gebhart/patrepeval huggingface dataset:
Abstract C199: Sorafenib targets BCR kinases and blocks migratory and microenvironmental survival signals in CLL cells. (2011)

Abstract Targeting deregulated kinases has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL). Here, we report that the multikinase inhibitor sorafenib selectively induces apoptosis in the majority of CLL cases, with preference for the IGVH unmutated cases and for lymph node-derived CLL cells. We also show that ERK inhibition by sorafenib in CLL cells is an early but not sustained event, thus downregulation of RAF/MEK/ERK pathway is not a crucial effect of this agent in CLL. Among all the different kinases modulated by sorafenib in CLL cells, the blockage of BCR-associated tyrosine kinases, SRC and SYK, is particularly relevant for its action. In line with this, we demonstrate a strong synergy when combining sorafenib with two pharmacological BCR inhibitors, R406 and dasatinib. Importantly, sorafenib overcomes BCR stimulation as well as the protective effect of the stromal coculture. This compound resensitizes CLL cells cultured with stroma to fludarabine- and bendamustine-induced apoptosis. Furthermore, sorafenib inhibits CLL migration toward CXCL12 and blocks both CXCL12- and BCR-induced FAK activation. All these results indicate that sorafenib could overcome the tumoral microenvironment and might be particularly effective in BCR signaling inhibition in CLL cells with higher migratory potential, especially in high risk patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C199.
Transducers For Heat Research (1985)

Series of transducers with seven different configurations enable measurement of forces and displacements in heart wall. New transducers small, cause minimal perturbation of heart function and attached and detached without causing excessive tissue damage. All units implanted or removed during single heartbeat, permitting rapid relocation for detail mapping.
Heterogeneous expression of the triggering receptor expressed on myeloid cells‐2 on adult murine microglia (2002)

Microglial activation is an early and common feature of almost all neuropathologies, including multiple sclerosis, Alzheimer's disease and mechanical injury. To better understand the relative contributions microglia make toward neurodegeneration and neuroprotection, we used TOGA(R) to identify molecules expressed by microglia and regulated by inflammatory signals. Triggering receptor expressed on myeloid cells-2 (TREM-2) was among the mRNAs identified as being expressed by unactivated microglia, but down-regulated by lipopolysaccharide/interferon gamma. In the healthy CNS, not all microglia expressed TREM-2. Microglial expression of TREM-2 varied not only between brain regions but also within each brain region. Brain regions with an incomplete blood-brain barrier had the lowest percentages of TREM-2- expressing microglia, whereas the lateral entorhinal and cingulate cortex had the highest percentages. A novel form of TREM-2b that lacked a transmembrane domain was detected, perhaps indicating a soluble form of the protein. Taken together, these data suggest that (1) subsets of microglia are specialized to respond to defined extracellular signals; and (2) regional variations in TREM-2 expression may contribute to the varying sensitivities of different brain regions to similar pathological signals.
A correlation for pressure drop in two‐phase cocurrent flow in packed beds (1967)

Abstract A correlations has been developed from considerations of single‐phase flow behavior to predict pressure drop across packed beds for two‐phase cocurrent flow. The correlation does no require one of the assumptions made in previous correlations, and thus it was not necessary to relate empirically any dimensionless groups through the use of experimental two‐phase flow data. The only empiricism involved in the use of this correlation is that required in correlating single‐phase pressure drops through packed beds, an art well developed in the literature. The correlation as developed here is at least as accurate as previous correlations in this area and may be more reliable when used for two‐phase systems not previously studied experimentally.
Presynaptic Inhibition of Norepinephrine Release From Sympathetic Nerve Endings by Endogenous Adenosine (1996)

