gebhart/patrepeval huggingface dataset:
The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus (2006)

Astrocytic gap junctions have been suggested to contribute to spatial buffering of potassium in the brain. Direct evidence has been difficult to gather because of the lack of astrocyte-specific gap junction blockers. We obtained mice with coupling-deficient astrocytes by crossing conditional connexin43-deficient mice with connexin30(-/-) mice. Similar to wild-type astrocytes, genetically uncoupled hippocampal astrocytes displayed negative resting membrane potentials, time- and voltage-independent whole-cell currents, and typical astrocyte morphologies. Astrocyte densities were also unchanged. Using potassium-selective microelectrodes, we assessed changes in potassium buffering in hippocampal slices of mice with coupling-deficient astrocytes. We demonstrate that astrocytic gap junctions accelerate potassium clearance, limit potassium accumulation during synchronized neuronal firing, and aid in radial potassium relocation in the stratum lacunosum moleculare. Furthermore, slices of mice with coupling-deficient astrocytes displayed a reduced threshold for the generation of epileptiform events. However, it was evident that radial relocation of potassium in the stratum radiatum was not dependent on gap junctional coupling. We suggest that the perpendicular array of individual astrocytes in the stratum radiatum makes these cells ideally suited for spatial buffering of potassium released by pyramidal cells, independent of gap junctions. In general, a surprisingly large capacity for K+ clearance was conserved in mice with coupling-deficient astrocytes, indicating that gap junction-dependent processes only partially account for K+ buffering in the hippocampus.
Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non–Small-Cell Lung Cancer: AVAPERL (MO22089) (2013)

In an unselected population of patients with nonsquamous NSCLC who had achieved disease control with platinum-based chemotherapy plus bevacizumab, bevacizumab plus pemetrexed maintenance was associated with a significant PFS benefit compared with bevacizumab alone. The combination was well tolerated.
Three decades of human monoclonal antibodies: Past, present and future developments (2009)

The hybridoma technique has been shown to be a most reproducible method for producing rodent monoclonal antibodies but poor results were obtained when it was used for generating human monoclonal antibodies. For immunotherapy, murine monoclonal antibodies are inadequate, whereas human monoclonal antibodies are virtually indispensable. Cellular, chemical, genetic and molecular methods to generate human monoclonal antibodies have been developed. Most often, the monoclonal antibodies for therapy are selected after deliberate vaccination, according to their high affinity towards an arbitrarily-chosen epitope of a pathogen or cellular antigen and therefore the selection is obviously skewed. A major hindrance of the production of therapeutic human monoclonal antibodies is the lack of an appropriate strategy to define and select the antibodies that would be effective in vivo. In contrast to antibodies induced by vaccination, there has been only a marginal interest in monoclonal antibodies which reflect antibodies of the innate immunity. In the future, human monoclonal antibodies that resemble antibodies that are ubiquitously present in sera of healthy individuals might serve as novel therapies in diseases such as Alzheimer's disease, where no other therapy exists.
Hickman Catheter Complications in Marrow Transplant Recipients (1986)

The complications associated with the insertion and use of 95 single lumen and 312 double lumen Hickman right atrial catheters in 357 marrow transplant recipients were retrospectively analyzed. Three-hundred (84%) first inserted catheters were in place for a median of 93 days (range, 16-209) without complications and were removed electively. Thirty-nine (9.6%) of all catheters were removed for infections and 24 (5.9%) for mechanical complications. Ninety-five patients (26.6%) had 111 episodes of septicemia involving 128 separate organisms and 25 patients had 25 episodes of localized catheter infection with 26 separate organisms. The most frequently isolated organism was coagulase-negative staphylococcus. Twelve of 24 removals due to mechanical complications were caused by accidental pulling of the catheter by the patient.
Effects of Human Growth Hormone in Men over 60 Years Old (1990)

Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occur in old age.
C-reactive protein measurement in general practice may lead to lower antibiotic prescribing for sinusitis. (2004)

The CRP rapid test has a substantial influence on the treatment of sinusitis, and implementing the test in general practice may lead to a reduction in antibiotic prescribing to patients with sinusitis.
Antiapoptotic Activity of the Herpesvirus Saimiri-Encoded Bcl-2 Homolog: Stabilization of Mitochondria and Inhibition of Caspase-3-Like Activity (1998)

