gebhart/patrepeval huggingface dataset:
Gliovirin, a new antibiotic from Gliocladium virens, and its role in the biological control of Pythium ultimum (1983)

A compound with antibiotic activity toward Pythium ultimum was isolated from potato dextrose broth shake cultures of Gliocladium virens, a common soil mycoparasite known to inhibit but not parasitize P. ultimum. The mass spectrum and an X-ray crystallograph of the purified antibiotic indicated that it was a new diketopiperazine, and we have given it the trivial name gliovirin. Gliovirin is highly toxic to P. ultimum but is inactive against other fungi associated with cotton seedling disease. The antibiotic does not persist in nonsterile soil where it is apparently inactivated by the soil microflora.An ultraviolet light induced mutant of G. virens deficient for gliovirin production was overgrown by P. ultimum in culture and did not protect cotton seedlings from damping-off in P. ultimum infested soil. A mutant with enhanced gliovirin production was more inhibitory to P. ultimum in culture than the parent isolate and showed similar efficacy as a seedling disease suppressant, even though its growth rate was reduced when compared to the parent isolate. These results indicate that gliovirin may be important to the antagonist–pathogen interaction.
Cimetidine suspension as adjuvant to energy restricted diet in treating obesity. (1993)

Cimetidine had no effect on weight loss in moderately obese patients. The study underlines the potential problem that blinding of patients to treatment can be compromised.
Trichloroethylene in organic synthesis (1994)

The literature data on the chemistry of trichloroethylene are surveyed. Reactions involving the addition of inorganic and organic reagents to trichloroethylene are examined and cycloaddition reactions with participation of trichloroethylene are classified. A systematic account is given of the reactions of trichloroethylene with various nucleophiles occurring with the substitution of 1-3 chlorine atoms by nucleophilic residues. The elimination and oxidation reactions of trichloroethylene as well as aspects of the practical application of its derivatives are considered. The analysis demonstrated the extensive possibilities for the synthesis of polyfunctional organic compounds of various classes from trichloroethylene. The bibliography includes 310 references.
Infrared, Raman and resonance Raman investigations of methylviologen and its radical cation (1982)

Abstract The infrared and Raman spectra of methylviologen (1,1′‐dimethyl‐4,4′‐bipyridine dication, MV 2+ ) have been measured from both the solid dichloride and aqueous solutions. The preresonance behaviour of MV 2+ Raman bands showed that the absorption at ˜196 nm is mainly responsible for the resonance scattering process in MV 2+ . In the region below 1700 cm −1 , nine polarized ( p ˜1/3) resonance Raman bands of the methylviologen radical cation, MV + , were assigned to in‐plane ring modes. Arguments are given that the chromophore of MV + may also partially include the methyl groups. The excitation profiles of the MV + fundamentals, measured with laser wavelengths covering the range 350.6–676.4 nm, reveal three main groups of modes, each behaving differently for the excitation in this range. Modes containing largely ν(CC) ring contributions are mainly coupled with electronic transitions at ˜395, ˜605 and ˜720 nm and yield simple excitation profiles. Modes involving principally the vibrations of the N + CH 3 group show complicated interference peaks in the whole range of the excitation profiles. γ(CCC) is mainly coupled with the absorption at ˜620 nm. Resonance Raman bands of the (MV + ) 2 dimer have been characterized through studies of the concentration dependence of the spectra.
Transport of metal oxide nanoparticles and single-walled carbon nanotubes in human mucus (2011)

Whether mucus layers lining entrance points into the body, including the lung airways, provide protection against the penetration of engineered nanoparticles remains poorly understood. We measured the diffusion coefficients of hundreds of individual nanoparticles of three different metal oxides (nMeOs) and two types of single-walled carbon nanotubes (SWCNTs) in undiluted human mucus. We found that the vast majority of these nanoparticles are efficiently trapped in human mucus and, further, that the mechanism of trapping is adhesive interactions as opposed to steric obstruction. However, a small fraction of zinc oxide (ZnO) nanoparticles moved at rates fast enough to penetrate airway mucus layers. We conclude that human mucus layers probably provide considerable protection for mucosal tissues from the penetration of most nMeOs and SWCNTs, and suggest that further investigation of the potential health risks of exposure to ZnO nanoparticles is warranted.
TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells (2010)

