Miracle-dz/UniFAR-FTUs huggingface dataset:
CTLs Target Th Cells That Acquire Bystander MHC Class I-Peptide Complex from APCs

CTLs can acquire MHC class I-peptide complexes from their target cells, whereas CD4+ T cells obtain MHC class II-peptide complexes from APCs in a TCR-specific manner. As a consequence, Ag-specific CTL can kill each other (fratricide) or CD4+ T cells become APCs themselves. The purpose of the acquisition is not fully understood and may be either inhibition or prolongation of an immunological response. In this study, we demonstrate that human CD4+ Th cells are able to capture membrane fragments from APC during the process of immunological synapse formation. The fragments contain not only MHC class II-peptide complexes but also MHC class I-peptide complexes, rendering these cells susceptible to CTL killing in an Ag-specific manner. The control of CD4+ Th cells by Ag-specific CTL, therefore, maybe another mechanism to regulate CD4+ T cell expansion in normal immune responses or cause immunopathoglogy during the course of viral infections such as HIV.
The Paf1 Complex Represses ARG1 Transcription in Saccharomyces cerevisiae by Promoting Histone Modifications

ABSTRACT The conserved multifunctional Paf1 complex is important for the proper transcription of numerous genes, and yet the exact mechanisms by which it controls gene expression remain unclear. While previous studies indicate that the Paf1 complex is a positive regulator of transcription, the repression of many genes also requires the Paf1 complex. In this study we used ARG1 as a model gene to study transcriptional repression by the Paf1 complex in Saccharomyces cerevisiae. We found that several members of the Paf1 complex contribute to ARG1 repression and that the complex localizes to the ARG1 promoter and coding region in repressing conditions, which is consistent with a direct repressive function. Furthermore, Paf1 complex-dependent histone modifications are enriched at the ARG1 locus in repressing conditions, and histone H3 lysine 4 methylation contributes to ARG1 repression. Consistent with previous reports, histone H2B monoubiquitylation, the mark upstream of histone H3 lysine 4 methylation, is also important for ARG1 repression. To begin to identify the mechanistic basis for Paf1 complex-mediated repression of ARG1, we focused on the Rtf1 subunit of the complex. Through an analysis of RTF1 mutations that abrogate known Rtf1 activities, we found that Rtf1 mediates ARG1 repression primarily by facilitating histone modifications. Other members of the Paf1 complex, such as Paf1, appear to repress ARG1 through additional mechanisms. Together, our results suggest that Rtf1-dependent histone H2B ubiquitylation and H3 K4 methylation repress ARG1 expression and that histone modifications normally associated with active transcription can occur at repressed loci and contribute to transcriptional repression.
Molecular Identification of a Putative Human Hyaluronan Synthase*

To identify the putative mammalian hyaluronan synthase, we cloned a human cDNA that is related to the Streptococcus hyaluronan synthase (HasA) and the Xenopus developmental protein DG42 which has been shown to have chitin synthase activity. The cDNA, for which we propose the name Has2, encodes a novel protein with a predicted molecular mass of 63.6 kDa. Has2 shows 55% amino acid identity with Xenopus DG42 and 52% identity with the mouse HAS protein, another putative hyaluronan synthase recently reported by Itano and Kimata (Itano, N., and Kimata, K. (1996) J. Biol. Chem. 271, 9875-9878). The deduced primary structure revealed the presence of several hydrophobic stretches which can form multiple transmembrane domains. It also demonstrated the complete conservation of amino acid residues that are known to be critical for N-acetylglucosaminyltransferase activity of yeast chitin synthase. When the Has2 cDNA was transfected into human 293 and Chinese hamster ovary cells, the production of hyaluronan in the transfected cells increased up to 34- and 9-fold, respectively. Strong expression of Has2 mRNA was observed in exponentially proliferating human IMR-90 fibroblasts but not in growth-arrested IMR-90 cells. These results suggest that the Has2 protein is a crucial component of the human hyaluronan synthase system.
Pattern of irritable bowel syndrome and its impact on quality of life in primary health care center attendees, Suez governorate, Egypt

Introduction Irritable bowel syndrome (IBS) is one of the most common disorders diagnosed by gastroenterologists and a common cause of general practice visits. Although this disease is not life threatening, patients with IBS seem to be seriously affected in their everyday life. The study was designed to explore the pattern of IBS in clinical practice and the impact on the quality of life. Methods This is a case control descriptive study. 117 individuals were included in this study. Rome II criteria were used for the diagnosis of IBS. Impact of IBS on patient's quality of life was determined by irritable bowel syndrome quality of life (IBS-QOL) questionnaire. Results Prevalence of IBS among the study sample was 34.2%. 10% were IBS-Diarrhea, 37.5% were IBS-Constipation and 52.5% were alternators. There is statistical insignificant relationship between IBS (+) and age while it was a significant relation regarding gender (more common among women 80%). There is statistical significance relationship between IBS (+) on one hand and marital status and occupational status on the other hand. Patients with IBS had statistically significant lower scores for all IBS- QOL domains compared with the control group. Conclusion IBS is a prevalent disorder that affects females more than males and it has significant impacts on work, lifestyle and social well-being.
Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis

Of the over 200 identified mammalian microRNAs (miRNAs), only a few have known biological activity. To gain a better understanding of the role that miRNAs play in specific cellular pathways, we utilized antisense molecules to inhibit miRNA activity. We used miRNA inhibitors targeting miR-23, 21, 15a, 16 and 19a to test efficacy of antisense molecules in reducing miRNA activity on reporter genes bearing miRNA-binding sites. The miRNA inhibitors de-repressed reporter gene activity when a miRNA-binding site was cloned into its 3′-untranslated region. We employed a library of miRNA inhibitors to screen for miRNA involved in cell growth and apoptosis. In HeLa cells, we found that inhibition of miR-95, 124, 125, 133, 134, 144, 150, 152, 187, 190, 191, 192, 193, 204, 211, 218, 220, 296 and 299 caused a decrease in cell growth and that inhibition of miR-21 and miR-24 had a profound increase in cell growth. On the other hand, inhibition of miR-7, 19a, 23, 24, 134, 140, 150, 192 and 193 down-regulated cell growth, and miR-107, 132, 155, 181, 191, 194, 203, 215 and 301 increased cell growth in lung carcinoma cells, A549. We also identified miRNA that when inhibited increased the level of apoptosis (miR-1d, 7, 148, 204, 210, 216 and 296) and one miRNA that decreased apoptosis (miR-214) in HeLa cells. From these screens, we conclude that miRNA-mediated regulation has a complexity of cellular outcomes and that miRNAs can be mediators of regulation of cell growth and apoptosis pathways.
Recalling semantic information about personally known faces and voices

Previous research that investigated whether biographical information about familiar people is harder to retrieve from voices than from faces produced contrasting results. However, studies that used a strict control of the content of spoken extracts reported that semantic information about familiar people is easier to retrieve when recognising a face than when recognising a voice. In all previous studies faces and voices of famous people were used as stimuli. In the present study, personally familiar people's voices and faces (standard faces and blurred faces) were used. Presenting such people (i.e., participants’ teachers) allowed controlling still more strictly the content of the spoken extracts since it was possible to ask all the target persons to speak the same words. In addition, it was previously stressed that we encounter famous people's faces in the media more frequently than we hear their voice. This methodological difficulty was presumably reduced when teachers’ faces were presented. Present results showed a significant decrease in retrieval of biographical information from familiar voices relative to blurred faces even though the level of overall recognition was similar for blurred faces and voices. The role of the relative distinctiveness of voices and faces is discussed and further investigation is proposed.
TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase*

