gebhart/patrepeval huggingface dataset:
Characterization of Major Structural Proteins of Measles Virus with Monoclonal Antibodies (1985)

We have prepared and characterized monoclonal antibodies against five major structural proteins, i.e. the HA, P, NP, F and M proteins, of measles virus. At least three non-overlapping antigenic sites were delineated on the HA protein, three on the P, four on the NP, four on the F and five on the M proteins by competitive binding assays. Antigenic sites on the HA and F proteins roughly represented functional domains defined by serological tests. The reactivity of monoclonal antibodies with various measles virus strains including those from subacute sclerosing panencephalitis (SSPE) and other members of the morbillivirus family was studied by immunofluorescence. A monoclonal antibody or set of monoclonal antibodies to each of the antigenic sites showed a characteristic pattern of cross-reactivity with heterologous strains. The HA and NP proteins were antigenically the most variable, followed by the F and M proteins, while the P protein was relatively stable. None of the 14 anti-M monoclonal antibodies reacted with non-virus-producing SSPE cells, strongly suggesting the absence of M protein in these cells.
Direct SIRPa Blockade Augments Macrophage Responses to Therapeutic Anticancer Antibodies (2014)

Abstract Antibody-dependent phagocytosis is a crucial mechanism underlying the efficacy of therapeutic antibodies for cancer. However, a major barrier to phagocytosis exists in the CD47-SIRPa interaction. CD47, a molecular “don’t eat me” signal, is highly expressed on many types of cancer and acts as a myeloid-specific immune checkpoint. By engaging SIRPa, an inhibitory receptor on macrophages, CD47 limits the ability of macrophages to respond to therapeutic antibodies. In this study, we developed anti-human SIRPa antibodies that block the interaction between CD47 and SIRPa. By themselves, these antibodies were not sufficient to induce human macrophage phagocytosis. However, when combined with a variety of tumor-specific antibodies, the anti-SIRPa antibodies exhibited remarkable synergy and augmented antibody-dependent phagocytosis of human cancer cells. Addition of anti-SIRPa antibodies improved phagocytosis of cancer in response to rituximab, cetuximab, and trastuzumab, among other therapeutic antibodies. Moreover, anti-SIRPa antibodies enhanced macrophage phagocytosis of lymphoma cells in response to anti-CD20 variants produced with each subclass of human IgG or glycoengineered anti-CD20 antibodies, indicating they could be effective for the majority of therapeutic antibodies that are clinically approved or under development. Importantly, both polarized macrophages and primary tumor-associated macrophages exhibited increased responses to therapeutic antibodies when SIRPa was blocked. In contrast to therapies targeting CD47 directly, anti-SIRPa antibodies benefit from more restricted expression of SIRPa and could have more favorable pharmacokinetic and toxicity profiles. They are an important addition to the growing arsenal of therapeutics targeting the CD47-SIRPa axis for cancer and could act as universal adjuvants to therapeutic antibodies. Disclosures Weiskopf: Stanford University: CD47/SIRPa blocking therapies Patents &amp; Royalties. Ring:Stanford University: CD47/SIRPa blocking therapies Patents &amp; Royalties. Guo:Stanford University: CD47/SIRPa blocking therapies Patents &amp; Royalties. Volkmer:Stanford University: CD47/SIRPa blocking therapies Patents &amp; Royalties. Weissman:Stanford University: CD47/SIRPa blocking therapies Patents &amp; Royalties.
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases (2007)