Viruses have evolved different strategies to interfere with host cell apoptosis. Herpesvirus saimiri (HVS) and other lymphotropic herpesviruses code for proteins that are homologous to the cellular antiapoptotic Bcl-2. In this study HVS-Bcl-2 was stably expressed in the human leukemia cell line Jurkat and in the murine T-cell hybridoma DO to assess its antiapoptotic spectrum and to gain further insight into its mode of action. HVS- Bcl-2 prevented apoptosis that occurs as a result of a disturbance of intracellular homeostasis by, for example, DNA damage or menadione, which gives rise to oxygen radicals. In Jurkat cells, HVS-Bcl-2 also inhibited apoptosis mediated by the death receptor CD95. In DO cells, HVS-Bcl-2 did not interfere with CD95-mediated apoptosis but blocked dexamethasone-induced cell death. Mitochondrial damage is a central coordinating event in apoptosis induced by different stimuli. To assess the integrity of mitochondria, we used rhodamine 123, which is released upon disturbance of the mitochondrial membrane potential, and determined the release of cytochrome c into the cytosol. Both signs of mitochondrial damage were prevented by HVS-Bcl-2. This viral protein also inhibited the generation of caspase-3-like DEVDase activity and blocked the cleavage of poly(ADP-ribose) polymerase, a natural substrate of caspase-3-like proteases. In conclusion, HVS-Bcl-2 protects against a great variety of apoptotic stimuli, stabilizes mitochondria, and acts upstream of the generation of caspase-3-like activity.
[Quantitative comparison of ventilator-induced work during simulated CPAP in eight demand-flow valve ventilators]. (1989)

The ventilator-induced work during continuous positive airway pressure (CPAP) mode in demand-valve ventilators was evaluated by using a piston pump as a simulator for active breathing. A piston pump delivered and withdrew a stroke volume of 500 ml at rates of 10, 20 and 40 cycle.min-1 with a sinusoidal waveform. A hot-wire flowmeter and a differential pressure transducer were interposed between the pump and ventilators and their signals were fed to a microcomputer to display a pressure-volume loop. The area of the loop was divided into the four parts. Inspiratory work associated with the opening of the demand valve was represented by the area of baseline airway pressure (BPa) during inspiration. The remaining area during inspiration reflected the work done by the ventilators. Expiratory work for overcoming the flow resistance of the expiratory apparatus was represented by the area above BPa during exhalation. The fourth was the area below the baseline during exhalation. The Puritan-Bennett 7200a, the Bear 5, the Siemens Servo 900C, the Hamilton Veolar, the Bird 6400ST, the Engström Erica, the Dräger EV-A, and the CPU-1 were examined at varying CPAP and pressure support levels. Because of demand valve oscillation throughout inspiration, the inspiratory workload of the Bear 5, the Siemens Servo 900C, the Hamilton Veolar, the Bird 6400ST, and the Dräger EV-A could not be calculated. Expiratory flow-resistive work was higher in the Siemens Servo 900C and the Bird 6400ST than the others. The present system can assess the entire performance of ventilators, and may serve to compare ventilators' performance.
National Institute of Mental Health Treatment of Depression Collaborative Research Program (1989)

We investigated the effectiveness of two brief psychotherapies, interpersonal psychotherapy and cognitive behavior therapy, for the treatment of outpatients with major depression disorder diagnosed by Research Diagnostic Criteria. Two hundred fifty patients were randomly assigned to one of four 16-week treatment conditions: interpersonal psychotherapy, cognitive behavior therapy, imipramine hydrochloride plus clinical management (as a standard reference treatment), and placebo plus clinical management. Patients in all treatments showed significant reduction in depressive symptoms and improvement in functioning over the course of treatment. There was a consistent ordering of treatments at termination, with imipramine plus clinical management generally doing best, placebo plus clinical management worst, and the two psychotherapies in between but generally closer to imipramine plus clinical management. In analyses carried out on the total samples without regard to initial severity of illness (the primary analyses), there was no evidence of greater effectiveness of one of the psychotherapies as compared with the other and no evidence that either of the psychotherapies was significantly less effective than the standard reference treatment, imipramine plus clinical management. Comparing each of the psychotherapies with the placebo plus clinical management condition, there was limited evidence of the specific effectiveness of interpersonal psychotherapy and none for cognitive behavior therapy. Superior recovery rates were found for both interpersonal psychotherapy and imipramine plus clinical management, as compared with placebo plus clinical management. On mean scores, however, there were few significant differences in effectiveness among the four treatments in the primary analyses. Secondary analyses, in which patients were dichotomized on initial level of severity of depressive symptoms and impairment of functioning, helped to explain the relative lack of significant findings in the primary analyses. Significant differences among treatments were present only for the subgroup of patients who were more severely depressed and functionally impaired; here, there was some evidence of the effectiveness of interpersonal psychotherapy with these patients and strong evidence of the effectiveness of imipramine plus clinical management. In contrast, there were no significant differences among treatments, including placebo plus clinical management, for the less severely depressed and functionally impaired patients.
A wide dynamic range CMOS image sensor with multiple short-time exposures (2006)

