gebhart/patrepeval huggingface dataset:
Conservation of a Glycine-rich Region in the Prion Protein Is Required for Uptake of Prion Infectivity (2010)

Prion diseases are associated with the misfolding of the endogenously expressed prion protein (designated PrP(C)) into an abnormal isoform (PrP(Sc)) that has infectious properties. The hydrophobic domain of PrP(C) is highly conserved and contains a series of glycine residues that show perfect conservation among all species, strongly suggesting it has functional and evolutionary significance. These glycine residues appear to form repeats of the GXXXG protein-protein interaction motif (two glycines separated by any three residues); the retention of these residues is significant and presumably relates to the functionality of PrP(C). Mutagenesis studies demonstrate that minor alterations to this highly conserved region of PrP(C) drastically affect the ability of cells to uptake and replicate prion infection in both cell and animal bioassay. The localization and processing of mutant PrP(C) are not affected, although in vitro and in vivo studies demonstrate that this region is not essential for interaction with PrP(Sc), suggesting these residues provide conformational flexibility. These data suggest that this region of PrP(C) is critical in the misfolding process and could serve as a novel, species-independent target for prion disease therapeutics.
Acute left ventricular failure after transcatheter closure of a secundum atrial septal defect in a patient with coronary artery disease: A critical reappraisal (2001)

We report a case of acute left ventricular failure after transcatheter closure of a single secundum atrial septal defect in a 68-year-old man with coronary artery disease. Just before the procedure, two coronary lesions had been treated with direct stenting. Transcatheter closure of atrial septal defects should always be deferred in ischemic heart disease patients who need percutaneous myocardial revascularization.
Mapping of a gene for hypergammaglobulinemia to the distal region on chromosome 4 in NZB mice and its contribution to systemic lupus erythematosus in (NZB×NZW)F1 mice (1994)

IgM class hypergammaglobulinemia develops spontaneously in the early life of NZB mice. To determine the chromosomal location of the NZB gene(s) linked to this hypergammaglobulinemia and possible contribution to systemic lupus erythematosus (SLE)-like autoimmune disease observed in (NZB x NZW)F1 hybrid mice, we examined (NZB x NZW)F1 x NZW backcross mice, using a mapping technique based on polymorphism in simple nucleotide sequence repeats. In light of our previous data, we directed attention to chromosome 4. A single NZB locus or tightly linked group of loci on the distal region (70-90 cM distal from the centromere), theoretically mapped to 14.3 cM distal from marker locus D4Mit48, had the strongest association with IgM hypergammaglobulinemia. The backcross progeny heterozygous for this locus on chromosome 4, in association with heterozygosity of the MHC haplotype (H-2d from NZB/H-2z from NZW) on chromosome 17, showed significantly higher serum levels of IgG anti-DNA antibodies and more severe lupus nephritis than did the progeny heterozygous for either one of the two loci or homozygous for both loci on chromosomes 4 and 17. The NZB gene in the distal region of chromosome 4 is likely to be responsible for terminal maturation of B cells and, in concert with the effect of H-2 heterozygosity, may predispose to the full expression of SLE in (NZB x NZW)F1 mice.
Double‐labeled immunofluorescence study of cutaneous nerves in psoriasis (1998)

The results of our study suggest that SP- and CGRP-containing neuropeptide nerve fibers are more dense in the psoriatic epidermis. Both SP and CGRP are chemotactic to neutrophils and mitogenic to keratinocytes and endothelial cells. In addition, SP activates T lymphocytes and induces adhesion molecules on the endothelial cells. Our observations suggest that neuropeptides may play a significant role in the inflammatory and proliferative process of psoriasis.
Polycyclic Aromatic Hydrocarbons Affect Functional Differentiation and Maturation of Human Monocyte-Derived Dendritic Cells (2002)

Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) are environmental carcinogens exhibiting potent immunosuppressive properties. To determine the cellular bases of this immunotoxicity, we have studied the effects of PAHs on differentiation, maturation, and function of monocyte-derived dendritic cells (DC). Exposure to BP during monocyte differentiation into DC upon the action of GM-CSF and IL-4 markedly inhibited the up-regulation of markers found in DC such as CD1a, CD80, and CD40, without altering cell viability. Besides BP, PAHs such as dimethylbenz(a)anthracene and benzanthracene also strongly altered CD1a levels. Moreover, DC generated in the presence of BP displayed decreased endocytic activity. Features of LPS-mediated maturation of DC, such as CD83 up-regulation and IL-12 secretion, were also impaired in response to BP treatment. BP-exposed DC poorly stimulated T cell proliferation in mixed leukocyte reactions compared with their untreated counterparts. In contrast to BP, the halogenated arylhydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin, which shares some features with PAHs, including interaction with the arylhydrocarbon receptor, failed to phenotypically alter differentiation of monocytes into DC, suggesting that binding to the arylhydrocarbon receptor cannot mimic PAH effects on DC. Overall, these data demonstrate that exposure to PAHs inhibits in vitro functional differentiation and maturation of blood monocyte-derived DC. Such an effect may contribute to the immunotoxicity of these environmental contaminants due to the major role that DC play as potent APC in the development of the immune response.
Finite-alphabet constant-amplitude training sequence for multiple-antenna broadband transmissions (2003)

We propose a method to identify training sequences for multiple-antenna transmissions over quasi-static frequency-selective channels. These sequences are constructed to belong to a standard constant-amplitude 2/sup m/-PSK constellation (such as BPSK, QPSK etc) to simplify the transmitter/receiver implementation. Many practical systems use training of predetermined length. Optimal sequences do not exist for all training sequence lengths and constellation alphabets. The proposed method allows us to identify training sequences that belong to a standard constellation for an arbitrary training sequence length and an arbitrary number of unknown channel taps. Performance bounds derived indicate that these sequences achieve near-optimum performance.
Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways (2004)

Fanconi anaemia (FA) is a chromosomal instability disorder characterized by cellular sensitivity to DNA interstrand crosslinking agents and a high risk of cancer. Six of the eight proteins encoded by the known FA genes form a nuclear complex which is required for the monoubiquitination of the FANCD2 protein. FANCD2 complexes and colocalizes with BRCA1, but its presumptive role in DNA repair has not yet been clearly defined. We used yeast two-hybrid analysis to test for interaction between FANCD2 and 10 proteins involved in homologous recombination repair. FANCD2 did not interact with RAD51, the five RAD51 paralogs, RAD52, RAD54 or DMC1. However, it bound to a highly conserved C-terminal site in BRCA2 that also binds FANCG/XRCC9. FANCD2 and BRCA2 can be coimmunoprecipitated from cell extracts of both human and Chinese hamster wild-type cells, thus confirming that the interaction occurs in vivo. Formation of nuclear foci of FANCD2 was normal in the BRCA2 mutant CAPAN-1 cells, which indicates that the recruitment of FANCD2 to sites of DNA-repair is independent of wild-type BRCA2 function. FANCD2 colocalized with RAD51 in foci following treatment with mitomycin C or hydroxyurea, and colocalized very tightly with PCNA after treatment with hydroxyurea. These findings suggest that FANCD2 may have a role in the cellular response to stalled replication forks or in the repair of replication-associated double-strand breaks, irrespective of the type of primary DNA lesion.
Clinical Pharmacology and Pharmacogenetics in a Genomics Era: The DMET Platform (2009)

