gebhart/patrepeval huggingface dataset:
Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials (2017)

Purpose Measures of response that are clinically meaningful and occur early are an unmet need in metastatic castration-resistant prostate cancer clinical research and practice. We explored, using individual patient data, week 13 circulating tumor cell (CTC) and prostate-specific antigen (PSA) response end points in five prospective randomized phase III trials that enrolled a total of 6,081 patients-COU-AA-301, AFFIRM, ELM-PC-5, ELM-PC-4, and COMET-1- ClinicalTrials.Gov identifiers: NCT00638690, NCT00974311, NCT01193257, NCT01193244, and NCT01605227, respectively. Methods Eight response end points were explored. CTC nonzero at baseline and 0 at 13 weeks (CTC0); CTC conversion (≥ 5 CTCs at baseline, ≤ 4 at 13 weeks-the US Food and Drug Administration cleared response measure); a 30%, 50%, and 70% decrease in CTC count; and a 30%, 50%, and 70% decrease in PSA level. Patients missing week-13 values were considered nonresponders. The discriminatory strength of each end point with respect to overall survival in each trial was assessed using the weighted c-index. Results Of the eight response end points, CTC0 and CTC conversion had the highest weighted c-indices, with smaller standard deviations. For CTC0, the mean (standard deviation) was 0.81 (0.04); for CTC conversion, 0.79 (0.03); for 30% decrease in CTC count, 0.72 (0.06); for 50% decrease in CTC count, 0.72 (0.06); for 70% decrease in CTC count, 0.73 (0.05); for 30% decrease in PSA level, 0.71 (0.03); for 50% decrease in PSA level, 0.72 (0.06); and for 70% decrease in PSA level, 0.74 (0.05). Seventy-five percent of eligible patients could be evaluated with the CTC0 end point, compared with 51% with the CTC conversion end point. Conclusion The CTC0 and CTC conversion end points had the highest discriminatory power for overall survival. Both are robust and meaningful response end points for early-phase metastatic castration-resistant prostate cancer clinical trials. CTC0 is applicable to a significantly higher percentage of patients than CTC conversion.
Anti-Insulin Actions of a Bovine Pituitary Diabetogenic Peptide on Glycogen Synthesis (1972)

The site(s) of action of a bovine pituitary diabetogenic peptide that produces hyperglycemia and hyperinsulinemia in vivo (dogs or humans) was investigated in vitro . When rat diaphragms were incubated with the peptide in the presence of insulin, the peptide depressed insulin-mediated ( a ) glucose uptake, ( b ) glycogen synthesis, and ( c ) glycogen synthase activation (conversion of D to I form). Incubation with the peptide alone resulted in small increases in ( a ), ( b ), and ( c ). Insulin-mediated glycogen synthase kinase inactivation was inhibited when both insulin and peptide were present ( d ), whereas glycogen synthase kinase activity was lowered by the peptide alone. High doses of insulin completely reversed inhibitory effects of the peptide on glycogen synthesis. Therefore, the hyperglycemic and anti-insulin properties of this peptide in vivo can possibly be explained by the partial blocking action of the peptide on insulin-mediated glucose uptake and glycogenesis.
SIRTF primary mirror design, analysis, and testing (1990)

The primary mirror assembly (PMA) requirements and concepts for the Space Infrared Telescope Facility (SIRTF) program are discussed. The PMA studies at NASA/ARC resulted in the design of two engineering test articles, the development of a mirror mount cryogenic static load testing system, and the procurement and partial testing of a full scale spherical mirror mounting system. Preliminary analysis and testing of the single arch mirror with conical mount design and the structured mirror with the spherical mount design indicate that the designs will meet all figure and environmental requirements of the SIRTF program.
Charge preamplifier in a 65 nm CMOS technology for pixel readout in the Grad TID regime (2016)

A charge preamplifier has been developed in a 65 nm CMOS technology for processing the signal from the inner pixel layers of the CMS detector, in view of the experiment upgrade for the High Luminosity (HL) LHC. The circuit is part of a readout channel implementing a time-over-threshold method for analog-to digital-conversion of the charge signal. Samples of the circuit have been exposed to high doses of ionizing radiation, up to 8 MGy, from a low energy proton source. The main purpose is to study the radiation-induced degradation of the preamplifier parameters (charge sensitivity, noise, signal shape), in view of its use in the harsh environment of the HL-LHC, where integrated ionizing doses in the range of 1 Grad are expected during the detector lifetime.
Excited-State Dynamics in 6-Thioguanosine from the Femtosecond to Microsecond Time Scale (2011)

Patients treated with the immunosuppressant and anticancer drugs 6-thioguanine, azathioprine, or mercaptopurine can metabolize and incorporate them in DNA as 6-thioguanosine. The skin of these patients is sensitive to UVA radiation, and long-term treatment can result in extremely high incidence of sunlight-induced skin cancer. In this contribution the photophysics of 6-thioguanosine have been studied in aqueous buffer solution and in acetonitrile after excitation with UVA light to provide mechanistic insights about the origin of its phototoxicity. It is shown that most of the initial excited-state population in the S(2)(ππ*, L(a)) state decays by ultrafast intersystem crossing to the triplet manifold. A triplet quantum yield of 0.8 ± 0.2 is determined in aqueous buffer solution. A minor fraction of the S(2) population bifurcates on an ultrafast time scale to populate the S(1)(n(S)π*) state, which decays back to the ground state in tens of picoseconds. Quantum-chemical calculations that include solvent effects support the experimental results. The high triplet yield of 6-thioguanosine, which we argue can result in photosensitization of molecular oxygen and photooxidative DNA damage, is proposed to explain the high phototoxicity exhibited by these pro-drugs in patients upon sunlight exposure. Finally, the experimental and computational results for 6-thioguanosine are compared with those reported for the DNA/RNA guanine monomers.
Identification of Enteroviruses in Naturally Infected Captive Primates (2008)

In a recent study, we investigated cases of diarrheal disease among monkeys at a U.S. primate center. In that study, enteroviruses were detected in a high proportion of the fecal specimens tested. To determine whether the enterovirus detections represented the circulation of one or more simian enteroviruses within the colony or the transmission of human enteroviruses from animal handlers, we determined in the present study the serotype identity of each virus by reverse transcription-PCR and sequencing of a portion of the VP1 gene, a region whose sequence corresponds to antigenic type. Enteroviruses were identified in 37 of 56 specimens (66%), 30 of 40 rhesus macaques, 5 of 11 pigtail macaques, 2 of 4 sooty mangabeys, and 0 of 1 chimpanzee. No previously known human viruses were detected. Three previously known simian enterovirus serotypes--SV6, SV19, and SV46--were among the viruses identified, but more than half of the identified viruses were previously unknown; these have been assigned as new types: EV92 and EV103.
Convenient One‐Pot Preparation of Dimethyl Bicyclo[2.2.2]octane‐1,4‐dicarbolylate, a Key Intermediate for a Novel Adenosine A<sub>1</sub> Receptor Antagonist. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Changes in Plasma Somatomedin‐C in Response to Ingestion of Diets with Variable Protein and Energy Content (1984)

We have attempted to determine the relative importance of dietary intake of protein and energy in restoring plasma immunoreactive somatomedin-C (Sm-C) concentrations after fasting. Ten healthy human volunteers were fasted for 5 days, then divided into two refeeding groups. One group (variable energy) was refed 1.0 g protein/kg ideal body weight, and in 9-day sequences, 11, 18 and 25 kcal of energy/kg. The other group (variable protein) was given 35 kcal energy/kg, and in 9-day sequences, 0.2, 0.4, and 1.0 g protein/kg. When subjects were refed the variable energy diets there was no significant increase in Sm-C at 11 kcal/kg (0.47 +/- 0.13 to 0.45 +/- 0.12 U/ml), suggesting that there is a threshold energy requirement below which optimal protein intake is not sufficient to raise the Sm-C. When subjects were refed 18 and 25 kcal/kg, it became apparent that the more energy added to the diet, the greater the absolute concentration of Sm-C attained (0.66 U/ml on 18 kcal/kg and 0.97 U/ml on 25 kcal/kg). Sm-C correlated with nitrogen balance (r = 0.58) during refeeding with the variable energy diets and was a good indicator of acute directional change in nitrogen balance. However, Sm-C was not a reliable indicator of nitrogen repletion, since it rose almost to control levels on the 25 kcal/kg diet while nitrogen balance remained slightly negative.(ABSTRACT TRUNCATED AT 250 WORDS)
Protocolli e Linee Guida attivi presso il Dipartimento di Scienze Mediche, Oncologiche e Radiologiche. (1998)

