gebhart/patrepeval huggingface dataset:
CD137 Agonist Therapy Can Reprogram Regulatory T Cells into Cytotoxic CD4+ T Cells with Antitumor Activity (2015)

Recent successes in immune therapeutic strategies aimed to improve control over tumor growth have sparked hope that long-lived control of cancer through stimulation of the immune system can be possible. However, the underlying immunological mechanisms that are induced by immunotherapeutic strategies are not well understood. In this study, we used the highly immunogenic Friend virus-induced FBL-3 tumor as a model to study the mechanisms of immunological tumor control by CD4(+) T cells in the course of CD137 (4-1BB) agonist immunotherapy in the absence of a CD8 T cell response. We demonstrate that treatment with a CD137 agonist resulted in complete FBL-3 tumor regression in CD8(+) T cell-deficient mice. CD137 signaling enhanced the production of proinflammatory cytokines and cytotoxic molecules in tumor-specific CD4(+) T cells. Interestingly, a subset of CD4(+)Foxp3(+) regulatory T cells was reprogrammed to eliminate immunogenic virus-induced tumor cells in response to CD137 agonist treatment. These cells expressed markers characteristic for Th cells (CD154) and produced the cytokine TNF-α or the T-box transcriptional factor Eomesodermin and granzyme B without loss of Foxp3 expression. Foxp3 Eomes double-positive CD4(+) T cells were capable of eliminating immunogenic virus-induced tumor cells in vivo. Thus, our data show that tumor-induced Foxp3(+)CD4(+) T cells can be reprogrammed into cytotoxic effector cells upon therapeutic costimulatory signaling and restore antitumor immunity.
DNA methylation profiling reveals novel biomarkers and important roles for DNA methyltransferases in prostate cancer (2011)

Candidate gene-based studies have identified a handful of aberrant CpG DNA methylation events in prostate cancer. However, DNA methylation profiles have not been compared on a large scale between prostate tumor and normal prostate, and the mechanisms behind these alterations are unknown. In this study, we quantitatively profiled 95 primary prostate tumors and 86 benign adjacent prostate tissue samples for their DNA methylation levels at 26,333 CpGs representing 14,104 gene promoters by using the Illumina HumanMethylation27 platform. A 2-class Significance Analysis of this data set revealed 5912 CpG sites with increased DNA methylation and 2151 CpG sites with decreased DNA methylation in tumors (FDR < 0.8%). Prediction Analysis of this data set identified 87 CpGs that are the most predictive diagnostic methylation biomarkers of prostate cancer. By integrating available clinical follow-up data, we also identified 69 prognostic DNA methylation alterations that correlate with biochemical recurrence of the tumor. To identify the mechanisms responsible for these genome-wide DNA methylation alterations, we measured the gene expression levels of several DNA methyltransferases (DNMTs) and their interacting proteins by TaqMan qPCR and observed increased expression of DNMT3A2, DNMT3B, and EZH2 in tumors. Subsequent transient transfection assays in cultured primary prostate cells revealed that DNMT3B1 and DNMT3B2 overexpression resulted in increased methylation of a substantial subset of CpG sites that showed tumor-specific increased methylation.
Identification of a novel herpes simplex virus type 1-induced glycoprotein which complexes with gE and binds immunoglobulin (1987)

We detected a glycoprotein on the surface of cells infected with herpes simplex virus type 1 (HSV-1) which, in conjunction with gE, binds immunoglobulin G (IgG). The novel glycoprotein, which has an apparent molecular mass of 70 kilodaltons and was provisionally named g70, was first detected in extracts of HSV-1-infected cells labeled by lactoperoxidase-catalyzed iodination and precipitated with rabbit sera or IgG and protein A-Sepharose. In subsequent experiments, g70 and gE were coprecipitated from extracts of HSV-1-infected cells labeled with [35S]methionine, [35S]cysteine, or 14C-amino acids. We were unable to precipitate a polypeptide analogous to g70 or gE from extracts of HSV-2-infected cells with rabbit IgG and protein A-Sepharose. Partial proteolytic peptide analysis indicated that g70 is structurally distinct from gE and gI). In addition, g70 was electrophoretically distinct from the HSV-1 Us4 glycoprotein gG. HSV-1 gE, expressed in mouse cells transfected with the gE gene, was not precipitated with rabbit IgG, nor could these cells bind radiolabeled IgG, suggesting that gE alone cannot act as an IgG (Fc) receptor. This result, coupled with the findings that gE and g70 are coprecipitated with IgG and with an anti-gE monoclonal antibody, suggests that gE and g70 form a complex which binds IgG. The electrophoretic mobilities of g70 molecules induced by different strains of HSV-1 differed markedly, arguing that g70 is encoded by the virus and is not a cellular protein induced by virus infection.
Transforming Growth Factor-β-Induced Differentiation of Smooth Muscle From a Neural Crest Stem Cell Line (2004)

During vascular development, nascent endothelial networks are invested with a layer of supporting cells called pericytes in capillaries or smooth muscle in larger vessels. The cellular lineage of smooth muscle precursors and factors responsible for regulating their differentiation remain uncertain. In vivo, cells derived from the multipotent neural crest can give rise to vascular smooth muscle in parts of the head and also the cardiac outflow tract. Although transforming growth factor-beta (TGF-beta) has previously been shown to induce some smooth muscle markers from primary cultures of neural crest stem cells, the extent of the differentiation induced was not clear. In this study, we demonstrate that TGF-beta can induce many of the markers and characteristics of vascular smooth muscle from a neural crest stem cell line, Monc-1. Within 3 days of in vitro treatment, TGF-beta induces multiple smooth muscle-specific markers, while downregulating epithelial markers present on the parent cells. Treatment with TGF-beta also induces a contractile phenotype that responds to the muscarinic agonist carbachol and is not immediately reversed on TGF-beta withdrawal. Examination of the signaling pathways involved revealed that TGF-beta activation of Smad2 and Smad3 appear to be essential for the observed differentiation. Taken together, this system provides a novel model of smooth muscle differentiation that reliably recapitulates the process observed in vivo and allows for dissection of the pathways and processes involved in this process.
Crystal Structure of Zeolite MCM-68:  A New Three-Dimensional Framework with Large Pores (2006)

The crystal structure of the aluminosilicate MCM-68 was solved from synchrotron powder diffraction data by the program FOCUS. The unit cell framework contains Si100.6Al11.4O224. This material crystallizes in space group P42/mnm, where, after Rietveld refinement, a = 18.286(1) Å and c = 20.208(2) Å. A three-dimensional framework is found that contains continuous 12-ring channels and two orthogonal, intersecting, undulating 10-ring channels. Rietveld refinement of the model coordinates optimizes the framework geometry, to match the observed intensity profile by Rwp = 0.1371, R(F2) = 0.1411. It is not possible to determine the location of approximately 0.84 K+ cations remaining in the unit cell after the material is steamed and then dehydrated. The framework model also successfully predicts observed electron diffraction data in two projections, and the tetragonal projection can be determined independently from these data by direct methods. The calculated density of the framework structure is 1.66 g/cm3, and the T-site framework density is 16.6 T/1000 Å3.
Ubiquitin is a heat shock protein in chicken embryo fibroblasts. (1985)

Clones containing heat-inducible mRNA sequences were selected from a cDNA library prepared from polyadenylated RNA isolated from heat-shocked chicken embryo fibroblasts. One recombinant DNA clone, designated clone 7, hybridized to a 1.2-kilobase RNA that was present in normal cells and increased fivefold during heat shock. Clone 7 also hybridized to an RNA species of 1.7 kilobases that was present exclusively in heat-shocked cells. In vitro translation of mRNA hybrid selected from clone 7 produced a protein product with a molecular weight of approximately 8,000. Increased synthesis of a protein of similar size was detected in chicken embryo fibroblasts after heat shock. DNA sequence analysis of clone 7 indicated its protein product has amino acid sequences identical to bovine ubiquitin. In addition, clone 7 contains tandem copies of the ubiquitin sequences contiguous to each other with no untranslated sequences between them. We discuss some possible roles for ubiquitin in the heat shock response.
Sec-Independent Protein Translocation by the Maize Hcf106 Protein (1997)