A wide dynamic range CMOS image sensor based on synthesis of long-time and multiple short-time exposure signals for high image quality in the whole illumination range is proposed. A key technique is a high-speed and high-resolution column-parallel integration type analog-to-digital converter (ADC) with nonlinear slope. A prototype wide dynamic range CMOS image sensor that captures a long-exposure and 3 short-exposure signals has been developed with 0.25 /spl mu/m 1-poly 4-metal CMOS image sensor technology. The dynamic range is expanded by a factor of 120 compared with the case of the single long-time exposure. The ADC has a good linearity. The maximum DNL is 0.3 LSB and 0.6 LSB for single- and multi-resolution mode, respectively.
Reliability and validity of commercially available, direct radioimmunoassays for measurement of blood androgens and estrogens in postmenopausal women. (2001)

In large-scale epidemiological studies on endogenous sex steroids and cancer risk, direct immunoassays of circulating hormone levels have the advantage of being fast and comparatively inexpensive while requiring only small sample volumes. On the other hand, indirect assays after organic extraction and chromatographic prepurification have the advantage of reducing specific interferences and matrix effects and hence are thought to have better validity. We compared direct assays of testosterone (T, six different assays), Delta4-androstenedione (A, four assays), estrone (E(1), one assay), and 17beta-estradiol (E(2), five assays) with measurements obtained by an indirect assay in a representative subset of 20 postmenopausal women who were part of a large prospective cohort study. Within-batch reproducibilities of the subject rankings by relative hormone levels were good (intraclass correlations >0.89) for all direct assays tested. Between batches, reproducibilities generally were also acceptable (r > 0.80) to good (r > 0.90) in terms of Pearson's correlations. The between-batch reproducibility in terms of intraclass correlations was systematically lower in terms of Pearson's correlations, however, because of between-batch variations in the absolute scale of measurements. The relative validity of direct versus indirect assays in terms of the subjects' ranking by relative hormone levels was also high for most of the kits tested for T, A, and E(1) (Pearson's correlations between 0.70 and 0.89) but was high for only two kits of five tested for E(2) (correlations of 0.86 and 0.84). On an absolute scale, mean measurement values were generally higher for direct assays than for the indirect assay and, for each hormone, varied substantially, depending on the kit used. Overall, the results of this study show that, with careful selection, commercial kits for direct radioimmunoassays of steroid hormones in postmenopausal serum can be found that may allow a reliable estimation of relative risks in epidemiological studies. However, standardization of the absolute scale of assays remains problematic.
Visible light induced DNA cleavage by the hybrid antitumor antibiotic dynemicin A (1990)

Dynemicin A, which is a hybrid antitumor antibiotic containing anthraquinone and enediyne cores, effectively breaks DNA strands upon irradiation with visible light of long wavelength. The preferential cutting sites of visible light induced DNA cleavage with dynemicin A are on the 3'-side of purine bases such as in 5'-AT and 5'-GT sequences. The observed nucleotide cutting specificity is remarkably similar to that of NADPH- (or thiol) induced DNA breakage with dynemicin A, suggesting the presence of the same DNA-cleaving intermediate. Indeed, the photoproduct of dynemicin A is chromatographically identical with the reaction product (dynemicin H) of the thiol-activated dynemicin A. On the basis of the present results, a reasonable mechanism for the visible light induced DNA cleavage of dynemicin A has been proposed.
Genomic and Gene Expression Profiling Defines Indolent Forms of Mantle Cell Lymphoma (2010)

Mantle cell lymphoma (MCL) is typically a very aggressive disease with poor outcomes, but some cases display an indolent behavior that might not necessitate treatment at diagnosis. To define molecular criteria that might permit recognition of such cases, we compared the clinicopathologic features, gene expression, and genomic profile of patients who had indolent or conventional disease (iMCL or cMCL). Patients with iMCL displayed nonnodal leukemic disease with predominantly hypermutated IGVH and noncomplex karyotypes. iMCL and cMCL shared a common gene expression profile that differed from other leukemic lymphoid neoplasms. However, we identified a signature of 13 genes that was highly expressed in cMCL but underexpressed in iMCL. SOX11 was notable in this signature and we confirmed a restriction of SOX11 protein expression to cMCL. To validate the potential use of SOX11 as a biomarker for cMCL, we evaluated SOX11 protein expression in an independent series of 112 cases of MCL. Fifteen patients with SOX11-negative tumors exhibited more frequent nonnodal presentation and better survival compared with 97 patients with SOX11-positive MCL (5-year overall survival of 78% versus 36%, respectively; P = 0.001). In conclusion, we defined nonnodal presentation, predominantly hypermutated IGVH, lack of genomic complexity, and absence of SOX11 expression as qualities of a specific subtype of iMCL with excellent outcomes that might be managed more conservatively than cMCL.
The sialoadhesin CD33 is a myeloid-specific inhibitory receptor (1999)

