gebhart/patrepeval huggingface dataset:
The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice (2006)

Abstract CEP-7055, a fully synthetic, orally active N,N-dimethylglycine ester of CEP-5214, a C3-(isopropylmethoxy)–fused pyrrolocarbazole with potent pan–vascular endothelial growth factor receptor (VEGFR) kinase inhibitory activity, has recently completed phase I clinical trials in cancer patients. These studies evaluated the antitumor efficacy of CEP-7055 using orthotopic models of glioblastoma and colon carcinoma in combination with temozolomide, and irinotecan and oxaliplatin, respectively, for their effects on primary and metastatic tumor burden and median survival. Chronic administration of CEP-7055 (23.8 mg/kg/dose) and temozolomide resulted in improvement of median survival of nude mice bearing orthotopic human glioblastoma xenografts compared with temozolomide alone (261 versus 192 days, respectively; P ≤ 0.02). Reductions in neurologic dysfunction, brain edema, hemorrhage, and intratumoral microvessel density (CD34 staining) were observed in glioma-bearing mice receiving CEP-7055 alone, temozolomide alone, and the combination of CEP-7055 and temozolomide relative to vehicle and to temozolomide monotherapy. The administration of CEP-7055 in combination with irinotecan (20 mg/kg/dose i.p. × 5 days), and to a lesser degree with oxaliplatin (10 mg/kg/dose i.v.), showed reductions on primary colon carcinoma and hepatic metastatic burden in the CT-26 tumor model relative to that achieved by irinotecan and oxaliplatin monotherapy. These data show the significant efficacy and tolerability of optimal efficacious doses of CEP-7055 when given in combination with temozolomide and irinotecan relative to monotherapy with these cytotoxic agents in preclinical orthotopic glioma and colon carcinoma models and lend support for the use of these treatment regimens in a clinical setting in patients with glioblastoma and colon carcinoma. [Mol Cancer Ther 2006;5(7):1744–53]
Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component. (1994)

Focal adhesion formation in fibroblasts results from complex transmembrane signaling processes initiated by extracellular matrix molecules. Although a role for integrins with attendant tyrosine kinases has been established, there is evidence that cell surface heparan sulfate proteoglycans (HSPGs) are also involved with an associated role of protein kinase C. The identity of the proteoglycan has remained elusive, but we now report that syndecan 4 (ryudocan/amphiglycan) is present in focal adhesions of a number of cell types. Affinity-purified antibodies raised against a unique portion of the cytoplasmic domain of syndecan 4 core protein recognized an HSPG of similar characteristics to those of syndecan 4. These antibodies stained focal adhesions only after cell permeabilization and recognized differing mammalian species. Syndecan 4 was associated with focal adhesions that contained either beta 1 or beta 3 integrin subunits and those that formed on substrates of fibronectin, laminin, vitronectin, or type I collagen. No focal adhesions were found that were vinculin-containing but lacked syndecan 4. In contrast, syndecan 2, whose cytoplasmic domain is closely homologous to syndecan 4, does not appear to be a focal adhesion component. Thus, syndecan 4 represents a new transmembrane focal adhesion component, probably involved in their assembly.
Enantioselective Syntheses of (−)- and (+)-Homocitric Acid Lactones (1996)

Highly enantioselective syntheses of enantiomers of homocitric acid lactones (R)-5a and (S)-5b are described. Thermal Diels-Alder cycloadditions of 2a and 2b to 1,3-butadiene produced adducts 3a and 3b, respectively. Oxidative ozonolysis of latter adducts gave products 4a and 4b which after acid treatment afforded a mixture with 5a and 5b as major component. Acid lactones 5a and 5b were converted into their dimethyl esters 6a and 6b which were purified by chromatography. After saponification, the products obtained were crystallized to yield (-)- and (+)-homocitric acid lactones ((R)-5a and (S)-5b). Diastereomeric excess (de) of Diels-Alder adducts 3a and 3b was determined by means of Mosher esters of glycols 8a, 8b, and racemic 8. Diels-Alder cycloaddition products of lactones 2a and 2b to 1,3-butadiene showed a diastereoselectivity of 96%.
Placebo-Controlled Phase 3 Study of Oral BG-12 or Glatiramer in Multiple Sclerosis (2012)