Interaction of myeloma cells with the bone marrow microenvironment is mediated in large part through different cytokines, especially VEGF and IL6. These cytokines, especially IL6, leads to upregulation of the JAK/STAT pathway in myeloma cell, contributing to increased proliferation, decreased apoptosis, and acquired drug resistance. Here, we examined the preclinical activity of a novel JAK2 inhibitor TG101209. TG101209 induced dose- and time-dependent cytotoxicity in a variety of multiple myeloma (MM) cell lines. The induction of cytotoxicity was associated with inhibition of cell cycle progression and induction of apoptosis in myeloma cell lines and patient-derived plasma cells. Evaluation of U266 cell lines and patient cells, which have a mix of CD45 positive and negative cells, demonstrated more profound cytotoxicity and antiproliferative activity of the drug on the CD45+ population relative to the CD45- cells. Exploring the mechanism of action of TG101209 indicated downregulation of pJak2, pStat3, and Bcl-xl levels with upregulation of pErk and pAkt levels indicating cross talk between signaling pathways. TG101209, when used in combination with the PI3K inhibitor LY294002, demonstrated synergistic cytotoxicity against myeloma cells. Our results provide the rationale for clinical evaluation of TG101209 alone or in combination with PI3K/Akt inhibitors in MM.
CF102 an A3 adenosine receptor agonist induces in vivo apoptosis of Hepatocellular carcinoma (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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The A3 adenosine receptor (A3AR) is highly expressed in solid tumors and has been suggested as a potent target for cancer treatment. In this study we first show that both human and rat Hepatocellular Carcinoma (HCC) cells highly express the A3AR and that CF102, a highly selective agonist to the receptor induces apoptosis of HCC in vivo . Increased A3AR expression levels were detected in tumor tissues and in peripheral blood mononuclear cells (PBMCs) derived from patients with HCC. Similar data was observed in N1S1 HCC tumor bearing rats, demonstrating that A3AR expression levels in the PBMCs reflect receptor status in the remote tumor. The high expression level of the receptor was directly correlated to over expression of NF-κB, known to act as a transcription factor of A3AR. To explore whether A3AR may be utilized as a specific target to combat HCC, CF102 was administered orally thrice daily to N1S1 tumor bearing rats. CF102 induced marked dose response inhibition of tumor growth via de-regulation of the NF-κB and the Wnt signal transduction pathways, resulting in apoptosis of tumor cells.Taken together, A3AR is highly expressed in tumors and PBMCs of HCC patients and tumor bearing rats. CF102 targets the A3AR, to induce apoptosis and tumor growth inhibition. The NF-κB signal transduction pathway is involved in receptor expression and functionality. These data suggest A3AR as a novel biomarker target therapy to be developed for the treatment of HCC.
Herpes vector–mediated expression of proenkephalin reduces bone cancer pain (2002)

We examined whether a herpes simplex virus vector that expresses human proenkephalin could be used to attenuate nociception in a model of bone cancer pain in mice. Osteolytic sarcoma cells were implanted into the medullary space of the right femur, followed by a subcutaneous inoculation of a replication-defective herpes simplex virus vector expressing human proenkephalin (vector SHPE) or a lacZ-expressing control vector (vector SHZ). SHPE-inoculated mice demonstrated a significant, naltrexone-reversible decrease in pain-related behavior assessed during open-field motor activity. These results suggest that gene transfer with an enkephalin-expressing vector may be used to treat pain resulting from cancer in bone.
DNA Inoculation Induces Neutralizing Immune Responses Against Human Immunodeficiency Virus Type 1 in Mice and Nonhuman Primates (1993)

