gebhart/patrepeval huggingface dataset:
Evaluation of the Desferrithiocin Pharmacophore as a Vector for Hydroxamates (1999)

A series of (S)-desmethyldesferrithiocin (DMDFT, 1) hydroxamates and a bis-salicyl polyether hydroxamate are evaluated for their iron-clearing properties in rodents; some of these are further assessed in primates. These hydroxamates include (S)-desmethyldesferrithiocin, N-methylhydroxamate (2); (S)-desmethyldesferrithiocin, N-[5-(acetylhydroxyamino)pentyl]hydroxamate (3); desmethyldesferrithiocin, N-benzylhydroxamate (4); (S,S)-N(1), N(8)-bis[4,5-dihydro-2-(3-hydroxy-2-pyridinyl)-4-thiazoyl]-N(1), N(8)-dihydroxy-3,6-dioxa-1,8-octanediamine (5); and N(1), N(8)-bis(2-hydroxybenzoyl)-N(1),N(8)-dihydroxy-3,6-dioxa-1, 8-octanediamine (6). The ligands are evaluated when given both orally (po) and subcutaneously (sc) in the bile-duct-cannulated rodent model. In iron-overloaded primates, ligands 1-4 are assessed when administered po and sc. The efficiencies of the hydroxamates are shown to vary considerably; giving the compounds sc consistently resulted in greater chelating efficiency in vivo. After oral administration in the primate, compound 3, a pentacoordinate unsymmetrical dihydroxamate, produces iron excretion sufficient to warrant further preclinical evaluation both as a potential orally active iron-chelating agent and as a parenteral iron chelator. The increased iron clearance of several of these ligands when administered sc versus po also underscores the idea that parenteral administration is a reasonable alternative to a less efficient, orally active device which would require large and frequent doses.
iHOPerator: user-scripting a personalized bioinformatics Web, starting with the iHOP website (2006)

This open-source script provides an extension to the iHOP website, demonstrating how user-scripts can personalize and enhance the Web browsing experience in a relevant biological setting. The novel, user-driven controls over the content and the display of Web resources made possible by user-scripts, such as the iHOPerator, herald the beginning of a transition from a resource-centric to a user-centric Web experience. We believe that this transition is a necessary step in the development of Web technology that will eventually result in profound improvements in the way life scientists interact with information.
Wall-less liquid pathways formed with three-dimensional microring arrays (2012)

This paper describes a method to construct microfluidic pathways without physical walls—wall-less microchannels. Compared to the previous wall-less microfluidics based on two-dimensional patterns, this method uses three-dimensional ring arrays and two immiscible liquids. The distant rings generate free-standing liquid pathways in order to minimize liquid surfaces contacted to solid walls. In the experimental study, we reduced the liquid-solid interface area per volume to 17.3% of that of the conventional microchannels with squared cross-sections. We envision that this aspect would be significant in micro/nano-fluidics, whose surface-area-to-volume ratio is extremely large.
A reagent for reduction of disulfide bonds in proteins that reduces disulfide bonds faster than does dithiothreitol (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA reagent for reduction of disulfide bonds in proteins that reduces disulfide bonds faster than does dithiothreitolRajeeva Singh and George M. WhitesidesCite this: J. Org. Chem. 1991, 56, 7, 2332–2337Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/jo00007a018https://doi.org/10.1021/jo00007a018research-articleACS PublicationsRequest reuse permissionsArticle Views1475Altmetric-Citations34LEARN 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
Total synthesis of (.+-.)-dihydroperiphylline (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of (.+-.)-dihydroperiphyllineHarry H. Wasserman and Haruo MatsuyamaCite this: J. Am. Chem. Soc. 1981, 103, 2, 461–462Publication Date (Print):January 1, 1981Publication History Published online1 May 2002Published inissue 1 January 1981https://doi.org/10.1021/ja00392a036RIGHTS & PERMISSIONSArticle Views290Altmetric-Citations58LEARN 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 (269 KB) Get e-Alertsclose Get e-Alerts
PD-1 marks dysfunctional regulatory T cells in malignant gliomas (2016)

