gebhart/patrepeval huggingface dataset:
Evidence-Based Platelet Transfusion Guidelines (2007)

Abstract Transfused platelets (plts) are either pooled random-donor platelet (plt) concentrates or single-donor apheresis plts. When stored for 5 days, all of these products are equally efficacious. A 10,000/μL prophylactic plt transfusion trigger has been documented to be both hemostatically efficacious and cost effective in reducing plt transfusion requirements. The optimal plt dose/transfusion is being evaluated in an ongoing clinical trial. Therapeutic plt transfusions to control or prevent bleeding with trauma or surgical procedures require higher transfusion triggers of 100,000/μL for neurosurgical procedures and between 50,000/μL and 100,000/μL for other invasive procedures or trauma. Leukoreduction has been documented to reduce plt alloimmunization rates, cytomegalovirus (CMV) transmission by transfusion, and febrile transfusion reactions. Whether it reduces immunomodulatory effects of transfusion (i.e., decreases infection rates and cancer recurrence) is still controversial, as is universal leukoreduction. Poor responses to plt transfusions are often multifactorial. For alloimmune plt refractoriness, HLA matching, cross-matching, and identification of the specificity of the patient’s antibodies with avoidance of mismatched donor antigens are all equally effective in identifying compatible plts for transfusion. Other causes of poor plt responses are splenomegaly, ABO mismatching, females with 2 or more pregnancies and males, use of heparin or amphotericin, bleeding, fever, graft-vs-host disease (GVHD), and vaso-occlusive disease (VOD).
Polymer Combination Increased Both Physical Stability and Oral Absorption of Solid Dispersions Containing a Low Glass Transition Temperature Drug: Physicochemical Characterization and <i>in Vivo</i> Study (2012)

The purpose of this study was establishing a solid dispersion formulation containing a low glass transition temperature (T(g)) and poorly water-soluble drug. Drug/polymer blends with differing physicochemical stabilities and oral absorption were prepared from copolyvidone (PVP-VA), polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) by a hot melt extrusion. HPMC drastically increased the drug oral absorption property, while PVP-VA or PVP stabilized solid dispersions during storage by increasing the T(g) in proportion to polymer concentration. Experimental T(g) values corresponded closely with theoretical T(g) values; indeed, the T(g) values of solid dispersion with HPMC did not increase significantly compared to the T(g) value for the drug alone. A solid dispersion formulation incorporating two different polymers-HPMC and either PVP-VA or PVP-maintained increased T(g), physicochemical stability, solubility, and bioavailability of the solid dispresions owing to each polymer. These findings suggested that both oral absorption and physicochemical stability of low-T(g) drug will be improved using less amount of solid dispersion of combined two polymers than polymer alone.
Heat-shock protein 90 (Hsp90) as a molecular target for therapy of gastrointestinal cancer. (2009)

Anticancer drug development strategies critically involve the identification of novel molecular targets which are crucial for tumorigenesis and metastasis. In this context, the molecular chaperone heat-shock protein 90 (Hsp90) has gained interest as a promising anticancer drug target, due to its importance in maintaining the stability, integrity, conformation and function of key oncogenic proteins. These Hsp90 "client proteins" have been demonstrated to play fundamental roles in the processes of signal transduction, cell proliferation and survival, cell cycle progression and apoptosis, as well as other features of malignant cells, such as invasion, tumor angiogenesis and metastasis. The cancer selectivity and antitumoral effects of Hsp90 inhibitors are mediated by simultaneous and combined actions, in terms of directly affecting multiple cancer targets and pathways. Several Hsp90 inhibitors, including the geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17AAG), have displayed convincing antineoplastic efficacy and cancer selectivity in a variety of preclinical models, including gastrointestinal carcinomas. Importantly, some Hsp90 inhibitors have now progressed to phase I/II clinical testing. Against this background, the following review focuses on the current preclinical experience and value of targeting Hsp90 for the therapy of gastrointestinal carcinomas.
Endoplasmic Reticulum Chaperone Proteins Calnexin and ERp57: Structure and Function (2010)

