gebhart/patrepeval huggingface dataset:
Microsatellite Instability as a Biomarker for PD-1 Blockade (2016)

Initial results by Le and colleagues, which were published in the June 25, 2015 issue of the New England Journal of Medicine, report significant responses of cancers with microsatellite instability (MSI) to anti-PD-1 inhibitors in patients who failed conventional therapy. This finding fits into a broader body of research associating somatic hypermutation and neoepitope formation with response to immunotherapy, with the added benefit of relying on a simple, widely used diagnostic test. This review surveys the pathogenesis and prognostic value of MSI, diagnostic guidelines for detecting it, and the frequency of MSI across tumors, with the goal of providing a reference for its use as a biomarker for PD-1 blockade. MSI usually arises from either germline mutations in components of the mismatch repair (MMR) machinery (MSH2, MSH6, MLH1, PMS2) in patients with Lynch syndrome or somatic hypermethylation of the MLH1 promoter. The result is a cancer with a 10- to 100-fold increase in mutations, associated in the colon with poor differentiation, an intense lymphocytic infiltrate, and a superior prognosis. Diagnostic approaches have evolved since the early 1990s, from relying exclusively on clinical criteria to incorporating pathologic features, PCR-based MSI testing, and immunohistochemistry for loss of MMR component expression. Tumor types can be grouped into categories based on the frequency of MSI, from colorectal (20%) and endometrial (22%-33%) to cervical (8%) and esophageal (7%) to skin and breast cancers (0%-2%). If initial results are validated, MSI testing could have an expanded role as a tool in the armamentarium of precision medicine.
Activation of a Diphtheria Toxin A Gene by Expression of Human Immunodeficiency Virus-1 Tat and Rev Proteins in Transfected Cells (1991)

Expression of a gene encoding the diphtheria toxin A (DT-A) fragment, controlled by tissue specific regulatory elements, has previously been used to kill selected cell populations. Here, we have examined the feasibility of controlling DT-A expression using regulatory systems from the human immunodeficiency virus (HIV-1) genome. Plasmids were constructed which express either DT-A or, as a model system, the luciferase (luc) reporter gene, under control of HIV-1 long terminal repeat (LTR) sequences (-167 to +80). While trans-activation by expression of the viral protein Tat was demonstrated, significant basal expression was observed. To reduce basal expression, cis-acting negative regulatory elements from the env region of the HIV-1 genome were inserted in the 3' untranslated region of both the luc and DT-A constructs. This dramatically reduced basal expression from the HIV LTR, and now both viral regulatory proteins Tat and Rev were required for maximal trans-activation. Such regulation of DT-A expression might be therapeutically applied to selectively kill HIV-infected cells in acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC).
Detection and Identification of Mycobacterium Species Isolates by DNA Microarray (2003)

Rapid identification of Mycobacterium species isolates is necessary for the effective management of tuberculosis. Recently, analysis of DNA gyrase B subunit (gyrB) genes has been identified as a suitable means for the identification of bacterial species. We describe a microarray assay based on gyrB gene sequences that can be used for the identification of Mycobacteria species. Primers specific for a gyrB gene region common to all mycobacteria were synthesized and used for PCR amplification of DNA purified from clinical samples. A set of oligonucleotide probes for specific gyrB gene regions was developed for the identification of 14 Mycobacterium species. Each probe was spotted onto a silylated glass slide with an arrayer and used for hybridization with fluorescently labeled RNA derived from amplified sample DNA to yield a pattern of positive spots. This microarray produced unique hybridization patterns for each species of mycobacteria and could differentiate closely related bacterial species. Moreover, the results corresponded well with those obtained by the conventional culture method for the detection of mycobacteria. We conclude that a gyrB-based microarray can rapidly detect and identify closely related mycobacterial species and may be useful in the diagnosis and effective management of tuberculosis.
Differential Expression of Functional Protease-Activated Receptor-2 (PAR-2) in Human Vascular Smooth Muscle Cells (1998)

The protease-activated family of G protein-coupled receptors includes PAR-1 and PAR-3, which are activated by thrombin, and PAR-2, which is activated by trypsin and tryptase. PAR-2 has recently been shown to be expressed in human endothelial cells. In the present studies, we have examined the expression of PAR-2 in other cells, particularly vascular smooth muscle, and tested whether the receptors are functional. The results show that PAR-2 is present in human aorta and coronary artery smooth muscle cells, as well as in arteries traversing the walls of the small intestine. It was also detected in human keratinocytes, sweat glands, intestinal smooth muscle, and intestinal epithelium, but not at all in myocardial smooth muscle and only inconsistently in intestinal veins and venules. Activation of aortic smooth muscle cells in culture with PAR-2 peptide agonists caused a transient increase in the cytosolic Ca2+ concentration. In contrast, PAR-2 mRNA could not be detected in saphenous vein smooth muscle cells, and the same cells placed in culture showed little, if any, response to the PAR-2 agonist peptides. These observations show that PAR-2 is widely distributed in human vascular smooth muscle, particularly in arteries. However, this is not a universal finding and at least some venous smooth muscle cells, including those in saphenous veins, apparently do not express the receptor in detectable amounts.
Laboratory and Theoretical Evaluation of Corrosion-Inhibiting Emulsions (2001)

