gebhart/patrepeval huggingface dataset:
Metabolic carbonyl reduction of anthracyclines — role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents (2017)

Anthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to secondary alcohol metabolites (i.e. doxorubicinol, daunorubicinol) catalyzed by carbonyl reductases (CBR) and aldo-keto reductases (AKR). These metabolites are suspected to be more cardiotoxic than their parent compounds. Moreover, overexpression of ANT-reducing enzymes (CBR and AKR) are found in many ANT-resistant cancers. The secondary metabolites show decreased cytotoxic properties and are more susceptible to ABC-mediated efflux than their parent compounds; thus, metabolite formation is considered one of the mechanisms of cancer resistance. Inhibitors of CBR and AKR were found to reduce the cardiotoxicity of ANT and the resistance of cancer cells, and therefore are being investigated as prospective cardioprotective and chemosensitizing drug candidates. In this review, the significance of a two-electron reduction of ANT, including daunorubicin, epirubicin, idarubicin, valrubicin, amrubicin, aclarubicin, and especially doxorubicin, is described with respect to toxicity and efficacy of therapy. Additionally, CBR and AKR inhibitors, including monoHER, curcumin, (-)-epigallocatechin gallate, resveratrol, berberine or pixantrone, and their modulating effect on the activity of ANT is characterized and discussed as potential mechanism of action for novel therapeutics in cancer treatment.
Surgical Injury and Metabolic Stress Enhance the Virulence of the Human Opportunistic Pathogen Pseudomonas aeruginosa (2005)

The intestinal environment of a stressed host contains soluble factors capable of inducing lethal virulence traits in human opportunistic pathogen P. aeruginosa.
Potential and utilization of thermophiles and thermostable enzymes in biorefining (2007)

In today's world, there is an increasing trend towards the use of renewable, cheap and readily available biomass in the production of a wide variety of fine and bulk chemicals in different biorefineries. Biorefineries utilize the activities of microbial cells and their enzymes to convert biomass into target products. Many of these processes require enzymes which are operationally stable at high temperature thus allowing e.g. easy mixing, better substrate solubility, high mass transfer rate, and lowered risk of contamination. Thermophiles have often been proposed as sources of industrially relevant thermostable enzymes. Here we discuss existing and potential applications of thermophiles and thermostable enzymes with focus on conversion of carbohydrate containing raw materials. Their importance in biorefineries is explained using examples of lignocellulose and starch conversions to desired products. Strategies that enhance thermostablity of enzymes both in vivo and in vitro are also assessed. Moreover, this review deals with efforts made on developing vectors for expressing recombinant enzymes in thermophilic hosts.
Cambian los hábitos de vida en las enfermeras que se incorporan por primera vez al trabajo en la Comunidad de Madrid (2005)

