gebhart/patrepeval huggingface dataset:
RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease (2016)

High density lipoproteins (HDL), through activity of the main protein component apolipoprotein A-I (ApoA-I), can reduce the risk of cardiovascular disease (CVD) by removing excess cholesterol from atherosclerotic plaque. In this study, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor RVX-208 increases ApoA-I gene transcription and protein production in human and primate primary hepatocytes. Accordingly, RVX-208 also significantly increases levels of ApoA-I, HDL-associated cholesterol, and HDL particle number in patients who received the compound in recently completed phase 2b trials SUSTAIN and ASSURE. Moreover, a post-hoc analysis showed lower instances of major adverse cardiac events in patients receiving RVX-208. To understand the effects of RVX-208 on biological processes underlying cardiovascular risk, we performed microarray analyses of human primary hepatocytes and whole blood treated ex vivo. Overall, data showed that RVX-208 raises ApoA-I/HDL and represses pro-inflammatory, pro-atherosclerotic and pro-thrombotic pathways that can contribute to CVD risk.
Site-selective spectroscopy of erbium-dopedSrTiO3,Sr2TiO4, andSr3Ti2O7 (1995)

The fluorescence spectra of erbium-doped strontium titanate were investigated as a function of sample preparation in order to probe the solid-state defect equilibrium. Erbium dopants double as donor dopants and as optical probes that reflect the variety of defect compensation mechanisms of strontium titanate. Erbium sites were correlated within the strontium titanate phases as a function of cation stoichiometry, dopant concentration, and annealing conditions. Unlike previously studied rare-earth ions, one erbium site apiece was assigned to the ${\mathrm{Sr}}_{2}$${\mathrm{TiO}}_{4}$ and ${\mathrm{Sr}}_{3}$${\mathrm{Ti}}_{2}$${\mathrm{O}}_{7}$ phases, while the ${\mathrm{SrTiO}}_{3}$ phase supported four sites. The relative distribution of two of the latter sites showed unprecedented sensitivity to ${\mathrm{SrTiO}}_{3}$ stoichiometry and preparation conditions. The observed changes in the site distribution do not agree with simple solid-state defect equilibrium models.
Layer Two Tunneling Protocol "L2TP" (1999)

This document describes the Layer Two Tunneling Protocol (L2TP).STD 51, RFC 1661 specifies multi-protocol access via PPP [RFC1661].L2TP facilitates the tunneling of PPP packets across an intervening network in a way that is as transparent as possible to both end-users and applications.Table of Contents 1.0 Introduction.....
Assembly of the 30S ribosomal subunit: Positioning ribosomal protein S13 in the S7 assembly branch (2004)

Studies of Escherichia coli 30S ribosomal subunit assembly have revealed a hierarchical and cooperative association of ribosomal proteins with 16S ribosomal RNA; these results have been used to compile an in vitro 30S subunit assembly map. In single protein addition and omission studies, ribosomal protein S13 was shown to be dependent on the prior association of ribosomal protein S20 for binding to the ribonucleoprotein particle. While the overwhelming majority of interactions revealed in the assembly map are consistent with additional data, the dependency of S13 on S20 is not. Structural studies position S13 in the head of the 30S subunit > 100 A away from S20, which resides near the bottom of the body of the 30S subunit. All of the proteins that reside in the head of the 30S subunit, except S13, have been shown to be part of the S7 assembly branch, that is, they all depend on S7 for association with the assembling 30S subunit. Given these observations, the assembly requirements for S13 were investigated using base-specific chemical footprinting and primer extension analysis. These studies reveal that S13 can bind to 16S rRNA in the presence of S7, but not S20. Additionally, interaction between S13 and other members of the S7 assembly branch have been observed. These results link S13 to the 3' major domain family of proteins, and the S7 assembly branch, placing S13 in a new location in the 30S subunit assembly map where its position is in accordance with much biochemical and structural data.
Induction of Acetylcholine Receptor Gene Expression by ARIA Requires Activation of Mitogen-activated Protein Kinase (1996)