Background: TANK has been shown to promote deubiquitination of TRAFs, but the mechanism involved is unclear. Results: TANK associates with MCPIP1 and USP10, thereby diminishing TRAF6 ubiquitination, which inhibits NF-κB activation by genotoxic stress and IL-1R/TLR activation. Conclusion: The deubiquitinating activity of TANK is achieved by its association with USP10. Significance: Modulating TANK may enhance cancer cell sensitivity to chemotherapy. DNA damage-induced NF-κB activation plays a critical role in regulating cellular response to genotoxic stress. However, the molecular mechanisms controlling the magnitude and duration of this genotoxic NF-κB signaling cascade are poorly understood. We recently demonstrated that genotoxic NF-κB activation is regulated by reversible ubiquitination of several essential mediators involved in this signaling pathway. Here we show that TRAF family member-associated NF-κB activator (TANK) negatively regulates NF-κB activation by DNA damage via inhibiting ubiquitination of TRAF6. Despite the lack of a deubiquitination enzyme domain, TANK has been shown to negatively regulate the ubiquitination of TRAF proteins. We found TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10, which was essential for the USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-κB activation upon DNA damage. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of TANK in human cells significantly enhanced NF-κB activation by genotoxic treatment, resulting in enhanced cell survival and increased inflammatory cytokine production. Furthermore, we found that the TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1β or LPS. In accordance, depletion of USP10 enhanced NF-κB activation induced by IL-1β or LPS. Collectively, our data demonstrate that TANK serves as an important negative regulator of NF-κB signaling cascades induced by genotoxic stress and IL-1R/Toll-like receptor stimulation in a manner dependent on MCPIP1/USP10-mediated TRAF6 deubiquitination.
Country of birth, socioeconomic position, and healthcare expenditure: a multilevel analysis of Malmö, Sweden

Study objective: The principle of equity aims to guarantee allocation of healthcare resources on the basis of need. Therefore, people with a low income and persons living alone are expected to have higher healthcare expenditures. Besides these individual characteristics healthcare expenditure may be influenced by country of birth. This study therefore aimed to investigate the role of country of birth in explaining individual healthcare expenditure. Design: Multilevel regression model based on individuals (first level) and their country of birth (second level). Setting: The city of Malmö, Sweden. Participants: All the 52 419 men aged 40–80 years from 130 different countries of birth, who were living in Malmö, Sweden, during 1999. Main results: At the individual level, persons with a low income and persons living alone showed a higher healthcare expenditure, with regression coefficients (and 95% confidence intervals) being 0.358 (0.325 to 0.392) and 0.197 (0.165 to 0.230), respectively. Country of birth explained a considerable part (18% and 13%) of the individual differences in the probability of having a low income and living alone, respectively. However, this figure was only 3% for having some health expenditure, and barely 0.7% with regard to costs in the 74% of the population with some health expenditure. Conclusions: Malmö is a socioeconomically segregated city, in which the country of birth seems to play only a minor part in explaining individual differences in total healthcare expenditure. These differences seem instead to be determined by individual low income and living alone.
Features of Magnetic Field Fluctuations in the Ionosphere at Swarm altitude

The magnetosphere-ionosphere system is recognized as a complex and active element affected by space weather and as a region where important scientific questions related to space weather impacts need to be answered. In this framework, there is a high priority on the understanding of how local, regional, and global-scale phenomena couple to produce observed responses across various scales. Turbulence provides one pathway by which energy cascades across scales from large to small ones where energy can be dissipated in the form of heating. The Swarm mission, that is a true multi-point and multi-purpose constellation, represents a unique opportunity to address some of these scientific questions. In detail, it gives us a chance of investigating the nature and the scaling features of magnetic field fluctuations for different geomagnetic activity levels, and unveiling the role played by turbulence of ionospheric plasma medium on the magnetic field fluctuations . Recently, using Swarm magnetic field data at high-latitude in the Northern Hemisphere, the local scaling indices of the 1st and 2nd order structure functions of the magnetic field fluctuations have been evaluated, showing their capability both to give new insights about the ionosphere-magnetosphere coupling and to provide information on the ionospheric turbulence. Here, we improve and extend the analysis by investigating the scaling features of the geomagnetic field fluctuations of external origin, recorded by Swarm A satellite during a period of 2 years (April 2014–March 2016). Maps of the local Hurst exponent values, which allow us to study scaling properties of the geomagnetic field’s spatial fluctuations are shown, both at high-latitudes (in the Northern and Southern Hemisphere) and at low- and mid-latitudes (  60°) according to two different geomagnetic activity conditions. The aim is to capture the essential features of the spatial fluctuations of the geomagnetic field and understand their origin s .
Statistical dialect classification based on mean phonetic features

Describes work done on a text-dependent method for automatic utterance classification and dialect model selection using mean cepstral and duration features on a per-phoneme basis. From transcribed dialect data, we build a linear discriminant to separate the dialects in feature space. This method is potentially much faster than our previous selection algorithm. We have been able to achieve error rates of 8% for distinguishing Northern US speakers from Southern US speakers, and average error rates of 13% on a variety of finer pairwise dialect discriminations. We also present a description of the training and test corpora collected for this work.
Nonalcoholic steatohepatitis in morbid obese patients: coffee consumption vs. disease severity.

INTRODUCTION Obesity correlates with nonalcoholic fatty liver disease (NAFLD) and occurs in 90 to 100% of severely obese individuals (body mass index [BMI] > 35 kg/m2). Coffee consumption (CC) has been associated with reduced progression of fibrosis in both hepatitis C infection and NAFLD; however, this topic is still under discussion when this liver disease affects severely obese individuals. OBJECTIVE To assess the association between CC, insulin resistance (IR) and histological NAFLD morbid obese patients. MATERIAL AND METHODS Cross-sectional study, including obese individuals undergoing bariatric surgery, liver biopsy and histological diagnosis between September 2013 and August 2014. The patients were classified into 3 groups according to their weekly CC: 0- 239.9 mL; 240-2099.9 mL and ≥ 2100 mL. RESULTS A total of 112 obese individuals were included (BMI = 41.9 ± 4.3 kg/m2), with a mean age of 34.7 ± 7.4 years; 68.6% were women. CC was reported by 72.3% of patients. There were no statistical significant differences between groups regarding the presence of IR (84.8% vs. 74.2% vs. 75.9%; p = 0.536). Progressively higher percentages of individuals with normal liver histology were observed (14.7% vs. 21.9% vs. 24.3%). NASH (65.7% vs. 70.3% vs. 57.5%) were observed among those who consumed greater coffee volumes (p = 0.812). In conclusion, obese individuals with elevated CC exhibited lower frequencies of NASH, although with no statistical significance in this sample.
A Novel Fuzzy-Sliding and Fuzzy-Integral-Sliding Controller for the Twin-Rotor Multi-Input–Multi-Output System

In this paper, a novel fuzzy-sliding and fuzzy-integral-sliding controller (FSFISC) is designed to position the yaw and pitch angles of a twin-rotor multi-input-multi-output system (TRMS). With the coupling effects, which are considered as the uncertainties, the highly coupled nonlinear TRMS is pseudodecomposed into a horizontal subsystem and a vertical subsystem (VS). The proposed FSFISC consists of a fuzzy-sliding controller and an FISC for the horizontal and the VSs, respectively. The reaching conditions and the stability of the TRMS with the proposed controller are guaranteed. Simulation results are included to indicate that TRMS with the presented FSFISC can greatly alleviate the chattering effect and remain robust to the external disturbances. In addition, the performance comparisons with the proportional-integral-differential (PID) approach using a modified real-value-type genetic algorithm are provided to show that the FSFISC has better performance in the aspects of error and control indexes.
Recombinant activated clotting factor VII (rFVIIa) in the treatment of surgical and spontaneous bleeding episodes in hemophilic patients

Inhibitors against replacement clotting factors occur in approximately 30%–40% of patients with hemophilia A and 1.5%–3% of patients with hemophilia B. In this group of patients, bleeding events are best treated with bypassing agents. Recombinant activated factor VII (rFVIIa) has become the first-line agent in treating surgical and non-surgical bleeding in many centres with efficacy at standard 90 μg/kg doses approaching 90%. The greater efficacy is associated with early initiation of treatment, as well as, possibly larger doses of rFVIIa. A higher concentration appears to be essential in initiating an adequate thrombin burst, which results in a stable clot. Higher dosage regimens, home therapy and continuous infusion regimens are continuously evolving as we strive to define optimal dosing strategies in hemophilia patients. rFVIIa has been a remarkably safe agent for hemophiliacs but with high dosages being advocated and older patients being given such doses outside a trial setting, thromboembolic events remain a concern.
Multiview Distributed Video Coding with encoder driven fusion

In this paper, a scheme based on multiview and Distributed Video Coding (DVC) is introduced. More specifically, a new fusion technique between temporal, homography and Disparity Compensation View Prediction (DCVP) side informations is introduced. For this purpose, a binary mask is computed at the encoder based on knowledge of the original video. This mask is compressed and then transmitted to the decoder. The latter merges the different side informations with the help of the reconstructed binary mask. The simulation results show that the fusion improves the rate-distortion performance over monoview DVC by a maximum gap of around 1.0 dB.
Evaluation of the Efficiency of Respiratory Protective Equipment based on the Biological Monitoring of Styrene in Fibreglass Reinforced Plastics Industries

Evaluation of the Efficiency of Respiratory Protective Equipment based on the Biological Monitoring of Styrene in Fibreglass Rein‐forced Plastics Industries: Shoji Nakayama, et al. Department of Public Health, Okayama University Graduate School of Medicine and Dentistry—The purpose of the present study was to determine the efficiency of respiratory protective equipment in a fibreglass reinforced plastic factory by comparing results of environmental and biological monitoring of exposure to styrene. Five factories including 39 workers were investigated. Three types of respiratory protective equipment were tested: one was a half‐mask air‐purifying respirator equipped with a cartridge for organic solvents, another was a disposable gauze respirator impregnated with charcoal filter, and the third was a dust‐proof respirator. The frequency of cartridge exchange of a half‐mask respirator was twice a day only at one factory, and that was less than once a month at other factories. The site concentrations exceeded 20 ppm at 10 of the 82 sampling points (12.2%), and 22 of the 39 workers’ (56.4%) personal exposure exceeded 20 ppm which is the current occupational exposure limit recommended by the Japan Society for Occupational Health. The efficiency of disposable gauze respirators and dust‐proof respirators was low or rather zero. The average efficiency of half‐mask respirators in which cartridges were exchanged twice a day and once a month was 83.6% and 46.6%, respectively. There was a significant disparity in the efficiency of the respirator depending on the frequency of cartridge exchange (p <0.05). Overall this study showed that even though a half‐mask respirator is used and its cartridge is exchanged every half a day, workers exposed to a styrene concentration at or over 122 ppm are expected to inhale more than 20 ppm of styrene.
Pharmacokinetic-Pharmacodynamic Modeling of Biomarker Response and Tumor Growth Inhibition to an Orally Available Heat Shock Protein 90 Inhibitor in a Human Tumor Xenograft Mouse Model

PF04942847 [2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide] was identified as an orally available, ATP-competitive, small-molecule inhibitor of heat shock protein 90 (HSP90). The objectives of the present study were: 1) to characterize the pharmacokinetic-pharmacodynamic relationship of the plasma concentrations of PF04942847 to the inhibition of HSP90-dependent protein kinase, AKT, as a biomarker and 2) to characterize the relationship of AKT degradation to tumor growth inhibition as a pharmacological response (antitumor efficacy). Athymic mice implanted with MDA-MB-231 human breast cancer cells were treated with PF04942847 once daily at doses selected to encompass ED50 values. Plasma concentrations of PF04942847 were adequately described by a two-compartment pharmacokinetic model. A time delay (hysteresis) was observed between the plasma concentrations of PF04942847 and AKT degradation; therefore, a link model was used to account for the hysteresis. The model reasonably fit the time courses of AKT degradation with the estimated EC50 of 18 ng/ml. For tumor growth inhibition, the signal transduction model reasonably fit the inhibition of individual tumor growth curves with the estimated EC50 of 7.3 ng/ml. Thus, the EC50 for AKT degradation approximately corresponded to the EC50 to EC80 for tumor growth inhibition, suggesting that 50% AKT degradation was required for significant antitumor efficacy (50–80%). The consistent relationship between AKT degradation and antitumor efficacy was also demonstrated by applying an integrated signal transduction model for linking AKT degradation to tumor growth inhibition. The present results will be helpful in determining the appropriate dosing regimen and guiding dose escalation to achieve efficacious systemic exposure in the clinic.