gebhart/patrepeval huggingface dataset:
The therapeutic role of oral tolerance in dextran sulfate sodium‐induced colitis viaTh1–Th2 balance and γδTcells (2013)

There is a defect in oral tolerance at day 7 in DSS-induced colitis. If taken orally, CEP may have a protective role in DSS-induced colitis, which may be related to the deflection from Th1 to Th2 in Peyer's patch and the reduction of γδ T cells in lamina proper lymphocytes in the intestine.
CD28 costimulation improves expansion and persistence of chimeric antigen receptor–modified T cells in lymphoma patients (2011)

Targeted T cell immunotherapies using engineered T lymphocytes expressing tumor-directed chimeric antigen receptors (CARs) are designed to benefit patients with cancer. Although incorporation of costimulatory endodomains within these CARs increases the proliferation of CAR-redirected T lymphocytes, it has proven difficult to draw definitive conclusions about the specific effects of costimulatory endodomains on the expansion, persistence, and antitumor effectiveness of CAR-redirected T cells in human subjects, owing to the lack of side-by-side comparisons with T cells bearing only a single signaling domain. We therefore designed a study that allowed us to directly measure the consequences of adding a costimulatory endodomain to CAR-redirected T cells. Patients with B cell lymphomas were simultaneously infused with 2 autologous T cell products expressing CARs with the same specificity for the CD19 antigen, present on most B cell malignancies. One CAR encoded both the costimulatory CD28 and the ζ-endodomains, while the other encoded only the ζ-endodomain. CAR+ T cells containing the CD28 endodomain showed strikingly enhanced expansion and persistence compared with CAR+ T cells lacking this endodomain. These results demonstrate the superiority of CARs with dual signal domains and confirm a method of comparing CAR-modified T cells within individual patients, thereby avoiding patient-to-patient variability and accelerating the development of optimal T cell immunotherapies.
Design of New Materials for Methane Storage (2004)

One of the strategic goals of the modern automobile manufacturing industry is to replace gasoline and diesel with alternative fuels such as natural gas. In this report, we elucidate the desired characteristics of an optimal adsorbent for gas storage. The U.S. Department of Energy has outlined several requirements that adsorbents must fulfill for natural gas to become economically viable, with a key criterion being the amount adsorbed at 35 bar. We explore the adsorption characteristics of novel metal-organic materials (IRMOFs and molecular squares) and contrast them with the characteristics of two zeolites, MCM-41, and different carbon nanotubes. Using molecular simulations, we uncover the complex interplay of the factors influencing methane adsorption, especially the surface area, the capacity or free volume, the strength of the energetic interaction, and the pore size distribution. We also explain the extraordinary adsorption properties of IRMOF materials and propose new, not yet synthesized IRMOF structures with adsorption characteristics that are predicted to exceed the best experimental results to date by up to 36%.
Molecular Machines: How Motion and Other Functions of Living Organisms Can Result from Reversible Chemical Changes (1993)

Abstract Certain model proteins dramatically fold and become more ordered on raising the temperature. When the temperature is raised to drive folding and assembly, these model proteins can lift weights and perform work; they can produce motion. The temperature of warm‐blooded animals, however, is kept constant. Therefore, motion cannot result from a change in temperature. In this case, a free energy change, caused, for example, by an increase in the concentration of a chemical, can lower the temperature at which the protein folding and assembly transition occurs from above to below physiological temperature. Raising the concentration of a chemical isothermally has indeed been shown to result in motion and the efficient performance of work. These model proteins and the mechanism they reveal provide insight into the molecular basis for diverse biological functions; they are models for the molecular machines that comprise the living organism, and they provide a new class of materials for both medical and nonmedical applications.
Classical conditioning induces long-term translocation of protein kinase C in rabbit hippocampal CA1 cells. (1988)

