gebhart/patrepeval huggingface dataset:
Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer. (2002)

The humanized monoclonal antibody Herceptin, which specifically targets HER-2/neu, exhibits growth inhibitory activity against HER-2/neu-overexpressing tumors and is approved for therapeutic use with proved survival benefit in patients with HER-2/neu-positive breast cancer. In the present study, we investigated whether Herceptin could affect the HER-2/neu-overexpressing gastric cancer cells based on antibody-dependent cell-mediated cytotoxicity (ADCC) and compared immune effector cells from gastric cancer patients with normal individuals on ADCC. HER-2/neu-expressing gastric cancer cells could be killed by Herceptin-mediated ADCC and the Herceptin-induced ADCC correlated with the degree of HER-2/neu expression on the gastric cancer cells. However, the Herceptin-mediated ADCC was significantly impaired in peripheral blood mononuclear cells from advanced disease patients (n = 10) compared with that in early disease (n = 12; P = 0.04) or healthy individuals (n = 10, P = 0.02). Moreover, natural killer (NK) cells purified from patients with advanced disease indicated less Herceptin-mediated ADCC in comparison with that from healthy donors (P = 0.04), whereas monocytes purified from the patients showed an almost equal amount of Herceptin-mediated ADCC in comparison with that from healthy individuals, indicating that NK cell dysfunction contributed to the impaired Herceptin-mediated ADCC in gastric cancer patients. Furthermore, the NK-cell dysfunction on Herceptin-mediated ADCC correlated with the down-regulation of CD16zeta expression in the patients, and interleukin 2 ex vivo treatment of NK cells could restore the impairment of Herceptin-mediated ADCC, concomitant to the normalization of the expression of CD16zeta molecules. Thus, some modalities such as interleukin 2 treatment aimed at reversing NK dysfunction may be necessary for successful Herceptin treatment of gastric cancer.
Purification and characterization of a new agarase from a marine bacterium, Vibrio sp. strain JT0107 (1993)

A marine bacterial strain that decomposes the cell walls of some seaweeds, including a Laminaria sp. and Undaria pinnatifida, has been isolated from seawater. This strain has been classified to the genus Vibrio. One of the enzymes which the bacteria secreted into the culture medium was isolated and purified 45-fold from the culture fluid by a combination of ammonium sulfate precipitation and successive rounds of anion-exchange column chromatography. Purified protein migrated as a single band (M(r), 107,000) on sodium dodecyl sulfate-polyacrylamide gels. By amino acid sequence analysis, it was determined that this protein had a single N-terminal sequence that did not exhibit identity with the sequences of other agarases from marine bacteria. This novel enzyme was found to be an endo-type beta-agarase (EC 3.2.1.81) which hydrolyzes the beta-1,4 linkage of agarose to yield neoagarotetraose [O-3,6-anhydro-alpha-L-galactopyranosyl (1-->3)-O-beta-D-galactopyranosyl(1-->4)-O-3,6-anhydro-alpha-L-galactopy ranosyl (1-->3)-D-galactose] and neoagarobiose [O-3,6-anhydro-alpha-L-galactopyranosyl (1-->3)-D-galactose] at a pH of around 8. The optimum temperature was 30 degrees C. This enzyme did not decompose sodium alginate or lambda-, iota-, or kappa-carrageenan. This enzyme may be of practical application in gene technology in the isolation of DNA fragments from agarose gels after electrophoresis.
Quantitative Analysis and Characterization of DNA Immobilized on Gold (2003)

We describe the complementary use of X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy to quantitatively characterize the immobilization of thiolated (dT)(25) single-stranded DNA (ssDNA) on gold. When electron attenuation effects are accurately accounted for in the XPS analysis, the relative coverage values obtained by the two methods are in excellent agreement, and the absolute coverage can be calculated on the basis of the XPS data. The evolution of chemically specific spectral signatures during immobilization indicates that at lower coverages much of the DNA lies flat on the surface, with a substantial fraction of the thymine bases chemisorbed. At higher immobilization densities, the (dT)(25) film consists of randomly coiled ssDNA molecules each anchored via the thiol group and at possibly one or two other bases. We use two examples to demonstrate how the quantitative analysis can be applied to practical problems: the effects of different buffer salts on the immobilization efficiency; the immobilization kinetics. Buffers with divalent salts dramatically increase the efficiency of immobilization and result in very high surface densities (>5 x 10(13)/ cm(2)), densities that may only be possible if the divalent counterions induce strong attractive intermolecular interactions. In contrast with previous reports of alkanethiol adsorption kinetics on gold, ssDNA immobilization in 1 M phosphate buffer does not occur with Langmuir kinetics, a result attributable to rearrangement within the film that follows the initial adsorption.
Comparative immunogenicities of Vi polysaccharide-protein conjugates composed of cholera toxin or its B subunit as a carrier bound to high- or lower-molecular-weight Vi (1989)

The effect of molecular weight or size of the components on the immunogenicity of polysaccharide-protein conjugates prepared with the native Vi capsular polysaccharide (Vi) (approximately 3 x 10(3) kilodaltons) or lower-molecular-weight Vi (Vis; approximately 46 kilodaltons) abound to cholera toxin (CT) or to its B subunit (CTB) was studied. In mice, Vi-CT, Vi-CTB, and Vis-CTB elicited higher Vi antibody levels than the Vi alone (P less than 0.0001). Vi-CT and Vi-CTB were more immunogenic than Vis-CTB (P less than 0.01). CT or Vi-CT elicited higher levels of CT antibodies, as measured by enzyme-linked immunosorbent assay, than did CTB or Vi-CTB. In rhesus monkeys, the Vi conjugates elicited higher Vi antibody levels than the Vi alone (P less than 0.01). Vi-CTB elicited higher levels of Vi antibody after each injection than did Vis-CTB. Similar levels of CT antibodies, as measured by enzyme-linked immunosorbent assay, were elicited by all three conjugates. In contrast, Vi-CT elicited higher levels of neutralizing antibodies than Vi-CTB or Vis-CTB when either CT or the related heat-labile toxin of Escherichia coli was used as the antigen. These results indicate that the holotoxin and the native Vi provide the most immunogenic components for conjugates designed to induce both Vi and CT antibodies.
Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle- cell lymphomas and t(11q13)-associated leukemias (1994)

Rearrangement and overexpression of CCND1 (BCL1/PRAD1), a member of the cyclin G1 gene family, are consistent features of t(11q13)-bearing B-lymphoid tumors (particularly mantle-cell lymphoma [MCL]). Its deregulation is thought to perturb the G1-S transition of the cell cycle and thereby to contribute to tumor development. As suggested by previously published studies, rearrangement of the 3' untranslated region (3' UTR) of CCND1 may contribute to its activation in some lymphoid tumors. To define further the prevalence of such rearrangements, we report here the result of the molecular study of 34 MCL and six t(11q13)-associated leukemias using a set of probes specific to the different parts of the CCND1 transcript. We also sequenced the entire cDNA of the overexpressed CCND1 transcripts in a t(11q13)-associated leukemia. DNA from four of these 40 patients showed rearrangement of the 3' UTR of CCND1 coexisting with major translocation cluster (MTC) rearrangement. Southern blot and sequence analyses showed that, as a result of these rearrangements, the 3' AU-rich region containing sequences involved in mRNA stability and in translational control is eliminated. Moreover, the finding that the CCND1 mRNA half-life was greater than 3 hours (normal tissues, 0.5 hours) in three t(11q13)-associated cell lines stresses the importance of posttranscriptional derangement in the activation of CCND1. Finally, we did not observe any mutation in the coding frame of the CCND1 cDNA analyzed.
The effectiveness and cost-effectiveness of ultrasound locating devices for central venous access: a systematic review and economic evaluation (2003)