While no genome-wide pharmacogenetics study has yet been published, the field of pharmacogenetics is moving towards exploratory, large-scale analyses of the interaction between genetic variation and drug treatment. The Drug Metabolizing Enzymes and Transporters (DMET) platform offers a standardized set of 1936 variants in 225 genes related to drug absorption, distribution, metabolism and elimination that is useful to scan the genome for previously unknown associations between variation in absorption, distribution, metabolism and elimination genes and pharmacokinetic and pharmacodynamic outcomes of drug treatment. The purpose of this review is to put the DMET platform into context within the current study designs that have been used in pharmacogenetics, and to explore the role that DMET has played - and will play - in future pharmacogenetics studies.
Thermal degradation and mass-spectrometric fragmentation processes of polyesters studied by time/temperature-resolved pyrolysis-field ionization mass spectrometry (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThermal degradation and mass-spectrometric fragmentation processes of polyesters studied by time/temperature-resolved pyrolysis-field ionization mass spectrometryBernd Plage and Hans Rolf SchultenCite this: Macromolecules 1990, 23, 10, 2642–2648Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1 May 1990https://pubs.acs.org/doi/10.1021/ma00212a008https://doi.org/10.1021/ma00212a008research-articleACS PublicationsRequest reuse permissionsArticle Views252Altmetric-Citations48LEARN 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
Enhanced resolution and throughput of Fresnel incoherent correlation holography (FINCH) using dual diffractive lenses on a spatial light modulator (SLM) (2012)

Fresnel incoherent correlation holography (FINCH) records holograms under incoherent illumination. FINCH was implemented with two focal length diffractive lenses on a spatial light modulator (SLM). Improved image resolution over previous single lens systems and at wider bandwidths was observed. For a given image magnification and light source bandwidth, FINCH with two lenses of close focal lengths yields a better hologram in comparison to a single diffractive lens FINCH. Three techniques of lens multiplexing on the SLM were tested and the best method was randomly and uniformly distributing the two lenses. The improved quality of the hologram results from a reduced optical path difference of the interfering beams and increased efficiency.
Diphtheria toxin. Effect of substituting aspartic acid for glutamic acid 148 on ADP-ribosyltransferase activity. (1985)

Photoaffinity labeling experiments with diphtheria toxin fragment A have implicated glutamic acid 148 as a constituent of the NAD binding site. To evaluate the role of this residue in ADP-ribosylation of elongation factor 2, we replaced it with aspartic acid by in vitro mutagenesis of a toxin gene fragment cloned in Escherichia coli. Fragment A containing aspartic acid at position 148 had less than 0.6% the ADP-ribosylation activity of wild-type fragment A. The mutation produced no change in sensitivity of fragment A to trypsin and little, if any, reduction in affinity of fragment A for NAD. These results indicate that glutamic acid 148 is essential for the ADP-ribosylation of elongation factor 2 and are consistent with other data suggesting that this residue may be at or near the catalytic center of the toxin.
Mouse and human embryonic stem cells (2013)

This mini-review focuses on the current state of knowledge in mouse and human embryonic stem (ES) cell biology. Methods of ES cell derivation, pluripotency assessment and problems associated with long-term cultivation in vitro are discussed. Attention is given to some unresolved questions of ES cell biology and the prospects for using ES cells in cell therapy.
Interleukin-6 signal transducer gp130 mediates oncostatin M signaling. (1992)

Oncostatin M (OM) is a multifunctional cytokine that is structurally and functionally related to interleukin 6 (IL-6) and leukemia inhibitory factor (LIF). The specific receptor for OM has been demonstrated (by chemical cross-linking) to be a 150-kDa protein in a number of cell lines. The IL-6 signal transducer, gp130, is also an affinity converter for the LIF receptor. It does not bind to either IL-6 or LIF, but associates with the alpha subunits of the receptors and transduces the signals. We examined the possible involvement of gp130 in OM binding and signaling. We demonstrate that: (a) anti-gp130 monoclonal antibodies (mAbs) block the inhibitory effect of OM on A375 cell growth, (b) the binding and cross-linking of 125I-OM to H2981 cells are completely abolished by anti-gp130 mAbs, (c) the cross-linked OM-receptor complex is immunoprecipitated by anti-gp130 mAbs, and (d) COS-7 cells transfected with the full-length cDNA encoding gp130 exhibit increased OM binding and cross-linking, which are also blocked by anti-gp130 mAbs. Therefore, we conclude that the 150-kDa OM binding protein previously characterized in a variety of cell lines is gp130. OM is the natural ligand for gp130 and gp130 mediates the biological responses of OM.
Liquid crystal systems for microwave applications : Single compounds and mixtures for microwave applications ; Dielectric, microwave studies on selected systems (2009)

