gebhart/patrepeval huggingface dataset:
Cloning and sequence determination of the gene for the human immunoglobulin epsilon chain expressed in a myeloma cell line. (1982)

Messenger RNA has been isolated from cells of the human myeloma line 266BL which synthesizes IgE of the myeloma ND. A fraction enriched in mRNA for the epsilon heavy chain was copied into DNA and the DNA was cloned in Escherichia coli. A chemically synthesized oligonucleotide probe, based on the experimentally determined sequence of the specific message, was used to screen colonies. The largest epsilon chain cDNA cloned, 2.0 kilobases, was characterized by restriction endonuclease mapping and DNA sequence analysis. It appears to encode the complete amino acid sequence of the epsilon chain, including a signal peptide at the NH2 terminus as well as untranslated sequences at the 5' and 3' ends of the mRNA. The missing part of the previously published amino acid sequence of the ND epsilon chain was determined from the DNA sequence.
Molecular Aspects and Mechanism of Action of Dihydrofolate Reductase Inhibitors (1993)

Derivatives of tetrahydrofolate (FH4) are involved in a variety of biosynthetic reactions. Inhibition of the enzyme dihydrofolate reductase (DHFR) depletes the available tetrahydrofolate and blocks the formation of thymidylate, purines, the amino acids methionine and glycine, and several other cell constituents. Lack of thymidylate disrupts DNA synthesis and cell growth ceases. Many folate analogues are competitive inhibitors of DHFR, and while some classes show no selectivity, suitably substituted diaminopyrimidines are several thousands times more active against bacterial than mammalian DHFR and are thus effective and safe antibiotics. The ease of isolation, stability and low molecular weight of DHFR has facilitated its study at a molecular level. Considerable knowledge has been accumulated about the interactions of inhibitors with the protein chain in and around the active site, but despite the availability of many sequences and several crystal structures the exact details of how subtle variations of inhibitor structure result in such large differences in affinity for the enzyme are not yet clear.
The in vitro function of lymphocytes from 25 cancer patients receiving four to seven consecutive days of recombinant IL-2. (1988)

Twenty-five cancer patients received human recombinant interleukin-2 (IL-2) for 4 to 7 consecutive days in a Phase I trial. IL-2 was administered either as a daily intravenous bolus infusion (lasting 15 min), or as a continuous infusion lasting 24 h each day. Prior studies have demonstrated that in vivo administration of IL-2 at high doses is associated with changes in the phenotype of circulating peripheral blood lymphocytes (PBL) (determined with monoclonal antibodies), and the induction of augmented in vitro natural killer activity (NK) by PBL obtained following in vivo IL-2. We have noted that fresh lymphocytes obtained after 4-7 consecutive days of IL-2 (greater than or equal to 10(6) U/m2/day) show an augmented ability to kill NK-sensitive and -insensitive target cells (K562 and Daudi targets, respectively), especially when tested with IL-2 present during the 4-h 51Cr release assay. We have further analyzed lymphocytes in a battery of in vitro proliferative and cytotoxic assays. We present here the summary of this quantitative analysis of their responses in both antigen-specific and -nonspecific immune responses. Striking in vitro changes were observed in the proliferative response to IL-2 and in cytotoxicity stimulated by (or requiring) in vitro IL-2. Proliferative responses to antigens and to mitogens were not as dramatically altered following in vivo IL-2, nor were allospecific or allo-activated cytotoxic interactions. These studies indicate that the most striking changes in lymphocyte function measured in vitro following in vivo IL-2 are seen in those functions requiring IL-2.
Epitope mapping and use of anti-idiotypic antibodies to the L6 monoclonal anticarcinoma antibody. (1990)

Mouse monoclonal anti-idiotypic antibodies (anti-ids) were raised against L6, a murine IgG2a monoclonal antibody specific for a cell surface antigen expressed by many human carcinomas. Ten distinct anti-ids were generated. Eight anti-ids were shown to inhibit the binding of L6 to its target antigen and were characterized in detail. The heavy and light chain variable region gene segments of the monoclonal antibody L6 linked to human constant regions (chimeric L6) were expressed separately or together, to map the epitopes recognized by the anti-ids. Individual anti-ids were shown to recognize heavy chain, light chain, or combinatorial variable region determinants. Defining these specificities enabled us to select particular anti-ids for assays to monitor the pharmacokinetics of either murine or chimeric L6 antibodies in the circulation of human patients. A quantitative enzyme-linked immunosorbent assay developed with two anti-ids accurately detects less than 5 ng/ml. Anti-ids specific for light chain variable region-encoded determinants were capable of recognizing L6 antigen-binding fragments bound to the surface of human carcinoma cells. These anti-ids can be used to study the binding of chimeric L6 antibody at the surface of tumor cells in histological sections of tumor biopsies.
Obesogenic environments: environmental approaches to obesity prevention (2015)

Childhood obesity is a major concern for public health. There are multiple factors (e.g., genetic, social, and environmental) that contribute to unhealthy weight gain. Drawing from findings on "obesogenic environments" and core principles of preventive strategies to reduce health inequalities, this paper gives an overview of recent childhood prevention programs that target aspects of the physical environment ("environmental changes"). Out of the ten reviews we screened (including more than 300 studies), we identified very few that addressed aspects of the environment. We focus here on 14 programs that follow different approaches to environmental changes (e.g., access to/quality of playgrounds, changes in school cafeterias). Altering the environment offers opportunities for healthier behaviors and seems to be an effective strategy to prevent childhood obesity. However, the evaluation of those (mostly) multidimensional interventions does not allow drawing firm conclusions about the single effect of environmental changes. We conclude that obesity prevention programs should combine person-based and environmental approaches.
Self-calibration of a camera from video of a walking human (2003)

Analysis of human activity from a video camera is simplified by the knowledge of the camera's intrinsic and extrinsic parameters. We describe a technique to estimate such parameters from image observations without requiring measurements of scene objects. We first develop a general technique for calibration using vanishing points and vanishing line. We then describe a method for estimating the needed points and line by observing the motion of a human in the scene. Experimental results, including error estimates, are presented.
Zeolite and molecular sieve synthesis (1992)

Zeolite and molecular sieve syntheses are reviewed. The synthesis of aluminum-rich zeolites, high-silica&#13;\nzeolites, and phosphate-based molecular sieves are evaluated. Unresolved mechanistic issues are outlined&#13;\nand areas for exploration suggested. The ability to plan zeolite and molecular sieve syntheses is discussed&#13;\nand a strategy for synthesizing a chiral zeolite is used to demonstrate the current limitations in "designing"&#13;\nnew molecular sieves.
Using capillary electrophoresis for failure analysis (1993)

Capillary electrophoresis (CE), an advanced solution analysis technique, can be used for failure analysis of corroded components. It has high sensitivity (concentrations as low as parts-per-trillion) and can detect quantitatively a large number of ionic species. CE determined the vapor-phase attack by organic acids, mainly acetic acid, on an electrical equipment enclosure. These acids most likely originated from the seasoning of the oak pallets used to transport the manufactured items, accumulating inside the shrink-wrap film used to bind packages to the pallet.
Robust Analog Precoding Designs for Millimeter Wave MIMO Transceivers (2016)

Millimeter wave communication provides high data rates thanks to large arrays at the transmitter and receiver, coupled with large bandwidth channels. Exploiting the arrays is challenging due to the need to configure precoding at the transmitter based on the large frequency selective channel. In this paper we exploit the power iteration principle and propose a robust analog precoding training algorithm that can be applied in both frequency division duplex transmission (FDD) systems and time division duplex transmission (TDD) systems with or without RF calibration. We further analyze the convergence of the proposed algorithm and show how it converges to the singular value decomposition optimality exponentially. We propose null space projection on top of the power iteration to form multiple orthogonal beams at the transmitter and receiver. Strongest tap selection with proper energy pruning is used to collect as much precoding gain as possible from a frequency selective fading channel. The exponential effective SINR mapping performance is evaluated and demonstrates that the overall approach works effectively. Numerical simulation results demonstrate algorithm robustness and the algorithm works effectively not only for the simplified millimeter wave directional channels, but also for more general rich scattering channels.
Antimalarial activity of the optical isomers of chloroquine diphosphate. (1979)

Optically pure d- and l-Chloroquine Diphosphate were examined for their efficacy against Plasmodium berghei in mice. The d-enantiomer is significantly more effective than the corresponding l-enantiomer, and in subcurative doses the d-enantiomer is also signficantly more active than the racemate. This increased activity has however no influence upon Chloroquine-resistant strains of P. berghei. The LD50 in non-infected mice is higher for the d-enantiomer than for either the racemate or the l-enantiomer when mice were treated orally one and 4 times. These differences in efficacy and toxicity between the d- and l-enantiomer of Chloroquine are however not as pronounced as those found for the enantiomers of many other drugs and furthermore these differences are limited to subcurative doses.
Identification of Host Proteins Associated with Retroviral Vector Particles by Proteomic Analysis of Highly Purified Vector Preparations (2007)

ABSTRACT The Moloney murine leukemia virus (MMLV) belongs to the Retroviridae family of enveloped viruses, which is known to acquire minute amounts of host cellular proteins both on the surface and inside the virion. Despite the extensive use of retroviral vectors in experimental and clinical applications, the repertoire of host proteins incorporated into MMLV vector particles remains unexplored. We report here the identification of host proteins from highly purified retroviral vector preparations obtained by rate-zonal ultracentrifugation. Viral proteins were fractionated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in-gel tryptic digested, and subjected to liquid chromatography/tandem mass spectrometry analysis. Immunogold electron microscopy studies confirmed the presence of several host membrane proteins exposed at the vector surface. These studies led to the identification of 27 host proteins on MMLV vector particles derived from 293 HEK cells, including 5 proteins previously described as part of wild-type MMLV. Nineteen host proteins identified corresponded to intracellular proteins. A total of eight host membrane proteins were identified, including cell adhesion proteins integrin β1 (fibronectin receptor subunit beta) and HMFG-E8, tetraspanins CD81 and CD9, and late endosomal markers CD63 and Lamp-2. Identification of membrane proteins on the retroviral surface is particularly attractive, since they can serve as anchoring sites for the insertion of tags for targeting or purification purposes. The implications of our findings for retrovirus-mediated gene therapy are discussed.
A gentle method for linking Tris to amino acids and peptides. (1993)

A gentle method for the addition of Tris to the carboxyl group of amino acids or peptides for the purpose of altering their solubility and/or for providing sites for further derivatization is described. Under mild alkaline conditions and in high concentrations of aqueous dimethylformamide, the amino group of Tris cleaves simple esters of N-protected amino acids or peptides to form an amino acid-Tris linkage. The effects of pH, temperature and dimethylformamide concentration on the rate and the efficiency of the reaction of Tris with benzyloxycarbonyl-alanine methyl ester were examined and the general applicability of the method demonstrated on a range of amino acid and small peptide substrates. Side-chain protection was not required and the degree of racemization was found to be lower than with conventional chemical coupling.
Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors (2010)

Advances in our understanding of the key mediators of chronic inflammation and tissue damage characteristic of rheumatoid arthritis (RA) have resulted in the development of novel therapies primarily targeting pro-inflammatory cytokines. Inhibitors of tumour necrosis factor (TNF) are the most widely used of the biological therapies at present with five different agents currently available; four are based on monoclonal anti-TNF antibodies and a soluble TNF receptor-Fc fusion protein. Long-term use of these molecules has proven to be highly effective in the majority of patients; however, around one-third have a suboptimal response potentially leading to further cartilage and bone damage, furthermore these agents are expensive compared with conventional therapies such as methotrexate. Many recent studies have attempted to identify therapeutic response biomarkers of TNF inhibitors which could be used to improve therapeutic targeting. The presence of rheumatoid factor and anti-cyclic citullinated protein antibodies, present in around 65% of RA patients, are associated with a poorer response to anti-TNF agents. Poorer response is also associated with levels of C-reactive protein and cartilage degradation product at initiation of treatment. Intriguingly, genetic studies of variants of TNF and of genes encoding members of the Toll-like receptors, nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling families have been associated with response to individual anti-TNF agents. Continued advances in technologies such as ultra high throughput sequencing and proteomics should facilitate the discovery of additional biomarkers of response to anti-TNF resulting in improved disease control and quality of life for RA patients and reduced costs for healthcare funders.
Zoom Zoom: Racing CARs for Multiple Myeloma (2013)

Chimeric antigen receptors redirect T cells to surface antigens. Discovery and validation of appropriate target antigens expand the possible indications for chimeric-antigen receptor (CAR)-T cells. B-cell maturation antigen (BCMA) is expressed only on mature B cells and plasma cells and promotes their survival. BCMA is a promising target for CAR-T cells in multiple myeloma.
Regulation of 1,25-Dihydroxyvitamin D3 Receptors by Vitamin D Analogs in Cultured Mammalian Cells* (1985)

The pig kidney cell line (LLC-PK1) has been shown to possess 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors and to exhibit functional responses to vitamin D metabolites. Here we report that these receptors appear to undergo homologous up-regulation by 1,25-(OH)2D3 and other vitamin D analogs. This phenomenon was also observed in other cell lines, including human skin fibroblasts and human mammary cancer cells (MCF-7). Treatment with active hormone or vitamin D analogs results in a substantial increase (200-400%) in the number of 1,25-(OH)2D3 receptors without altering the affinity of receptor for hormone. The up-regulated receptor, like the basal receptor, has an apparent Kd of about 0.04 nM and sediments at 3.3S on hypertonic sucrose gradients. In addition, approximately 50% of the total receptors from both control and treated cells bind to DNA-cellulose and elute at 0.18 m KCl. These results indicate that the up-regulated receptor is similar to the classical 1,25-(OH)2D3 receptor. While the time necessary to achieve the maximal receptor increment is 16-20 h, there is a rapid component in the rise observed within 5 min. The maximal effect persists for 4-6 h after hormone removal. The increased binding is not a result of differential receptor localization or extractability. 1,25-(OH)2D3, 1,24,25-trihydroxyvitamin D3, 24,25-(OH)2D3, and 25-hydroxyvitamin D3 all increase receptor binding to similar levels, and the dose required closely reflects the affinities of the various metabolites for the receptor. Treatment of cells with the RNA synthesis inhibitor actinomycin D indicates that the increase in receptors is partially dependent on RNA synthesis. Mutant skin fibroblasts from patients with vitamin D-dependent rickets type II, containing nonresponsive 1,25-(OH)2D3 receptors, failed to exhibit the characteristic up-regulation observed in normal cells. Taken together, these results indicate that vitamin D metabolites regulate the number of 1,25-(OH)2D3 receptors in part by receptor occupancy and, more importantly, by a receptor-mediated induction mechanism.
A proton nuclear magnetic resonance study of purine and pyrimidine nucleoside 5'-diphosphates. Extent of macrochelate formation in monomeric metal ion complexes and promotion of self-stacking by metal ions (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA proton nuclear magnetic resonance study of purine and pyrimidine nucleoside 5'-diphosphates. Extent of macrochelate formation in monomeric metal ion complexes and promotion of self-stacking by metal ionsKurt H. Scheller and Helmut SigelCite this: J. Am. Chem. Soc. 1983, 105, 18, 5891–5900Publication Date (Print):September 1, 1983Publication History Published online1 May 2002Published inissue 1 September 1983https://pubs.acs.org/doi/10.1021/ja00356a029https://doi.org/10.1021/ja00356a029research-articleACS PublicationsRequest reuse permissionsArticle Views232Altmetric-Citations84LEARN 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
Intermediary metabolism of fast-growth tumor cells. (1998)

Tumor cells show several modifications in their metabolism in comparison with normal cells. In particular, tumor cells show an accelerated glycolysis and a low O2 dependence, which are metabolic modifications involved in the resistance of many tumor cell lines to radiation. Thus, a strategy to enhance the radiosensitivity could be the transformation of the glycolytic metabolism of tumor cells into an oxidative type of metabolism, i.e., to induce the ATP supply to depend solely on oxidative phosphorylation. Therefore, this review emphasizes the relevance of oxidative phosphorylation on tumor cells regarding (a) its contribution to ATP supply for cell duplication during the proliferative phase, and (b) the possible therapeutic implications of having oxidative rather than glycolytic tumor cells.
Focal adhesion-associated proteins p125FAK and paxillin are substrates for bradykinin-stimulated tyrosine phosphorylation in Swiss 3T3 cells. (1994)

In this study we examined the involvement of the focal adhesion-associated proteins p125FAK and paxillin as substrates for bradykinin (BK)-stimulated tyrosine phosphorylation in Swiss 3T3 cells and the potential role of protein kinase C and Ca2+ in these events. BK (1 microM) stimulated tyrosine phosphorylation of p125FAK and paxillin. In addition, BK also increased the phosphotyrosine content of the src transformation-associated protein p130. The responses were rapid and transient and peaked at approximately 1 min after BK addition. Furthermore, the responses were dose-dependent with half-maximal effects occurring at 1-10 nM BK. The phosphotyrosine content of p125FAK, paxillin, and p130 was also increased following stimulation with phorbol 12-myristate 13-acetate (PMA) (0.1 microM). In contrast, PMA had no effect on the phosphotyrosine content of p125, a Ras-GAP-associated tyrosine phosphoprotein that we recently identified. Long term pretreatment (18 h) of cells with 0.3 microM PMA partially attenuated BK-stimulated phosphorylation of p125FAK but was without effect on phosphorylation of paxillin and Ras-GAP-associated p125. Furthermore, only a small inhibition of BK- and PMA-stimulated phosphorylation of p125FAK was observed following pretreatment with 25 microM BAPTA/AM. In all, these results show that multiple mechanisms are involved in BK-stimulated tyrosine phosphorylation of p125FAK, paxillin, Ras-GAP-associated p125, and src transformation-associated p130.
A method for linking VL and VH region genes that allows bulk transfer between vectors for use in generating polyclonal IgG libraries. (1994)

Libraries of Ab fragments have been produced by others from light and heavy chain cDNAs derived from populations of B lymphocytes and expressed in bacteria. However, such libraries have not been transferred to eukaryotic expression vectors to generate polyclonal libraries of intact glycosylated Abs that can mediate effector functions. We present a method for transferring pairs of linked VL-VH region genes between circular prokaryotic and eukaryotic vectors. The key feature of the transfer is that the VL and VH region genes are linked head to head (<-->) in opposite transcriptional orientations. To illustrate this method, a pair of VL and VH region cDNAs derived from an existing hybridoma cell line were linked head to head by PCR, transferred as a unit between vectors, and expressed as an IgG Ab with Ag binding activity. Although we tested the transfer of a single VL-VH region gene pair, this system is expected to allow the bulk transfer of physically linked VL-VH region gene combinations between different circular vectors and the expression of the same library as either Ab fragments or intact Abs.