Immunotherapies targeting the immune checkpoint receptor programmed cell death protein 1 (PD-1) have shown remarkable efficacy in treating cancer. CD4<sup>+</sup>CD25<sup>hi</sup>FoxP3<sup>+</sup> Tregs are critical regulators of immune responses in autoimmunity and malignancies, but the functional status of human Tregs expressing PD-1 remains unclear. We examined functional and molecular features of PD-1<sup>hi</sup> Tregs in healthy subjects and patients with glioblastoma multiforme (GBM), combining functional assays, RNA sequencing, and cytometry by time of flight (CyTOF). In both patients with GBM and healthy subjects, circulating PD-1<sup>hi</sup> Tregs displayed reduced suppression of CD4<sup>+</sup> effector T cells, production of IFN-γ, and molecular signatures of exhaustion. Transcriptional profiling of tumor-resident Tregs revealed that several genes coexpressed with PD-1 and associated with IFN-γ production and exhaustion as well as enrichment in exhaustion signatures compared with circulating PD-1<sup>hi</sup> Tregs. CyTOF analysis of circulating and tumor-infiltrating Tregs from patients with GBM treated with PD-1-blocking antibodies revealed that treatment shifts the profile of circulating Tregs toward a more exhausted phenotype reminiscent of that of tumor-infiltrating Tregs, further increasing IFN-γ production. Thus, high PD-1 expression on human Tregs identifies dysfunctional, exhausted Tregs secreting IFN-γ that exist in healthy individuals and are enriched in tumor infiltrates, possibly losing function as they attempt to modulate the antitumoral immune responses.
Lenvatinib: A Potential Breakthrough in Advanced Hepatocellular Carcinoma? (2016)

Treatment of advanced hepatocellular carcinoma (HCC) has reached a plateau after the approval of sorafenib in 2007. Several molecularly targeted therapies have failed to show significant improvement in survival outcomes compared with sorafenib, due to flaws in the design of clinical trials or failure to understand and correct for the competing co-morbidity of liver dysfunction. Lenvatinib is a multitargeted tyrosine kinase inhibitor with potent antiangiogenic effects, and has recently been approved for differentiated thyroid cancer. Lenvatinib has shown highly promising response data in Phase I/II clinical trials in HCC, although with some concerns regarding its toxicity profile. The pivotal Phase III REFLECT trial comparing lenvatinib to sorafenib has been completed, and the results of this trial will determine whether lenvatinib represents a breakthrough in the current crisis affecting HCC drug development.
Cinematic primitives for multimedia (1991)

The development of robust frameworks in interactive multimedia for representing story elements to the machine so that they can be retrieved in multiple contexts is addressed. Interactive multimedia is discussed as a user-directed form of storytelling, and the nature of cinematic storytelling is examined. It is proposed that content can be represented in layers. This model for layered information will allow programs to take advantage of the relation between cinematic sequences and the world they represent. The collection of content by the camera and microphone is considered in this context. The use of the methodology to build meaningful, context-rich sequences is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Preparation, structure, and properties of the superconducting compound seriesBi2Sr2Can−1CunOywithn=1,2, and 3 (1988)

Crystals of the three Bi-based cuprates of general formula ${\mathrm{Bi}}_{2}{\mathrm{Sr}}_{2}{\mathrm{Ca}}_{n\ensuremath{-}1}{\mathrm{Cu}}_{n}{\mathrm{O}}_{y}$ with $n=1,2, \mathrm{and} 3$ have been isolated and their structural and physical properties investigated. The structures are similar, differing only in the number of Cu${\mathrm{O}}_{2}$-Ca-Cu${\mathrm{O}}_{2}$ slabs packed along the $c$ axis. The insertion of one and two slabs increases $c$ from 24.6 to 30.6 and 37.1 \AA{}. Transmission electron microscopy shows there are stacking faults within the crystals in agreement with our x-ray data and its analysis. Resistivity, ac susceptibility, and dc magnetization measurements demonstrate superconductivity in the $n=1,2, \mathrm{and} 3$ phases at 10, 85, and 110 K, respectively. The observed transition temperatures and the stacking fault densities are dependent upon sample processing, in particular, the annealing temperatures and cooling rates. The transition temperature is, within the accuracy of our chemical titration, independent of the average copper valency that was determined to be 2.15 \ifmmode\pm\else\textpm\fi{} 0.03 for each of the three compounds.
Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance (2006)

