Miracle-dz/UniFAR-FTUs huggingface dataset:
Slo3, a Novel pH-sensitive K+ Channel from Mammalian Spermatocytes*

Potassium channels have evolved to play specialized roles in both excitable and inexcitable tissues. Here we describe the cloning and expression of Slo3, a novel potassium channel abundantly expressed in mammalian spermatocytes. Slo3 represents a new and unique type of potassium channel regulated by both intracellular pH and membrane voltage. Reverse transcription-polymerase chain reaction, Northern analysis, and in situ hybridization show that Slo3 is primarily expressed in testis in both mouse and human. Because of its sensitivity to both pH and voltage, Slo3 could be involved in sperm capacitation and/or the acrosome reaction, essential steps in fertilization where changes in both intracellular pH and membrane potential are known to occur. The protein sequence of mSlo3 (the mouse Slo3 homologue) is similar to Slo1, the large conductance, calcium- and voltage-gated potassium channel. These results suggest that Slo channels comprise a multigene family, defined by a combination of sensitivity to voltage and a variety of intracellular factors. Northern analysis from human testis indicates that a Slo3 homologue is present in humans and conserved with regard to sequence, transcript size, and tissue distribution. Because of its high testis-specific expression, pharmacological agents that target human Slo3 channels may be useful in both the study of fertilization as well as in the control or enhancement of fertility.
Early post-treatment with pentoxifylline or dibutyryl cAMP attenuates Escherichia coli-induced acute lung injury in guinea pigs.

We examined effects of early post-treatment with the methylxanthine pentoxifylline (PTXF), or the cell-permeable adenosine 3', 5'-cyclic monophosphate (cAMP) analog dibutyryl cAMP (db-cAMP) on Escherichia-coli-induced acute lung injury in guinea pigs. Acute lung injury was assessed by measurements of lung water (lung wet/dry weight ratio; W/D ratio), the concentration ratio of 125I-albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared with plasma (albumin index; BAL-AI or tissue-AI), and total differential leukocyte count in BAL fluid. Mean arterial pressure (Pa) and peripheral WBC counts were monitored continuously over the 8-h experiment. Septicemia was induced by a bolus injection of 2 x 10(9)/kg live E. coli. Thirty minutes later the animals received a bolus injection followed by continuous infusion of PTXF (20 mg/kg + 20 mg/kg/h; n = 8) or db-cAMP (2 mg/kg + 2 mg/kg/h; n = 8) or saline (septic control; n = 8). Nonseptic control groups were also studied. The lung W/D ratio, BAL-AI, lung tissue-AI, and BAL leukocyte count increased significantly in the septic control group. The PTXF-septic and db-cAMP-septic groups showed no significant increase in lung W/D ratio, BAL-AI, and lung tissue-AI. However, there was no difference in BAL total and differential leukocyte count as compared with the septic control group. PTXF and db-cAMP had no effect on E. coli-induced changes in peripheral WBC count and Pa. Comparison in vitro experiments demonstrated that PTXF and db-cAMP inhibited the endotoxin-induced (E. coli) chemiluminescent response of isolated guinea-pig polymorphonuclear leukocytes (PMN). (ABSTRACT TRUNCATED AT 250 WORDS)
Toward Sustainable Freemium Software: The Roles of User Satisfaction and Use Context

Freemium software provides basic features free of charge and premium features for additional payment. It is a prevailing business model in the software industry. The model could be a long-awaited solution for software providers suffering from sustainability and retention problems. However, software providers are still experiencing low conversion rates from free users to paid users. Satisfactory services do not guarantee additional spending by free users for services. User satisfaction with core services has been considered a key component of user loyalty. However, this belief is being challenged. This study investigates the effect of satisfaction on loyalty intentions (continuance intention and intention to purchase) of freemium software. The study develops a research model based upon the use context framework including user characteristics, relational characteristics, and marketplace characteristics. The results from a series of regressions show that satisfaction affects continuance intention but does not influence purchase intention although it indirectly affects purchase intention by interacting with various characteristics. The results suggest several strategies that freemium software providers can pursue according to their objectives. Rather than satisfactory services, interactions among users or carefully designed additional features can lead to sustainable profitability.
Changes in the faecal microbiota of mares precede the development of post partum colic.

