gebhart/patrepeval huggingface dataset:
Abstract 4711: Novel mechanism involved in the regulation ofoncogenic Axl receptor tyrosine kinase in cancer (2020)

Abstract Background: Oncogenic receptor tyrosine kinase Axl is overexpressed and plays an important role in multiple human cancers. However the mechanisms of Axl overexpression in cancer remain unclear. This study is to investigate the mechanisms that regulate Axl expression in pancreatic cancer. Experimental procedures: The interactions between HPK1, Axl and c-Cbl were examined using co-immunoprecipitation and immunoblotting. Inhibitors of endocytic pathway and immunofluorescence were used to examine the underlying mechanisms of HPK1-mediated Axl degradation. The functional significance of HPK1-mediated Axl degradation in the invasive capability of pancreatic ductal adenocarcinoma (PDAC) cells and it downstream signaling pathways were examined using HPK1 stable PDAC cells. Immunohistochemistry was used to examine the in vivo correlation between HPK1 and Axl in human pancreatic intraepithelial neoplasia. The RNA sequencing data of HPK1 and Axl expression and survival data of 176 pancreatic cancer patients in the Cancer Genome Atlas (TCGA) database were downloaded from the Human Protein Atlas (https://www.proteinatlas.org). The expression of HPK1 and Axl was categorized as low or high using the cutoff values set by TCGA (3.42 for HPK1 and 14.09 for Axl). Survival analysis were performed using the Kaplan-Meier method and the log-rank test was used to evaluate the statistical significance of differences. Results: We identified Axl as a novel HPK1-interacting protein and demonstrated for the first time that HPK1 down-regulated Axl and decreased the half-life of Axl protein. HPK1-mediated Axl degradation was inhibited by leupeptin, baflomycin A1 and monensin which inhibit endocytic pathway. HPK1 accelerates the movement of Axl from the plasma membrane onto endosomes in pancreatic cancer cells after treated with Gas6. HPK1 increased the binding of Axl to c-Cbl, promoted Axl ubiquitination, decreased Axl signaling including phospho-Akt and phospho-Erk, and decreased the invasion capability of pancreatic cancer. More importantly, we showed that Axl expression inversely correlated with HPK1 expression in human pancreatic intraepithelial neoplasia (P=0.005). Low expression of HPK1 and high expression of Axl correlated significantly with poor survival in patients with PDAC (P&amp;lt;0.001). Conclusions: Our results suggest a novel tumor suppressor mechanism of HPK1 in which it targets Axl for degradation via the endocytic pathway. Loss of HPK1 may contribute to Axl overexpression and enhance its downstream signaling and tumor invasion in pancreatic cancer. Citation Format: Hua Wang, Xianzhou Song, Hironari Akasaka, Reza Abbasgholizadeh, Ji-Hyun Shin, Craig D. Logsdon, Anirban Maitra, Andrew J. Bean, Huamin Wang. Novel mechanism involved in the regulation ofoncogenic Axl receptor tyrosine kinase in cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4711.
Molecular regulation, membrane association and secretion of tumor cathepsin B (1999)

Upregulation, membrane association and secretion of cathepsin B have been shown to occur in many types of tumors and to correlate positively with their invasive and metastatic capabilities. To further understand changes in cathepsin B activity and localization, we have been examining its regulation at many levels including transcription and trafficking. Our studies indicate that there may be three promoter regions in the cathepsin B gene. Of these, continued examination of the promoter upstream of exon 1 has indicated possible control by several regulatory factors including E-box and Sp-1 binding elements. Upregulation of cathepsin B at this level may account for some of the secretion of cathepsin B found in tumors. We have also gathered evidence that endo- and exocytosis of cathepsin B may be regulated by ras and ras-related proteins in addition to previously described trafficking systems. There is also evidence that several populations of lysosomes may exist and that trafficking to different populations may determine whether cathepsin B is secreted from the tumor cell or remains intracellular. Our results indicate that membrane association and secretion of cathepsin B is not a random process in the tumor cell, but rather part of a tightly controlled system.
Histone deacetylase inhibitors induce caspase‐dependent apoptosis and downregulation of daxx in acute promyelocytic leukaemia with t(15;17) (2001)

Histone deacetylase (HDAC) appears to play an important role in the pathogenesis of acute promyelocytic leukaemia (APL) as it is recruited by both PML-RARalpha and PLZF/RAR alpha in leukaemic cells with t(15;17) and t(11;17) respectively. Recent studies have demonstrated that HDAC inhibitors can be therapeutically used in various neoplastic disorders including APL. Cell differentiation was considered the major mechanism of the anti-leukaemic effects of HDAC inhibitors in APL. However, most of these studies either evaluated the effect of HDAC inhibitors in combination with all-trans retinoic acid (ATRA) or focused on the less common form of APL with t(11;17). To investigate the cellular effects of HDAC inhibitors, including sodium butyrate, trichostatin A, and suberoylanilide hydroxamic acid (SAHA), we used two APL cell lines, NB4 and the ATRA-resistant derivative NB4.306. Moreover, primary cells from five patients with cytogenetic evidence for t(15;17) were also studied. Our results demonstrated that HDAC inhibitors induce distinct caspase-dependent apoptosis in APL, which showed both concentration-and time-dependence. In addition, changes in the apoptosis-regulatory proteins, daxx, bcl-2 and bax were analysed. HDAC inhibitors induced downregulation of daxx, but no significant changes were detected in bcl-2 or bax. In conclusion, apoptosis induced by HDAC inhibitors in APL could provide an effective strategy for treatment of patients with t(15;17).
Therapeutic antibodies: successes, limitations and hopes for the future (2009)

With more than 20 molecules in clinical use, monoclonal antibodies have finally come of age as therapeutics, generating a market value of $11 billion in 2004, expected to reach $26 billion by 2010. While delivering interesting results in the treatment of several major diseases including autoimmune, cardiovascular and infectious diseases, cancer and inflammation, clinical trials and research are generating a wealth of useful information, for instance about associations of clinical responses with Fc receptor polymorphisms and the infiltration and recruitment of effector cells into targeted tissues. Some functional limitations of therapeutic antibodies have come to light such as inadequate pharmacokinetics and tissue accessibility as well as impaired interactions with the immune system, and these deficiencies point to areas where additional research is needed. This review aims at giving an overview of the current state of the art and describes the most promising avenues that are being followed to create the next generation of antibody-based therapeutic agents.
Statistical pattern recognition: a review (2000)

The primary goal of pattern recognition is supervised or unsupervised classification. Among the various frameworks in which pattern recognition has been traditionally formulated, the statistical approach has been most intensively studied and used in practice. More recently, neural network techniques and methods imported from statistical learning theory have been receiving increasing attention. The design of a recognition system requires careful attention to the following issues: definition of pattern classes, sensing environment, pattern representation, feature extraction and selection, cluster analysis, classifier design and learning, selection of training and test samples, and performance evaluation. In spite of almost 50 years of research and development in this field, the general problem of recognizing complex patterns with arbitrary orientation, location, and scale remains unsolved. New and emerging applications, such as data mining, web searching, retrieval of multimedia data, face recognition, and cursive handwriting recognition, require robust and efficient pattern recognition techniques. The objective of this review paper is to summarize and compare some of the well-known methods used in various stages of a pattern recognition system and identify research topics and applications which are at the forefront of this exciting and challenging field.
Capsaicin Receptor in the Pain Pathway (2000)