In patients with relapsing-remitting multiple sclerosis, BG-12 (at both doses) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec; CONFIRM ClinicalTrials.gov number, NCT00451451.).
α-Aminoxy Acids: New Possibilities from Foldamers to Anion Receptors and Channels (2008)

Naturally occurring peptides serve important functions as enzyme inhibitors, hormones, neurotransmitters, and immunomodulators in many physiological processes including metabolism, digestion, pain sensitivity, and the immune response. However, due to their conformational flexibility and poor bioavailability, such peptides are not generally viewed as useful therapeutic agents in clinical applications. In an effort to solve these problems, chemists have developed peptidomimetic foldamers, unnatural oligomeric molecules that fold into rigid and well-defined secondary structures mimicking the structures and biological functions of these natural peptides. We have designed peptidomimetic foldamers that give predictable, backbone-controlled secondary structures irrespective of the nature of the side chains. This Account presents our efforts to develop a novel class of peptidomimetic foldamers comprising alpha-aminoxy acids and explore their applications in the simulation of ion recognition and transport processes in living systems. Peptides constructed from alpha-aminoxy acids fold according to the following rules: (1) A strong intramolecular eight-membered-ring hydrogen bond forms between adjacent alpha-aminoxy acid residues (the alpha N-O turn). The chirality of the alpha-carbon, not the nature of the side chains, determines the conformation of this chiral N-O turn. (2) While homochiral oligomers of alpha-aminoxy acids form an extended helical structure (1.8 8 helix), heterochiral ones adopt a bent reverse turn structure. (3) In peptides of alternating alpha-amino acids and alpha-aminoxy acids, the seven-membered-ring intramolecular hydrogen bond, that is, the gamma-turn, is initiated by a succeeding alpha N-O turn. Thus, this type of peptide adopts a novel 7/8 helical structure. In investigating the potential applications of alpha-aminoxy acids, we have found that the amide NH units of alpha-aminoxy acids are more acidic than are regular amide NH groups, which makes them better hydrogen bond donors when interacting with anions. This property makes alpha-aminoxy acids ideal building blocks for the construction of anion receptors. Indeed, we have constructed both cyclic and acyclic anion receptors that have strong affinities and good (enantio-)selectivities toward chloride (Cl(-)) and chiral carboxylate ions. Taking advantage of these systems' preference for Cl(-) ions, we have also employed alpha-aminoxy acid units to construct a synthetic Cl(-) channel that can mediate the passage of Cl(-) ions across cell membranes. Continued studies of these peptidomimetic systems built from alpha-aminoxy acids should lead to a broad range of applications in chemistry, biology, medicine, and materials science.
Antiaggregative-Rivalry Pheromone of the Mountain Pine Beetle,1 and a New Arrestant of the Southern Pine Beetle1, 2 (1974)

Journal Article Antiaggregative-Rivalry Pheromone of the Mountain Pine Beetle, and a New Arrestant of the Southern Pine Beetle, Get access J. A. Rudinsky, J. A. Rudinsky Search for other works by this author on: Oxford Academic PubMed Google Scholar M. E. Morgan, M. E. Morgan Search for other works by this author on: Oxford Academic PubMed Google Scholar L. M. Libbey, L. M. Libbey Search for other works by this author on: Oxford Academic PubMed Google Scholar T. B. Putnam T. B. Putnam 3 3Dep Entomol. (J.A.R.), Dep. Food Sci. Technol., Oregon State Univ., Corvallis 97331. Search for other works by this author on: Oxford Academic PubMed Google Scholar Environmental Entomology, Volume 3, Issue 1, 1 February 1974, Pages 90–98, https://doi.org/10.1093/ee/3.1.90 Published: 01 February 1974 Article history Received: 05 July 1973 Published: 01 February 1974
Mechanisms of Fibrosis in Coal Workers' Pneumoconiosis. Increased Production of Platelet-Derived Growth Factor, Insulin-Like Growth Factor Type I, and Transforming Growth Factor Beta and Relationship to Disease Severity (1994)