ATP is coreleased with norepinephrine from sympathetic nerve endings and subsequently broken down to adenosine. In animal preparations, adenosine can inhibit norepinephrine release by stimulation of presynaptic receptors. We tested this feedback mechanism in humans by using a specific nucleoside transport inhibitor (draflazine) as a pharmacological tool to allow accumulation of endogenous adenosine in the synaptic cleft. In a dose-finding study on draflazine infusions into the brachial artery (n=10), we identified an optimal dose of 250 ng/min per deciliter of forearm tissue that induced considerable local nucleoside transport inhibition (approximately 40%) without systemic effects. In the main study, we investigated the effects of this draflazine dose on sympathetic-mediated norepinephrine spillover during lower body negative pressure (-25 mm Hg) by the use of the [3H]norepinephrine isotope dilution technique (n=25). Lower body negative pressure induced a significant increase in total body norepinephrine spillover, forearm norepinephrine appearance rate, forearm vascular resistance, and heart rate. During draflazine infusion into the brachial artery, the responses to lower body negative pressure were preserved for all parameters, with the exception of the median increase in forearm norepinephrine appearance rate, which was reduced from 54% to 2% (P <.05). We conclude that accumulation of endogenous adenosine in the synaptic cleft during sympathetic stimulation can inhibit norepinephrine release from sympathetic nerve endings.
Characterization of Six<i>Leuconostoc fallax</i>Bacteriophages Isolated from an Industrial Sauerkraut Fermentation (2002)

Six bacteriophages active against Leuconostoc fallax strains were isolated from industrial sauerkraut fermentation brines. These phages were characterized as to host range, morphology, structural proteins, and genome fingerprint. They were exclusively lytic against the species L. fallax and had different host ranges among the strains of this species tested. Morphologically, three of the phages were assigned to the family Siphoviridae, and the three others were assigned to the family Myovidae: Major capsid proteins detected by electrophoresis were distinct for each of the two morphotypes. Restriction fragment length polymorphism analysis and randomly amplified polymorphic DNA fingerprinting showed that all six phages were genetically distinct. These results revealed for the first time the existence of bacteriophages that are active against L. fallax and confirmed the presence and diversity of bacteriophages in a sauerkraut fermentation. Since a variety of L. fallax strains have been shown to be present in sauerkraut fermentation, bacteriophages active against L. fallax are likely to contribute to the microbial ecology of sauerkraut fermentation and could be responsible for some of the variability observed in this type of fermentation.
Capacitive coupled electrodeless discharge backlight driven by square pulses (2002)

Characteristic properties of backlight arraying electrodeless fluorescent lamps assembled with capacitive coupled electrode connector have been investigated in various frequencies with a switching inverter. In the backlight of a 17-in diagonal with 12 lamps driven by square pulses, the efficiency of 65/spl sim/70 lm/W and the luminance of 5000/spl sim/10 000 cd/m/sup 2/ have been achieved in the frequency range of 40/spl sim/80 kHz where the higher frequency provides the lower operating voltage in the range of 1.0/spl sim/2.0 kV.
Genotypic Diversity, Antimicrobial Resistance, and Virulence Factors of Human Isolates and Probiotic Cultures Constituting Two Intraspecific Groups of <i>Enterococcus faecium</i> Isolates (2008)

The intraspecific relationships among a collection of Enterococcus faecium isolates comprising probiotic cultures and human clinical isolates were investigated through the combined use of two high-resolution DNA-fingerprinting techniques. In addition, the incidences of antimicrobial resistance and virulence traits were investigated. A total of 128 E. faecium isolates from human clinical or nonclinical sources or used as probiotic cultures were subjected to fluorescent amplified fragment length polymorphism (FAFLP) fingerprinting and pulsed-field gel electrophoresis (PFGE) analysis of SmaI macrorestriction patterns. Susceptibilities to 16 antimicrobial agents were tested using broth microdilution, and the presence of the corresponding resistance genes was investigated using PCR. Multiplex PCR was used to detect the presence of the enterococcal virulence genes asa1, gelE, cylA, esp, and hyl. The results of the study showed that two intraspecific genomic groups (I and II) were obtained in FAFLP analysis. PFGE analysis demonstrated high variability within these two groups but also indicated that some probiotic cultures were indistinguishable and that a number of clinical isolates may be reisolations of commercial probiotic cultures. Compared to group II, which contained the majority of the probiotic isolates and fewer human clinical isolates, higher phenotypic and genotypic resistance frequencies were observed in group I. Two probiotic isolates were phenotypically resistant to erythromycin, one of which contained an erm(B) gene that was not transferable to enterococcal recipients. None of the probiotic E. faecium isolates demonstrated the presence of the tested virulence genes. The previously reported observation that E. faecium consists of two intraspecific genomic groups was further substantiated by FAFLP fingerprinting of 128 isolates. In combination with antimicrobial resistance and virulence testing, this grouping might represent an additional criterion in assessing the safety of new potential probiotic E. faecium isolates.
CD38 expression and NAD<sup>+</sup>‐induced intracellular Ca<sup>2+</sup> mobilization in isolated retinal Müller cells (2002)