Emerging evidence suggests critical roles for APCs in suppressing immune responses. Here, we show that zymosan, a stimulus for TLR2 and dectin-1, regulates cytokine secretion in DCs and macrophages to induce immunological tolerance. First, zymosan induces DCs to secrete abundant IL-10 but little IL-6 and IL-12(p70). Induction of IL-10 is dependent on TLR2- and dectin-1-mediated activation of ERK MAPK via a mechanism independent of the activation protein 1 (AP-1) transcription factor c-Fos. Such DCs stimulate antigen-specific CD4+ T cells poorly due to IL-10 and the lack of IL-6. Second, zymosan induces F4-80+ macrophages in the splenic red pulp to secrete TGF-beta. Consistent with these effects on APCs, injection of zymosan plus OVA into mice results in OVA-specific T cells that secrete little or no Th1 or Th2 cytokines, but secrete robust levels of IL-10, and are unresponsive to challenge with OVA plus adjuvant. Finally, coinjection of zymosan with OVA plus LPS suppresses the response to OVA via a mechanism dependent on IL-10, TGF-beta, and lack of IL-6. Together, our data demonstrate that zymosan stimulates IL-10+ IL-12(p70)- IL-6low regulatory DCs and TGF-beta+ macrophages to induce immunological tolerance. These data suggest several targets for pharmacological modulation of immune responses in various clinical settings.
Advanced layout of a fiber Bragg grating strain gauge rosette (2006)

A temperature-compensated strain-sensing scheme based on fiber Bragg gratings (FBGs) that is suitable for strain mapping applications is described. FBGs are bonded to a backing patch, together with an extra grating that is used for temperature compensation/measurement. The patch provides a simpler and more robust way of attaching the FBGs to a structure than directly mounting a bare fiber, though it was necessary to design it in such a way that there was minimal reduction in the strain transferred from the structure to the sensing fibers. Finite element (FE) analysis was used to help design the patch, which was then constructed accordingly. The authors have demonstrated experimentally that the use of the backing patch produces a reduction in strain sensitivity of only around 4%, which is slightly better than theoretically predicted values. The temperature measuring FBG had to be bonded in such a way that it experienced the changes in temperature, but not the strain, to which the structure was subjected. A design for doing this was developed and proven. The use of a backing patch to develop a rosette configuration of Bragg gratings, each having a different peak reflective wavelength, is described. The rosette configuration is one that is frequently used with electrical strain gauges and allows here to determine both the magnitude and the direction of strain.
Physical Therapy for Acute Low Back Pain (2008)

Adherence to the recommendation for active care was associated with better clinical outcomes and decreased subsequent use of prescription medication, MRI, and injections. Improving adherence to this recommendation may present an opportunity to improve the cost-effectiveness of care for acute LBP.
Tissue microarray: a new technology for amplification of tissue resources. (2001)

Tissue microarrays are a method of harvesting small disks of tissue from a range of standard histologic sections and placing them in an array on a recipient paraffin block such that hundreds of cases can be analyzed simultaneously. This technique allows maximization of tissue resources by analysis of small-core biop sies of blocks, rather than complete sections. Using this technology, a carefully planned array can be constructed with cases from pathology tissue block archives, such that a 20-year survival analysis can be performed on a cohort of 600 or more patients by use of only a few microliters of antibody in a single experiment. The reflex criticism of this technique is that the tissue analyzed is not representative, especially in antigens with heterogeneous staining patterns. This review addresses this issue, as well as the issue of antigen preservation or durability, which validates construction of arrays from archives. Strategies and methods of construction and analysis of the arrays are discussed, as well as some other unusual array applications. This technique can provide a highly efficient, high-throughput mechanism for evaluation of protein expression in large cohorts. It has the potential to allow validation of new genes at a speed comparable to the rapid rate of gene discovery afforded by DNA microarrays.
Cyclisation of N-prop-2-ynylbenzylamines : preparation of a 1,2-dihydroisoquinoline and a 2-benzazepine (1969)

N-Prop-2-ynylbenzylamines undergo acid-catalysed ring-closure to form heterocyclic bases. The results of two cyclisations are reported. With a terminal acetylene group, the product was a 1,2-dihydroisoquinoline. In contrast, with a phenyl-substituted acetylene the reaction gave a 2-benzazepine. Mass spectra have been obtained for both products, and a reaction mechanism is postulated.
Overproduction of ornithine decarboxylase caused by relief of translational repression is associated with neoplastic transformation. (1994)

