gebhart/patrepeval huggingface dataset:
Increasing prevalence of penicillin-resistant pneumococcal infections in children in southern Israel (1994)

Although penicillin-resistant pneumococci (PR-PnC) are recognized as an increasing problem worldwide, data on the prevalence of these strains among pediatric patients are incomplete. The present study was conducted in southern Israel (1) to investigate the frequency of PR-PnC in invasive and middle ear infections in pediatric patients and (2) to assess the impact of resistance on the potential role of the candidate conjugate vaccines in preventing childhood PR-PnC infections. A total of 120 blood or cerebrospinal fluid isolates from 1987 to 1993 and 78 ear isolates from 1992 to 1993 were serogrouped and tested for susceptibility to antibacterial agents. The prevalence of PR-PnC among invasive isolates increased from 16% in the years 1987 to 1991 to 36% in 1992 to 1993 (P = 0.019). This increase was noted mainly for intermediately resistant strains (minimal inhibitory concentration, 0.12 to 1.0 micrograms/ml) whereas the prevalence of highly resistant strains was 3 and 2% for the 2 periods, respectively. The prevalence of PR-PnC among ear isolates in 1992 to 1993 was 42%. Resistance to other antimicrobial agents (one or more of the following: tetracycline, erythromycin, clindamycin and chloramphenicol) was found in 16 (8%) isolates, and multiple resistance (resistance to > or = 3 antibacterial agents) was found in 9 (5%) isolates. Sixty-five (99%) of the 66 resistant isolates belong to Serogroups 6, 14, 19 and 23. The prevalence of these 4 serogroups rose from 37% in 1987 to 1991 to 66% in 1992 to 1993 (P = 0.043). This rise was mainly because of Serogroup 23, the prevalence of which rose from 3% in 1987 to 1991 to 23% in 1992 to 1993 (P < 0.001). Eighty-five percent of all isolates belonging to Serogroup 23 were resistant to penicillin. Because Serogroups 6, 14, 19 and 23 are among the commonest pediatric pneumococcal strains, the newly developed conjugate pneumococcal vaccines contain these 4 serogroups. The selection of antibiotic-resistant strains has thus led to a change in the spectrum of serotypes causing invasive disease and to a situation of potential increase in vaccine coverage for the proposed pneumococcal conjugate vaccines.
Bcl6 promotes follicular helper T‐cell differentiation and PD‐1 expression in a Blimp1‐independent manner in mice (2017)

The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (T<sub>FH</sub> ) cells: Bcl6 promotes and Blimp1 inhibits T<sub>FH</sub> -cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the T<sub>FH</sub> -cell marker PD-1. However, Bcl6 and Blimp1 repress each other's expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control T<sub>FH</sub> -cell differentiation by generating mice with T-cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice). Our data indicate that Blimp1 does not control T<sub>FH</sub> -cell differentiation independently of Bcl6. However, a population of T follicular regulatory (T<sub>FR</sub> ) cells developed independently of Bcl6 in dcKO mice. We have also analyzed regulation of IL-10 and PD-1, two genes controlled by both Bcl6 and Blimp1, and observed that Bcl6 regulates both genes independently of Blimp1. We found that Bcl6 positively regulates PD-1 expression by inhibiting the ability of T-bet/Tbx21 to repress Pdcd1 transcription. Our data provide a novel mechanism for positive control of gene expression by Bcl6, and illuminate how Bcl6 and Blimp1 control T<sub>FH</sub> -cell differentiation.
Phase 2, multicenter, safety and efficacy study of pidilizumab in patients with metastatic melanoma. (2014)