To identify the clinical relevance of cytokines involved in the development of lung fibrosis observed in patients with coal workers' pneumoconiosis (CWP), we investigated the BAL fluid contents and AM secretions of three mediators that modulate fibroblast growth: platelet-derived growth factor (PDGF), Type I insulin-like growth factor (IGF-I), and transforming growth factor Type beta (TGF-beta). Our study population consisted of 25 patients with CWP (16 simple pneumoconiosis, SP, 9 progressive massive fibrosis, PMF, 9 control subjects, and 6 patients with idiopathic pulmonary fibrosis (IPF). The fibrotic potency of AM supernatants was also tested for their ability to promote the growth of a human lung fibroblast cell line appreciated by [3H]-thymidine incorporation. PDGF and IGF-I concentrations were increased in BAL fluids of patients with PMF compared with SP and control subjects, whereas TGF-beta concentration was significantly higher in BAL fluid of patients with SP compared with PMF and control subjects. PDGF, IGF-I, and TGF-beta concentrations in AM supernatants followed the same profile observed in BAL fluids, suggesting that AM is one of the main cell sources of PDGF, IGF-I, and TGF-beta in the lung of pneumoconiotic patients. After treatment by acidification, which activated the latent form of TGF-beta, AM from patients with SP induced an inhibition of [3H]-thymidine incorporation and fibroblast growth was restored after neutralization of TGF-beta by specific antibodies. In contrast, AM supernatants from patients with PMF and IPF promoted the proliferation of fibroblasts and treatment by acidification did not modify this effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Combinations of Affinity-Enhancing Mutations in a T Cell Receptor Reveal Highly Nonadditive Effects within and between Complementarity Determining Regions and Chains (2010)

Understanding the energetic and structural response to multiple mutations in a protein-protein interface is a key aspect of rational protein design. Here we investigate the cooperativity of combinations of point mutations of a T cell receptor (TCR) that binds in vivo to HLA-A2 MHC and a viral peptide. The mutations were obtained from two sources: a structure-based design study on the TCR alpha chain (nine mutations) and an in vitro selection study on the TCR beta chain (four mutations). In addition to combining the highest-affinity variants from each chain, we tested other combinations of mutations within and among the chains, for a total of 23 TCR mutants that we measured for binding kinetics to the peptide and major histocompatibility complex. A wide range of binding affinities was observed, from 2- to 1000-fold binding improvement versus that of the wild type, with significant nonadditive effects observed within and between TCR chains. This included an amino acid-dependent cooperative interaction between CDR1 and CDR3 residues that are separated by more than 9 A in the wild-type complex. When analyzing the kinetics of the mutations, we found that the association rates were primarily responsible for the cooperativity, while the dissociation rates were responsible for the anticooperativity (less-than-additive energetics). On the basis of structural modeling of anticooperative mutants, we determined that side chain clash between proximal mutants likely led to nonadditive binding energies. These results highlight the complex nature of TCR association and binding and will be informative in future design efforts that combine multiple mutant residues.
Mouse Peptidoglycan Recognition Protein PGLYRP-1 Plays a Role in the Host Innate Immune Response againstListeria monocytogenesInfection (2010)

The role of mouse peptidoglycan recognition protein PGLYRP-1 in innate immunity against Listeria monocytogenes infection was studied. The recombinant mouse PGLYRP-1 and a polyclonal antibody specific to PGLYRP-1 were prepared. The mouse PGLYRP-1 showed antibacterial activities against L. monocytogenes and other Gram-positive bacteria. PGLYRP-1 mRNA expression was induced in the spleens and livers of mice infected with L. monocytogenes. The viable bacterial number increased, and the production of cytokines such as gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) was reduced in mice when mice had been injected with anti-PGLYRP-1 antibody before infection. The levels of IFN-γ and TNF-α titers in the organs were higher and the viable bacterial number was reduced in mice injected with recombinant mouse PGLYRP-1 (rmPGLYRP-1) before infection. PGLYRP-1 could directly induce these cytokines in spleen cell cultures. The elimination of intracellular bacteria was upregulated in NMuLi hepatocyte cells overexpressing PGLYRP-1. The enhancement of the elimination of L. monocytogenes from the organs was observed in IFN-γ(-/-) mice by rmPGLYRP-1 administration but not in TNF-α(-/-) mice. These results suggest that PGLYRP-1 plays a role in innate immunity against L. monocytogenes infection by inducing TNF-α.
NR2B Selective NMDA Receptor Antagonists (2002)

