gebhart/patrepeval huggingface dataset:
Matrix metalloproteinases and their inhibitors (1995)

The progressive breakdown of connective tissues of the articular joints is a major feature of the arthritides and becomes an irreversible process leading to permanent loss of function and disability. Recent research has been directed at the analysis of the relative roles of different cell types and the different classes of proteinases that they produce in such deg-radative processes. It is known that proteinases of all mechanistic classes have the potential to degrade individual connective tissue macromolecules in vitro, but the elucidation of their precise role in vivo is more difficult. The current view is that the initial step in the breakdown of the matrix in both physiological and pathological situations is an extracellular process, often involving matrix metalloproteinases (MMPs) which function at neutral pH. In certain special environments, cysteine proteinases with more acidic pH optima are also active and in rapid resorption or inflammatory events, serine proteinases are released by invading cells. Mechanical disruption and the presence of free radicals can also augment the degradative process. Matrix fragments are subsequently phagocytosed for processing intracellularly within the lysosomal system. These processes are normally tightly regulated by a complex interplay of cell-cell and cell-matrix interactions involving the production of proteinases, activators and inhibitors and other regulatory molecules. The accelerated breakdown of connective tissue seen in diseases such as rheumatoid arthritis may be due largely to a breakdown in these regulatory mechanisms.
A2BReceptors Mediate the Antimitogenic Effects of Adenosine in Cardiac Fibroblasts (2001)

Adenosine inhibits growth of cardiac fibroblasts; however, the adenosine receptor subtype that mediates this antimitogenic effect remains undefined. Therefore, the goals of this study were to determine which adenosine receptor subtype mediates the antimitogenic effects of adenosine and to investigate the signal transduction mechanisms involved. In rat left ventricular cardiac fibroblasts, PDGF-BB (25 ng/mL) stimulated DNA synthesis ((3)H-thymidine incorporation), cellular proliferation (cell number), collagen synthesis ((3)H-proline incorporation), and MAP kinase activity. The adenosine receptor agonists 2-chloroadenosine and 5'-N-methylcarboxamidoadenosine, but not N(6)-cyclopentyladenosine, 4-aminobenzyl-5'-N-methylcarboxamidoadenosine, or CGS21680, inhibited the growth effects of PDGF-BB, an agonist profile consistent with an A(2B) receptor-mediated effect. The adenosine receptor antagonists KF17837 and 1,3-dipropyl-8-p-sulfophenylxanthine, but not 8-cyclopentyl-1,3-dipropylxanthine, blocked the growth-inhibitory effects of 2-chloroadenosine and 5'-N-methylcarboxamidoadenosine, an antagonist profile consistent with an A(2) receptor-mediated effect. Antisense, but not sense or scrambled, oligonucleotides to the A(2B) receptor stimulated basal and PDGF-induced DNA synthesis, cell proliferation, and collagen synthesis. Moreover, the growth-inhibitory effects of 2-chloroadenosine, 5'-N-methylcarboxamidoadenosine, and erythro-9-(2-hydroxy-3-nonyl) adenine plus iodotubericidin (inhibitors of adenosine deaminase and adenosine kinase, respectively) were abolished by antisense, but not scrambled or sense, oligonucleotides to the A(2B) receptor. Our findings strongly support the hypothesis that adenosine causes inhibition of CF growth by activating A(2B) receptors coupled to inhibition of MAP kinase activity. Thus, A(2B) receptors may play a critical role in regulating cardiac remodeling associated with CF proliferation. Pharmacologic or molecular biological activation of A(2B) receptors may prevent cardiac remodeling associated with hypertension, myocardial infarction, and myocardial reperfusion injury after ischemia.
Nanog Overcomes Reprogramming Barriers and Induces Pluripotency in Minimal Conditions (2010)