In this work dielectric and microwave investigations on different nematic liquid crystalline systems are presented. New knowledge about the influence of the chemical structure of molecules on the microwave performance was obtained. This information was used for the preparation of new, optimized nematic mixtures with high values of tunability and low dielectric losses in the microwave region. These new mixtures can be used for producing new devices like phase shifters or varactors. The dielectric measurements of investigated mixtures show that there is no direct influence of dielectric properties in the low frequency region on the GHz region.
Modulation of Aldehyde Dehydrogenase and Retinoid Signaling Induces the Expansion of Human Hematopoietic Stem Cells. (2005)

Abstract Aldehyde dehydrogenases are cytosolic enzymes that convert aldehydes into carboxylic acids. Human aldehyde dehydrogenase 1 (ALDH1) is highly expressed in the liver and in hematopoietic stem cells (HSCs). Although ALDH1 is a selectable marker of HSCs, its HSC-specific function is unknown. We hypothesized that ALDH might play a critical role in HSC fate determinations since it is required for the production of retinoic acids, which are broadly implicated in tissue differentiation, tissue patterning and embryonic development in vertebrates. In this study, highly purified human CD34+CD38−lin− HSCs were cultivated with early acting cytokines, thrombopoietin, stem cell factor and Flt-3 ligand (TSF) in the presence or absence of the competitive ALDH inhibitor, diethylaminobenzaldehyde (DEAB). Treatment of human BM and CB HSCs with TSF x 7 days caused a loss of CD34+CD38− cells in culture, morphologic differentiation, amplification of committed colony forming cells (CFCs) and a loss of primitive cells capable of repopulating non-obese diabetic/severe combined immunedeficient mice (SCID-Repopulating Cells, SRCs). Conversely, 7 day culture of BM and CB HSCs with TSF plus 100 μM DEAB blocked the morphologic differentiation and lineage commitment of HSCs in culture, expanded the CD34+CD38− population, and amplified SRCs 2-fold compared to input, indicating a fundamental role for ALDH in HSC differentiation. The effects of DEAB could be reversed by the co-administration of the retinoic acid receptor (RAR) agonist, all-trans retinoic acid (ATRA), suggesting that the ability of ALDH to produce retinoic acids is important in determining HSC fate. Via screening studies of direct ligands of RAR and RXR, we also identified a selective RXR modulator which functioned similarly to DEAB by impeding HSC differentiation and causing the 4-fold expansion of SRCs. Interestingly, treatment with either DEAB or the RXR modulator reversed the down-modulation of HOXB4 transcription that was otherwise observed in CD34+CD38−lin- cells during culture with cytokines, suggesting that inhibition of ALDH or RXR modulation may promote HSC self-renewal via discrete interactions with other regulatory pathways. Modulation of ALDH activity and retinoid signaling is a novel and effective strategy to amplify human HSCs.
Learning interface agents (1993)

Interface agents are computer programs that employ Artificial Intelligence techniques in order to provide assistance to a user dealing with a particular comput-er application. The paper discusses an interface agent which has been modelled closely after the metaphor of a personal assistant. The agent learns how to as-sist the user by (i) observing the user’s actions and imitating them, (ii) receiving user feedback when it takes wrong actions and (iii) being trained by the us-er on the basis of hypothetical examples. The paper discusses how this learning agent was implemented us-ing memory-based learning and reinforcement learning techniques. It presents actual results from two proto-type agents built using these techniques: one for a meeting scheduling application and one for electronic mail. It argues that the machine learning approach to building interface agents is a feasible one which has several advantages over other approaches: it provides a customized and adaptive solution which is less cost-ly and ensures better user acceptability. The paper also argues what the advantages are of the particular learning techniques used.
Modulation of mEPSCs in Olfactory Bulb Mitral Cells by Metabotropic Glutamate Receptors (1997)

