gebhart/patrepeval huggingface dataset:
Voltage-dependent ion channels in small-cell lung cancer cells. (1989)

Small-cell carcinoma of the lung is a highly lethal form of cancer associated with a wide variety of paraneoplastic syndromes. Using the patch-clamp technique, we have directly demonstrated the presence of voltage-gated K+, Na+, and Ca2+ channels in three cell lines of human small-cell carcinoma, NCI-H128, NCI-H69, and NCI-H146. Whole-cell currents were measured from the tumor cells held at -80 mV and depolarized to -60 to +120 mV. Outward K+ current (IK), which was found in every cell tested, reached 1.58 +/- 0.12 nA (mean +/- SE, n = 24 cells) for H128 cells and 2.14 +/- 0.18 nA (n = 41) for H69 cells in response to a test potential of +80 mV. Unlike H69 and H128 tumor cells, IK from H146 cells occasionally exhibited partial inactivation during the 60-ms pulse length and reached 0.94 +/- 0.15 nA (n = 18) in response to a +80 mV test potential. IK from each of the cell lines was significantly reduced by 4-aminopyridine and tetraethylammonium. The rapidly inactivating inward Na+ current (INa), recorded in H146 cells and about 30% of the H69 and H128 cells tested, demonstrated a peak amplitude of 58 +/- 6 pA (n = 11) at 0 mV and a reversal potential of 47 +/- 2 mV (n = 11). Externally applied tetrodotoxin quickly suppressed INa. For the H128 and H69 tumor cells, inward Ca2+ current (ICa), observed in about 25% of the cells exposed to 10 mM [Ca2+]o, peaked at 5.1 +/- 0.4 ms (n = 5) with an amplitude of 46 +/- 14 pA (n = 5) at +20 mV and partially inactivated over the 40-ms depolarization. In H128 cells exposed to isotonic Ba2+ (110 mM), inward currents with time courses similar to those of ICa were recorded. Nearly all H146 tumor cells demonstrated a significant inward Ca2+ current which peaked with an amplitude of 93 +/- 16 pA (n = 26) at +30 to +40 mV in the presence of 10 mM [Ca2+]o. Application of test potentials 2 s in duration revealed that H146 ICa inactivated in a voltage-dependent manner with a time constant on the order of seconds. Adjustment of the holding potential from -80 mV to -40 mV had no observable effect on the amplitude of the evoked current. These voltage-dependent ion channels may have integral roles in several small-cell carcinoma bioelectric phenomena, including secretion, resting membrane potential, and action potential generation.(ABSTRACT TRUNCATED AT 400 WORDS)
Systemic Inflammatory Response in Acute Cholangitis and after Subsequent Treatment (2000)

There is a considerable systemic inflammatory response during cholangitis, which is dramatically reduced one week after endoscopic treatment.
Preparation of Spirocyclic Polyethers by Intramolecular Heck Reactions (1994)

The first examples of forming spirocyclic polyethers by multiple Heck cyclizations are reported.The formation of carbon-carbon bonds is central to synthetic organic chemistry.In recent years, palladium catalyzed insertions of aryl and alkenyl halides and triflates (Heck reactions) have emerged as unusually versatile reactions for carbon-carbon bond formation.l.2 Inaamolecular insertions are particularly valuable, since they take place with a wide variety of substituted alkenes.3Work in this area from our laboratories has focused on the remarkable ability of inaamolecular Heck reactions to forge quaternary carbon centers (e.g., 1 -t 2).4The power of intramolecular Heck reactions is highlighted by our recent use of this chemisuy as the key strategic element of concise total syntheses of several structurally diverse natural product^.^Since multiple cyclizations that proceed in a spirocyclic mode have proven to be particularly efficient,Zd we were interested in seeing if s p i n heterocycles could be prepared also in this manner.Our initial investigations of this sequence for the synthesis of spirocyclic polyethers (3 + 4) are the subject of this report -~ **Dedicated with respect to Dr.
TRILL using Pseudo-Wire Emulation (PWE) Encapsulation (2005)

A new layer of encapsulation is required with RBridges. This layer
must contain at least a time-to-live and an RBridge identifier field.
This document proposes that the reuse of the encapsulation defined by
PWE3 for encapsulation of Ethernet frames over an MPLS packet switched
network.
Elongation factor 2 mutants deficient in diphthamide formation show temperature-sensitive cell growth. (1994)

Protein synthesis elongation factor 2 (EF-2) from eukaryotes contains an unusual modified histidine residue, termed diphthamide. Diphthamide has been shown to be a site of ADP-ribosylation by bacterial toxins, but its function remains obscure. We expressed mutant genes of EF-2 with substitutions of 19 other amino acids for His-699, which is modified to diphthamide, in yeast cells and found that they can be classified into three groups. In the first group (Group 1), replacement of His-699 by the basic amino acid Arg or Lys showed not only loss of EF-2 activity but also inhibitory effects on the growth of cells co-expressing wild-type EF-2. In the second group (Group 2), replacement with Gly, Pro, Ser, or Asp resulted in nonfunctional EF-2, but it did not affect the growth of cells co-expressing wild-type EF-2. In the third group (Group 3), replacement by one of the other 13 amino acids resulted in a functional EF-2. In the Group 3 mutants, EF-2 was not ribosylated by diphtheria toxin, indicating that the mutant EF-2s did not form diphthamide. However, the viable cells grew more slowly than cells expressing wild-type EF-2 and showed temperature sensitivities. This result suggests that diphthamide may confer heat resistance on EF-2, although it still may be active without diphthamide at a normal temperature.
Machine Learning Classification of Buildings for Map Generalization (2017)

A critical problem in mapping data is the frequent updating of large data sets. To solve this problem, the updating of small-scale data based on large-scale data is very effective. Various map generalization techniques, such as simplification, displacement, typification, elimination, and aggregation, must therefore be applied. In this study, we focused on the elimination and aggregation of the building layer, for which each building in a large scale was classified as “0-eliminated,” “1-retained,” or “2-aggregated.” Machine-learning classification algorithms were then used for classifying the buildings. The data of 1:1000 scale and 1:25,000 scale digital maps obtained from the National Geographic Information Institute were used. We applied to these data various machine-learning classification algorithms, including naive Bayes (NB), decision tree (DT), k-nearest neighbor (k-NN), and support vector machine (SVM). The overall accuracies of each algorithm were satisfactory: DT, 88.96%; k-NN, 88.27%; SVM, 87.57%; and NB, 79.50%. Although elimination is a direct part of the proposed process, generalization operations, such as simplification and aggregation of polygons, must still be performed for buildings classified as retained and aggregated. Thus, these algorithms can be used for building classification and can serve as preparatory steps for building generalization.
URLs for Telephone Calls (2000)

This document specifies URL (Uniform Resource Locator) schemes tel, fax and modem for specifying the location of a terminal in the phone network and the connection types (modes of operation) that can be used to connect to that entity. This specification covers voice calls (normal phone calls, answering machines and voice messaging systems), facsimile (telefax) calls and data calls, both for POTS and digital/mobile subscribers.
Angiopoietin-2 specific CVX-060 inhibits tumor growth cooperatively with chemotherapy (2008)