Transcription of genes encoding nicotinic acetylcholine receptor (AChR) subunits (alpha, beta, gamma or epsilon, and delta) is highest in nuclei localized to the synaptic region of the muscle, which contributes to maintain a high density of AChRs at the postjunctional membrane. ARIA (AChR inducing activity) is believed to be the trophic factor utilized by motor neurons to stimulate AChR synthesis in the subsynaptic area. To elucidate the signaling mechanism initiated by ARIA, we established stable C2C12 cell lines carrying the nuclear lacZ gene under the control of the mouse epsilon subunit promoter or chicken alpha subunit promoter. ARIA stimulated tyrosine phosphorylation of erbB proteins in these C2C12 cells within 15 s with a peak at 5 min. Immediately following tyrosine phosphorylation of erbB proteins, mitogen-activated protein (MAP) kinase was activated which occurred within 30 s and peaked at 8 min after ARIA stimulation. Concomitantly, expression of AChR genes was induced by ARIA. ARIA-induced AChR subunit transgene expression was observed only in differentiated myotubes and not in myoblasts, suggesting that downstream signaling component(s) are regulated in a manner dependent on the myogenic program. Inhibition of the MAP kinase activity by using a specific MAP kinase kinase inhibitor or by overexpressing dominant negative mutants of Raf or MAP kinase kinase attenuated or abolished the ARIA-induced activation of AChR alpha and epsilon subunit gene expression. These results indicate that regulation of AChR gene expression by ARIA in C2C12 cells requires activation of the MAP kinase signaling pathway.
Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease (2010)

Non-erosive reflux disease and EE patients presented increased TRPV1 receptors mRNA and protein, although no correlation with acid exposure was demonstrated. Increased TRPV1 in the esophageal mucosa may contribute to symptoms both in NERD and EE patients and possibly account for peripheral mechanisms responsible for esophageal hypersensitivity in NERD patients.
MyD88-Dependent Activation of B220−CD11b+LY-6C+ Dendritic Cells during Brucella melitensis Infection (2007)

Abstract IFN-γ is a key cytokine controlling Brucella infection. One of its major function is the stimulation of Brucella-killing effector mechanisms, such as inducible NO synthase (iNOS)/NOS2 activity, in phagocytic cells. In this study, an attempt to identify the main cellular components of the immune response induced by Brucella melitensis in vivo is made. IFN-γ and iNOS protein were analyzed intracellularly using flow cytometry in chronically infected mice. Although TCRβ+CD4+ cells were the predominant source of IFN-γ in the spleen, we also identified CD11b+LY-6C+LY-6G−MHC-II+ cells as the main iNOS-producing cells in the spleen and the peritoneal cavity. These cells appear similar to inflammatory dendritic cells recently described in the mouse model of Listeria monocytogenes infection and human psoriasis: the TNF/iNOS-producing dendritic cells. Using genetically deficient mice, we demonstrated that the induction of iNOS and IFN-γ-producing cells due to Brucella infection required TLR4 and TLR9 stimulation coupled to Myd88-dependent signaling pathways. The unique role of MyD88 was confirmed by the lack of impact of Toll-IL-1R domain-containing adaptor inducing IFN-β deficiency. The reduction of IFN-γ+ and iNOS+ cell frequency observed in MyD88-, TLR4-, and TLR9-deficient mice correlated with a proportional lack of Brucella growth control. Taken together, our results provide new insight into how immune responses fight Brucella infection.
How much dystrophin is enough: the physiological consequences of different levels of dystrophin in themdxmouse (2015)

Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly understood. In order to robustly evaluate functional improvement, we used in situ protocols in the mdx mouse to measure muscle strength and resistance to eccentric contraction-induced damage. Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. We reveal that 15% homogeneous dystrophin expression is sufficient to protect against eccentric contraction-induced injury. In addition, we demonstrate a >40% increase in specific isometric force following repeated administrations. Strikingly, we show that changes in muscle strength are proportional to dystrophin expression levels. These data define the dystrophin restoration levels required to slow down or prevent disease progression and improve overall muscle function once a dystrophic environment has been established in the mdx mouse model.
Biological Control of Dollar Spot Disease of Creeping Bentgrass (1991)

Top-dressing creeping bentgrass with sand-cornmeal or chopped grain colonized by fungi or bacteria was tested as a means of suppressing the intensity of epidemics of dollar spot disease incited by Sclerotinia homoeocarpa. In a greenhouse, 45- to 90-day-old turfgrass grown in cups was top-dressed with 1,500 cm 3 /m 2 of sand-cornmeal infested by myceliumof S. homoeocarpa, followed by an equal amount of sand-cornmeal infested by potential antagonists. Four of 24 potential antagonists inhibited the growth of S. homoeocarpa and suppressed disease by 25-90% (...)
Metronidazole Treatment in Pregnancy (1978)

ABSTRACT Vaginal trichomoniasis was treated with standard courses of oral metronidazole in 597 pregnant women. In 283 other pregnant women, the infection remained untreated. The incidences of low‐birth‐weight infants, stillbirths and congenital abnormalities were not affected by metronidazole treatment of trichomoniasis in pregnancy.
Integration of InP/InGaAsP photodetectors onto silicon-on-insulator waveguide circuits (2005)

The integration of optical functionalities on a chip has been a long standing goal in the optical community. Given the call for more integration, Silicon-on-Insulator (SOI) is a material system of great interest. Although mature CMOS technology can be used for the fabrication of passive optical functionality, particular photonic functions like efficient light emission still require III-V semiconductors. We present the technology for heterogeneous integration of III-V semiconductor optical components and SOI passive optical components using benzocyclobutene (BCB) die to wafer bonding. InP/InGaAsP photodetectors on SOI waveguide circuits were fabricated. The developed process is compatible with the fabrication of InP/InGaAsP light emitters on SOI.
Carbamazepine‐Induced Release of Serotonin from Rat Hippocampus In Vitro (1998)

We conclude that CBZ (a) releases serotonin from hippocampal slices independent of exocytosis and by a mechanism not involving the neuronal membrane serotonin transporter, and (b) at high enough concentration, blocks the neuronal serotonin transporter.
Laboratory Investigation of Cerebrospinal Fluid Proteins (1990)

Analysis of CSF proteins is useful in the diagnosis and management of neurological diseases in the following situations: 1. In inflammatory conditions when there is breakdown of blood-CSF barrier integrity. Meningitis is a medical emergency, with CSF total protein measurement being only a screening test. 2. In the detection of immune responses within the CNS. This is by far the most important application in a routine clinical setting, as it is now a firmly established criterion in the diagnosis of multiple sclerosis. Oligoclonal bands restricted to the CSF are the only reliable indicators of intrathecal immunoglobulin G synthesis and are practically always associated with inflammatory disease of the CNS. The method fo choice for detecting oligoclonal bands is isoelectric focusing with immunofixation. Quantitative measurement of IgG in the CSF is of no value in diagnostic pathology. 3. In destructive brain diseases when brain-specific proteins are released into the CSF, measurement of these proteins can give prognostic information.
A fluorimetric enzyme assay for the diagnosis of sanfilippo disease type A (MPS IIIA) (1995)

Summary 4‐Methylumbelliferyl‐ α ‐ d ‐ N ‐sulphoglucosaminide (MU‐ α ‐GlcNS) was synthesized and shown to be a substrate for the lysosomal heparin sulphamidase. Sanfilippo A patients' fibroblasts ( n =42) and lymphocytes ( n =1) showed 0–3% of mean normal heparin sulphamidase activity; in total leukocytes from patients ( n =8) sulphamidase activity was clearly deficient. In fibroblasts from obligate heterozygotes for Sanfilippo A, the sulphamidase activity was reduced in 9 out of 10 cases. Heparin sulphamidase desulphates MU‐ α GlcNS to MU‐ α GlcNH 2 and further hydrolysis during a second incubation is required to liberate 4‐methylumbelliferone, which can be measured. Yeast α ‐glucosidase, which has low but sufficient α ‐glucosaminidase activity, was used to hydrolyse the reaction intermediate MU‐ α GlcNH 2 to release 4‐methylumbelliferone and free glucosamine.
Optimization of Liganded Polyethylenimine Polyethylene Glycol Vector for Nucleic Acid Delivery (2014)