Protein kinases play a pivotal role in cell signaling, and dysregulation of many kinases has been linked to disease development. A large number of kinase inhibitors are therefore currently under investigation in clinical trials, and so far seven inhibitors have been approved as anti-cancer drugs. In addition, kinase inhibitors are widely used as specific probes to study cell signaling, but systematic studies describing selectivity of these reagents across a panel of diverse kinases are largely lacking. Here we evaluated the specificity of 156 validated kinase inhibitors, including inhibitors used in clinical trials, against 60 human Ser/Thr kinases using a thermal stability shift assay. Our analysis revealed many unexpected cross-reactivities for inhibitors thought to be specific for certain targets. We also found that certain combinations of active-site residues in the ATP-binding site correlated with the detected ligand promiscuity and that some kinases are highly sensitive to inhibition using diverse chemotypes, suggesting them as preferred intervention points. Our results uncovered also inhibitor cross-reactivities that may lead to alternate clinical applications. For example, LY333'531, a PKCbeta inhibitor currently in phase III clinical trials, efficiently inhibited PIM1 kinase in our screen, a suggested target for treatment of leukemia. We determined the binding mode of this inhibitor by x-ray crystallography and in addition showed that LY333'531 induced cell death and significantly suppressed growth of leukemic cells from acute myeloid leukemia patients.
Transient IFN-γ synthesis in the lymph node draining a dermal site loaded with UV-irradiated herpes simplex virus type 1: an NK- and CD3-dependent process regulated by IL-12 but not by IFN-α/β (2000)

Our previous studies have shown that UV-inactivated, non-replicating herpes simplex virus type 1 (UV-HSV-1) triggers early and transient synthesis of IFN-alpha/beta in the mouse regional lymph node when delivered upstream (i.e. in the ear dermis). In this study, it is demonstrated, by use of a quantitative RT-PCR readout assay, that IFN-gamma mRNA expression was rapidly and transiently upregulated in draining lymph nodes when UV-HSV-1 was delivered in the ear dermis of C57Bl/6 mice. An increased number of IFN-gamma-producing cells was also detected in the lymph node by flow cytometric analysis. Two different subsets of cells, namely DX5(+) NK cells and CD3epsilon(+) T cells, accounted for this early IFN-gamma synthesis. Prompt upregulation of IFN-alpha and IL-12p40 mRNA was also recorded. We took advantage of IFN-alpha/beta-receptor knockout and wild-type 129 mice to study a potential role of IFN-alpha/beta in the signalling pathway leading to IFN-gamma transcription/translation. IFN-gamma mRNA upregulation still occurred in IFN-alpha/beta-receptor(-/-) mice, showing that IFN-alpha/beta was dispensable. The use of IL-12-neutralizing antibodies, prior to UV-HSV-1 delivery, confirmed the major role played by IL-12 in the early/transient IFN-gamma burst.
Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia (2013)

Long-acting coagulation factors, including rFVIIIFc and rFIXFc, have the potential to change current paradigms of care for hemophilia A and B, respectively. Less frequent infusions may provide prolonged protection from bleeding and bleed resolution with fewer injections. In addition, long-acting coagulation factors provide an opportunity for improved individualized treatment for hemophilia.
Identification and Characterization of 4-Methylbenzyl 4-[(Pyrimidin-2-ylamino)methyl]piperidine-1-carboxylate, an Orally Bioavailable, Brain Penetrant NR2B SelectiveN-Methyl-d-Aspartate Receptor Antagonist (2007)

The discovery of a novel series of NR2B subtype selective N-methyl-d-aspartate (NMDA) antagonists is reported. Initial optimization of a high-throughput screening lead afforded an aminopyridine derivative 13 with significant NR2B antagonist potency but limited selectivity over hERG-channel and other off-target activities. Further structure-activity studies on the aminoheterocycle moiety and optimization of the carbamate led to the highly potent 2-aminopyrimidine derivative 20j with a significantly improved off-target activity profile and oral bioavailability in multiple species coupled with good brain penetration. Compound 20j demonstrated efficacy in in vivo rodent models of antinociception, allodynia, and Parkinson's disease.
A Cell Signal Pathway Involving Laminin-5, α3β1 Integrin, and Mitogen-activated Protein Kinase Can Regulate Epithelial Cell Proliferation (1999)