The endoplasmic reticulum is responsible for folding of newly synthesized proteins. Chaperone proteins, calreticulin and calnexin, with the thiol-oxidoreductase ERp57, interact with nascent proteins in a cycle of quality control to ensure proteins are folded correctly. In this study, we investigated the tissue-specific expression of both calnexin and ERp57 throughout embryonic development. We found that calnexin is primarily expressed in neurological tissue and cartilage which is not surprising considering that targeted deletion of calnexin results in live mice with severe motor defects. Targeted deletion of the Pdia3 gene, which encodes ERp57, in mice is embryonic lethal at embryonic day 13.5. ERp57 expressed mainly in lung, liver and neurological tissue suggesting that ERp57 may have a critical role in the development of these tissues. Both calnexin and ERp57 play a role in quality control and my findings suggest that calnexin- and ERp57-deficient cells are under persistent stress and adapt to maintain ER homeostasis during. We also show here that STAT3-dependent signalling is increased in the absence of ERp57 and this can be rescued by expression of ER-targeted ERp57 but not by cytoplasmic-targeted protein, indicating that ERp57 affects STAT3 signalling from the lumen of the ER. ERp57 effects on STAT3 signalling are enhanced by ER luminal complex formation between ERp57 and calreticulin. We also used site-specific mutagenesis to disrupt cysteine and histidine residues in the N- and P-domains of calnexin. We identified that disruption Cys161/195 in calnexin resulted in significant loss of its chaperone activity for glycoyslated substrates. Disruption of Cys361/367 also had minor impacts on the function of calnexin as chaperone for glycosylated substrates. Mutations to H202, Cys161/195 and Cys361/367 resulted in enhanced binding of ERp57 to calnexin. In conclusion, these observations suggest that the cysteine residues within calnexin are important to the structure and function of calnexin. Research presented in this thesis highlights the diversity of the functions of ER proteins calnexin and ERp57 and understanding the ER-associated molecular mechanisms within a cell will undoubtedly give us essential knowledge regarding healthy and normal development.
Development and evaluation of a novel decellularized vascular xenograft (2002)

Although autogenous saphenous vein remains the standard for coronary and infrapopliteal bypass, many patients do not have a suitable vein. Attempts at developing a small-caliber vascular graft have failed largely due to occlusion, neointimal hyperplasia, or aneurismal degradation. We have designed and characterized a novel small-caliber vascular xenograft that may overcome these failure modes. To reduce immune reactions, porcine common carotid arteries were decellularized by enzymatic and detergent treatments. Histology and electron microscopic examination showed complete removal of cellular components while the extracellular matrix structure remained intact. To reduce thrombogeneity, decellularized vascular grafts were covalently linked with heparin. The efficiency of heparin linkage was demonstrated with toluidine blue staining and the antithrombogeneity of the heparin-treated grafts was demonstrated with a clot time test. Mechanical testing of the graft was performed. Decellularized-heparin-treated grafts were similar in compliance to fresh vessels and burst testing showed grafts to withstand pressures exceeding 10 times physiologic blood pressure. There was no difference in suture retention strength between fresh vessels and decellularized-heparin-treated grafts. Decellularized, heparinized grafts were implanted in dogs as carotid artery bypass grafts and showed smooth muscle cells densely populating the wall, and endothelial cells lining the lumen by two months. This study provides a new strategy to develop a small-caliber vascular graft with excellent mechanical properties, antithrombogeneity, and tissue compatibility.
Highly Active Silica Gel‐Supported Metathesis (Pre)Catalysts (2005)

Abstract Highly active Hoveyda–Grubbs and Hoveyda–Blechert type (pre)catalysts, immobilized on silica gel, are presented. These (pre)catalysts are synthesized in a few steps from readily available precursors and demonstrate high activity in a number of test metathesis reactions. The catalyst is easily separated by simple filtration of the non‐swelling material.
Fabrication of High-Quality Perovskite Oxide Films by Lateral Epitaxy Verified with RHEED Oscillation (1993)

Epitaxial growth of SrTiO 3- x and SrVO 3- y films by laser molecular beam epitaxy (laser MBE) has been controlled on an atomic scale. Reflection-high-energy-electron-diffraction (RHEED) intensity oscillation persisting for more than 50 periods was observed during the homoepitaxial growth of SrTiO 3- x film, indicating the lateral epitaxy in a unit cell layer-by-layer mode. The conductivity of SrTiO 3- x ultrathin films was sensitive to the oxygen pressure at the deposition to a far greater extent than was that of SrVO 3- y films.
The 6-Deoxytetracyclines. IX. Imidomethylation (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe 6-Deoxytetracyclines. IX. ImidomethylationMichael J. Martell, Adma S. Ross, and James H. BootheCite this: J. Med. Chem. 1967, 10, 3, 359–363Publication Date (Print):May 1, 1967Publication History Published online1 May 2002Published inissue 1 May 1967https://doi.org/10.1021/jm00315a016RIGHTS & PERMISSIONSArticle Views74Altmetric-Citations7LEARN 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 InReddit PDF (604 KB) Get e-Alerts Get e-Alerts
Sequential order of T and B cell epitopes affects immunogenicity but not antibody recognition of the B cell epitope. (1995)

Synthetic peptide constructs, co-linearly linking a MUC1 mucin B cell epitope peptide to a known murine T cell epitope, both in T-B and B-T orientations, show that induction of high murine anti-MUC1 antibody titers is dependent on the presence and orientation of the T cell determinant. However, the sequential order of the epitopes does not affect binding of anti-B cell epitope antibodies to the constructs. Haplotype mismatching leads to a significant lowering of the anti-MUC1 antibody responses, implicating a central role for the T cell epitope in eliciting anti-B cell epitope responses. Secondary structure analysis by circular dichroism spectroscopy reveals the T-B construct to be partially ordered, while the B-T peptide adopts a highly ordered conformation in trifluoroethanol. These studies suggest that the sequential order of epitopes may significantly alter the immunogenicity of the peptide but may not necessarily affect its antigenicity. Immunogenicity of the peptide constructs may be governed by subtle differences in secondary structure, leading to variation in the way peptides are presented or processed within cells governing immune responses. These findings have relevance for the construction of peptides to be utilized as potential synthetic vaccines and for the design of peptide immunogens.
Positioning FBAR technology in the frequency and timing domain (2011)

This paper will focus on the technical differentiation of FBAR from other mechanical resonator technologies for timing applications. The talk will also touch on a recent modification of FBAR (the Zero Drift Resonator, ZDR) that is temperature compensated. A further technology differentiator is the size of the chip-scale packaged resonator. Using the same technology used in manufacturing Avago Technologies' filter duplexer (over 3 billion sold) allows us to leverage qualified processes and thus go to market quickly. Furthermore, the silicon lid is perfectly suitable for placing integrated circuits and this is being done. All of these factors, (wide tuning range, high Q, high frequency, small size, integrated circuitry) are being used to differentiate potential products for the Time and Frequency Markets.
Misincorporation by AMV reverse transcriptase shows strong dependence on the combination of template and substrate nucleotides (1986)

