gebhart/patrepeval huggingface dataset:
The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local T H 17 Responses (2016)

Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses.
An Early History of Gene Transfer and Therapy (1994)

The term "gene therapy" was coined to distinguish it from the Orwellian connotations of "human genetic engineering," which, in turn, was derived from the term "genetic engineering." Genetic engineering was first used at the Sixth International Congress of Genetics held in 1932 and was taken to mean "the application of genetic principles to animal and plant breeding." Once the basics of molecular genetics and gene transfer in bacteria were established in the 1960s, gene transfer into animals and humans using either viral vectors and/or genetically modified cultured cells became inevitable. Despite the early exposition of the concept of gene therapy, progress awaited the advent of recombinant DNA technology. The lack of trustworthy techniques did not stop many researchers from attempting to transfer genes into cells in culture, animals, and humans. Viral genomes were used for the development of the first relatively efficient methods for gene transfer into mammalian cells in culture. In the late 1970s, early transfection techniques were combined with selection systems for cultured cells and recombinant DNA technology. With the development of retroviral vectors in the early 1980s, the possibility of efficient gene transfer into mammalian cells for the purpose of gene therapy became widely accepted.
Thymic Dysfunction and Time of Infection Predict Mortality in Human Immunodeficiency Virus‐Infected Infants (1998)

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.
Rho‐associated kinases are crucial for myofibroblast differentiation and production of extracellular matrix in scleroderma fibroblasts (2008)

Abstract Objective Rho‐associated kinases (Rock) are the major cellular mediators of Rho GTPases and play an important role in the organization of the actin cytoskeleton. Inhibitors of Rock are currently being evaluated for the treatment of pulmonary arterial hypertension. This study was undertaken to analyze the role of Rock in the activation of fibroblasts in systemic sclerosis (SSc). Methods Rock signaling was inhibited using chemical inhibitors and small interfering RNA. The expression of extracellular matrix (ECM) proteins and α‐smooth muscle actin was analyzed by real‐time polymerase chain reaction, Western blotting, and SirCol assay. Metabolic activity was quantified by MTT assay. Cell viability was assessed by staining with annexin V and propidium iodide. The role of MAP kinases was investigated using selective inhibitors and Western blotting. Results Inhibition of Rock strongly reduced the synthesis of the major ECM proteins at the messenger RNA level as well as the protein level. Counterregulatory changes in the expression of tissue inhibitors of metalloproteinases and matrix metalloproteinases were not observed. Inhibition of Rock prevented myofibroblast differentiation. Transforming growth factor β activated ERK in a Rock‐dependent manner, and ERK mediated in part the stimulatory effects of Rock on myofibroblast differentiation. Toxic adverse effects of the inhibition of Rock were not observed. Conclusion Our findings demonstrate that Rock potently stimulates the differentiation of resting fibroblasts into myofibroblasts and the production of ECM at biologically relevant concentrations without cell toxicity. These findings, along with the beneficial effects of Rock inhibition on vascular disease, indicate that inhibition of Rock might be an interesting novel therapeutic approach for the treatment of SSc.
PILCO: A Model-Based and Data-Efficient Approach to Policy Search (2011)

In this paper, we introduce pilco, a practical, data-efficient model-based policy search method. Pilco reduces model bias, one of the key problems of model-based reinforcement learning, in a principled way. By learning a probabilistic dynamics model and explicitly incorporating model uncertainty into long-term planning, pilco can cope with very little data and facilitates learning from scratch in only a few trials. Policy evaluation is performed in closed form using state-ofthe-art approximate inference. Furthermore, policy gradients are computed analytically for policy improvement. We report unprecedented learning efficiency on challenging and high-dimensional control tasks. 1. Introduction and Related
Management of irritable bowel syndrome (2003)

The diagnosis of irritable bowel syndrome (IBS) is made on clinical grounds with appropriate limited investigations to exclude organic disease. IBS is common and may have a significant impact on a patient's quality of life. Psychological symptoms are common. IBS may benefit from pharmacological and non-pharmacological management. Specific measures should be directed towards the dominant symptoms of constipation or diarrhoea. Several new drugs are currently under evaluation and may prove valuable for subgroups of patients with IBS. Successful management requires a combination of reassurance and explanation about the natural history of the condition.
Identification of mRNA/Protein (mRNP) Complexes Containing Purα, mStaufen, Fragile X Protein, and Myosin Va and their Association with Rough Endoplasmic Reticulum Equipped with a Kinesin Motor (2002)