Capsaicin, the main pungent ingredient in ‘hot’ chili peppers, elicits burning pain by activating specific (vanilloid) receptors on sensory nerve endings. The cloned capsaicin receptor (VR1) is a nonselective cation channel with six transmembrane domains that is structurally related to a member of the TRP (transient receptor potential) channel family. VR1 is activated not only by capsaicin but also by increases in temperature that reach the noxious range (>43°C). Protons potentiate the effects of capsaicin or heat on VR1 activity by markedly decreasing the capsaicin concentration or temperature at which the channel is activated. Furthermore, a significant increase in proton concentration (pH <5.9) can evoke channel activity at room temperature. The analysis of single-channel currents in excised membrane patches suggests that capsaicin, heat or protons gate VR1 directly. VR1 can therefore be viewed as a molecular integrator of chemical and physical stimuli that elicit pain. VRL-1, a VR1 homologue, is not activated by vanilloids or protons, but can be activated by elevation in ambient temperature exceeding 52°C. These findings indicate that related ion channels may account for thermal responsiveness over a range of noxious temperature.
Diagnostic implication of specific immunoglobulin G patterns of children born to HIV-infected mothers (1989)

We analysed HIV-specific immunoglobulin G (IgG) responses to gag and env peptides in infants born to HIV-positive mothers. Questions of interest were whether there are early specific markers for prognosis, and whether any specific IgG is related to the prevention of vertical transmission of infection. Fifty-three children, 0-24 months old and born to HIV-1-infected mothers, were retrospectively divided into two groups based on HIV seroreactivity or non-reactivity at 15 months of age. Their sera were used to find reactivities important in diagnosis and/or prediction of the putative HIV disease. Three important findings emerged. First, a low IgG titer against the very immunodominant penv9 in newborns was found to be associated with rapid progression to AIDS. This difference was clearly reflected in the reactivity to a small peptide representing amino acid (aa) 598-606. The second interesting finding was the putative hypervariable loop on gp120 (especially aa 324-338), reactivity to which was found only in the uninfected group, and was seen in six out of 19 uninfected children under 6 months of age. This specific response was not caused by a generally high total anti-HIV reactivity, and may indicate a role of protective antibodies against vertical transmission. The response to this region in the infected group, on the other hand, was directed to the amino terminal half of the putative loop, in particular peptide 53, aa 304-318. Finally, response to a part of the amino terminal end of P17 was seen in seven out of eight infected children over 6 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin receptor kinase domain autophosphorylation regulates receptor enzymatic function. (1992)

We have studied a series of insulin receptor molecules in which the 3 tyrosine residues which undergo autophosphorylation in the kinase domain of the beta-subunit (Tyr1158, Tyr1162, and Tyr1163) were replaced individually, in pairs, or all together with phenylalanine or serine by in vitro mutagenesis. A single-Phe replacement at each of these three positions reduced insulin-stimulated autophosphorylation of solubilized receptor by 45-60% of that observed with wild-type receptor. The double-Phe replacements showed a 60-70% reduction, and substitution of all 3 tyrosine residues with Phe or Ser reduced insulin-stimulated tyrosine autophosphorylation by greater than 80%. Phosphopeptide mapping each mutant revealed that all remaining tyrosine autophosphorylation sites were phosphorylated normally following insulin stimulation, and no new sites appeared. The single-Phe mutants showed insulin-stimulated kinase activity toward a synthetic peptide substrate of 50-75% when compared with wild-type receptor kinase activity. Insulin-stimulated kinase activity was further reduced in the double-Phe mutants and barely detectable in the triple-Phe mutants. In contrast to the wild-type receptor, all of the mutant receptor kinases showed a significant reduction in activation following in vitro insulin-stimulated autophosphorylation. When studied in intact Chinese hamster ovary cells, insulin-stimulated receptor autophosphorylation and tyrosine phosphorylation of the cellular substrate pp185 in the single-Phe and double-Phe mutants was progressively lower with increased tyrosine replacement and did not exceed the basal levels in the triple-Phe mutants. However, all the mutant receptors, including the triple-Phe mutant, retained the ability to undergo insulin-stimulated Ser and Thr phosphorylation. Thus, full activation of the insulin receptor tyrosine kinase is dependent on insulin-stimulated Tris phosphorylation of the kinase domain, and the level of autophosphorylation in the kinase domain provides a mechanism for modulating insulin receptor kinase activity following insulin stimulation. By contrast, insulin stimulation of receptor phosphorylation on Ser and Thr residues by cellular serine/threonine kinases can occur despite markedly reduced tyrosine autophosphorylation.
Malabsorption in Intestinal Scleroderma (1966)

THE etiology of malabsorption in patients suffering from intestinal scleroderma has been the subject of considerable debate. Impaired intestinal motility, lymphatic obstruction and reduced arterial blood supply, as well as involvement of the intestinal wall by the disease, have all been suggested as possible etiologic factors, without, however, acceptable supporting evidence,1 , 2 The possibility of bacterial overgrowth in atonic loops of bowel has been considered by several observers2 3 4; McBrien and Lockhart Mummery4 reported temporary improvement of intestinal absorption in 1 patient during therapy with a broad-spectrum antibiotic.This report relates our experience with the use of a broad-spectrum antibiotic in . . .
Ionic Liquids in Photopolymerizable Holographic Materials (2011)

A variety of materials have been used to record hologram, such as silver halide emulsions, hardened dichromated gelatin, ferroelectric crystals, photochromics, photoresist, photodichroics and photopolymerizable materials Photopolymerizable holographic materials due to their low cost and dry processing have attracted great interest in academics and industry. They have broad applications in holographic memories, recording media, LCD displays, helmet-mounted display, optical interconnects, waveguide couples, holographic diffusers, laser eye protection devices, automotive lighting, and security holograms. The photopolymerizable holographic composite contains mainly a matrix binder, a photopolymerizable monomer, an initiator system, a plasticizer and additives Due to the inter diffusion of the unpolymerized monomers in a holographic film, areas with high and low refractive index are formed during the irradiation with an interference pattern. Many photopolymer systems have been developed including binary photopolymer composites, organic-inorganic nanocomposites, a hybrid organic-inorganic host consisting of porous glass, and a system using monomers capable of cationic ring-opening polymerization. The addition of a plasticizer or an additive can increase the refractive index modulation and the final diffraction efficiency. Monroe et al. reported that tri(2-ethylhexyl)phosphate, glyceryl tributyrate, polyethylene glycol or f u n c t i o n a l p o l y e t h y l e n e g l y c o l e t c . a s plasticizers may increase the refractive index modulation Frank recommended photopolymerizable compositions with triglycerides as additives, which provide a stable holographic material with high refractive index modulation Tucker et al. used trithiocarbonate as additive to increase the diffraction efficiency, uniformity and reproducibility in the formation of electrically switchable holographic gratings Finally, one publication reports about an additive to improve the sensitivity of photopolymerizable hologram material Ionic liquids are organic salts that are liquid at ambient temperatures, preferably at room temperature. They are nonvolatile, thermally and chemically stable, highly polar liquids, high ionic conductivity, large electrochemical window and ease of solubilization of a large organic molecules and transition metal complexes Applications of ionic liquids include their use in synthesis, catalysis, separation, electrochemistry, electrolytes, lubrication, biomass processing, drug delivery and others. The cations of ionic liquids are www.intechopen.com
Fundamentals of Database Systems (1989)

From the Publisher:
Fundamentals of Database Systems combines clear explanations of theory and design, broad coverage of models and real systems, and excellent examples with up-to-date introductions to modern database technologies. This edition is completely revised and updated, and reflects the latest trends in technological and application development. Professors Elmasri and Navathe focus on the relational model and include coverage of recent object-oriented developments. They also address advanced modeling and system enhancements in the areas of active databases, temporal and spatial databases, and multimedia information systems. This edition also surveys the latest application areas of data warehousing, data mining, web databases, digital libraries, GIS, and genome databases. New to the Third Edition
Reorganized material on data modeling to clearly separate entity relationship modeling, extended entity relationship modeling, and object-oriented modeling Expanded coverage of the object-oriented and object/relational approach to data management, including ODMG and SQL3 Uses examples from real database systems including OracleTM and Microsoft AccessAE Includes discussion of decision support applications of data warehousing and data mining, as well as emerging technologies of web databases, multimedia, and mobile databases Covers advanced modeling in the areas of active, temporal, and spatial databases Provides coverage of issues of physical database tuning Discusses current database application areas of GIS, genome, and digital libraries
Use of bacterial expression cloning to localize the epitopes for a series of monoclonal antibodies against apolipoprotein B100. (1990)

