gebhart/patrepeval huggingface dataset:
Absorption of drugs from the stomach. I. The rat. (1957)

When gastric contents are acid, the rat stomach rapidly absorbs most acidic drugs. In contrast, all but the very weakest basic drugs are poorly absorbed. When gastric contents are alkaline, absorption of acidic drugs is impeded and that of basic drugs facilitated. These observations have been presented in terms of the hypothesis that the gastric mucosa is predominantly a lipoid barrier. Gastric absorption of drugs can be explained by the diffusion of the unionized form of a weak electrolyte across such a barrier. The unionized forms of drugs traverse the mucosa at rates approaching deutenium oxide movement and usually more rapidly than ethanol. Rapid absorption by the stomach is not limited by gastric mucosal blood flow. When absorption is rapid, diffusion and mixing within the gastric lumen may become the limiting factors.
Identification of Tomato Spotted Wilt-like Virus on Watermelon in Taiwan (1992)

The causal agent of an unusual disease affecting watermelon (Citrullus lanatus) in Taiwan was identified as tomato spotted wilt-like virus in the tospovirus group on the basis of particle morphology, host reactions, serology, and transmission by thrips. Host symptoms included leaf crinkling, mottling, yellow spotting, short internodes, upright growth of younger branches, and tip necrosis (.)
Preclinical Evaluation of <sup>18</sup>F-RO6958948, <sup>11</sup>C-RO6931643, and <sup>11</sup>C-RO6924963 as Novel PET Radiotracers for Imaging Tau Aggregates in Alzheimer Disease (2017)

Tau aggregates and amyloid-β (Aβ) plaques are key histopathologic features in Alzheimer disease (AD) and are considered targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. This article describes the preclinical in vitro and in vivo characterization of 3 novel compounds-RO6958948, RO6931643, and RO6924963-that bind specifically to tau aggregates and have the potential to become PET tracers for future human use. <b>Methods:</b> RO6958948, RO6931643, and RO6924963 were identified as high-affinity competitors at the <sup>3</sup>H-T808 binding site on native tau aggregates in human late-stage AD brain tissue. Binding of tritiated compounds to brain tissue sections of AD patients and healthy controls was analyzed by macro- and microautoradiography and by costaining of tau aggregates and Aβ plaques on the same tissue section using specific antibodies. All 3 tracer candidates were radiolabeled with a PET nuclide and tested in vivo in tau-naïve baboons to assess brain uptake, distribution, clearance, and metabolism. <b>Results:</b><sup>3</sup>H-RO6958948, <sup>3</sup>H-RO6931643, and <sup>3</sup>H-RO6924963 bound with high affinity and specificity to tau aggregates, clearly lacking affinity for concomitant Aβ plaques in human AD Braak V tissue sections. The specificity of all 3 radioligands for tau aggregates was supported, first, by binding patterns in AD sections comparable to the tau-specific radioligand <sup>3</sup>H-T808; second, by very low nonspecific binding in brain tissue devoid of tau pathology, excluding significant radioligand binding to any other central nervous system target; and third, by macroscopic and microscopic colocalization and quantitative correlation of radioligand binding and tau antibody staining on the same tissue section. RO6958948, RO6931643, and RO6924963 were successfully radiolabeled with a PET nuclide at high specific activity, radiochemical purity, and yield. After intravenous administration of <sup>18</sup>F-RO6958948, <sup>11</sup>C-RO6931643, and <sup>11</sup>C-RO6924963 to baboons, PET scans indicated good brain entry, rapid washout, and a favorable metabolism pattern. <b>Conclusion:</b><sup>18</sup>F-RO6958948, <sup>11</sup>C-RO6931643, and <sup>11</sup>C-RO6924963 are promising PET tracers for visualization of tau aggregates in AD. Head-to-head comparison and validation of these tracer candidates in AD patients and healthy controls will be reported in due course.
C=C-conjugated carbodiimides as 2-aza dienes in intramolecular [4+2] cycloadditions. One-pot preparation of quinoline, .alpha.-carboline, and quinindoline derivatives (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTC=C-conjugated carbodiimides as 2-aza dienes in intramolecular [4+2] cycloadditions. One-pot preparation of quinoline, .alpha.-carboline, and quinindoline derivativesPedro Molina, Mateo Alajarin, Angel Vidal, and Pilar Sanchez-AndradaCite this: J. Org. Chem. 1992, 57, 3, 929–939Publication Date (Print):January 1, 1992Publication History Published online1 May 2002Published inissue 1 January 1992https://pubs.acs.org/doi/10.1021/jo00029a026https://doi.org/10.1021/jo00029a026research-articleACS PublicationsRequest reuse permissionsArticle Views957Altmetric-Citations94LEARN 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
BET bromodomain-mediated interaction between ERG and BRD4 promotes prostate cancer cell invasion (2016)