En los profesionales de enfermería que comienzan a trabajar por primera vez se dan dos circunstancias que provocan estrés: entorno laboral desconocido y la percepción de incapacidad para afrontar la práctica clínica. Todo ello puede influir en la modificación de sus hábitos de vida, por lo que planteamos una exploración de dicho problema en relación con el consumo de tabaco y el sueño. Objetivo: Determinar los cambios de hábitos de vida con respecto a las variables tabaco y sueño en aquellas enfermeras que se incorporan por primera vez al trabajo. Metodología: Estudio observacional analítico de una cohorte de estudiantes de 3er curso de enfermería que terminan su carrera universitaria en Junio de 2006 y ejercen como enfermeras en la Comunidad de Madrid durante al menos dos meses en el período de tiempo comprendido entre el 1 de julio de 2006 y el 30 de septiembre de 2006. Variables: Sociodemográficas, ámbito laboral, tiempo trabajado, turnicidad y carga laboral, consumo de tabaco y hábitos de sueño. Recogida de datos: Cuestionarios administrados a los alumnos seleccionados de 3er curso de las Escuelas Universitarias de Enfermería elegidas y los mismos sujetos tras su incorporación al mercado laboral. Análisis de los datos: Descripción de las características de la muestra y comparación de medias en relación con el consumo de tabaco y las horas de sueño antes y después de la incorporación al mercado laboral. Abstract: Nursing professionals who start working after graduation have to face two stressing issues: An unknown working environment and a feeling of incapacity to deal with the clinical duties. These issues can modify life habits in this population. Objective: To determine the changes in smoking and sleep habits in nurses who start working after graduation. Methodology: Prospective study of a cohort of nursing students who get graduated on June 2006 and work at least 2 months in the Comunidad de Madrid between July 1st and September 30th 2006. Variables: Sociodemographics, work environment, period of work, usual shift and work load, consumption of cigarrettes and sleep habits. Elegible students will be interviewed prior and after working start. Descriptive statistics of the sample characteristics and a mean comparison regarding cigarrettes consume and sleeping time prior and after working start will be performed Centro de Trabajo: Servicio de Neonatología. Hosp. Gen. Univ. Gregorio Marañón Fecha del Trabajo: 15/06/2005 Palabra Clave: Tabaco, sueño, estrés, trabajo, hábitos de vida y enfermería Key Words: Smoking, sleep habits, stress, work, life habits, nursing
Role of endogenous ATP at the incision area in a rat model of postoperative pain (2001)

The aim of the present study is to characterize the role of endogenous ATP leaked from damaged cells in a rat model of postoperative pain using behavioural and immunocytochemical approaches. We found that systemic (i.v.) and local (incision area) administration of a P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) before surgery significantly attenuated mechanical allodynia caused by an incision of the plantar surface of the hindpaw. Furthermore, PPADS significantly reduced the incision-evoked c-Fos protein expression, a marker of neuronal activity, in the dorsal horn of the spinal cord. The present findings suggest that excitatory signaling by endogenous ATP leaked from damaged cells via PPADS-sensitive P2 receptors is necessary for the induction of the postoperative pain characterized by mechanical allodynia.
Development of Guidelines for the Management of Severe Head Injury (1995)

Organized neurosurgery has taken a major step forward in developing guidelines for the management of severe head injury. This represents the first area in which neurosurgeons have tackled this difficult but important undertaking. The head injury guidelines, which are to be published soon, are evidenced-based, i.e., they are based upon published data rather than on expert opinion. The quality of data has been carefully analyzed and graded. The level of the recommendations, i.e., standard, guideline, or option, is based upon the strength of the data available. An attempt is made to provide a summary of the terminology and methodology used to develop guidelines. Arguments for and against practice guidelines are also summarized.
Multiple hypothesis tracking for multiple target tracking (2004)

Multiple hypothesis tracking (MHT) is generally accepted as the preferred method for solving the data association problem in modern multiple target tracking (MTT) systems. This paper summarizes the motivations for MHT, the basic principles behind MHT and the alternative implementations in common use. It discusses the manner in which the multiple data association hypotheses formed by MHT can be combined with multiple filter models, such as used by the interacting multiple model (IMM) method. An overview of the studies that show the advantages of MHT over the conventional single hypothesis approach is given. Important current applications and areas of future research and development for MHT are discussed.
Fc receptors and immunoglobulin binding factors 1 (1991)