Laminin-5 (LN5) is a matrix component of epithelial tissue basement membranes and plays an important role in the initiation and maintenance of epithelial cell anchorage to the underlying connective tissue. Here we show that two distinct LN5 function-inhibitory antibodies, both of which bind the globular domain of the alpha3 subunit, inhibit proliferation of epithelial cells. These same antibodies also induce a decrease in mitogen-activated protein kinase activity. Inhibition of proliferation by the function-perturbing LN5 antibodies is reversed upon removal of the antibodies and can be overcome by providing the antibody-treated cells with exogenous LN5 and rat tail collagen. Because epithelial cells use the integrin receptor alpha3beta1 to interact with both LN5 and rat tail collagen, we next investigated the possibility that integrin alpha3beta1 is involved in mediating the proliferative impact of LN5. Proliferation of human epithelial cells is significantly inhibited by a function-perturbing alpha3 integrin antibody. In addition, antibody activation of beta1 integrin restores the proliferation of epithelial cells treated with LN5 function-perturbing antibodies. These data indicate that a complex comprising LN5 and alpha3beta1 integrin is multifunctional and contributes not only to epithelial cell adhesion but also to the regulation of cell growth via a signaling pathway involving mitogen-activated protein kinase. We discuss our study in light of recent evidence that LN5 expression is up-regulated at the leading tips of tumors, where it may play a role in tumor cell proliferation.
Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. The Sepsis Intervention Group (1995)

<h3>Objective.</h3> —To assess the value of measuring circulating concentrations of mediators (endotoxin, tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], and interleukin-6 [IL-6]) and their endogenous antagonists (antiendotoxin core antibody [EndoCAb], interleukin-1 receptor antagonist [IL-1ra], and soluble TNF receptors [sTNF-R]) in predicting mortality and organ failure in sepsis syndrome. <h3>Design.</h3> —Cohort study with a follow-up period of 30 days. <h3>Setting.</h3> —Intensive therapy units of five tertiary referral centers in Scotland. <h3>Subjects.</h3> —A total of 146 intensive therapy unit patients with sepsis syndrome underwent repeated sampling during a 10-day period following admission to an intensive therapy unit. <h3>Main Outcome Measures.</h3> —Circulating concentrations of mediators and antagonists were compared in survivors and nonsurvivors. <h3>Results.</h3> —Median Acute Physiology and Chronic Health Evaluation II score was 23 (range, 8 to 40). Mortality at 30 days was 49%. On entry to the study, circulating endotoxin was detected in 66% of patients, TNF-α in 14%, and IL-1β in 29%. Levels did not predict mortality or organ failure. Patients with IL-6 concentrations in excess of 3000 pg/mL had an increased mortality rate (64% vs 40%,<i>P</i>=.02). The incidence of IgG EndoCAb depletion on entry to the study was 26% in nonsurvivors and 10% in survivors (<i>P</i>=.02). Initial concentrations of both type I and type II sTNF-R were significantly higher in nonsurvivors (<i>P</i>&lt;.01). Initial circulating IL-1ra concentrations were not of value in predicting mortality. Cytokine antagonists were present in concentrations 30- to 100 000-fold greater than their corresponding cytokine. <h3>Conclusion.</h3> —The observed high circulating levels of the cytokine antagonists IL-1ra and sTNF-R and the relatively small proportion of patients developing EndoCAb depletion may contribute to the limitations of therapies that aim to augment natural defenses against endotoxin or the proinflammatory cytokines. (<i>JAMA</i>. 1995;274:172-177)
Algorithmic music as intelligent game music (2014)

Current game music systems typically involve the playback of prerecorded audio tracks which are crossfaded in response to game events such as level changes. However, crossfading can limit the expressive power of musical transitions, and can make fine grained structural variations difficult to achieve. We therefore describe an alternative approach in which music is algorithmically generated based on a set of high-level musical features that can be controlled in real-time according to a player’s progression through a game narrative. We outline an implementation of the approach in an actual game, focusing primarily on how the music system traces the game’s emotional narrative by periodically querying certain narrative parameters and adjusting the musical features of its output accordingly.
Formation of 6‐keto prostaglandin E1 in mammalian kidneys (1983)

