gebhart/patrepeval huggingface dataset:
Cyclosporin A and sanglifehrin A enhance chemotherapeutic effect of cisplatin in C6 glioma cells (2010)

Glioma is the most common type of brain tumors in adults, and treatment of high-grade gliomas is still palliative. Studies to date have revealed only modest effect in attenuating growth of these tumors with single agent therapy, but combination treatment appears to be more effective. Cyclophilin A (CypA), a target of immunosuppressive drugs cyclosporin A (CsA) and sanglifehrin A (SFA), is an intracellular protein that has peptidyl-prolyl cis-trans isomerase (PPIase) enzymatic activity. Previously, we showed that overexpressed CypA induced chemoresistance in cancer cells. Here we provide evidence that combination of cisplatin with either CsA or SFA synergistically enhances apoptotic cell death in C6 glioma cells, compared with single agent treatment. Enhanced apoptotic cell death is a result of an increase in ROS generation and a decrease in intracellular glutathione levels. Consistently, CypA knockdown by siRNA also enhances cisplatin-induced apoptosis. Immunohistochemical analysis showed increased expression of CypA in human glioblastoma multiforme, but not in normal human astrocytes. CypA was also shown to be up-regulated in C6 glioma cells during hypoxia. In conclusion, CsA or SFA in combination with cisplatin synergistically enhances cisplatin-induced apoptosis in C6 glioma cells via inhibition of PPIase activity of CypA, indicating that development of new drugs that selectively inhibit the CypA PPIase activity without immune suppression may facilitate alleviation of chemoresistance in treatment of high-grade glioma.
T-cell antigens in cancer. (1994)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Genetic heterogeneity of X‐linked mental retardation with fragile X Association of tight linkage to factor IX and incomplete penetrance in males (1987)

X-linked mental retardation with fragile X or Martin-Bell Syndrome (MBS) is a frequent cause of mental retardation. So far segregation analysis of MBS in pedigrees ascertained by different, incomplete criteria has produced results, difficult to interpret, which suggest genetic complexity (Sherman et al. 1985). Biochemical and cell biological studies have failed to provide an assay for genetic heterogeneity in MBS and linkage analysis is the only available method. Such analysis, however, is complicated by the incomplete penetrance of the disease in males and the variable penetrance and expression of the defect in heterozygous females. We have used a new approach to test the heterogeneity of recombination between MBS and the coagulation factor IX gene or the anonymous probe 52A in a group of nine families who have sought genetic counselling at Guy's Hospital. We find that both our families alone and our families plus apparently complete samples of pedigrees reported in the literature, separate into two groups: one tightly and one loosely linked to factor IX. In the combined family sample these represent respectively 0.3 and 0.7 of the total and show recombination fractions of 0.0-0.15 and 0.25-0.5. Furthermore, the families with non-penetrant carrier males show tighter linkage to factor IX than the others, thus confirming the suggestion of a systematic difference among MBS families in the recombination between the disease and the factor IX locus. By contrast, no significant differences were found in the recombination between 52A and factor IX in the two groups of MBS families or in these families versus those with Hunter syndrome examined in our laboratory. The causes of the linkage heterogeneity we describe are not known. At least two alternatives can be considered: The existence of two MBS loci or differences in the recombination between a single MBS locus and the factor IX gene. The association between incomplete penetrance and tight linkage to factor IX as well as the discontinuous variation in recombination fraction we have observed seem to favour the former alternative.
Estimating a Random Walk First-Passage Time From Noisy or Delayed Observations (2012)

