Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic metastable atmospheric regime identification in an AGCM

In this study we apply a recently developed clustering method for the systematic identification of metastable atmospheric regimes in high-dimensional data sets generated by atmospheric models. The novelty of this approach is that it decomposes the phase space in, possibly, over-lapping clusters and simultaneously estimates the most likely switching sequence amongst the clusters. The parameters of the clustering and switching are estimated by a Finite Element approach. The switching amongst the clusters can be described by a Markov transition matrix. Possible metastable regime behavior is assessed by inspecting the eigenspectrum of the associated transition probability matrix. Here we apply the recently introduced metastable data-analysis method to high-dimensional data sets produced by a barotropic model and a comprehensive atmospheric General Circulation Model (GCM). We are able to successfully identify significant and dynamically relevant metastable regimes in both models. The metastable regimes in the barotropic model correspond to blocked and zonal states. Similar regime states were already previously identified in highly reduced phase spaces of just one- and two-dimensions in the same model. Next the clustering method is applied to a comprehensive atmospheric GCM where 7 significant flow regimes are identified. The spatial structures of the regimes correspond amongst others to both phases of the Northern Annular Mode and Pacific blocking. The regimes are maintained predominantly by transient eddy fluxes of low-pass filtered anomalies. It is demonstrated how the dynamical description of the slow process switching between the regimes can be acquired from the analysis results and an investigation of the resulting simplified dynamical model with respect to predictability is performed. A predictability study shows that a simple Markov model is able to predict the regimes up to 6 days ahead, which is comparable to the ability of high resolution state-of-the-art numerical weather prediction models to accurately predict the onset and decay of blockings. The implications of our results for the derivation of reduced models for extended-range predictability are discussed.
The regulation and importance of glucose uptake in the isolated Atlantic cod heart: rate-limiting steps and effects of hypoxia

SUMMARY This study investigated the regulation of glucose uptake in Atlantic cod (Gadus morhua) hearts. Isolated hearts were perfused with or without glucose in the medium, under either normoxic or severely hypoxic conditions. Working at basal levels, hearts did not require extracellular glucose to maintain power under aerobic conditions. However, cardiac performance was significantly reduced without exogenous glucose under oxygen-limiting conditions. The addition of the glucose transporter inhibitor cytochalasin B caused hypoxic hearts to fail early, and hearts perfused with a glucose analogue, 2-deoxyglucose (2-DG), increased glucose uptake 3-fold under hypoxia. The uptake of 2-DG was only partially inhibited when cytochalasin B was added to the medium. Isolated ventricle strips were also incubated in the presence of 2-DG and the extracellular marker mannitol. Glucose uptake (glucose transport plus intracellular phosphorylation) was assessed by measuring the initial rate of 2-deoxyglucose-6-phosphate (2-DG-6-P) accumulation. At 1 mmol l-1 2-DG, the rate of 2-DG uptake remained linear for 60 min, and 2-DG-6-P, but not free 2-DG, accumulation was increased. The fact that intracellular 2-DG did not increase indicates that glucose transport is the rate-limiting step for glucose utilization in non-stimulated cardiac tissue. Replacement of Na+ by choline in the incubation medium did not affect 2-DG uptake, providing evidence that Na+-coupled glucose transport is absent in cod cardiac tissue. Similar to cytochalasin B, glucose uptake was also inhibited by phloridzin, suggesting that facilitated, carrier-mediated glucose transport occurs in cod hearts. Under the conditions employed in these experiments, it is clear that (1) activation of glucose transport is required to support hypoxic performance, (2) the rate-limiting step for glucose utilization is glucose transport rather than glucose phosphorylation, (3) 2-DG uptake accurately reflects glucose transport activity and (4) glucose uptake in cod hearts does not involve an Na+-dependent mechanism.
Pronunciation Evaluation in Read and Spontaneous Speech: A Comparison between human ratings and automatic scores

This paper describes two experiments aimed at exploring the relationship between objective properties of speech and perceived pronunciation quality in read and spontaneous speech, with a view to determining whether such quantitative measures can be used to develop objective pronunciation tests. Read and spontaneous speech of two groups of 60 learners of Dutch as a second language was scored for pronunciation quality by human raters and was analysed by means of a continuous speech recognizer to calculate six quantitative measures of speech quality related to speech timing. The results show that quantitative, temporal measures of speech are strongly related to pronunciation quality, in both read and spontaneous speech, although not all variables suitable for measuring pronunciation quality in read speech are as effective in spontaneous speech. In particular, measures that express the rate at which sounds are produced without taking the frequency and distribution of pauses into account appear to be unsuitable for measuring pronunciation quality in spontaneous speech.
Patterns of Secondary Prevention in Older Patients Undergoing Coronary Artery Bypass Grafting During Hospitalization for Acute Myocardial Infarction