DNA, or genetic, inoculation mimics aspects of attenuated vaccines in that synthesis of specific foreign proteins is accomplished in the host. These proteins can be processed and presented on the relevant major histocompatibility complex (MHC) antigens and ultimately become the subject of immune surveillance. Very recently, we have described the use of the new technology to generate immune responses in mice against the human immunodeficiency virus type 1 (HIV-1) envelope using a gp160 DNA construct. Further analysis of this technology specifically in regard to HIV vaccine design is clearly important. In this report, we describe the analysis of additional HIV constructs as immunogens in both mice and report the use of this genetic immunization technology in nonhuman primates. In these studies, successful seroconversion occurs in more than 70% of the mice following the second immunization with 100 micrograms of construct DNA; three and four immunizations result in routinely 100% seroconversion of the mice. Furthermore, the same strategy has successfully seroconverted primates following their second inoculation, resulting in the generation of both antiviral and neutralizing antibodies in this animal species. These studies are the first report of which we are aware that demonstrate successful immunization of nonhuman primates through genetic vaccination technology and the first to describe genetic immunization of primates against HIV antigens. This technology has relevance for the development of safe and efficacious immunization strategies against HIV because it provides for relevant antigen production in vivo without the use of infectious agents.
Identification of Novel Human Genes Evolutionarily Conserved inCaenorhabditis elegansby Comparative Proteomics (2000)

Modern biomedical research greatly benefits from large-scale genome-sequencing projects ranging from studies of viruses, bacteria, and yeast to multicellular organisms, like Caenorhabditis elegans. Comparative genomic studies offer a vast array of prospects for identification and functional annotation of human ortholog genes. We presented a novel comparative proteomic approach for assembling human gene contigs and assisting gene discovery. The C. elegans proteome was used as an alignment template to assist in novel human gene identification from human EST nucleotide databases. Among the available 18,452 C. elegans protein sequences, our results indicate that at least 83% (15,344 sequences) of C. elegans proteome has human homologous genes, with 7,954 records of C. elegans proteins matching known human gene transcripts. Only 11% or less of C. elegans proteome contains nematode-specific genes. We found that the remaining 7,390 sequences might lead to discoveries of novel human genes, and over 150 putative full-length human gene transcripts were assembled upon further database analyses. [The sequence data described in this paper have been submitted to the
Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin, stem cell factor, and interleukin-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro (1995)

Thrombopoietin (Tpo), the ligand for the c-mpl receptor, is a major regulator of platelet production in vivo. Treatment of mice with purified recombinant Tpo increases platelet count fourfold and expands colony-forming unit-megakaryocyte (CFU-Meg) numbers. Other cytokines including interleukin-3 (IL-3), IL-6, IL-11, erythropoietin (Epo), and stem cell factor (SCF) can stimulate megakaryopoiesis. Therefore, we examined the effects of recombinant murine Tpo in combination with these cytokines on megakaryopoiesis in vitro. Murine marrow cells were cultured in agar in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% horse serum and beta-mercaptoethanol in the presence of recombinant growth factors, and CFU-Meg colonies were counted on day 5. Megakaryocyte ploidy was analyzed using murine marrow cells cultured for 5 days in IMDM supplemented with 1% nutridoma-SP and recombinant growth factors. Megakaryocytes were identified by labeling with the 4A5 antibody and ploidy was analyzed by flow cytometry. Tpo supported the growth of CFU-Meg in a dose-dependent manner. Although the addition of SCF (50 ng/mL), Epo (2 U/mL), or IL-11 (50 ng/mL) alone exerted only a modest effect on CFU-Meg growth, the combination of SCF plus Tpo, Epo plus Tpo, or IL-11 plus Tpo resulted in a synergistic enhancement of the number of CFU-Meg colonies. IL-3 alone supported CFU-Meg colony growth, and the effects of IL-3 plus Tpo or IL-6 plus Tpo on colony growth appeared to be approximately additive. Fifty percent of megakaryocytes generated in cultures containing IL-3 or Epo displayed < or = 16 N ploidy. In contrast, cultures containing Tpo uniquely generated large numbers (30% to 35% of the total) of megakaryocytes with > or = 64N ploidy. These results show that Tpo stimulates both proliferation of committed megakaryocytic progenitor cells and maturation of megakaryocytes, and that two multipotent cytokines, SCF and IL-11, as well as a late-acting erythroid cytokine, Epo, can synergize with Tpo to stimulate proliferation of CFU-Meg.
1.5-/spl mu/m AlGaInAs quantum well lasers grown by the digital alloy technique (2000)

