Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic Constraint on Plasmablast Growth and Extrinsic Limits of Plasma Cell Survival

B cells recruited into splenic antibody responses grow exponentially, either in extrafollicular foci as plasmablasts, or in follicles where they form germinal centers. Both responses yield plasma cells. Although many splenic plasma cells survive <3 d, some live much longer. This study shows that early plasma cell death relates to a finite capacity of the spleen to sustain plasma cells rather than a life span endowed by the cell's origin or the quality of antibody it produces. Antibody responses were compared where the peak numbers of plasma cells in spleen sections varied between 100 and 5,000 cells/mm2. In each response, plasmablast clones divided some five times, with the peak numbers of plasma cells produced relating directly to the number of B cells recruited into the response. The spleen seems to have the capacity to sustain between 20 and 100 plasma cells/mm2. When this number is exceeded, there is a loss of excess cells. Immunoglobulin variable region gene sequencing, and 5-bromo-2′-deoxyuridine pulse–chase studies indicate that long-lived splenic plasma cells are a mixture of cells derived from the extrafollicular and germinal center responses and cells derived from virgin and memory B cells. Only a proportion has switched immunoglobulin class.
Acute Loss of Intestinal CD4+ T Cells Is Not Predictive of Simian Immunodeficiency Virus Virulence1

The predictive value of acute gut-associated lymphoid tissue (GALT) CD4+ T cell depletion in lentiviral infections was assessed by comparing three animal models illustrative of the outcomes of SIV infection: pathogenic infection (SIVsmm infection of rhesus macaques (Rh)), persistent nonprogressive infection (SIVagm infection of African green monkeys (AGM)), and transient, controlled infection (SIVagm infection of Rh). Massive acute depletion of GALT CD4+ T cells was a common feature of acute SIV infection in all three models. The outcome of this mucosal CD4+ T cell depletion, however, differed substantially between the three models: in SIVsmm-infected Rh, the acute GALT CD4+ T cell depletion was persistent and continued with disease progression; in SIVagm, intestinal CD4+ T cells were partially restored during chronic infection in the context of normal levels of apoptosis and immune activation and absence of damage to the mucosal immunologic barrier; in SIVagm-infected Rh, complete control of viral replication resulted in restoration of the mucosal barrier and immune restoration. Therefore, our data support a revised paradigm wherein severe GALT CD4+ T cell depletion during acute pathogenic HIV and SIV infections of humans and Rh is necessary but neither sufficient nor predictive of disease progression, with levels of immune activation, proliferation and apoptosis being key factors involved in determining progression to AIDS.
Sparten- und Formattrends im deutschen Fernsehen

Im Programmjahr 2009 sahen an einem Durchschnittstag rund sieben von zehn in Deutschland lebenden Personen ab drei Jahren zumindest kurz fern. Im Durchschnitt waren sie dann 293 Minuten vor dem Fernsehgerät im Wohnzimmer oder einem der anderen Fernsehgeräte im Haushalt zu finden. Für die Gesamtbevölkerung in Fernsehhaushalten – also Seher(innen) und Nichtseher(innen) am Durchschnittstag – betrug die Sehdauer statistisch 212 Minuten pro Tag. Hinter dieser Fernsehnutzung stehen eine Vielzahl unterschiedlicher Programme, Sendungen, Einund Umschaltverhaltensweisen, auch zum Beispiel zielgruppenspezifische Segmentationen. Das stärkste Fernsehprogramm – gemessen an Marktanteilen – war im Jahr 2009 das Erste der ARD mit 12,7 Prozent vor dem ZDF und RTL mit jeweils 12,5 Prozent. Sat.1 kam auf 10,4 Prozent, ProSieben auf 6,6 Prozent und VOX lag mit 5,4 Prozent noch über der 5-Prozent-Marke. Die Dritten Programme erreichten gemeinsam einen Jahresmarktanteil von 13,5 Prozent. (2) Im Folgenden steht die Perspektive der genutzten Sparten bzw. der in diesen jeweils besonders stark genutzten Sendungen von insgesamt 20 erfassten Programmen im Mittelpunkt.
MicroRNAs in Myeloid Hematological Malignancies

