whereas the level of interleukin-10 was potentiated. By GCSB-5, the level of nuclear factor-κB p65 protein expression was significantly attenuated but, on the other hand, the level of inhibitor of κB-α protein expression was increased. These results indicate that GCSB-5 is a potential therapeutic agent for the protection of articular cartilage against progression of osteoarthritis through inhibition of MMPs activity, inflammatory mediators, and NF-κB activation.
A meta-analytic study of changes in brain activation in depression

Objective:A large number of studies with considerably variable methods have been per- formed to investigate brain regions involved in the pathophysiology of major depressive disorder. The aim of this study was to use a quantitative meta-analytic technique to synthesise the results of much of this research.Methods:Three separate quantitative meta-analytical studies were conducted using the Activation Likelihood Estimation technique. Analysis was performed on three types of studies: (1) those conducted at rest comparing brain activation in patients with depression and controls; (2) those involving brain changes following antidepressant treatment; and (3) those comparing brain activation patterns induced by the induction of positive or negative emotion in patients with depression com- pared with controls.Results:There appears to be a complex series of areas of the brain implicated in the pathophysiology of depression although limited overlap was found across imaging paradigms. This included a network of regions including frontal and temporal cortex as well as the insula and cer- ebellum that are hypoactive in depressed subjects and in which there is increase in activity with treat- ment. There was a corresponding set of subcortical and limbic regions in which opposite changes were found.Conclusions:There is limited overlap between the brain regions identified using differing imaging methods. The most consistently identified regions include areas of the anterior cingulate, dorsolateral, medial and inferior prefrontal cortex, insula, superior temporal gyrus, basal ganglia and cerebellum. Further research is required to identify if different imaging methods are identifying complementary networks that are equally involved in the disorder.Hum Brain Mapp 29:683-695, 2008. V C 2007Wiley-Liss,Inc.
Expanding Relativistic Shells and Gamma-Ray Burst Temporal Structure

Many models of gamma-ray bursts (GRBs) involve a shell expanding at extreme relativistic speeds. The shell of material expands in a photon-quiet phase for a period t0 and then becomes gamma-ray active, perhaps due to inhomogeneities in the interstellar medium or the generation of shocks. Based on kinematics, we relate the envelope of the emission of the event to the characteristics of the photon-quiet and photon-active phases. We initially assume local spherical symmetry wherein, on average, the same conditions prevail over the shell's surface within angles the order of Γ–1, where Γ is the Lorentz factor for the bulk motion. The contribution of the curvature to the temporal structure is comparable to the contribution from the overall expansion. As a result, GRB time histories from a shell should have an envelope similar to “FRED” (fast rise, exponential decay) events in which the rise time is related to the duration of the photon-active phase and the fall time is related to the duration of the photon-quiet phase. This result depends only on local spherical symmetry and, since most GRBs do not have such envelopes, we introduce the “shell symmetry” problem: the observed time history envelopes of most GRBs do not agree with that expected for a relativistic expanding shell.Although FREDs have the signature of a relativistic shell, they may not be due to a single shell, as required by some cosmological models. Some FREDs have precursors in which the peaks are separated by more than the expansion time required to explain FRED shape. Such a burst is most likely explained by a central engine; that is, the separation of the multiple peaks occurs because the central site produced multiple releases of energy on timescales comparable to the duration of the event. Alternatively, there still could be local spherical symmetry of the bulk material, but with a low “filling factor”; that is, only a few percent of the viewable surface (which is already very small, 4πΓ–2) ever becomes gamma-ray active.Long complex bursts present a myriad of problems for the models. The duration of the event at the detector is ~t0/(2Γ2). The long duration cannot be due to large t0, since it requires too much energy to sweep up the interstellar medium. Nor can it be due to small Σ if the time variation is due to ambient objects, since the density of such objects is unreasonable (~1018Γ–4 pc–3 for typical parameters). Long events must explain why they almost always violate local spherical symmetry or why they have low filling factors.Both precursor and long complex events are likely to be “central engines” that produce multiple releases of energy over ~100 s. One promising alternative scenario is one in which the shell becomes thicker than the radius of the curvature within Γ–1. Then it acts as a parallel slab, eliminating the problems associated with local spherical symmetry.
Evaluation of an online bioterrorism continuing medical education course