Puralpha, which is involved in diverse aspects of cellular functions, is strongly expressed in neuronal cytoplasm. Previously, we have reported that this protein controls BC1 RNA expression and its subsequent distribution within dendrites and that Puralpha is associated with polyribosomes. Here, we report that, following treatment with EDTA, Puralpha was released from polyribosomes in mRNA/protein complexes (mRNPs), which also contained mStaufen, Fragile X Mental Retardation Protein (FMRP), myosin Va, and other proteins with unknown functions. As the coimmunoprecipitation of these proteins by an anti-Puralpha antibody was abolished by RNase treatment, Puralpha may assist mRNP assembly in an RNA-dependent manner and be involved in targeting mRNPs to polyribosomes in cooperation with other RNA-binding proteins. The immunoprecipitation of mStaufen- and FMRP-containing mRNPs provided additional evidence that the anti-Puralpha detected structurally or functionally related mRNA subsets, which are distributed in the somatodendritic compartment. Furthermore, mRNPs appear to reside on rough endoplasmic reticulum equipped with a kinesin motor. Based on our present findings, we propose that this rough endoplasmic reticulum structure may form the molecular machinery that mediates and regulates multistep transport of polyribosomes along microtubules and actin filaments, as well as localized translation in the somatodendritic compartment.
Interfering With Gene Expression (2000)

An explosion of recent evidence is revealing a new cellular pathway for silencing specific genes at the messenger RNA (mRNA) level that may protect organisms against viruses and genetic damage. This mechanism, which is very widespread--it occurs in organisms ranging from the mold
 Neurospora to plants, worms, simple vertebrates like the zebrafish, and perhaps even mammals--is apparently triggered when the cell senses some kind of danger, such as a replicating virus or abnormal mRNA. By learning how the cell directs an RNA-cutting enzyme (ribonuclease) to specifically degrade just the mRNAs related to the trigger without affecting other genes, researchers have been able to devise a new method of inactivating specific genes--an ability that should be very useful for studying gene function and might also be used to create genetically modified plants and other organisms.
IgG antibodies that recognize epitope Gly40-Arg43 in domain I of β2–glycoprotein I cause LAC, and their presence correlates strongly with thrombosis (2004)

Anti-beta(2)-glycoprotein I antibodies are known to have a heterogeneous reactivity against beta(2)-glycoprotein I. We performed this study to characterize the epitope on beta(2)-glycoprotein I to which pathologic anti-beta(2)-glycoprotein I antibodies are directed. Plasma samples from 198 patients with various systemic autoimmune diseases were tested for the presence of lupus anticoagulant and anti-beta(2)-glycoprotein I immunoglobulin G (IgG) antibodies. The reactivity of the anti-beta(2)-glycoprotein I-positive samples was further tested by coating recombinant full-length beta(2)-glycoprotein I and 8 deletion mutants of beta(2)-glycoprotein I onto hydrophilic and hydrophobic enzyme-linked immunosorbent assay (ELISA) plates. Full-length beta(2)-glycoprotein I with point mutations in domain I at positions 8, 40, and 43 were used in inhibition experiments. Fifty-two patients with anti-beta(2)-glycoprotein I IgG antibodies could be divided into 2 patterns. Type A antibodies only recognize domain I when coated onto hydrophobic plates; they do not recognize domain I coated onto hydrophilic plates. Type B antibodies have heterogeneous reactivity for all domains. Type A antibodies recognize the epitope around amino acids Gly40-Arg43 and cause lupus anticoagulant activity. In contrast to type B antibodies, those of type A strongly correlated with thrombosis. In conclusion, antibodies directed at domain I (epitope comprising Gly40 and Arg43) have lupus anticoagulant activity and strongly associate with thrombosis.
Prospective motion correction in brain imaging: A review (2012)

Motion correction in magnetic resonance imaging by real-time adjustment of the imaging pulse sequence was first proposed more than 20 years ago. Recent advances have resulted from combining real-time correction with new navigator and external tracking mechanisms capable of quantifying rigid-body motion in all 6 degrees of freedom. The technique is now often referred to as "prospective motion correction." This article describes the fundamentals of prospective motion correction and reviews the latest developments in its application to brain imaging and spectroscopy. Although emphasis is placed on the brain as the organ of interest, the same principles apply whenever the imaged object can be approximated as a rigid body. Prospective motion correction can be used with most MR sequences, so it has potential to make a large impact in clinical routine. To maximize the benefits obtained from the technique, there are, however, several challenges still to be met. These include practical implementation issues, such as obtaining tracking data with minimal delay, and more fundamental problems, such as the magnetic field distortions caused by a moving object. This review discusses these challenges and summarizes the state of the art. We hope that this work will motivate further developments in prospective motion correction and help the technique to reach its full potential.
Cyclosporin A and verapamil enhancement of daunorubicin-produced nucleolar protein B23 translocation in daunorubicin-resistant and -sensitive human and murine tumor cells. (1989)