MicroRNAs are 19-24 nucleotides noncoding RNAs which silence modulate the expression of target genes by binding to the messenger RNAs. Myeloid malignancies include a broad spectrum of acute and chronic disorders originating from from the clonal transformation of a hematopoietic stem cell. Specific genetic abnormalities may define myeloid malignancies, such as translocation t(9;22) that represent the hallmark of chronic myeloid leukemia. Although next-generation sequencing pro-vided new insights in the genetic characterization and pathogenesis of myeloid neoplasms, the molecular mechanisms underlying myeloid neoplasms are lacking in most cases. Recently, several studies have demonstrated that the expression levels of specific miRNAs may vary among patients with myeloid malignancies compared with healthy individuals and partially unveiled how miRNAs participate in the leukemic transformation process. Finally, in vitro experiments and pre-clinical model provided preliminary data of the safety and efficacy of miRNA inhibitory molecules, opening new avenue in the treatment of myeloid hematological malignancies.
Reviewing primary Sjögren's syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This process leads to sicca syndrome, which is the combination of dryness of the eyes, oral cavity, pharynx, larynx and/or vagina. Extraglandular manifestations may also be prevalent in patients with pSS, including cutaneous, musculoskeletal, pulmonary, renal, hematological and neurological involvement. The pathogenesis of pSS is currently not well understood, but increased activation of B cells followed by immune complex formation and autoantibody production are thought to play important roles. pSS is diagnosed using the American-European consensus group (AECG) classification criteria which include subjective symptoms and objective tests such as histopathology and serology. The treatment of pSS warrants an organ based approach, for which local treatment (teardrops, moistures) and systemic therapy (including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDS) and biologicals) can be considered. Biologicals used in the treatment of pSS mainly affect the total numbers of B cells (B cell depletion (Rituximab)) or target proteins required for B cell proliferation and/or activation (e.g. B cell activating factor (BAFF)) resulting in decreased B cell activity. The aim of this review is to provide physicians a general overview concerning the pathogenesis, diagnosis and management of pSS patients.
A synaptic mechanism for network synchrony

Within neural networks, synchronization of activity is dependent upon the synaptic connectivity of embedded microcircuits and the intrinsic membrane properties of their constituent neurons. Synaptic integration, dendritic Ca2+ signaling, and non-linear interactions are crucial cellular attributes that dictate single neuron computation, but their roles promoting synchrony and the generation of network oscillations are not well understood, especially within the context of a defined behavior. In this regard, the lamprey spinal central pattern generator (CPG) stands out as a well-characterized, conserved vertebrate model of a neural network (Smith et al., 2013a), which produces synchronized oscillations in which neural elements from the systems to cellular level that control rhythmic locomotion have been determined. We review the current evidence for the synaptic basis of oscillation generation with a particular emphasis on the linkage between synaptic communication and its cellular coupling to membrane processes that control oscillatory behavior of neurons within the locomotor network. We seek to relate dendritic function found in many vertebrate systems to the accessible lamprey central nervous system in which the relationship between neural network activity and behavior is well understood. This enables us to address how Ca2+ signaling in spinal neuron dendrites orchestrate oscillations that drive network behavior.
MicroRNAs in myeloproliferative neoplasms

The chronic myeloproliferative neoplasms (MPN), including polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), are clonal stem cell disorders characterized by dysregulated haematopoietic stem cell expansion and production of red cells, white cells and platelets alone or in combination. An acquired mutation JAK2V617F can be found in all three disorders and shows many of the phenotypic abnormalities of the diseases in murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18–24 nucleotide single‐stranded non‐protein‐coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. There is growing evidence that miRNAs regulate haematopoiesis in both haematopoietic stem cells and committed progenitor cells. Here, we review the field of miRNA biology and its regulatory roles in normal haematopoiesis with an emphasis on miRNA deregulations in MPNs. Continued research into how miRNAs impact JAK2V617F clonal expansion, differential haematopoiesis among different MPNs, disease progression and leukaemia transformation will lead to a better understanding of the development of these disorders, their clinical manifestations, and their treatment.
Edinburgh Research Explorer Dependencies revisited for improving data quality