Induced pluripotency requires the expression of defined factors and culture conditions that support the self-renewal of embryonic stem (ES) cells. Small molecule inhibition of MAP kinase (MEK) and glycogen synthase kinase 3 (GSK3) with LIF (2i/LIF) provides an optimal culture environment for mouse ES cells and promotes transition to naive pluripotency in partially reprogrammed (pre-iPS) cells. Here we show that 2i/LIF treatment in clonal lines of pre-iPS cells results in the activation of endogenous Nanog and rapid downregulation of retroviral Oct4 expression. Nanog enables somatic cell reprogramming in serum-free medium supplemented with LIF, a culture condition which does not support induced pluripotency or the self-renewal of ES cells, and is sufficient to reprogram epiblast-derived stem cells to naive pluripotency in serum-free medium alone. Nanog also enhances reprogramming in cooperation with kinase inhibition or 5-aza-cytidine, a small molecule inhibitor of DNA methylation. These results highlight the capacity of Nanog to overcome multiple barriers to reprogramming and reveal a synergy between Nanog and chemical inhibitors that promote reprogramming. We conclude that Nanog induces pluripotency in minimal conditions. This provides a strategy for imposing naive pluripotency in mammalian cells independently of species-specific culture requirements.
Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine474 (1993)

Thrombomodulin (TM) is an endothelial cell thrombin receptor that converts thrombin from a procoagulant to an anticoagulant enzyme. It has previously been shown that TM is expressed in both a high-M(r) form containing chondroitin sulphate and a low-M(r) form lacking this modification. Site-directed mutagenesis of a soluble human TM derivative (TMD1) was employed to determine the attachment site(s) of this functionally important oligosaccharide on the core protein. Although there are four serine residues within the Ser/Thr-rich domain of TMD1 that might support glycosaminoglycan assembly, our analysis demonstrates that the primary site of attachment is at Ser474, and evidence is presented for low levels of attachment at Ser472. It was possible to improve the overall degree of attachment by mutating Ser472 to glutamic acid (so as to conform Ser474 to the xylosyltransferase acceptor consensus acidic-Gly-Ser-Gly-acidic); however, a significant proportion (approx. 35%) of the total TM still lacked a glycosaminoglycan moiety. Mutants that possess a substitution for Ser474 show an increased mobility of their low-M(r) form on SDS/PAGE compared with native TMD1. Isolation and sequencing of a C-terminal peptide demonstrated that this serine is modified in the low-M(r) form of native TMD1. An apparent 'acceptor consensus overlap' at Ser474 suggests that the mechanism behind the glycosaminoglycan split of TM may involve a competition for substrate between xylosyltransferase and N-acetylgalactosaminyltransferase.
Regulatory Aspects of Cellulase Biosynthesis and Secretion (1989)

The cellulase enzyme system consists of cellobiohydrolase, endoglucanase, and beta-glucosidase and has been extensively studied with respect to its biosynthesis, properties, mode of action, application, and, most recently, secretion mechanisms. A knowledge of the factors governing the biosynthesis and secretion of these enzymes at the molecular level will be useful in maximizing enzyme productivity in extracellular fluid. Among other topics, the regulatory effects of sorbose (a noninducing sugar which is not a product of cellulose hydrolysis) on cellulase synthesis and release are described. Cellulase genes have recently been cloned into a number of microorganisms with a view to understanding the gene structure and expression and to obtaining the enzyme components in pure form. The factors governing biosynthesis and secretion of cellulases in recombinant cells are also discussed. Cellulases are known to be glycoproteins, therefore, the role of O- and N-linked glycosylation on enzyme stability and secretion is also detailed.
Utility of gallium-67 scintigraphy in low-grade non-Hodgkin's lymphoma. (1996)

When modern technology is used, 67Ga scintigraphy has good sensitivity in patients with LGNHL. It therefore can be used to monitor response to therapy and to provide early detection of disease recurrence in these patients.
Purification, cDNA Cloning, and Gene Mapping of the Small Subunit of Human DNA Polymerase ε (1997)