Activating and inhibitory receptors act in concert to regulate cellular activation. Inhibitory receptors are characterized by the presence of a characteristic sequence known as an immunoreceptor tyrosine-based inhibitory motif (ITIM) in their cytoplasmic tail. Phosphorylated ITIM serve as docking sites for the SH2-containing phosphatases which then inhibit signal transduction. CD33 is a member of the immunoglobulin superfamily and contains two immunoglobulin-like domains, a transmembrane region and a cytoplasmic tail that has two potential ITIM sequences. CD33 expression is restricted to cells of myelomonocytic lineage. The precise function of CD33 is unknown although it is a lectin that binds sialic acid residues in N- and O-glycans on cell surfaces. Co-immunoprecipitation studies demonstrate that CD33 associates with the SH2-containing tyrosine phosphatase SHP-1 in monocytes. The proximal ITIM is necessary and sufficient for SHP-1 binding which is mediated by the aminoterminal SH2 domain. Treatment of SHP-1 with a phosphopeptide representing the proximal CD33 ITIM results in increased SHP-1 enzymatic activity. CD33 exerts an inhibitory effect on tyrosine phosphorylation and Ca(2+) mobilization when co-engaged with the activating FcgammaRI receptor. This data indicates that CD33 is an inhibitory receptor that may regulate FcgammaRI signal transduction.
Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the rapid evolution of virulence and drug resistance (2004)

Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the approximately 2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive community-acquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: approximately 6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC(476)), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.
ADAMTS5 Is a Biomarker for Prediction of Response to Infliximab in Patients with Rheumatoid Arthritis (2010)

The baseline ADAMTS5 mRNA level is a candidate biomarker for prediction of the response to IFX in patients with RA.
The conversion of serine at the active site of subtilisin to cysteine: a "chemical mutation". (1966)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Direct gene replacement of the mouse α(1,3)‐galactosyltransferase gene with human α(1,2)‐fucosyltransferase gene: Converting α‐galactosyl epitopes into H antigens (1997)

Abstract: The chronic donor organ shortage has led to the production of transgenic animals. We assume that cells or organs derived from possible animal donors carrying a large amount of α‐galactosyl epitopes should not be transplanted into humans, because a corresponding amount of immunosuppressants would be needed to prolong the survival of such xenografts in the recipients. This may not only make the recipients compromised hosts but also introduce some unknown or uncontrollable pathogens into society at large. We also assume that gene manipulation itself should not be a detriment to possible transgenic animals. To explore possibilities that not only can minimize the possible detrimental factors to humans, such as α‐galactosyl epitopes, but also can minimize the possible detriment to transgenic animals, such as random integration of the extraneous genes with or without uncontrollable regulatory sequences, we have produced a DNA construct that replaces the mouse oc(1,3)‐galactosyltransferase gene (GT) with the human a(1,2)‐fucosyltransferase (FT) minigene (promoterless for the expression of FT) at the GT locus. The mouse fibrosarcoma cell line, L929, was transfected with the construct. Colonies were obtained after incubation with non‐heat‐inactivated human serum. Southern blot analysis demonstrated that one allele of the mouse GT gene was replaced with the FT minigene at the GT locus without integration of any selectable marker genes. The immunostaining analysis with lectins showed that the transfectants expressed H antigens, which suggested that H antigens were expressed by the intrinsic GT promoter. Thus gene replacement, knock‐in, of the mouse GT with the human FT without integration of any selectable marker genes in the GT locus was shown to be possible. This is especially important in producing transgenic animals for the clinical application of xenografts into humans.
Excited States of Flavins Characterised by Absorption, Prompt and Delayed Emission Spectra (1970)

The angles between the two principal long wavelength absorption oscillators of FMN and some other flavins have been measured by two methods. A novel technique involving dichroic bleaching gave a value (approx. 35°) consistent with that obtained from the polarisation of fluorescence extrapolated to infinite viscosity. Flavins trapped in polyacrylamide films display E‐type delayed fluorescence and phosphorescence depending on the temperature. The variations in lifetimes and intensities of these two delayed emissions with temperature have been studied. The Arrhenius activation energies have been analysed in terms of a scheme that gives information about the interrelationships between different electronic states of flavins.
ChemInform Abstract: Catalytic Asymmetric Diels‐Alder Reactions (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.