It has recently been shown that anthracycline antibiotic-resistant tumor cells are less responsive to daunorubicin-stimulated B23 nucleolar phosphoprotein translocation than drug-sensitive cells. Since cyclosporin A and verapamil reverse primary acquired and secondary cross-resistance to daunorubicin, we investigated the effect of these agents on nucleolar B23 translocation in sensitive and resistant tumors. We compared modified to baseline B23 phosphoprotein distribution between predominantly nucleolar, mixed nucleolar-nuclear, or nuclear immunofluorescence using a monoclonal anti-B23 antibody in parental drug-sensitive and multidrug-resistant acute lymphatic leukemia and in daunorubicin-sensitive and -resistant murine hepatoma. Our experiments show that cyclosporin A and verapamil alone have no effect on B23 phosphoprotein translocation, but that the addition of either agent to sensitive parental or resistant tumor sublines markedly enhances daunorubicin-stimulated translocation. This effect correlates with the correction of impaired daunorubicin inhibition of RNA synthesis by cyclosporin A and verapamil in the resistant sublines. Our observations suggest that nucleolar B23 phosphoprotein is an important site in the modulation of anthracycline antibiotic antitumor activity.
Homocysteine transport by systems L, A and y+L across the microvillous plasma membrane of human placenta (2009)

Elevated maternal plasma levels of homocysteine (Hcy) are associated with pregnancy complications and adverse neonatal outcomes, suggesting placental transport of Hcy may impact on fetal development. However, such transport mechanisms have not been defined. In this study we characterise Hcy transport mechanisms across the microvillous plasma membrane (MVM) of the syncytiotrophoblast, the transporting epithelium of human placenta. Three candidate transport systems, systems L, A and y(+)L, were examined utilising competitive inhibition to investigate the effects of Hcy on the uptake of well-characterised radiolabelled substrates for each system into isolated MVM vesicles, and that of model substrates on 10 microm [(35)S]l-Hcy uptake. System L activity was inhibited by both l-Hcy and dl-Hcy, comparable to model substrates including 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH). System L constituted the major transport mechanism, with significant BCH inhibition (69%) of [(35)S]l-Hcy uptake. System A activity was also inhibited by l-Hcy and dl-Hcy with a smaller contribution (21%) to [(35)S]l-Hcy uptake. Inhibition by l-Hcy and dl-Hcy of system y(+)L activity was Na(+) sensitive with a significant inhibition constant (K(i)) shift observed following K(+) replacement; l-arginine reduced [(35)S]l-Hcy uptake by 19%. Kinetic modelling of [(35)S]l-Hcy uptake resolved two, Na(+)-independent, transport components (K(m) 72 microm and 9.7 mm). This study provides evidence for the involvement of systems L, A and y(+)L in placental Hcy transport. Such transport, by competing with endogenous amino acids for transporter activity, could have major implications for syncytiotrophoblast metabolism and function as well as fetal development.
Determining Shale Permeability to Gas by Simultaneous Analysis of Various Pressure Tests (2012)

Summary A model-assisted analysis is presented of pressure-pulse-transmission data obtained under different pressure conditions with core plugs of shale-gas formations. Applications and validations for steady-state and transient-state laboratory tests are provided. Best-estimate values of the intrinsic permeability and tortuosity at a reference condition and the Langmuir volume and pressure are determined by matching the solution of a modified Darcy model to several pressure-pulse-transmission flow tests with core samples simultaneously. The data-interpretation model considers the prevailing characteristics of the apparent permeability under the various flow regimes involving gas flow through extremely low-permeability core samples. Further, the present fully pressure-dependent shale-and gas-property formulation allows for model-assisted extrapolation from the reference conditions to field conditions once the unknown model parameters have been estimated under laboratory conditions. The improved method provides a better match to the measurements of the pressure tests than previous models, which assume only Darcy flow.
Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment (2015)

Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with delayed graft function, graft rejection, chronic rejection and chronic graft dysfunction. Ischemia/reperfusion affects many regulatory systems at the cellular level as well as in the renal tissue that result in a distinct inflammatory reaction of the kidney graft. Underlying factors of ischemia reperfusion include energy metabolism, cellular changes of the mitochondria and cellular membranes, initiation of different forms of cell death-like apoptosis and necrosis together with a recently discovered mixed form termed necroptosis. Chemokines and cytokines together with other factors promote the inflammatory response leading to activation of the innate immune system as well as the adaptive immune system. If the inflammatory reaction continues within the graft tissue, a progressive interstitial fibrosis develops that impacts long-term graft outcome. It is of particular importance in kidney transplantation to understand the underlying mechanisms and effects of ischemia/reperfusion on the graft as this knowledge also opens strategies to prevent or treat ischemia/reperfusion injury after transplantation in order to improve graft outcome.
Sarcoplasmic reticulum function in skinned fibers of hypertrophied rat ventricle (1989)

This study was designed to examine the Ca2+ sensitivity of the contractile system and the ability of the sarcoplasmic reticulum (SR) to accumulate and release Ca2+ in chemically (saponin) skinned cardiac fibers obtained from normal and pressure-overloaded hypertrophied rat left ventricles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta 6-8 wk before study. Age- and weight-matched normal rats served as controls. Pressure over-load increased the left ventricular weight-to-body weight ratio by 51%. There were no differences in the Ca2+-tension relationship between normal and hypertrophied preparations at Ca2+ concentrations of 10(-7) to 10(-4) M. Caffeine-induced Ca2+ release from the maximally Ca2+ -loaded SR was also not different between the two groups at caffeine concentrations of 0.5-30 mM. However, when the relative amount of Ca2+ accumulated in the SR with 10(-6), 3 x 10(-6), or 10(-5) M Ca2+ loading solutions for various loading periods was estimated by the area under the 25 mM caffeine-induced contraction, the accumulation of Ca2+ was significantly slower in hypertrophied fibers than in normal fibers. We conclude that depressed Ca2+ accumulation by the SR plays a role in modulation of contractile performance in this model of chronic pressure overload in rats.
Locally Repairable Codes with Functional Repair and Multiple Erasure Tolerance (2015)

We consider the problem of designing [n; k] linear codes for distributed storage systems (DSS) that satisfy the (r, t)-Local Repair Property, where any t'(&lt;=t) simultaneously failed nodes can be locally repaired, each with locality r. The parameters n, k, r, t are positive integers such that r
TRH and Cyclo (His-Pro) Concentrations in the Young Rat Brain are Altered by Liquid Protein Diet (1987)

Effects of liquid protein diet (LPD), that is known to be poor in protein quality, on brain TRH and cyclo (His-Pro) concentrations were explored in young male rats. At day 23 of weaning, the animals were fed either a 20% casein diet ad libitum or a 20% LPD, or were pair-fed with a 20% casein diet. They were decapitated at day 35 or day 48. The body weight of those in the LPD group decreased significantly, and the loss was sustained in comparison with those in the pair-fed and ad libitum groups. The extrahypothalamic cyclo (His-Pro) concentrations were significantly greater in the LPD group than in the pair-fed and ad libitum groups throughout the experimental period, whereas these concentrations were similar in the pair-fed and ad libitum groups. At day 48, TRH concentrations in the hypothalamus and extrahypothalamus also increased in the LPD group in comparison with the concentrations in ad libitum group. These data indicate that quality of the protein component in the diet has a potential effect on alteration in the neuropeptides, TRH and cyclo (His-Pro), in the young rat brain.
Organ maintenance of human sebaceous glands: in vitro effects of 13-cis retinoic acid and testosterone (1990)

Human sebaceous glands were isolated by shearing, and maintained for 7 days either on defined medium, on medium supplemented with 3 microM-testosterone or on medium supplemented with both 3 microM-testosterone and 1 microM-13-cis retinoic acid. Freshly isolated glands retained their in vivo morphology. On maintenance, the glands retained their freshly isolated rates of cell division, but the sebocytes showed increased keratinization and there was multilayering of the peripheral undifferentiated cells. However, glands maintained in the presence of 1 microM-13-cis retinoic acid showed very little luminal keratinization and only a small degree of multilayering. On autoradiography, freshly isolated glands retained their in vivo pattern of [methyl-3H]thymidine incorporation. Similar patterns were seen when glands were maintained for 7 days with or without testosterone. However, in the presence of both testosterone and 13-cis retinoic acid there was only slight graining. Following 7 days maintenance the rate of lipogenesis fell significantly. This was partially reversed by testosterone, but further inhibited by 13-cis retinoic acid. The patterns of lipids that are synthesised after a week's maintenance are very similar to those seen in freshly isolated glands, except that the squalene:cholesterol ratio is reversibly regulated by 3 microM-testosterone and 1 microM-retinoic acid. Protein synthesis was maintained at the same rates as for freshly isolated glands under all conditions of maintenance. Whereas DNA synthetic rates were maintained in the presence of testosterone, they were significantly inhibited by 13-cis retinoic acid. Glandular wet weights were retained under all conditions of maintenance, except that they were significantly reduced by 13-cis retinoic acid. This study shows that human sebocytes continue to divide on organ maintenance, but that they do not differentiate fully. However, this provides the first demonstration that 13-cis retinoic acid acts on human sebaceous glands directly, reducing the rate of cell division and the rate of lipogenesis, which shows that the maintained human sebaceous gland might provide a useful model for studying the effect of 13-cis retinoic acid on human sebocytes.