1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha to a stable metabolite with chromatographic and biological activity identical to that of authentic 6-keto PGE1. Activity was found in the kidney cortex but not medulla, was inhibited by NAD+ or NADP+ (5 mM) and showed an optimum temperature requirement of 37 degrees C. 3 Guinea-pig kidney converted PGI2 but not 6-keto PGF1 alpha to a labile, biologically active metabolite which was not 6-keto pge1. 4 No conversion of prostacyclin or 6-keto PGF1 alpha to biologically active metabolites occurred in cell-free homogenates of rat kidney, liver and colon or guinea-pig liver and colon. 5 6-keto PGE1 rapidly lost spasmogenic activity on the rat stomach strip following incubation with rabbit or guinea-pig kidney supernatant in the absence of added cofactors. No loss of activity occurred on incubation with rat kidney. 6 Rutin (50 microM) potently inhibited synthesis of 6-keto PGE1 from added PGI2 by rabbit kidney cortex. This reaction was potentiated by a similar concentration of sulphasalazine, carbenoxolone, imidazole, papaverine or indomethacin. 7 The relevance of these findings for the possible physiological and pathological roles of 6-keto PGE1 in the kidney is discussed.
Characterization and Functional Properties of Rice Bran Proteins Modified by Commercial Exoproteases and Endoproteases (2000)

ABSTRACT: Large portions of rice bran protein cannot be solubilized by mild solvents, but endoprotease use increases protein recovery. Bran was treated with 2 commercial proteases to achieve 8% to 9% peptide bond hydrolysis. The exo‐ plus endprotease was preferred to just using endopeptidases as it allowed the production of protein hydrolysates with enhanced functional properties. Solubility and emulsification activity and stability of hydrolysates produced with the protease blends were greater than that produced with endoprotease alone. These high value hydrolysates, produced from rice bran, an underutilized rice milling coproduct, are suitable for many processed foods, particularly those requiring potent solubility and emulsification at mildly acidic conditions.
Structure, function and evolution of the XPD family of iron–sulfur-containing 5′→3′ DNA helicases (2009)

The XPD (xeroderma pigmentosum complementation group D) helicase family comprises a number of superfamily 2 DNA helicases with members found in all three domains of life. The founding member, the XPD helicase, is conserved in archaea and eukaryotes, whereas the closest homologue in bacteria is the DinG (damage-inducible G) helicase. Three XPD paralogues, FancJ (Fanconi's anaemia complementation group J), RTEL (regular of telomere length) and Chl1, have evolved in eukaryotes and function in a variety of DNA recombination and repair pathways. All family members are believed to be 5'-->3' DNA helicases with a structure that includes an essential iron-sulfur-cluster-binding domain. Recent structural, mutational and biophysical studies have provided a molecular framework for the mechanism of the XPD helicase and help to explain the phenotypes of a considerable number of mutations in the XPD gene that can cause three different genetic conditions: xeroderma pigmentosum, trichothiodystrophy and Cockayne's syndrome. Crystal structures of XPD from three archaeal organisms reveal a four-domain structure with two canonical motor domains and two unique domains, termed the Arch and iron-sulfur-cluster-binding domains. The latter two domains probably collaborate to separate duplex DNA during helicase action. The role of the iron-sulfur cluster and the evolution of the XPD helicase family are discussed.
CYP24, the enzyme that catabolizes the antiproliferative agent vitamin D, is increased in lung cancer (2006)

1Alpha,25-dihydroxyvitamin D3 (1,25D3) displays potent antiproliferative activity in a variety of tumor model systems and is currently under investigation in clinical trials in cancer. Studies were initiated to explore its potential in nonsmall cell lung cancer (NSCLC), as effective approaches to the treatment of that disease are needed. In evaluating factors that may affect activity in NSCLC, the authors found that CYP24 (25-hydroxyvitamin D3-24-hydroxylase), the enzyme that catabolizes 1,25D3, is frequently expressed in NSCLC cell lines but not in the nontumorigenic bronchial epithelial cell line, Beas2B. CYP24 expression by RT-PCR was also detected in 10/18 primary lung tumors but in only 1/11 normal lung tissue specimens. Tumor-specific CYP24 upregulation was confirmed at the protein level via immunoblot analysis of patient-matched normal lung tissue and lung tumor extracts. Enzymatically active CYP24 is expected to desensitize NSCLC cells to 1,25D3. The authors therefore implemented a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for 1,25D3 and its CYP24-generated metabolites to determine whether NSCLC cells express active enzyme. Analysis of NSCLC cell cultures revealed time-dependent loss of 1,25D3 coincident with the appearance of CYP24-generated metabolites. MK-24(S)-S(O)(NH)-Ph-1, a specific inhibitor of CYP24, slowed the loss of 1,25D3 and increased 1,25D3 half-life. Furthermore, combination of 1,25D3 with MK-24(S)-S(O)(NH)-Ph-1 resulted in a significant decrease in the concentration of 1,25D3 required to achieve maximum growth inhibition in NSCLC cells. These data suggest that increased CYP24 expression in lung tumors restricts 1,25D3 activity and support the preclinical evaluation of CYP24 inhibitors for lung cancer treatment.
Antioxidant Potential of a Novel Tetrapeptide Derivative in Isoproterenol-Induced Myocardial Necrosis in Rats (2002)