The delivery of nucleic acids into cells is an attractive approach for cancer therapy. Polyethylenimine (PEI) is among the most efficient nonviral carriers. Recent studies have demonstrated that PEI can be conjugated to targeting ligands, such as epidermal growth factor (EGF) and transferrin (Schaffert et al., 2011; Abourbeh et al., 2012; Ogris et al., 1999). Herein we present a simplified protocol for producing homogeneous preparations of PEGylated linear PEI: LPEI-PEG2k. We generated two well-characterized copolymers, with ratios of LPEI to PEG of 1:1 and 1:3. These copolymers were further conjugated through disulfide bonds to a Her-2 targeting moiety, Her-2 affibody. This reaction yielded two triconjugates that target Her-2 overexpressing tumors. Polyplexes were formed by complexing plasmid DNA with the triconjugates. We characterized the biophysical properties of the conjugates, and found that the triconjugate 1:3 polyplex had lower ζ potential, larger particle size, and more heterogeneous shape than the triconjugate 1:1 polyplex. Triconjugate 1:1 and triconjugate 1:3 polyplexes were highly selective toward cells that overexpress Her-2 receptors, but triconjugate 1:1 polyplex was more efficient at gene delivery. Our studies show that the biophysical and biological properties of the conjugates can be profoundly affected by the ratio of LPEI:PEG2k:ligand. The procedure described here can be adapted to generate a variety of triconjugates, simply by changing the targeting moiety.
Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors (2012)

The safety profile of MEDI-547 does not support further clinical investigation in patients with advanced solid tumors.
Synthesis and Biology of a 7-Nitro-2,1,3-benzoxadiazol-4-yl Derivative of 2-Phenylindole-3-acetamide:  A Fluorescent Probe for the Peripheral-Type Benzodiazepine Receptor (1997)

ADVERTISEMENT RETURN TO ISSUELetterNEXTSynthesis and Biology of a 7-Nitro-2,1,3-benzoxadiazol-4-yl Derivative of 2-Phenylindole-3-acetamide: A Fluorescent Probe for the Peripheral-Type Benzodiazepine ReceptorAlan P. Kozikowski, Maria Kotoula, Dawei Ma, Noureddine Boujrad, Werner Tückmantel, and Vassilios PapadopoulosView Author Information Drug Discovery Laboratory, Institute of Cognitive and Computational Sciences, and Department of Cell Biology, Georgetown University Medical Center, 3970 and 3900 Reservoir Road, NW, Washington, D.C. 20007 Cite this: J. Med. Chem. 1997, 40, 16, 2435–2439Publication Date (Web):August 1, 1997Publication History Received31 March 1997Published online1 August 1997Published inissue 1 August 1997https://pubs.acs.org/doi/10.1021/jm970220whttps://doi.org/10.1021/jm970220wrapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views801Altmetric-Citations43LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Fluorescence,Labeling,Ligands,Reaction products,Receptors Get e-Alerts
New N-(Pyridin-4-yl)-(indol-3-yl)acetamides and Propanamides as Antiallergic Agents (1999)

A series of new N-(pyridin-4-yl)-(indol-3-yl)alkylamides 44-84 has been prepared in the search of novel antiallergic compounds. Synthesis of the desired ethyl (2-methyindol-3-yl)acetates 1-4 was achieved by indolization under Fischer conditions; Japp-Klingemann method followed by 2-decarboxylation afforded the ethyl (indol-3-yl)alkanoates 17-25. Amidification was successfully carried out by condensation of the corresponding acids or their N-aryl(methyl) derivatives with 4-aminopyridine promoted by 2-chloro-1-methylpyridinium iodide. Efforts to improve the antiallergic potency of the title series by variation of the indole substituents (R1, R2, R) and the length of the alkanoic chain (n = 1, 2, 3) led to the selection of N-(pyridin-4-yl)-[1-(4-fluorobenzyl)indol-3-yl]acetamide 45, out of 41 compounds. This amide was 406-fold more potent than astemizole in the ovalbumin-induced histamine release assay, using guinea pig peritoneal mast cells, with an IC50 = 0.016 microM. Its inhibitory activity in IL-4 production test from Th-2 cells was identical to that of the reference histamine antagonist (IC50 = 8.0 microM) and twice higher in IL-5 assay: IC50 = 1.5 and 3.3 microM, respectively. In vivo antiallergic activity evaluation confirmed efficiency of 45 in sensitized guinea pig late phase eosinophilia inhibition, after parenteral and oral administration at 5 and 30 mg/kg, respectively. Its efficiency in inhibition of microvascular permeability was assessed in two rhinitis models; ovalbumin and capsaicin-induced rhinorrhea could be prevented after topical application of submicromolar concentrations of 45 (IC50 = 0.25 and 0.30 microM); and it also exerted significant inhibitory effect in the first test after iv and oral administration, with ID50 = 0.005 and 0.46 mg/kg.
A critical stem-loop structure in the CR4-CR5 domain of mammalian telomerase RNA (2002)

Telomerase is an enzyme that maintains telomere length by adding telomeric sequence repeats onto chromosome ends. The telomerase ribonucleoprotein complex consists of two essential components, a reverse transcriptase and an RNA molecule that provides the template for telomeric repeat synthesis. A common secondary structure of vertebrate telomerase RNA has been proposed based on a phylogenetic comparative analysis of 35 sequences. Here we report the identification of an additional essential base-paired region in the CR4-CR5 domain of mammalian telomerase RNA, termed P6.1. Mouse telomerase RNAs with mutations that disrupted base pairings in the P6.1 helix were unable to reconstitute telomerase activity in vivo. In contrast, an RNA mutant with compensatory mutations that restored base pairings in the P6.1 helix restored telomerase activity. In an in vitro reconstitution system stable base pairing of the P6.1 stem was required for the RNA-protein interaction between the CR4-CR5 domain and the telomerase reverse transcriptase (TERT) protein. Interestingly, two RNA mutations, one that extends the P6.1 stem and one that alters the conserved nucleotides of the L6.1 loop, allowed RNA-protein binding but significantly impaired telomerase activity. These data establish the presence of the P6.1 stem-loop and its importance for the assembly and enzymatic activity of the mammalian telomerase complex.
Materials Selection for an Ink Jet Printer (1977)

An ink jet printer includes a system of parts that supplies, filters, pumps, circulates, and pulses a jet of ink. These parts, made of various materials (metals, plastics, rubbers, adhesives), must satisfy the mechanical and electrical requirements of the system while being compatible with the chemical composition of the ink. This paper describes the selection and evaluation of these materials for a particular ink and printer design.
Text compaction for display on very small screens (2001)

Very small screens, such as the LCD displays on cellular telephones, pose unique problems for the display of textual messages. This paper presents a collection of techniques used to compact email text for display on mobile devices. These techniques range from simple string manipulations to more sophisticated linguistic processing. The techniques have been implemented in a commercial product for four languages: English, French, German and Spanish.
ChemInform Abstract: MODIFICATION OF 2‐BROMOETHOXYCARBONYL PROTECTIVE GROUPS TO 2‐PHOSPHONIOETHOXYCARBONYL PROTECTIVE FUNCTIONS OF AMINO ACIDS (1976)

Abstract Durch Umsetzung der N‐geschützten Aminosäuren (III), die aus entsprechenden Komponenten (I) und (II) erhältlich sind, mit den Phosphinen (IV) werden die Phosphonioäthoxycarbonylderivate (V) gebildet.
Assessment of Immunity Status in Patients with Pancreatic Cancer (2006)

Wound infection and abscess are the common post operative complications in pancreatic cancer patients. The aim of this study was to evaluate the status of immunity in patients with cancer in the head of pancreas by analyzing the levels of immunoglobulins, compliments, acute phase reactants and the efficiency of neutrophils for phagocytosis. The study was conducted on 89 patients with cancer in the pancreatic acini/pancreatic duct/head of pancreas/periampullary region and on equal number of age and sex matched normal healthy volunteers. All the patients were in a need to undergo either pancreaticoduodenectomy or duodenal preserving resection of head of the pancreas. The levels of IgM, IgA, IgE, C3, C4, C-reactive proteins, haptaglobin, α2 macroglobulin were assayed in the blood samples. The level of phagocytosis and bactericidal activity were evaluated in neutrophils. The level of IgM was significantly low and the levels of IgA and IgE were significantly high in pancreatic cancer patients. The levels of C-reactive protein, haptaglobin, α2 macroglobulin , C3 and C4 were elevated significantly. The phagocytic efficiency and the bactericidal action of polymorphonuclear lymphocytes and mononuclear cells were low in pancreatic cancer patients when compared to normal control subjects. In pancreatic cancer patients the antibody mediated immunity is disturbed and the acute phase response is stimulated to counteract the infection and the abnormal metabolites released from malignant cells. The functional impairment of phagocytes might be responsible for the post operative complications in pancreatic cancer patients.