Dependency theory is almost as old as relational databases themselves, and has traditionally been used to improve the quality of schema, among other things. Recently there has been renewed interest in dependencies for improving the quality of data. The increasing demand for data quality technology has also motivated revisions of classical dependencies, to capture more inconsistencies in real-life data, and to match, repair and query the inconsistent data. This paper aims to provide an overview of recent advances in revising classical dependencies for improving data quality.
String-level learning of confidence transformation for Chinese handwritten text recognition

Handwritten text recognition systems commonly combine character classification confidence scores and context models for evaluating candidate segmentation-recognition paths, and the classification confidence is usually optimized at character level. On comparing the performance of class-dependent and class-independent confidence transformation (CT), this paper proposes two regularized class-dependent CT methods, and particularly, a string-level confidence learning method under the Minimum Classification Error (MCE) criterion. In experiments of online Chinese handwritten text recognition, the string-level confidence learning method was shown to effectively improve the recognition performance.
Inferences on the Common Mean of Several Log‐Normal Populations: The Generalized Variable Approach

This paper proposes a novel approach for the confidence interval estimation and hypothesis testing of the common mean of several log‐normal populations using the concept of generalized variable. Simulation studies demonstrate that the proposed approach can provide confidence intervals with satisfying coverage probabilities and can perform hypothesis testing with satisfying type‐I error control even at small sample sizes. Overall, it is superior to the large sample approach. The proposed method is illustrated using two examples. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta‐analysis of controlled clinical trials

Context: Exercise is widely perceived to be beneficial for glycemic control and weight loss in patients with type 2 diabetes. However, clinical trials on the effects of exercise in patients with type 2 diabetes have had small sample sizes and conflicting results. Objective: To systematically review and quantify the effect of exercise on glycosylated hemoglobin (HbA(1c)) and body mass in patients with type 2 diabetes. Data sources: Database searches of MEDLINE, EMBASE, Sport Discuss, Health Star, Dissertation Abstracts and the Cochrane Controlled Trials Register for the period up to and including December 2000. Additional data sources included bibliographies of textbooks and articles identified by the database searches. Study selection: We selected studies that evaluated the effects of exercise interventions (duration ≥ = 8 weeks) in adults with type 2 diabetes. Fourteen (11 randomized and three non‐randomized) controlled trials were included. Studies that included drug cointerventions were excluded. Data extraction: Two reviewers independently extracted baseline and post‐intervention means and SDs for the intervention and control groups. The characteristics of the exercise interventions and the methodological quality of the trials were also extracted. Data synthesis: Twelve aerobic training studies [mean (SD), 3.4 (0.9) times/week for 18 (15) weeks] and two resistance training studies [mean (SD), 10 (0.7) exercises, 2.5 (0.7) sets, 13 (0.7) repetitions, 2.5 (0.4) times/week for 15 (10) weeks] were included in the analyses. The weighted mean post‐intervention HbA(1c) was lower in the exercise groups compared with the control groups (7.65% vs 8.31%; weighted mean difference, 0.66%; P < 0.001). The difference in post‐intervention body mass between exercise groups and control groups was not significant (83.02 kg vs 82.48 kg; weighted mean difference, 0.54; P= 0.76). Conclusion: Exercise training reduces HbA(1c) by an amount that should decrease the risk of diabetic complications, but no significantly greater change in body mass was found when exercise groups were compared with control groups.
In vivo induction of heat shock proteins in the substantia nigra following L‐DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state