9001 Background: Pidilizumab (CT-011), a humanized anti PD-1 IgG1k, was studied in two Phase 2 studies in aggressive and indolent lymphomas showing clinical activity correlated with PD-1/PD-L1+ lymphocytes. Thus, we initiated a Phase 2 multicenter, randomized, open-label, study to evaluate the safety and efficacy of pidilizumab in patients (pts) with metastatic melanoma (MM). Methods: Eligibility criteria: measurable disease; Stage IV clearly progressive; ECOG 0-1; ≤ 3 prior systemic therapies for MM; stabilized brain mets allowed; 6 weeks from prior ipilimumab (Ipi), no prior PD-1/PD-L1/PD-L2 blockade. Pts were randomized to 2 dose levels (1.5 or 6 mg/kg IV q2 wk X 27), each with 50 pts and each balance stratified by prior Ipi (yes/no). Results: 103 pts were randomized; 75% M1c, 15.5% brain mets, 30% elevated LDH, 33% disease spread to ≥ 3 organs. 77% received prior systemic therapy for MM; 51% prior Ipi, 7.8% prior Braf inhibitor, 44% prior biologics (cytokines). 45% did not respond to most recent therapy. 45% received pidilizumab less than 4 months after prior therapy. ORR using irRC for all pts was 5.9% [90% CI: 2.3, 12.0] and 10.0% [90% CI: 1.8, 28.3] for 1.5mg/kg & prior Ipi. Pts with prior Ipi had higher irSD (53.7% vs 20.5%) and slightly longer median PFS (2.8 vs 1.9 months). Overall Survival at 12 months (12mo survival) was 64.5% (90% CI: 55.6, 72.0), with insignificant differences between strata or doses and irrespective of therapies given before study entry or after study withdrawal; 12mo survival for pts without prior or post-study Ipi (n=26) was 55.7% [90% CI: 35.6, 71.8], 12mo survival for pts with B-RAF V600 WT tumors (n=63) was 69.3% [90% CI: 58.2, 78.1]. 12mo survival for M1c pts (n=77) was 67.2%; [90% CI: 57.0, 75.5]. The most frequent AEs were fatigue (43%), diarrhea (22.5%), arthralgia (21%) and SAEs of pneumonia (5%) and dyspnea (3%). Conclusions: Despite low response rates, pidilizumab therapy results in substantial 12mo survival in heavily pretreated pts. The 12mo survival appears comparable to that of other anti- PD-1 MAbs. Treatment is very well tolerated. Further studies of pidilizumab in pts with MM are warranted, preferably in combination with other therapeutics. Clinical trial information: NCT01435369.
The Kinetics of HCO<sub>3</sub><sup>−</sup> Synthesis Related to Fluid Secretion, pH Control, and CO<sub>2</sub> Elimination (1988)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Resolution of Inflammation in Type 2 Diabetes (2016)

Unresolved inflammation is a key factor linking metabolic dysregulation and the immune system in type 2 diabetes. Successful regulation of acute inflammation requires biosynthesis of specialized pro-resolving lipid mediators, such as resolvin E1 (RvE1), and activation of cognate g-protein coupled receptors (GPCR). RvE1 binds to BLT-1 on neutrophils and ERV-1/ChemR23 on monocyte/macrophages. The mechanism by which innate immune cells in metabolic diseases fail to respond to endogenous pro-resolution signals is not well understood. The goal of the studies presented was to investigate the expression and function of ERV-1 receptor on neutrophils from type 2 diabetes subjects. Results demonstrate that neutrophils from type 2 diabetic subjects expressed significantly increased ERV-1 receptor on their cell surface that was functional, as determined by phosphorylation of the signalling protein, ribosomal S6 (rS6). Healthy neutrophils express functional BLT-1 and low levels of minimally functional ERV-1. Stimulation with TNFα or LPS increased expression of ERV1 on neutrophils of both healthy and diabetic subjects. Increased expression of ERV1 was reversed by pre- and post- treatment with RvE1. TNFα or LPS stimulation increased phospho-rS6 significantly more in type 2 diabetic neutrophils than healthy subjects. Receptor antagonism experiments revealed that the phospho-rS6 increase was mediated by BLT-1 in healthy subject neutrophils and ERV1 in diabetic subject neutrophils. Diabetic neutrophil ERV-1 over expression was reversed by RvE1 treatment in a dose response manner (1-10nM). Analysis of the bioactive lipid metabolome revealed higher expression of inflammatory mediators in type 2 diabetes serum than healthy control with slightly reduced levels of RvE1 in type 2 diabetics (by ELISA). Neutrophil phagocytosis of pathogenic bacteria and inert bioparticles was impaired in type 2 diabetes. RvE1, signalling through ERV-1 but not BLT-1, partially rescued deficient phagocytosis by type 2 diabetic neutrophils with a clear shift of the dose response requiring increased RvE1. The dose of RvE1 required to activate resolution signals in type 2 diabetic neutrophils is significantly higher than healthy controls. Overall the findings in this dissertation further our understanding of the importance of expression and function of key resolution receptors in health versus disease and dysregulation of inflammation in type 2 diabetes.
Phase relationship, vaporization, and thermodynamic properties of the lanthanum-boron system (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhase relationship, vaporization, and thermodynamic properties of the lanthanum-boron systemEdmund Storms and Barbara MuellerCite this: J. Phys. Chem. 1978, 82, 1, 51–59Publication Date (Print):January 1, 1978Publication History Published online1 May 2002Published inissue 1 January 1978https://pubs.acs.org/doi/10.1021/j100490a014https://doi.org/10.1021/j100490a014research-articleACS PublicationsRequest reuse permissionsArticle Views323Altmetric-Citations76LEARN 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 optionsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Improved Control over Particle Sizes and Stability of Concentrated Fluorocarbon Emulsions by Using Mixed Fluorocarbon/Hydrocarbon Molecular Dowels (1994)