NR2B antagonists have received considerable attention in recent years. In this class of excitatory amino acid receptor antagonists NR2B antagonists have shown efficacy in neuroprotection, anti-hyperalgesic and anti-Parkinson animal models. Several groups are involved in developing these compounds as therapeutic agents and evaluating newer therapeutic targets for these agents. Until recently benzylpiperidine and phenylpiperidine templates, which were based on the structures of Ifenprodil and Eliprodil, formed the basis of most SAR in this area. A few chemical leads in this class such as CP-101,606, Ro25,6981 and PD0196860 have been identified as possible development leads which have generated significant interest in this area. In addition to the efforts of Pfizer (Parke-Davis), Roche and E.Merck, several other industrial and academic research groups have continued to work in the NR2B area and recently Merck and Roche have reported new chemical leads as NR2B antagonists with significantly different biaryl templates. These new advances have raised hope, for potential success of the NR2B antagonists as new therapeutic agents, for the treatment of several pathophysiological indications.
Arsenicals in the Isoquinoline Series (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTArsenicals in the Isoquinoline SeriesBill Elpern and Cliff S. HamiltonCite this: J. Am. Chem. Soc. 1946, 68, 8, 1436–1438Publication Date (Print):August 1, 1946Publication History Published online1 May 2002Published inissue 1 August 1946https://pubs.acs.org/doi/10.1021/ja01212a012https://doi.org/10.1021/ja01212a012research-articleACS PublicationsRequest reuse permissionsArticle Views172Altmetric-Citations23LEARN 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
Role of TGF-β in proliferative vitreoretinal diseases and ROCK as a therapeutic target (2008)

Cicatricial contraction of preretinal fibrous membrane is a cause of severe vision loss in proliferative vitreoretinal diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). TGF-beta is overexpressed in the vitreous of patients with proliferative vitreoretinal diseases and is also detectable in the contractile membranes. Therefore, TGF-beta is presumed to contribute to the cicatricial contraction of the membranes, however, the underlying mechanisms and TGF-beta's importance among various other factors remain to be elucidated. Vitreous samples from PDR or PVR patients caused significantly larger contraction of hyalocyte-containing collagen gels, compared with nonproliferative controls. The contractile effect was strongly correlated with the vitreal concentration of activated TGF-beta2 (r = 0.82, P < 0.0001). PDR or PVR vitreous promoted expression of alpha-smooth muscle actin (alpha-SMA) and phosphorylation of myosin light chain (MLC), a downstream mediator of Rho-kinase (ROCK), both of which were dramatically but incompletely suppressed by TGF-beta blockade. In contrast, fasudil, a potent and selective ROCK inhibitor, almost completely blocked the vitreous-induced MLC phosphorylation and collagen gel contraction. Fasudil disrupted alpha-SMA organization, but it did not affect its vitreal expression. In vivo, fasudil significantly inhibited the progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells by electroretinographic and histological analyses. These results elucidate the critical role of TGF-beta in mediating cicatricial contraction in proliferative vitreoretinal diseases. ROCK, a key downstream mediator of TGF-beta and other factors might become a unique therapeutic target in the treatment of proliferative vitreoretinal diseases.
Identification of an aprotinin antiviral domain (1994)

Digestion of the proteinase inhibitor aprotinin, by clostripain, a cysteine proteinase, yielded five oligopeptide fragments. Two fragments exhibited both antiviral and antibacterial activities, two fragments only antiviral activity, and one fragment showed no antimicrobial activity. One of the former oligopeptides showed antiviral activity against human herpes simplex virus type 1 and bovine parainfluenza virus type 3. It consisted of the hexapeptide Y-F-Y-N-A-K corresponding to amino acids 21-26 of intact aprotinin. An identical synthetic peptide had the same antiviral spectrum as the natural hexapeptide, exhibited no antibacterial activity, and was also devoid of trypsin inhibiting activity. Intact aprotinin, in contrast, is ineffective against human herpes simplex virus 1 and bovine parainfluenza virus 3 but possesses antibacterial properties against several bacterial species [(1992) J. Appl. Bact. 72, 180-187].
FAST AND INCREMENTAL ROUTABILITY CHECK OF A TOPOLOGICAL ROUTING USING A CUT-BASED ENCODING (1997)