HeLa DNA polymerase epsilon (pol epsilon), possibly involved in both DNA replication and DNA repair, consists of a catalytic subunit of 261 kDa and a tightly bound peptide with a relative molecular mass of 55 kDa. The cDNA of the 261-kDa polypeptide has been independently cloned, sequenced, and then overexpressed in insect cells to give a soluble, but catalytically unstable protein, suggesting that the small subunit of HeLa pol epsilon might be important for stability. HeLa pol epsilon has been isolated by immunoaffinity purification to obtain sequence information which enabled the cloning of a full-length human cDNA encoding the small subunit. The clone encoded nine proteolytic peptides obtained from the subunit. The 59,434-Da predicated polypeptide has 26% identity and 44% homology to the yeast pol epsilon 80-kDa subunit, DPB2. Using fluorescence in situ hybridization, the human pol epsilon p59 locus (DPE2) was assigned to chromosome 14q13-q21.
Humoral Immune Response to AAV (2013)

Adeno-associated virus (AAV) is a member of the family Parvoviridae that has been widely used as a vector for gene therapy because of its safety profile, its ability to transduce both dividing and non-dividing cells, and its low immunogenicity. AAV has been detected in many different tissues of several animal species but has not been associated with any disease. As a result of natural infections, antibodies to AAV can be found in many animals including humans. It has been shown that pre-existing AAV antibodies can modulate the safety and efficacy of AAV vector-mediated gene therapy by blocking vector transduction or by redirecting distribution of AAV vectors to tissues other than the target organ. This review will summarize antibody responses against natural AAV infections, as well as AAV gene therapy vectors and their impact in the clinical development of AAV vectors for gene therapy. We will also review and discuss the various methods used for AAV antibody detection and strategies to overcome neutralizing antibodies in AAV-mediated gene therapy.
YM150, an Oral Direct Factor Xa Inhibitor, as Prophylaxis for Venous Thromboembolism in Patients with Elective Primary Hip Replacement Surgery. A Dose Escalation Study. (2005)

Activated factor X (FXa) is a pivotal blood coagulation factor positioned at the crossroads of the extrinsic and intrinsic coagulation cascade. Inhibitors of FXa are anticoagulants that could be used in the prevention and treatment of thrombosis and venous thromboembolism (VTE). YM150 is a once daily, orally active FXa inhibitor. A randomized, enoxaparin-controlled, dose escalation study was performed in 174 patients undergoing elective primary hip replacement surgery to assess safety and efficacy of 7–10 days treatment with oral doses of YM150 (3, 10, 30 or 60 mg once daily starting 6–10 h after surgery) or s.c. enoxaparin (40 mg once daily starting 12 h before surgery). Safety is defined as major and/or clinically relevant non-major bleeding, and efficacy as venous thromboembolism detected by mandatory bilateral venography on the last treatment day and/or symptomatic VTE. The study was open-label with blinded evaluation of all outcomes by an independent Adjudication Committee. There were no major bleeds. Three clinically relevant non-major bleeds were reported, 1 (2.9%; 95% CI: 0–16%) in the 3 mg and 2 (5.7%; 1–19%) in the 10 mg YM150 dose groups. No trend was observed in the incidence of minor bleeds with dose of YM150 in the range 10 mg to 60 mg daily. The proportion of patients with minor bleeding events in the enoxaparin group (22%; 95% CI: 10–39%) was similar to that in the YM150, 60 mg daily group (24%; 11–41%). 147 patients (84%) were considered to have an evaluable venogram. The incidences of VTE were 52% (95% CI: 31–72%), 39% (22–57%), 23% (9–40%), and 19% (7–37%) for the respective 3, 10, 30 and 60 mg YM150 once daily dose groups in comparison with 39% (22–57%) for enoxaparin. Logistic regression analysis revealed a statistically significant dose-related trend (p=0.006) for patients reaching the VTE endpoint during YM150 treatment. No trend in any of the measured safety parameters was observed with study treatment (YM150 or enoxaparin) or dose of YM150. Oral, once daily doses of YM150, 10 mg to 60 mg administered 6 to 10 h after primary hip replacement, were shown to be safe, well tolerated and effective in this study.
Good to Great - (Why Some Companies Make the Leap and others Don't) (2009)

Good is the enemy of great level 5 leadership first who - then what confront the brutal facts (yet never lose faith) hedgehog concept a culture of discipline technology accelerators the flywheel and the doom loop from good to great to built to last.
The cloche and spadetail Genes Differentially Affect Hematopoiesis and Vasculogenesis (1998)

In vertebrates, hematopoietic and vascular progenitors develop from ventral mesoderm. The first primitive wave of hematopoiesis yields embryonic red blood cells, whereas progenitor cells of subsequent definitive waves form all hematopoietic cell lineages. In this report we examine the development of hematopoietic and vasculogenic cells in normal zebrafish and characterize defects in cloche and spadetail mutant embryos. The zebrafish homologs of lmo2, c-myb, fli1, flk1, and flt4 have been cloned and characterized in this study. Expression of these genes identifies embryonic regions that contain hematopoietic and vascular progenitor cells. The expression of c-myb also identifies definitive hematopoietic cells in the ventral wall of the dorsal aorta. Analysis of b316 mutant embryos that carry a deletion of the c-myb gene demonstrates that c-myb is not required for primitive erythropoiesis in zebrafish even though it is expressed in these cells. Both cloche and spadetail mutant embryos have defects in primitive hematopoiesis and definitive hematopoiesis. The cloche mutants also have significant decreases in vascular gene expression, whereas spadetail mutants expressed normal levels of these genes. These studies demonstrate that the molecular mechanisms that regulate hematopoiesis and vasculogenesis have been conserved throughout vertebrate evolution and the clo and spt genes are key regulators of these programs.
Neutrophils in chronic inflammatory airway diseases: can we target them and how?: Fig. 1— (2010)

Neutrophils in chronic inflammatory airway diseases: can we target them and how?
Incorporation of Mn12single molecule magnets into mesoporous silica (2003)

The incorporation of four Mn12 derivatives, namely [Mn12O12(O2CR)16(H2O)4] (R = CH3 (1), CH3CH2 (2), C6H5 (3), C6F5 (4)), into the hexagonal channels of the MCM-41 mesoporous silica has been studied. Only the smallest clusters 1 and 2, i.e. those with compatible size with the pores of MCM-41, could enter into the mesoporous silica. Powder X-ray diffraction analysis, HRTEM images and N2 adsorption–desorption isotherm experiments show that the well-ordered hexagonal structure of MCM-41 is preserved and that the Mn12 clusters are inside the pores. The magnetic properties of the MCM-41/2b nanocomposite material obtained in CH2Cl2 indicate that the structure of the cluster is maintained after incorporation on the MCM-41 walls, but some differences appear in the case of the MCM-41/1 and MCM-41/2a nanocomposite materials obtained in CH3CN. Calcination of the composite samples leads to materials with magnetic properties that are very different from those obtained after calcination of pristine 1 and 2. The incorporation of the Mn12 clusters inside the MCM-41 pores may induce the formation of new Mn–oxide nanoparticles after the loss of the carboxylate ligands. The incorporation of Mn12 derivatives into UVM-7, a mesoporous silica with a hierarchical pore system at two different length scales, gives rise to similar results.
The metabolically obese, normal-weight individual revisited. (1998)

Nearly 20 years ago, it was suggested that individuals exist who are not obese on the basis of height and weight, but who, like people with overt obesity, are hyperinsulinemic, insulin-resistant, and predisposed to type 2 diabetes, hypertriglyceridemia, and premature coronary heart disease. Since then it has become increasingly clear that such metabolically obese, normal-weight (MONW) individuals are very common in the general population and that they probably represent one end of the spectrum of people with the insulin resistance syndrome. Available evidence also suggests that MONW individuals could account for the higher prevalence of type 2 diabetes, cardiovascular disease, and other disorders in people with a BMI in the 20-27 kg/m2 range who have gained modest amounts of weight (2-10 kg of adipose mass) in adult life. Specific factors that appear to predispose MONW, as well as more obese individuals, to insulin resistance include central fat distribution, inactivity, and a low VO2max. Because these factors are potentially reversible and because insulin resistance may contribute to the pathogenesis of many diseases, it is our premise that a compelling argument can be made for identifying MONW individuals and treating them with diet, exercise, and possibly pharmacological agents before these diseases become overt, or at least early after their onset. One reason for doing so is that disorders such as type 2 diabetes may be accompanied by irreversible consequences, e.g., ischemic heart disease and nephropathy, at the time of diagnosis or shortly thereafter. Another is that MONW individuals in general should be younger and more amenable and responsive to diet and exercise therapy than are obese patients with established disease. That long-term diet and exercise can work is suggested by two large studies in which, over 5-6 years, the incidence of diabetes was diminished in nonobese and minimally obese patients with impaired glucose tolerance. Based on these considerations and the emerging worldwide epidemic of type 2 diabetes, we believe that studies to assess whether therapies aimed at young MONW individuals can prevent the development of type 2 diabetes and other diseases, including perhaps obesity itself, are urgently needed.
Plastic Properties (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPlastic PropertiesKeith L. Smith and Russell Van. CleveCite this: Ind. Eng. Chem. 1958, 50, 1, 12–16Publication Date (Print):January 1, 1958Publication History Published online1 May 2002Published inissue 1 January 1958https://pubs.acs.org/doi/10.1021/ie50577a024https://doi.org/10.1021/ie50577a024research-articleACS PublicationsRequest reuse permissionsArticle Views537Altmetric-Citations21LEARN 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 options Get e-Alerts
Relative multiplexing for minimising switching in linear-optical quantum computing (2017)