We have carried out a systematic investigation of the efficiency of misincorporation by Avian Myeloblastosis Virus reverse transcriptase with all possible combinations of dNTP substrate, template nucleotide, and the nucleotide at the 3' terminus of the primer. A series of synthetic oligonucleotide primers were annealed to single stranded M13 DNA templates, and a single dNTP was misincorporated at the primer 3' end using AMV reverse transcriptase. The proportion and pattern of misincorporation and incorporation in all 64 situations was assayed using [5'-32p] labelled primers, and the products were separated on denaturing polyacrylamide gels. Correct incorporations occurred more readily than misincorporations. The efficiency of misincorporation depended on the individual primer, but, comparing primers, a clear dependence on the template nucleotide was observed for the preferential misincorporation of different dNTPs. The exact combination of template and dNTP was important; although purine:pyrimidine (dNTP substrate:template nucleotide) and pyrimidine:purine misincorporations occurred comparatively readily, some pyrimidine:pyrimidine and purine:purine reactions were equally efficient and yet others were never seen to occur. Some misincorporations were facilitated by subsequent correct incorporations, but despite this our results suggest that the level of misincorporation is limited by the rate of reaction and enzyme inactivation rather than by exonuclease activity.
ChemInform Abstract: QUINAZOLINES AND 1,4‐BENZODIAZEPINES. LXXIII. THE RING EXPANSION OF 2‐CHLOROMETHYLQUINAZOLINE 3‐OXIDES WITH NITROMETHANE (1976)

Abstract Chloracetaldehyd (II) reagiert mit den o‐Amino‐benzophenonen (I) zu den Dihydrochinazolin‐N‐oxiden (III), die mit Braunstein zu (IV) dehydiert werden.
Design and synthesis of a photocleavable biotinylated nucleotide for DNA analysis by mass spectrometry (2004)

We report here the design, synthesis and evaluation of a novel photocleavable (PC) biotinylated nucleotide analog, dUTP-PC-Biotin, for DNA polymerase extension reaction to isolate DNA products for mass spectrometry (MS) analysis. This nucleotide analog has a biotin moiety attached to the 5-position of 2'-deoxyribouridine 5'-triphosphate via a photocleavable 2-nitrobenzyl linker. We have demonstrated that dUTP-PC-Biotin can be faithfully incorporated by the DNA polymerase Thermo Sequenase into the growing DNA strand in a DNA polymerase extension reaction and that its incorporation does not hinder the addition of the subsequent nucleotide. Therefore, the DNA extension fragments generated by using the dUTP-PC-Biotin can be efficiently isolated by a streptavidin-coated surface and recovered by near-UV light irradiation at room temperature in mild condition for further analysis without using any chemicals or heat. Single and multiple primer extension reactions were performed using the dUTP-PC-Biotin to generate DNA products for MALDI-TOF MS analysis. Such nucleotide analogs that carry a biotin and a photocleavable linker will allow the isolation and purification of DNA products under mild conditions for MS-based genetic analysis by DNA sequencing or multiplex single nucleotide polymorphism (SNP) detection. Furthermore, these nucleotide analogs should also be useful in isolating DNA-protein complexes under non-denaturing conditions.
Unique selection determinant in polyclonal V delta 2-J delta 1 junctional regions of human peripheral gamma delta T lymphocytes. (1994)

Human peripheral gamma delta T lymphocytes are characterized by the preferential expression of a TCR consisting of a V delta 2-J delta 1-C delta chain and a V gamma 9-J gamma 1.2-C gamma 1 chain, which are virtually absent on thymocytes. Here we report the identification of a unique selection determinant that is located in the polyclonal V delta 2-J delta 1 junctional regions of peripheral gamma delta T lymphocytes. The selection determinant was discovered by the presence of an invariant T nucleotide at the relative second position of the V delta 2-J delta 1 junctional regions of peripheral polyclonal gamma delta T lymphocytes. Comparison of published sequences from peripheral gamma delta T lymphocytes confirmed the presence of this invariant T nucleotide (90%) in healthy individuals and in patients with various diseases. Translation of the relative first codon of the V delta 2-J delta 1 junctional regions revealed strikingly high frequencies of the homologous hydrophobic amino acids leucine (46%), valine (35%), and isoleucine (5%) at this position. The invariant T nucleotide was absent in polyclonal thymocytes and out-of-frame V delta 2-J delta 1 junctional regions, which proves that selection occurred at the protein level and not at the genomic level. No selection determinant could be identified in V gamma 9-J gamma 1.2 junctional regions, but the frequently occurring invariable, so-called canonical junctional region provided evidence for biased recombination processes. Although the obtained data do not allow discrimination between thymic selection and/or peripheral Ag-driven expansion, the identification of a strong selection determinant consisting of only one amino acid at a fixed position in V delta 2-J delta 1 junctional regions of virtually all peripheral polyclonal V delta 2/V gamma 9 T lymphocytes provides a new perception of TCR specificity and selection processes at the TCR protein level.
Treatment of multiple myeloma (2003)

Autologous peripheral blood stem cell (PBSC)-supported high-dose melphalan is now considered standard therapy for myeloma, at least for younger patients. The markedly reduced toxicity of allotransplants using nonmyeloablative regimens (mini-allotransplantations) may hold promise for more widely exploiting the well-documented graft-versus-myeloma (GVM) effect. New active drugs include immunomodulatory agents, such as thalidomide and CC-5013 (Revimid; Celgene, Warren, NJ), and the proteasome inhibitor, PS 341 (Velcade; Millenium, Cambridge, MA), all of which not only target myeloma cells directly but also exert an indirect effect by suppressing growth and survival signals elaborated by the bone marrow microenvironment's interaction with myeloma cells. Among the prognostic factors evaluated, cytogenetic abnormalities (CAs), which are present in one third of patients with newly diagnosed disease, identify a particularly poor prognosis subgroup with a median survival not exceeding 2 to 3 years. By contrast, in the absence of CAs, 4-year survival rates of 80% to 90% can be obtained with tandem autotransplantations. Fundamental and clinical research should, therefore, focus on the molecular and biologic mechanisms of treatment failure in the high-risk subgroup.
The surface morphology of embryonic and adult chick lens‐fiber cells (1980)

The surface morphology of lens fibers in embryonic and adult chicken lenses has been studied by scanning electron microscopy. As the elongating epithelial cells enter into a state of terminal differentiation they elaborate a number of cellular processes interconnecting neighboring fibers. The interlocking devices take the shapes of balls on a short stalk, tonguelike flaps, and fingerlike processes that fit into complementarily shaped sockets, imprints, and fingerprints, respectively, of adjoining fibers. Gap junctions comprising more than 50% of the fiber-cell membrane may serve as ultrastructural interlocking devices. The interlocking devices and gap junctions are probably necessary to maintain fiber order--a critical requirement for lens transparency. With increase maturation, the uniform morphology of the fibers and their interlocking devices is lost. The highly repetitive ordered alignment of young uniformly shaped fiber cells acts to minimize large-particle scatter. The results of this study show a progressive loss of uniform shape and order in chicken fibers of advanced maturity. This phenomenon of lens development may be the basis for the increase in light scattering seen in aged lenses of other species such as man.
Mechanical vibration analysis using an optical sensor (2002)

A laser-based contactless displacement measurement system developed at the National Optics Institute is used for data acquisition to analyze the mechanical vibrations exhibited by vibrating structures and machines. The analysis of these vibrations requires a number of signal processing operations which include the determination of the system conditions through a classification of various observed vibration signatures and the detection of changes in the vibration signature in order to identify possible trends. This information is also combined with the physical characteristics and contextual data (operating mode, etc.) of the system under surveillance to allow the evaluation of certain characteristics like fatigue, abnormal stress, life span, etc., resulting in a high level classification of mechanical behaviors and structural faults according to the type of application.
Decreased serum levels of TGF-β1 are associated with renal damage in female patients with systemic lupus erythematosus (2011)

This study demonstrates significantly reduced serum levels of both total and active TGF-β1 in women with SLE compared with healthy women. Total TGF-β1 levels are correlated negatively with ESR and positively with blood platelets. Total TGF-β1 levels were lower in SLE patients with high disease activity and severe organ damage. Importantly, the severity of the renal damage was associated with decreased serum levels of total TGF-β1, suggesting that TGF-β1 might be involved in pathogenesis of renal damage caused by lupus nephritis.