Receptors for the Fc portion of Ig (Fc receptors, FcR) are found on all cell types of the immune system. Three types of FcR react with IgG: Fc gamma RI is a high-affinity receptor binding IgG monomers whereas Fc gamma RII and Fc gamma RIII are low-affinity receptors binding IgG immune complexes; the three types of Fc gamma R are members of the Ig superfamily. Two FcR react with IgE:Fc epsilon RI is a multichain receptor binding IgE with high affinity; it is composed of an IgE-binding alpha chain, homologous to Fc gamma RIII, and of gamma and beta chains that are necessary for receptor expression and signal transduction. The low-affinity Fc epsilon RII is the only FcR described so far that is not a member of the Ig superfamily but resembles animal lectins; it is composed of a transmembrane chain with an intracytoplasmic NH2 terminus. Fc alpha R has homology with Fc gamma R and is a member of the Ig superfamily. Receptors for IgM and IgD are not characterized yet. Finally, Ig transport is made by FcR-like molecules such as the poly-Ig receptor or an MHC-like receptor found on neonatal intestine. A remarkable property of most FcR is the fact that they are released in cell supernatants and circulate in biological fluids as immunoglobulin binding factors (IBF) generated either by cleavage at the cell membrane or by splicing of FcR transmembrane exon. Immunoglobulin binding factors may interfere with Ig-mediated functions and have direct immunoregulatory activities. Involvement of FcR or IBF has been postulated in several diseases, and monoclonal antibodies to FcR are beginning to be used in therapeutics, particularly to target cytotoxic effector lymphocytes and monocytes to tumor cells.
Localization of an origin of replication in Corynebacterium diphtheriae broad host range plasmid pNG2 that also functions in Escherichia coli (1990)

Subcloning and protoplast transformation studies identified a 2.6 kb fragment of Corynebacterium diphtheriae plasmid pNG2 which contains an origin of replication (oriR). Molecular combination of the 2.6 kb oriR cartridge with Escherichia coli plasmid pUC18CmR enabled the E. coli cloning vector to replicate within several species of Corynebacterium host cells. A 2.6 kb plasmid formed from the oriR cartridge alone is capable of replicating in E. coli. This suggests that a single origin could be used in vectors shuttling between Corynebacterium spp. and E. coli.
The prognostic significance of multiple morphologic features and biologic markers in ductal carcinoma in situ of the breast (2004)

The current results confirmed the value of conventional histopathologic parameters, as outlined in the Van Nuys classification system, in predicting local recurrence of DCIS. Using traditional logistic analyses, no significant correlation was found between a variety of biologic markers and disease recurrence.
Electric-field-induced phase changes in poly(vinylidene fluoride) (1978)

The antipolar crystal form of poly(vinylidene fluoride) can be made piezoelectric and pyroelecric by the temporary application of electric fields in excess of 1 MV/cm at room temperature. Infrared and x-ray diffraction data reveal that the polarization occurs in two stages. At fields near 1 MV/cm, a phase transition to a polar form II occurs with presumably no change in chain conformation. Fields near 5 MV/cm cause a change in conformation to produce form I. Our results indicate that at least a portion of the residual polarization occurs within the crystal phase of the polymer.
Innate immunity in the liver (2003)

Assuming that defects in the hepatic innate immune system that promote Th-1 cytokine polarization are common pathogenic mechanisms for hepatic insulin resistance and nonalcoholic steatohepatitis, therapies that inhibit inflammatory activity may be beneficial for these disorders.
Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. (1985)

We describe the development of a simple and highly sensitive double antibody sandwich enzyme-linked immunosorbent assay (ELISA) for measuring IgG and IgM anticardiolipin antibodies (ACA). Microtitre plates were coated with cardiolipin at a concentration of 45 micrograms/ml by evaporation under nitrogen. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (PBS/FCS) for 2 h. Then sera (100 microliters) at a dilution of 1:100 were incubated in the wells for 1 h. Affinity purified goat anti-human IgG or IgM (100 microliters) at a concentration of 1 microgram/ml was subsequently added and allowed to incubate for 1 h; detection of ACA was achieved using an alkaline phosphatase conjugated rabbit anti-goat IgG reagent by reading the colorimetric yield at 405 nm after incubation with substrate. Reference serum pools were established to study reproducibility of the assay throughout its sensitivity range, and Standard curves were established. The quantitative normal range was 0-9.0 Anticardiolipin ELISA Units (AEU) for IgG and 0-8.0 (AEU) for IgM-ACA. A strong correlation was found between the ELISA and radioimmunoassay methods for measuring ACA of both IgG and IgM classes. Results from 65 patients with systemic lupus erythematosus (SLE) and 45 patients with seropositive rheumatoid arthritis are also reported. The advantages of the ELISA method for quantitative determination of ACA levels, should make it a useful and reliable method for clinical and experimental monitoring of patients with SLE and associated autoimmune disorders.
Atomic-Resolution Measurement of Oxygen Concentration in Oxide Materials (2004)

