Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute ethanol alters multiple histone modifications at model gene promoters in the cerebral cortex.

BACKGROUND Ethanol (EtOH) exposure alters gene expression in the cerebral cortex (CCx); however, mechanisms of EtOH-induced gene regulation are not well understood. We hypothesized that EtOH regulates gene expression by differentially altering histone modifications at gene promoters that are up- and down-regulated by EtOH. Such epigenetic mechanisms may ultimately contribute to EtOH-induced neuro-adaptations that underlie tolerance, dependence, and EtOH-use disorders. METHODS Eight-week-old, male C57BL/6J mice were treated with 3 g/kg EtOH (intraperitoneally) or saline and sacrificed 6 hours after injection; the CCx and hippocampus (HC) were immediately removed and flash frozen. Chromatin immunoprecipitation was used to study the association of model gene promoters with histone modifications. Western blot was used to detect global changes in the histone modifications studied. We also used a polymerase chain reaction (PCR) array to identify changes in expression of chromatin-modifying enzymes. RESULTS In CCx, acute EtOH decreased expression of Gad1, Hdac2, and Hdac11, which was associated with decreased histone acetylation at the Gad1 and Hdac2 promoters; we also identified increased expression of Mt1, Mt2, Egr1, which was associated with increased H3K4me3 levels at the Mt2 promoter and decreased H3K27me3 levels at the Mt1 promoter. We identified an increase in global levels of H3K4me3 in CCx as well as a global increase in H3K9ac and H3K14ac in HC. The PCR array identified decreased expression of Csrp2 bp, Hdac2, and Hdac11 as well as increased expression of Kat2b in CCx. CONCLUSIONS Acute EtOH induces chromatin remodeling at model up- and down-regulated genes in CCx. Different patterns of histone modifications at these gene promoters indicate that EtOH may be acting through multiple histone-modifying enzymes to alter gene expression; in particular, differential expression of Kat2b, Hdac2, Hdac11, and Csrp2 bp in CCx may mediate EtOH-induced chromatin remodeling. Additional studies are necessary to determine the relationship between EtOH-induced changes in histone-modifying enzymes, specific EtOH-induced histone modifications, and gene expression.
In vivo layer-resolved characterization of oral dysplasia via nonlinear optical micro-spectroscopy

Optical spectroscopy has proven to be a powerful technique for studying neoplastic transformation in epithelial tissue. Since specific intra-layer precancerous changes originate in the stratified layers of the oral mucosa, layer-resolved analysis will likely improve both our understanding of the mechanism of premalignant transformation, and clinical diagnostic outcomes. However, the native fluorescence signal in linear spectroscopy typically originates from a multi-layered focal volume. In this study, nonlinear spectroscopy was exploited for in vivo layer-resolved discrimination between normal and dysplastic tissue for the first time. Our results revealed numerous intra-layer specific differences.
Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation

The apical cytoplasm of airway epithelium (AE) contains abundant labile zinc (Zn) ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG)-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.
Confidence-based stopping criteria for active learning for data annotation

The labor-intensive task of labeling data is a serious bottleneck for many supervised learning approaches for natural language processing applications. Active learning aims to reduce the human labeling cost for supervised learning methods. Determining when to stop the active learning process is a very important practical issue in real-world applications. This article addresses the stopping criterion issue of active learning, and presents four simple stopping criteria based on confidence estimation over the unlabeled data pool, including maximum uncertainty, overall uncertainty, selected accuracy, and minimum expected error methods. Further, to obtain a proper threshold for a stopping criterion in a specific task, this article presents a strategy by considering the label change factor to dynamically update the predefined threshold of a stopping criterion during the active learning process. To empirically analyze the effectiveness of each stopping criterion for active learning, we design several comparison experiments on seven real-world datasets for three representative natural language processing applications such as word sense disambiguation, text classification and opinion analysis.
Substantially Modified Ratios of Effector to Regulatory T Cells During Chemotherapy in Ovarian Cancer Patients Return to Pre-Treatment Levels at Completion: Implications for Immunotherapy

Ovarian cancer is the leading cause of death from gynaecological malignancy. Despite improved detection and treatment options, relapse rates remain high. Combining immunotherapy with the current standard treatments may provide an improved prognosis, however, little is known about how standard chemotherapy affects immune potential (particularly T cells) over time, and hence, when to optimally combine it with immunotherapy (e.g., vaccines). Herein, we assess the frequency and ratio of CD8+ central memory and effector T cells as well as CD4+ effector and regulatory T cells (Tregs) during the first 18 weeks of standard chemotherapy for ovarian cancer patients. In this pilot study, we observed increased levels of recently activated Tregs with tumor migrating ability (CD4+CD25hiFoxp3+CD127−CCR4+CD38+ cells) in patients when compared to controls. Although frequency changes of Tregs as well as the ratio of effector T cells to Tregs were observed during treatment, the Tregs consistently returned to pre-chemotherapy levels at the end of treatment. These results indicate T cell subset distributions associated with recurrence may be largely resistant to being “re-set” to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients.
Facilitation of quadriceps activation following a concentrically controlled knee flexion movement: the influence of transition rate.