REASONS FOR PERFORMING STUDY Disruptions in the gastrointestinal microbiota may trigger development of post partum colic. OBJECTIVES To determine the effects of the periparturient period on the faecal microbiome and identify associations between the faecal microbiota and post partum colic. STUDY DESIGN Longitudinal case-control study. METHODS Pre- and post partum faecal samples were collected from mares on 3 farms in central Kentucky. Next generation sequencing of the V4 region of the 16S rRNA gene was performed on samples from 13 mares that developed colic, 13 mares that did not display colic and 5 nonpregnant controls. RESULTS There were 4,523,727 sequences from 85 samples evaluated (mean ± s.d. 53,220 ± 29,160, range 8442-122,535). Twenty-five phyla were identified, although only Firmicutes, Verrucomicrobia, Actinobacteria and Proteobacteria were present at a relative abundance of 1% or greater. The faecal microbiota of late-term mares differed from nonpregnant mares, with differences in microbial community membership and structure but not the relative abundance of major phyla. There was limited impact of foaling and the post partum period on the faecal microbiome. Faecal samples obtained from mares prior to episodes of colic had significantly higher relative abundance of Proteobacteria (8.2%, P = 0.0006) compared with samples from mares that did not display colic (3.7%). All samples with a relative abundance of Firmicutes of ≤50% preceded colic, as did 6/7 (86%) samples with >4% Proteobacteria. Differences in microbiota membership and structure were also present between mares that developed large colon volvulus and matched controls that did not have colic. Sixty-one indicator operational taxon units were identified for the control (vs. volvulus) samples, and these were dominated by Lachnospiraceae (n = 38) and Ruminococcaceae (n = 8). CONCLUSIONS Foaling had minimal effects on the mares' faecal microbiota. Numerous differences in the faecal microbiota preceded colic. Associations between Firmicutes (particularly Lachnospiraceae and Ruminococcaceae) and Proteobacteria and development of colic could lead to measures to predict and prevent colic. The Summary is available in Chinese - see Supporting information.
Equity Price Prediction with Neural Networks: Technical Analysis of the Italian Market

This article studies the relationship between popular technical analysis indicators and the returns of the Italian S&P MIB, active as the index of the Borsa Italiana until 2009. The study innovates by applying a mixed analysis that combines classic signals offered by the indicators with the power of neural networks. The neural algorithms are applied to study the target technical analysis indicators with more accurate regression power and efficient error minimization. Through a simple hidden-layer, back-propagation algorithm, regressions give interesting results in terms of the forecasting potential of the analyzed indicators. The final step of the study is the conclusions section, commenting on results and summarizing the indications from the multivariate stage analysis. The article also comments on the power of the indicators to reveal potential investment opportunities. The results of the study are backdated but still very significant considering the revived interest of the financial community toward the application of adaptive systems to the solution of financial issues.
Subclass and molecular form of immunoglobulin A antibodies to Actinobacillus actinomycetemcomitans in juvenile periodontitis

Patients with juvenile periodontitis frequently have elevated levels of serum immunoglobulin A (IgA) antibodies to antigens of Actinobacillus actinomycetemcomitans. IgA occurs in two subclasses, IgA1 and IgA2, and in monomeric and polymeric forms. Because IgA1 is susceptible to cleavage by IgA1 proteases produced by microorganisms found at mucosal sites and in the gingival crevice, we wished to determine the IgA subclass distribution of antibodies to antigens of A. actinomycetemcomitans. The molecular form was examined because it may indicate the origin of the IgA and because the form differs in acute and chronic infections. There is also evidence that monomeric and polymeric IgA have different biological functions. Serum was taken from patients with juvenile periodontitis before and at intervals during and after initiation of therapy. IgA subclass distribution was determined against a sonic extracts of A. actinomycetemcomitans ATCC 2952a (serotype b) by using monoclonal anti-subclass reagents in an enzyme-linked immunosorbent assay. To determine the molecular form of the antibodies, sera were separated by high-performance liquid chromatography on a size-exclusion column. Fractions were assayed for antibody activity by the enzyme-linked immunosorbent assay, and described above. The results of the subclass analysis of the sera indicated that while both IgA1 and IgA2 antibodies to A. actinomycetemcomitans sonic extract are often found before, during, and after treatment, IgA1 antibodies dominated the response. There was a predominance of monomeric IgA1 antibodies to A. actinomycetemcomitans sonic extracts in most samples before, during, and after treatment. The monomeric form is consistent with what is seen in other chronic infections. The predominance of IgA1 antibodies implies that any protective effects of the IgA response to A. actinomycetemcomitans could be compromised by microbial IgA1 proteases.
Systemic sclerosis in an Afro-Caribbean population: a review of demographic and clinical features.

OBJECTIVE To assess the clinical and selected demographic features of patients with systemic sclerosis (SS) seen over a 10-year period at the Rheumatology service of the Queen Elizabeth Hospital, Barbados. To compare these data with what is known to obtain in other ethnic populations. DESIGN AND METHODS A chart review involving all patients who were found to have SS based on the American College of Rheumatology clinical criteria was conducted between 1996 and 2006. RESULTS Twenty-seven patients with SS were identified in this predominantly Afro-Caribbean population. The prevalent and incident cases numbered 10 and 17 respectively. Twenty-six of these patients were female and the mean age at diagnosis was 37.3 years. Diffuse cutaneous involvement was seen in 63% of cases and limited cutaneous involvement in 37%. The most common clinical features in descending order of frequency were Raynaud's phenomenon, gastroesophageal reflux, pigmentary skin changes, digital pitting/ulceration, telangiectasia and pulmonary disease. CONCLUSION In a predominantly Afro-Caribbean population, SS was uncommonly seen, had a marked female preponderance and an earlier age of onset than that seen in Caucasian populations. As expected, diffuse disease was the more common subtype and digital pitting, pigmentary skin changes, and pulmonary disease were amongst the most frequent clinical features. Telangiectasia were found more frequently than the literature suggests is typical for patients of African descent.
Ototoxicity Resulting From Combined Administration of Cisplatin and Gentamicin

The hypothesis that cisplatin can augment the ototoxicity of gentamicin was tested. Seven groups of 11 guinea pigs each were given a single dose of cisplatin either alone or 14 days before, at the beginning, midway through, or at the end of a course of gentamicin administered daily for 14 days. Blood and perilymph gentamicin and cisplatin concentrations were determined in three of the animals from each group. Auditory damage was determined in the remaining 8 animals electrophysiologically by measuring the compound action potential and alternating‐current cochlear potential. Hair cell damage was determined using the surface preparation technique. An augmented ototoxic effect occurred when the cisplatin was given early in the 14‐day course of gentamicin and did not occur when it was given at the end of treatment.
Gene Therapy With the Angiogenic Cytokine Secretoneurin Induces Therapeutic Angiogenesis by a Nitric Oxide–Dependent Mechanism

Rationale: The neuropeptide secretoneurin induces angiogenesis and postnatal vasculogenesis and is upregulated by hypoxia in skeletal muscle cells. Objective: We sought to investigate the effects of secretoneurin on therapeutic angiogenesis. Methods and Results: We generated a secretoneurin gene therapy vector. In the mouse hindlimb ischemia model secretoneurin gene therapy by intramuscular plasmid injection significantly increased secretoneurin content of injected muscles, improved functional parameters, reduced tissue necrosis, and restored blood perfusion. Increased muscular density of capillaries and arterioles/arteries demonstrates the capability of secretoneurin gene therapy to induce therapeutic angiogenesis and arteriogenesis. Furthermore, recruitment of endothelial progenitor cells was enhanced by secretoneurin gene therapy consistent with induction of postnatal vasculogenesis. Additionally, secretoneurin was able to activate nitric oxide synthase in endothelial cells and inhibition of nitric oxide inhibited secretoneurin-induced effects on chemotaxis and capillary tube formation in vitro. In vivo, secretoneurin induced nitric oxide production and inhibition of nitric oxide attenuated secretoneurin-induced effects on blood perfusion, angiogenesis, arteriogenesis, and vasculogenesis. Secretoneurin also induced upregulation of basic fibroblast growth factor and platelet-derived growth factor-B in endothelial cells. Conclusions: In summary, our data indicate that gene therapy with secretoneurin induces therapeutic angiogenesis, arteriogenesis, and vasculogenesis in the hindlimb ischemia model by a nitric oxide–dependent mechanism.
sFRP2 Suppression of Bone Morphogenic Protein (BMP) and Wnt Signaling Mediates Mesenchymal Stem Cell (MSC) Self-renewal Promoting Engraftment and Myocardial Repair*

Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for ischemic injury; however, inadequate survival of implanted cells in host tissue is a substantial impediment in the progress of cellular therapy. Secreted Frizzled-related protein 2 (sFRP2) has recently been highlighted as a key mediator of MSC-driven myocardial and wound repair. Notably, sFRP2 mediates significant enhancement of MSC engraftment in vivo. We hypothesized that sFRP2 improves MSC engraftment by modulating self-renewal through increasing stem cell survival and by inhibiting differentiation. In previous studies we demonstrated that sFRP2-expressing MSCs exhibited an increased proliferation rate. In the current study, we show that sFRP2 also decreased MSC apoptosis and inhibited both osteogenic and chondrogenic lineage commitment. sFRP2 activity occurred through the inhibition of both Wnt and bone morphogenic protein (BMP) signaling pathways. sFRP2-mediated inhibition of BMP signaling, as assessed by levels of pSMAD 1/5/8, was independent of its effects on the Wnt pathway. We further hypothesized that sFRP2 inhibition of MSC lineage commitment may reduce heterotopic osteogenic differentiation within the injured myocardium, a reported adverse side effect. Indeed, we found that sFRP2-MSC-treated hearts and wound tissue had less ectopic calcification. This work provides important new insight into the mechanisms by which sFRP2 increases MSC self-renewal leading to superior tissue engraftment and enhanced wound healing.
CortexNet: a Generic Network Family for Robust Visual Temporal Representations

In the past five years we have observed the rise of incredibly well performing feed-forward neural networks trained supervisedly for vision related tasks. These models have achieved super-human performance on object recognition, localisation, and detection in still images. However, there is a need to identify the best strategy to employ these networks with temporal visual inputs and obtain a robust and stable representation of video data. Inspired by the human visual system, we propose a deep neural network family, CortexNet, which features not only bottom-up feed-forward connections, but also it models the abundant top-down feedback and lateral connections, which are present in our visual cortex. We introduce two training schemes - the unsupervised MatchNet and weakly supervised TempoNet modes - where a network learns how to correctly anticipate a subsequent frame in a video clip or the identity of its predominant subject, by learning egomotion clues and how to automatically track several objects in the current scene. Find the project website at this https URL.
Towards the use of bioresorbable fibers in time‐domain diffuse optics

In the last years bioresorbable materials are gaining increasing interest for building implantable optical components for medical devices. In this work we show the fabrication of bioresorbable optical fibers designed for diffuse optics applications, featuring large core diameter (up to 200 μm) and numerical aperture (0.17) to maximize the collection efficiency of diffused light. We demonstrate the suitability of bioresorbable fibers for time‐domain diffuse optical spectroscopy firstly checking the intrinsic performances of the setup by acquiring the instrument response function. We then validate on phantoms the use of bioresorbable fibers by applying the MEDPHOT protocol to assess the performance of the system in measuring optical properties (namely, absorption and scattering coefficients) of homogeneous media. Further, we show an ex‐vivo validation on a chicken breast by measuring the absorption and scattering spectra in the 500–1100 nm range using interstitially inserted bioresorbable fibers. This work represents a step toward a new way to look inside the body using optical fibers that can be implanted in patients. These fibers could be useful either for diagnostic (e. g. for monitoring the evolution after surgical interventions) or treatment (e. g. photodynamic therapy) purposes. Picture: Microscopy image of the 100 μm core bioresorbable fiber.
Levosimendan Increases Diastolic Coronary Flow in Isolated Guinea-Pig Heart by Opening ATP-Sensitive Potassium Channels

Levosimendan, a novel calcium sensitizer developed for the treatment of acute heart failure, is an inodilator that increases coronary flow. Because it was recently shown that levosimendan stimulates potassium current through KATP channels in isolated rat arterial cells, our aim was to assess whether the levosimendan-induced increase in coronary flow is due to the opening of the KATP channels in coronary smooth muscle. The effect of levosimendan on the diastolic coronary flow velocity (DCFV) was measured in the Langendorff perfused spontaneously beating guinea-pig heart in the absence and presence of glibenclamide. Pinacidil was used as a reference compound, and the protein kinase C inhibitor bisindolylmaleimide was used to study the dilatory effect of levosimendan when the KATP channels in smooth muscle are not inhibited by PKC-dependent phosphorylation. Levosimendan (0.01–1 &mgr;M) increased DCFV concentration-dependently and was noncompetitively antagonized by 0.1 &mgr;M glibenclamide, whereas pinacidil was inhibited competitively by glibenclamide. In the presence of glibenclamide the positive inotropic and chronotropic effects of levosimendan were unaltered. The effect of bisindolylmaleimide and levosimendan on DCFV was additive. The results indicate that levosimendan induced coronary vasodilation through the opening of the KATP channels. Levosimendan and pinacidil probably have different binding sites on the KATP channels. The additive effect of bisindolylmaleimide and levosimendan on the increase of DCFV suggests that the latter binds to the unphosphorylated form of the channel.
Best practices in diagnostic immunohistochemistry: myoepithelial markers in breast pathology.

CONTEXT Numerous immunohistochemical stains have been shown to exhibit exclusive or preferential positivity in breast myoepithelial cells relative to their luminal/epithelial counterparts. These myoepithelial markers provide invaluable assistance in accurately classifying breast proliferations, especially in core biopsies. Although numerous myoepithelial markers are available, they differ in their sensitivity, specificity, and ease of interpretation, which may be attributed, to a large extent, to the variable immunoreactivity of these markers in stromal cells including myofibroblasts, vessels, luminal/epithelial cells, and tumor cells. OBJECTIVE To review commonly used myoepithelial markers in breast pathology and a selection of diagnostic scenarios where they may be useful. DATA SOURCES The information outlined in this review article is based on our experiences with routine cases and a review of English-language articles published between 1987 and 2008. CONCLUSIONS To demonstrate the presence or absence of myoepithelial cells, a panel-based approach of 2 or more markers is recommended. Markers that most effectively combine sensitivity, specificity, and ease of interpretation include smooth muscle myosin heavy chains, calponin, p75, p63, P-cadherin, basal cytokeratins, maspin, and CD10. These markers, however, display varying cross-reactivity patterns and variably reduced expression in the myoepithelial cells bordering in situ carcinomas. The choice of a myoepithelial marker should be dependent on a combination of factors, including published evidence on its diagnostic utility, its availability, performance characteristics that have been achieved in a given laboratory, and the specific diagnostic scenario. When its use is deemed necessary, immunohistochemistry for myoepithelial cells in breast pathology is most effective when conceptualized as supplemental, rather than central to routine morphologic interpretation.