The mRNAs for two key enzymes in polyamine biosynthesis, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), both long 5' untranslated regions (5'UTRs) that could be important in the regulation of enzyme levels by affecting the translation of these mRNAs. In order to test this hypothesis, ODC and AdoMetDC activities were measured in 3T3 cells and in 3T3 cells overexpressing eIF-4E (P2 cells). eIF-4E has been reported to be a limiting factor in the translation of mRNAs with extensive secondary structures in the 5'UTR. AdoMetDC activity was not greatly different in the two cell lines, but ODC activity was much greater in the P2 cells. These results were confirmed by transfecting these cells with plasmids containing a luciferase complementary DNA fused to follow the 5'UTR from ODC or AdoMetDC. The ODC 5'UTR construct produced a higher luciferase activity in the P2 cells. The high level of expression of ODC may be a critical factor in the transformed phenotype of the P2 cells since the ability of these cells to grow in soft agar was blocked by levels of the ODC inhibitor, alpha-difluoromethylornithine, that reduced the ODC activity to values comparable to those of the parent 3T3 cells. These results provide more evidence for a critical role of ODC activity in neoplastic transformation and for the importance of its translational regulation in cell growth and transformation.
Highly Enantioselective Hydrogenation of .beta.-Keto Esters under Mild Conditions (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHighly Enantioselective Hydrogenation of .beta.-Keto Esters under Mild ConditionsMark J. Burk, T. Gregory P. Harper, and Christopher S. KalbergCite this: J. Am. Chem. Soc. 1995, 117, 15, 4423–4424Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ja00120a035https://doi.org/10.1021/ja00120a035research-articleACS PublicationsRequest reuse permissionsArticle Views1283Altmetric-Citations129LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
ChemInform Abstract: Semisynthesis of Taxol and Taxotere (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Highly Reliable MA BE-SONOS (Metal-Al<inf>2</inf>O<inf>3</inf> Bandgap Engineered SONOS) Using a SiO<inf>2</inf> Buffer Layer (2008)

A metal-high-k bandgap-engineered SONOS (MA BE-SONOS) with an additional SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> buffer layer is proposed. The thin SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> (5 ~ 6 nm) layer between the high-k (Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> ) and nitride serves to prevent shallow trap generation. Contrary to the previously proposed MANOS or MA BE-SONOS devices using a simple high-k top dielectric, this composite structure eliminates the unstable high-k/nitride interface. Experimental results show that this new device can well suppress the erase saturation, just like MANOS. On the other hand, the data retention is greatly improved, owing to the much more stable interface between the nitride-trapping layer and top oxide. Very large memory window (> 7 V) with excellent cycling endurance, read disturb immunity, and data retention has been successfully demonstrated. Theoretical model is also proposed to explain the principle of this device.
Retaining Customers With Shopping Convenience (2009)

Our empirical research investigates the impact of dimensions of shopping convenience (decision, access, search, transaction, and after-sales convenience) on customer retention, including customer behavioral loyalty (shares of wallet and visits) and attitudinal loyalty (exit intention). Our findings show that for utilitarian shopping, behavioral and attitudinal loyalty are partly affected by different dimensions. Decision and access convenience, dimensions that come into play prior to the purchase, are most important for share of visits and share of wallet. Apart from decision convenience, exit intention is very much affected by transaction convenience, which is an in-store dimension. Furthermore, comparing our results with results of hedonic shopping purposes shows that major differences exist.
BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak (2001)

The BH3-only proteins Bim and Bad bind to the antiapoptotic Bcl-2 proteins and induce apoptosis in wild-type cells and cells from either bax(-/-) or bak(-/-) animals. In contrast, constitutively active forms of Bim and Bad failed to induce apoptosis in bax(-/-)bak(-/-) cells. Expression of Bax restored susceptibility of the cells to Bim and Bad. In addition, Bax but not Bim or Bad sensitized the bax(-/-)bak(-/-) cells to a wide variety of cell death stimuli including UV irradiation, chemotherapeutic agents, and ER stress. These results suggest that neither activation of BH3-only proteins nor suppression of pro-survival Bcl-2 proteins is sufficient to kill cells in the absence of both Bax and Bak. Furthermore, whereas mouse embryo fibroblasts (MEF) expressing only Bax or Bak displayed resistance to transformation, bax(-/-)bak(-/-) MEF were nearly as prone to oncogenic transformation as p53(-/-) MEF. Thus, the function of either Bax or Bak appears required to initiate most forms of apoptosis and to suppress oncogenic transformation.
Study on the Design of the Digital Control Machine-tool Operating System (2009)

The ergonomics is an independent subject developed from the beginning of the 20th century, and it is the frontier applied science which studies the comprehensive performances such as comfort ability, production efficiency and safety under various conditions. In the article, a series of human oriented designs were studied for the software and hardware interfaces of the digital control machine-tool based on the theory of the ergonomics and the human-oriented principle.