gebhart/patrepeval huggingface dataset:
Simultaneous Targeting of Tumor Antigens and the Tumor Vasculature Using T Lymphocyte Transfer Synergize to Induce Regression of Established Tumors in Mice (2013)

Most systemic cancer therapies target tumor cells directly, although there is increasing interest in targeting the tumor stroma that can comprise a substantial portion of the tumor mass. We report here a synergy between two T-cell therapies, one directed against the stromal tumor vasculature and the other directed against antigens expressed on the tumor cell. Simultaneous transfer of genetically engineered syngeneic T cells expressing a chimeric antigen receptor targeting the VEGF receptor-2 (VEGFR2; KDR) that is overexpressed on tumor vasculature and T-cells specific for the tumor antigens gp100 (PMEL), TRP-1 (TYRP1), or TRP-2 (DCT) synergistically eradicated established B16 melanoma tumors in mice and dramatically increased the tumor-free survival of mice compared with treatment with either cell type alone or T cells coexpressing these two targeting molecules. Host lymphodepletion before cell transfer was required to mediate the antitumor effect. The synergistic antitumor response was accompanied by a significant increase in the infiltration and expansion and/or persistence of the adoptively transferred tumor antigen-specific T cells in the tumor microenvironment and thus enhanced their antitumor potency. The data presented here emphasize the possible beneficial effects of combining antiangiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer.
IL-2 Receptor β-Dependent STAT5 Activation Is Required for the Development of Foxp3+ Regulatory T Cells (2007)

IL-2(-/-) mice develop autoimmunity despite having relatively normal numbers of regulatory T cells (Tregs). In contrast, we demonstrate that IL-2(-/-) x IL-15(-/-) and IL-2Rbeta(-/-) mice have a significant decrease in Treg numbers. Ectopic expression of foxp3 in a subset of CD4(+) T cells rescued Treg development and prevented autoimmunity in IL-2Rbeta(-/-) mice, suggesting that IL-2Rbeta-dependent signals regulate foxp3 expression in Tregs. Subsequent analysis of IL-2Rbeta-dependent signal transduction pathways established that the transcription factor STAT5 is necessary and sufficient for Treg development. Specifically, T cell-specific deletion of STAT5 prevented Treg development; conversely, reconstitution of IL-2Rbeta(-/-) mice with bone marrow cells expressing an IL-2Rbeta mutant that exclusively activates STAT5 restored Treg development. Finally, STAT5 binds to the promoter of the foxp3 gene suggesting that IL-2Rbeta-dependent STAT5 activation promotes Treg differentiation by regulating expression of foxp3.
Sulphydryl modifications alter scramblase activity in murine sickle cell disease (2006)

Increased oxidant stress has been suggested to play a role in the process of phosphatidylserine (PS) externalization in the red blood cells of sickle cell patients. Inhibition of the ATP-driven translocation from outer to inner monolayer (flippase) by sulphydryl modification has been established. The present study showed that phospholipid scrambling was also sensitive to protein sulphydryl modification. Treatment with N-ethylmaleimide lead to enhanced PS exposure and a lower Ca(++) requirement for scrambling. In contrast, pyridyldithioethylamine treatment inhibited PS exposure. Red blood cells from a murine model for sickle cell disease exhibited a reduced response to both reagents, suggestive of previous sulphydryl modifications to the protein(s) involved in phospholipid scrambling. We conclude that sulphydryl modifications to both scramblase and flippase underlie the enhanced formation of PS-exposing cells in sickle cell disease.
ANTINEOPLASTIC AGENTS: IX. N-BENZYL-N-BIS(2-HALOETHYL)AMINES (1963)

A number of N-bis(2-chloroethyl)amines and three N-bis(2-iodoethyl)benzylamines have been prepared for cancer chemotherapy studies. The chloro-nitrogen mustards were readily obtained by aluminum chloride – lithium aluminum hydride reduction of the corresponding N-bis(2-chloroethyl)amides. A convenient procedure for converting N-bis(2-chloroethyl)-benzylamine hydrochlorides to N-bis(2-iodoethyl)benzylamine hydroiodides, employing sodium iodide, was also developed.
A New Algorithm for DNA Sequence Assembly (1995)

Since the advent of rapid DNA sequencing methods in 1976, scientists have had the problem of inferring DNA sequences from sequenced fragments. Shotgun sequencing is a well-established biological and computational method used in practice. Many conventional algorithms for shotgun sequencing are based on the notion of pairwise fragment overlap. While shotgun sequencing infers a DNA sequence given the sequences of overlapping fragments, a recent and complementary method, called sequencing by hybridization (SBH), infers a DNA sequence given the set of oligomers that represents all subwords of some fixed length, k. In this paper, we propose a new computer algorithm for DNA sequence assembly that combines in a novel way the techniques of both shotgun and SBH methods. Based on our preliminary investigations, the algorithm promises to be very fast and practical for DNA sequence assembly.
Molecular Shape of the Cationic Lipid Controls the Structure of Cationic Lipid/Dioleylphosphatidylethanolamine-DNA Complexes and the Efficiency of Gene Delivery (2001)

Pyridinium amphiphiles, abbreviated as SAINT, are highly efficient vectors for delivery of DNA into cells. Within a group of structurally related compounds that differ in transfection capacity, we have investigated the role of the shape and structure of the pyridinium molecule on the stability of bilayers formed from a given SAINT and dioleoylphosphatidylethanolamine (DOPE) and on the polymorphism of SAINT/DOPE-DNA complexes. Using electron microscopy and small angle x-ray scattering, a relationship was established between the structure, stability, and morphology of the lipoplexes and their transfection efficiency. The structure with the lowest ratio of the cross-sectional area occupied by polar over hydrophobic domains (SAINT-2) formed the most unstable bilayers when mixed with DOPE and tended to convert into the hexagonal structure. In SAINT-2-containing lipoplexes, a hexagonal topology was apparent, provided that DOPE was present and complex assembly occurred in 150 mm NaCl. If not, a lamellar phase was obtained, as for lipoplexes prepared from geometrically more balanced SAINT structures. The hexagonal topology strongly promotes transfection efficiency, whereas a strongly reduced activity is seen for complexes displaying the lamellar topology. We conclude that in the DOPE-containing complexes the molecular shape and the nonbilayer preferences of the cationic lipid control the topology of the lipoplex and thereby the transfection efficiency.
Modulation of Adipose Tissue Expression of Murine Matrix Metalloproteinases and Their Tissue Inhibitors With Obesity (2002)

The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and 4 tissue inhibitors of MMPs (TIMPs) were measured by semiquantitative RT-PCR in adipose tissue isolated from mice maintained for 15 weeks on a standard or high-fat diet. In mice on standard diet, with the exception of MMP-8, all MMP and TIMP transcripts were detected in both gonadal and subcutaneous depots. In obese mice, the expression of MMP-3, -11, -12, -13, and -14 and TIMP-1 mRNAs was upregulated, whereas that of MMP-7, -9, -16, and -24 and TIMP-4 was downregulated. Most MMP and TIMP mRNAs were expressed at higher levels in stromal-vascular cells than in mature adipocytes. Analysis of adipose tissue by in situ fluorescent zymography revealed MMP-dependent proteolytic activities, demonstrating the presence of active MMPs in the intact tissue. In vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes was associated with substantial modulations of MMP and TIMP expression. Moreover, this in vitro adipogenesis was reduced in the presence of a synthetic MMP inhibitor. Thus, the adipose tissue expresses a large array of MMPs and TIMPs, which modulate adipocyte differentiation.
RECEPTORS MEDIATING SOME ACTIONS OF HISTAMINE (1966)

The specific antagonism of some actions of histamine by low concentrations of anti- histamine drugs characterizes one type of histamine receptor for which we suggest the symbol H. Such receptors occur in guinea-pig ileum and bronchi Several other actions of histamine, for example, stimulation of gastric acid secretion, inhibition of rat uterus and stimulation of isolated atria, cannot be specifically antagonized These actions are likely to be mediated by other histamine receptors.
Update on Antiviral DNA Vaccine Research (1998–2000) (2000)

DNA vaccines can induce protective cellular and humoral immune responses and have therefore been used during the last decade to develop vaccines against a variety of different pathogens. Because current antiviral vaccines predominantly generate humoral immunity, DNA immunization may be especially useful to provide long-term protection against viral diseases that also require cellular immunity (e.g. HIV). A significant number of articles published in the field of DNA vaccines are dealing with viral diseases, reflecting the need for better and alternative vaccination strategies against viruses. The success of DNA immunization depends on a variety of parameters (e.g. type of antigen, method of application and usage of adjuvants). Therefore, different strategies have been explored to modulate the induced immune response with respect to the requirements necessary to protect against a specific pathogen (e.g. induction of mucosal or cell-mediated immunity). The following article provides an update on different aspects of antiviral DNA vaccine research that have previously been reviewed by others.
Electroanalysis with Carbon Paste Electrodes (2012)

Because of their simple preparation and low expense, carbon pastes and carbon paste electrodes are widely used in a myriad of instrumental measurements. With an emphasis on practical applications, Electroanalysis with Carbon Paste Electrodes provides a comprehensive overview of carbon paste electrodes. The text offers a comprehensive and unpreceden
Widespread ectopic expression of olfactory receptor genes (2006)

The OR superfamily as a whole, show widespread, locus-dependent and heterogeneous expression, in agreement with a neutral or near neutral evolutionary model for transcription control. These results cannot reject the possibility that small OR subsets might play functional roles in different tissues, however considerable care should be exerted when offering a functional interpretation for ectopic OR expression based only on transcription information.
Polymorphisms of the β 2 -Adrenergic Receptor Determine Exercise Capacity in Patients With Heart Failure (2000)

The beta(2)-adrenergic receptor (beta(2)AR) exists in multiple polymorphic forms with different characteristics. Their relevance to heart failure (HF) physiology is unknown. Cardiopulmonary exercise testing was performed on 232 compensated HF patients with a defined beta(2)AR genotype. Patients with the uncommon Ile164 polymorphism had a lower peak VO(2) (15.0+/-0.9 mL. kg(-1). min(-1)) than did patients with Thr164 (17.9+/-0.9 mL. kg(-1). min(-1), P<0.0001). The percentage achieved of predicted peak VO(2) was also lower in patients with Ile164 (62. 3+/-4.5% versus 71.5+/-5.1%, P=0.045). The relative risk of a patient having a VO(2) </=14 mL. kg(-1). min(-1) who had Ile164 was 8.0 (P=0.009). Catheterization-based invasive exercise testing revealed depressed changes in the exercise-induced cardiac index, systemic vascular resistance, stroke volume, and VO(2) in patients with Ile164. The polymorphisms at position 16 also impacted exercise capacity: peak VO(2) for Arg16 versus Gly16 was 17.0+/-0.8 versus 15. 6+/-0.5 mL. kg(-1). min(-1), respectively (P=0.03). Because the polymorphisms at loci 16 and 27 can occur together, 4 homozygous combinations exist. Patients with Arg16/Glu27 had the highest percentage achieved of predicted peak VO(2) (75. 7+/-6.4%), whereas those with Gly16/Gln27 had the lowest (55.3+/-2. 8%, P=0.0032). The above findings were not confounded by baseline clinical characteristics, including beta-blocker usage. We conclude that the beta(2)AR polymorphisms Ile164, Gly16, and the combination of Gly16 and Gln27 are associated with depressed exercise performance in HF and represent a genetically determined factor in the pathophysiology of HF.
The Voltammetric Response of Nanometer-Sized Carbon Electrodes (2002)

