gebhart/patrepeval huggingface dataset:
Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy (2011)

Cancer stem cell (SC) chemoresistance may be responsible for the poor clinical outcome of non-small-cell lung cancer (NSCLC) patients. In order to identify the molecular events that contribute to NSCLC chemoresistance, we investigated the DNA damage response in SCs derived from NSCLC patients. We found that after exposure to chemotherapeutic drugs NSCLC-SCs undergo cell cycle arrest, thus allowing DNA damage repair and subsequent cell survival. Activation of the DNA damage checkpoint protein kinase (Chk) 1 was the earliest and most significant event detected in NSCLC-SCs treated with chemotherapy, independently of their p53 status. In contrast, a weak Chk1 activation was found in differentiated NSCLC cells, corresponding to an increased sensitivity to chemotherapeutic drugs as compared with their undifferentiated counterparts. The use of Chk1 inhibitors in combination with chemotherapy dramatically reduced NSCLC-SC survival in vitro by inducing premature cell cycle progression and mitotic catastrophe. Consistently, the co-administration of the Chk1 inhibitor AZD7762 and chemotherapy abrogated tumor growth in vivo, whereas chemotherapy alone was scarcely effective. Such increased efficacy in the combined use of Chk1 inhibitors and chemotherapy was associated with a significant reduction of NSCLC-SCs in mouse xenografts. Taken together, these observations support the clinical evaluation of Chk1 inhibitors in combination with chemotherapy for a more effective treatment of NSCLC.
Adapting to Climate Change: Who Should Pay (2007)

In Massachusetts v. EPA,2 the Supreme Court, for the first time, acknowledged the reality of climate change. The state of Massachusetts brought suit to challenge the Environmental Protection Agency's (EPA) refusal to limit carbon dioxide (CO2) emissions from automobiles.3 To gain standing, the State had to demonstrate that it was injured by climate change.4 Central to its claim of injury was the allegation that sea level rise, caused by climate change, had already begun to eat away at its coastlines and would increasingly do so in the future.5 The State also cited the funds that it would be required to spend to ameliorate the im-
From Cascaded Catalytic Nucleic Acids to Enzyme–DNA Nanostructures: Controlling Reactivity, Sensing, Logic Operations, and Assembly of Complex Structures (2014)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTFrom Cascaded Catalytic Nucleic Acids to Enzyme–DNA Nanostructures: Controlling Reactivity, Sensing, Logic Operations, and Assembly of Complex StructuresFuan Wang, Chun-Hua Lu, and Itamar Willner*View Author Information Institute of Chemistry, The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem 91904, Israel*E-mail: [email protected]Cite this: Chem. Rev. 2014, 114, 5, 2881–2941Publication Date (Web):February 27, 2014Publication History Received4 July 2013Published online27 February 2014Published inissue 12 March 2014https://doi.org/10.1021/cr400354zCopyright © 2014 American Chemical SocietyRIGHTS & PERMISSIONSACS Editors’ ChoiceArticle Views24383Altmetric-Citations535LEARN 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 InReddit PDF (35 MB) Get e-AlertscloseSUBJECTS:Chemical structure,Genetics,Nanostructures,Nucleic acids,Peptides and proteins Get e-Alerts
Elastase released from human granulocytes stimulated with N‐formyl‐chemotactic peptide prevents activation of tumor cell prourokinase (pro‐uPA) (1989)

Proteolytic enzymes released from granulocytes upon stimulation with the chemotactic N-formyl peptide FNLPNTL (in the presence of cytochalasin B) prevented activation of tumor cell single-chain urokinase-type plasminogen activator (pro-uPA) by plasmin. Elastase was identified by the use of eglin C (elastase inhibitor) and a monoclonal antibody to elastase as the functional proteolytic enzyme in granulocyte supernatants. Action of purified granulocyte elastase on pro-uPA generated enzymatically inactive two-chain uPA linked by disulfide bridges which was indistinguishable by SDS-PAGE from plasmin-generated HMW-uPA. The major elastase cleavage site in pro-uPA was located between Ile159 and Ile160. a minor one between Thr165 and Thr166. Elastase cannot substitute for plasmin in the proteolytic activation of pro-uPA to enzymatically active HMW-uPA. However, when pro-uPA was first activated by plasmin to form enzymatically active HMW-uPA, this enzymatic activity was not impaired by subsequent elastase treatment.
Evaluation of magnetic materials for very high frequency power applications (2008)

This paper investigates the loss characteristics of several commercial rf magnetic materials for power conversion applications in the 10 MHz to 100 MHz range. A measurement method is proposed that provides a direct measurement of inductor quality factor QL as a function of inductor current at rf frequencies, and enables indirect calculation of core loss as a function of flux density. Possible sources of error in measurement and calculation are evaluated and addressed. The proposed method is used to identify loss characteristics of different commercial rf magnetic core materials. The loss characteristics of these materials, which have not previously been available, are illustrated and compared in tables and figures. The results of this paper are thus useful for design of magnetic components for very high frequency applications.
IL-15 an immunoregulatory and anti-cancer cytokine. Recent advances. (2006)

Interleukins are mediators of inflammation, immunity and cancer. IL-15 is a cytokine produced by several leukocytes including phagocytes in response to infections and other signals that trigger innate immunity. IL-15 has many homologies to interleukin-2 (IL-2) and like IL-2, stimulates NK cells. This cytokine acts also on memory CD8+ T-cell. IL-15, therefore acts, probably through selective inhibition of tumor promoting molecules, as a new compound for the adjuvant treatment of solid tumors. In this review we propose a newly revised mechanism of interleukin 15 in inflammation and cancer.
Improving vision in adult amblyopia by perceptual learning (2004)

Practicing certain visual tasks leads, as a result of a process termed "perceptual learning," to a significant improvement in performance. Learning is specific for basic stimulus features such as local orientation, retinal location, and eye of presentation, suggesting modification of neuronal processes at the primary visual cortex in adults. It is not known, however, whether such low-level learning affects higher-level visual tasks such as recognition. By systematic low-level training of an adult visual system malfunctioning as a result of abnormal development (leading to amblyopia) of the primary visual cortex during the "critical period," we show here that induction of low-level changes might yield significant perceptual benefits that transfer to higher visual tasks. The training procedure resulted in a 2-fold improvement in contrast sensitivity and in letter-recognition tasks. These findings demonstrate that perceptual learning can improve basic representations within an adult visual system that did not develop during the critical period.
A Conformational Switch in Nuclear Hormone Receptors Is Involved in Coupling Hormone Binding to Corepressor Release (1997)

Nuclear hormone receptors are ligand-regulated transcription factors that modulate gene expression in response to small, hydrophobic hormones, such as retinoic acid and thyroid hormone. The thyroid hormone and retinoic acid receptors typically repress transcription in the absence of hormone and activate it in the presence of hormone. Transcriptional repression is mediated, in part, through the ability of these receptors to physically associate with ancillary polypeptides called corepressors. We wished to understand the mechanism by which corepressors are recruited to unliganded nuclear hormone receptors and are released on the binding of hormone. We report here that an alpha-helical domain located at the thyroid hormone receptor C terminus appears to undergo a hormone-induced conformational change required for release of corepressor and that amino acid substitutions that abrogate this conformational change can impair or prevent corepressor release. In contrast, retinoid X receptors appear neither to undergo an equivalent conformational alteration in their C termini nor to release corepressor in response to cognate hormone, consistent with the distinct transcriptional regulatory properties displayed by this class of receptors.
Molecular genetics of human serum albumin: restriction enzyme fragment length polymorphisms and analbuminemia. (1983)

By using cDNA probes for the human albumin gene, four restriction enzyme fragment length polymorphisms (RFLPs) were discovered that were transmitted by codominant autosomal inheritance. Among Caucasians, the gene frequencies were 0.04/0.96 for Msp I/5', 0.43/0.57 for Hae III/3', 0.44/0.56 for Hae III/5', and 0.04/0.42/0.54 for Pst I/5'. These common variants provide a marker for chromosome 4 (q11-q13). A calculation of the extent of DNA variation at the albumin locus revealed that 1/95 nucleotide sites was affected by a RFLP, a figure similar to that found in the globin system. Restriction enzyme fragment study of the DNA of a human analbuminemic individual revealed no gross structural rearrangements of the albumin locus. The exact nature of abnormality will require more study.
Disposition of the plant phenol ellagic acid in the mouse following oral administration by gavage (1988)

1. The absorption, distribution and elimination of 3H-ellagic acid, a putative antimutagen and anticarcinogen, was studied in male Swiss-Webster mice following oral administration. 2. Levels of 3H-ellagic acid were highest in blood 30 min after administration, in urine and bile 120 min post-administration, and in liver, lung and kidney 15 min after administration [corrected]. 3. Free ellagic acid and its conjugates were present in urine, bile and blood. H.p.l.c. analysis of the organic solvent extracts of urine, bile and blood indicated the presence of four metabolites in urine, two in blood and one in bile. 4. Sulphate ester, glucuronide and glutathione conjugates of ellagic acid were present in urine, bile and blood. H.p.l.c. analysis of organic solvent extracts after aryl sulphatase or beta-glucuronidase treatment showed that ellagic acid was the major component present. 5. Absorption of 3H-ellagic acid occurred mostly within two hours after oral administration. Levels in blood, bile and tissues were low and almost all of the absorbed dose was excreted in urine. 6. More than 53% of the orally administered 3H-ellagic acid remained in the gastrointestinal tract at 24 h. Approximately 19% was excreted in faeces and 22% in urine at 24 h. 7. Of the 24 h faecal radioactivity 93% was extractable into organic solvents and more than 80% of this fraction was free ellagic acid. Only one metabolite was found in faeces.
Aqueous shift reagents for high‐resolution cation NMR. VI. Titration curves for in vivo23Na and 1H2O MRS obtained from rat blood (1993)

Frequency shift/concentration calibration curves applicable to the use of shift reagents (SRs) for in vivo 23Na MRS studies can be obtained from experiments with whole blood. Here, they are reported for titrations of rat blood with the SRs DyTTHA3- and TmDOTP5-. There are a number of considerations that must be made in order to derive accurate calibration curves from the experimental data. These include the effects of bulk magnetic susceptibility (BMS, since the SRs are paramagnetic), the effects of water flux (since addition of the SR stock solution to blood renders the plasma hyperosmotic), and the consequences of restricted distribution of the SR anion in the erythrocyte suspension. We give in some detail the BMS shift theory that obtains in this case and show also how it applies to excised perfused organ as well as in vivo studies. Also, we report significant effects of adjuvant Ca2+ additions in the TmDOTP5- titrations. These are very important to the successful use of this SR in vivo. Finally, our considerations of BMS lead naturally to an understanding of its manifestations in the shifts of the 1H2O resonance frequencies of cell suspensions and tissues induced by SRs. Since these are being increasingly reported, and often misinterpreted, we devote an experiment and some discussion to this subject. We show that this phenomenon cannot be used to quantitatively discriminate intra- and extracellular 1H2O signals.
Controlled Translocation of Individual DNA Molecules through Protein Nanopores with Engineered Molecular Brakes (2011)

Protein nanopores may provide a cheap and fast technology to sequence individual DNA molecules. However, the electrophoretic translocation of ssDNA molecules through protein nanopores has been too rapid for base identification. Here, we show that the translocation of DNA molecules through the α-hemolysin protein nanopore can be slowed controllably by introducing positive charges into the lumen of the pore by site directed mutagenesis. Although the residual ionic current during DNA translocation is insufficient for direct base identification, we propose that the engineered pores might be used to slow down DNA in hybrid systems, for example, in combination with solid-state nanopores.
BMP-7 influences pattern and growth of the developing hindbrain of mouse embryos (1997)

ABSTRACT The expression pattern of bone morphogenetic protein-7 (BMP-7) in the hindbrain region of the headfold and early somite stage developing mouse embryo suggests a role for BMP-7 in the patterning of this part of the cranial CNS. In chick embryos it is thought that BMP-7 is one of the secreted molecules which mediates the dorsalizing influence of surface ectoderm on the neural tube, and mouse surface ectoderm has been shown to have a similar dorsalizing effect. While we confirm that BMP-7 is expressed in the surface ectoderm of mouse embryos at the appropriate time to dorsalize the neural tube, we also show that at early stages of hindbrain development BMP-7 tran-scripts are present in paraxial and ventral tissues, within and surrounding the hindbrain neurectoderm, and only later does expression become restricted to a dorsal domain. To determine more directly the effect that BMP-7 may have on the developing hindbrain we have grafted COS cells expressing BMP-7 into the ventrolateral mesoderm abutting the neurectoderm in order to prolong BMP-7 expression in the vicinity of ventral hindbrain. Three distinct actvities of BMP-7 are apparent. Firstly, as expected from previous work in chick, BMP-7 can promote dorsal characteristics in the neural tube. Secondly, we show that it can also attenuate the expression of sonic hedgehog (Shh) in the floorplate without affecting Shh expression in the notochord. Finally, we find that ectopic BMP-7 appears to promote growth of the neurectoderm. These findings are discussed with respect to possible timing mechanisms necessary for the coordination of hindbrain dorsoventral patterning.
108. The oxidation of 2-hydroxyquinoxaline and its derivatives with hydrogen peroxide (1948)

G. T. Newbold and F. S. Spring, J. Chem. Soc., 1948, 519 DOI: 10.1039/JR9480000519
F protein-F protein interaction within the Sendai virus identified by native bonding or chemical cross-linking. (1987)

The spatial arrangement of the F protein spike in the Sendai virus was studied after purifying the protein and reconstituting it in lipid vesicles (Sechoy, O., Philippot, J. R., and Bienvenue, A. (1986) Biochim. Biophys. Acta 857, 1-12). The different components of the F protein spikes were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under various conditions of treatment, i.e. at different temperatures and sodium dodecyl sulfate concentrations, using different detergents for F protein solubilization (Triton X-100 and octyl glucoside), by fast protein liquid chromatography analysis, and by chemical cross-linking between subunits with bifunctional agents such as dimethyl adipimidate and dithiobis(succinimidyl propionate). The F protein spike appeared to be a structurally stable complex, composed of a noncovalent association of four homooligomers, each consisting of two peptides, F1 and F2, linked by a disulfide bond. Octyl glucoside and Triton X-100 solubilized the F protein, preserving the tetramer, which is probably the native form. Using chemical cross-linking, a covalent bond was formed between two monomers. We hypothesize that the tetrameric form of the F protein in its native form (spike) consists of two identical dimers that can be chemically cross-linked in a stable complex.
Mechanisms of gene regulation by endogenous and artificially introduced antisense RNA (1992)

Conference Article| November 01 1992 Mechanisms of gene regulation by endogenous and artificially introduced antisense RNA Wolfgang Nellen; Wolfgang Nellen * 1Max-Planck-lnstitut f. Biochemie, 8033 Martinsried, Germany *To whom correspondence should be addressed. Search for other works by this author on: This Site PubMed Google Scholar Martin Hildebrandt; Martin Hildebrandt † 1Max-Planck-lnstitut f. Biochemie, 8033 Martinsried, Germany Search for other works by this author on: This Site PubMed Google Scholar Beatrice Mahal; Beatrice Mahal 1Max-Planck-lnstitut f. Biochemie, 8033 Martinsried, Germany Search for other works by this author on: This Site PubMed Google Scholar Axel Möhrle; Axel Möhrle ‡ 1Max-Planck-lnstitut f. Biochemie, 8033 Martinsried, Germany Search for other works by this author on: This Site PubMed Google Scholar Petra Kröger; Petra Kröger 1Max-Planck-lnstitut f. Biochemie, 8033 Martinsried, Germany Search for other works by this author on: This Site PubMed Google Scholar Markus Maniak; Markus Maniak § 1Max-Planck-lnstitut f. Biochemie, 8033 Martinsried, Germany Search for other works by this author on: This Site PubMed Google Scholar Rebecca Oberhauser; Rebecca Oberhauser 1Max-Planck-lnstitut f. Biochemie, 8033 Martinsried, Germany Search for other works by this author on: This Site PubMed Google Scholar May Sadiq May Sadiq ‖ 1Max-Planck-lnstitut f. Biochemie, 8033 Martinsried, Germany Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1992) 20 (4): 750–754. https://doi.org/10.1042/bst0200750 Article history Received: June 19 1992 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation Wolfgang Nellen, Martin Hildebrandt, Beatrice Mahal, Axel Möhrle, Petra Kröger, Markus Maniak, Rebecca Oberhauser, May Sadiq; Mechanisms of gene regulation by endogenous and artificially introduced antisense RNA. Biochem Soc Trans 1 November 1992; 20 (4): 750–754. doi: https://doi.org/10.1042/bst0200750 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: dsRNase, double strand specific ribonuclease This content is only available as a PDF. © 1992 Biochemical Society1992 Article PDF first page preview Close Modal You do not currently have access to this content.
Intrathecal non-NMDA excitatory amino acid receptor antagonists inhibit pain behaviors in a rat model of postoperative pain (1998)

Evidence indicates that excitatory amino acids (EAAs) like glutamate and aspartate are important in the processing of nociceptive information in the dorsal horn of the spinal cord. Recently, the role of particular EAA receptors in pain transmission and facilitated pain states has been examined utilizing spinal administration of specific receptor antagonists. Most investigators have studied the involvement of N-methyl-D-aspartate (NMDA) EAA receptors in hyperalgesia and nociception; less is known about the importance of non-NMDA EAA receptors in animal models of persistent pain. To study the role of spinal non-NMDA EAA receptors in pain behaviors caused by an incision, we examined the effect of i.t. administered non-NMDA EAA receptor antagonists in a rat model of postoperative pain. Rats with i.t. catheters were anesthetized and underwent a plantar incision. Withdrawal threshold to punctate stimulation applied adjacent to the wound using von Frey filaments, response frequency to application of a non-punctate stimulus applied directly to the wound and non-evoked pain behaviors were measured before and after administration of i.t. 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo[f]quinoxaline-7-sulfonamide (NBQX), 6,7-dinitroquinoxaline-2,3-dione (DNQX), or vehicle. A separate group of animals were also tested for motor impairment caused by these drugs. In the vehicle-treated group, the median withdrawal threshold for punctate hyperalgesia decreased from 522 mN before surgery to 39 mN 2 h later; hyperalgesia was persistent. Intrathecal administration of 5 or 10 nmol of NBQX returned the withdrawal threshold toward preincision values; the median withdrawal thresholds were 158 and 360 mN, respectively. Intrathecal administration of 10 nmol of DNQX similarly increased the withdrawal threshold after incision. In separate groups of animals, i.t. administration of 5 or 10 nmol of NBQX decreased the response frequency to a non-punctate stimulus applied directly to the incision from 100+/-0% 2 h after surgery to 22+/-11 and 0+/-0% 30 min after drug injection, respectively. Similar results were observed with i.t. administration of 10 nmol of DNQX. Intrathecal NBQX also inhibited non-evoked pain behavior. In conclusion, non-NMDA receptor antagonists produced a marked decrease in pain behaviors in this model of postoperative pain. Thus, non-NMDA receptors are important for the maintenance of short-term pain behaviors caused by an incision and drugs blocking these receptors may be useful for the treatment of postoperative pain in patients.
An Orally Bioavailable, Functionally Selective Inverse Agonist at the Benzodiazepine Site of GABAA α5 Receptors with Cognition Enhancing Properties (2004)

(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (13) has been identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors. 13 is orally bioavailable, readily penetrates the CNS, and enhances performance in animal models of cognition. It does not exhibit the convulsant, proconvulsant, or anxiogenic activity associated with nonselective GABA(A) inverse agonists.