Bacterial expression of apolipoprotein (apo) B cDNA constructs has been used to map a series of monoclonal antibodies (mAbs) to apoB by immunoblotting. In some cases assignments have been confirmed and refined by (i) semipurification of expressed protein, CNBr digestion, and assignment of the immunoreactive fragments; (ii) controlled digestion of the cDNA with the exonuclease Bal31 and bacterial expression of the truncated proteins that result; or (iii) expression of specific segments of cDNA amplified by the polymerase chain reaction. Forty mAbs were mapped to a minimum of 17 separate determinants on apoB. Tryptic fragments have been used to confirm the epitope assignments. In addition, this approach in conjunction with immunoassay, enables some deductions to be made about the trypsin-accessible regions in low density lipoprotein (LDL). The cleavage pattern obtained predicts retention of structure in the cysteine-rich domain of the amino terminus and also in the LDL receptor binding region. Trypsinized LDL was shown to bind to the LDL receptor by an authentic process, using monoclonal antibodies as competing ligands. In conjunction with the previous paper (Milne, R. W., Theolis, R., Maurice, R., Pease, R. J., Weech, P. K., Rassart, E., Fruchart, J.-C., Scott, J., and Marcel, Y. L. (1989) J. Biol. Chem. 265, 19754-19760) the mapped mAbs have been used to define the receptor-binding domain of apoB100 in LDL.
DNA Sequencing by Hybridization with Arrays of Samples or Probes (2003)

This chapter focuses on sequencing by hybridization (SBH), an advanced DNA sequencing technique first proposed in 1987 (1). SBH procedures determine DNA sequence information by screening DNA oligomers (typically 7-to 11-mers) for their ability to hybridize with target DNA. The set of overlapping oligomers that matches the target DNA is then used to assemble its sequence. The theory, practice, and history of SBH are reviewed in refs. 2 and 3.
Near-Infrared Determination of Several Physical Properties of Hydrocarbons (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNear-Infrared Determination of Several Physical Properties of HydrocarbonsD. E. Honigs, T. B. Hirschfeld, and G. M. HieftjeCite this: Anal. Chem. 1985, 57, 2, 443–445Publication Date (Print):February 1, 1985Publication History Published online1 May 2002Published inissue 1 February 1985https://pubs.acs.org/doi/10.1021/ac50001a028https://doi.org/10.1021/ac50001a028research-articleACS PublicationsRequest reuse permissionsArticle Views139Altmetric-Citations31LEARN 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
The Effect of Adding Zeroes to Feedforward Controllers (1991)

The effect of adding zeroes to two types of feedforward controllers, stable pole zero cancelling (SPZC) controllers and zero phase error tracking (ZPET) contollers, is discussed. When there are uncancellable zeroes in the feedback system, additional zeroes in the feedforward controller can reduce the tracking and/or the contour error. For multi-axis contouring with mismatched axis dynamics, a ZPET controller cancels the phase error and provides good contouring accuracy. With a SPZC controller which does not cancel the phase lag, the axes can be “matched” for equal phase lag by adding zeroes to the feedforward controller.
Fabrication of Silicon Oxide Nanodots with an Areal Density Beyond 1 Teradots Inch−2 (2011)

The combination of solvent annealing, surface reconstruction, and a tone-reversal etching procedure provides an attractive approach to utilize block copolymer (BCP) lithography to fabricate highly ordered and densely packed silicon oxide nano-dots on a surface. The obtained silicon oxide nano-dots feature an areal density of 1.3 teradots inch(-2) .