gebhart/patrepeval huggingface dataset:
Abstract A164: The small molecule UAE inhibitor TAK-243 (MLN7243) prevents DNA damage repair and reduces cell viability/tumor growth when combined with radiation, carboplatin and docetaxel (2015)

Abstract Clinical results of VELCADE® (bortezomib) For Injection have prompted evaluation of other enzymes within the ubiquitin proteasome system (UPS) as druggable targets for human cancer. We have identified a first in class investigational drug, TAK-243 (MLN7243), which targets the ubiquitin activating enzyme, UAE (UBA1), an essential cellular enzyme responsible for activating &amp;gt; 99% of all cellular ubiquitin. Ubiquitin is involved in multiple cellular processes including ubiquitin-dependent protein turnover, cell cycle progression, regulation of apoptosis, protein localization and response to DNA damage. Experiments combining targeted siRNA knockdown with TAK-243 identified DNA damage repair genes necessary for UAE inhibitor-induced cell death. A more focused approach revealed TAK-243 treatment blocked essential monoubiquitination events within the Translesion synthesis (TLS), Fanconi Anemia (FA) and Homologous recombination (HR) pathways. Inhibition of UAE prevented mono-ubiquitin signaling of key mediators within these pathways, including PCNA and FANCD2, by blocking formation of their specific E2-ubiquitin thioesters. In vitro cell-based assays combining TAK-243 with ultraviolet (UV) and radiation, both known to induce DNA damage, yielded inhibition of cell growth and enhanced DNA damage as observed through colony formation assays and Comet assay detection, respectively. Xenograft tumor bearing mice were treated with carboplatin or docetaxel, combined with TAK-243, to evaluate combination benefits in vivo. Synergistic and additive anti-tumor combination benefits were observed in animals treated with TAK-243 + carboplatin and TAK-243 + docetaxel. These important mechanistic in vitro and in vivo studies indicate the dependency of ubiquitination signaling in DNA damage repair and provide a mechanistic rationale for combining radiation, carboplatin or docetaxel with TAK-243 in the clinical setting. Currently, TAK-243 is being evaluated in a solid tumor phase I clinical trial evaluating safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity (ClinicalTrials.gov identifier: NCT02045095). Citation Format: Michael A. Milhollen, Judi Shi, Tary Traore, Jessica Huck, Darshan Sappal, Jennifer Duffy, Eric Lightcap, Yuko Ishii, Jeff Ciavarri, Paul Fleming, Neil Bence, Marc L. Hyer. The small molecule UAE inhibitor TAK-243 (MLN7243) prevents DNA damage repair and reduces cell viability/tumor growth when combined with radiation, carboplatin and docetaxel. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A164.
Knowledge, attitudes, beliefs, and behaviors of pregnant women approached to participate in a Tdap maternal immunization randomized, controlled trial (2016)

Immunization with pertussis vaccine during pregnancy is recommended in a number of countries to prevent newborn deaths from whooping cough. In some jurisdictions, vaccine uptake during pregnancy is low. We undertook a survey of the knowledge, attitudes, beliefs, and behaviors of pregnant women who had been approached to participate in a randomized, controlled trial of tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy. A total of 346 women completed the survey. Knowledge about pertussis and pertussis vaccine was generally low; the mean number of correct answers was 10.65 out of 19 questions. Attitudes toward maternal immunization were generally favorable; 51.7%-94.7% of women had positive responses to 10 attitudinal statements. Substantial uncertainty was shown in responses to a number of the attitudinal statements related to vaccination during pregnancy; 22.3%-45.7% neither agreed nor disagreed with the statements. Importantly, 89% of women reported that they would get immunized with pertussis vaccine during pregnancy if their physician recommended it. We conclude that a national recommendation to be immunized with pertussis vaccine during pregnancy supported by their physicians' recommendation would be well received by Canadian women.
Estradiol Induces Export of Sphingosine 1-Phosphate from Breast Cancer Cells via ABCC1 and ABCG2 (2010)

Sphingosine 1-phosphate (S1P), a potent sphingolipid mediator produced by sphingosine kinase isoenzymes (SphK1 and SphK2), regulates diverse cellular processes important for breast cancer progression acting in an autocrine and/or paracrine manner. Here we show that SphK1, but not SphK2, increased S1P export from MCF-7 cells. Whereas for both estradiol (E(2)) and epidermal growth factor-activated SphK1 and production of S1P, only E(2) stimulated rapid release of S1P and dihydro-S1P from MCF-7 cells. E(2)-induced S1P and dihydro-S1P export required estrogen receptor-alpha, not GPR30, and was suppressed either by pharmacological inhibitors or gene silencing of ABCC1 (multidrug resistant protein 1) or ABCG2 (breast cancer resistance protein). Inhibiting these transporters also blocked E(2)-induced activation of ERK1/2, indicating that E(2) activates ERK via downstream signaling of S1P. Taken together, our findings suggest that E(2)-induced export of S1P mediated by ABCC1 and ABCG2 transporters and consequent activation of S1P receptors may contribute to nongenomic signaling of E(2) important for breast cancer pathophysiology.
ChemInform Abstract: Benzimidazoles as New Scaffold of Sirtuin Inhibitors: Green Synthesis, in vitro Studies, Molecular Docking Analysis and Evaluation of Their Anticancer Properties. (2014)

