gebhart/patrepeval huggingface dataset:
Paclitaxel induces apoptosis and reduces proliferation by targeting epidermal growth factor receptor signaling pathway in oral cavity squamous cell carcinoma (2015)

Oral cavity cancer is common worldwide. Furthermore, the epidermal growth factor receptor (EGFR) signaling pathway is considered to be constitutively activated in oral cancers. Paclitaxel is widely accepted as an antitumor drug as it effectively inhibits the cell cycle. This study predominantly explores the possible molecule mechanism of paclitaxel on oral cancer treatment. Cell viability was first detected using an MTT assay. Cell apoptosis was examined by Hoechst staining and flow cytometry using an annexin-V and propidium iodide kit. Specific EGFR signaling pathways were further explored through western blot analysis. Abnormal protein expression levels were determined via immunofluoresence. Additionally, the protein levels of matrix metalloproteinase (MMP)-2 and 9 were determined using ELISA. Paclitaxel significantly inhibited oral cancer cell viability in a time- and dose-dependent manner. Paclitaxel also enhanced oral cancer cell apoptosis via increased Bim and Bid protein expression. Furthermore, paclitaxel was observed to inhibit oral cancer cell proliferation through increased MMP-2 and MMP-9 protein levels. Paclitaxel inhibited the growth of the oral cancer cell line, tea8113 malignant proliferation and enhanced tea8113 cell apoptosis through inhibiting the EGFR signaling pathway.
Primary and Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer: An Update (2012)

Epidermal growth factor receptor (EGFR) is a critical target in the treatment of nonsmall cell lung cancer (NSCLC). The mutations involving EGFR are more prevalent in patients of Asian ancestry, women, never smokers, and those with adenocarcinoma histology. Primary mechanism of resistance to EGFR-TKIs includes in frame insertion mutation in exon 20, de novo T790M mutation also on exon 20, activating mutations in KRAS, loss of PTEN, and amplification of c-MET whereas acquired resistance results from development of secondary alteration in ATP domain of T790M. There are many novel targeting agents in development to overcome resistance to EGFR TKIs.
The catalytic domain of MMP‐1 studied through tagged lanthanides (2011)

Pseudocontact shifts (pcs) and paramagnetic residual dipolar couplings (rdc) provide structural information that can be used to assess the adequacy of a crystallographic structure to represent the solution structure of a protein. This can be done by attaching a lanthanide binding tag to the protein. There are cases in which only local rearrangements are sufficient to match the NMR data and cases where significant secondary structure or domain rearrangements from the solid state to the solution state are needed. We show that the two cases are easily distinguishable. Whereas the use of solution restraints in the latter case is described in the literature, here we deal with how to obtain a better model of the solution structure in a case (the catalytic domain of the matrix metalloproteinase MMP-1) of the former class.
Transplantation of CNS Fragments into the Brain of Shiverer Mutant Mice: Extensive Myelination by Implanted Oligodendrocytes (1983)

Solid fragments of olfactory bulb from new-born normal (B6CBA and C57BL6) mice were implanted into new-born shiverer (shi/shi) brains. The shiverer mouse being characterized by the absence of myelin basic protein (MBP), myelination due to implanted oligodendrocytes can be detected in the shiverer brain using an antiserum anti-MBP. Observation of sagittal sections of the host brains revealed very extensive areas of normal myelination from the level of the graft (rostral thalamus) up to the caudal brain (diencephalon, cerebellum, pons). Thus, oligodendrocytes contained in the implant migrate out of the graft over long distances in the host brain, before they differentiate and synthesize myelin. These results raise the question of the behaviour of oligodendrocytes in normal development.
Model checking in industrial hardware design (1995)

Article Free Access Share on Model checking in industrial hardware design Authors: Jörg Bormann Siemens Corporate R&D, D-81730 Munich, Germany Siemens Corporate R&D, D-81730 Munich, GermanyView Profile , Jörg Lohse Siemens Corporate R&D, D-81730 Munich, Germany Siemens Corporate R&D, D-81730 Munich, GermanyView Profile , Michael Payer Siemens Corporate R&D, D-81730 Munich, Germany Siemens Corporate R&D, D-81730 Munich, GermanyView Profile , Gerd Venzl Siemens Corporate R&D, D-81730 Munich, Germany Siemens Corporate R&D, D-81730 Munich, GermanyView Profile Authors Info & Claims DAC '95: Proceedings of the 32nd annual ACM/IEEE Design Automation ConferenceJanuary 1995 Pages 298–303https://doi.org/10.1145/217474.217545Online:01 January 1995Publication History 27citation349DownloadsMetricsTotal Citations27Total Downloads349Last 12 Months9Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
The Association Between Quantitative Measures of Dementia and of Senile Change in the Cerebral Grey Matter of Elderly Subjects (1968)