Assessment (HTA) Programme was set
Aerosolized 3-Bromopyruvate Inhibits Lung Tumorigenesis without Causing Liver Toxicity (2012)

3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. However, the chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been tested. In this study, we investigated the chemopreventive activity of 3-bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice. We found that 3-bromopyruvate significantly decreased tumor multiplicity and tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given large doses of 3-bromopyruvate, confirmed in this study, we decided to test the chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10 mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate did not accompany any liver toxicity indicating that it is a safer route of administering this compound. Treatment with 3-bromopyruvate increased immunohistochemical staining for cleaved caspase-3, suggesting that the lung tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis. 3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced hexokinase activity, and blocked energy metabolism in cancer cells, finally triggered cancer cell death and induced apoptosis through caspase-3, and PARP in human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung tumorigenesis, in part through induction of apoptosis, merits further investigation of this compound as a chemopreventive agent for human lung cancer.
Inhibition of ATR Leads to Increased Sensitivity to Hypoxia/Reoxygenation (2004)

The transient opening and closing of tumor vasculature result in periods of severe oxygen deprivation (hypoxia) followed by reoxygenation. This exerts a positive selective pressure for cells that have lost their sensitivity to killing by reduced oxygen levels. These cells are effectively resistant to hypoxia-induced apoptosis and conventional therapeutic approaches. Here we show hypoxia-induced S-phase arrest results in regions of single-stranded DNA in stalled replication forks and signals the activation of ATR. S-phase cells represent the most sensitive phase of the cell cycle to the stress of hypoxia/reoxygenation. Loss of ATR or inhibition of ATR kinase activity results in a further loss of reproductive viability in S-phase cells when exposed to hypoxic conditions followed by reoxygenation but has little effect on the inhibition of DNA synthesis. This is, at least in part, mediated via Chk1 signaling because loss of Chk1 also results in increased sensitivity to hypoxia/reoxygenation. The observed decrease in reproductive survival is in part because of the accumulation of DNA damage in S-phase cells during hypoxia exposure in the absence of full ATR activity. Therefore, ATR acts to protect stalled replication forks during hypoxia exposure. In conclusion, ATR and Chk1 play critical roles in the cellular response to hypoxia/reoxygenation, and inhibitors of ATR and Chk1 represent new hypoxic cell cytotoxins.
A common framework for syntactic annotation (2001)

It is widely recognized that the proliferation of annotation schemes runs counter to the need to re-use language resources, and that standards for linguistic annotation are becoming increasingly mandatory. To answer this need, we have developed a representation framework comprised of an abstract model for a variety of different annotation types (e.g., morpho-syntactic tagging, syntactic annotation, co-reference annotation, etc.), which can be instantiated in different ways depending on the annotator s approach and goals. In this paper we provide an overview of our representation framework and demonstrate its applicability to syntactic annotation. We show how the framework can contribute to comparative evaluation and merging of parser output and diverse syntactic annotation schemes.
Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factor of vertebrates. (1988)

Delta (D1) is required for normal segregation of the embryonic ectoderm into neural and epidermal cell lineages in Drosophila melanogaster. Loss-of-function mutations in D1 and other zygotic neurogenic loci lead to expansion of the neuroblast population at the expense of the dermoblast population within the ectoderm. Characterization of the transcriptional organization and maternal/embryonic expression within the chromosomal interval corresponding to D1 reveals that the locus encodes multiple transcripts: a minimum of two maternal transcripts, approximately 4.5 and 3.6 kb in length, and four zygotic transcripts, approximately 5.4 (two distinct species), 3.5, and 2.8 kb in length. These transcripts differ on the bases of differential splicing and differential polyadenylation site choice. The DNA sequence of a cDNA clone representing the predominant transcripts of the locus indicates that D1 encodes a transmembrane protein homologous to blood coagulation factors and epidermal growth factor. The relationship between coding sequences and transcript-specific exons within the locus suggests that D1 encodes multiple translational products.
Tumor Selectivity of Hsp90 Inhibitors: The Explanation Remains Elusive (2006)

Two recent papers attempt to solve both the tumor selectivity and the in vivo tumor accumulation profiles seen with some Hsp90 inhibitors. They spotlight the higher affinity of ansamycins' hydroquinone over the quinone form for Hsp90 and further discuss its possible contribution to ansamycins' tumor selectivity.
Motor evoked potentials (MEP) and evoked pressure curves (EPC) from the urethral compressive musculature (UCM) by functional magnetic stimulation in healthy volunteers and patients with neurogenic incontinence (2004)

MEP and EPC from the UCM proved to be a well tolerated disgnostic tool in patients with neurogenic incontinence that distinguished central and peripheral lesions of the motor efferent pathways to the UCM.
Nanoelectrochemistry: Metal Nanoparticles, Nanoelectrodes, and Nanopores (2008)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTNanoelectrochemistry: Metal Nanoparticles, Nanoelectrodes, and NanoporesRoyce W. Murray, *View Author Information Kenan Laboratories of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290* E-mail, [email protected]; telephone, 919-962-6296; fax, 919-962-2542. Cite this: Chem. Rev. 2008, 108, 7, 2688–2720Publication Date (Web):June 18, 2008Publication History Received27 July 2007Published online18 June 2008Published inissue 1 July 2008https://pubs.acs.org/doi/10.1021/cr068077ehttps://doi.org/10.1021/cr068077eresearch-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views20237Altmetric-Citations1043LEARN 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:Electrodes,Gold,Metal nanoparticles,Nanoparticles,Nanopores Get e-Alerts
Oxidative decarboxylation of isocitric acid in the presence of montmorillonite (1990)

Abstract Isocitric acid oxidative decarboxylation was realized in the absence and in the presence of homoionic Na + -, Mn 2+ -, and Cu 2+ -montmorillonite. The catalytic activity of the clay depends upon the nature of the interlayer exchangeable cation. Isocitric acid is transformed into α-ketoglutaric acid under the action of the clay mineral saturated with Na + cations which do not form a complex with the isocitrate anion. Nevertheless, the reaction rate is very much lower than in the presence of the enzymatic system (isocitrate dehydrogenase enzyme and nicotinamide adenine dinucleotide phosphate coenzyme). The reaction mechanism in the presence of clay is given showing the different steps of the transformation.
Umlagerungen in der Thiazolreihe (1959)

Abstract 3‐Phenyl‐thiazolon‐2‐hydrazone und ihre Derivate lagern sich mit Säuren leicht in die isomeren 3‐Amino‐2‐phenylimino‐thiazolone um. Es werden Synthese und Konstitutionsbeweis dieser Verbindungen mitgeteilt. Die komplizierten Verhältnisse beim Ringschluß von α‐Halogenketonen mit Thiosemicarbaziden werden geklärt. Je nach 1‐ und 4‐Substituenten des Thiosemicarbazids entstehen verschiedene Endprodukte. Die Konstitution einiger in der Literatur beschriebenen Thiazolderivate wird berichtigt.
Restoring large-scale brain networks in PTSD and related disorders: a proposal for neuroscientifically-informed treatment interventions (2015)

Neuroscientifically-informed treatment interventions will be essential to future research agendas aimed at targeting specific PTSD and related symptoms.
Angiopoietins and Tie2 in health and disease. (2005)