Müller cells of the vertebrate retina are prominent radial glia that provide essential support to sustain homeostasis of the tissue, including redistribution of external potassium, uptake and metabolism of neurotransmitters, and secretion of factors that stabilize the retina. Meeting this diversity of functional supports requires that Müller cells express numerous receptors, transporters, enzymes, and tissue factors. In this study, we provide evidence that adds to the dimensions of Müller cell function by demonstrating a unique relationship between external NAD(+) and the mobilization of internal calcium, expressed in the form of calcium waves. The cellular mechanism that supports internal mobilization of calcium appears to depend on a complex multifunctional ectoenzyme, CD38, which converts NAD(+) into the intracellular Ca(2+)-mobilizing second-messenger cyclic ADP-ribose (cADPR) and could function as a detector for extracellular NAD(+), thus providing a novel signal detection system for evaluating the extracellular environment. Our results are consistent with a model of intracellular Ca(2+) mobilization in which membrane-bound CD38 binds extracellular NAD(+) and triggers intracellular Ca(2+) waves either by direct conversion of NAD(+) to cADPR or by activating intracellular cADPR synthesis. Our preliminary results indicate that the Ca(2+) waves induced by external NAD(+) propagate through an internal pathway that depends on the activation of ryanodine receptors, which appear to be distributed throughout the Müller cell cytosol. Because NAD(+) is likely to be enhanced when cells are stress or damaged, CD38 could enable Müller cells to detect NAD(+) under these circumstances and respond appropriately. Alternatively, NAD(+) could also represent a novel extracellular, paracrine function that mediates signaling between glial cells and/or other cellular elements of the retina.
Magnitudeak lantzeko egoera didaktikoak: txanpon sistema (2015)

espanolEste trabajo tiene dos objetivos principales, por un lado, identificar las dificultades que los alumnos presentan a la hora de hacer actividades aritmetizadas sobre magnitudes y, por otro, proporcionar al alumnado nuevas estrategias para resolver problemas y hacer frente a esas dificultades. Para responder a estas preguntas, se presenta un marco teorico donde se explican algunas tecnicas de resolucion de problemas, teorias que tienen al alcance los profesores a la hora de disenar los problemas y las claves para entender por que los alumnos resuelven mal los problemas. A continuacion se disenan dos propuestas sobre magnitudes; una de ellas se ha llevado a la practica en un aula de segundo nivel de primer ciclo de Primaria. Finalizamos con el analisis de los resultados obtenidos donde se ve que las herramientas reflejadas en el marco teorico tienen validez practica a la hora de interpretar la resolucion que hacen los alumnos. euskaraLan honek bi helburu nagusi ditu, alde batetik, magnitudeen gaineko jarduera aritmetizatuak egiterako orduan ikasleek dituzten zailtasunak identifikatzea, eta bestetik, zailtasun horiei aurre egiteko eta buruketak ebazteko ikasleei estrategia berriak ematea. Galdera horiei erantzuteko, marko teoriko bat aurkezten da non azalduko diren buruketak egiteko hainbat teknika, irakasleak buruketak diseinatzeko orduan eskura dituzten teoriak eta ikasleek buruketak gaizki zergatik egiten dituzten ulertzeko gakoak. Ondoren, magnitudeen inguruko bi proposamen diseinatu dira eta horietako bat lehenengo zikloko bigarren mailako ikasgela batean eraman da praktikara. Lorturiko emaitzen analisi batekin amaitzen da, non ikusten den marko teorikoaren tresnek balio praktikoa dutela ikasleen ebazpena interpretatzerakoan.
A Lutetium Cyclopentadienyl‐Phosphazene Constrained Geometry Complex (CGC): First Isolobal Analogues of Group 4 Cyclopentadienyl‐Silylamido CGC Systems (2005)