2493 Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are ligands of the endothelial cell receptor Tie2. Ang-1 is essential for maintaining stable vasculature. In remodeling endothelial cells, Ang-2 serves as an endogenous Ang-1 antagonist. Ang-2 promotes the dissociation of pericytes from existing blood vessels, and results in unstable blood vessels, which can proliferate and migrate to form new blood vessels in the presence of VEGF. Ang-2 over-expression in many cancers correlates with more invasive disease and poorer prognosis. CVX-060, a specific Ang-2 binding CovX-Body TM , was produced by fusing a chemically modified pharmacophore to the Fab binding site of a specially designed antibody. CVX-060 blocked Ang-2-Tie2 interaction with an IC 50 of 1nM. The anti-tumor activity of CVX-060 was evaluated in staged Colo-205. Significant reduction in tumor growth ( P P P + CD14 + or CD11b + cell number examined by immunohistochemistry were reduced by 76% in CVX-060 treated tumors compared to the Vehicle group ( P TM CVX-060 can effectively reduce Ang-2 protein level and Tie2 + macrophages inside the tumor mass, and inhibit tumor angiogenesis and growth. Significant combination benefit was also observed with other standard of care agents.
Novel pristinamycin‐responsive expression systems for plant cells (2001)

Novel gene regulation systems were designed for plant cells responsive to the streptogramin antibiotic pristinamycin. The pristinamycin-repressible plant gene regulation concept (PIPpOFF) is based on a transcriptional activator (PIT) which consists of the Pip protein, the repressor of the pristinamycin resistance operon of Streptomyces coelicolor, fused to the VP16 transactivation domain of the Herpes simplex virus. PIT mediates pristinamycin-repressible activation of a synthetic plant promoter (P(pPIR)) in tobacco cells consisting of a nine Pip-binding site-containing artificial operator (PIR3) placed upstream of a TATA-box derived from the cauliflower mosaic virus 35S promoter (P(CaMV35S)). Pristinamycin interferes with induction by negatively regulating the DNA-binding capacity of the Pip moiety of PIT. A second, streptogramin-inducible plant gene regulation system (PIPpON) was constructed by combining Pip expression with a plant-specific pristinamycin-inducible promoter (P(pPIRON)). P(pPIRON) consists of a PIR3 module cloned downstream of the strong constitutive plant promoter P(CaMV35S). As in the native Streptomyces configuration, Pip binds to its cognate sequence within P(pPIRON) in the absence of regulating antibiotic and silences the chimeric plant promoter. Upon addition of pristinamycin, Pip is released from the PIR3 operator and full P(CaMV35S)-driven expression of desired plant genes is induced. The PIPpOFF and PIPpON systems performed well in Nicotiana tabacum suspension cultures and promise to provide an attractive extension of existing plant gene regulation technology for basic plant research or biopharmaceutical manufacturing using plant tissue culture.
Monoclonal antibodies specific for O-antigenic polysaccharides of Shigella flexneri: clones binding to II, II:3,4, and 7,8 epitopes (1983)

Hybrid cells producing monoclonal antibodies against the O-antigens of Shigella flexneri were obtained by polyethylene glycol-mediated fusion of myeloma cells and lymphocytes from BALB/c mice immunized with whole heat-killed S. flexneri bacteria of serotypes 2a and 2b. Clones were selected for their binding specificity to structurally defined S. flexneri lipopolysaccharides (LPS). The following three groups were identified as recognizing three different epitopes: monoclonal antibodies binding to (i) S. flexneri LPS with the II:3,4 antigens, (ii) S. flexneri LPS with the II:3,4 antigens and the II:7,8 antigens, and (iii) S. flexneri LPS with the 7,8 group antigen only. Of cloned and characterized antibodies, more than 90% had either the mu or gamma 3 heavy chain and 98% had the kappa light chain. The exquisite specificity of each monoclonal antibody preparation was in complete contrast to the polyclonal specificities seen in sera from immunized rabbits. Even absorbed rabbit S. flexneri typing sera contained antibodies reacting with several different LPS, i.e., they were not type antigen specific. Ascites from immunoglobulin G monoclonal antibody preparations representing the three different specificities were used for sensitizing Staphylococcus aureus Cowan 1 bacteria and were used in coagglutination. In testing 211 clinical isolates of all different serotypes of S. flexneri, the reagents were shown to be sensitive and specific in correctly identifying all S. flexneri II and 7,8 antigen-containing strains with no false positives. Two isolated immunoglobulin M antibody clones specific for the II:3,4 and 7,8 antigens were used as successfully for identification by direct slide agglutination. These results suggest that the monoclonal reagents are superior to conventional typing antisera.
The Economic Impact of Pandemic Influenza in the United States: Priorities for Intervention (1999)

We estimated the possible effects of the next influenza pandemic in the United States and analyzed the economic impact of vaccine-based interventions. Using death rates, hospitalization data, and outpatient visits, we estimated 89,000 to 207,000 deaths; 314,000 to 734,000 hospitalizations; 18 to 42 million outpatient visits; and 20 to 47 million additional illnesses. Patients at high risk (15% of the population) would account for approximately 84% of all deaths. The estimated economic impact would be US$71.3 to $166.5 billion, excluding disruptions to commerce and society. At $21 per vaccinee, we project a net savings to society if persons in all age groups are vaccinated. At $62 per vaccinee and at gross attack rates of 25%, we project net losses if persons not at high risk for complications are vaccinated. Vaccinating 60% of the population would generate the highest economic returns but may not be possible within the time required for vaccine effectiveness, especially if two doses of vaccine are required.
Corticotropin Releasing Factor (CRF) Receptor Modulators:  Progress and Opportunities for New Therapeutic Agents (2000)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTCorticotropin Releasing Factor (CRF) Receptor Modulators: Progress and Opportunities for New Therapeutic AgentsPaul J. Gilligan, David W. Robertson, and Robert ZaczekView Author Information DuPont Pharmaceuticals Company, Experimental Station, P.O. Box 80500, Wilmington, Delaware 19880-0500 Cite this: J. Med. Chem. 2000, 43, 9, 1641–1660Publication Date (Web):April 18, 2000Publication History Received30 November 1999Published online18 April 2000Published inissue 1 May 2000https://pubs.acs.org/doi/10.1021/jm990590fhttps://doi.org/10.1021/jm990590freview-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views722Altmetric-Citations147LEARN 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 SUBJECTS:Antagonists,Peptides and proteins,Receptors,Rodent models,Stress Get e-Alerts
The activity and kinetic properties of mevalonate kinase in superovulated rat ovary (1970)

Methods are described for the assay and partial purification of mevalonate kinase from superovulated rat ovary. The total activity of mevalonate kinase in superovulated rat ovary was 1.6+/-0.14units/g wet wt.; it was unchanged by the administration of luteinizing hormone in vivo. The K(m) of a partially purified preparation of mevalonate kinase for dl-Mevalonate was 3.6+/-0.5mum; its K(m) for MgATP(2-) was 120+/-7.7mum. The enzyme was inhibited by geranyl pyrophosphate and farnesyl pyrophosphate, but not by isopentenyl pyrophosphate or 3,3'-dimethylallyl pyrophosphate. dl-mevalonate 5-phosphate inhibited at high concentrations. With both geranyl pyrophosphate and farnesyl pyrophosphate the inhibition was competitive with respect to MgATP(2-). The K(i) for inhibition by geranyl pyrophosphate was 1.3+/-0.2mum; the K(i) for inhibition by farnesyl pyrophosphate was 1.0+/-0.3mum. These findings are discussed with reference to the control by luteinizing hormone of steroidogenesis from acetate.
Masking and Discrimination (1966)

With the same experimental technique, two sets of related experiments have been performed. In one, a band of random noise is used to mask a pure tone. In the other experiment, the intensity difference limen for the band of noise has been determined. Thresholds for masking and discrimination were obtained with help of a Békésy audiometer. A large range of bandwidths (5–12 000 cps) and five central frequencies (500, 1000, 2000, 4000, and 8000 cps) have been employed. Both sets of data agree qualitatively with data appearing in the literature. From the discrimination data, it appears that, for small bandwidths, inherent intensity fluctuations of bands of noise determine the maximum intensity discrimination. These fluctuations should influence the masking situation to the same degree. The similarity of masking and discrimination thresholds in the region of small bandwidth lends support to this prediction. Thus, it is argued why masking data should not be judged in terms of a fixed standard (as Fletcher has done) in order to arrive at values for the critical bandwidth. If one judges masking data in terms of the discriminatory power that the ear exhibits for the masking noise employed, one arrives at critical-bandwidth data much more in line with generally accepted data. The accuracy with which these can be determined is so poor that one should consider masking experiments of this kind as totally unsuited to measure the critical bandwidth.
A palladium-catalyzed synthesis of ketones from acid chlorides and organozinc compounds (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA palladium-catalyzed synthesis of ketones from acid chlorides and organozinc compoundsRoger A. GreyCite this: J. Org. Chem. 1984, 49, 12, 2288–2289Publication Date (Print):June 1, 1984Publication History Published online1 May 2002Published inissue 1 June 1984https://pubs.acs.org/doi/10.1021/jo00186a043https://doi.org/10.1021/jo00186a043research-articleACS PublicationsRequest reuse permissionsArticle Views583Altmetric-Citations71LEARN 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
Extracellular Monomeric Tau Protein Is Sufficient to Initiate the Spread of Tau Protein Pathology (2014)

Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live-cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau-derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau.
Molecular Mechanisms of Cardiovascular Toxicity of Targeted Cancer Therapeutics (2010)

In 2002, Hoshijima and Chien drew largely theoretical parallels between the dysregulation of the signaling pathways driving cancer and those driving cardiac hypertrophy (Hoshijima M, Chien KR. J Clin Invest. 2002;109:849-855). On the surface, this statement appeared to stretch the limits of reason, given the fact that cancer cells are known for their proliferative capacity, and adult cardiomyocytes are, except under unusual circumstances, terminally differentiated and incapable of re-entering the cell cycle. However, on closer examination, there are numerous parallels between signaling pathways that drive tumorigenesis and signaling pathways that regulate hypertrophic responses and survival in cardiomyocytes. Indeed, this issue appears to be at the core of the cardiotoxicity (often manifest as a dilated cardiomyopathy) that can result from treatment with agents typically referred to as "targeted therapeutics," which target specific protein kinases that are dysregulated in cancer. Herein, we examine the cardiotoxicity of targeted therapeutics, focusing on the underlying molecular mechanisms, thereby allowing an understanding of the problem but also allowing the identification of novel, and sometimes surprising, roles played by protein kinases in the heart.
Matched-Transmission Technique for Channels With Intersymbol Interference (1972)

A new transmission scheme for channels with intersymbol interference named "matched-transmission (MT) technique" is proposed. An implementation of the MT system is presented and its relations with conventional techniques are described. It is shown that the partial response scheme is a special case of our new technique. The performance of the MT technique is discussed from the view point of the output signal-to-noise ratio and the system is shown to attain asymptotically the bound performance predicted by the information theory.
Humoral immune response in hens naturally infected withSalmonellaEnteritidis against outer membrane proteins and other surface structural antigens (2004)

A simple procedure for obtaining surface exposed antigens of Salmonella Enteritidis is described. A heat treatment of whole bacteria in saline solution induced the release of small membrane vesicles containing outer membrane components as well as surface appendage components, such as fimbriae and flagellin. The characterization of the structural components of this extract, called HE, was established by SDS-PAGE and immunoblotting using polyclonal and monoclonal specific antibodies. Five major groups of proteins were identified: flagellin, porins, OmpA, SEF21 and SEF14 fimbriae. The immunogenicity of these proteins was studied by immunoblotting with serum samples from naturally infected hens. Flagellin, porins, OmpA, SEF14 and SEF21 fimbriae were immunogenic in the S. Enteritidis infected hens (frequency of reactants: 47.3, 97.3, 64.7, 50.0 and 60.8%, respectively); porins also reacted with sera from non infected hens (66.7%). The immunogenicity of these antigens in infected birds provide promise that they may serve as components of an effective subcellular vaccine for poultry salmonellosis.