A Gaussian random walk (or a Wiener process), possibly with drift, is observed in a noisy or delayed fashion. The problem considered in this paper is to estimate the first time <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\tau $</tex></formula> the random walk reaches a given level. Specifically, the average <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$p$</tex></formula> -moment ( <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$p\geq 1$</tex></formula> ) optimization problem <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\inf _{\eta} {\BBE} \vert \eta -\tau \vert ^{p}$</tex></formula> is investigated where the infimum is taken over the set of stopping times that are defined on the observation process. When there is no drift, optimal stopping rules are characterized for both types of observations. When there is a drift, upper and lower bounds on <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\inf _{\eta} {\BBE} \vert \eta -\tau \vert ^{p}$</tex></formula> are established for both types of observations. The bounds are tight in the large-level regime for noisy observations and in the large-level-large-delay regime for delayed observations. Noteworthy, for noisy observations there exists an asymptotically optimal stopping rule that is a function of a single observation. Simulation results are provided that corroborate the validity of the results for non-asymptotic settings.
HEAP: a sensory driven distributed manipulation system (1991)

Dextrous hands used in robotic systems require equally dextrous control architectures in order to perform the complex tasks that the hands were built for. Even with its multitude of degrees of freedom, the hand must closely interact with the arm on which it is mounted. Coordination with the arm takes place at the planning level, where desired motions for the hand and arm are synchronised. At the reflexive level, more dynamic interactions between the hand and arm are required, such that the arm is capable of using the force information from the hand, to modify its own trajectory. This coupling between mechanisms is not restricted to hands and arm, and a multilayered control architecture is needed so that the actions of various mechanisms and active sensors are coordinated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Flow Through Gels as a Tool to Generate 3D Concentration Profiles in Hydrogel-Filled Devices (2018)

Laminar flow patterning is an iconic microfluidic technology used to locally deliver chemicals to specific regions on a two-dimensional surface with high spatial fidelity. Here we present a novel extension of this technology by flow patterning inside cured, three-dimensional (3D) hydrogels. We control the pressures at the inlets to shape the size and position of a region of high solute concentration in the main channel filled with a cured collagen 1 hydrogel. This method allows solutes to be delivered with 50 micron accuracy within the gel, as evidenced by control of concentration profiles of 40 kDa fluorescent dye.
Partial Protection of Carbohydrate Derivatives. Part 23.1Simple, Efficient Procedure for the Preparation of 3′- and 2′-0-(Tetrahydropyran-2-YL)Ribonucleoside Derivatives Involving Highly Regioselective 2′,5′-DI-O-Acylation or that Followed by Acyl Migration on Silica Gel and Subsequent O-(Tetrahydropyran-2-YL)Ation (1987)

Abstract Acylation of ribonucleosides with an acyl chloride (1.2–1.5 and 2.2–3.0 mol. equiv. toward the D-ribofuranosyl moiety) in pyridine was induced with high regioselectivity to give the corresponding 2′-acylates and 2′,5′-diacylates, respectively, which were effectively converted into the corresponding 3′-acylates and 3′,5′-diacylates, respectively, by passage down a column of silica gel, followed by crystallization from a solvent. All of the 2′,5′- and 3′,5′-diacylates thus obtained were converted to the corresponding 3′- and 2′-0-(tetrahydropyran-2-yl) derivatives by the usual manner, i.e., (tetrahydropyran-2-yl)ation and subsequent O-deacylation.
High Levels of Tumor miR-187-3p—A Potential Tumor-Suppressor microRNA—Are Correlated with Poor Prognosis in Colorectal Cancer (2022)

This study demonstrated that in spite of its repression and role as a tumor suppressor in CRC, high levels of miR-187-3p in tumors were correlated with poor prognosis and higher levels of peripheral inflammation-related blood markers.
Identification of a Novel Autoantibody Against Pancreatic Secretory Trypsin Inhibitor in Patients with Autoimmune Pancreatitis (2006)

These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.
Independent reliability assessment of the laser transmitter for the ESA-NASA Laser Interferometer Space Antenna (LISA) Program (Conference Presentation) (2023)

As part of the laser development process, NASA’s Goddard Space Flight Center (GSFC) requested support from the NASA Engineering and Safety Center (NESC) to independently assess the Technology Readiness Level (TRL) of the LISA Laser System (LS). The independent assessment included the following tasks: (a) assess the design for weaknesses and suggest improvements to mitigate risks, (b) assess the laser reliability plan for weaknesses and suggest improvements to mitigate risks and improve effectiveness, and (c) assess the current redundancy plan on laser subsystems for weaknesses and suggest improvements to mitigate risks and improve effectiveness. The presentation will focus on the assessment findings and the current development progress of the LISA laser to meet the mission requirements with a delivery of a form, fit, and functional TRL6 laser to the LISA mission by late 2023.
Probiotics: insights and new opportunities for Clostridioides difficile intervention (2022)