Abstract C 5 Me 4 HPMe 2 reacts with 1‐adamantyl azide to form the firstexample of a new family of cyclopentadienylideneaminophosphorane ligands ( 1 ). Metallation of 1 with Lu(CH 2 SiMe 3 ) 3 (THF) 2 leads to the first cyclopentadienyl‐phosphazene CGC 2 , isolobal to known group 4 cyclopentadienyl‐silylamido CGC systems. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Binding of Upstream Stimulatory Factor to an E-box in the 3′-Flanking Region Stimulates α1(I) Collagen Gene Transcription (1997)

Since several lines of evidence implicate the 3'-flanking region in regulating alpha1(I) collagen gene transcription, we analyzed 12. 4-kilobase pairs of 3'-flanking sequence of the murine alpha1(I) collagen gene for transcriptional elements. A region of the 3'-flanking region stimulated expression of the heterologous beta-globin gene promoter in an enhancer trap plasmid and of the alpha1(I) collagen gene promoter in a collagen-luciferase reporter gene construct when located 3' to the luciferase reporter gene. DNase I footprinting analysis demonstrated the presence of three regions where DNA binding proteins specifically interact within this 3'-stimulatory region. Inspection of the DNA sequence revealed a consensus E-box, a binding site for basic helix-loop-helix proteins, in one of the protein binding sites. Mobility shift assays demonstrated that upstream stimulatory factors (USF) USF-1 and USF-2 bind to this E-box. Mutating the E-box in the context of the 3'-flanking region confirmed that it contributes to the enhancement of transcriptional activity of the alpha1(I) collagen gene promoter. Mutations in all three protein binding sites abolished transcriptional activation by the 3'-flanking region, suggesting a complex interaction among the trans-acting factors in enhancing transcriptional activity. Thus, a region of the 3'-flanking region of the alpha1(I) collagen gene stimulates transcription of the alpha1(I) collagen gene promoter, and USF-1 and USF-2 contribute to this transcriptional stimulation.
A Novel Method for the Elution of Sirolimus (Rapamycin) in Drug-Eluting Stents (2011)

A sensitive and robust method for the determination of the elution of an active drug substance, sirolimus, from drug-eluting coronary stents was developed using a USP Apparatus 4 elution system. The closed-loop configuration of the elution apparatus and the small volume of eluent allow the low drug levels that elute from a single stent to be reproducibly monitored.
Polymers of Intrinsic Microporosity Derived from Novel Disulfone-Based Monomers (2009)

The synthesis of three novel disulfone-based monomers from readily available hexafluorobenzene and thiols for the preparation of homopolymers and copolymers of intrinsic microporosity (PIMs) is described. The disulfonyl-based PIMs derived from 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethylspirobisindane (TTSBI) with tetrafluoroterephthalonitrile (TFTPN) and disulfone-based monomers were prepared at high temperature (160 °C) within 1 h. Three new copolymers (monomer molar ratio of TTSBI and disulfone-based monomers = 3:1) show a good combination of properties, such as excellent film-forming characteristics and gas transport properties. Compared with a previously reported microporous nitrile-based homopolymer, referred to as PIM-1, the present sulfone-based copolymers have higher gas selectivities for O2/N2 and CO2/N2, while showing some reduction in pure-gas permeabilities. The relationship between the structure and gas permeation behavior of the copolymers is discussed.
Determination of Cathepsins B and H in Sera and Synovial Fluids of Patients with Different Joint Diseases (1990)

Synovial fluids and sera of patients with inflammatory and metabolic joint diseases contain different cysteine proteinases. The quantities of cathepsins B and H were determined by newly developed specific enzyme-linked immunoassay tests (ELISA), with detection limits of 0.5 microgram/l for cathepsin B and 3 micrograms/l for cathepsin H. The values of cathepsin B in normal sera ranged from 0.6 microgram/l to 2 micrograms/l, whereas in sera of patients with joint diseases they ranged from 1.7 micrograms/l to 18 micrograms/l. Cathepsin H was not found in sera (values below 3 micrograms/l), but was measurable in patients' synovial fluids. Patients with rheumatoid arthritis have on average the highest values of cathepsin B in synovial fluids, whereas patients with undifferentiated arthritis have the highest values of cathepsin H. The results show that cathepsins B and H are present in arthritic synovial fluids, where they may be implicated in destructive processes. There is yet no clear correlation between the quantity of each cathepsin released in synovia and the clinical diagnosis or the stage of the disease.
Patient defined dichotomous end points for remission and clinical improvement in ulcerative colitis (2005)