The ageing of many populations in recent years has directed increasing attention to the social, medical and biological problems of senescence. The psychological changes associated with ageing occupy a central position in inquiries in this field. The expectation of mental disorder shows a steep increase with advancing chronological age, and beyond 75 years a large part of this increase is accounted for by disorders associated with degenerative changes in the central nervous system for which we lack remedies at the present time. Larsson et al . (1963) have estimated that the aggregate morbidity risk for these disorders up to the age of 70 is 0·4 per cent., up to age 75, 1·2 per cent. and up to age 80, 5 per cent. For higher ages estimates were probably less reliable, but the calculated risk up to the age of 90 was 5·2 per cent. In a survey of a random sample of elderly people aged 65 and over in the general population, Kay et al . (1964), found a total of 4·2 per cent. of elderly subjects to be suffering from senile dementia, 2·9 per cent. being mild cases. The condition is generally recognized as being a major cause of serious infirmity among the elderly in psychiatric, geriatric, general medical and community practice alike.
Design and x-ray crystal structures of high-potency nonsteroidal glucocorticoid agonists exploiting a novel binding site on the receptor (2009)

Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal structure of this truncated D-alaninamide derivative 13. Compound 11 displays properties compatible with development as an intranasal solution formulation, whereas oral bioavailability has been demonstrated with a related truncated exemplar 14. Data with the pyrrolidinone amide 12 demonstrate the potential for further elaboration within the "meta" channel to deliver compounds with selectivity for the desired transrepressive activity of glucocorticoids. The discovery of these interactions with this important receptor offers significant opportunities for the design of novel GR modulators.
Oct4/Sox2-Regulated miR-302 Targets Cyclin D1 in Human Embryonic Stem Cells (2008)

Oct4 and Sox2 are transcription factors required for pluripotency during early embryogenesis and for the maintenance of embryonic stem cell (ESC) identity. Functional mechanisms contributing to pluripotency are expected to be associated with genes transcriptionally activated by these factors. Here, we show that Oct4 and Sox2 bind to a conserved promoter region of miR-302, a cluster of eight microRNAs expressed specifically in ESCs and pluripotent cells. The expression of miR-302a is dependent on Oct4/Sox2 in human ESCs (hESCs), and miR-302a is expressed at the same developmental stages and in the same tissues as Oct4 during embryogenesis. miR-302a is predicted to target many cell cycle regulators, and the expression of miR-302a in primary and transformed cell lines promotes an increase in S-phase and a decrease in G(1)-phase cells, reminiscent of an ESC-like cell cycle profile. Correspondingly, the inhibition of miR-302 causes hESCs to accumulate in G(1) phase. Moreover, we show that miR-302a represses the productive translation of an important G(1) regulator, cyclin D1, in hESCs. The transcriptional activation of miR-302 and the translational repression of its targets, such as cyclin D1, may provide a link between Oct4/Sox2 and cell cycle regulation in pluripotent cells.
The Electrical Characteristics of Boron‐Implanted InP (1986)

The electrical characteristics of B+‐implanted were examined. Depending on the concentration of B atoms, two phenomena were observed. Thermally stable carrier depletion was obtained in the region containing B atoms higher than . In the region with the lower B concentration, n‐type carriers were generated. The residual defects, impurities, and Fe atoms in substrates did not contribute to the carrier generation. The carrier generation has been observed also in , but not in . We have concluded that the carrier generation has a close relation to In atoms in III–V semiconductor substrates.
Strand-specific 5′-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity (2007)