The bacterial Sec and signal recognition particle (ffh-dependent) protein translocation mechanisms are conserved between prokaryotes and higher plant chloroplasts. A third translocation mechanism in chloroplasts [the proton concentration difference (DeltapH) pathway] was previously thought to be unique. The hcf106 mutation of maize disrupts the localization of proteins transported through this DeltapH pathway in isolated chloroplasts. The Hcf106 gene encodes a receptor-like thylakoid membrane protein, which shows homology to open reading frames from all completely sequenced bacterial genomes, which suggests that the DeltapH pathway has been conserved since the endosymbiotic origin of chloroplasts. Thus, the third protein translocation pathway, of which HCF106 is a component, is found in both bacteria and plants.
Novel Platelet Inhibitors (2001)

Platelet-inhibitory drugs are of proven benefit to individuals who suffer from atherosclerotic cardiovascular disease. Despite substantial effort to identify more potent platelet-inhibitory agents, aspirin, an irreversible inhibitor of platelet cyclooxygenase activity, remains the standard against which other drugs are judged. Drugs that appear to be at least as efficacious as aspirin in specific clinical settings include the thienopyridines ticlopidine and clopidogrel, specific inhibitors of ADP-stimulated platelet function, and the phosphodiesterase 3 inhibitor cilostazol. Ligand binding to the platelet integrin alphaIIbbeta3 (GPIIb-IIIa), a prerequisite for platelet thrombus formation, has been a prominent target for drug development. Currently, three types of alphaIIbbeta3 antagonists are available: the monoclonal antibody Fab fragment abciximab, cyclic peptides based on the Arg-Gly-Asp (RGD) or related amino acid motifs, and RGD-based peptidomimetics. The efficacy of each type of alphaIIbbeta3 antagonist in the setting of acute coronary artery disease has been confirmed in multicenter clinical trials.
Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype. (1992)

We report the molecular cloning of a fragment of human genomic DNA called S12, containing an open reading frame of 1170 nucleotides, which encodes a receptor for serotonin of 390 amino acids. The receptor function of the S12 protein was demonstrated by functional expression in mouse LS12 cells obtained by stable transfection of Ltk- cells, and LM5S12 cells, derived from LM5 cells (Ltk- cells previously transfected with the M5 muscarinic acetylcholine receptor). Adenylyl cyclase studies showed that the S12 receptor is able to mediate inhibition of adenylyl cyclase in response to serotonin in both types of cells. As studied in LM5S12 cells, the S12 receptor did not promote Ca2+ mobilization from internal stores, nor did it significantly modulate the sustained increase in [Ca2+]i elicited by stimulation of the phospholipase C stimulating M5 acetylcholine receptor. The pharmacologic profile of S12 as seen in adenylyl cyclase assays is as follows: (EC50 in nM): serotonin, full agonist (37 nM), 5-carboxamidotryptamine, full agonist (10 nM), sumatriptan, full agonist (50 nM), metergoline, partial agonist (10 nM), methysergide, partial agonist (40 nM), yohimbine, partial agonist (150 nM), metitepin, antagonist (KB = 0.7 to 1.2 nM). We propose that the human S12 serotonin receptor is a receptor of the 5-hydroxytryptamine1D subtype.
Targets and strategies for T-cell based vaccines in patients with B-cell chronic lymphocytic leukemia (2006)

T-cell based immunotherapies might be a novel option for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), a disease characterized by a prolonged natural course. Different strategies of active immunotherapy have been tested in vitro to enhance a specific T-cell response against tumor cells and an anti-leukemic effect has been observed in B-CLL patients after allogenic stem cell transplantation. Several antigens have been characterized as tumor/leukemia associated antigens (T/LAAs) in B-CLL with the potential to elicit specific anti-tumor response encompassing idiotype immunoglobulin, oncofetal antigen-immature laminin receptor protein (OFAiLRP), survivin, as well as fibromodulin, the receptor for hyaluronic acid mediated motility (RHAMM/CD168) and the murine double-minute 2 oncoprotein (MDM2). This study presents an overview of possible targets and genetherapeutical maneuvers for future immunotherapies of B-CLL patients and summarizes recent clinical vaccination trials with dendritic cells (DCs) for B-CLL.
Microvascular Response to Compartment Syndrome-Like External Pressure Elevation (1999)

Our study disproves the critical closing theory but complies-in particular because of the supposed constriction-induced increase of venular resistance-with the hypothesis of reduced arteriovenous pressure gradients as the cause of flow cessation in compartment syndrome. The necessity of a substantially increased perfusion pressure gradient to restart blood flow in arterioles, capillaries, and venules confirms the existence of yield stress in these microvessels. The high susceptibility of capillaries to elevated external pressure indicates the necessity of early fasciotomy to restore impaired nutritive circulation in cases of compartment syndrome.
Mass spectrometry analysis of CD4‐associating proteins using affinity chromatography and affinity tag‐mediated purification of tryptic peptides (2003)