Summary form only given.1.5-/spl mu/m lasers are of particular interest since this wavelength enjoys the dual role of being optimum for fiber optics and the lowest that is considered eye-safe. Our investigations are focussed on digital alloy (DA) MBE grown lattice matched and strained AlGaInAs multiquantum well lasers. The DA method reduces many growth complexities associated with quaternary materials. The AlGaInAs alloys produce a better conduction band offset than InGaAsP on InP.
Characterization of a Fungal Maleylacetoacetate Isomerase Gene and Identification of Its Human Homologue (1998)

We have previously used Aspergillus nidulans as a fungal model for human phenylalanine catabolism. This model was crucial for our characterization of the human gene involved in alcaptonuria. We use here an identical approach to characterize at the cDNA level the human gene for maleylacetoacetate isomerase (MAAI, EC 5.2.1.2), the only as yet unidentified structural gene of the phenylalanine catabolic pathway. We report here the first characterization of a gene encoding a MAAI enzyme from any organism, the A. nidulans maiA gene. maiA disruption prevents growth on phenylalanine (Phe) and phenylacetate and results in the absence of MAAI activity in vitro and Phe toxicity. The MaiA protein shows strong amino acid sequence identity to glutathione S-transferases and has MAAI activity when expressed in Escherichia coli. maiA is clustered with fahA and hmgA, the genes encoding the two other enzymes of the common part of the Phe/phenylacetate pathways. Based on the high amino acid sequence conservation existing between other homologous A. nidulans and human enzymes of this pathway, we used the MaiA sequence in data base searches to identify human expressed sequence tags encoding its putative homologues. Four such cDNAs were sequenced and shown to be encoded by the same gene. They encode a protein with 45% sequence identity to MaiA, which showed MAAI activity when expressed in E. coli. Human MAAI deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone, the diagnostic compound resulting from fumarylacetoacetate hydrolase deficiency in humans and fungi. Culture supernatants of an A. nidulans strain disrupted for maiA are succinylacetone-negative but specifically contain cis and/or trans isomers of 2, 4-dioxohept-2-enoic acid. We suggest that this compound(s) might be diagnostic for human MAAI deficiency.
Characteristics and Stability Analyses of Transient One-Dimensional Two-Phase Flow Equations and Their Finite Difference Approximations (1978)

Equation systems describing one-dimensional, transient, two-phase flow with separate continuity, momentum, and energy equations for each phase are classified by use of the method of characteristics. The main purpose of this paper is to study the mathematical nature of these equations, not their physics, although it is realized that these two problems are not entirely independent. Many of the equation systems possess complex-valued characteristics and hence, according to well-known mathematical theorems, are not well-posed as initial-value problems (IVPs). Real-valued characteristics are necessary but not sufficient to ensure well-posedness. In the absence of lower order source or sink terms, that can affect the well-posedness of IVPs, the complex characteristics associated with these two-phase flow equations imply unbounded exponential growth for disturbances of all wavelengths.Analytical and numerical examples show that the ill posedness of IVPs for the two-phase flow partial differential equations that possess complex characteristics produce unstable numerical schemes. These unstable numerical schemes can produce apparently stable and even accurate results if the growth rate resulting from the complex characteristics remains small throughout the time span of the numerical experiment or if sufficient numerical damping is present for the increment size used. Other examples show that clearly nonphysical numerical instabilities resulting from the complex characteristics can be produced. These latter types of numerical instabilities are shown to be removed by the addition of physically motivated differential terms that eliminate the complex characteristics. These terms should not destroy long-wavelength physical instabilities that arise and that may sometimes be calculated approximately using ill-posed equation systems.
Structure of a Molluscan Cardioexcitatory Neuropeptide (1977)