Using high-resolution imaging at negative spherical aberration of the objective lens in an aberration-corrected transmission electron microscope, we measure the concentration of oxygen in Sigma3[111] twin boundaries in BaTiO3 thin films at atomic resolution. On average, 68% of the boundary oxygen sites are occupied, and the others are left vacant. The modified Ti2O9 group unit thus formed reduces the grain boundary energy and provides a way of accommodating oxygen vacancies occurring in oxygen-deficient material by the formation of a nanotwin lamellae structure. The atomically resolved measurement technique offers the potential for studies on oxide materials in which the electronic properties sensitively depend on the local oxygen content.
Genome structure of a Saccharomyces cerevisiae strain widely used in bioethanol production (2009)

Bioethanol is a biofuel produced mainly from the fermentation of carbohydrates derived from agricultural feedstocks by the yeast Saccharomyces cerevisiae. One of the most widely adopted strains is PE-2, a heterothallic diploid naturally adapted to the sugar cane fermentation process used in Brazil. Here we report the molecular genetic analysis of a PE-2 derived diploid (JAY270), and the complete genome sequence of a haploid derivative (JAY291). The JAY270 genome is highly heterozygous (approximately 2 SNPs/kb) and has several structural polymorphisms between homologous chromosomes. These chromosomal rearrangements are confined to the peripheral regions of the chromosomes, with breakpoints within repetitive DNA sequences. Despite its complex karyotype, this diploid, when sporulated, had a high frequency of viable spores. Hybrid diploids formed by outcrossing with the laboratory strain S288c also displayed good spore viability. Thus, the rearrangements that exist near the ends of chromosomes do not impair meiosis, as they do not span regions that contain essential genes. This observation is consistent with a model in which the peripheral regions of chromosomes represent plastic domains of the genome that are free to recombine ectopically and experiment with alternative structures. We also explored features of the JAY270 and JAY291 genomes that help explain their high adaptation to industrial environments, exhibiting desirable phenotypes such as high ethanol and cell mass production and high temperature and oxidative stress tolerance. The genomic manipulation of such strains could enable the creation of a new generation of industrial organisms, ideally suited for use as delivery vehicles for future bioenergy technologies.
Growth factor activation of an amiloride-sensitive Na+/H+ exchange system in quiescent fibroblasts: coupling to ribosomal protein S6 phosphorylation. (1982)

Chinese hamster lung fibroblast cells (CCl39) enter the G0/G1 nonproliferative state after serum deprivation. In this report, we show that reinitiation of DNA synthesis by serum or the combination of purified human thrombin and insulin (1-10 microgram/ml) is preceded by very early stimulation of ionic fluxes (Na+/Rb+) and protein phosphorylation (27,000 daltons, 62,000 daltons, and the ribosomal S6 proteins). The potentiating action of insulin on thrombin-stimulated DNA synthesis is also observed on thrombin-stimulated Na+ influx, Rb+ influx, and protein S6 phosphorylation. Moreover, we demonstrate that CCl39 cells possess a Na+/H+ exchange system sensitive to amiloride. Half-maximal inhibition of growth factor-activated Na+ influx and Na+-dependent H+ efflux is obtained with 3-10 microM amiloride. Two lines of evidence indicate that the extrusion of H+ via the activation of the Na+/H+ exchanger is coupled to protein S6 phosphorylation: serum-stimulated phosphorylation is blocked by (i) amiloride at a concentration that abolishes serum-stimulated Na+ influx and (ii) protonophores that acidify the cell interior. The present data support the idea that the regulation of intracellular pH is a key event in the mechanism of growth factor action.
The Relative Activities of the C2GnT1 and ST3Gal-I Glycosyltransferases Determine O-Glycan Structure and Expression of a Tumor-associated Epitope on MUC1 (2001)