Olfactory bulb mitral cells express group I (mGluR1), group II (mGluR2), and group III (mGluR7 and mGluR8) metabotropic glutamate receptors. We examined the role of these mGluRs on excitatory synaptic transmission in cultured mitral cells with the use of whole cell patch-clamp recordings. The effects of group-selective mGluR agonists and antagonists were tested on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylate (ACPD) or the group-I-selective agonist 3,5-dihydroxyphenylglycine evoked an inward current accompanied by a decrease in membrane conductance, consistent with the previously described closure of potassium channels by group I agonists. The increased cellular excitability was accompanied by an increase in mEPSC frequency in some cells. When calcium entry was blocked by cadmium, ACPD or the group-II-selective agonist 2-(2,3-dicarboxycyclopropyl)-glycine reduced the mEPSC frequency. L-2-amino-4-phosphonobutyric acid (L-AP4), a group-III-selective agonist, caused a similar decrease. The concentration-dependence of L-AP4-mediated inhibition was most consistent with activation of mGluR8. We investigated two possible effector mechanisms for the group III presynaptic receptor. Bath application of forskolin or 3-isobutyl-1-methylxantine had no effect on mEPSC frequency. Increasing calcium influx by raising extracellular K+ caused a large increase in the mEPSC frequency but did not enhance L-AP4-mediated inhibition. Thus inhibition of mEPSCs involves a mechanism downstream of calcium entry and appears to be independent of adenosine 3',5'-cyclic monophosphate. Our results indicate that both group II and III receptors can inhibit glutamate release at mitral cell terminals. Although group II/III receptors had a similar effect on mEPSCs, differences in location on nerve terminals and in glutamate sensitivity suggest that each mGluR may have discrete actions on mitral cell activity.
Molecular cloning and functional characterization of human lymphotactin (1995)

We describe the isolation of a cDNA that encodes human lymphotactin (Ltn), a new class of lymphocyte-specific chemokine. Human Ltn shows similarity to some members of the C-C chemokine family but has lost the first and third cysteine residues that are characteristic of the C-C and C-X-C chemokines. Ltn is chemotactic for lymphocytes but not for monocytes, a characteristic that makes it unique among chemokines. In addition, calcium flux desensitization studies indicate that Ltn uses a unique receptor. The human Ltn gene maps to a different chromosome than do the C-C and C-X-C chemokine families. Taken together, these characteristics indicate that Ltn is the first example of a new class of human chemokines with preferential effects on lymphocytes.
Micropatterning of 3D Microenvironments for Living Biosensor Applications (2014)

Micro-scale printing and patterning of living cells has multiple applications including tissue engineering, cell signaling assays, and the fabrication of cell-based biosensors. In this work, a molecular printing instrument, the Bioforce Nano eNabler, was modified to enable micron-scale -quill-pen based printing of mammalian cells in a 3D hyaluronan/gelatin based hydrogel. Specifically, photo-initiated -thiol-ene click chemistry was used to couple the thiol groups of thiolated hyaluronan/thiolated gelatin to the alkene groups of 4-arm polyethylene glycol (PEG)-norbornene molecules. Rapid photopolymerization enabled direct printing and controlled curing of living cells within the hydrogel matrix. The resulting hydrogels were biocompatible with human adipose-derived stem cells, NIH-3T3 cells, and mouse embryonic stem cells. The utility of this printing approach was also explored for cell-based biosensors. Micro-printed cells expressing a redox sensitive variant of the green fluorescent protein (roGFP-R12) showed a measurable fluorescent response to addition of oxidizing and then reducing agents. This work represents a novel approach to micron-scale cell patterning, and its potential for living, cell-based biosensors.
Multiphoton Spectroscopy (1967)

Machine learning (ML) is transforming all areas of science. The complex and time-consuming calculations in molecular simulations are particularly suitable for an ML revolution and have already been profoundly affected by the application of existing ML ...Read More
Hypermethylation of the GATA Genes in Lung Cancer (2004)

These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly.