gebhart/patrepeval huggingface dataset:
Molecular cloning of nonspecific cross-reacting antigens in human granulocytes (1991)

To clarify the molecular structures of nonspecific cross-reacting antigens (NCAs), a family of glycoproteins antigenically related to carcinoembryonic antigen (CEA), in human granulocytes, we have screened a cDNA library of human leukocytes using a cDNA probe for the N-terminal domain (domain-N) of NCA-50, an NCA species in tumor cells. In 95 positive clones randomly selected, we identified six NCA or NCA-related cDNA clones including NCA-50, biliary glycoprotein protein a, and W272 (CGM6) which have previously been reported, and three new clones, W236, W264, and W282, encoding three novel NCA species. W236 and W264 consist of a domain-N, a putative transmembrane domain, and a possible cytoplasmic domain. The domain-N of W264 is 89% similar to that of NCA-50 at amino acid level, whereas the domain-N of W236 is only 49 and 43% similar to those of NCA-50 and pregnancy-specific beta 1-glycoprotein-11 (PSG11), respectively, indicating that W236 belongs to a new subfamily within the CEA family. The third clone W282 encodes a protein consisting of a domain-N virtually identical to that of W264 and a short hydrophilic C-terminal domain. W264 and W282 seem to be derived from a single gene by alternative splicing of RNA. These three new species are particularly unique in respect that they lack the repetitive immunoglobulin-related domains that have been universally found in the human CEA gene family members. The biochemical and immunochemical properties of the recombinant proteins of these cDNA clones, however, did not coincide with those of six NCA species previously identified in granulocytes at protein level, suggesting that, in granulocytes, there exist at least 12 NCA or NCA-related species whose expression is under complex control.
Multilingual acoustic models for speech recognition and synthesis (2004)

In this paper, we review the design of a common phone alphabet for up to fifteen languages and describe its application in two important components of a seamless multilingual conversational system, namely speech recognition and synthesis. We report on experiments that demonstrate the advantages of multilingual acoustic models both for the recognition of foreign names and non-native speech, and describe the usefulness of a common phone alphabet for the construction of unit selection based mono- and bilingual speech synthesis systems.
In vitro efficacy of immuno-chemotherapy with anti-EGFR human Fab-Taxol conjugate on A431 epidermoid carcinoma cells (2007)

The aims of this study were to generate a human Fab fragment against EGFR; conjugate it to paclitaxel (Taxol) as an immuno-chemotherapy agent; and investigate its in vitro anti-tumor efficacy on A431 epidermoid carcinoma cells. A431 cells (EGFR-positive), NIH 3T3 cells (EGFR-negative), and purified EGFR were used for subtractive panning on a human naïve Fab phage library to generate a human anti-EGFR Fab fragment that binds the EGFR extracellular domain in native conformation and subsequently internalizes it into the cytosol. The Fab was then conjugated with the chemotherapeutic Taxol, and cell proliferation inhibition and apoptosis (TUNEL) assays were conducted to determine the effect of this Fab-drug conjugate on A431 cells. The specificity and internalization property of this Fab were characterized by immunoprecipitation, fluorescence staining, flow cytometry, and Hum-Zap assay. The binding affinity to purified EGFR was 30 nM. The Fab-Taxol conjugate inhibited A431 cell proliferation at low concentrations and in a dose-responsive manner; more than 70% inhibition was observed at 52 pM. Furthermore, almost 100% of cells underwent apoptosis after treatment with Fab-Taxol at 26 pM for 48 hours. Our findings suggest that this Fab-Taxol conjugate could be a potential immuno-chemotherapeutic drug for clinical treatment of EGFR-overexpressing tumors.
Preventing data errors with continuous testing (2015)

Today, software systems that rely on data are ubiquitous, and ensuring the data's quality is an increasingly important challenge as data errors result in annual multi-billion dollar losses. While software debugging and testing have received heavy research attention, less effort has been devoted to data debugging: identifying system errors caused by well-formed but incorrect data. We present continuous data testing (CDT), a low-overhead, delay-free technique that quickly identifies likely data errors. CDT continuously executes domain-specific test queries; when a test fails, CDT unobtrusively warns the user or administrator. We implement CDT in the ConTest prototype for the PostgreSQL database management system. A feasibility user study with 96 humans shows that ConTest was extremely effective in a setting with a data entry application at guarding against data errors: With ConTest, users corrected 98.4% of their errors, as opposed to 40.2% without, even when we injected 40% false positives into ConTest's output. Further, when using ConTest, users corrected data entry errors 3.2 times faster than when using state-of-the-art methods.
Evaluation of optical coherence quantitation of analytes in turbid media by use of two wavelengths (1999)