The role of the Ca2+/phospholipid-dependent, diacylglycerol-activated enzyme protein kinase C (PKC) in rabbit eyelid conditioning was examined. PKC was partially purified from the CA1 region of hippocampal slices from naive, pseudoconditioned, and conditioned rabbits 24 hr after the rabbits were well conditioned. Crude membrane and cytosol fractions were prepared. In conditioned rabbits, significantly more PKC activity (63.3%) was associated with the membrane fraction (and significantly less with the cytosol fraction) compared to naive (42.0%) and pseudoconditioned (44.7%) animals. These differences in distribution of enzyme activity were paralleled by differences in stimulation of enzyme activity by Ca2+, phospholipid, and diacylglycerol. There were no between-group differences in basal protein kinase activity. These results suggest that there is a long-term translocation of PKC from cytosol to membrane as a result of conditioning. Autoradiographic binding of radioactive phorbol 12,13-dibutyrate to PKC demonstrated that almost all specific binding was in the stratum radiatum, a region containing the proximal apical dendrites of CA1 pyramidal neurons. Therefore, this may be the site of the conditioning-specific PKC translocation, a locus well-suited to underlie the biophysical effects of conditioning.
A single amino acid substitution affects multiple overlapping epitopes in the major antigenic site of foot-and-mouth disease virus of serotype C (1990)

Neutralizing monoclonal antibodies (nMAbs) elicited against foot-and-mouth disease virus (FMDV) of serotype C were assayed with field isolates and variant FMDVs using several immunoassays. Of a total of 36 nMAbs tested, 23 recognized capsid protein VP1 and distinguished at least 13 virion conformation-independent epitopes involved in neutralization of FMDV C. Eleven epitopes of FMDV C-S8c1 have been located in segments 138-156 or 192-209 of VP1 by quantifying the reactivity of nMAbs with synthetic peptides and with nMAb-resistant mutants of FMDV C-S8c1 carrying defined amino acid substitutions. The main antigenic site of FMDV C-S8c1 (VP1 residues 138 to 150) consists of multiple (at least 10), distinguishable, overlapping epitopes. Some amino acid replacements abolished one of the epitopes, whereas other replacements affected several epitopes in this region. The conservative substitution His(146)----Arg, found in many nMAb-resistant mutants analysed, abolished the reactivity of the virus with all nMAbs that recognized epitopes in the main antigenic site of FMDV C-S8c1. This indicates that a minimum genetic change can result in a highly amplified phenotypic effect, as regards the antigenicity of FMDV.
Animal Caries Models for Evaluating Fluoride Dentifrices (1995)

To determine the ability of animal caries models to evaluate the cariostatic potential of fluoride dentifrices, we examined four different coronal caries models. These currently used rat caries models were: Francis' hypomineralized area model, Gaffar's CARA rat model, the Connecticut model, and the Indiana model. Available data indicated that all of these models were capable of detecting significant cariostatic benefits from clinically proven fluoride dentifrices. For the most part, these animal models were also able to demonstrate a response to increasing concentrations of fluoride, particularly if the fluoride was provided in an ionic rather than a complexed form. Data were also presented which indicated the potential for animal caries models to be used to predict the clinical benefits of non-fluoride systems as well as the utility of fluoride systems for the prevention of root-surface caries. It is concluded that animal caries models play a significant role in the development and evaluation of fluoride and other systems for the clinical prevention of dental caries.
Safety of Melatonin in Long-Term Use(?) (1997)

There are no published long-term safety data on the use of melatonin for whatever purpose, assuming long term to mean more than 6 months of daily medication. In the light of its physiological role in animals, the potential deleterious effects include inhibition of reproductive function, delayed timing of puberty, and influence (when taken during pregnancy and lactation) on the circadian status of the fetus and neonate and on future development. Its interactions with other medications are virtually unexplored. For most positive effects published, there also exist negative reports. There are insufficient data on its use in organic or psychiatric disease for any evaluations to be made. There are insufficient data on dose, formulation, and consequent relationships of individual pharmacokinetics and pharmacodynamics for recommendations at present. However, in normal healthy adults over 18 years old, not pregnant or lactating, with no personal or family histories of psychiatric disorder, and unmedicated except for oral contraceptives and minor analgesics (if necessary), the only significant short-term side effect in the author's experience has been sleepiness following oral ingestion of synthetic melatonin (5 mg or less, oral fast release), licensed for human experimental use and for prescription on a named-patient basis.
Neurobiological and immunogenetic aspects of narcolepsy: Implications for pharmacotherapy (2018)

Excessive daytime sleepiness (EDS) and cataplexy are common symptoms of narcolepsy, a sleep disorder associated with the loss of hypocretin/orexin (Hcrt) neurons. Although only a few drugs have received regulatory approval for narcolepsy to date, treatment involves diverse medications that affect multiple biochemical targets and neural circuits. Clinical trials have demonstrated efficacy for the following classes of drugs as narcolepsy treatments: alerting medications (amphetamine, methylphenidate, modafinil/armodafinil, solriamfetol [JZP-110]), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), sodium oxybate, and the H<sub>3</sub>-receptor inverse agonist/antagonist pitolisant. Enhanced catecholamine availability and regulation of locus coeruleus (LC) norepinephrine (NE) neuron activity is likely central to the therapeutic activity of most of these compounds. LC NE neurons are integral to sleep/wake regulation and muscle tone; reduced excitatory input to the LC due to compromise of Hcrt/orexin neurons (likely due to autoimmune factors) results in LC NE dysregulation and contributes to narcolepsy/cataplexy symptoms. Agents that increase catecholamines and/or LC activity may mitigate EDS and cataplexy by elevating NE regulation of GABAergic inputs from the amygdala. Consequently, novel medications and treatment strategies aimed at preserving and/or modulating Hcrt/orexin-LC circuit integrity are warranted in narcolepsy/cataplexy.
Current Status and Future Development of Catalyst Materials and Catalyst Layers for Proton Exchange Membrane Fuel Cells: An Industrial Perspective (2017)

Proton exchange membrane fuel cells (PEMFCs) have already penetrated many commercial markets (e.g., portable power, backup power, materials handling, and buses) and are poised to greatly expand in the automotive market with both Toyota and Hyundai recently commercializing small fleets. As this occurs, catalysts for PEMFCs will experience ever greater demands on cost, activity, and durability. This Perspective outlines the technology timeline and characteristics of the most promising catalysts currently being developed and discusses the remaining challenges for both platinum group metal and nonprecious metal catalysts. Finally, the importance of combined catalyst and catalyst layer design strategies is highlighted, and a brief discussion on the future outlook of this field is provided.
Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience (2008)

Vitreoretinal involvement of lymphoma can be controlled effectively and without serious adverse reactions by intravitreal MTX injections. The treatment protocol described herein has resulted in no intraocular recurrence so far and has had bearable side effects. The accumulating clinical results bring us to propose the consideration of this protocol as a good first-line treatment option for intraocular lymphoma.
Synthesis of Ecteinascidin ET-743 and Phthalascidin Pt-650 from Cyanosafracin B (2000)

An efficient new process is described for the synthesis of ecteinascidin ET-743 (1) and phthalascidin (2), starting from readily available cyanosafracin B (3).
A recessive cellular mutation in v-fes-transformed mink cells restores contact inhibition and anchorage-dependent growth. (1988)

A contact-inhibited revertant of mink cells transformed by the Gardner-Arnstein strain of feline sarcoma virus was isolated by fluorescence-activated sorting of cells stained with the mitochondria-specific dye rhodamine 123. The revertant cell line exhibited a decrease in its proliferative rate and saturation density and a complete loss of its capacity for anchorage-independent growth, but it remained tumorigenic when inoculated into nude mice. The revertant cells retained a rescuable Gardner-Arnstein feline sarcoma provirus, expressed high levels of the v-fes oncogene product and its associated tyrosine kinase activity, manifested elevated levels of phosphotyrosine-containing cellular proteins similar to those observed in v-fes-transformed cells, and were refractory to retransformation by retroviruses containing the v-fes, v-fms, and v-ras oncogenes. Fusion of the revertant and parental cells generated somatic cell hybrids which formed colonies in semisolid medium, indicating that the block in transformation was recessive. These data together with the observation that the revertant phenotype is unstable in continuous culture suggest that the loss of transformation is due to the presence of limiting quantities of a gene product which functions downstream of the v-fes-coded kinase in the mitogenic pathway.
Modeling targeted layered containment of an influenza pandemic in the United States (2008)

Planning a response to an outbreak of a pandemic strain of influenza is a high public health priority. Three research groups using different individual-based, stochastic simulation models have examined the consequences of intervention strategies chosen in consultation with U.S. public health workers. The first goal is to simulate the effectiveness of a set of potentially feasible intervention strategies. Combinations called targeted layered containment (TLC) of influenza antiviral treatment and prophylaxis and nonpharmaceutical interventions of quarantine, isolation, school closure, community social distancing, and workplace social distancing are considered. The second goal is to examine the robustness of the results to model assumptions. The comparisons focus on a pandemic outbreak in a population similar to that of Chicago, with approximately 8.6 million people. The simulations suggest that at the expected transmissibility of a pandemic strain, timely implementation of a combination of targeted household antiviral prophylaxis, and social distancing measures could substantially lower the illness attack rate before a highly efficacious vaccine could become available. Timely initiation of measures and school closure play important roles. Because of the current lack of data on which to base such models, further field research is recommended to learn more about the sources of transmission and the effectiveness of social distancing measures in reducing influenza transmission.
Triterpenoid Dihydro-CDDO-Trifluoroethyl Amide Protects against Maladaptive Cardiac Remodeling and Dysfunction in Mice: A Critical Role of Nrf2 (2012)

These findings demonstrate that dh404 prevents pathological cardiac remodeling and dysfunction by activating Nrf2, indicating a therapeutic potential of dh404 for cardiac disease.
Book Review: Metabotropic Glutamate Receptors: Electrical and Chemical Signaling Properties (2002)

Over the last two decades, glutamate has been established as the main excitatory neurotransmitter in the mammalian brain. Glutamate released from synapses activates ion channel-forming receptors at postsynaptic cells and consequently mediates fast postsynaptic potentials. These receptors are termed ionotropic glutamate receptors (iGluRs). The subsequent discovery of metabotropic glutamate receptors (mGluRs) revealed that glutamate can also mediate slow synaptic potentials, modulate ion channels, and directly couple to GTP binding proteins. In contrast to the iGluRs, the mGluRs possess seven transmembrane domains and a large intracellular C-terminus that involves interactions with a variety of other intracellular signaling systems. Eight functionally distinct mGluR subtypes are known to be localized to specific neuron types at presynaptic and/or postsynaptic membranes. Their physiological functions involve the generation of slow excitatory and inhibitory synaptic potentials, modulation of synaptic transmission, synaptic integration, and plasticity. The classical role of glutamate as a fast excitatory synaptic transmitter was largely extended by mGluRs acting as a neuromodulator and even as an activator of inhibitory mechanisms at certain synapses.
Real-time PCR using molecular beacons for accurate detection of the Y chromosome in single human blastomeres (2000)

We describe a highly accurate method for determining the sex of human embryos via real-time polymerase chain reaction (PCR) amplification of highly-conserved, moderately-repeated sequences within the TSPY genes on the Y chromosome and the U2 genes on chromosome 17. Individual male lymphocytes, female lymphocytes, and blastomeres from donated cleavage-stage embryos were lysed prior to PCR using an optimized buffer containing proteinase K. Molecular beacons, a new type of fluorescent probe, were used to detect and quantify accumulating amplicons during each cycle of PCR carried out in closed tubes. The present work is part of an ongoing study to construct and implement a new, convenient and reliable system of preimplantation genetic diagnosis (PGD).
Identification of Small Molecules that Sensitize Resistant Tumor Cells to Tumor Necrosis Factor-Family Death Receptors (2006)

Two major pathways for apoptosis have been identified, involving either mitochondria (intrinsic) or tumor necrosis factor (TNF)-family death receptors (extrinsic) as initiators of caspase protease activation and cell death. Because tumor resistance to TNF-family death receptor ligands is a common problem, helping malignant cells evade host immune defenses, we sought to identify compounds that selectively sensitize resistant tumor cells to death receptor ligands. We screened a 50,000-compound library for agents that enhanced anti-FAS antibody-mediated killing of FAS-resistant PPC-1 prostate cancer cell, then did additional analysis of the resulting hits to arrive at eight compounds that selectively sensitized PPC-1 cells to anti-FAS antibody (extrinsic pathway agonist) without altering sensitivity to staurosporine and etoposide (VP-16; intrinsic pathway agonists). These eight compounds did not increase Fas surface levels and also sensitized PPC-1 cells to apoptosis induced by TNF-family member TNF-related apoptosis-inducing ligand, consistent with a post-receptor mechanism. Of these, two reduced expression of c-FLIP, an intracellular antagonist of the extrinsic pathway. Characterization of the effects of the eight compounds on a panel of 10 solid tumor cell lines revealed two structurally distinct compounds that frequently sensitize to extrinsic pathway agonists. Structure-activity relation studies of one of these compounds revealed a pharmacophore from which it should be possible to generate analogues with improved potency. Altogether, these findings show the feasibility of identifying compounds that selectively enhance apoptosis via the extrinsic pathway, thus providing research tools for uncovering resistance mechanisms and a starting point for novel therapeutics aimed at restoring sensitivity of tumor cells to immune effector mechanisms.
Novel Views of Objects from a Single Image (2016)

Taking an image of an object is at its core a lossy process. The rich information about the three-dimensional structure of the world is flattened to an image plane and decisions such as viewpoint and camera parameters are final and not easily revertible. As a consequence, possibilities of changing viewpoint are limited. Given a single image depicting an object, novel-view synthesis is the task of generating new images that render the object from a different viewpoint than the one given. The main difficulty is to synthesize the parts that are disoccluded; disocclusion occurs when parts of an object are hidden by the object itself under a specific viewpoint. In this work, we show how to improve novel-view synthesis by making use of the correlations observed in 3D models and applying them to new image instances. We propose a technique to use the structural information extracted from a 3D model that matches the image object in terms of viewpoint and shape. For the latter part, we propose an efficient 2D-to-3D alignment method that associates precisely the image appearance with the 3D model geometry with minimal user interaction. Our technique is able to simulate plausible viewpoint changes for a variety of object classes within seconds. Additionally, we show that our synthesized images can be used as additional training data that improves the performance of standard object detectors.
Bacterial Protein Toxins: An Overview (2003)

This short overview attempts to highlight the current state of the art relevant to bacterial protein toxins. In particular we outline the major achievements in this field during the past decade and briefly describe some significant hallmarks of toxinological research since the advent of modern methodologies elucidating the biochemistry, genetics, and cell biology of these fascinating bacterial effectors.
Adenosine Diphosphoglucose-Starch Glucosyltransferases from Developing Kernels of Waxy Maize (1971)

TWO ADENOSINE DIPHOSPHOGLUCOSE: alpha-1,4-glucan alpha-4-glucosyl-transferases were extracted from kernels of waxy maize harvested 22 days after pollination and separated by gradient elution from a diethylaminoethyl-cellulose column. Both fractions could utilize amylopectin, amylose, glycogen, maltotriose and maltose as primers. The rate of glucose transfer from adenosine diphosphoglucose to rabbit liver glycogen of fraction II was 78% of the rate of glucose transfer to amylopectin, but with fraction I the rate of transfer of glucose to rabbit liver glycogen was 380% of that observed to amylopectin. Glucan synthesis in the absence of added primer was found in fraction I in the presence of 0.5 m sodium citrate and bovine serum albumin. The unprimed product was a methanol-precipitable glucan with principally alpha-1,4 linkages and some alpha-1,6 linkages, and its iodine spectrum was similar to that of amylopectin.