Small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide catalytic sequence-specific cleavage of fully or nearly fully complementary target mRNAs or control translation and/or stability of many mRNAs that share 6-8 nucleotides (nt) of complementarity to the siRNA and miRNA 5' end. siRNA- and miRNA-containing ribonucleoprotein silencing complexes are assembled from double-stranded 21- to 23-nt RNase III processing intermediates that carry 5' phosphates and 2-nt overhangs with free 3' hydroxyl groups. Despite the structural symmetry of a duplex siRNA, the nucleotide sequence asymmetry can generate a bias for preferred loading of one of the two duplex-forming strands into the RNA-induced silencing complex (RISC). Here we show that the 5'-phosphorylation status of the siRNA strands also acts as an important determinant for strand selection. 5'-O-methylated siRNA duplexes refractory to 5' phosphorylation were examined for their biases in siRNA strand selection. Asymmetric, single methylation of siRNA duplexes reduced the occupancy of the silencing complex by the methylated strand with concomitant elimination of its off-targeting signature and enhanced off-targeting signature of the phosphorylated strand. Methylation of both siRNA strands reduced but did not completely abolish RNA silencing, without affecting strand selection relative to that of the unmodified siRNA. We conclude that asymmetric 5' modification of siRNA duplexes can be useful for controlling targeting specificity.
Chemistry and structure elucidation of the kedarcidin chromophore (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry and structure elucidation of the kedarcidin chromophoreJohn E. Leet, Daniel R. Schroeder, David R. Langley, Kimberly L. Colson, Stella Huang, Steven E. Klohr, Mike S. Lee, Jerzy Golik, Sandra J. Hofstead, and Cite this: J. Am. Chem. Soc. 1993, 115, 18, 8432–8443Publication Date (Print):September 1, 1993Publication History Published online1 May 2002Published inissue 1 September 1993https://pubs.acs.org/doi/10.1021/ja00071a062https://doi.org/10.1021/ja00071a062research-articleACS PublicationsRequest reuse permissionsArticle Views451Altmetric-Citations95LEARN 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
β-catenin mutation and overexpression in hepatocellular carcinoma (2001)

beta-catenin mutation and deregulation may play an important role in hepatocarcinogenesis. Nonnuclear type beta-catenin overexpression appeared to have pathologic and prognostic significance.
Analysis of input-polarization-induced phase noise in interferometric fiber-optic sensors and its reduction using polarization scrambling (1990)

The dependence of the phase shift of an interferometric fiber sensor on the input state of polarization is analyzed, and it is shown that fluctuations in the input polarization to a fiber interferometer can lead to the generation of excess phase noise. The relationship between this effect and the variation in visibility with input polarization is described and theoretically confirmed. The use of depolarized source light to eliminate input-polarization-induced excess phase noise is theoretically and experimentally demonstrated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Chemistry and synthetic utility of cobalt-complexed propargyl cations (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry and synthetic utility of cobalt-complexed propargyl cationsKenneth M. NicholasCite this: Acc. Chem. Res. 1987, 20, 6, 207–214Publication Date (Print):June 1, 1987Publication History Published online1 May 2002Published inissue 1 June 1987https://pubs.acs.org/doi/10.1021/ar00138a001https://doi.org/10.1021/ar00138a001research-articleACS PublicationsRequest reuse permissionsArticle Views2646Altmetric-Citations516LEARN 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
Application of the scintillation proximity assay technique to the determination of drugs (1994)

The established ranitidine radioimmunoassay technique (RIA) has been adapted to a scintillation proximity assay (SPA) format by use of micro-titre plates. This automated method enables the bioanalyst to more than halve the ‘hands-on’ time involved in RIA.
E-selectin mediates leukocyte rolling in interleukin-1-treated rabbit mesentery venules (1994)

The selectins are lectin-like cell surface glycoproteins that have been implicated in playing a crucial role in the initiation of leukocyte adhesion to endothelial cells (ECs) during inflammation. Binding of selectins under conditions of flow mediates leukocyte rolling, which in vivo is almost exclusively observed in venular microvessels. We have shown in previous experiments that intraperitoneal treatment of rabbits with interleukin-1 beta (IL-1) increases leukocyte rolling in exteriorized mesenteries. In the present study, we used immunohistochemistry of mesenteries and found that IL-1 induced a marked E-selectin immunoreactivity, preferentially in venules. We therefore hypothesized that the increased rolling in response to IL-1 may be related to the induction of E-selectin on venular ECs. Intravital microscopy was used to investigate interactions between leukocytes and ECs after intraperitoneal application of IL-1. The rabbit E-selectin monoclonal antibody (MoAb) 9H9 significantly reduced rolling of leukocytes by approximately 40%. Vehicle alone, class- matched control MoAb or the nonblocking anti-E-selectin MoAb 14G2 had no effect on rolling. These results indicate that leukocytes roll on inflamed venular ECs partly through interactions with E-selectin. Furthermore, we propose that the restricted E-selectin immunoreactivity by venular ECs contributes to the remarkable difference seen between arterioles and venules in exhibiting leukocyte rolling in vivo.
Synthesis and Incorporation of C(5′)‐Ethynylated Uracil‐Derived Phosphoramidites into RNA (2004)

Abstract The D ‐ allo‐ and L ‐ talo ‐hept‐6‐ynofuranosyluracil‐derived phosphoramidites 11A and 11T were prepared in 9–10% yield over eight steps from the previously described propargylic alcohols 1A and 1T , respectively. The corresponding nucleotides were incorporated into rU 14 by standard solid‐phase synthesis. While the duplex consisting of rU 14 with one L ‐ talo ‐hept‐6‐ynofuranosyluracil in the middle of the strand and rA 14 ( I ⋅ V ) had the same melting point as the reference duplex rU 14 ⋅rA 14 ( I ⋅ II ), the duplex with one D ‐ allo ‐hept‐6‐ynofuranosyluracil in the middle of rU 14 and rA 14 ( I ⋅ III ) melted 1.5° lower than the reference duplex. The duplex I ⋅ VI consisting of rU 14 with six L ‐ talo ‐hept‐6‐ynofuranosyluracils distributed over the entire strand and rA 14 showed a melting point that is 11° lower than the reference duplex. The corresponding duplex I ⋅ IV of rU 14 possessing six D ‐ allo ‐hept‐6‐ynofuranosyluracils and rA 14 showed a melting point which is more than 20° below the one of the reference duplex. These results are in qualitative agreement with the predictions based on the conformational analysis of the nucleosides and the interference of the ethynyl moiety with the hydration of the oligonucleotides.
The mechanism of the inhibition of the mitochondrial pyruvate transportater by α-cyanocinnamate derivatives (1976)

Pyruvate transport into rat liver mitochondria is inhibited by a variety of thiol reagents. alpha-Cyanocinnamate and its derivates, potent and reversible inhibitors of pyruvate transport, react reversibly with mercaptoethanol and cysteine to form addition products. It is concluded that these inhibitors react with an essential thiol group on the pyruvate carrier.
MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4 (1999)

Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as well as pathophysiologic, mechanisms.
THE INTERLEUKIN-12/INTERLEUKIN-12-RECEPTOR SYSTEM: Role in Normal and Pathologic Immune Responses (1998)

▪ Abstract Interleukin-12 (IL-12) is a heterodimeric cytokine that plays a central role in promoting type 1 T helper cell (Th1) responses and, hence, cell-mediated immunity. Its activities are mediated through a high-affinity receptor composed of two subunits, designated β1 and β2. Of these two subunits, β2 is more restricted in its distribution, and regulation of its expression is likely a central mechanism by which IL-12 responsiveness is controlled. Studies with neutralizing anti-IL-12 antibodies and IL-12-deficient mice have suggested that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular pathogens. However, IL-12 appears also to play a central role in the genesis of some forms of immunopathology. Inhibition of IL-12 synthesis or activity may be beneficial in diseases associated with pathologic Th1 responses, such as multiple sclerosis or Crohn's disease. On the other hand, administration of recombinant IL-12 may have utility in the treatment of diseases associated with pathologic Th2 responses such as allergic disorders and asthma.
Baculovirus expression of functional P210 BCR-ABL oncogene product. (1989)

The chronic myelogenous leukemia-associated P210 BCR-ABL oncogene protein product has been produced using the baculovirus expression system. High-level expression of the P210 BCR-ABL protein required the removal of GC rich 5' non-coding sequences. P210 BCR-ABL synthesized in insect cells is an active tyrosine protein kinase indistinguishable from P210 BCR-ABL isolated from human cells. Both proteins utilize angiotensin II as a phosphate acceptor in vitro with a Km for ATP of approximately 1.5 microM. P210 BCR-ABL produced in insect cells undergoes autophosphorylation in vitro and in vivo. Gel filtration of P210 BCR-ABL reveals that the protein elutes as a high molecular weight complex of about 800 kD. Approximately 4 to 5 mg of P210 BCR-ABL is produced in one liter of infected insect cells. Following cell disruption and a three-step ion exchange and gel filtration purification procedure, 0.4 mg of soluble P210 BCR-ABL is obtained per liter of suspension culture. An alternative procedure employing detergent extraction and immunoaffinity chromatography gave higher yields and purity from smaller amounts of infected cell extracts. The availability of intact, soluble and enzymatically active P210 BCR-ABL represents a significant advance for studying the biochemical and biophysical properties of the ABL oncogene family of proteins.
Measurement of Cetuximab and Panitumumab-Unbound Serum EGFR Extracellular Domain Using an Assay Based on Slow Off-Rate Modified Aptamer (SOMAmer) Reagents (2013)

This SOMAmer-based serum EGFR ECD assay accurately and specifically measures EGFR in serum. Detection of significant amounts of drug-unbound EGFR in patients undergoing cetuximab or panitumumab treatment could be an indicator of poor drug response. Further studies are needed to evaluate the utility of the assay as an indicator of drug efficacy or as a guide to dosing.