Introduction: Much of the international community has an increased awareness of potential biologic, chemical, and nuclear threats and the need for physicians to rapidly acquire new knowledge and skills in order to protect the public's health. The present study evaluated the educational effectiveness of an online bioterrorism continuing medical education (CME) activity designed to address clinical issues involving suspected bioterrorism and reporting procedures in the United States. Methods: This was a retrospective survey of physicians who had completed an online CME activity on bioterrorism compared with a nonparticipant group who had completed at least 1 unrelated online CME course from the same medical school Web site and were matched on similar characteristics. An online survey instrument was developed to assess clinical and systems knowledge and confidence in recognition of illnesses associated with a potential bioterrorism attack. A power calculation indicated that a sample size of 100 (50 in each group) would achieve 90% power to detect a 10% to 15% difference in test scores between the two groups. Results: Compared with nonparticipant physicians, participants correctly diagnosed anthrax (p = .01) and viral exanthem (p = .01), but not smallpox, more frequently than nonparticipants. Participants knew more frequently than nonparticipants who to contact regarding a potential bioterrorism event (p = .03) Participants were more confident than nonparticipants about finding information to guide diagnoses of patients with biologic exposure (p = .01), chemical exposure (p = .02), and radiation exposure (p = .04). Discussion: An online bioterrorism course shows promise as an educational intervention in preparing physicians to better diagnose emerging rare infections, including those that may be associated with a bioterrorist event, in increasing confidence in diagnosing these infections, and in reporting of such infections for practicing physicians.
Sidewall Adhesion Evolution in Epitaxial Polysilicon as a Function of Impact Kinetic Energy and Stopper Area

This paper investigates the evolution of adhesion forces during dynamic contacts, which simulate realistic shocks. The developed method accounts for the differences in offset, resonance, and quality factor among the devices under test to precisely predict (and monitor) the kinetic impact energy during shocks. The results clearly show that adhesion force grows and stabilizes at an increasing amplitude with the applied impact energy. This dynamic adhesion is also dependent on the contact area, while the native adhesion on the same specimens was independent of it. Finally, a relaxation of the adhesion force with a very long time constant is observed after the end of the tests.
Characterization of the Physiological Response following In Vivo Administration of Astragalus membranaceus

The botanical, Astragalus membranaceus, is a therapeutic in traditional Chinese medicine. Limited literature exists on the overall in vivo effects of A. membranaceus on the human body. This study evaluates the physiological responses to A. membranaceus by measuring leukocyte, platelet, and cytokine responses as well as body temperature and blood pressure in healthy individuals after the in vivo administration of A. membranaceus. A dose-dependent increase in monocytes, neutrophils, and lymphocytes was measured 8–12 hours after administration and an increase in the number of circulating platelets was seen as early as 4 hours. A dynamic change in the levels of circulating cytokines was observed, especially in interferon-γ and tumor necrosis factor-α, IL-13, IL-6, and soluble IL-2R. Subjective symptoms reported by participants were similar to those typically experienced in viral type immune responses and included fatigue, malaise, and headache. Systolic and diastolic blood pressure were reduced within 4 hours after administration, while body temperature mildly increased within 8 hours after administration. In general, all responses returned to baseline values by 24 hours. Collectively, these results support the role of A. membranaceus in priming for a potential immune response as well as its effect on blood flow and wound healing.
Supraglacial pond evolution in the Everest region, central Himalaya, 2015–2018

Abstract. Supraglacial ponds are characteristic of debris-covered glaciers and greatly enhance local melt rates. They can grow rapidly and coalesce to form proglacial lakes, which represent a major hazard. Here, we use Sentinel-2A satellite imagery (10 m) to quantify the spatiotemporal changes of 6,425 supraglacial ponds for 10 glaciers in the Everest region, Nepal, between 2015 and 2018. During the study period, ponded area increased on all glaciers, but showed substantial temporal and spatial variation, and the rate of pond growth increased substantially relative to 2000–2015 (Watson et al., 2016). Both Imja and Spillway Lake expanded and Khumbu Glacier developed a chain of connected ponds. 54 % of ponds were associated with an ice-cliff, but the proportion of ponds with cliffs decreased during the study period. Pond location generally corresponded to lower surface velocity, but this relationship was not ubiquitous. Ponds are now predominantly found at mid-elevations on our study glaciers, suggesting that conditions conducive to pond formation have advanced up-glacier compared to general theory. Results demonstrate the need to utilize high-resolution imagery (
The gall of subordination: changes in gall bladder function associated with social stress

Diverse physiological and behavioural mechanisms allow animals to effectively deal with stressors, but chronic activation of the stress axis can have severe consequences. We explored the effects of chronic social stress on agonistic behaviour and gall bladder function, a critical but widely neglected component of stress‐induced gastrointestinal dysfunction. Prolonged cohabitation with dominant individuals elicited behavioural modifications and dramatically increased bile retention in subordinate convict cichlid fish (Archocentrus nigrofasciatum). The key predictor of gall bladder hypertrophy was social subordination rather than status‐related differences in food intake or body size. Stress‐induced inhibition of gall bladder emptying could affect energy assimilation such that subordinate animals would not be able to effectively convert energy‐rich food into mass gain. These results parallel changes in gall bladder function preceding cholesterol gallstone formation in humans and other mammals. Thus, social stress may be an important diagnostic criterion in understanding pathologies associated with gall bladder dysfunction.
A randomized trial of therapies for type 2 diabetes and coronary artery disease.

BACKGROUND Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established. METHODS We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention. RESULTS At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003). CONCLUSIONS Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)
Diffusion Tensor Imaging of the Subcortical Auditory Tract in Subjects with Congenital Cochlear Nerve Deficiency

BACKGROUND AND PURPOSE: Cochlear nerve deficiency (CND), including aplasia and hypoplasia, is a rare cause of congenital hearing loss. The purpose of this study was to evaluate the neuronal integrity of the subcortical auditory pathway in subjects with CND by diffusion tensor MR imaging (DTI). MATERIALS AND METHODS: Twelve subjects with unilateral congenital CND were included in this prospective study. Twelve normal-hearing subjects served as controls. DTIs were acquired from these subjects on a 3T MR imaging scanner. Several indices including axial diffusivity (λ‖), radial diffusivity (λ⊥), mean diffusivity (MD), and fractional anisotropy (FA) along the auditory pathway were extracted. Two regions of interest were selected bilaterally for evaluation: the lateral lemniscus (LL) and inferior colliculus (IC). The mean values of λ‖, λ⊥, MD, and FA at both regions of interest were compared between the ipsilateral and contralateral sides of subjects with CND with those in the control group. RESULTS: Significant decrease of FA and increase of MD on both the ipsilateral and contralateral sides of patients with CND as compared with normal subjects in both LL and IC were found. The decrease of FA was due to the increase of λ⊥, whereas λ‖ remained unchanged. CONCLUSIONS: The maintained axial diffusion implied that the orientation of neural fibers along the subcortical auditory pathway in subjects with unilateral CND is intact. However, the reduction in FA and increase in λ⊥ on both the ipsilateral and contralateral sides might be attributed to axonal loss and/or demyelination of the subcortical auditory tract in these subjects.
Lessons learned from 25 years of process improvement: the rise and fall of the NASA software engineering laboratory

For 25 years the NASA/GSFC Software Engineering Laboratory (SEL) has been a major resource in software process improvement activities. But due to a changing climate at NASA, agency reorganization, and budget cuts, the SEL has lost much of its impact. In this paper we describe the history of the SEL and give some lessons learned on what we did right, what we did wrong, and what others can learn from our experiences. We briefly describe the research that was conducted by the SEL, describe how we evolved our understanding of software process improvement, and provide a set of lessons learned and hypotheses that should enable future groups to learn from and improve on our quarter century of experiences.
MicroRNA Alterations of Pancreatic Intraepithelial Neoplasias

Purpose: MicroRNA (miRNA) alterations are likely to contribute to the development of pancreatic cancer and may serve as markers for the early detection of pancreatic neoplasia. Experimental Design: To identify the miRNA alterations that arise during the development of pancreatic cancer, we determined the levels of 735 miRNAs in 34 pancreatic intraepithelial neoplasias (PanIN) and 15 normal pancreatic duct samples isolated by laser capture microdissection using TaqMan miRNA microarrays. Differential expression of selected miRNAs was confirmed by FISH analysis and by quantitative real-time reverse transcription PCR (qRT-PCR) analysis of selected candidate miRNAs in an independent set of PanIN and normal duct samples. Results: We identified 107 aberrantly expressed miRNAs in different PanIN grades compared with normal pancreatic duct samples and 35 aberrantly expressed miRNAs in PanIN-3 lesions compared with normal pancreatic duct samples. These differentially expressed miRNAs included those that have been previously identified as differentially expressed in pancreatic ductal adenocarcinomas (PDAC; including miR-21, miR-200a/b/c, miR-216a/b, miR-217, miR-146a, miR-155, miR-182, miR-196b, miR-203, miR-222, miR-338-3p, miR-486-3p, etc.) as well as miRNAs not previously described as differentially expressed in these lesions (miR-125b, miR-296-5p, miR-183*, miR-603, miR-625/*, miR-708, etc.). miR-196b was the most selectively differentially expressed miRNA in PanIN-3 lesions. Conclusions: Many miRNAs undergo aberrant expression in PanIN lesions and are likely to be important in the development of PDAC. The miRNAs, such as miR-196b, whose expression is limited to PanIN-3 lesions or pancreatic cancers could be useful as diagnostic markers. Clin Cancer Res; 18(4); 981–92. ©2011 AACR.
Maize Endosperm ADP–Glucose Pyrophosphorylase SHRUNKEN2 and BRITTLE2 Subunit Interactions

ADP–glucose pyrophosphorylase (AGP) represents a key regulatory step in polysaccharide synthesis in organisms ranging from bacteria to plants. Higher plant AGPs are complex in nature and are heterotetramers consisting of two similar but distinct subunits. How the subunits are assembled into enzymatically active polymers is not yet understood. Here, we address this issue by using naturally occurring null mutants of the Shrunken2 (Sh2) and Brittle2 (Bt2) loci of maize as well as the yeast two-hybrid expression system. In the absence of the maize endosperm large AGP subunit (SH2), the BT2 subunit remains as a monomer in the developing endosperm. In contrast, the SH2 protein, in the absence of BT2, is found in a complex of 100 kD. A direct interaction between SH2 and BT2 was proven when they were both expressed in yeast. Several motifs are essential for SH2:BT2 interaction because truncations removing the N or C terminus of either subunit eliminate SH2:BT2 interactions. Analysis of subunit interaction mutants (sim) also identified motifs essential for protein interactions.
Conservation of mucosal associated invariant T (MAIT) cells and the MR1 restriction element in ruminants, and abundance of MAIT cells in spleen

MHC-related protein 1 (MR1) is a highly conserved MHC class I-like molecule. Human and murine mucosal associated invariant T (MAIT) cells are restricted by MR1 and express an invariant T cell receptor. Even though MR1 protein expression on the cell surface has not been demonstrated in vivo or ex vivo, it is assumed that MR1 presents a bacterial antigen from the intestinal lumen to MAIT cells because MAIT cells are present in the lamina propria and their expansion is dependent on the presence of intestinal micro flora. The existence of bovine MAIT cells and MR1 has been demonstrated recently although ovine MAIT cells and MR1 have not yet been described. We cloned bovine and ovine MR1 transcripts, including splice variants, and identified an anti human MR1 antibody that recognizes cells transfected with the bovine homolog. Using this antibody, no MR1 staining was detected using cells freshly isolated from blood, thymus, spleen, colon, ileum, and lymph node. MAIT cells are known to be enriched in the CD4/CD8 double negative peripheral blood T cell population, but their relative abundance in different tissues is not known. Comparison of the amount of MAIT cell-specific TCR transcript to the amount of constant α chain transcript revealed that numbers of MAIT cells are low in neonates and increase by 3-weeks of age. In 3-month old animals, MAIT cells are abundant in spleen and less so in ileum, peripheral blood, lymph node, colon, and thymus.
Gait speed and survival in older adults.

CONTEXT Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates. OBJECTIVE To evaluate the relationship between gait speed and survival. DESIGN, SETTING, AND PARTICIPANTS Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%, women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s. MAIN OUTCOME MEASURES Survival rates and life expectancy. RESULTS There were 17,528 deaths; the overall 5-year survival rate was 84.8% (confidence interval [CI], 79.6%-88.8%) and 10-year survival rate was 59.7% (95% CI, 46.5%-70.6%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19% to 87% in men and from 35% to 91% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization. CONCLUSION In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.