A novel tetrapeptide derivative Boc-Lys(Boc)-Arg-Asp-Ser(tbu)-OtBu (PEP1261) has been tested in vivo in isoproterenol (ISO) hydrochloride (HCl)-induced myocardial necrosis in rats. ISO x HCl induces myocardial necrosis in rats which is accompanied by the distinct increase in heart weight, marked electrocardiographic changes, increase in the levels of serum marker enzymes and lipid peroxides and decrease in the levels of antioxidants. PEP1261 (5 mg/kg body weight i.p.) pre- and post-treatment effectively decreases serum marker enzyme levels, while the electrocardiographic changes get restored towards normalcy. PEP1261 also inhibits the action of the free radicals toxicity by increasing the levels of antioxidants and histological studies confirm the above findings. This study shows that PEP1261 could serve as an excellent cardioprotective agent possessing membrane-stabilizing action.
Synthesis and .sigma. Binding Properties of 1'- and 3'-Halo- and 1',3'-Dihalo-N-normetazocine Analogs (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and .sigma. Binding Properties of 1'- and 3'-Halo- and 1',3'-Dihalo-N-normetazocine AnalogsRichmond Danso-Danquah, Xu Bai, X. Zhang, S. Wayne Mascarella, Wanda Williams, Bethel Sine, Wayne D. Bowen, and F. Ivy CarrollCite this: J. Med. Chem. 1995, 38, 15, 2986–2989Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/jm00015a023https://doi.org/10.1021/jm00015a023research-articleACS PublicationsRequest reuse permissionsArticle Views93Altmetric-Citations8LEARN 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
The complete sequence of the capsid p40 gene from infectious laryngotracheitis virus (1990)

Journal Article The complete sequence of the capsid p40 gene from infectious laryngotracheitis virus Get access A.M. Griffin A.M. Griffin Institute for Animal Health, Houghton LaboratoryHoughton, Huntingdon PE17 2DA, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 12, 25 June 1990, Page 3664, https://doi.org/10.1093/nar/18.12.3664 Published: 25 June 1990 Article history Received: 05 May 1990 Published: 25 June 1990
A molecular profile of a hematopoietic stem cell niche (2002)

The hematopoietic microenvironment provides a complex molecular milieu that regulates the self-renewal and differentiation activities of stem cells. We have characterized a stem cell supportive stromal cell line, AFT024, that was derived from murine fetal liver. Highly purified in vivo transplantable mouse stem cells are maintained in AFT024 cultures at input levels, whereas other primitive progenitors are expanded. In addition, human stem cells are very effectively supported by AFT024. We suggest that the AFT024 cell line represents a component of an in vivo stem cell niche. To determine the molecular signals elaborated in this niche, we undertook a functional genomics approach that combines extensive sequence mining of a subtracted cDNA library, high-density array hybridization and in-depth bioinformatic analyses. The data have been assembled into a biological process oriented database, and represent a molecular profile of a candidate stem cell niche.
SPARC-null Mice Exhibit Lower Intraocular Pressures (2009)

SPARC-null mice have lower IOPs than do their WT counterparts with equal CCTs. The rate of aqueous turnover suggests that the mechanism is enhanced outflow resistance.