Background—Aggressive risk factor modification decreases cardiovascular events and mortality in patients after coronary artery bypass grafting (CABG). Little is known regarding the use of secondary prevention in older patients undergoing CABG during hospitalization for acute myocardial infarction (AMI). Methods and Results—Medical records were reviewed for a sample of 37,513 patients hospitalized with AMI in the United States between April 1998 and March 1999. Patients ≥65 years of age who underwent CABG after AMI (n=2,267 [8%]) were evaluated for the prescription of 4 therapies at discharge: aspirin, &bgr;-blockers, angiotensin-converting enzyme (ACE) inhibitors, and lipid lowering, in eligible patients without contraindications to therapy and compared with patients who did not undergo CABG (n=26,484 [92%]). Patients undergoing CABG had higher rates of aspirin than patients who did not undergo CABG (88.0% versus 83.2%, P =0.0002). However, CABG patients were less likely to receive &bgr;-blockers (61.5% versus 72.1%, P <0.0001), ACE inhibitors (55.5% versus 72.1%, P <0.0001), or lipid lowering (34.7% versus 55.7%, P <0.0001) prescriptions than patients who did not undergo CABG. After adjustment for disease severity, patients undergoing CABG were no longer more likely to receive discharge aspirin, and the magnitude of other differences in care increased. Conclusions—Evidence-based discharge therapies are underutilized in older patients who underwent CABG during hospitalization for AMI. Although national efforts focusing on improving short-term surgical mortality have been successful, strategies should be developed to increase the utilization of therapies known to improve long-term mortality in patients undergoing CABG.
Molecular portrait of a rare case of metastatic glioblastoma: somatic and germline mutations using whole-exome sequencing

for driver mutations. We found 4 variations in genes identiﬁed as tumor sup-pressors: RB1 deletion of 5 bases (Gln257fs), CREBBP stop mutation (Gln1027*), ARID1A1 one-base deletion (p.Val1867A-lafs), and BRCA2 stop mutation (Gln2164*). We ﬁnally performed a number variation (CNV) analysis, obtaining a of deletions in TP53, PTEN, ERBB2, RTEL1, CDKN2A, in BRCA2 RTEL1
Supervised Multilayer Sparse Coding Networks for Image Classification

In this paper, we propose a novel multilayer sparse coding network capable of efficiently adapting its own regularization parameters to a given dataset. The network is trained end-to-end with a supervised task-driven learning algorithm via error backpropagation. During training, the network learns both the dictionaries and the regularization parameters of each sparse coding layer so that the reconstructive dictionaries are smoothly transformed into increasingly discriminative representations. We also incorporate a new weighted sparse coding scheme into our sparse recovery procedure, offering the system more flexibility to adjust sparsity levels. Furthermore, we have devised a sparse coding layer utilizing a 'skinny' dictionary. Integral to computational efficiency, these skinny dictionaries compress the high dimensional sparse codes into lower dimensional structures. The adaptivity and discriminability of our 13-layer sparse coding network are demonstrated on four benchmark datasets, namely Cifar-10, Cifar-100, SVHN and MNIST, most of which are considered difficult for sparse coding models. Experimental results show that our architecture overwhelmingly outperforms traditional one-layer sparse coding architectures while using much fewer parameters. Moreover, our multilayer architecture fuses the benefits of depth with sparse coding's characteristic ability to operate on smaller datasets. In such data-constrained scenarios, we demonstrate our technique can overcome the limitations of deep neural networks by exceeding the state of the art in accuracy.
The Learning About My Pain study protocol: Reducing disparities with literacy-adapted psychosocial treatments for chronic pain, a comparative behavioral trial

Chronic pain is a critical public health problem that affects over 100 million Americans. Medical pain treatments carry undesirable side effects, whereas low-risk psychosocial treatments offer notable benefits, in combination or in isolation. This report presents the protocol for the Learning About My Pain study, one of the first comparative-effectiveness trials funded by the Patient-Centered Outcomes Research Institute. Adhering to published standards for clinical trials (e.g. Standard Protocol Items: Recommendations for Intervention Trials), it provides an overview of the trial (n = 294), comparing cognitive-behavioral and education pain interventions to usual care, and a detailed description of how its methodology reduces the risks from bias.
Discrepancies between Verbal and Performance IQS and Subtest Scatter on the Wisc-R for Juvenile Delinquents

The present study examined discrepancies in Verbal and Performance IQs and subtest scatter on the WISC-R for 121 male juvenile delinquents. While statistically significant Verbal-Performance discrepancies and subtest scatter were evidenced, these indices of scatter did not differ from normative data provided by Kaufman in 1976. It was concluded that the WISC-R may not be useful as a differential diagnostic indicator for juvenile delinquency but may be beneficial as a tool for making remedial prescriptive recommendations.
Varicella-zoster virus infection of adult rat sensory neurons in vitro

We report here an in vitro model of neuronal infection by varicella-zoster virus (VZV). Such a model has been achieved by using dissociated adult rat dorsal root ganglia cells infected by cocultivation with VZV-infected MRC5 cells or with cell-free virus. Indirect VZV immunolabeling, in situ hybridization, and neuron-specific immunolabeling demonstrated that VZV infection occurred selectively in neurons. VZV-specific immunolabeling detected a few neurons 1 or 2 days postinfection but not later. Genome detection using cloned VZV DNA probes revealed a hybridization signal primarily with RNA. Within 1 to 6 days postinfection, a progressive increase of VZV-specific hybridization was observed in up to 50% of the neurons. RNAs corresponding to immediate-early, early, and late genes were found, and transcripts of immediate-early gene 63 were particularly abundant.
The Epworth Sleepiness Scale in the Identification of Obstructive Sleep Apnea

The Epworth sleepiness scale (ESS) is often used clinically to screen for the manifestations of the behavioral morbidity associated to obstructive sleep apnea (OSA). The purpose of this study was to assess the sensitivity of the ESS in the identification of OSA, as defined by an elevated apnea-hypopnea index. A retrospective chart review of 268 consecutive patients diagnosed with OSA at a multidisciplinary sleep medicine clinic was conducted. The ESS obtained a relatively low sensitivity (66%) in the identification of an apnea-hypopnea index of 5 and above at the suggested cutoff of 10 and increased to 76% at 8. The results of the study showed only fair discriminatory ability of the ESS as a screener for OSA. A score of 8 (instead of 10) is suggested as the cutoff among clinic populations being screened for a sleep disorder.
Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

BACKGROUND We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
PGC‐1α protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model

Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. We sought to determine whether peroxisome proliferator–activated receptor γ coactivator 1α (PGC‐1α) would have a beneficial effect on this disease. Methods: PGC‐1α transgenic mice were crossed with SOD1 mutant G93A DL mice. Results: We observed a moderate but non‐significant increase in average lifespan in PGC‐1α/G93A DL mice, as compared with G93A DL mice (292 ± 3 days vs. 274 ± 7 days). Although the onset of ALS was not altered, progression of the disease was significantly slower (∽34% increase in duration) in the PGC‐1α/G93A DL mice. These mice also exhibited markedly improved performance on the rotarod test, and the improved motor activity was associated with a decreased loss of motor neurons and less degeneration of neuromuscular junctions. Conclusion: A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astrocytes of the PGC‐1α/G93A DL mice may contribute to neuronal protection. Muscle Nerve 2011
REPORT : Short Form of the VIA Inventory of Strengths : Construction and Initial Tests of Reliability and Validity

©ARC Page | 229 Abstract Assessment of character strengths became a focus of both research and clinical practice with the emergence of positive psychology at the beginning of the 21st century. The VIA Inventory of Strengths (VIA-IS), a selfreport instrument, has emerged as the primary instrument for measuring personal strengths and virtues. However, use of the instrument has been compromised by its 240-item length. This study created a briefer version consisting of 120 items, using the 5 items with the highest corrected item-total correlations. The new 120-item version demonstrated reasonable reliability and validity, based on three samples of people who completed the original VIA-IS and two additional samples who completed only the new developed short form.
The Role of E3 in pH Protection during Alphavirus Assembly and Exit

ABSTRACT Alphaviruses are small enveloped viruses whose surface is covered by spikes composed of trimers of E2/E1 glycoprotein heterodimers. During virus entry, the E2/E1 dimer dissociates within the acidic endosomal environment, freeing the E1 protein to mediate fusion of the viral and endosome membranes. E2 is synthesized as a precursor, p62, which is cleaved by furin in the late secretory pathway to produce mature E2 and a small peripheral glycoprotein, E3. The immature p62/E1 dimer is acid resistant, but since p62 is cleaved before exit from the acidic secretory pathway, low pH-dependent binding of E3 to the spike complex is believed to prevent premature fusion. Based on analysis of the structure of the Chikungunya virus E3/E2/E1 complex, we hypothesized that interactions of E3 residues Y47 and Y48 with E2 are important in this binding. We then directly tested the in vivo role of E3 in pH protection by alanine substitutions of E3 Y47 and Y48 (Y47/48A) in Semliki Forest virus. The mutant was nonviable and was blocked in E1 transport to the plasma membrane and virus production. Although the Y47/48A mutant initially formed the p62/E1 heterodimer, the dimer dissociated during transport through the secretory pathway. Neutralization of the pH in the secretory pathway successfully rescued dimer association, E1 transport, and infectious particle production. Further mutagenesis identified the critical contact as the cation-π interaction of E3 Y47 with E2. Thus, E3 mediates pH protection of E1 during virus biogenesis via interactions strongly dependent on Y47 at the E3-E2 interface.
For Personal Use. Only Reproduce with Permission from the Lancet Primary Biliary Cirrhosis

53 Primary biliary cirrhosis is a chronic cholestatic liver disease of unknown cause. Progressive bile-duct injury from portal and periportal inflammation could result in progressive fibrosis and eventual cirrhosis. Evidence to date suggests that immunological and genetic factors might cause the disease. Affected individuals are typically middle-aged women with asymptomatic rises of serum hepatic biochemical variables. Fatigue, pruritus, or unexplained hyperlipidaemia at initial presentation might also suggest a diagnosis of primary biliary cirrhosis. Serum antimitochondrial antibody positivity is nearly diagnostic of the disease. Disease identification is important because effective medical treatment with ursodeoxycholic acid can halt disease progression and extend survival free of liver transplantation. Mathematical models that accurately characterise the natural history of primary biliary cirrhosis may also assist in determining the optimum timing for liver transplantation when indicated. Epidemiology Primary biliary cirrhosis affects all races, yet seems to cluster within specific geographical areas. 1 Women are mainly affected, with a female/male ratio of 9/1. The median age of disease onset is 50 years, but varies between 20 and 90 years. Estimates of annual incidence 2,3 and prevalence 3,4 range from 2 to 24 cases per million and 19 to 240 cases per million population, respectively. Data from Olmsted County, Minnesota, USA, 4 suggest a stable incidence rate over the past 25 years but a higher prevalence than described in Canada. 5 Differences in methodology and case definitions have impeded comparisons between series. The worldwide variation in disease prevalence suggests that environmental factors are needed for phenotypic expression of primary biliary cirrhosis. From a population-based study in northern England 6 and a large case-control US investigation, 7 presence of tobacco use and extrahepatic autoimmune disorders have been associated with the disease when compared with controls. First-degree relatives of people with primary biliary cirrhosis are also known to have at least a twofold increased risk of autoimmune diseases. A high rate of urinary-tract infections in smokers with the disease has raised the possibility of an infectious cause. 8 Data of the association between gravidity and primary biliary cirrhosis are conflicting. Genetics Genetic predisposition to autoimmunity in primary biliary cirrhosis has been associated with alleles from MHC loci. However, class 2 MHC loci, including DR8, DQA1*0102, and DQ/␤1*0402, have only been reported in selected patients with the disorder. 11–13 The haplotypes DR3, DR8, and DR4 are more frequent in white populations by contrast with DR2 and DR8 haplotypes in Japanese patients. …
Galeterone Prevents Androgen Receptor Binding to Chromatin and Enhances Degradation of Mutant Androgen Receptor

Purpose: Galeterone inhibits the enzyme CYP17A1 and is currently in phase II clinical trials for castration-resistant prostate cancer (CRPC). Galeterone is also a direct androgen receptor (AR) antagonist and may enhance AR degradation. This study was undertaken to determine the molecular basis for AR effects and their therapeutic potential. Experimental Design: Effects of galeterone on AR expression and activities were examined in prostate cancer cell lines. Results: Similar to the AR antagonist enzalutamide, but in contrast to bicalutamide, galeterone did not induce binding of a constitutively active VP16-AR fusion protein to reporter genes and did not induce AR recruitment to endogenous androgen-regulated genes based on chromatin immunoprecipitation. Galeterone at low micromolar concentrations that did not induce cellular stress responses enhanced AR protein degradation in LNCaP and C4-2 cells, which express a T878A mutant AR, but not in prostate cancer cells expressing wild-type AR. Further transfection studies using stable LNCaP and PC3 cell lines ectopically expressing wild-type or T878A-mutant ARs confirmed that galeterone selectively enhances degradation of the T878A-mutant AR. Conclusions: Similar to enzalutamide, galeterone may be effective as a direct AR antagonist in CRPC. It may be particularly effective against prostate cancer cells with the T878A AR mutation but may also enhance degradation of wild-type AR in vivo through a combination of direct and indirect mechanisms. Finally, these findings show that conformational changes in AR can markedly enhance its degradation and thereby support efforts to develop further antagonists that enhance AR degradation. Clin Cancer Res; 20(15); 4075–85. ©2014 AACR.