Abstract New benzimidazole derivative (Ve) displays equipotent inhibitory activities for sirtuin‐1 as well as better inhibitory activities for sirtuin‐2 compared to standard controls cambinol and tenovin‐6.
Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. (1991)

A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)
Method of sintering materials with microwave radiation (2023)

A method of sintering ceramic materials following: A compacted article comprising inorganic particles coated with carbon is provided, the carbon providing improved microwave coupling. The compacted article is then heated by microwave radiation to a temperature and for a period of time sufficient to sinter the compacted article.
Comparative Lipidomics Profiling of Human Atherosclerotic Plaques (2011)

This comprehensive analysis of plaque lipids demonstrates the potential of lipidomics for unraveling the lipid heterogeneity within atherosclerotic lesions.
Cardiovascular responses to static exercise in distance runners and weight lifters (1980)

Sixty individuals including 17 competitive weight lifters (CWL), 12 competitive long-distance runners (LDR), 7 amateur (noncompetitive) weight lifters (AWL), 14 heavy controls (HC), and 10 light controls (LC) were studied at supine rest and during static exercise at 40% of maximal voluntary contraction. Blood pressures were similar in all groups at rest (R) and exercise (EX), but the heart rate (HR) and calculated double product (DP) of the LDR were lower at rest (HR: 53 +/- 2.9 beats/min, DP: 6,346 +/- 402) and at fatigue (HR: 78 +/- 5.4 beats/min. DP: 12,739 +/- 1,011) compared to the control group (R-HR: 69 +/- 2.2 beats/min, DP: 8,553 +/- 372; EX-HR: 97 +/- 3.5 beats/min, DP: 16,345 +/- 836). The LDR demonstrated higher end-diastolic volume index (EDVI) and higher end-systolic volume index (ESVI) at rest (EDVI: 84 +/- 3.7, ESVI: 31 +/- 2.7 ml/m2) and at the time of fatigue (EDVI: 90 +/- 5, ESVI: 37 +/- 2.7 ml/m2) compared to the LC group (R-EDVI: 61 +/- 4.4, ESVI: 22 +/- 2.2; EX-EDVI: 75 +/- 3.4, ESVI: 27 +/- 3.2 ml/m2). The CWL, AWL, and control groups had similar HR, DP, and cardiac volumes at rest and during exercise. These data suggest that competitive endurance (dynamic exercise) training alters the cardiovascular response to static exercise. On the other hand, weight lifting (static exercise) training does not alter the cardiovascular response to static exercise.
Use of Severely Steatotic Grafts in Liver Transplantation (2007)

Due to the urgent need of liver grafts, severely steatotic grafts should be no longer discarded for OLT. Maximal effort must be spent when dealing with these high-risk organs but the use of severely steatotic grafts may save the lives of many patients who would die on the waiting list.
Alternating Misfit Layered Transition/Alkaline Earth Metal Chalcogenide Ca3Co4O9 as a New Class of Chalcogenide Materials for Hydrogen Evolution (2014)

Layered misfit chalcogenide structures have garnered much attention and prestige in several applications such as thermoelectric materials and high-temperature superconductors. However, its potentials for important electrochemical applications such as hydrogen evolution and oxygen reduction reactions have not been systematically studied. Till date, such applications have mainly applied precious metal and oxides with perovskite- or spinel-based structures. In this work, we synthesized a misfit layered mixed oxide in the form of Ca3Co4O9 and investigated its structural, morphological, and electrochemical properties. The misfit layered Ca3Co4O9 has promising capabilities as electrocatalyst for hydrogen evolution and oxygen reduction processes. A Tafel slope of 87 mV/decade for hydrogen evolution reaction was achieved by Ca3Co4O9, while the overpotential for oxygen reduction reaction was lowered up to 38 mV in comparison to glassy carbon. Moreover, a comparably higher heterogeneous electron transfer rate of 3.76 × 10–4 cm s–1 was achieved for Ca3Co4O9 compared to 3.11 × 10–4 cm s–1 for glassy carbon. The affordability and electrocatalytic properties have endowed Ca3Co4O9 as a potential replacement for precious metal in electrocatalysis and electrochemical sensing applications.
Color Atlas of Emergency Trauma (2003)

This full-color atlas presents nearly 700 images from the largest and busiest trauma center in North America. The images bring the reader to the bedside of patients with the full spectrum of common and uncommon traumatic injuries including motor vehicle accidents, falls, lacerations, burns, impalements, stabbings, and gunshot wounds. The clinical, operative, and autopsy photographs; X-ray, ultrasound, CT, MRI, and angiography radiographs; and original illustrations depicting injury patterns guide clinicians in recognizing, prioritizing, and managing trauma patients by using the physical cues paramount to the emergency setting. Organized by major body regions into separate chapters on the head, face, neck, chest, abdomen, musculoskeletal system, spine and soft tissue, the thorough text of this comprehensive atlas discusses management guidelines, emergency workup protocols, and common pitfalls. The Color Atlas of Emergency Trauma is an essential resource for those involved in trauma care.
High flip angle imaging of metallic stents: Implications for MR angiography and intraluminal signal interpretation (2003)

Intraluminal stent signal characterization by MRI is generally hampered by signal loss from the metallic stent material. This signal loss is related to magnetic susceptibility and RF shielding. Even when stent materials with low magnetic susceptibility are used, RF shielding can still be problematic. In this article we have shown that high flip angle imaging enables morphology assessment and tissue characterization in stents made of stainless steel 316L, NiTinol, and ABI-alloy.
Searching MEDLINE for Randomized Clinical Trials Involving Care of the Newborn (1989)

Randomized clinical trials make up only a small fraction of published articles concerning care of the newborn infant and an even smaller fraction of articles about all human subjects. The busy pediatrician who wants to keep abreast of the medical literature requires strategies to detect such relevant studies promptly and reliably. Computer searching of MEDLINE is an attractive, potentially powerful but not sufficiently validated means of achieving this goal. Therefore, the sensitivity, specificity, and positive predictive value of two MEDLINE search strategies designed to detect randomized clinical trials for prevention and treatment of newborn diseases among all original articles about human subjects appearing in ten pediatric and general medical journals during 1985 were determined. The yield of both MEDLINE searches was compared to that of a manual search. Fifty-three randomized clinical trials of newborn care were identified by hand search among 233 articles concerning care of the newborn and 2,988 original articles about human subjects. The sensitivities of the MEDLINE searches were 53% and 34%, respectively, and the positive predictive values were 82% and 69%, respectively. Specificity of both computer searches was virtually 100%. Twenty-one randomized clinical trials were not identified by either MEDLINE search strategy, 17 of them for failure of the indexer to assign any methodologic terms at all or failure to assign sufficiently stringent methodologic terms. Consequently, sensitivities were higher, 77% and 68% respectively, when no methodologic terms were used during repeat searches. However, positive predictive values decreased concomitantly to 20% or less.(ABSTRACT TRUNCATED AT 250 WORDS)
HIV-1–specific CD4+ T lymphocyte turnover and activation increase upon viral rebound (2005)

HIV-specific CD4(+) T helper lymphocytes are preferred targets for infection. Although complete interruption of combination antiretroviral therapy (ART) can form part of therapeutic manipulations, there is grave concern that the resumption of viral replication might destroy, perhaps irreversibly, these T helper populations. High viremia blocks the proliferation capacity of HIV-specific helper cells. However, cytokine production assays imply that some antigen-specific effector function is retained. Despite this careful work, it remains unclear whether the return of HIV-1 replication physically destroys HIV-1–specific T helper cells in the peripheral blood. Difficulties in producing stable peptide-MHC class II complexes and the very low frequencies of antigen-specific CD4(+) T cells have delayed the application of this powerful technique. Here we employ HLA class II tetramers and validate a sensitive, quantitative cell-enrichment technique to detect HIV-1 T helper cells. We studied patients with early-stage HIV infection who were given a short, fixed course of ART as part of a clinical study. We did not find significant deletion of these cells from the peripheral circulation when ART was stopped and unfettered HIV replication returned. The turnover of these virus-specific cells increased and they adopted an effector phenotype when viremia returned.
The Attachments of the Fiber Bundles of the Posterior Cruciate Ligament: An Anatomic Study (2007)

The results of this study may be applied to the design of guidance systems for double-bundle PCL reconstruction techniques and as a reference for graft tunnel placement in in vitro or clinical follow-up studies.
Reversible molecular switching of molecular beacon: controlling DNA hybridization kinetics and thermodynamics using mercury(ii) ions (2008)

We report that the hydrogen-bonding pattern in a molecular beacon can be replaced by metal-dependent pairs of Hg(2+) and DNA thymine (T) bases. A molecular beacon based on T-Hg(2+)-T exhibits a lower background signal and higher thermostability than regular molecular beacons.
Data from Gene Expression Signatures Identify Novel Therapeutics for Metastatic Pancreatic Neuroendocrine Tumors (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Pancreatic neuroendocrine tumors (pNETs) are uncommon malignancies noted for their propensity to metastasize and comparatively favorable prognosis. Although both the treatment options and clinical outcomes have improved in the past decades, most patients will die of metastatic disease. New systemic therapies are needed.&lt;/p&gt;Experimental Design:&lt;p&gt;Tissues were obtained from 43 patients with well-differentiated pNETs undergoing surgery. Gene expression was compared between primary tumors versus liver and lymph node metastases using RNA-Seq. Genes that were selectively elevated at only one metastatic site were filtered out to reduce tissue-specific effects. Ingenuity pathway analysis (IPA) and the Connectivity Map (CMap) identified drugs likely to antagonize metastasis-specific targets. The biological activity of top identified agents was tested &lt;i&gt;in vitro&lt;/i&gt; using two pNET cell lines (BON-1 and QGP-1).&lt;/p&gt;Results:&lt;p&gt;A total of 902 genes were differentially expressed in pNET metastases compared with primary tumors, 626 of which remained in the common metastatic profile after filtering. Analysis with IPA and CMap revealed altered activity of factors involved in survival and proliferation, and identified drugs targeting those pathways, including inhibitors of mTOR, PI3K, MEK, TOP2A, protein kinase C, NF-kB, cyclin-dependent kinase, and histone deacetylase. Inhibitors of MEK and TOP2A were consistently the most active compounds.&lt;/p&gt;Conclusions:&lt;p&gt;We employed a complementary bioinformatics approach to identify novel therapeutics for pNETs by analyzing gene expression in metastatic tumors. The potential utility of these drugs was confirmed by &lt;i&gt;in vitro&lt;/i&gt; cytotoxicity assays, suggesting drugs targeting MEK and TOP2A may be highly efficacious against metastatic pNETs. This is a promising strategy for discovering more effective treatments for patients with pNETs.&lt;/p&gt;&lt;/div&gt;
Visualizing Pore Packing and Topology in MOFs (2022)

Metal organic frameworks (MOFs) can have open pore structures with high surface areas and applications in hydrogen storage, carbon dioxide capture, water harvesting from air, chemical separations, and catalysis. The chemical structure of these crystalline solids can initially appear daunting. Simplification by considering the arrangement of the pores and by identifying the links and vertices as well as switching between multiple representations can make visualization of these structures accessible.
Synthesis of acyclic, cis olefinic pheromones by way of nickel-catalyzed Grignard reactions (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of acyclic, cis olefinic pheromones by way of nickel-catalyzed Grignard reactionsErnest Wenkert, Vitor F. Ferreira, Enrique L. Michelotti, and Marco TingoliCite this: J. Org. Chem. 1985, 50, 5, 719–721Publication Date (Print):March 1, 1985Publication History Published online1 May 2002Published inissue 1 March 1985https://pubs.acs.org/doi/10.1021/jo00205a042https://doi.org/10.1021/jo00205a042research-articleACS PublicationsRequest reuse permissionsArticle Views549Altmetric-Citations47LEARN 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
Oxidative damage to the eye lens caused by cigarette smoke and fuel smoke condensates. (1994)

Cigarette smoking is reported to increase the risk of cataract. Likewise, the use of smoky cooking fuel is implicated in the etiology of cataract. In an effort to understand the cellular and molecular basis, the in vitro and in vivo cataractogenetic effects of these smoke condensates have been studied using isolated rat lenses and pigmented rats. Isolated capsulated rat lenses are incubated with cigarette smoke condensate (CSC) and firewood smoke condensate (FSC) for varying periods, with and without antioxidants, in the presence and absence of light. CSC and FSC permeate the lens capsule, impart colour and opacify the lens in a light- and dose-dependent manner. Antioxidants offer partial inhibition against the above damage. The condensates contain polycyclic aromatics which generate reactive oxygen species such as O2 photodynamically, and ppb levels of Fenton metal ions which induce oxidative reactions through .OH. Smoke induced damage possibly occurs through systemic absorption and transport of toxic components to several tissues, and specially into the lens, wherein the turnover is slow, leading to chronic accumulation causing oxidative damage to the constituent molecules and to consequent lenticular opacity.
Classical Entanglement in Electromagnetic Beams (2013)

We study classical entanglement for an optical beam with two binary degrees of freedom: polarization and spatial parity; and demonstrate experimentally a measurement of Bell’s inequality and show its usefulness as a quantitative tool in classical optical coherence theory.