Many performance-driven routing algorithms do not consider outability. Routing trees are built assuming that there are no other wires. The main reason for this is that it is NP-hard to guarantee routability. Even checking for routability is a time-consuming process. This limits the usefulness of many performance-driven routing algorithms because unroutable designs are useless. Previous online routability checking is not fast enough for the many iterative improvement steps in a performance-driven routing algorithm. This paper provides such an algorithm. We propose a versatile topological routing encoding that not only allows an efficient routability check, but also provides proximity information for crosstalk and manufacturability analysis. Our routing model is applicable to a wide range of technologies, including PCB, MCM and standard cell ASIC. It allows rectilinear, octilinear or Euclidean wiring metric and arbitrary-shaped obstacles. It is gridless and supports variable wire width and spacing. Our algorithm is fast enough to be integrated into any iterative improvement schemes such as simulated annealing. Our basic observation is that the placement of obstacles is fixed but rerouting is very frequent. So we emphasize on an efficient rerouting and routability check step but pushes the complexity to building a data structure that depends only on the placement of the obstacles.
Resin flow through fiber beds during composite manufacturing processes. Part I: Review of newtonian flow through fiber beds (1992)

Abstract A critical part of any master model used to simulate or control a composite material manufacturing process is the description of resin flow through the fiber bed. We present here a review of both theoretical and experimental studies of fluid flow through porous media, including fiber beds. For the practical porosity range of interest in continuous fiber composites processing (0.3&lt; ϵ &lt; 0.6), the permeability cannot be accurately described using the Blake‐Kozeny‐Carman equation, even though the flow is Newtonian at very low Reynold's number. For aligned fiber situations, the Kozeny constant, k , deviates radically from theory, depends on bed nonuniformities, and is only constant over very narrow porosity ranges. Thus, one cannot experimentally determine k at high porosities and use this value to describe low porosity situations. Theoretical attempts, based on perfectly spaced and aligned arrays of cylinders, adequately describe the transverse permeability of ideal fiber beds in the high porosity range, but do not succeed at porosities below 0.6. For axial flow through aligned fiber beds, the theory yields permeabilities much lower than are experimentally observed throughout the entire porosity range. For randomly arranged fibers, random cylinder theory also predicts permeabilities that are significantly lower than are measured.
A 5&#x2013;9-mw, 0.2&#x2013;2.5-GHz CMOS low-if receiver for spectrum-sensing cognitive radio sensor networks (2013)

A low-power, wideband CMOS receiver for spectrum-sensing cognitive radio sensor networks is presented. The low-IF receiver equipped with an inverter-based LNA-balun and I/Q sub-threshold rectifier enables low-power and high-speed spectrum sensing. For further extension to support higher data-rate radio systems, our local oscillator provides a frequency-dividing function when a low-phase-noise signal source is optionally used. A prototype chip fabricated in a 65-nm CMOS process can support a wide frequency range of 0.2-2.5 GHz with 43-dB maximum gain, 6-dB NF, and -9-dBm IIP3 and only occupies 0.6 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> while consuming as low as 5-9 mW at a 0.6-V supply.
Controlled microstructure oxide coatings for chemical sensors (1990)

The use of porous oxide coatings, formed using sol-gel chemistry routes, as the discriminating elements of acoustic wave (AW) chemical sensors, is investigated. These coatings provide several unique advantages: durability, high adsorption capacity based on large surface areas, and chemical selectivity based on both molecular size and chemical interactions. The porosity of these coatings is determined by performing nitrogen adsorption isotherms using the AW device response to monitor the uptake of nitrogen at 77 K. The chemical sensitivity and selectivity obtained with this class of coatings is demonstrated using several examples: hydrous titanate ion exchange coatings, zeolite/silicate microcomposite coatings, and surface modified silicate films.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>