The angiopoietins are a class of growth factors that activate the Tie2 receptor and play important roles in the regulation of angiogenesis. Proper regulation of angiogenesis is required for both embryonic vascular development and physiological processes in the adult such as wound healing and the female reproductive cycle, while aberrant regulation of angiogenesis contributes to a number of pathological conditions. As a result, an increasing amount of attention has been directed toward analysis of the expression and function of the angiopoietins and Tie2. Mounting evidence suggests that not only does altered expression of these molecules play a pivotal role in processes requiring vessel growth and remodeling, but has been implicated in a variety of other biological and pathological processes as well. These data suggest that modulation of the Ang/Tie2 system may prove to be a desirable therapeutic goal in the treatment of a diverse array of pathological conditions.
Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design (2002)

The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S(4) pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K(i) = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K(i) values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K(i) = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.
Efficacy of PHA-848125, a Cyclin-Dependent Kinase Inhibitor, on the K-RasG12DLA2 Lung Adenocarcinoma Transgenic Mouse Model: Evaluation by Multimodality Imaging (2010)

K-ras is the most frequently mutated oncogene in non-small cell lung cancer (NSCLC), the most common form of lung cancer. Recent studies indicate that NSCLC patients with mutant K-ras do not respond to epidermal growth factor receptor inhibitors. In the attempt to find alternative therapeutic regimes for such patients, we tested PHA-848125, an oral pan cyclin-dependent kinase inhibitor currently under evaluation in phase II clinical trial, on a transgenic mouse model, K-Ras(G12D)LA2, which develops pulmonary cancerous lesions reminiscent of human lung adenocarcinomas. We used magnetic resonance imaging and positron emission tomography to follow longitudinally disease progression and evaluate therapeutic efficacy in this model. Treatment of K-Ras(G12D)LA2 mice with 40 mg/kg twice daily for 10 days with PHA-848125 induced a significant tumor growth inhibition at the end of treatment (P < 0.005) and this was accompanied by a reduction in the cell membrane turnover, as seen by 11C-Choline-positron emission tomography (P < 0.05). Magnetic resonance imaging data were validated versus histology and the mechanism of action of the compound was verified by immunohistochemistry, using cyclin-dependent kinase-related biomarkers phospho-Retinoblastoma and cyclin A. In this study, multimodality imaging was successfully used for the preclinical assessment of PHA-848125 therapeutic efficacy on a lung adenocarcinoma mouse model. This compound induced a volumetric and metabolic anticancer effect and could represent a valid therapeutic approach for NSCLC patients with mutant K-ras.
Second generation knockout sickle mice: the effect of HbF (2001)

Abstract Sickle transgenic mice expressing exclusively human globins are desirable for studying pathophysiology and testing gene therapy strategies, but they must have significant pathology and show evidence of amelioration by antisickling hemoglobins. Mice were generated that expressed exclusively human sickle hemoglobin with 3 levels of HbF using their previously described sickle constructs (cointegrated human miniLCRα2 and miniLCRβS [PNAS 89:12150, 1992]), mouse α- and β-globin-knockouts, and 3 different human γ-transgenes. It was found that, at all 3 levels of HbF expression, these mice have balanced chain synthesis, nearly normal mean corpuscular hemoglobin, and, in some cases, F cells. Mice with the least adult HbF expression were the most severe. Progressive increase in HbF from less than 3% to 20% to 40% correlated with progressive increase in hematocrit (22% to 34% to 40%) and progressive decrease in reticulocyte count (from 60% to 30% to 13%). Urine concentrating ability was normalized at high HbF, and tissue damage detected by histopathology and organ weight were ameliorated by increased HbF. The γ-transgene that produces intermediate levels of HbF was introduced into knockout sickle mice described by Pàszty and coworkers that express the miniLCRα1GγAγδβStransgene and have fetal but not adult expression of HbF. It was found that the level of HbF required to ameliorate low hematocrit and normalize urine concentrating defect was different for the miniLCRα2βS and miniLCRα1GγAγδβS mice. We conclude that knockout mice with the miniLCRα2βS transgene and postnatal expression of HbF have sufficiently faithful sickle pathology to serve as a platform for testing antisickling interventions.