gebhart/patrepeval huggingface dataset:
Induction of antigen-specific T cell anergy: An early event in the course of tumor progression (1998)

The priming of tumor-antigen-specific T cells is critical for the initiation of successful anti-tumor immune responses, yet the fate of such cells during tumor progression is unknown. Naive CD4(+) T cells specific for an antigen expressed by tumor cells were transferred into tumor-bearing mice. Transient clonal expansion occurred early after transfer, accompanied by phenotypic changes associated with antigen recognition. Nevertheless, these cells had a diminished response to peptide antigen in vitro and were unable to be primed in vivo. The development of antigen-specific T cell anergy is an early event in the tumor-bearing host, and it suggests that tolerance to tumor antigens may impose a significant barrier to therapeutic vaccination.
Proteasome-Mediated Proteolysis of Estrogen Receptor: A Novel Component in Autologous Down-Regulation (1999)

Regulation of estrogen receptor (ER) concentration is a key component in limiting estrogen responsiveness in target cells. Yet the mechanisms governing ER concentration in the lactotrope cells of the anterior pituitary, a major site of estrogen action, are undetermined. In this study, we used a lactotrope cell line, PR1, to explore regulation of ER protein by estrogen. Estrogen treatment resulted in an approximate 60% decrease in ER steady state protein levels. Suprisingly, the decline in ER protein was apparent within 1 h of estrogen treatment and occurred in the absence of protein synthesis and transcription. Direct regulation of ER protein was further confirmed by pulse chase analysis, which showed that ER protein half-life was shortened from greater than 3 h to 1 h in the presence of estrogen. The estrogen-induced degradation of ER protein could be prevented by pretreatment with peptide aldehyde inhibitors of proteasome protease whereas inhibitors of calpain and lysosomal proteases were ineffective. Inhibition of proteasome activity maintained ER protein at a level equivalent to control cells not stimulated with estrogen but increased estrogen-binding activity by 1.75-fold. Proteolytic regulation of ER by the proteasome is not limited to pituitary lactotrope cells but is also operational in MCF-7 breast cancer cells, suggesting that this may be a common regulatory pathway used by estrogen. These studies describe a nongenomic action of estrogen that involves nuclear ER: rapid proteolysis of ER protein via a proteasome-mediated pathway.
13C-bicarbonate breath test as a measure of gastric emptying. (1991)

Radionuclide studies are widely used to estimate the gastric emptying rate of solids and liquids. Unfortunately, these methods carry the risk of radiation exposure and require expensive and complex equipment. Carbon-13, a stable, nonradioactive isotope, has been used successfully as a marker in the gastrointestinal tract for other purposes. A preliminary study using ingested NaH13CO3 and measuring 13CO2 breath excretion suggested that this test might be a simple, noninvasive, and inexpensive method for determining gastric emptying. To determine the efficacy of NaH13CO3 as a noninvasive marker for gastric emptying, the resulting 13CO2 breath excretion was determined simultaneously with standard radiolabeled meal measurements of gastric emptying of liquids and solids in 15 patients. 13CO2 breath excretion did not correlate with the gastric emptying of either solids or liquids, as determined by radionuclide techniques. These results suggest that NaH13CO3 is not a reliable indicator of gastric emptying. Factors other than gastric emptying may affect the rate of 13CO2 absorption and exhalation, rendering it unreliable as a measure of gastric emptying.
Functional domains of the insulin receptor responsible for chemotactic signaling. (1994)

The insulin receptor mediates a variety of cellular responses to insulin, including glucose transport, endocytosis, and cell proliferation. The role of the insulin receptor in mediating cellular motility has not, however, been extensively investigated. In this report, we demonstrate that chinese hamster ovary (CHO) cells that normally have low concentrations of insulin receptor display chemotaxis toward insulin after overexpression of the wild type human insulin receptor. Chemotaxis toward insulin proceeded through a pertussis toxin-sensitive pathway and required both tyrosine kinase activity and tyrosine autophosphorylation of the regulatory region of the beta-subunit. In contrast, the autophosphorylation sites in the carboxyl terminus of the receptor were not required for chemotactic activity. A mutation in the juxtamembrane region, which disabled tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), also prevented the chemotactic response, suggesting a possible role for IRS-1 in chemotactic signaling. In the absence of insulin receptor, however, the presence of excess transfected IRS-1 was not sufficient to mediate chemotaxis toward insulin. These results demonstrate that the intact insulin receptor can stimulate a chemotactic signaling pathway and that this initial pathway more closely correlates with that for insulin-stimulated cell proliferation than for insulin-stimulated receptor endocytosis.
To branch or not to branch (2011)