The study of protein interactions using mass spectrometry (MS) for identification of the components of purified protein complexes is leading to the description of increasingly valuable data on protein function. Commonly proteins in a given complex are identified via MS analysis of in-gel digests of gel electrophoretically separated proteins. In this study, we have evaluated the use of an approach employing the digest of the whole protein complex to identify directly the proteins present in a purification of the CD4 receptor complex. We used a cysteinyl affinity capture method to reduce the complexity of the peptide mixture that was obtained from the tryptic digest of the whole protein complex to the rather limited mixture of only cysteine-containing peptides. Here we report the use of this approach with MS for identification of the CD4 receptor complex components CD4 and p56lck, along with several other proteins present in the detergent-solubilized fractions from the purification. We have been able to identify these proteins using peptide sequence data obtained from cysteine-containing peptides. With appropriate control experiments, we have demonstrated the specific nature of the CD4-p56lck interaction. In contrast, the other proteins identified are shown to arise from nonspecific interactions during the affinity chromatography purification suggesting a possible loss of specific interactions during the chromatography procedure. We found that the complexity of the mixture was reduced such that only 10% of the peptides derived from tryptic digest of the identified proteins were detected. This represents only one-third of the cysteine-containing peptides, however, suggesting that this approach does not enable detection of all individual proteins.
Complexity and Diversity of Mammalian Adenylyl Cyclases (1996)

Molecular cloning has permitted identification of several novel isoforms of mammalian adenylyl cyclase; these proteins now comprise a family of at least 10. All of the membrane-bound enzymes are activated by the alpha subunit of G alpha, a receptor-regulated, heterotrimeric guanine nucleotide-binding protein, and by the diterpene forskolin. Certain cyclases are also activated by Ca(2+)-calmodulin, while some are inhibited by the alpha subunits of the three Gi proteins. The discovery of new isoforms has also revealed unanticipated mechanisms of regulation, including activation or inhibition by the G-protein beta gamma subunit complex, inhibition by G(o) alpha, inhibition by Ca2+, and phosphorylation by protein kinases C and A. The effects of activators are often highly synergistic or conditional, suggesting function of these enyzmes as coincidence detectors. The plethora of receptors, G proteins, and adenylyl cyclases permits assembly of very complex signaling systems with a wide variety of integrative characteristics.
Triplet Emitters for Organic Light‐Emitting Diodes: Basic Properties (2007)

This chapter contains sections titled: Introduction Electro-Luminescence and the Population of Excited States Multilayer Design of an OLED Electron–Hole Recombination, Relaxation Paths, and Light Emission Electronic Excitations and Excited States Ligand-Centered (LC) Transitions: States and Splittings Metal-Centered Transitions and States Metal-to-Ligand Charge Transfer/Ligand-Centered Transitions: States in Organo-Transition Metal Triplet Emitters Introductory MO Model and Energy States Extended MO Model and Energy States Spin–Orbit Coupling, Triplet Substates, Zero-Field Splitting, and Radiative Decay Rates Zero-Field Splitting (ZFS) of the Emitting Triplet, Photophysical Trends, and Ordering Scheme for Organo-Transition Metal Compounds Ordering Scheme Photophysical Properties and ZFS Singlet–Triplet Splitting Intersystem Crossing Rates Emission Decay Time and Photoluminescence Quantum Yield Zero-Field Splitting – Summarizing Remarks Emission Band Structures and Vibrational Satellites Localization/Delocalization and Geometry Changes in the Excited Triplet State Characterization of the Lowest Triplet State Based on High-Resolution Spectroscopy: Application to Pt(thpy)2 Highly Resolved Electronic Transitions Symmetry and Grouptheoretical Considerations Characterization of the Lowest Triplet State Based on Decay Time Measurements: Application to Ir(ppy)3 Phosphorescence Dynamics and Spin–Lattice Relaxation: Background and Case Study Applied to Pt(thpy)2 Processes of Spin–Lattice Relaxation The Direct Process The Orbach Process The Raman Process Population and Decay Dynamics of the Triplet Substates of Pt(thpy)2 The Triplet State Under Application of High Magnetic Fields: Properties of Ir(btp)2(acac) Vibrational Satellite Structures: Case Studies Applied to Pt(thpy)2 and Ir(btp)2(acac) Vibrational Satellites: Background Franck–Condon Activity Herzberg–Teller Activity Pt(thpy)2 Emission: Temperature- and Time-Dependence of the Vibrational Satellite Structure Herzberg–Teller-Induced Emission from Substate I: The 1.3 K Spectrum Franck–Condon Activity in the Emissions from Substates II and III: The 20 K Spectrum Time-Resolved Emission and Franck–Condon/Herzberg–Teller Activities Ir(btp)2(acac) Emission: Low-Temperature Vibrational Satellite Structure Environmental Effects on Triplet State Properties: Case Studies Applied to Ir(btp)2(acac) Energy Distribution of Sites Zero-Field Splittings at Different Sites Emission Decay and Spin–Lattice Relaxation Times Emission Linewidths and Spectral Broadening Effects Inhomogeneous Linewidths Homogeneous Linewidths Line Broadening Effects on the Example of Pt(thpy)2 Phenomenological Simulation of Spectral Broadening Conclusions
Solution Conformations of Helix-Forming β-Amino Acid Homooligomers (2000)

The conformational properties of β-peptides comprised of enantiomerically pure trans-2-aminocyclohexanecarboxylic acid (ACHC) or trans-2-aminocyclopentanecarboxylic acid (ACPC) units were studied by NMR spectroscopy in organic solvents. In pyridine-d5 solution, ACPC hexamer 1 and ACPC octamer 2 displayed well-defined helical structures characterized by a series of 12-membered hydrogen-bonded rings (“12-helix”). The solution structures calculated from the NMR-derived constraints were very similar to the conformations found previously for 1 and 2 in the solid state. ACHC tetramer 3 displayed a different sort of helical conformation, characterized by a series of 14-membered hydrogen-bonded rings (“14-helix”), in methanol-d3 solution. This solution conformation is similar to that previously found in the crystal structure of 3.
Critical role for Rsk2 in T-lymphocyte activation (2007)

During T-cell activation, a number of cytokine-activated signaling cascades, including the Jak-STAT, phosphoinositol 3-kinase (PI 3-kinase), and mitogen-activated protein kinase (MAPK) pathways, play important roles in modulating the expression of target genes and mediating a cellular response. We now report that interleukin 2 (IL-2) and IL-15, but not IL-7, rapidly activate the p90 ribosomal S6 kinases, Rsk1 and Rsk2, in human T lymphocytes. Surprisingly, mouse spleen T cells transduced with either the wild-type or a dominant-negative (DN) Rsk2-expressing retrovirus could not be recovered, in contrast to the normal survival of T cells transduced with retroviruses expressing wild-type or DN mutants of Rsk1 or Rsk3. Examination of Rsk2 knockout (KO) mice revealed normal T-cell development, but these T cells had delayed cell-cycle progression and lower production of IL-2 in response to anti-CD3 and anti-CD28 stimulation in vitro. Moreover, Rsk2 KO mice had defective homeostatic T-cell expansion following sublethal irradiation in vivo, which is known to involve T-cell receptor (TCR), IL-2, and/or IL-15 signals, each of which we demonstrate can rapidly and potently activate Rsk2 in mouse T cells. These results indicate an essential nonredundant role of Rsk2 in T-cell activation.
Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag (2009)

The properties of therapeutic proteins can be enhanced by chemical modification. Methods for site-specific protein conjugation are critical to such efforts. Here, we demonstrate that recombinant proteins expressed in mammalian cells can be site-specifically modified by using a genetically encoded aldehyde tag. We introduced the peptide sequence recognized by the endoplasmic reticulum (ER)-resident formylglycine generating enzyme (FGE), which can be as short as 6 residues, into heterologous proteins expressed in mammalian cells. Cotranslational modification of the proteins by FGE produced products bearing a unique aldehyde group. Proteins bearing this "aldehyde tag" were chemically modified by selective reaction with hydrazide- or aminooxy-functionalized reagents. We applied the technique to site-specific modification of monoclonal antibodies, the fastest growing class of biopharmaceuticals, as well as membrane-associated and cytosolic proteins expressed in mammalian cells.