The use of a surfactant system consisting in equimolar amounts of egg yolk phospholipids and of a mixed fluorocarbon/hydrocarbon amphiphile (C8H17CH = CHC8F17) allows the preparation of concentrated (90% w/v, i.e. 47% v/v) emulsions of perfluorooctyl bromide (perflubron), with average particle sizes ranging from 0.12 to 16 microns post-sterilization, depending on the surfactant/fluorocarbon ratio. Emulsion droplet diameters varied linearly as a function of the emulsifier's concentration, thus allowing easy pre-determination of the emulsion's average particle size. Excellent stability was observed for the dowel-containing emulsions for at least 6 months at 40 degrees C over the whole domain of particle sizes investigated.
Multifunctional DNA conjugates for the in vitro selection of new catalysts (2000)

DNA-substrate conjugates are required for the direct in vitro selection of novel DNA catalysts for reactions between two small reactants. Here we describe the introduction of all necessary features into ssDNA by a novel, multifunctional primer containing a flexible PEG spacer, an o-nitrobenzyl moiety allowing for selective photocleavage, and anthracene as a reactant, a fluorescence label and/or an immobilization tag. These components were checked individually and by a mock selection.
An algorithm for speech segregation of co-channel speech (2009)

This paper introduces an algorithm to separate speech streams from a single-channel speech mixture. Most current speech segregation algorithms allocate speech regions to participating speakers depending on which speaker dominates in which spectro-temporal region. The proposed method is a different approach to speech segregation, in that it separates the participating speaker streams rather than decide in the favor of the dominating speaker. The algorithm depends on a lease-squares fitting approach to model the speech mixture as a sum of complex exponentials. The algorithm gives results that are better than an existent algorithm when tested on the same task. The performance on a different database yielded good segregation results, even for Target-to-Masker ratios as low as -15 dB. The algorithm has immense promise for improvement and practical implementation.
Focused In Vivo Genetic Analysis of Implanted Engineered Myofascial Constructs (2009)

Successfully engineering functional muscle tissue either in vitro or in vivo to treat muscle defects rather than using the host muscle transfer would be revolutionary. Tissue engineering is on the cutting edge of biomedical research, bridging a gap between the clinic and the bench top. A new focus on skeletal muscle tissue engineering has led investigators to explore the application of satellite cells (autologous muscle precursor cells) as a vehicle for engineering tissues either in vitro or in vivo. However, few skeletal muscle tissue-engineering studies have reported on successful generation of living tissue substitutes for functional skeletal muscle replacement. Our model system combines a novel aligned collagen tube and autologous skeletal muscle satellite cells to create an engineered tissue repair for a surgically created ventral hernia as previously reported [SA Fann, L Terracio, W Yan, et al., A model of tissue-engineered ventral hernia repair, J Invest Surg. 2006;19(3):193-205]. Several key features we specifically observe are the significant persistence of transplanted skeletal muscle cell mass within the engineered repair, the integration of new tissue with adjacent native muscle, and the presence of significant neovascularization. In this study, we report on our experience investigating the genetic signals important to the integration of neoskeletal muscle tissue. The knowledge gained from our model system applies to the repair of severely injured extremities, maxillofacial reconstructions, and restorative procedures following tumor excision in other areas of the body.
Structure-based development of novel sirtuin inhibitors (2011)