STUDY DESIGN Single group repeated measures design. OBJECTIVE To determine if the rate of transition between knee flexion and extension influences the subsequent concentric activation of the quadriceps and knee extension torque during reciprocal movements. BACKGROUND Preloading a muscle by stretching, a prior isometric or eccentric muscle action, or a prior movement controlled concentrically by the antagonist muscle group increases the maximal torque-generating capability of the agonist. We hypothesized that the rate of transition from the prior movement may be the critical factor that influences the degree of muscle facilitation and torque potentiation. Rapid reversal of antagonistic movements has been postulated as a potential facilitatory mechanism. METHODS Knee extension torque and electromyographic (EMG) amplitude (dependent variables) from 2 of the vasti muscles were recorded while subjects (N = 20; 12 men, 8 women, mean age, 28.5+/-2.68 years) maximally activated their quadriceps at 3 constant angular velocities, 100 degrees/s, 200 degrees/s, and 300 degrees/s, and 2 preload conditions, SLOW and RAPID (independent variables). In the SLOW transition condition, subjects actively flexed their knee to 110 degrees from an extended position, paused in this position for 3 seconds, and then extended to 0 degrees. In the RAPID transition condition, the same movement from knee flexion to extension was performed without a pause. RESULTS Peak torque, the root-mean-square (RMS) average, peak (peak rectified and smoothed), and initial (100 milliseconds prior to torque onset) EMG amplitudes were all significantly greater during the RAPID transition condition. Peak torque decreased with increasing movement velocity. There were no interactions between the preload conditions and angular velocity on peak torque or the EMG amplitude variables. There was also no influence of velocity on the EMG amplitude variables. CONCLUSIONS The effect of preloading the quadriceps by prior concentric activation of the hamstrings is dependent on the rate of transition between the flexion and extension movements and is due primarily to neural facilitation.
Stabilizing decentralized systems with arbitrary information structure

A seminal result in decentralized control is the development of fixed modes by Wang and Davison in 1973 - that plant modes which cannot be moved with a static decentralized controller cannot be moved by a dynamic one either, and that the other modes which can be moved can be shifted to any chosen location with arbitrary precision. These results were developed for perfectly decentralized, or block diagonal, information structure, where each control input may only depend on a single corresponding measurement. Furthermore, the results were claimed after a preliminary step was demonstrated, omitting a rigorous induction for each of these results, and the remaining task is nontrivial.
Emerging corticosteroid agonists for the treatment of asthma

Introduction: Asthma is one of the most frequent chronic diseases worldwide. For decades, asthma has been treated with bronchodilators and inhaled corticosteroids (ICS). However, adverse effects of ICS and disease heterogeneity necessitate improvements in the existing treatment regimes. Recently approved ICS show improved pharmocodynamic properties. Nevertheless, emerging drugs acting on the same receptor as the ICS, glucocorticoid receptor agonists (GRAs), are under current research. These drugs exhibit selective action on the glucocorticoid receptor (GR), which may improve their adverse effect profile, compared to the currently approved ICS that act unselectively on the GR. Areas covered: The present article reviews emerging GRAs for the treatment of asthma. Furthermore, the more recently approved ICS with improved safety profiles are reviewed. Expert opinion: Compared with drugs acting on other pathological pathways, research in GRAs for asthma is sparse. However, a few promising agents acting selectively on the GR are currently under investigation and may reach approval for asthma treatment. These drugs exhibit improved pharmacodynamic properties due to selectivity in the mechanism of action, including promotion of transrepression and reduction of transactivation. However, competition from already approved ICS and other emerging treatment options may lead to cessation of development of the new GRAs.
Railway deformation detected by DInSAR over active sinkholes in the Ebro Valley evaporite karst, Spain

Abstract. Subsidence was measured for the first time on railway tracks in the central sector of Ebro Valley (NE Spain) using Differential Synthetic Aperture Radar Interferometry (DInSAR) techniques. This area is affected by evaporite karst and the analysed railway corridors traverse active sinkholes that produce deformations in these infrastructures. One of the railway tracks affected by slight settlements is the Madrid–Barcelona high-speed line, a form of transport infrastructure highly vulnerable to ground deformation processes. Our analysis based on DInSAR measurements and geomorphological surveys indicates that this line shows dissolution-induced subsidence and compaction of anthropogenic deposits (infills and embankments). Significant sinkhole-related subsidence was also measured by DInSAR techniques on the Castejon–Zaragoza conventional railway line. This study demonstrates that DInSAR velocity maps, coupled with detailed geomorphological surveys, may help in the identification of the railway track sections that are affected by active subsidence.
Angiotensin II Induces Endothelial Xanthine Oxidase Activation: Role for Endothelial Dysfunction in Patients With Coronary Disease

Objective—Xanthine oxidase (XO), a major source of superoxide, has been implicated in endothelial dysfunction in atherosclerosis. Mechanisms, however, leading to endothelial XO activation remain poorly defined. We tested the effect of angiotensin II (Ang II) on endothelial XO and its relevance for endothelial dysfunction in patients with coronary disease. Methods and Results—XO protein levels and XO-dependent superoxide production were determined in cultured endothelial cells in response to Ang II. In patients with coronary disease, endothelium-bound XO activity as determined by ESR spectroscopy and endothelium-dependent vasodilation were analyzed before and after 4 weeks of treatment with the AT1-receptor blocker losartan, the XO inhibitor allopurinol, or placebo. Ang II substantially increased endothelial XO protein levels and XO-dependent superoxide production in cultured endothelial cells, which was prevented by NAD(P)H-oxidase inhibition. In vivo, endothelium-bound XO activity was reduced by losartan and allopurinol, but not placebo therapy in patients with coronary disease. XO inhibition with oxypurinol improved endothelium-dependent vasodilation before, but not after losartan or allopurinol therapy. Conclusions—These findings suggest a novel mechanism whereby Ang II promotes endothelial oxidant stress, ie, by redox-sensitive XO activation. In patients with coronary disease, losartan therapy reduces endothelium-bound XO activity likely contributing to improved endothelial function.
5132 - CONSTRAINT-DEPENDENT FRACTURE TOUGHNESS OF GLASS AND PMMA

Data on Mode I fracture collected in an extensive program of uniaxial and biaxial tests of glass and PMMA specimens are compared in an effort to quantify uniformly the constraint effects in brittle and quasi-brittle materials. We seek to refine our understanding of the interplay between of the constraint-related parameters of crack growth resistance tests and the results of single-point characterization of fracture toughness. The long-term aim is to develop a sufficiently general engineering approach allowing one to predict the critical values of loads and displacements and the amounts of the subcritical crack extension in plates and shells made from brittle and ductile metallic or nonmetallic materials. It is demonstrate that in general terms, the changes of the plane strain fracture toughness characteristics with constraint may occur in a roughly similar manner for brittle, quasi-brittle, and ductile materials.
Study of clinical profile and antibiotic sensitivity pattern in culture positive typhoid fever cases.

OBJECTIVES The present study was designed to analyze the clinical profile and antibiotic sensitivity pattern in the cases of culture positive typhoid fever. METHOD The study was conducted over a period of 1 year. Total of 46 culture positive cases of Typhoid fever were included in the study. The sensitivity pattern of isolates from blood culture was recorded. The modes of presentation, clinical course, lab investigation reports were also recorded. RESULTS Out of 46 cases, 33 (71.7%) were males and 13 (28.3%) were females. Average age of presentation was 26.17 years. Fever was present in all patients. Resistance of S . typhi to amoxycillin, chloramphenicol and co-trimoxazole were significantly high. Ciprofloxacin showed resistance in 2 (4.3%) cases. Sensitivity to ceftriaxone was 100% in our study. CONCLUSION Typhoid fever is one of the most common health problem in Nepal. Various drugs are being used in the treatment of typhoid fever, in the mean time resistance to many of them are emerging. An appropriate antibiotic has to be initiated only after culture sensitivity in typhoid fever.
Improving zinc accumulation in cereal endosperm using HvMTP1, a transition metal transporter

Summary Zinc (Zn) is essential for all life forms, including humans. It is estimated that around two billion people are deficient in their Zn intake. Human dietary Zn intake relies heavily on plants, which in many developing countries consists mainly of cereals. The inner part of cereal grain, the endosperm, is the part that is eaten after milling but contains only a quarter of the total grain Zn. Here, we present results demonstrating that endosperm Zn content can be enhanced through expression of a transporter responsible for vacuolar Zn accumulation in cereals. The barley (Hordeum vulgare) vacuolar Zn transporter HvMTP1 was expressed under the control of the endosperm‐specific D‐hordein promoter. Transformed plants exhibited no significant change in growth but had higher total grain Zn concentration, as measured by ICP‐OES, compared to parental controls. Compared with Zn, transformants had smaller increases in concentrations of Cu and Mn but not Fe. Staining grain cross sections with the Zn‐specific stain DTZ revealed a significant enhancement of Zn accumulation in the endosperm of two of three transformed lines, a result confirmed by ICP‐OES in the endosperm of dissected grain. Synchrotron X‐ray fluorescence analysis of longitudinal grain sections demonstrated a redistribution of grain Zn from aleurone to endosperm. We argue that this proof‐of‐principle study provides the basis of a strategy for biofortification of cereal endosperm with Zn.
Dynamic modelling of a two-link flexible manipulator system incorporating payload

This paper presents dynamic modelling of a two-link flexible manipulator based on closed-form equations of motion. The kinematic model is based on standard frame transformation matrices describing both rigid rotation and modal displacement, under small deflection assumption. The Lagrangian approach is used to derive the dynamic model of the structure. Links are modelled as Euler-Bernoulli beams with proper clamped-mass boundary conditions. A dynamic model of the system, incorporating structural damping, hub inertia and payload, is developed using finite assumed mode methods. Explicit equations of motions are detailed by assuming two modes of vibration for each link. Moreover, effects of payload on the response of the flexible manipulator are discussed. Extensive results that validate the theoretical derivation are presented in the time and frequency domains.
Gustatory and olfactory function in rheumatoid arthritis

Objectives: To evaluate the gustatory and olfactory functions of patients with rheumatoid arthritis (RA) compared to sex- and age-matched healthy subjects and to investigate a potential relationship between disease activity [using the 28-joint Disease Activity Score (DAS28)] and chemosensory capacity. Furthermore, to dissect possible impacts of standard anti-inflammatory medications on the gustatory and olfactory functions. Methods: Patients with established RA underwent standardized assessment of their gustatory and olfactory functions. The patients were also examined for their disease activity, had their specific blood-test results analysed, and were asked to answer a standardized questionnaire about their quality of life, the negative effects of their disease, and about comorbidities. Results: A total of 101 RA patients (75 women, 26 men, mean age: 57.9 ± 13.8 and 64.2 ± 10.9 years, respectively) were analysed. In relation to age- and sex-related subjects, both female and male RA patients had a significantly decreased taste score (p < 0.001) and also a significantly decreased olfactory score (p < 0.05), indicating that a substantial number of patients suffer from hypogeusia or hyposmia. This abnormality did not correlate with disease activity, the duration of the disease, disease-modifying anti-rheumatic drug (DMARD) or tumour necrosis factor (TNF) inhibitor use, and the loss of the chemosensory functions, together indicating that hypogeusia and hyposmia are frequent clinical manifestations in RA patients independent of the inflammatory activity of their disease. Conclusion: The results indicate that there is a significant decrease in the olfactory and gustatory function in RA patients compared to those of healthy controls, which can seriously and substantially affect the quality of the patients' life.
An fMRI Study of the Neural Systems Involved in Visually Cued Auditory Top-Down Spatial and Temporal Attention

Top-down attention to spatial and temporal cues has been thoroughly studied in the visual domain. However, because the neural systems that are important for auditory top-down temporal attention (i.e., attention based on time interval cues) remain undefined, the differences in brain activity between directed attention to auditory spatial location (compared with time intervals) are unclear. Using fMRI (magnetic resonance imaging), we measured the activations caused by cue-target paradigms by inducing the visual cueing of attention to an auditory target within a spatial or temporal domain. Imaging results showed that the dorsal frontoparietal network (dFPN), which consists of the bilateral intraparietal sulcus and the frontal eye field, responded to spatial orienting of attention, but activity was absent in the bilateral frontal eye field (FEF) during temporal orienting of attention. Furthermore, the fMRI results indicated that activity in the right ventrolateral prefrontal cortex (VLPFC) was significantly stronger during spatial orienting of attention than during temporal orienting of attention, while the DLPFC showed no significant differences between the two processes. We conclude that the bilateral dFPN and the right VLPFC contribute to auditory spatial orienting of attention. Furthermore, specific activations related to temporal cognition were confirmed within the superior occipital gyrus, tegmentum, motor area, thalamus and putamen.