Prostate cancer (PCa) that becomes resistant to hormone castration and next-generation androgen receptor (AR)-targeted therapies, called castration-resistant prostate cancer (CRPC), poses a significant clinical challenge. A better understanding of PCa progression and key molecular mechanisms could bring novel therapies to light. One potential therapeutic target is ERG, a transcription factor aberrantly up-regulated in PCa due to chromosomal rearrangements between androgen-regulated gene TMPRSS2 and ERG. Here we show that the most common PCa-associated truncated ERG T1-E4 (ERGΔ39), encoded by fusion between TMPRSS2 exon 1 and ERG exon 4, binds to bromodomain-1 (BD1) of bromodomain containing protein 4 (BRD4), a member of the bromodomain and extraterminal domain (BET) family. This interaction is partially abrogated by BET inhibitors JQ1 and iBET762. Meta-analysis of published ERG (T1-E4) and BRD4 chromatin immunoprecipitation-sequencing (ChIP-seq) data demonstrates overlap in a substantial portion of their binding sites. Gene expression profile analysis shows some ERG-BRD4 co-target genes are upregulated in CRPC compared to hormone-naïve counterparts. We provide further evidence that ERG-mediated invasion of PCa cells was significantly enhanced by an acetylation-mimicking mutation in ERG that augments the ERG-BRD4 interaction. Our findings reveal that PCa-associated ERG can interact and co-occupy with BRD4 in the genome, and suggest this druggable interaction is critical for ERG-mediated cell invasion and PCa progression.
A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein β and NF-κB activity in Hodgkin and anaplastic large cell lymphomas (2005)

The immunosuppressive macrolide rapamycin and its derivative everolimus (SDZ RAD, RAD) inhibit the mammalian target of rapamycin (mTOR) signaling pathway. In this study, we provide evidence that RAD has profound antiproliferative activity in vitro and in NOD/SCID mice in vivo against Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) cells. Moreover, we identified 2 molecular mechanisms that showed how RAD exerts antiproliferative effects in HL and ALCL cells. RAD down-regulated the truncated isoform of the transcription factor CCAAT enhancer binding protein beta (C/EBPbeta), which is known to disrupt terminal differentiation and induce a transformed phenotype. Furthermore, RAD inhibited constitutive nuclear factor kappaB (NF-kappaB) activity, which is a critical survival factor of HL cells. Pharmacologic inhibition of the mTOR pathway by RAD therefore interferes with essential proliferation and survival pathways in HL and ALCL cells and might serve as a novel treatment option.
Low threshold AlGaAs BH lasers fabricated by one-step MOCVD (1988)

Buried-heterojunction (BH) AlGaAs lasers were fabricated by one-step MOCVD epitaxial growth on an inverse mesa etched GaAs substrate. A low threshold current of 6 mA was obtained and the lasing wavelength was approximately 780 nm. The laser beam shape was nearly circular with an aspect ratio less than 1.3.
Crystal Structure of the Oxygenase Component (HpaB) of the 4-Hydroxyphenylacetate 3-Monooxygenase from Thermus thermophilus HB8 (2007)

The 4-hydroxyphenylacetate (4HPA) 3-monooxygenase is involved in the initial step of the 4HPA degradation pathway and catalyzes 4HPA hydroxylation to 3,4-dihydroxyphenylacetate. This enzyme consists of two components, an oxygenase (HpaB) and a reductase (HpaC). To understand the structural basis of the catalytic mechanism of HpaB, crystal structures of HpaB from Thermus thermophilus HB8 were determined in three states: a ligand-free form, a binary complex with FAD, and a ternary complex with FAD and 4HPA. Structural analysis revealed that the binding and dissociation of flavin are accompanied by conformational changes of the loop between beta5 and beta6 and of the loop between beta8 and beta9, leading to preformation of part of the substrate-binding site (Ser-197 and Thr-198). The latter loop further changes its conformation upon binding of 4HPA and obstructs the active site from the bulk solvent. Arg-100 is located adjacent to the putative oxygen-binding site and may be involved in the formation and stabilization of the C4a-hydroperoxyflavin intermediate.
Realization of diamagnetic levitation of column-shaped graphite (2015)

The completely passive levitation of a column-shaped graphite object is achieved. Graphite is a typical diamagnetic material. Diamagnetic materials have a property of generating repulsive force in magnetic field. Most diamagnetic levitation systems use high-oriented pyrolytic graphite (PG) sheets because sufficient force for levitation is easily obtained. In contrast, column-shaped graphites are proposed as the target of levitation in this work. Experimental apparatus for diamagnetic levitation is fabricated. The apparatus uses a two-dimensional Halbach array made of cubic neodymium magnets. The magnetic fields in the apparatus are analyzed numerically and experimentally. It is shown that the stable diamagnetic levitation of a column-shaped graphite can be achieved. The floator is fabricated by combining the pencil leads made from graphite. Then the diamagnetic forces acting on the floator are measured. In addition, the effects of anisotropy of graphite on the levitation characteristics are discussed.
CREB: a multifaceted regulator of neuronal plasticity and protection (2010)

