Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of GnRH-II on the ESC proliferation, apoptosis and VEGF secretion in patients with endometriosis in vitro.

OBJECTIVE To study the effect of GnRH-II on the cell proliferation, apoptosis and secreting vascular endothelial growth factor (VEGF) of ectopic, eutopic and normal endometrial stromal cells (ESC) from patients with or without endometriosis (EMs) in vitro. METHODS The ectopic, eutopic and normal ESC were isolated, cultured and identified, then added 0 M, 10(-10) M, 10(-8) M, 10(-6) M GnRH-II. The growth and proliferation of three ESC were measured by MTT assay; the cell apoptosis were detected with the method of Hoechst staining and Flow Cytometry test; ELISA was used to measure the VEGF concentration change by three ESC secretion. RESULTS GnRH-II inhibited the proliferation of ectopic, eutopic ESC from patients with endometriosis and normal ESC from control patients, in a dose- and time-dependent manner (P<0.05); GnRH-II increased the apoptotic rate of three ESC in a dose-dependent manner (P<0.05); The concentration of VEGF in three ESC was significantly decreased after the treatment of GnRH-II, in a dose-dependent manner (P<0.01); And these above effects were the strongest on the ectopic than on the eutopic or normal, there were statistical significance (P<0.05); and three was no significantly difference between the eutopic and normal (P>0.05). CONCLUSIONS GnRH-II significantly inhibited the cell proliferation, induced cell apoptosis and decreased the VEGF secreting of ectopic, eutopic and normal ESC in EMs in vitro, and these effects were the strongest on ectopic ESC, which suggested that GnRH-II may become a new effective treatment for endometriosis.
Conductivity and dielectric characterization of polymer nanocomposites

Abstract: Dielectric relaxations are present in both polymers and polymer matrix composites. In polymer nanocomposites recorded relaxation phenomena include contributions from both the polymeric matrix and the presence of nanofiller. Dielectric data could provide valuable information regarding polymer/nanofiller interactions, distribution of nanoinclusions and nanocomposite’s morphology, improving our knowledge upon their structure–properties relationship. The electrical performance of nanocomposites can be adjusted by selecting the appropriate type and amount of nanofiller. Transition from insulating to conductive behaviour can be studied in terms of the scaling law of percolation theory. Finally, the influence of temperature and frequency on conductivity data can be exploited in revealing the occurring charge transport mechanisms.
Laminin isoforms of lymph nodes and predominant role of α5‐laminin(s) in adhesion and migration of blood lymphocytes

During extravasation and within lymph nodes (LNs), blood lymphocytes interact with laminins (Lms), major components of vascular basement membranes (BMs) and of reticular fibers (RFs), a fibrillar extracellular matrix. However, the identity and role of these laminin isoform(s) are poorly known. By using confocal microscopy examination of human LNs, we show that BMs of high endothelial venules (HEVs) express laminin α3, α4, α5, β1, β2, and γ1 chains and that the same chains, in addition to α2, are found in RFs. In functional studies with laminin isoforms covering all Lm α chains, α5‐laminin (Lm‐511) was the most adhesion‐ and migration‐promoting isoform for human blood lymphocytes, followed by α3‐ (Lm‐332) and α4‐ (Lm‐411) laminins, and the lymphocytes used the α6β1 integrin as the primary receptor for the α5‐laminin. Moreover, Lm‐511 strongly costimulated T cell proliferation, and blood lymphocytes were able to secrete α4‐ and α5‐laminins following stimulation. The LN cell number in laminin α4‐deficient mice compared with wild‐type did not differ significantly. This study demonstrates a predominant role for α5‐laminin(s) in blood lymphocyte biology and identifies LN laminins and their integrin receptors in blood lymphocytes.
Model Selection and Stability in k-means Clustering

Clustering Stability methods are a family of widely used model selection techniques applied in data clustering. Their unifying theme is that an appropriate model should result in a clustering which is robust with respect to various kinds of perturbations. Despite their relative success, not much is known theoretically on why or when do they work, or even what kind of assumptions they make in choosing an ’appropriate’ model. Moreover, recent theoretical work has shown that they might ’break down’ for large enough samples. In this paper, we focus on the behavior of clustering stability using k-means clustering. Our main technical result is an exact characterization of the distribution to which suitably scaled measures of instability converge, based on a sample drawn from any distribution in R satisfying mild regularity conditions. From this, we can show that clustering stability does not ’break down’ even for arbitrarily large samples, in the k-means framework that we study. Moreover, it allows us to identify the factors which influence the behavior of clustering stability for any sample size. This leads to some interesting preliminary observations about what kind of assumptions are made when using these methods. While often reasonable, these assumptions might also lead to unexpected consequences.
The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway

Autophagy and the Cvt pathway are examples of nonclassical vesicular transport from the cytoplasm to the vacuole via double-membrane vesicles. Apg8/Aut7, which plays an important role in the formation of such vesicles, tends to bind to membranes in spite of its hydrophilic nature. We show here that the nature of the association of Apg8 with membranes changes depending on a series of modifications of the protein itself. First, the carboxy-terminal Arg residue of newly synthesized Apg8 is removed by Apg4/Aut2, a novel cysteine protease, and a Gly residue becomes the carboxy-terminal residue of the protein that is now designated Apg8FG. Subsequently, Apg8FG forms a conjugate with an unidentified molecule “X” and thereby binds tightly to membranes. This modification requires the carboxy-terminal Gly residue of Apg8FG and Apg7, a ubiquitin E1-like enzyme. Finally, the adduct Apg8FG-X is reversed to soluble or loosely membrane-bound Apg8FG by cleavage by Apg4. The mode of action of Apg4, which cleaves both newly synthesized Apg8 and modified Apg8FG, resembles that of deubiquitinating enzymes. A reaction similar to ubiquitination is probably involved in the second modification. The reversible modification of Apg8 appears to be coupled to the membrane dynamics of autophagy and the Cvt pathway.
Anthropogenic pressures and their impacts on the hyporheic zone: ecological implications for gravel spawning fish

To study the structures and functions ofthe hyporheic zone in running waters under anthropogenic pressures and to detect key processes in the habitats of gravel spawning fish, an extensive study was carried out at the River Lahn (Germany). In this article we present results ofthe River Lahn investigation as part of a wider study on fish spawning conditions at the River Diemel and the River Ulster (study sites detailed in Table l). The vertical hydraulic exchange of water and water constituents were identified as key processes in the functioning of the hyporheic zones. These processes were influenced by abiotic factors ( discharge, sediment transport, emissions o f oxygenconsuming organic material deriving from point and diffuse sources) as well as by biotic factors (periphyton biomass dynamics, microbial nutrient turnover, bioturbation). The latter appears to be underestimated in river ecology, and biotic control of hyporheic functions may be much more important than generally assumed.
Multistable Decision Switches for Flexible Control of Epigenetic Differentiation

It is now recognized that molecular circuits with positive feedback can induce two different gene expression states (bistability) under the very same cellular conditions. Whether, and how, cells make use of the coexistence of a larger number of stable states (multistability) is however largely unknown. Here, we first examine how autoregulation, a common attribute of genetic master regulators, facilitates multistability in two-component circuits. A systematic exploration of these modules' parameter space reveals two classes of molecular switches, involving transitions in bistable (progression switches) or multistable (decision switches) regimes. We demonstrate the potential of decision switches for multifaceted stimulus processing, including strength, duration, and flexible discrimination. These tasks enhance response specificity, help to store short-term memories of recent signaling events, stabilize transient gene expression, and enable stochastic fate commitment. The relevance of these circuits is further supported by biological data, because we find them in numerous developmental scenarios. Indeed, many of the presented information-processing features of decision switches could ultimately demonstrate a more flexible control of epigenetic differentiation.
Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection

Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections.
A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

Background Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers. Objective This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects. Methods Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored. Results The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects. Limitations The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%. Conclusion MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD. Trial Registration ClinicalTrials.gov NCT00316602
Regional Hemodynamic Effects of a Digitalis Glycoside in the Conscious Dog with and without Experimental Heart Failure

The effects of intravenous ouabain (G-strophanthin), 20 μg/kg, on the superior mesenteric, renal, and external iliac beds were studied over a 30-minute period in eight normal conscious dogs before, and in five of them after, cholinergic blockade and in six conscious dogs with heart failure produced by tricuspid avulsion and progressive pulmonary stenosis. Blood flows were measured with Doppler ultrasonic and electromagnetic flowmeters. In normal dogs, prior to cholinergic blockade, ouabain caused early increases in mesenteric, renal, and external iliac resistances but later, between 15 and 30 minutes, mesenteric resistance decreased below the control level while renal and external iliac resistances remained elevated. After cholinergic blockade, the ouabain-induced alterations in renal and iliac resistance were unaltered, but the later decline in resistance in the mesenteric bed was reversed, resulting in sustained constriction. The late decline in mesenteric resistance also was not observed in the conscious animal after the injection of ouabain, 5 μg/kg, directly into the mesenteric artery or in the majority of dogs given ouabain intravenously after having been anesthetized with pentobarbital sodium. In the conscious dogs with heart failure, ouabain resulted in increased renal and iliac resistances initially, and in vasodilatation later while mesenteric resistance fell initially and remained below control for the entire 30 minutes. Thus, in the normal conscious dog, ouabain causes vasoconstriction in the regional vascular beds, apparently by its direct vascular action, and, in addition, a cholinergically mediated vasodilatation in the mesenteric bed. In the conscious dog with heart failure, ouabain increases blood flow to all beds, reducing the compensatory vasoconstriction of the low output state.
Comparison of Visual Quality between Aspheric and Spherical IOLs

Purpose To determine if aspheric intraocular lens (IOL) implantation produces the same degree of postoperative ocular aberration and contrast sensitivity as spherical IOL implantation. Methods In this randomized prospective comparative study, 60 eyes of 30 cataract surgery patients were randomly assigned to receive a spherical IOL (Rayner 620H) in one eye and an aspheric IOL (Rayner 920H) in the contralateral eye. All patients were examined at 1 month postoperatively. Primary outcomes of contrast sensitivity and ocular wavefront higher order aberrations (HOAs) were assessed. Results Aspheric IOLs (median total HOAs 0.26 root mean square [RMS]; range 0.13-0.82 RMS) produced significantly lower total HOAs than spherical IOLs (median total HOAs 0.34 RMS; range 0.18-1.08 RMS; p<0.05). Contrast sensitivity was significantly better with aspheric IOLs (median contrast sensitivity 1.8 log units; range 1.35-1.8 log units) than with spherical IOLs (median contrast sensitivity 1.65 log units; range 1.35-1.8 log units; p<0.05). Conclusions When compared with a structurally (platform and material) similar spherical IOL (Rayner 620H), aspheric IOLs (Rayner 920H) appear to significantly reduce HOAs and yield better levels of contrast sensitivity under photopic conditions.
Genetic sequence variants and the development of secondary primary cancers in patients with head and neck cancers

Secondary primary cancers (SPCs), a major cause of morbidity and mortality in head and neck cancers (HNCs), are commonly associated with field cancerization. We comprehensively evaluated 23 germline sequence variants (from published literature) in 17 genes from 7 biological pathways associated with the HNC survival. Because cancer prognosis correlates with disease aggressiveness, the factors that determine aggressive disease may influence field cancerization process to favor SPC development. We thus hypothesized that the same sequence variants associated with HNC survival can also be associated with SPC.
Linear Motif Atlas for Phosphorylation-Dependent Signaling

Created with both in vitro and in vivo data, NetPhorest is an atlas of consensus sequence motifs for 179 kinases and 104 phosphorylation-dependent binding domains and reveals new insight into phosphorylation-dependent signaling. An Atlas of Phosphorylation NetPhorest is a community resource that uses phylogenetic trees to organize data from both in vivo and in vitro experiments to derive sequence specificities for 179 kinases and 104 domains (SH2, PTB, BRCT, WW, and 14–3–3) that bind to phosphorylated sites. The resulting atlas of linear motifs revealed that oncogenic kinases tend to be less specific in the target sequences they phosphorylate than their non-oncogenic counterparts, that autophosphorylation sites tend to be more variable than other substrates of a given kinase, and that coupling interaction domains with kinase domains may allow phosphorylation site specificity to be low while still maintaining substrate specificity. Systematic and quantitative analysis of protein phosphorylation is revealing dynamic regulatory networks underlying cellular responses to environmental cues. However, matching these sites to the kinases that phosphorylate them and the phosphorylation-dependent binding domains that may subsequently bind to them remains a challenge. NetPhorest is an atlas of consensus sequence motifs that covers 179 kinases and 104 phosphorylation-dependent binding domains [Src homology 2 (SH2), phosphotyrosine binding (PTB), BRCA1 C-terminal (BRCT), WW, and 14–3–3]. The atlas reveals new aspects of signaling systems, including the observation that tyrosine kinases mutated in cancer have lower specificity than their non-oncogenic relatives. The resource is maintained by an automated pipeline, which uses phylogenetic trees to structure the currently available in vivo and in vitro data to derive probabilistic sequence models of linear motifs. The atlas is available as a community resource (http://netphorest.info).
Association of CFTR gene mutation with bronchial asthma

Mutation on both the copies of cystic fibrosis transmembrane conductance regulator (CFTR) gene results in cystic fibrosis (CF), which is a recessively transmitted genetic disorder. It is hypothesized that individuals heterozygous for CFTR gene mutation may develop obstructive pulmonary diseases like asthma. There is great heterogeneity in the phenotypic presentation and severity of CF lung disease. This could be due to genetic or environmental factors. Several modifier genes have been identified which may directly or indirectly interact with CFTR pathway and affect the severity of disease. This review article discusses the information related to the association of CFTR gene mutation with asthma. Association between CFTR gene mutation and asthma is still unclear. Report ranges from studies showing positive or protective association to those showing no association. Therefore, studies with sufficiently large sample size and detailed phenotype are required to define the potential contribution of CFTR in the pathogenesis of asthma.
Habitat surveys as a tool to assess the benefits of stream rehabilitation II: macroinvertebrate communities

Many streams in Europe have been physically degraded by human manipulation and habitats have consequently been lost (e.g. M0LLER 1995). In Denmark, cultivation o f farmland during the last century has resulted in extensive straightening and culverting of watercourses and more than 90% of Denmark's 35,000 km of natural streams has been physically modified (IVERSEN et al. 1993). One way to counteract this degradation is to rehabilitate riparian and instream habitats. Consequently, numerous stream restoration projects have been undertaken in Denmark in recent years to improve stream physical conditions and thereby increase the rate of ecosystem recovery (e.g. HANSEN 1996). Hitherto, however, only a few investigations have documented the benefits of stream rehabilitation projects on stream biota (e.g. FRIBERG et al. 1994, 1998). One reason has been the laek of a method to assess habitat improvements able to link the changed physical features to the biota. The aim of the present paper is to investigate if a habitat classification based on physical features in a restored reach of the River Gelsa is reflected in macroinvertebrate species composition within these habitats.
Persistence of High-Dose Oxaliplatin-Induced Neuropathy at Long-Term Follow-Up

Oxaliplatin (L-OHP) has become a standard treatment for advanced colorectal cancer and a valid option for patients in the adjuvant setting. Compared with cisplatin, L-OHP has no renal toxicity, only mild hematological and gastrointestinal toxicity, while neurotoxicity is the limiting toxicity. This side effect has been described as a transient distal dysesthesia, enhanced by exposure to cold, and as a dose-related cumulative mild sensitive neuropathy. We studied two groups of patients (18 and 13) with advanced colorectal cancer, treated with median cumulative doses of L-OHP 862 mg/m2 and 1,033.5 mg/m2. All the patients had been evaluated previously, during treatment, after discontinuation and after a long follow-up of 5 years to verify the incidence and the characteristics of the neuropathy induced by this antineoplastic agent. The clinical and neurophysiological examinations showed an acute and transient neurotoxicity and a cumulative dose-related sensory neuropathy in nearly all the patients. The reversibility of these effects was studied. Five patients continue to manifest symptoms and signs of neurotoxicity after a long follow-up, indicating persistence of this peculiar type of neuropathy.
Combining Clinical and Epidemiologic Features for Early Recognition of SARS

Early recognition and rapid initiation of infection control precautions are currently the most important strategies for controlling severe acute respiratory syndrome (SARS). No rapid diagnostic tests currently exist that can rule out SARS among patients with febrile respiratory illnesses. Clinical features alone cannot with certainty distinguish SARS from other respiratory illnesses rapidly enough to inform early management decisions. A balanced approach to screening that allows early recognition of SARS without unnecessary isolation of patients with other respiratory illnesses will require clinicians not only to look for suggestive clinical features but also to routinely seek epidemiologic clues suggestive of SARS coronavirus exposure. Key epidemiologic risk factors include 1) exposure to settings where SARS activity is suspected or documented, or 2) in the absence of such exposure, epidemiologic linkage to other persons with pneumonia (i.e., pneumonia clusters), or 3) exposure to healthcare settings. When combined with clinical findings, these epidemiologic features provide a possible strategic framework for early recognition of SARS.