Many existing schemes for linear-optical quantum computing (LOQC) depend on multiplexing (MUX), which uses dynamic routing to enable near-deterministic gates and sources to be constructed using heralded, probabilistic primitives. MUXing accounts for the overwhelming majority of active switching demands in current LOQC architectures. In this manuscript we introduce relative multiplexing (RMUX), a general-purpose optimisation which can dramatically reduce the active switching requirements for MUX in LOQC, and thereby reduce hardware complexity and energy consumption, as well as relaxing demands on performance for various photonic components. We discuss the application of RMUX to the generation of entangled states from probabilistic single-photon sources, and argue that an order of magnitude improvement in the rate of generation of Bell states can be achieved. In addition, we apply RMUX to the proposal for percolation of a 3D cluster state in [PRL 115, 020502 (2015)], and we find that RMUX allows an 2.4x increase in loss tolerance for this architecture.
Locating high-affinity fatty acid-binding sites on albumin by x-ray crystallography and NMR spectroscopy (2005)

Human serum albumin (HSA) is a versatile transport protein for endogenous compounds and drugs. To evaluate physiologically relevant interactions between ligands for the protein, it is necessary to determine the locations and relative affinities of different ligands for their binding site(s). We present a site-specific investigation of the relative affinities of binding sites on HSA for fatty acids (FA), the primary physiological ligand for the protein. Titration of HSA with [(13)C]carboxyl-labeled FA was used initially to identify three NMR chemical shifts that are associated with high-affinity binding pockets on the protein. To correlate these peaks with FA-binding sites identified from the crystal structures of FA-HSA complexes, HSA mutants were engineered with substitutions of amino acids involved in coordination of the bound FA carboxyl. Titration of [(13)C]palmitate into solutions of HSA mutants for either FA site four (R410A/Y411A) or site five (K525A) within domain III of HSA each revealed loss of a specific NMR peak that was present in spectra of wild-type protein. Because these peaks are among the first three to be observed on titration of HSA with palmitate, sites four and five represent two of the three high-affinity long-chain FA-binding sites on HSA. These assignments were confirmed by titration of [(13)C]palmitate into recombinant domain III of HSA, which contains only sites four and five. These results establish a protocol for direct probing of the relative affinities of FA-binding sites, one that may be extended to examine competition between FA and other ligands for specific binding sites.
Müllerian Duct Regression in the Embryo Correlated with Cytotoxic Activity Against Human Ovarian Cancer (1979)

A significant cytotoxicity index was obtained when human ovarian cancer cells in a microcytotoxicity assay were exposed during the S (DNA-synthesizing) phase of the cell cycle to purified fractions of testis exhibiting high Müllerian inhibiting substance bioactivity. The same effect was not observed when these fractions were tested against human glioblastoma or fibroblast lines. Most human ovarian cancers are said to resemble Müllerian tissues histologically. Müllerian inhibiting substance may thus deserve further study as a potential chemotherapeutic agent.