Increasing evidence suggests a critical role for oxidative and nitrosative stress in the pathogenesis of most important neurodegenerative disorders. Parkinson’s disease (PD) is a neurodegenerative disease characterized by a severe depletion in number of dopaminergic cells of the substantia nigra (SN). Administration of L‐DOPA (LD) is the more effective treatment for patients with PD. However, the vast majority of patients suffer LD‐related complications, which represent the major problem in the clinical management of PD. In the present study, LD administration to rats resulted in a significant dose‐dependent increase in Hsp70 synthesis which was specific for the SN. The amount of 70 kDa protein increased after 6 h treatment reaching the maximal induction after 24–48 h. Induction of Hsp70 in the SN was associated with a significant increase in constitutive Hsc70 and mitochondrial Hsp60 stress proteins, and with increased expression of mitochondrial complex I whereas no significant changes were found in the activity of complex IV. In the same experimental conditions, a significant decrease in reduced glutathione was observed, which was associated with an increased content of oxidized glutathione content as well as nitric oxide (NO) synthase activity, NO metabolites and nitrotyrosine immunoreactivity. Interestingly, Hsp70 induction, iNOS up‐regulation and nitrotyrosine formation have been confirmed also in SN and striatum of rats treated with LD and carbidopa, this latter being an inhibitor of the peripheral DOPA decarboxylase. Our data are in favor of the importance of the heat shock signal pathway as a basic mechanism of defense against neurotoxicity elicited by free radical oxygen and nitrogen species produced in aging and neurodegenerative disorders.
Elastomeric functional biodegradable copolyester amides and copolyester urethanes

The present invention provides elastomeric copolyester amides, elastomeric copolyester urethanes, and methods for making them. Based on α- amino acids, appropriate physical properties, chemical properties, and polymers having biodegradability. This polymer is useful as a carrier or other bioactive substances of the drug. This polymer is one or more or may be coupled to the drug, or may be admixed, or combinations thereof. The present invention also provides a method of using a medical device for covalent immobilization of a drug, pharmaceutical, the polymer of the present invention for use as a carrier or bioactive agent.
Quantitative structure-activity relationship (QSAR) studies for predicting activation of the ryanodine receptor type 1 channel complex (RyR1) by polychlorinated biphenyl (PCB) congeners

A quantitative structure-activity relationship (QSAR) was developed to predict the congener specific ryanodine receptor type RyR1 activity of all 209 polychlorinated biphenyl (PCB) congeners. A three-variable QSAR equation was obtained via stepwise forward linear regression on an unsupervised forward selection reduced data set from an initial database. Application of the QSAR towards predicting EC2x values for all 209 PCB congeners indicated good agreement in substitution pattern trends between the experimental and estimated data sets. The QSAR model predicts a less than two-fold increase in maximal potency among all congeners outside the experimental database, and it appears that no high-potency PCB congeners with EC2x values much less than 0.2 μ M exist. Increasing RyR1-neuro toxicity equivalents with increasing homologue number and Aroclor chlorination likely reflect indirect molecular controls on toxicity, since congeners with multiple ortho substituents—the primary structural feature controlling a lack of coplanarity and resulting neurotoxicity—are more likely to be found in higher homologues.
Support for efficiently processing complex queries over a P2P substrate

Recently, there has been some research emphasis on strategies to improve query functionality in distributed hash-table-based (DHT) peer-to-peer (P2P) systems, but no approach was able to define how complex schemas and queries can be implemented efficiently on top of it. In this paper, we propose a peer partitioned data management system (PPDM) for schema definition and query processing. We introduce "schema spaces" that allows complex schemas to be defined over a convenient set of nodes and define how simple and more complex schemas and queries are handled by the PPDM, laying the foundations for complex data management over P2P.
Impact of Pretreated Switchgrass and Biomass Carbohydrates on Clostridium thermocellum ATCC 27405 Cellulosome Composition: A Quantitative Proteomic Analysis

Background Economic feasibility and sustainability of lignocellulosic ethanol production requires the development of robust microorganisms that can efficiently degrade and convert plant biomass to ethanol. The anaerobic thermophilic bacterium Clostridium thermocellum is a candidate microorganism as it is capable of hydrolyzing cellulose and fermenting the hydrolysis products to ethanol and other metabolites. C. thermocellum achieves efficient cellulose hydrolysis using multiprotein extracellular enzymatic complexes, termed cellulosomes. Methodology/Principal Findings In this study, we used quantitative proteomics (multidimensional LC-MS/MS and 15N-metabolic labeling) to measure relative changes in levels of cellulosomal subunit proteins (per CipA scaffoldin basis) when C. thermocellum ATCC 27405 was grown on a variety of carbon sources [dilute-acid pretreated switchgrass, cellobiose, amorphous cellulose, crystalline cellulose (Avicel) and combinations of crystalline cellulose with pectin or xylan or both]. Cellulosome samples isolated from cultures grown on these carbon sources were compared to 15N labeled cellulosome samples isolated from crystalline cellulose-grown cultures. In total from all samples, proteomic analysis identified 59 dockerin- and 8 cohesin-module containing components, including 16 previously undetected cellulosomal subunits. Many cellulosomal components showed differential protein abundance in the presence of non-cellulose substrates in the growth medium. Cellulosome samples from amorphous cellulose, cellobiose and pretreated switchgrass-grown cultures displayed the most distinct differences in composition as compared to cellulosome samples from crystalline cellulose-grown cultures. While Glycoside Hydrolase Family 9 enzymes showed increased levels in the presence of crystalline cellulose, and pretreated switchgrass, in particular, GH5 enzymes showed increased levels in response to the presence of cellulose in general, amorphous or crystalline. Conclusions/Significance Overall, the quantitative results suggest a coordinated substrate-specific regulation of cellulosomal subunit composition in C. thermocellum to better suit the organism's needs for growth under different conditions. To date, this study provides the most comprehensive comparison of cellulosomal compositional changes in C. thermocellum in response to different carbon sources. Such studies are vital to engineering a strain that is best suited to grow on specific substrates of interest and provide the building blocks for constructing designer cellulosomes with tailored enzyme composition for industrial ethanol production.
Coxibs and their aftermath: an (opinionated) commentary, based on some historical viewpoints

Five historical viewpoints are presented, each foreshadowing to some degree that it was only a matter of time before we would (re)learn that imbalanced anti-prostanoid therapy was a potentially lethal strategy. Positive outcomes from this coxib debacle might be more willingness to (i) acknowledge our lack of understanding concerning normal homeostatic mechanisms involving the autopharmacology and pleiotropic functions of prostanoids and acyclic eicosanoids (leukotrienes, lipoxins, resolvins, etc.); (ii) revisit the question of salicylate versus aspirin for therapies not requiring anti-thrombotic prophylaxis; (iii) re-examine some leads provided by natural/alternate therapies for inflammatory disorders; and (iv) reconsider the downside of over-reliance upon the present patent system as the main shield and driver of drug innovation.
IMAGING THE NUCLEAR ENVIRONMENT OF NGC 1365 WITH THE HUBBLE SPACE TELESCOPE

The region surrounding the active nucleus of the barred spiral galaxy NGC 1365 is observed in the (Oiii)5007 line and neighbouring continuum using the Faint Object Cam- era (FOC) aboard the Hubble Space Telescope (HST). In the continuum light numerous bright \super star clusters" (SSCs) are seen in the nuclear region. They tend to fall on an elongated ring around the nucleus and contribute about 20 % of the total continuumfluxinthiswavelengthregime.Withoutapplyingany extinction correction the brightest SSCs have an absolute lumi- nosity MB = 14: 1 0: 3 and are very compact with radii R < 3 pc. Complementary ground-based spectroscopy gives an extinction estimate AB =2 : m 5 0 : m 5 towards these regions, indicating a true luminosity MB = 16: 6 0: m 6. The bright compact radio source NGC 1365:A is found to coincide spatially with one of the SSCs. We conclude that it is a \radio supernova". TheHSTobservationsresolvetheinnerstructureofthecon- ical outflow previously seen in the (Oiii)5007 line in ground- based observations, and reveal a complicated structure of in- dividual emission-line clouds, some of which gather in larger agglomerations. The total luminosity in the (Oiii) line amounts to L(OIII) ' 3:710 40 erg s 1 where about 40 % is emitted by the clouds.