We introduce a novel method for determining analyte concentration as a function of depth in a highly scattering media by use of a dual-wavelength optical coherence tomography system. We account for the effect of scattering on the measured attenuation by using a second wavelength that is not absorbed by the sample. We assess the applicability of this technique by measuring the concentration of water in an Intralipid phantom, using a probe wavelength of 1.53 microm and a reference wavelength of 1.31 microm. The results of our study show a strong correlation between the measured absorption and the water content of the sample. The accuracy of the technique, however, was limited by the dominance of scattering over absorption in the turbid media. Thus, although the effects of scattering were minimized, significant errors remained in the calculated absorption values. More-accurate results could be obtained with the use of more powerful superluminescent diodes and a choice of wavelengths at which absorption effects are more significant relative to scattering.
Measurements of cells in culture by scanning acoustic microscopy (1990)

A novel method allowing the determination of thickness, attenuation and impedance of both living and fixed cells in culture using a single image recorded with a scanning acoustic microscope is described. The method is based on the recording of the image data locating the surface of the cell far below the geometric focus. In this way only the normal incident acoustic wave is used for image formation. Higher values of impedance and attenuation coefficients were found in the cell periphery than in the central part of the cell. This phenomenon is suggested to be due to the different organization of cytoskeletal elements.
Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice (1991)

Indole-3-carbinol (I3C) is a potent inducer of cytochrome P450 enzymes in many species, including humans. We therefore studied alterations in the cytochrome P450-dependent metabolism of estradiol in different strains of mice consuming I3C in semisynthetic powdered diets at doses ranging from 250 to 5000 p.p.m. (34-700 mg/kg/day) for different periods of time. In short-term metabolic studies (3 weeks), wet liver weight increased in SW and C3H/OuJ mice in a dose-responsive manner. Dietary I3C increased the cytochrome P450 content measured in hepatic microsomes, as well as the extent of estradiol 2-hydroxylation, up to 5-fold. In a long-term feeding experiment (8 months), female C3H/OuJ mice consumed synthetic diets containing I3C at 0, 500 or 2000 p.p.m. Mammary tumor incidence and multiplicity were significantly lower at both doses of I3C, and tumor latency was prolonged in the high-dose group. We conclude that I3C is an inducer of hepatic P450-dependent estrogen metabolism in mice, and that it is chemopreventive in the C3H/OuJ mouse mammary tumor model. This protective effect may be mediated in part by the increased 2-hydroxylation and consequent inactivation of endogenous estrogens.
An Annotated Corpus of Relational Strategies in Customer Service (2017)

We create and release the first publicly available commercial customer service corpus with annotated relational segments. Human-computer data from three live customer service Intelligent Virtual Agents (IVAs) in the domains of travel and telecommunications were collected, and reviewers marked all text that was deemed unnecessary to the determination of user intention. After merging the selections of multiple reviewers to create highlighted texts, a second round of annotation was done to determine the classes of language present in the highlighted sections such as the presence of Greetings, Backstory, Justification, Gratitude, Rants, or Emotions. This resulting corpus is a valuable resource for improving the quality and relational abilities of IVAs. As well as discussing the corpus itself, we compare the usage of such language in human-human interactions on TripAdvisor forums. We show that removal of this language from task-based inputs has a positive effect on IVA understanding by both an increase in confidence and improvement in responses, demonstrating the need for automated methods of its discovery.
Wortmannin-sensitive Trafficking Pathways in Chinese Hamster Ovary Cells (1996)

Phosphatidylinositol (PI) 3'-kinases are a family of lipid kinases implicated in the regulation of cell growth by oncogene products and tyrosine kinase growth factor receptors. The catalytic subunit of the p85/p110 PI 3'-kinase is homologous to VPS-34, a phosphatidylinositol-specific lipid kinase involved in the sorting of newly synthesized hydrolases to the yeast vacuole. This suggests that PI 3'-kinases may play analogous roles in mammalian cells. We have measured a number of secretory and endocytic trafficking events in Chinese hamster ovary cells in the presence of wortmannin, a potent inhibitor of PI 3'-kinase. Wortmannin caused a 40-50% down-regulation of surface transferrin receptors, with a dose dependence identical to that required for maximal inhibition of the p85/p110 PI 3'-kinase in intact cells. The redistribution of transferrin receptors reflected a 60% increase in the internalization rate and a 35% decrease in the recycling rate. Experiments with fluorescent transferrin showed that entry of transferrin receptors into the recycling compartment and efflux of receptors out of the compartment were slowed by wortmannin. Wortmannin altered the morphology of the recycling compartment, which was more vesiculated than in untreated cells. Using Semliki Forest virus as a probe, we also found that delivery of the endocytosed virus to its lysosomal site of degradation was slowed by wortmannin, whereas endosomal acidification was unaffected. In contrast to these effects on endocytosis and recycling, wortmannin did not affect intracellular processing of newly synthesized viral spike proteins. Wortmannin did induce missorting of the lysosomal enzyme cathepsin D to the secretory pathway, but only at a dose 20-fold greater than that required to inhibit p85/p110 PI 3'-kinase activity or to redistribute transferrin receptors. Our data demonstrate the presence of wortmannin-sensitive enzymes at three distinct steps of the endocytic cycle in Chinese hamster ovary cells: internalization, transit from early endosomes to the recycling and degradative compartments, and transit from the recycling compartment back to the cell surface. The wortmannin-sensitive enzymes critical for endocytosis and recycling are distinct from those involved in sorting newly synthesized lysosomal enzymes.
The Syk Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of EBV-Associated Lymphoma (2016)

Abstract Epstein-Barr virus (EBV) is associated with the development of several cancers including Burkitt's Lymphoma, Hodgkin Lymphoma, Nasopharyngeal and Gastric Carcinomas. EBV-encoded Latent Membrane Protein 2A (LMP2A), a BCR mimic, is expressed in cancer cells and is essential for transformation, migration and inhibition of differentiation. LMP2A/λ-MYC double transgenic mice develop splenomegaly and lymphoma much faster than mice that express Myc only. LMP2A induces cancer phenotype by recruiting and activating BCR signaling components such as Lyn and Syk kinases to the SH2 motifs found on its N terminal cytoplasmic domain. In this study, we explored inhibition of Syk kinase activity with a novel Syk/FLT-3 inhibitor TAK-659, in lymphomas from these transgenic mice to assess SYK inhibition as a potential therapeutic strategy for EBV-associated malignancies. The cell lines developed from LMP2A/Myc transgenic mice derived lymphomas showed higher basal pSYK levels than Myc lymphoma cell lines. TAK-659 treatment resulted in early apoptosis within 8hrs in LMP2A/Myc lymphoma cells in comparison to 24 hrs in Myc lymphoma cells. In both pre-tumor and tumor transfer models in vivo, compared with placebo and Myc tumors, LMP2A/MYC mice treated with TAK-659 did not develop splenomegaly and tumor development was totally inhibited in these mice indicating SYK signaling is essential for tumor development in LMP2A/Myc mice. In addition, metastasis of tumor cells into BM was abrogated. TAK-659 killed tumor cells but not host cells in spleen and tumors. Taken together our data show that TAK-659, even in low nanomolar concentrations, inhibits pSYK and induces apoptosis in LMP2A/Myc tumor cells. It also inhibits splenomegaly and tumor development in our autochthonous and syngeneic tumor transfer models of EBV-associated lymphoma by targeting tumor cells while sparing non-tumor cells. Therefore, TAK-659 may provide an effective therapeutic option for the treatment of EBV-associated malignancies and should be explored further in clinical trials. Disclosures Kannan: Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Huck:Takeda Pharmaceuticals International Co, Cambridge, MA: Employment. Yu:Takeda Pharmaceuticals International Co, Cambridge, MA: Employment. Zhang:Takeda Pharmaceuticals International Co, Cambridge, MA: Employment. Gordon:Northwestern University: Patents &amp; Royalties: Patent for gold nanoparticles pending.
Toward Statistical Machine Translation without Parallel Corpora (2012)

We estimate the parameters of a phrasebased statistical machine translation system from monolingual corpora instead of a bilingual parallel corpus. We extend existing research on bilingual lexicon induction to estimate both lexical and phrasal translation probabilities for MT-scale phrasetables. We propose a novel algorithm to estimate reordering probabilities from monolingual data. We report translation results for an end-to-end translation system using these monolingual features alone. Our method only requires monolingual corpora in source and target languages, a small bilingual dictionary, and a small bitext for tuning feature weights. In this paper, we examine an idealization where a phrase-table is given. We examine the degradation in translation performance when bilingually estimated translation probabilities are removed and show that 80%+ of the loss can be recovered with monolingually estimated features alone. We further show that our monolingual features add 1.5 BLEU points when combined with standard bilingually estimated phrase table features. 1
Tissue-specific Expression of βKlotho and Fibroblast Growth Factor (FGF) Receptor Isoforms Determines Metabolic Activity of FGF19 and FGF21 (2007)

The fibroblast growth factor (FGF) 19 subfamily of ligands, FGF19, FGF21, and FGF23, function as hormones that regulate bile acid, fatty acid, glucose, and phosphate metabolism in target organs through activating FGF receptors (FGFR1-4). We demonstrated that Klotho and betaKlotho, homologous single-pass transmembrane proteins that bind to FGFRs, are required for metabolic activity of FGF23 and FGF21, respectively. Here we show that, like FGF21, FGF19 also requires betaKlotho. Both FGF19 and FGF21 can signal through FGFR1-3 bound by betaKlotho and increase glucose uptake in adipocytes expressing FGFR1. Additionally, both FGF19 and FGF21 bind to the betaKlotho-FGFR4 complex; however, only FGF19 signals efficiently through FGFR4. Accordingly, FGF19, but not FGF21, activates FGF signaling in hepatocytes that primarily express FGFR4 and reduces transcription of CYP7A1 that encodes the rate-limiting enzyme for bile acid synthesis. We conclude that the expression of betaKlotho, in combination with particular FGFR isoforms, determines the tissue-specific metabolic activities of FGF19 and FGF21.
Tetracarbonylcyclopentadienyl Compounds of the Group V Transition Metals (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTetracarbonylcyclopentadienyl Compounds of the Group V Transition MetalsRobert P. M. Werner, Allen H. Filbey, and Switlana A. ManastyrskyjCite this: Inorg. Chem. 1964, 3, 2, 298–300Publication Date (Print):February 1, 1964Publication History Published online1 May 2002Published inissue 1 February 1964https://pubs.acs.org/doi/10.1021/ic50012a048https://doi.org/10.1021/ic50012a048research-articleACS PublicationsRequest reuse permissionsArticle Views146Altmetric-Citations40LEARN 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
Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma (2011)

Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O(6)-methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was frequently co-expressed with nestin and vimentin but rarely with CD133 and the NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D proteomics of 11 randomly selected biopsies revealed upregulation of an antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients. Expression of PRDX-1 was associated with significantly reduced products of oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates and sensitised them to IR in vivo. Our data establish NG2 as an important prognostic factor for GBM patient survival, by mediating resistance to radiotherapy through induction of ROS scavenging enzymes and preferential DNA damage signalling.
Loss of NLRX1 Exacerbates Neural Tissue Damage and NF-κB Signaling following Brain Injury (2017)

Traumatic and nontraumatic brain injury results from severe disruptions in the cellular microenvironment leading to massive loss of neuronal populations and increased neuroinflammation. The progressive cascade of secondary events, including ischemia, inflammation, excitotoxicity, and free-radical release, contribute to neural tissue damage. NLRX1 is a member of the NLR family of pattern recognition receptors and is a potent negative regulator of several pathways that significantly modulate many of these events. Thus, we hypothesized that NLRX1 limits immune system signaling in the brain following trauma. To evaluate this hypothesis, we used <i>Nlrx1<sup>-/-</sup></i> mice in a controlled cortical impact (CCI) injury murine model of traumatic brain injury (TBI). In this article, we show that <i>Nlrx1<sup>-/-</sup></i> mice exhibited significantly larger brain lesions and increased motor deficits following CCI injury. Mechanistically, our data indicate that the NF-κB signaling cascade is significantly upregulated in <i>Nlrx1<sup>-/-</sup></i> animals. This upregulation is associated with increased microglia and macrophage populations in the cortical lesion. Using a mouse neuroblastoma cell line (N2A), we also found that NLRX1 significantly reduced apoptosis under hypoxic conditions. In human patients, we identify 15 NLRs that are significantly dysregulated, including significant downregulation of NLRX1 in brain injury following aneurysm. We further demonstrate a concurrent increase in NF-κB signaling that is correlated with aneurysm severity in these human subjects. Together, our data extend the function of NLRX1 beyond its currently characterized role in host-pathogen defense and identify this highly novel NLR as a significant modulator of brain injury progression.