Carbon electrodes of nanometer size have been fabricated by electrochemical etching of carbon fibers followed by deposition of electrophoretic paint. These electrodes have been characterized with steady-state voltammetry using a range of redox probes. These redox probes were chosen because they show a range of formal potentials and kinetic rate constants (k0) and are charged to different extents. The voltammetric response of these electrodes in both the presence and absence of supporting electrolyte has been investigated. In the presence of supporting electrolyte, well-defined steady-state voltammograms of sigmoidal shape have been obtained on electrodes with effective radii as small as 1 nm. In the absence of supporting electrolyte, however, the voltammetric behavior varies with the redox system. Deviation from the expected migration−diffusion response is observed when the electrode is smaller than 20 nm for the reduction of the multicharged cationic species hexammineruthenium(III) (Ru(NH3)63+). Deviation from the ideal behavior of migration-coupled diffusion is exhibited at electrodes even of micrometer size during the reduction of the multicharged hexacyanoferrate(III) anion (Fe(CN)63-), which has a median reduction potential and relatively low k0. Such an effect is also observed for the oxidation of the hexacyanoferrate(II) anion (Fe(CN)64-). In comparison, the hexachloroiridate(IV) anion (IrCl62-), with a higher k0 and more positive reduction potential, shows deviations similar to those seen for hexaammineruthenium(III); i.e., no deviation from expected behavior is seen until the electrode size is less than ca. 20 nm. It is argued that the dynamic diffuse double-layer effect rather than the Frumkin effect is the major source of the observed nonideal behavior. The results indicate that the dynamic diffuse double-layer effect can function even when the electrode reaction is reversible or quasi-reversible and becomes more pronounced at very small electrodes. The nature of size effects on the voltammetric response at nanometer size electrodes are discussed.
Biosynthesis, modification, and biodegradation of bacterial medium-chain-length polyhydroxyalkanoates. (2007)

Medium-chain-length polyhydroxyalkanoates (MCL-PHAs), which have constituents with a typical chain length of C6-C14, are polyesters that are synthesized and accumulated in a wide variety of Gram-negative bacteria, mainly pseudomonads. These biopolyesters are promising materials for various applications because they have useful mechanical properties and are biodegradable and biocompatible. The versatile metabolic capacity of some Pseudomonas spp. enables them to synthesize MCL-PHAs that contain various functional substituents; these MCL-PHAs are of great interest because these functional groups can improve the physical properties of the polymers, allowing the creation of tailor-made products. Moreover, some functional substituents can be modified by chemical reactions to obtain more useful groups that can extend the potential applications of MCL-PHAs as environmentally friendly polymers and functional biomaterials for use in biomedical fields. Although MCL-PHAs are water-insoluble, hydrophobic polymers, they can be degraded by microorganisms that produce extracellular MCL-PHA depolymerase. MCL-PHA-degraders are relatively uncommon in natural environments and, to date, only a limited number of MCL-PHA depolymerases have been investigated at the molecular level. All known MCL-PHA depolymerases share a highly significant similarity in amino acid sequences, as well as several enzymatic characteristics. This paper reviews recent advances in our knowledge of MCL-PHAs, with particular emphasis on the findings by our research group.
Ondansetron plus Metopimazine Compared with Ondansetron Alone in Patients Receiving Moderately Emetogenic Chemotherapy (1993)

Ondansetron plus metopimazine is a highly effective and safe antiemetic regimen that is markedly superior to treatment with ondansetron alone in patients receiving moderately emetogenic chemotherapy.
Beyond Triplet Loss: A Deep Quadruplet Network for Person Re-identification (2017)

Person re-identification (ReID) is an important task in wide area video surveillance which focuses on identifying people across different cameras. Recently, deep learning networks with a triplet loss become a common framework for person ReID. However, the triplet loss pays main attentions on obtaining correct orders on the training set. It still suffers from a weaker generalization capability from the training set to the testing set, thus resulting in inferior performance. In this paper, we design a quadruplet loss, which can lead to the model output with a larger inter-class variation and a smaller intra-class variation compared to the triplet loss. As a result, our model has a better generalization ability and can achieve a higher performance on the testing set. In particular, a quadruplet deep network using a margin-based online hard negative mining is proposed based on the quadruplet loss for the person ReID. In extensive experiments, the proposed network outperforms most of the state-of-the-art algorithms on representative datasets which clearly demonstrates the effectiveness of our proposed method.
Application of combinatorial library methods in cancer research and drug discovery. (1997)