Summary Measurement and correlation of the typical properties of the corrosion-inhibiting emulsions that affect their placement and gradual decomposition in oil wells are presented. The mechanisms of the emulsion breakup and inhibitor release by shearing and heating are determined, formulated, and verified by experimental data. The viscosity, drying and stability processes, surface tension, repetitive film coating on tubing and casing walls, and inhibitor resolution of typical water-external and oil-external emulsions are correlated by relevant theories.
PennCNV: An integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data (2007)

Comprehensive identification and cataloging of copy number variations (CNVs) is required to provide a complete view of human genetic variation. The resolution of CNV detection in previous experimental designs has been limited to tens or hundreds of kilobases. Here we present PennCNV, a hidden Markov model (HMM) based approach, for kilobase-resolution detection of CNVs from Illumina high-density SNP genotyping data. This algorithm incorporates multiple sources of information, including total signal intensity and allelic intensity ratio at each SNP marker, the distance between neighboring SNPs, the allele frequency of SNPs, and the pedigree information where available. We applied PennCNV to genotyping data generated for 112 HapMap individuals; on average, we detected approximately 27 CNVs for each individual with a median size of approximately 12 kb. Excluding common rearrangements in lymphoblastoid cell lines, the fraction of CNVs in offspring not detected in parents (CNV-NDPs) was 3.3%. Our results demonstrate the feasibility of whole-genome fine-mapping of CNVs via high-density SNP genotyping.
New focusing and dispersive planar component based on an optical phased array (1988)

A novel focusing and dispersive component is presented which is based on a phased array of bent optical waveguides. It combines good optical properties with small dimensions and can be realised with (high-quality) optical lithography. Applications are (de)multiplexers, wavelength filters and polarisation splitters.
Molecular mechanism for analgesia involving specific antagonism of α9α10 nicotinic acetylcholine receptors (2006)

alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of alpha9alpha10 nAChRs is not known. Here we show that selective block (rather than stimulation) of alpha9alpha10 nAChRs is analgesic in an animal model of nerve injury pain. In addition, blockade of this nAChR subtype reduces the number of choline acetyltransferase-positive cells, macrophages, and lymphocytes at the site of injury. Chronic neuropathic pain is estimated to affect up to 8% of the world's population; the numerous analgesic compounds currently available are largely ineffective and act through a small number of pharmacological mechanisms. Our findings not only suggest a molecular mechanism for the treatment of neuropathic pain but also demonstrate the involvement of alpha9alpha10 nAChRs in the pathophysiology of peripheral nerve injury.
Cutting Edge: Deficiency in the E3 Ubiquitin Ligase Cbl-b Results in a Multifunctional Defect in T Cell TGF-β Sensitivity In Vitro and In Vivo (2006)

Mice deficient in the E3 ubiquitin ligase Cbl-b have CD28-independent T cells and develop autoimmunity. We previously reported that Cbl-b-/- CD4+CD25- T effector cells are resistant in vitro to the antiproliferative effects of CD4+CD25+ regulatory T cells and TGF-beta. We have now asked whether the resistance noted in Cbl-b-/- T cells is restricted solely to TGF-beta's antiproliferative effects, whether the TGF-beta resistance has in vivo relevance, and whether a defect can be identified in the TGF-beta signaling pathway. We now demonstrate the following: 1) in vitro, Cbl-b deficiency prevents the TGF-beta-mediated induction of Foxp3+ functional regulatory T cells; 2) in vivo, Cbl-b-/- mice show a significantly enhanced response to a tumor that is strictly TGF-beta regulated; and 3) Cbl-b-/- T effector cells have defective TGF-beta-mediated Smad2 phosphorylation. These studies are the first to document that the E3 ubiquitin ligase Cbl-b plays an integral role in T cell TGF-beta signaling, and that its absence results in multifunctional TGF-beta-related defects that have important disease-related implications.
Nonsurgical repigmentation therapies in vitiligo. Meta-analysis of the literature. (1998)

Class 3 corticosteroids and UV-B therapy are the most effective and safest therapies for localized and for generalized vitiligo, respectively.
A statistical model for microcellular multipath propagation environment (2002)

Multipath propagation characteristics are of great importance in evaluating the performance of digital systems and designing wireless links. This paper describes statistical multipath propagation modeling for microcells in indoor, pedestrian, and vehicular environments. The channel impulse response is measured to clarify the statistical characteristics in urban areas, residential areas and indoors. The measuring channel sounder is the sliding correlator using 30 Mbit/s PN code with center frequency of 2.6 GHz. The measurements clarify the features of delay profile, mean RMS (root mean square) delay spread and local (or instantaneous) RMS delay spread. Furthermore, tapped-delay-line parameters for multipath propagation simulators based on this modeling are proposed. The proposed model is applicable to the evaluation of transmission characteristics of wireless digital communication systems in multipath fading environments.
Adverse chemical effects on the plasma-deposited amorphous silicon carbide passivation layer of thermal ink-jet thin-film heaters (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdverse chemical effects on the plasma-deposited amorphous silicon carbide passivation layer of thermal ink-jet thin-film heatersP. L. Gendler and L. S. ChangCite this: Chem. Mater. 1991, 3, 4, 635–641Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://pubs.acs.org/doi/10.1021/cm00016a015https://doi.org/10.1021/cm00016a015research-articleACS PublicationsRequest reuse permissionsArticle Views91Altmetric-Citations1LEARN 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-Alertsclose Get e-Alerts
Investigation of Cyclobenzaprine Hydrochloride Release from Oral Osmotic Delivery Systems Containing a Water-Swellable Polymer (2002)

Oral osmotic delivery systems containing polyethylene oxide (PEO, a water-swellable polymer) were designed and the release of cyclobenzaprine hydrochloride (model drug) from the devices was investigated. The systems consisted of model drug, mannitol (osmotic agent), and increasing amounts of PEO surrounded by a semipermeable membrane drilled with a delivery orifice. There was a decrease in drug release rate with PEO in the core. This may be due to solubility-modulating properties of the polymer. Visual inspection of the devices with PEO showed significant swelling during dissolution testing. Swelling (internal pressure) may influence water inhibition rate into the core and subsequently drug release rate. The release rates were a function of membrane thickness. The release rates were independent of orifice size (range of 150-510 microns diameter) and hydrodynamic conditions for the devices. This would be advantageous in the delivery of drugs in man.
Context Effects and Inefficient Initiation at Non-AUG Codons in Eucaryotic Cell-Free Translation Systems (1989)

The context requirements for recognition of an initiator codon were evaluated in vitro by monitoring the relative use of two AUG codons that were strategically positioned to produce long (pre-chloramphenicol acetyl transferase [CAT]) and short versions of CAT protein. The yield of pre-CAT initiated from the 5'-proximal AUG codon increased, and synthesis of CAT from the second AUG codon decreased, as sequences flanking the first AUG codon increasingly resembled the eucaryotic consensus sequence. Thus, under prescribed conditions, the fidelity of initiation in extracts from animal as well as plant cells closely mimics what has been observed in vivo. Unexpectedly, recognition of an AUG codon in a suboptimal context was higher when the adjacent downstream sequence was capable of assuming a hairpin structure than when the downstream region was unstructured. This finding adds a new, positive dimension to regulation by mRNA secondary structure, which has been recognized previously as a negative regulator of initiation. Translation of pre-CAT from an AUG codon in a weak context was not preferentially inhibited under conditions of mRNA competition. That result is consistent with the scanning model, which predicts that recognition of the AUG codon is a late event that occurs after the competition-sensitive binding of a 40S ribosome-factor complex to the 5' end of mRNA. Initiation at non-AUG codons was evaluated in vitro and in vivo by introducing appropriate mutations in the CAT and preproinsulin genes. GUG was the most efficient of the six alternative initiator codons tested, but GUG in the optimal context for initiation functioned only 3 to 5% as efficiently as AUG. Initiation at non-AUG codons was artifactually enhanced in vitro at supraoptimal concentrations of magnesium.
Radiomics to Identify High-Risk Atherosclerotic Plaque From Computed Tomography (2017)

Measure what is measurable, and make measurable what is not so.
[Association of ENA-78, IP-10 and VEGF gene polymorphism with idiopathic pulmonary fibrosis]. (2009)

-156C allele for ENA-78 may be a risk factor of IPF and -1596T allele for IP-10 a beneficial factor of IPF. The VEGF (+405G/C) gene polymorphism has no effect upon the predisposition to IPF.
Pass-Through of Imported Input Prices to Domestic Producer Prices (2016)

Motivated by stylized facts pointing to a dominant role of imported inputs in transmitting external price shocks to domestic prices, this paper zooms in to study the pass-through of imported input costs to domestic producer prices. Our approach constructs effective input price indices from sector-level price data combined with sector-level information on input-output linkages. Applying an error correction model specification to sector-level output and input prices, the long-run pass-through rate of effective imported input costs to domestic producer prices is estimated to be around 70 percent in Korea and almost 100 percent in selected European countries.
Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA. (1989)

A general and efficient transfection procedure, based on compacted lipopolyamine-coated plasmids, has been developed. The active species is obtained by simple addition of excess synthetic lipospermine solution to the DNA and binds within minutes to the cell membrane. This technique has been developed on endocrine cells of the intermediate lobe of the pituitary as a general tool for physiological work on primary cells; it is not toxic and does not interfere with physiological regulations in melanotrope cells. A variety of eukaryotic cell cultures also have been transfected with success for transient and stable expression.
Resonant magnetotunneling through individual self-assembled InAs quantum dots (1996)

Resonant peaks are observed in the low-temperature current-voltage I(V) characteristics of a single-barrier GaAs/AlAs/GaAs diode with InAs quantum dots incorporated in the AlAs tunnel barrier. We argue that each peak arises from single-electron tunneling through a discrete zero-dimensional state of an individual InAs dot in the barrier. Each peak splits into sharp components for magnetic field B\ensuremath{\parallel}I; the I(V) curve probes the density of Landau-quantized states in the emitter-accumulation layer. A dot size of \ensuremath{\approxeq}10 nm was estimated from the diamagnetic peak shift for B\ensuremath{\perp}I. \textcopyright{} 1996 The American Physical Society.
Characterization of recombinant plant cinnamate 4‐hydroxylase produced in yeast (1994)

Helianthus tuberosus cinnamate 4-hydroxylase (CYP73 or CA4H), a member of the P450 superfamily which catalyses the first oxidative step of the phenylpropanoid pathway in higher plants by transforming cinnamate into p-coumarate, was expressed in the yeast Saccharomyces cerevisiae. The PCR-amplified CA4H open reading frame was inserted into pYeDP60 under the transcriptional control of a galactose-inducible artificial promoter. Engineered S. cerevisiae strains producing human P450 reductase or normal or overproduced amounts of yeast P450 reductase were transformed to express recombinant CA4H. When grown on galactose, yeast cells produced CA4H holoprotein bound to the endoplasmic reticulum membrane as judged from the reduced iron/carbon monoxide difference spectrum centered at 452 nm and from typical cinnamate 4-hydroxylase activity upon coupling with the different P450 reductases and NADPH. Some CA4H protein was found also addressed to the yeast mitochondria but as a low-activity form. The spectral and kinetic characterizations of the yeast-produced CA4H in different redox protein environments are presented using both assays on yeast microsomal fractions and bioconversions on living cells. Results indicate that the microsomal system constituted by the overexpressed yeast P450 reductase and CA4H is characterized by a 1:1 coupling between NADPH oxidation and cinnamate hydroxylation and by one of the highest turnover numbers reported for an NADPH-dependent P450 reaction. Based on spectral perturbation and inhibition studies, coumarate appeared to have no detectable affinity for the enzyme. A possible geometry of the substrate recognition pocket is discussed in the light of these data.
Home Care of a Malnourished AIDS Client (1994)

Many HIV positive clients experience malnutrition that may decrease the quality and length of life. The case study in this article includes study questions that provide the home healthcare nurse an opportunity to plan interventions that may increase nutrient intake.
IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis (2014)

Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. IL-17A is a proinflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study, we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. The 26-wk-old apolipoprotein E-deficient mice were fed a standard chow diet and treated either with IL-17A mAb (n = 15) or irrelevant Ig (n = 10) for 16 wk. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (p = 0.001) by reducing inflammatory burden and cellular infiltration (p = 0.01) and improved lesion stability (p = 0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, and sensitization of APCs toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a proinflammatory milieu and upregulation of molecules expressed by the IL-17A-induced macrophage subtype. In this study, we show that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in apolipoprotein E-deficient mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte/macrophage lineage. In addition, translational experiments underline the relevance for the human system.
Picoplatin overcomes resistance to cell toxicity in small-cell lung cancer cells previously treated with cisplatin and carboplatin (2010)

Our study demonstrates that picoplatin can overcome carboplatin and cisplatin resistance. The results suggest decreased platinum accumulation as a potential mechanism of platinum resistance in SCLC cells, provide candidate markers (e.g. several genes in the Hox, glutathione biosynthetic process, and MAGE families) that may serve as signatures for platinum resistance, support distinct effects of picoplatin on SCLC cells compared to other platinums, and provide a rationale to develop picoplatin for the treatment of recurrent SCLC following initial therapy with cisplatin or carboplatin.