Since its initial characterization over 20 years ago, there has been intense and unwavering interest in understanding the role of the transcription factor cAMP-responsive element binding protein (CREB) in nervous system physiology. Through an array of experimental approaches and model systems, researchers have begun to unravel the complex and multifaceted role of this transcription factor in such diverse processes as neurodevelopment, synaptic plasticity, and neuroprotection. Here we discuss current insights into the molecular mechanisms by which CREB couples synaptic activity to long-term changes in neuronal plasticity, which is thought to underlie learning and memory. We also discuss work showing that CREB is a critical component of the neuroprotective transcriptional network, and data indicating that CREB dysregulation contributes to an array of neuropathological conditions.
Steam volatile aroma constituents of roasted cocoa beans (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteam volatile aroma constituents of roasted cocoa beansMichel. Van Praag, Herbert S. Stein, and Merrick S. TibbettsCite this: J. Agric. Food Chem. 1968, 16, 6, 1005–1008Publication Date (Print):November 1, 1968Publication History Published online1 May 2002Published inissue 1 November 1968https://pubs.acs.org/doi/10.1021/jf60160a011https://doi.org/10.1021/jf60160a011research-articleACS PublicationsRequest reuse permissionsArticle Views669Altmetric-Citations99LEARN 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
Illustrated Dictionary of Eponymic Syndromes and Diseases and Their Synonyms. (1970)

Ever since the unfortunate recent death of the wonderful English humorist, Stephen Potter, the father of gamesmanship, we apostles have been obliged to seek a new champion. Since the eponym has always been the favorite weapon of the medical "one-upsman" (the died-in-the-wool Roundsman), a likely candidate for the laurels might have been Stanley Jablonski, author of this marvelous book of eponyms. But he will be refused endorsement by the hard core because of his terribly hedgy note in the "Introduction"; he said "This book does not reflect my approval or disapproval of eponyms —it merely recognizes that they exist." I venture that no eponymist worth his salt will rally behind such a weak-kneed neutrality. But, he has compiled the best book of eponyms I have seen. I challenged the book with my best shots, but Jablonski parried every riposte. It is complete from Abderhalden-Fanconi syndrome to Zwahlen's syndrome. The pleasure
Behavior of taxi customers in hailing vacant taxis: a nested logit model for policy analysis (2015)

Summary This study models and examines the taxi customers' preferences for hailing vacant taxis on streets. A stated preference survey was conducted to randomly select and interview 1242 taxi customers at taxi stands and pedestrians on streets, who had experiences of taking taxis recently, about their choices under different given hypothetical scenarios. In total, 4968 observations were collected and used for developing the discrete choice models for the analysis. To account for the potential correlations among alternatives, two nested logit models are developed, calibrated, and compared with a standard multinomial logit model in the investigation. The results of likelihood ratio test demonstrate that one of the developed nested logit models is better than the standard multinomial logit model to describe the search behavior of taxi customers. The model results also show that the walking time to and the waiting time at the location for hailing taxis, the extra travel time to the destination because of local circulation for finding a way from the pickup location heading to a passenger's destination, as well as the taxi customers' perceptions for walking to and waiting at taxi stands were found as significant factors to influence their decisions. In addition, the results of market segmentation analysis illustrate the variations in taxi‐search strategies of taxi customers in different districts and regions. Some policy implications on introducing more taxi stands and improving the utilization rates of taxi stands are also discussed. We believe that the proposed models, findings, and discussion are useful for developing micro‐simulation models to evaluate the performance of road traffic networks with taxi services and developing simulation‐based optimization models to answer policy questions related to taxi services. Copyright © 2015 John Wiley & Sons, Ltd.
1,4‐Addition of triorganozincates and silyldiorganozincates to α,β‐unsaturated ketones (1986)

Abstract Lithium and magnesium triorganozincates, prepared by combination of ZnCl 2 (TMEDA) with 3 molar equivalents of RLi or RMgX, or from dialkylzinc and 1 molar equivalent of RLi or RMgX, react with 2‐cyclohexen‐1‐one ( 1 ) under mild conditions to produce moderate to good yields of the 1,4‐addition products 2 . The approximate reactivity order obtained from the product distribution using unsymmetrical zincates is t BuCH 2 Lt; t Bu, Me < Ph, i Bu < Et, n Bu, i Pr, CHCH 2 ≪ Me 2 PhSi. The latter groups are transferred with good selectivity from mixed reagents derived from Me 2 Zn. This sequence differs strikingly from that exhibited by unsymmetrical cuprates which transfer neopentyl very easily, and also tert ‐butyl more easily than the corresponding zincates. The methylation with Me 3 ZnLi is catalyzed by cobalt complexes. Other enones ( 7 – 13 ) generally give poor yields, and the cobalt‐catalyzed methylation of isophorone ( 3 ) is complicated by a Kharasch‐type deconjugation. Mixed silyldialkylzincates, Me 2 PhSiZnR 2 Li, produce the β‐silyl ketones from a variety of unhindered or moderately hindered enones in practically useful yields; one example of an α,β‐unsaturated ester ( 12 ) is also included.
Combined Data Partitioning and FMO in Distortion Modeling for Video Trace Generation with Lossy Network Parameters (2007)

The emergence of fourth generation wireless networks poses great challenges in video transport. Two of these prominent challenges are: a) providing and maintaining visually acceptable video quality given variations in channel conditions and b) the accurate measurement of this quality in network simulators using standard verbose trace flies. To address these challenges, in this paper, we propose and analyze an end-to-end (E2E) model for mean packet loss probability of H.264/AVC-based data partitioning (DP) substreams. The model we're presenting is based on the extended Gilbert model. We then incorporate the parametric formulation in our proposed base layer trace format that records E2E distortion coefficients for DP streams on a per slice level.
Transplanting Normal Vascular Proangiogenic Cells to Tumor-Bearing Mice Triggers Vascular Remodeling and Reduces Hypoxia in Tumors (2010)

Blood vessels deliver oxygen and nutrients to tissues, and vascular networks are spatially organized to meet the metabolic needs for maintaining homeostasis. In contrast, the vasculature of tumors is immature and leaky, resulting in insufficient delivery of nutrients and oxygen. Vasculogenic processes occur normally in adult tissues to repair "injured" blood vessels, leading us to hypothesize that bone marrow mononuclear cells (BMMNC) may be able to restore appropriate vessel function in the tumor vasculature. Culturing BMMNCs in endothelial growth medium resulted in the early outgrowth of spindle-shaped attached cells expressing CD11b/Flt1/Tie2/c-Kit/CXCR4 with proangiogenic activity. Intravenous administration of these cultured vascular proangiogenic cells (VPC) into nude mice bearing pancreatic cancer xenografts and Pdx1-Cre;LSL-Kras(G12D);p53(lox/+) genetically engineered mice that develop pancreatic ductal adenocarcinoma significantly reduced areas of hypoxia without enhancing tumor growth. The resulting vasculature structurally mimicked normal vessels with intensive pericyte coverage. Increases in vascularized areas within VPC-injected xenografts were visualized with an ultrasound diagnostic system during injection of a microbubble-based contrast agent (Sonazoid), indicating a functional "normalization" of the tumor vasculature. In addition, gene expression profiles in the VPC-transplanted xenografts revealed a marked reduction in major factors involved in drug resistance and "stemness" of cancer cells. Together, our findings identify a novel alternate approach to regulate abnormal tumor vessels, offering the potential to improve the delivery and efficacy of anticancer drugs to hypoxic tumors.
Chemotherapy of gastrointestinal cancer (1972)

At present, useful chemotherapy in gastrointestinal cancer is almost restricted to carcinomas of the colon and rectum in which 5-fluorouracil and several related fluoropyrimidines can produce clinically useful responses in 15 to 20% of patients. Other agents may have produced some benefit less consistently, and additional new agents are presently being studied. Although occasional responses are seen in gastric cancer and rarely in carcinoma of the esophagus, results to date in those diseases are disappointing. Present studies are aimed at employing combinations of chemotherapeutic agents since such regimens have proved to be more useful than single drugs in those diseases which are generally responsive to chemotherapy. Studies of the influence of antitumor drugs in patients with early minimal residual disease are also being pursued in an attempt to achieve more frequent and more prolonged benefit.
Autologous Fat Grafting: Comparison of Techniques (2000)

Background. Despite more than a century of reporting in the medical literature, controversy still surrounds both the efficacy and longevity of autologous fat transplantation in subcutaneous soft tissue augmentation. Objective. To summarize the existing literature relating to the effectiveness of this procedure and to highlight differences in technique that may play a role in reported treatment successes and failures. Methods. Review of the literature and reporting of authors' observations and results. Conclusion. Autologous fat transplantation can be a gratifyingly effective treatment for subcutaneous augmentation that may produce permanent results in some cases. This article aims to clarify some of the differences in technique employed by doctors in this field and aims to enable the reader to better see the subtle, but sometimes important differences in methods used.