Sirtuins are NAD+-dependent protein deacetylases regulating metabolism, stress responses, and aging processes. Mammalia possess seven Sirtuin isoforms, Sirt1-7, which differ in their subcellular localization and in the substrate proteins they deacetylate. The physiological roles of Sirtuins and their potential use as therapeutic targets for metabolic and aging-related diseases have spurred interest in the development of small-molecule Sirtuin modulators. Here, we describe an approach exploiting the structures available for four human Sirtuins for the development of isoform-specific inhibitors. Virtual docking of a compound library into the peptide binding pockets of crystal structures of Sirt2, 3, 5 and 6 yielded compounds potentially discriminating between these isoforms. Further characterization in activity assays revealed several inhibitory compounds with little isoform specificity, but also two compounds with micromolar potency and high specificity for Sirt2. Structure comparison and the predicted, shared binding mode of the Sirt2-specific compounds indicate a pocket extending from the peptide-binding groove as target side enabling isoform specificity. Our family-wide structure-based approach thus identified potent, Sirt2-specific inhibitors as well as lead structures and a target site for the development of compounds specific for other Sirtuin isoform, constituting an important step toward the identification of a complete panel of isoform-specific Sirtuin inhibitors.
THE RATE OF BACTERICIDAL ACTION OF TRIETHYLENE GLYCOL VAPOR ON MICROORGANISMS DISPERSED INTO THE AIR IN SMALL DROPLETS12 (1949)

Journal Article THE RATE OF BACTERICIDAL ACTION OF TRIETHYLENE GLYCOL VAPOR ON MICROORGANISMS DISPERSED INTO THE AIR IN SMALL DROPLETS Get access WILLIAM LESTER, Jr., WILLIAM LESTER, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar O. H. ROBERTSON, O. H. ROBERTSON Search for other works by this author on: Oxford Academic PubMed Google Scholar THEODORE T. PUCK, THEODORE T. PUCK 3Department of Biophysics, University of ColoradoDenver, Colo. Search for other works by this author on: Oxford Academic PubMed Google Scholar HENRY WISE HENRY WISE WITH THE TECHNICAL ASSISTANCE or MABEL SMITH Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 50, Issue 2, September 1949, Pages 175–188, https://doi.org/10.1093/oxfordjournals.aje.a119352 Published: 01 September 1949 Article history Received: 16 May 1949 Published: 01 September 1949
The ability of atypical antipsychotic drugs vs. haloperidol to protect PC12 cells against MPP<sup>+</sup>‐induced apoptosis (2003)

The present study examined the effects of the atypical antipsychotic drugs clozapine, olanzapine, quetiapine and risperidone, on N-methyl-4-phenylpyridinium ion-induced apoptosis and DNA damage in PC12 cells, and explored the molecular mechanisms underlying these effects. Haloperidol, a typical antipsychotic drug, was used for comparison. Exposure of PC12 cells to 50 micro m N-methyl-4-phenylpyridinium ion for 24 h resulted in a 35-45% loss of cells in culture. Pretreatment with the aforementioned atypical antipsychotic drugs significantly reduced the N-methyl-4-phenylpyridinium ion-induced cell loss, whereas haloperidol (10-100 micro m) did not have this protective effect. Hoechst 33258 staining revealed the apoptotic nuclear features of the N-methyl-4-phenylpyridinium ion-induced cell death, and showed that the atypical antipsychotic drugs, but not haloperidol, effectively prevented PC12 cells from this N-methyl-4-phenylpyridinium ion-induced apoptosis. DNA fragmentation assays further confirmed the N-methyl-4-phenylpyridinium ion-induced nuclear fragmentation. Pretreatment with the atypical antipsychotic drugs completely prevented this nuclear fragmentation, whereas haloperidol only partially prevented it. In vitro oligonucleotide assays indicated an activation of a specific glycosylase that recognizes and cleaves bases (at the 8-hydroxyl-2-deoxyguanine site) that were damaged by N-methyl-4-phenylpyridinium ion. Pretreatment with the atypical antipsychotic drugs more effectively attenuated this N-methyl-4-phenylpyridinium ion-induced activation than did haloperidol. Northern blot analyses showed that the atypical antipsychotic drugs, but not haloperidol, blocked the N-methyl-4-phenylpyridinium ion-induced substantial increase of copper/zinc superoxide dismutase mRNA in PC12 cells. Atypical antipsychotic drugs slightly up-regulated the expression of copper/zinc superoxide dismutase mRNA, whereas haloperidol strongly increased the expression of copper/zinc superoxide dismutase mRNA. These data may account for the different therapeutic effects and side-effect profiles of typical and atypical antipsychotic drugs in schizophrenia.
Image Formation and Halo Removal in Diffraction Phase Microscopy with Partially Coherent Illumination (2014)

We present a quantitative model which describes the observed phase reductions and halo-effect in quantitative phase imaging systems under partial spatial coherence and provide a practical method to eliminate the halo and obtain accurate topography.
The voting model for people search (2009)

An expert search engine aims to assist users with their expertise need - instead of ranking documents, possible candidate experts in an enterprise organisation with relevant expertise are suggested in response to a query. This thesis investigates people search tasks such as expert search, and how persons can be ranked in response to a query, such that those with relevant expertise to the query are ranked first. The expertise areas of the persons are represented by documentary evidence of expertise, known as candidate profiles. The statement of this research work is that people search tasks in general and expert search in particular can be successfully and effectively modelled using a voting paradigm.
A corrugated capacitor cell (CCC) for megabit dynamic MOS memories (1983)

A new dRAM cell named "CCC" (Corrugated Capacitor Cell) has been successfully developed based on the one-device cell concept. This CCC is characterized by an etched-moat storage-capacitor extended into the substrate, resulting in an almost independent increase in storage capacitance without cell size enlargement. A typical value of 45 fF has been obtained with 4 × 8 µm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> CCC having a 2.5-µm deep moat and a capacitor insulator equivalent to 15 nm SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> in thickness. A signal of 200 mV is realized in 32 kbit dRAM operation with a folded-bit line arrangement having 128 bit identical CCC's. The CCC concept is promising for generations of 1 Mbit dRAM's and beyond.
Using content-derived names for configuration management (1997)

Configuration marragement of compiled sojiware artt~acts (programs, iibraries, icons, etc.) is a growing problem as sojtware reuse becomes more prevalent.For an application composed from reused libraries and modules to function correctly, ail of the required jiles must be available and be the correct version. In this paper, we present a simple scheme to address this problem: content-derived names (CDNS). Computing an object's mme automatically using digital signatures greatly eases the problem of disambiguating multiple versions of an object. By using content-derived names, developers can ensure that only those software components that have been tested together are permitted to run together.
Valproic acid, but not its non-teratogenic analogue 2-isopropylpentanoic acid, affects proliferation, viability and neuronal differentiation of the human teratocarcinoma cell line NTera-2. (1998)

The antiepileptic drug valproic acid (VPA) is an established human teratogen that affects neural development in human fetuses exposed to the drug during early pregnancy. The development of simple cell culture models that reflect normal neuronal development will be useful for the screening of neural developmental toxicity of new drugs and for the identification of the specific molecular targets for the teratogenic action. The present study tests a human NT2 cell line for its suitability to serve as such a model. Treatment with VPA, but not with its non-teratogenic-analogue, 2-isopropylpentanoic acid (IPPA), inhibited cell growth, had a cytotoxic effect and blocked retinoic acid-induced neuronal differentiation of NT2 cells. Differentiation was evaluated by immunostaining for neurofilament proteins, microtubule associated proteins-2 (MAP-2), tau and neural cell adhesion molecule, NCAM. However once differentiation had taken place, VPA did not revert this process, although it did affect neuronal aggregation and neurite fasciculation. These results suggest that the human NT2 cell line might be useful for identifying drugs affecting neuronal development in humans.