Combinatorial chemistry is now considered as one of the most important recent advances in medicinal chemistry. There are five general approaches in combinatorial peptide library methods: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the 'one-bead one-compound' library method; and synthetic library methods using affinity chromatography selection. Except for the biological library approach, which is limited to peptide libraries with eukaryotic amino acids, all the other four synthetic approaches are applicable to peptide, non-peptide oligomer or small molecule libraries. Although non-peptide or small molecule libraries are generally prepared by a synthetic approach, recent advances in biosynthetic methods using enzymes may enable one to prepare chemical libraries that are otherwise difficult to synthesize chemically. In the 'one-bead one-compound' library method every member of the library is screened in parallel, but the chemical structure of the positive compound-bead has to be determined either directly or via an encoding strategy. A reliable high-throughput biological assay is needed for a successful combinatorial library screen. Solid-phase binding or functional assays as well as solution phase assays have been used successfully in various library methods. There has been enormous progress in the technological advances of molecular biology and the fundamental understanding of the molecular basis of cancer in recent years. By applying combinatorial chemistry and computational chemistry to the many cancer targets that have recently been identified, it is hopeful that more potent, more specific and less toxic anti-cancer agents will be developed in the foreseeable future. In addition to being a great tool for drug discovery, combinatorial chemistry has also proven to be invaluable in basic research. A few specific examples of the applications of combinatorial chemistry in basic cancer research and drug discovery are described in this mini-review.
Structure, Function, and Inhibition of Chemokines (2002)

Chemokines are the largest family of cytokines in human immunophysiology. These proteins are defined by four invariant cysteines and are categorized based on the sequence around the first two cysteines, which leads to two major and two minor subfamilies. Chemokines function by activating specific G protein-coupled receptors, which results in, among other functions, the migration of inflammatory and noninflammatory cells to the appropriate tissues or compartments within tissues. Some of these proteins and receptors have been implicated or shown to be involved in inflammation, autoimmune diseases, and infection by HIV-1. The three-dimensional structure of each monomer is virtually identical, but the quaternary structure of chemokines is different for each subfamily. Structure-function studies reveal several regions of chemokines to be involved in function, with the N-terminal region playing a dominant role. A number of proteins and small-molecule antagonists have been identified that inhibit chemokine activities. In this review, we discuss aspects of the structure, function, and inhibition of chemokines.
Estrogen Binding, Receptor mRNA, and Biologic Response in Osteoblast-Like Osteosarcoma Cells (1988)

High specific activity estradiol labeled with iodine-125 was used to detect approximately 200 saturable, high-affinity (dissociation constant ≅ 1.0 n M ) nuclear binding sites in rat (ROS 17/2.8) and human (HOS TE85) clonal osteoblast-like osteosarcoma cells. Of the steroids tested, only testosterone exhibited significant cross-reactivity with estrogen binding. RNA blot analysis with a complementary DNA probe to the human estrogen receptor revealed putative receptor transcripts of 6 to 6.2 kilobases in both rat and human osteosarcoma cells. Type I procollagen and transforming growth factor-β messenger RNA levels were enhanced in cultured human osteoblast-like cells treated with 1 n M estradiol. Thus, estrogen can act directly on osteoblasts by a receptor-mediated mechanism and thereby modulate the extracellular matrix and other proteins involved in the maintenance of skeletal mineralization and remodeling.
Selective reduction of disulfides by tris(2-carboxyethyl)phosphine (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective reduction of disulfides by tris(2-carboxyethyl)phosphineJohn A. Burns, James C. Butler, John Moran, and George M. WhitesidesCite this: J. Org. Chem. 1991, 56, 8, 2648–2650Publication Date (Print):April 1, 1991Publication History Published online1 May 2002Published inissue 1 April 1991https://pubs.acs.org/doi/10.1021/jo00008a014https://doi.org/10.1021/jo00008a014research-articleACS PublicationsRequest reuse permissionsArticle Views8846Altmetric-Citations596LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts