gebhart/patrepeval huggingface dataset:
Direct Detection of Phospholamban and Sarcoplasmic Reticulum Ca-ATPase Interaction in Membranes Using Fluorescence Resonance Energy Transfer (2004)

We used fluorescence resonance energy transfer (FRET) to detect and quantitate the interaction of the sarcoplasmic reticulum Ca-ATPase (SERCA) with phospholamban (PLB) in membranes. PLB inhibits SERCA only at submicromolar Ca. It has been proposed that relief of inhibition at micromolar Ca is due to dissociation of the inhibitory complex. To test this hypothesis, we co-reconstituted donor-labeled SERCA and acceptor-labeled I40A-PLB (superinhibitory, monomeric PLB mutant) in membranes of defined lipid and protein composition, with full retention of Ca-dependent ATPase activity and inhibitory regulation by PLB. FRET from SERCA to PLB was measured as a function of membrane concentrations of PLB and SERCA, and functional activity was measured on the same samples. The data revealed clearly that the stoichiometry of binding is one PLB per SERCA, and that binding is a strict function of the ratio of total PLB to SERCA in the membrane. We conclude that the dissociation constant of PLB binding to SERCA is far less than physiological PLB membrane concentrations. Binding at low Ca (pCa 6.5), where I40A-PLB inhibits SERCA, was virtually identical to that at high Ca (pCa 5.0), where no inhibition was observed. However, the limiting energy transfer at saturating PLB was less at high Ca, indicating a greater donor-acceptor distance. We conclude that (a) the affinity of PLB for SERCA is so great that PLB is essentially a SERCA subunit under physiological conditions and (b) relief of inhibition at micromolar Ca is due to a structural rearrangement within the SERCA-PLB complex, rather than dissociation.
A novel self-aligned fabrication process for microwave static induction transistors in silicon carbide (2000)

A novel multiple-self-aligned fabrication process is developed for recessed gate microwave static induction transistors (SITs) in silicon carbide (SiC). This process is demonstrated by fabricating 4H-SiC SITs having record f/sub T/ of 7 GHz.
The electric field and current density in a low-pressure inductive discharge measured with different B-dot probes (1997)

The magnitude and relative phase of the time varying magnetic field in an inductively coupled discharge have been measured with two dB/dt (B-dot) probes: One B-dot probe was enclosed by a dielectric tube (as is commonly used in dB/dt measurements) while the other, a thin wire probe, was immersed directly into the plasma. Each probe was used to measure the radial and axial component of dB/dt. A comparison of rf electric fields and currents obtained by the two probes showed essentially different results. The disagreement is interpreted to be due to a large local disturbance of the plasma density and current caused by the dielectric tube.
Activation of central trigeminovascular neurons by cortical spreading depression (2010)

We propose that CSD constitutes a nociceptive stimulus capable of activating peripheral and central trigeminovascular neurons that underlie the headache of migraine with aura.
Cytotoxicity of a Perfluorocarbon Blood Substitute to Macrophages in Vitro (1983)

Murine macrophage and macrophage-depleted splenocyte cultures were incubated under ambient oxygen with a commercially available perfluorocarbon blood substitute. The perfluorocarbon preparation was found to be selectively cytotoxic to macrophages. This finding may be significant in view of the preliminary therapeutic usage of these preparations. In addition, perfluorocarbons may be useful as a means of selectively removing macrophages from tissue and organ cultures.
Expression of the Peptide Antibiotic Human β-Defensin 1 in Cultured Gingival Epithelial Cells and Gingival Tissue (1998)

Human beta-defensin-1 (hBD-1) is a member of the family of small cationic antimicrobial peptides that have been identified in several mucosal epithelia. Because human gingival epithelium is a site that is constantly challenged by oral microorganisms, we examined the expression of hBD-1 in human gingival epithelial and fibroblast cell cultures and tissue samples. Cell cultures were challenged with cell wall extracts of Porphyromonas gingivalis or Fusobacterium nucleatum, Escherichia coli lipopolysaccharide, tumor necrosis factor alpha, or phorbol myristate acetate. hBD-1 mRNA was detected in unstimulated and stimulated cultures by reverse transcription (RT)-PCR using several primer sets specific for hBD-1. Gingival epithelial cells, but not gingival fibroblasts, expressed a product of the predicted size for hBD-1 mRNA. The sequence of the PCR product was identical to that of hBD-1. hBD-1 mRNA expression was not significantly modulated by any of the stimulants tested. Human gingival tissues from noninflamed and inflamed sites were also analyzed by RT-PCR. hBD-1 mRNA was expressed in all tissue samples. The relative expression of hBD-1 mRNA was similar in noninflamed and inflamed tissues obtained from each of four patients undergoing treatment for periodontitis. However, the relative expression of hBD-1 mRNA varied in gingival biopsies obtained from 15 different normal individuals, and the relative hBD-1 expression was unrelated to interleukin-8 expression. Our findings show the constitutive expression of hBD-1 mRNA in cultured epithelial cells and gingival tissues but not gingival fibroblasts. These findings suggest that expression of hBD-1 may play a role as part of the innate host defenses in maintaining normal gingival health.
Homologous Recombination Based Gene Therapy (1999)

Homologous recombination based gene therapy has the potential to develop into a powerful therapeutic modality for genetic diseases. It can offer permanent expression and normal regulation of corrected genes in appropriate cells or organs and probably can be used for treating dominantly inherited diseases such as polycystic kidney disease.
Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor alpha gene induction. (1994)

Cells adapt to adverse environmental conditions through a wide range of responses that are conserved throughout evolution. Physical agents such as ionizing radiation are known to initiate a stress response that is triggered by the recognition of DNA damage. We have identified a signaling pathway involving the activation of phospholipase A2 and protein kinase C in human cells that confers x-ray induction of the tumor necrosis factor alpha gene. Treatment of human cells with ionizing radiation or H2O2 was associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolished radiation-mediated arachidonate production as well as the subsequent activation of protein kinase C and tumor necrosis factor alpha gene expression. These findings demonstrate that ionizing radiation-mediated gene expression in human cells is regulated in part by extranuclear signal transduction. One practical application of phospholipase A2 inhibitors is to ameliorate the adverse effects of radiotherapy associated with tumor necrosis factor alpha production.
The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. (2001)

The epithelial mucin MUC1 is overexpressed on the cell surface of many epithelial malignancies as well as on some B-cell lymphomas and multiple myelomas. Recently, we identified two HLA-A2-restricted T-cell epitopes derived from the MUC1 protein. To further extend the potential application of these peptides, we analyzed the expression of MUC1 on blast cells from patients with acute myelogenous leukemia (AML; n = 43) and several other hematological malignancies including acute lymphoblastic leukemia (n = 24), chronic lymphocytic leukemia (n = 36), hairy cell leukemia (n = 9), follicular lymphoma (n = 7), and multiple myeloma (n = 12). Using reverse transcription-PCR and MUC1-specific monoclonal antibodies, MUC1 expression was found in 67% of AML samples and 92% of myeloma samples. To analyze the presentation of MUC1 peptides by primary AML blasts, we induced MUC1-specific CTLs in vitro using peptide-pulsed dendritic cells from HLA-A2+ healthy donors as antigen-presenting cells. These CTLs efficiently lysed in an antigen-specific and HLA-A2-restricted manner not only target cells pulsed with the antigenic peptide but also tumor cell lines including multiple myeloma cells and primary AML blasts that constitutively expressed both MUC1 and HLA-A2. The specificity of the CTLs was confirmed in a cold target inhibition assay. Our data demonstrate that MUC1-derived peptides are tumor antigens in AML and several other hematological malignancies that could potentially be used for immunotherapeutic approaches.
Data compression on a database system (1985)

A general-purpose data-compression routine—implemented on the IMS database system—makes use of context to achieve better compression than Huffman's method applied character by character. It demonstrates that a wide variety of data can be compressed effectively using a single, fixed compression routine with almost no working storage.
MG-63 osteoblast-like cells enhance the osteoprotegerin expression of PC-3 prostate cancer cells. (2009)

The enhancement of the OPG expression in PC-3 cells by MG-63 cells is not mediated by IGF-1, IL-6 and TGFbeta1.
Synergistic Effects of Foretinib with HER-Targeted Agents in MET and HER1- or HER2-Coactivated Tumor Cells (2011)

The HER and MET receptor tyrosine kinases (RTK) are coactivated in a subset of human tumors. This study characterizes MET and HER expression and signaling in a panel of human tumor cell lines and the differential susceptibility of these cell lines to single agents or combinations of foretinib, a multikinase MET inhibitor, with HER-targeted agents, erlotinib or lapatinib. Most MET-amplified tumor lines without HER1 or HER2 amplification are sensitive to foretinib, whereas MET-amplified lines with HER1 or HER2 amplification are more sensitive to the combination of foretinib with lapatinib or erlotinib. Interestingly, MET-overexpressing tumor cell lines with HER1 or HER2 amplification also exhibited reduced sensitivity to lapatinib or erlotinib in the presence of hepatocyte growth factor (HGF), indicating MET activation can decrease the effectiveness of HER1/2 inhibitors in some cell lines. Consistent with this observation, the effect of HGF on lapatinib or erlotinib sensitivity in these cells was reversed by foretinib, other MET inhibitors, or siRNA to MET. Western blot analyses showed that combining foretinib with erlotinib or lapatinib effectively decreased the phosphorylation of MET, HER1, HER2, HER3, AKT, and ERK in these cells. Furthermore, HER2-positive advanced or metastatic breast cancer patients treated with lapatinib who had higher tumor MET expression showed shorter progression-free survival (19.29 weeks in MET-high patients vs. 28.14 weeks in MET-low patients, P < 0.0225). These data suggest that combination therapy with foretinib and HER-targeted agents should be tested as a treatment option for HER1- or HER2-positive patients with MET-amplified or -overexpressing tumors.
Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers (2015)

A(H1N1)pdm09 influenza A viruses predominated in the 2013-2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses.
The addition of 4,4,6-trimethyl-1,3,2-dioxaborinane to allenes (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe addition of 4,4,6-trimethyl-1,3,2-dioxaborinane to allenesRichard H. FishCite this: J. Am. Chem. Soc. 1968, 90, 16, 4435–4439Publication Date (Print):July 1, 1968Publication History Published online1 May 2002Published inissue 1 July 1968https://pubs.acs.org/doi/10.1021/ja01018a041https://doi.org/10.1021/ja01018a041research-articleACS PublicationsRequest reuse permissionsArticle Views255Altmetric-Citations33LEARN 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
Temperature-dependent Optical Properties of In0.34Ga0.66As(subscript 1-x)N(subscript x)/GaAs Single Quantum Well with High Nitrogen Content for 1.55μm Application Grown by Molecular Beam Epitaxy (2005)

The temperature dependence of optical properties of InGaAsN/GaAs single-quantum wells grown by solid source molecular beam epitaxy (MBE) with N contents varied from 0% to 5.3% was investigated by photoluminescence (PL). The evolution of the peak positions of InGaAs/GaAs sample are in agreement with the empirical Varshni model. However, pronounced temperature-dependent S-shaped peak positions were observed in PL spectra while increasing nitrogen concentration. The activation energy of InGaAsN/GaAs SQWs is observed to decrease with nitrogen incorporation, which is contrary to the expectation of the bandgap reduction. This phenomenon suggests that the existence of defect-related nonradiative processes is due to nitrogen incorporation. The results of measurement demonstrate that the nitrogen incorporation into the InGaAsN has strong influence not only on carrier localization but also on the optical quality. In addition, the growth of high nitrogen content (5.3%) shows that the InGaAsN might be the potential candidate for long-wavelength optoelectronic devices.
High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses (2012)

Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAF mutations have been observed in Langerhans cell histiocytosis (LCH). We investigated the frequency of BRAF mutations in several types of histiocytoses. Histology from 127 patients with histiocytoses were reviewed. Detection of BRAF(V600) mutations was performed by pyrosequencing of DNA extracted from paraffin embedded samples. Diagnoses of Erdheim-Chester disease (ECD), LCH, Rosai-Dorfman disease, juvenile xanthogranuloma, histiocytic sarcoma, xanthoma disseminatum, interdigitating dendritic cell sarcoma, and necrobiotic xanthogranuloma were performed in 46, 39, 23, 12, 3, 2, 1, and 1 patients, respectively. BRAF status was obtained in 93 cases. BRAF(V600E) mutations were detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other histiocytoses. Four patients with ECD died of disease. The high frequency of BRAF(V600E) in LCH and ECD suggests a common origin of these diseases. Treatment with vemurafenib should be investigated in patients with malignant BRAF(V600E) histiocytosis.
Enzyme-Activated Fluorogenic Probes for Live-Cell and in Vivo Imaging (2018)

Fluorogenic probes, small-molecule sensors that unmask brilliant fluorescence upon exposure to specific stimuli, are powerful tools for chemical biology. Those probes that respond to enzymatic catalysis illuminate the complex dynamics of biological processes at a level of spatiotemporal detail and sensitivity unmatched by other techniques. Here, we review recent advances in enzyme-activated fluorogenic probes for biological imaging. We organize our survey by enzyme classification, with emphasis on fluorophore masking strategies, modes of enzymatic activation, and the breadth of current and future applications. Key challenges such as probe selectivity and spectroscopic requirements are described alongside therapeutic, diagnostic, and theranostic opportunities.
Registration of 3-d intraoperative MR images of the brain using a finite-element biomechanical model (2001)

We present a new algorithm for the nonrigid registration of three-dimensional magnetic resonance (MR) intraoperative image sequences showing brain shift. The algorithm tracks key surfaces of objects (cortical surface and the lateral ventricles) in the image sequence using a deformable surface matching algorithm. The volumetric deformation field of the objects is then inferred from the displacements at the boundary surfaces using a linear elastic biomechanical finite-element model. Two experiments on synthetic image sequences are presented, as well as an initial experiment on intraoperative MR images showing brain shift. The results of the registration algorithm show a good correlation of the internal brain structures after deformation, and a good capability of measuring surface as well as subsurface shift. We measured distances between landmarks in the deformed initial image and the corresponding landmarks in the target scan. Cortical surface shifts of up to 10 mm and subsurface shifts of up to 6 mm were recovered with an accuracy of 1 mm or less and 3 mm or less respectively.
Sphingosine 1-Phosphate Activates Nuclear Factor-κB through Edg Receptors (2001)

Sphingosine 1-phosphate (S1P) exerts a variety of actions as a second messenger or as an agonist that binds to one or more members of the Edg family of G protein-coupled receptors. By using human embryonic kidney 293 cells, we show that S1P activates nuclear factor-kappa B (NF-kappa B) in a receptor-dependent fashion. Edg-3 and Edg-5, which are coupled to G(i), G(q), and G(13), affect activation of NF-kappa B, whereas Edg-1, which is coupled to G(i) alone, does not. We find that the activation of NF-kappa B requires protein kinase C and Ca(2+), probably downstream of G(q), but that the activation of Rho alone by S1P, whether through G(q) or G(13), does not translate into the activation of NF-kappa B. G beta gamma has little effect of its own but potentiates the activation of NF-kappa B achieved through other G proteins. We conclude that the activation of NF-kappa B by S1P is a receptor-mediated process that relies primarily on the activation of a phospholipase C by G(q) and secondarily on effector regulation through other G proteins.
The Spliceosome (1993)

The spliceosome is a large RNA-protein complex that catalyses the removal of introns from nuclear pre-mRNA. A wide range of biochemical and genetical studies shows that the spliceosome comprises three major RNA-protein subunits, the U1, U2 and [U4/U6.U5] small nuclear ribonucleoprotein particles (snRNPs), and an additional group of non-snRNP protein splicing factors. Rapid progress is being made in unravelling the interactions which take place between these factors during the splicing reaction. The emerging picture of the spliceosome reveals a highly dynamic structure that assembles on pre-mRNA transcripts in a stepwise pathway and is organised, at least in part, by complex RNA base-pairing interactions between the small nuclear RNAs (snRNAs) and the intron substrate. Many of these interactions can be detected both in mammalian and yeast spliceosomes, suggesting that the basic splicing mechanism is an ancient one that has been highly conserved during evolution.
Elicitation of Honest Preferences for the Assignment of Individuals to Positions (1983)

The problem of eliciting honest preferences from individuals who must be assigned to a set of positions is considered. Individuals know that they will be charged for the positions to which they are assigned. A set of prices that provide no incentive for the individual to misrepresent his preferences is suggested. It is shown that these prices constitute an element of the optimal solution to the dual of a linear programming assignment problem. Both the optimal allocation and the prices to be charged can be derived by solving two linear programming problems once preferences have been elicited. The procedure can usefully be viewed as a simulation of a competitive market under conditions where such a market cannot be expected to function well. It results in an efficient allocation where all resources are valued at their opportunity costs and "consumer surplus" is maximized; its outcome thus has the desirable properties of competitive market equilibria.
Treatment ofClostridium difficileInfection (2008)

Recent outbreaks of Clostridium difficile infection (CDI) in North America have been due to a more virulent, possibly more resistant strain that causes more-severe disease, making prompt recognition of cases and optimal management of infection essential for a successful therapeutic outcome. Treatment algorithms are presented to help guide the management of patients with CDI. Metronidazole has been recommended as initial therapy since the late 1990s and continues to be the first choice for all but seriously ill patients and those with complicated or fulminant infections or multiple recurrences of CDI, for whom vancomycin is recommended. Other options for recurrent CDI, such as probiotics and currently available anion-exchange resins, have limited efficacy and are potentially harmful. Intravenous immunoglobulin may benefit patients with refractory, recurrent, or severe disease, but no controlled data are available. Two antimicrobials available in the United States for other indications, nitazoxanide and rifaximin, have been used successfully for CDI treatment but, like metronidazole, lack United States Food and Drug Administration approval for this indication. Experimental treatments currently in clinical development include a toxin-binding polymer, tolevamer; 2 poorly absorbed antimicrobials, OPT-80 (formerly known as Difimicin) and ramoplanin; monoclonal antibodies; and a C. difficile vaccine.