A cardioexcitatory substance from ganglia of the clam Macrocallista nimbosa, formerly designated peak C, is the tetrapeptide amide Phe-Met-Arg-Phe-NH2. Its structure was determined by the combined use of Edman dansyl degradation and tryptic digestion. The structure was confirmed by synthesis. This neuropeptide is active at about 10(-8)M when assayed on molluscan muscle.
The limitations of corticosteroid therapy in Crohn’s disease (2001)

Corticosteroids are highly effective in inducing clinical remission in patients with active Crohn's disease. However, the role of corticosteroids in the treatment of this disease is primarily ameliorative because they are ineffective in maintaining remission or healing mucosal lesions. Nearly half of the patients who initially respond to corticosteroid therapy develop a dependency on corticosteroids or have a relapse within 1 year. In addition, use of these agents is often limited by a relatively high risk of serious adverse effects that can involve nearly every major body system. These effects include: bone loss, which can develop with even short-term and low-dose corticosteroid therapy; metabolic complications such as glucose intolerance and diabetes mellitus; increased intraocular pressure and glaucoma; and potentially lethal infections. To minimize the risk of toxicity, corticosteroids are increasingly recommended for short-term use only at the lowest effective dose to induce remission in patients with moderately to severely active Crohn's disease. Corticosteroid formulations with low systemic bioavailability, such as controlled-release budesonide, may be associated with a lower rate of dermatologic adverse effects but appear to be somewhat less effective than conventional corticosteroids in inducing remission in patients with active Crohn's disease. Immunosuppressive agents such as azathioprine, 6-mercaptopurine, and methotrexate have demonstrated corticosteroid-sparing effects, facilitating the withdrawal of corticosteroids when initiated as maintenance therapy. Infliximab can be used as an alternative to corticosteroids.
Comparison Between Model Simulations and Field Results for In‐Situ Biorestoration of Chlorinated Aliphatics: Part 1. Biostimulation of Methanotrophic Bacteria (1991)

Abstract A nonsteady‐state model is presented for the in‐situ biostimulation of a microbial population in saturated porous media. The model includes basic processes of microbial growth, utilization of electron donor and acceptor, advective transport, dispersion, and sorption in porous media. Model simulations are compared with results from a series of controlled field experiments at the Moffett Naval Air Station, where the growth of an indigenous population of methane‐utilizing bacteria (methanotrophs) was stimulated by the controlled addition of dissolved methane and oxygen (DO) into a semiconfined aquifer. Simulations provide good matches to the observed transient uptake of methane and DO, demonstrating that the observed response resulted from the growth of methanotrophs in the test zone. Simulations duplicate results from alternate pulsed addition of methane (electron donor) and oxygen (electron acceptor), used as a means for distributing microbial growth throughout the test zone. The model permits estimation of changes in microbial population distribution at various stages of the two‐year experiment. Temporal changes in model‐fitted kinetic parameters indicate that the microbial population evolved to one that more effectively utilized the methane at lower concentrations. These analyses demonstrate that a relatively simple model, which includes basic microbial and transport processes, can be of use in the design and evaluation of in‐situ biotreatment processes. The model user, however, must provide judgment in the selection of appropriate input parameters, as well as being aware of model limitations.
Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease (2015)

The pattern recognition receptors of the innate immune system are part of the first line of defence against pathogens. However, they also have the ability to respond to danger signals that are frequently elevated during tissue damage and at sites of inflammation. Inadvertent activation of pattern recognition receptors has been proposed to contribute to the pathogenesis of many conditions including inflammatory rheumatic diseases. Prolonged inflammation most often results in pain and damage to tissues. In particular, the Toll-like receptors and nucleotide-binding oligomerisation domain-like receptors that form inflammasomes have been postulated as key contributors to the inflammation observed in rheumatoid arthritis, osteoarthritis, gout and systemic lupus erythematosus. As such, there is increasing interest in targeting these receptors for therapeutic treatment in the clinic. Here the role of pattern recognition receptors in the pathogenesis of these diseases is discussed, with an update on the development of interventions to modulate the activity of these potential therapeutic targets.
Dominant frequency differences in atrial fibrillation patients with and without left ventricular systolic dysfunction (2008)

Dominant frequency stability supports stable arrhythmia sources as the mechanism of PEAF with (without) LVSD, but not of PAAF.