PSD-95, a synaptic scaffolding protein, plays important roles in the regulation of dendritic spine morphology and glutamate receptor signaling. We have recently shown that PSD-95 also plays an extrasynaptic role during development. PSD-95 shapes dendrite branching patterns in cultured rat hippocampal neurons by altering microtubule dynamics via an association with the microtubule end-binding protein-3 (EB3). We discovered that PSD-95 interacts directly with EB3 and that the result of this interaction decreases EB3 binding to and EB3 comet lifetime on microtubules. This decrease in lifetime also correlates to decreased dendrite branching. Here we present an additional effect of PSD-95 overexpression on microtubules. Neurons that overexpress PSD-95 show increased distance between microtubules in a manner that is not fully dependent on the interaction between PSD-95 and EB3. We discuss these new data in the context of the role of PSD-95 in shaping the dendritic arbor, and we extend our findings to include a discussion of how PSD-95 may guide neurons toward a more mature and synapse-oriented growth stage.
Expression and V(D)J recombination activity of mutated RAG-1 proteins (1993)

Journal Article Expression and V(D)J recombination activity of mutated RAG-1 proteins Get access Moshe J. Sadofsky, Moshe J. Sadofsky Laboratory of Molecular Biology, NIDDK, NIHBethesda MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Joanne E. Hessw, Joanne E. Hessw Laboratory of Molecular Biology, NIDDK, NIHBethesda MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar J.Fraser McBlane, J.Fraser McBlane Laboratory of Molecular Biology, NIDDK, NIHBethesda MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin Gellert Martin Gellert * Laboratory of Molecular Biology, NIDDK, NIHBethesda MD 20892, USA * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 21, Issue 24, 11 December 1993, Pages 5644–5650, https://doi.org/10.1093/nar/21.24.5644 Published: 11 December 1993 Article history Received: 02 September 1993 Revision received: 31 October 1993 Accepted: 31 October 1993 Published: 11 December 1993
Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. (1990)

The HER-2/neu proto-oncogene is homologous with, but distinct from, the epidermal growth factor receptor. Current evidence indicates that this gene is frequently amplified and/or overexpressed in some human breast and ovarian cancers and that these alterations may be clinically important; however, little is known about the expression pattern of the gene in normal tissues. Using immunohistochemistry and northern blot analyses to identify the HER-2/neu protein and transcript respectively, we have evaluated a variety of normal adult and fetal tissues for HER-2/neu expression. HER-2/neu protein was identified on cell membranes of epithelial cells in the gastro-intestinal, respiratory, reproductive, and urinary tract as well as in the skin, breast and placenta. Northern hybridization confirmed the presence of the 4.5 kb transcript encoding the protein in these tissues. The amount of HER-2/neu message and protein was generally higher in fetal tissues than in the corresponding normal adult tissues. HER-2/neu expression levels in these normal tissues were similar to the levels found in non-amplified, non-overexpressing breast cancers and breast cancer cell lines. Southern hybridization of extracted DNA showed that none of the normal tissues expressing HER-2/neu had amplification of the gene. These results confirm that HER-2/neu is normally a membrane constituent of a variety of epithelial cell types.
Construction of a diabody (small recombinant bispecific antibody) using a refolding system (2000)

Diabodies are the recombinant bispecific antibodies (BsAbs), constructed from heterogeneous single-chain antibodies. Usually, diabodies have been prepared from bacterial periplasmic fraction using a co-expression vector (i.e. genes encoding two chains were tandemly located under the same promoter). Some diabodies, however, cannot be expressed as a soluble material owing to inclusion body formation, which limits the utilization of diabodies in various fields. Here we report an improved method for the construction of diabodies using a refolding system. As a model, a bispecific diabody binding to adenocarcinoma-associated antigen MUC1 and to CD3 on T cells was studied. One chain consisted of a VH specific for MUC1 linked to a VL specific for CD3 with a short polypeptide linker (GGGGS). The second was composed of a VL specific for MUC1 linked to a VH specific for CD3. The two hetero scFvs were independently obtained from intracellular insoluble fractions of Escherichia coli, purified, mixed stoichiometrically (at an equivalent molar ratio of 1:1) and refolded. The refolded two hetero scFv has a hetero-dimeric structure, with complete specificity for both target cells [i.e. MUC1 positive cells and CD3 positive lymphokine-activated killer cells with a T cell phenotype (T-LAK)]. Evaluation of the in vitro efficacy of T-LAK with the diabody by growth inhibition assay of cancer cells demonstrated maximum growth inhibition of cancer cells to reach approximately 98% at an effector:target ratio (E:T ratio) of 10, almost identical with that with anti-MUC1xanti-CD3 chemically synthesized BsAbs (c-BsAbs). This is the first report of the construction of a diabody using a refolding system.
EL SARCÓFAGO TARDORROMANO DE TONA (BARCELONA) (2000)

El presente estudio aborda de manera monográfica la problemática existente en referencia a los fragmentos de sarcórfago tardorromano hallados en 1943 en la localidad barcelonesa de Tona. A pesar de su innegable interés histórico e iconográfico, hasta el momento presente los fragmentos apenas han recibido una atención promenorizada por parte de la comunidad científica. Su estudio nos permite confirmar la existencia de talleres locales de escultura funeraria activos en la zona a caballo entre los siglos IV-V, así como el modo en que la Hispania del momento recibe, asimila y materializa los modelos iconográficos procedentes de Roma.Palabras Clave. Antigüedad Tardía, Escultura tardorromana, iconografía, sarcófagos cristianos antiguos.AbstractThe Present Study focuses on the two Sacorphagus fragments discovered in 1943 in the little Village of Tona (Barcelona). Despite of their historical and iconographical value, until the present day both Fragments were almost ignored by most of the Scholars. The new Study of the Fragments brings now precious Information about the local Production of Sarcophagi int the Roman Hispania between the 4th and 5th Centuries. Furthermore the study give also new light on the process of reception and transformation of iconographical models coming from the city of Rome.Keywords. Late Antiquity, Late roman Sculpture, Iconography, Ancient Christian Sacophagi.
Cyclosporin Metabolism in Human Liver Microsomes and Its Inhibition by Other Drugs (1990)

The metabolism of cyclosporin was studied in human liver microsomes. There was no metabolism in the presence of cytochrome C or carbon monoxide or in the absence of cofactors, suggesting metabolism by cytochrome P-450 enzymes. The metabolism was inhibited by ketoconazole and erythromycin, by the steroids methylprednisolone and oestradiol, and by the calcium antagonists diltiazem, nifedipine, prenylamine and verapamil. These in vitro findings correlate well with previously published clinical reports suggesting that these drugs may inhibit the metabolism of cyclosporin in vivo. Our observations suggest that metabolic interactions between cyclosporin and other drugs in vivo may be predicted in vitro under proper experimental conditions.
Role of volatile fatty acids in colonization resistance to Clostridium difficile in gnotobiotic mice (1987)

Clostridium difficile is an agent involved in the development of antibiotic-associated pseudomembranous colitis. The purpose of this work was to investigate the role of volatile fatty acids (VFAs) in resistance to colonization by C. difficile by using a gnotobiotic animal model. Accordingly, germfree mice were associated with different hamster flora, and the VFAs in their cecal contents were measured by gas chromatography. The results showed that VFAs were produced mainly by the intestinal flora, especially by the strictly anaerobic bacteria. In these associated mice, the concentrations of acetic, propionic, and butyric acids were higher than those of other acids, but at pH 6.8 the MICs of these three acids in vitro for C. difficile were more than 200 mu eq/ml. In gnotobiotic mice monoassociated with C. difficile and in the isolated ceca of these mice, VFAs did not inhibit the growth of C. difficile. In gnotobiotic mice which were diassociated with C. difficile and C. butyricum and given drinking water with a lactose concentration of 20%, the cecal contents included about the same amount of butyric acid as did those of the monoassociated mice, although the population of C. difficile remained the same. Therefore, it is suggested that VFAs alone cannot inhibit intestinal colonization by C. difficile and that, consequently, other inhibitory mechanisms are also present.
Initial Experience in Humans with a New Retrievable Inferior Vena Cava Filter (2002)

This preliminary experience in humans confirms the efficacy of the RNF. It also demonstrates the feasibility and safety of retrieval up to 134 days after implantation.
Deterministic Usage of the Digital Signature Algorithm (DSA) and Elliptic Curve Digital Signature Algorithm (ECDSA) (2013)

This document defines a deterministic digital signature generation procedure.Such signatures are compatible with standard Digital Signature Algorithm (DSA) and Elliptic Curve Digital Signature Algorithm (ECDSA) digital signatures and can be processed with unmodified verifiers, which need not be aware of the procedure described therein.Deterministic signatures retain the cryptographic security features associated with digital signatures but can be more easily implemented in various environments, since they do not need access to a source of high-quality randomness.
Checking linked data structures (2002)

In the program checking paradigm, the original program is run on the desired input, and its output is checked by another program called a checker. Recently, the notion of program checking has been extended from its original formulation of checking functions to checking a sequence of operations which query and alter the state of an object external to the program, e.g., checking the interactions between a client and the manager (server) of a data structure. In this expanded paradigm, the checker acts as an intermediary between the client, which generates the requests, and the server, which processes them. The checker is allowed a small amount of reliable memory and may provide a probabilistic guarantee of correctness for the client. We present off-line and on-line checkers for data structures such as linked lists, trees, and graphs. Previously, the only data structures for which such checkers existed were random access memories, stacks, and queues.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Molecular Cloning and Characterization of the Human Prostanoid DP Receptor (1995)

A cDNA encoding a functional human prostanoid DP (hDP) receptor has been constructed from a genomic clone and a fragment cloned by 3'-rapid amplification of cDNA ends-polymerase chain reaction. The hDP receptor consists of 359 amino acid residues with a predicted molecular mass of 40,276 and has the putative heptahelical transmembrane domains characteristics of G-protein-coupled receptors. The deduced amino acid sequence of the hDP receptor, when compared with all other members of the prostanoid receptor family, shows the highest degree of identity with the hIP and hEP2 receptors, followed by the hEP4 receptor. Radioreceptor binding studies using membranes prepared from mammalian COS-M6 cells transiently transfected with an expression vector containing the DP receptor cDNA showed that the rank order of affinities for prostaglandins and prostaglandin analogs, in competition for [3H]prostaglandin D2 (PGD2) specific binding sites, was as predicted for the DP receptor, with PGD2 >> PGE2 > PGF2 alpha = iloprost > U46619. The signal transduction pathway of the cloned hDP receptor was studied by transfecting the hDP expression vector in HEK 293(EBNA) cells. Activation of the hDP receptor with PGD2 resulted in an elevation of intracellular cAMP and in mobilization of Ca2+, but did not lead to generation of inositol 1,4,5-trisphosphate. Northern blot analysis of human tissue showed that the hDP receptor was a very discrete tissue distribution and was detectable only in retina and small intestine. In summary, we have cloned and expressed a functional cDNA for the hDP receptor.
Denaturing high performance liquid chromatography: high throughput mutation screening in familial hypertrophic cardiomyopathy and SNP genotyping in motor neurone disease (2005)

DHPLC is a high throughput, sensitive, specific, and robust platform for the detection of DNA variants, such as disease causing mutations or SNPs. It enables rapid and accurate screening of large genomic regions.
Heparin-Protein Interactions (2002)

Heparin, a sulfated polysaccharide belonging to the family of glycosaminoglycans, has numerous important biological activities, associated with its interaction with diverse proteins. Heparin is widely used as an anticoagulant drug based on its ability to accelerate the rate at which antithrombin inhibits serine proteases in the blood coagulation cascade. Heparin and the structurally related heparan sulfate are complex linear polymers comprised of a mixture of chains of different length, having variable sequences. Heparan sulfate is ubiquitously distributed on the surfaces of animal cells and in the extracellular matrix. It also mediates various physiologic and pathophysiologic processes. Difficulties in evaluating the role of heparin and heparan sulfate in vivo may be partly ascribed to ignorance of the detailed structure and sequence of these polysaccharides. In addition, the understanding of carbohydrate-protein interactions has lagged behind that of the more thoroughly studied protein-protein and protein-nucleic acid interactions. The recent extensive studies on the structural, kinetic, and thermodynamic aspects of the protein binding of heparin and heparan sulfate have led to an improved understanding of heparin-protein interactions. A high degree of specificity could be identified in many of these interactions. An understanding of these interactions at the molecular level is of fundamental importance in the design of new highly specific therapeutic agents. This review focuses on aspects of heparin structure and conformation, which are important for its interactions with proteins. It also describes the interaction of heparin and heparan sulfate with selected families of heparin-binding proteins.
Input space versus feature space in kernel-based methods (1999)

This paper collects some ideas targeted at advancing our understanding of the feature spaces associated with support vector (SV) kernel functions. We first discuss the geometry of feature space. In particular, we review what is known about the shape of the image of input space under the feature space map, and how this influences the capacity of SV methods. Following this, we describe how the metric governing the intrinsic geometry of the mapped surface can be computed in terms of the kernel, using the example of the class of inhomogeneous polynomial kernels, which are often used in SV pattern recognition. We then discuss the connection between feature space and input space by dealing with the question of how one can, given some vector in feature space, find a preimage (exact or approximate) in input space. We describe algorithms to tackle this issue, and show their utility in two applications of kernel methods. First, we use it to reduce the computational complexity of SV decision functions; second, we combine it with the Kernel PCA algorithm, thereby constructing a nonlinear statistical denoising technique which is shown to perform well on real-world data.