We found specific cut off values for disease activity indices that identify patients who have significantly improved or achieved remission in an objective, sensitive, and specific manner. These cut offs should help in the interpretation of the outcomes of clinical trials in ulcerative colitis.
Mitochondrial oxidative phosphorylation defects in parkinson's disease (1991)

Parkinson's disease has been associated with defects in oxidative phosphorylation (Oxphos). We analyzed mitochondria isolated from muscle biopsies of 6 patients with Parkinson's disease for deficiencies in Oxphos enzymes and for mutations in the mitochondrial DNA. Oxphos enzyme assays were compared to the 5 to 95% confidence intervals from 16 control subjects. Four patients had complex I defects, whereas 1 patient had a complex IV defect. A genetic basis for Parkinson's disease was suggested by the presence of affected relatives of 2 patients with Parkinson's disease. Known pathological mitochondrial DNA mutations (insertion-deletions or point mutations) were not found. We conclude that Parkinson's disease is a systemic disorder of Oxphos, probably of a complex genetic etiology. Premature cell death in the nigrostriatal dopamine pathway could be due to energetic impairment and accentuated free radical generation caused by an Oxphos defect.
Klinefelter's syndrome in adolescence. (1982)

Twelve boys with Klinefelter's syndrome (47,XXY) identified by sex chromatin screening at birth were examined at between ages 16 and 18 years, together with 12 controls matched for social class and birth order from the same newborn population. Physical examination, psychometric assessment, personality, and degree of psychosexual development were assessed without knowledge of the karyotype. Anthropometry showed increased leg length and decreased head circumference in the XXY boys. Gynaecomastia was present in 4 boys, and testicular volume was reduced in the majority but one boy had normal sized testes. On the Wechsler intelligence scale there was a significant reduction in verbal score but not in either performance or full-scale score compared with the controls. Although appreciable differences were found in growth, personality, intelligence test scores, and psychosexual development, these were of small degree.
Abietane Acids: Sources, Biological Activities, and Therapeutic Uses (1993)

The biological activities of natural abietane acids and their derivatives have been reviewed from 1967 to 1992. Antimicrobial, antiulcer, and cardiovascular activities are the most representative for this class of diterpenoids, while others like allergenic, antiallergic, filmogenic, surfactant, antifeedant, etc. activities, which determine several uses of abietane acids, have also been reported.
Optimization of the Bend Strength of Flat‐Layered Alumina−Zirconia Composites (2007)

We have made a theoretical study of the bend strength of flat, multilayered alumina−zirconia composites. We used the linear theory of elasticity to calculate the stresses in materials subjected to a three‐point bending test, including the thermal residual stresses that result from the fabrication process. We studied symmetrically and non‐symmetrically layered composites with a variable number of layers, with the focus on the optimization of individual layer thicknesses to get the highest composite strength. Using typical strength data for particulate composites from the literature, we found that it is sensible to optimize the composite with up to seven layers as taking even more layers does not further improve the composite strength significantly. Furthermore, there is a qualitative difference in the total stress distribution through the sample thickness in the case of optimized and non‐optimized structure, respectively.
Quality Characteristics of Muffin Added Red Yeast Rice Flour (2007)

Red yeast rice flour, which is a natural functional material, was used in muffin production at different concentrations ranging from 0 to 10%. The initial pasting temperature was not affected by the addition of red yeast rice flour, whereas peak viscosity and final viscosity decreased with increasing concentrations. The lightness value of the muffins decreased, however, the redness value increased with increasing amounts of red yeast rice flour. The bulk of the muffins was generally reduced by the addition of red yeast rice flour. At the 10% concentration, hardness and viscosity were similar to the control, and there were no changes in springiness or cohesiveness. For the sensory evaluation, parameters such as appearance, color, texture, taste, and overall acceptability increased significantly from the control at the 3% concentration of red yeast rice flour, but flavor decreased with increasing amounts of red yeast rice flour. Based on these results and the sensory evaluation specifically, the optimal amount of red yeast rice flour added to the muffins was the 3% concentration.