<i>Clostridioides difficile</i> infection (CDI) is a life-threatening disease caused by the Gram-positive, opportunistic intestinal pathogen <i>C. difficile</i>. Despite the availability of antimicrobial drugs to treat CDI, such as vancomycin, metronidazole, and fidaxomicin, recurrence of infection remains a significant clinical challenge. The use of live commensal microorganisms, or probiotics, is one of the most investigated non-antibiotic therapeutic options to balance gastrointestinal (GI) microbiota and subsequently tackle dysbiosis. In this review, we will discuss major commensal probiotic strains that have the potential to prevent and/or treat CDI and its recurrence, reassess the efficacy of probiotics supplementation as a CDI intervention, delve into lessons learned from probiotic modulation of the immune system, explore avenues like genome-scale metabolic network reconstructions, genome sequencing, and multi-omics to identify novel strains and understand their functionality, and discuss the current regulatory framework, challenges, and future directions.
A linearly polarized (LP) reader antenna for LP and orientation insensitive (OI) chipless RFID tags (2016)

A single element linearly polarized (LP) aperture coupled microstrip patch antenna (ACMPA) in microwave frequency band is presented in this paper. The paper starts with the requirement for developing a low profile, low cost, lightweight, wideband LP antenna suitable for commercial chipless RFID tag readers. Then, a thorough review is done on existing low profile wideband antenna designs to find out a suitable match with all required reader antenna specifications. From the literature analysis, ACMPA design technique is found as the best match for developing the reader antenna, which is followed next. First, antenna specifications are listed for developing a single element LP ACMPA. Then, a single element is designed and optimized to achieve the targeted values, which is fabricated and assembled next. After that, this ACMPA is measured in a vector network analyzer (VNA), which fulfills the set targets. Next, tag reading performance of the antenna in three different measurement setups is evaluated through measurement of `O' slot loaded orientation insensitive (OI) tags. These tag measurement results have confirmed the usability of the developed antenna in commercial tag reader.
Behavioral and neurobiological changes in C57BL/6 mice exposed to cuprizone. (2009)

C57BL/6 mice were given 0.2% cuprizone (CPZ) for 2 to 6 weeks while controls ate the same diet without CPZ. At various time points the animals were subjected to behavioral tests and their brains were analyzed. Mice exposed to CPZ for 2 and 3 weeks displayed more climbing behavior and lower prepulse inhibition, suggesting an increase in central nervous system activity and impaired sensorimotor gating. In addition, they showed lower activities of monoamine oxidase and dopamine beta hydroxylase in the hippocampus and prefrontal cortex, and had higher dopamine but lower norepinephrine levels in the prefrontal cortex. Mice exposed to CPZ for 4 to 6 weeks had less social interaction, which is an animal correlate of social withdrawal of patients with schizophrenia. Also, these CPZ-exposed mice showed evident brain demyelination, myelin break down, and loss of oligodendrocytes. At all time points the CPZ-exposed mice spent more time in the open arms of an elevated plus maze and exhibited spatial working memory impairment. These data are in line with evidence from human studies suggesting a putative role of white matter abnormality in the pathophysiology of schizophrenia.
Joint entropy of continuously differentiable ultrasonic waveforms (2013)

This study is based on an extension of the concept of joint entropy of two random variables to continuous functions, such as backscattered ultrasound. For two continuous random variables, X and Y, the joint probability density p(x,y) is ordinarily a continuous function of x and y that takes on values in a two dimensional region of the real plane. However, in the case where X=f(t) and Y=g(t) are both continuously differentiable functions, X and Y are concentrated exclusively on a curve, γ(t)=(f(t),g(t)), in the x,y plane. This concentration can only be represented using a mathematically "singular" object such as a (Schwartz) distribution. Its use for imaging requires a coarse-graining operation, which is described in this study. Subsequently, removal of the coarse-graining parameter is accomplished using the ergodic theorem. The resulting expression for joint entropy is applied to several data sets, showing the utility of the concept for both materials characterization and detection of targeted liquid nanoparticle ultrasonic contrast agents. In all cases, the sensitivity of these techniques matches or exceeds, sometimes by a factor of two, that demonstrated in previous studies that employed signal energy or alternate entropic quantities.
A Conserved DrosophilaTransportin-Serine/Arginine-rich (SR) Protein Permits Nuclear Import ofDrosophila SR Protein Splicing Factors and Their Antagonist Repressor Splicing Factor 1 (2002)

Members of the highly conserved serine/arginine-rich (SR) protein family are nuclear factors involved in splicing of metazoan mRNA precursors. In mammals, two nuclear import receptors, transportin (TRN)-SR1 and TRN-SR2, are responsible for targeting SR proteins to the nucleus. Distinctive features in the nuclear localization signal between Drosophila and mammalian SR proteins prompted us to examine the mechanism by which Drosophila SR proteins and their antagonist repressor splicing factor 1 (RSF1) are imported into nucleus. Herein, we report the identification and characterization of a Drosophila importin beta-family protein (dTRN-SR), homologous to TRN-SR2, that specifically interacts with both SR proteins and RSF1. dTRN-SR has a broad localization in the cytoplasm and the nucleus, whereas an N-terminal deletion mutant colocalizes with SR proteins in nuclear speckles. Far Western experiments established that the RS domain of SR proteins and the GRS domain of RSF1 are required for the direct interaction with dTRN-SR, an interaction that can be modulated by phosphorylation. Using the yeast model system in which nuclear import of Drosophila SR proteins and RSF1 is impaired, we demonstrate that complementation with dTRN-SR is sufficient to target these proteins to the nucleus. Together, the results imply that the mechanism by which SR proteins are imported to the nucleus is conserved between Drosophila and humans.
Multicenter Evaluation of the VERSANT Hepatitis B Virus DNA 3.0 Assay (2004)

The VERSANT hepatitis B virus (HBV) 3.0 Assay (branched DNA [bDNA]) (referred to herein as VERSANT 3.0) was evaluated at four external sites for analytical sensitivity, specificity, reproducibility, linearity of quantification, and limits of detection. In addition, each of the test evaluation sites provided HBV DNA-positive clinical samples that were previously analyzed by one of three commercially available HBV DNA quantitative tests: Digene Hybrid Capture II HBV DNA Test (Digene); VERSANT HBV DNA 1.0 Assay (bDNA) (VERSANT 1.0); and COBAS AMPLICOR HBV Monitor Test (COBAS AMPLICOR). These samples were reexamined using VERSANT 3.0. The results from these studies showed that VERSANT 3.0 has high specificity (99.3%), excellent reproducibility (between-run coefficient of variation [CV] = 1.6 to 9.4%; within-run CV = 6.5 to 20.7%), and a broad linear range of quantification (2.0 x 10(3) to 1.0 x 10(8) HBV DNA copies/ml) that facilitate the monitoring of HBV DNA levels at diagnosis and throughout the course of treatment. In general, correlation was very good between results obtained from clinical samples analyzed by VERSANT 3.0 and the comparative HBV DNA quantitative assays (VERSANT 1.0, R(2) = 0.900; Digene, R(2) = 0.985; COBAS AMPLICOR, R(2) = 0.771). The greatest differences in comparative quantitation occurred at HBV DNA levels approaching the limits of the dynamic ranges for the comparative assays. The performance characteristics of the new VERSANT 3.0 assay demonstrated that it provides a reliable and robust method for routinely monitoring serum HBV DNA levels in assessing disease activity and determining response to antiviral treatment.
Westheimer to Receive Tillyer Award (1978)

School of Optometry, University of California, Berkeley, California * Optometrist, Ph.D., Member of Faculty, F.A.A.O.
Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment (2018)

Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)-expressing B cells and γδ T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and γδ T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients.
Novel roles for T-bet in CD8 differentiation during chronic viral infections (44.8) (2009)

Abstract The T-box transcription factor, T-bet, was shown recently to play an important role in memory CD8 T-cell differentiation. During an acute infection, higher levels of T-bet induced the formation of shorter-lived effectors, while lower levels induced long-lived memory CD8s. However, the role of T-bet, or any transcription factor, in regulating CD8 differentiation during chronic infections has not been examined. We infected mice with the chronic Clone-13 strain of lymphocytic choriomeningitis virus (LCMV), whose antigen-specific CD8s become highly dysfunctional (i.e. exhausted). Surprisingly, T-bet levels in these exhausted CD8s exposed to a chronic inflammatory environment are lower than ag-specific cells generated during infection with an acute (Armstrong) strain. Its expression correlated inversely with that of the inhibitory surface receptor, PD-1, which is known to contribute to T cell exhaustion. T-bet deficient mice infected with Clone-13 had higher levels of PD-1; in addition, they exhibited a severe defect in viral control and lost their antigen-specific CD8s after 2-3 weeks. Finally, we show that T-bet binds to the PD-1 promoter in CD8s from LCMV-infected hosts. Thus, during a chronic viral infection, T-bet is critical for the maintenance of antigen-specific CD8 T-cells, and it may regulate T-cell exhaustion, at least in part, by acting directly on the PD-1 locus.
Shuttleworthia (2015)

Abstract Shutt.le.worth'ia. N.L. fem. n. Shuttleworthia named to honor Cyril Shuttleworth, the distinguished British microbiologist. Slightly curved short rods which occur singly, in pairs, short chains, or diphtheroidal arrangements. Rods 0.4–0.6 µm in diameter and 1.0–2.5 µm in length. Gram‐stain‐positive , non‐spore‐forming , and nonmotile . Obligately anaerobic . Optimal growth temperature 30–37 °C. Several different colony morphologies exist. DNA G + C content ( mol %): 50–51 (HPLC). Type species : Shuttleworthia satelles Downes, Munson, Radford, Spratt and Wade 2002, 1474 VP . Taxonomic and Nomenclature Notes According to the List of Prokaryotic names with Standing in Nomenclature (LPSN), the taxonomic status of the genus Shuttleworthia is: synonym (last update, February 2025) * . Correct name: Shuttleworthella LPSN classification: Bacteria / Bacillati / Bacillota / Clostridia / Eubacteriales / Lachnospiraceae / Shuttleworthella The genus Shuttleworthia can also be recovered in the Genome Taxonomy Database (GTDB) as g__Shuttleworthia (version v220) ** . GTDB classification: d__Bacteria / p__Bacillota_A / c__Clostridia / o__Lachnospirales / f__Lachnospiraceae / g__Shuttleworthia * Meier‐Kolthoff et al. ( 2022 ). Nucleic Acids Res , 50 , D801 – D807 ; DOI: 10.1093/nar/gkab902 ** Parks et al. ( 2022 ). Nucleic Acids Res , 50 , D785 – D794 ; DOI: 10.1093/nar/gkab776
Meta-Q-Learning (2020)

This paper introduces Meta-Q-Learning (MQL), a new off-policy algorithm for meta-Reinforcement Learning (meta-RL). MQL builds upon three simple ideas. First, we show that Q-learning is competitive with state of the art meta-RL algorithms if given access to a context variable that is a representation of the past trajectory. Second, using a multi-task objective to maximize the average reward across the training tasks is an effective method to meta-train RL policies. Third, past data from the meta-training replay buffer can be recycled to adapt the policy on a new task using off-policy updates. MQL draws upon ideas in propensity estimation to do so and thereby amplifies the amount of available data for adaptation. Experiments on standard continuous-control benchmarks suggest that MQL compares favorably with state of the art meta-RL algorithms.