In breast cancer, the O-glycans added to the MUC1 mucin are core 1- rather than core 2-based. We have analyzed whether competition by the glycosyltransferase, ST3Gal-I, which transfers sialic acid to galactose in the core 1 substrate, is key to this switch in MUC1 glycosylation that results in the expression of the cancer-associated SM3 epitope. Of the three enzymes known to convert core 1 to core 2, by the addition of GlcNAc to GalNAc in core1 C2GnT1 is the dominant enzyme expressed in normal breast tissue. Expression of C2GnT1 is low or absent in around 50% of breast cancers, whereas expression of ST3Gal-I is consistently increased. Mapping of ST3Gal-I and C2GnT1 within the Golgi pathway showed some overlap. To examine functional competition, the enzymes were overexpressed in T47D cells, which normally make core 1-based structures, have no detectable C2GnT1 activity and express the SM3 epitope. Overexpression of C2GnT1 resulted in loss of binding of SM3 to MUC1, accompanied by a decrease in the GalNAc/GlcNAc ratio, indicative of a switch to core 2 structures. Transfection of a C2GnT1 expressing line with ST3Gal-I restored SM3 binding and reduced GlcNAc incorporation into MUC1 O-glycans. Thus, even when C2GnT1 is expressed, the O-glycans added to MUC1 become core 1-dominated structures, provided expression of ST3Gal-I is increased as it is in breast cancer.
Phosphatidylinositol 3-Kinase Function Is Required for Transforming Growth Factor β-mediated Epithelial to Mesenchymal Transition and Cell Migration (2000)

We have studied the role of phosphatidylinositol 3-OH kinase (PI3K)-Akt signaling in transforming growth factor beta (TGFbeta)-mediated epithelial to mesenchymal transition (EMT). In NMuMG mammary epithelial cells, exogenous TGFbeta1 induced phosphorylation of Akt at Ser-473 and Akt in vitro kinase activity against GSK-3beta within 30 min. These responses were temporally correlated with delocalization of E-cadherin, ZO-1, and integrin beta(1) from cell junctions and the acquisition of spindle cell morphology. LY294002, an inhibitor of the p110 catalytic subunit of PI3K, and a dominant-negative mutant of Akt blocked the delocalization of ZO-1 induced by TGFbeta1, whereas transfection of constitutively active p110 induced loss of ZO-1 from tight junctions. In addition, LY294002 blocked TGFbeta-mediated C-terminal phosphorylation of Smad2. Consistent with these data, TGFbeta-induced p3TP-Lux and p(CAGA)(12)-Lux reporter activities were inhibited by LY294002 and transiently expressed dominant-negative p85 and Akt mutants in NMuMG and 4T1 cells. Dominant-negative RhoA inhibited TGFbeta-induced phosphorylation of Akt at Ser-473, whereas constitutively active RhoA increased the basal phosphorylation of Akt, suggesting that RhoA in involved in TGFbeta-induced EMT. Finally, LY294002 and neutralizing TGFbeta1 antibodies inhibited ligand-independent constitutively active Akt as well as basal and TGFbeta-stimulated migration in 4T1 and EMT6 breast tumor cells. Taken together, these data suggest that PI3K-Akt signaling is required for TGFbeta-induced transcriptional responses, EMT, and cell migration.
Design and synthesis of a protein .beta.-turn mimetic (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign and synthesis of a protein .beta.-turn mimeticGary L. Olson, Matthew E. Voss, David E. Hill, Michael Kahn, Vincent S. Madison, and Charles M. CookCite this: J. Am. Chem. Soc. 1990, 112, 1, 323–333Publication Date (Print):January 1, 1990Publication History Published online1 May 2002Published inissue 1 January 1990https://pubs.acs.org/doi/10.1021/ja00157a050https://doi.org/10.1021/ja00157a050research-articleACS PublicationsRequest reuse permissionsArticle Views633Altmetric-Citations85LEARN 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 Get e-Alerts