Monografia contenente informazioni sul trattamento delle principali neoplasie
Lipase‐Catalyzed Kinetic Resolution of (±)‐1‐(2‐Furyl) Ethanol in Nonaqueous Media (2014)

S-1-(2-Furyl) ethanol serves as an important chiral building block for the preparation of various natural products, fine chemicals, and is widely used in the chemical and pharmaceutical industries. In this work, lipase-catalyzed kinetic resolution of (R/S)-1-(2-furyl) ethanol using different acyl donors was investigated. Vinyl esters are good acyl donors vis-à-vis alkyl esters for kinetic resolution. Among them, vinyl acetate was found to be the best acyl donor. Different immobilized lipases such as Rhizomucor miehei lipase, Thermomyces lanuginosus lipase, and Candida antarctica lipase B were evaluated for this reaction, among which C. antarctica lipase B, immobilized on acrylic resin (Novozym 435), was found to be the best catalyst in n-heptane as solvent. The effect of various parameters was studied in a systematic manner. Maximum conversion of 47% and enantiomeric excess of the substrate (ees ) of 89% were obtained in 2 h using 5 mg of enzyme loading with an equimolar ratio of alcohol to vinyl acetate at 60 °C at a speed of 300 rpm in a batch reactor. From the analysis of progress curve and initial rate data, it was concluded that the reaction followed the ordered bi-bi mechanism with dead-end ester inhibition. Kinetic parameters were obtained by using nonlinear regression. This process is more economical, green, and easily scalable than the chemical processes.
Interactions between Crystalline and Amorphous Domains in Semicrystalline Polymers:  Small-Angle X-ray Scattering Studies of the Brill Transition in Nylon 6,6 (1999)

The lamellar structures in nylon 6,6 were characterized at several temperatures using synchrotron small-angle X-ray scattering (SAXS) to monitor the changes during the Brill transition at ∼160 °C (TB). The integrated intensity and the coherence length of the lamellar stacks increase during heating above TB. In contrast, during cooling, the intensity increases below TB whereas the coherence length increases up to TB and remains unchanged upon further cooling. The increase in SAXS intensity observed above TB during heating is attributed to the enhanced contrast resulting from a decrease in the packing density of the amorphous chain segments. It is suggested that the changes in the packing of the crystalline stems, as they do occur during crystalline phase transitions, provoke a proportionate response in the packing of the amorphous chain segments in the interlamellar regions. The thermal expansion coefficient of the amorphous segments calculated from the X-ray diffraction data above TB is 5.9 × 10-4/K (molar thermal expansion coefficient, 854 × 10-10 m3/(mol K)), and this is in reasonable agreement with the published values.
Platform Architecture A Two-Level Optimization Approach (2002)

Introduction to Platform Architecture in Products VW Golf 2 -Automotive Platforming Example:A Two-Level Optimization Approach 3 -Discussion
Robert L. Hill, 1928-2012 (2013)

at the age of 84. Bob Hill was recognized for his numerous contributions to the field of protein biochemistry, his mentorship of graduate students and post-docs that maintain active careers, and his commitment to the education of the generations that follow him.His career became entwined with the field of glycobiology through his study of glycosyltransferases, enzymes that carry out the biosynthesis of complex glycans on glycoproteins and glycolipids.His demonstration of the strict specificities of glycosyltransferases led to a deeper understanding of glycan biosynthesis
Site‐specific <scp>T</scp> – <scp>DNA</scp> integration in <i> <scp>A</scp> rabidopsis thaliana </i> mediated by the combined action of <scp>CRE</scp> recombinase and ϕ <scp>C</scp> 31 integrase (2013)

Random T-DNA integration into the plant host genome can be problematic for a variety of reasons, including potentially variable transgene expression as a result of different integration positions and multiple T-DNA copies, the risk of mutating the host genome and the difficulty of stacking well-defined traits. Therefore, recombination systems have been proposed to integrate the T-DNA at a pre-selected site in the host genome. Here, we demonstrate the capacity of the ϕC31 integrase (INT) for efficient targeted T-DNA integration. Moreover, we show that the iterative site-specific integration system (ISSI), which combines the activities of the CRE recombinase and INT, enables the targeting of genes to a pre-selected site with the concomitant removal of the resident selectable marker. To begin, plants expressing both the CRE and INT recombinase and containing the target attP site were constructed. These plants were supertransformed with a T-DNA vector harboring the loxP site, the attB sites, a selectable marker and an expression cassette encoding a reporter protein. Three out of the 35 transformants obtained (9%) showed transgenerational site-specific integration (SSI) of this T-DNA and removal of the resident selectable marker, as demonstrated by PCR, Southern blot and segregation analysis. In conclusion, our results show the applicability of the ISSI system for precise and targeted Agrobacterium-mediated integration, allowing the serial integration of transgenic DNA sequences in plants.
A Study on the Wind Power Generation Fluctuation of Multiple Sites (2009)

The use of renewable energy sources such as the sun and wind is increasing steadily. High penetration of wind power may affect electric power system frequency, because the fluctuations in wind power generation are much larger than that of conventional power plants. To evaluate wind power fluctuation and its effect on the power systems, it is important to acquire actual fluctuation data of wind farm power.In this paper, the authors report the results of an analysis of wind power fluctuation and smoothing effect from data measured at existing wind power sites in the Hokuriku region. A novel index is proposed to evaluate the smoothing effect, and impacts of high wind penetration are estimated using this index. This paper also proposes a control strategy of battery storage system for stabilizing wind farm output.
Temporal Relationship Between hCG Induced Desensitization of LH/hCG Responsive Adenylyl Cyclase and Down regulation of LH/hCG Receptors in the Rat Testis (1981)

A single s.c. injection of 75 IU of human chorionic gonadotropin (hCG) into adult male rats caused a transient desensitization of the LH/hCG responsive adenylyl cyclase (AC) in membrane particles from rat testis. Two hours after the injection of hCG, LH/hCG responsive AC was reduced by 40%, whereas LH binding was still normal. After 24 hr LH/HCG responsive AC was lost, whereas LH binding only showed a marginal decrease. During the next 2-3 days there was a gradual loss of LH/HCG receptors, which reached a nadir at day 4 (14% of control levels). At day y and 9 following the hCG injection LH/hCG receptors and LH/hCG responsive AC gradually returned towards normal. Fluoride (F-) stimulated AC activity showed only minor changes throughout the period investigated. The initial loss of AC responsiveness to hCG was associated with maximal levels of circulating hCG. However, desensitization persisted for several days after hCG was cleared form the circulation. AC desensitization preceded LH receptor downregulation and may support the notion that uncoupling of the catalytic subunit of the AC from Leydig cell LH/hCG receptors is a requirement for subsequent receptor internalization.
<b>Weakening of d<sub>π</sub>p<sub>π</sub>-Bonds by Coördination</b> (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTWeakening of dπpπ-Bonds by CoördinationHubert. Schmidbaur and Max. SchmidtCite this: J. Am. Chem. Soc. 1962, 84, 6, 1069–1070Publication Date (Print):March 1, 1962Publication History Published online1 May 2002Published inissue 1 March 1962https://pubs.acs.org/doi/10.1021/ja00865a052https://doi.org/10.1021/ja00865a052research-articleACS PublicationsRequest reuse permissionsArticle Views46Altmetric-Citations45LEARN 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
EARLY-STAGE DESIGN AND EVALUATION FOR NUCLEAR POWER PLANT CONTROL ROOM UPGRADES (2016)

As control rooms are modernized with new digital systems at nuclear power plants, it is necessary to evaluate operator performance with these systems as part of a verification and validation process. While there is regulatory and industry guidance for some modernization activities, there are no well defined standard processes or predefined metrics available for assessing what is satisfactory operator interaction with new systems, especially during the early design stages. This paper proposes a framework defining the design process and metrics for evaluating human system interfaces as part of control room modernization. The process and metrics are generalizable to other applications and serve as a guiding template for utilities undertaking their own control room modernization activities. CONTROL ROOM MODERNIZATION Main control room (MCR) modernization is a necessity at nuclear power plants (NPPs). With life extensions of plants beyond the original 40-year operating licenses, there is strong impetus to upgrade aging systems to achieve greater efficiencies and maintain high operational reliabilities. Since existing MCRs in United States (U.S.) plants are largely
Percutaneous penetration and pharmacodynamics: Wash-in and wash-off of sunscreen and insect repellent (2015)

Increased awareness of skin cancer and mosquito-transmitted diseases has increased use of insect repellents and sunscreens. The challenge in setting recommendations for use and reapplication, especially when used concomitantly, lies in finding the balance between applying a durable product effective in withstanding natural and physical factors such as water, sweat, temperature and abrasion, while limiting percutaneous absorption and decreasing risk of potential dermal and systemic toxicity. Inorganic sunscreens show no or little percutaneous absorption or toxic effects in comparison to organic sunscreens, which show varying levels of dermal penetration and cutaneous adverse effects. An alternative to N,N-diethyl-m-toluamide (DEET), the traditional gold standard compound in insect repellents, picaridin appears as efficacious, has lower risk of toxicity, and when used simultaneously with sunscreen may decrease percutaneous absorption of both compounds. Conversely, combined use of DEET and sunscreen results in significantly higher absorption of both compounds. It is important to increase consumer awareness of "washing in" of various compounds leading to increased risk of toxicity, as well as differences in reapplication need due to "washing off" caused by water, sweat and abrasion. Although much remains to be studied, to maximize efficacy and decrease toxicity, contemporary research tools, including dermatopharmokinetics, should aid these prospective advances.
Antiviral Activity of Cyclosaligenyl Prodrugs of Acyclovir, Carbovir and Abacavir (2001)

The cyclosaligenyl (cycloSal) derivatives of the monophosphates of three acyclic or carbocyclic guanosine analogues, for example, acyclovir (ACV), carbovir (CBV) and abacavir (ABC), were investigated for their activity against retrovirus (HIV, Moloney sarcoma virus) and herpes simplex virus (HSV) activity in cell culture. The extent of the antiviral potency of the prodrugs depended on the nature of the nucleoside, the substituent on the cycloSal moiety and the virus investigated. Most notably, and unlike the parent compound ACV, cycloSal-ACV monophosphate (MP) prodrugs retained pronounced activity against ACV-resistant (thymidine kinase-deficient) HSV-1 and also gained anti-HIV activity. While the cycloSal-CBVMP prodrugs did not show enhanced activity compared with the parent compound CBV, the cycloSal-ABCMP prodrugs afforded markedly increased potency against both HSV and HIV. Our data indicate that the cycloSal prodrug approach can be useful to deliver directly the MP derivatives of nucleoside analogues into the intact, virus-infected cells, thus improving and extending the antiviral potency and spectrum of the drugs against retro- and herpesvirus strains.
Kinetics and mechanism of oxidative addition of aryl iodides to iridium(I) complexes (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetics and mechanism of oxidative addition of aryl iodides to iridium(I) complexesR. J. Mureinik, M. Weitzberg, and J. BlumCite this: Inorg. Chem. 1979, 18, 4, 915–918Publication Date (Print):April 1, 1979Publication History Published online1 May 2002Published inissue 1 April 1979https://doi.org/10.1021/ic50194a003RIGHTS & PERMISSIONSArticle Views218Altmetric-Citations26LEARN 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 (548 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts