gebhart/patrepeval huggingface dataset:
1,6-Reductive Coupling of Hindered o-Vinyl Diaryl Ketones1 (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,6-Reductive Coupling of Hindered o-Vinyl Diaryl Ketones1REYNOLD C. FUSON, EARL H. HESS, and MEHM TIN MONCite this: J. Org. Chem. 1961, 26, 4, 1042–1044Publication Date (Print):April 1, 1961Publication History Published online1 May 2002Published inissue 1 April 1961https://pubs.acs.org/doi/10.1021/jo01063a016https://doi.org/10.1021/jo01063a016research-articleACS PublicationsRequest reuse permissionsArticle Views32Altmetric-Citations1LEARN 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
Artemisinin: current status (1994)

The compounds derived from the Chinese medicinal plant qinghao (Artemisia annua) are the most rapidly acting of all antimalarial drugs. They are effective when given parenterally, orally or by suppository. No serious adverse effect has yet been reported in humans. The artemisinin derivatives already have an established role in the treatment of multi-drug resistant falciparum malaria, but their wider use will depend on the results of current mortality and toxicity studies.
Multidisciplinary Aerospace System Design: Principles, Issues and Onera Experience (2012)

With the increasing complexity of aerospace systems, it has become more and more necessary to adopt a global, integrated approach from the very early steps and throughout the design process. Tightly coupling aerodynamics, propulsion, structure, trajectory, guidance and navigation, while also taking into account environmental and societal constraints, as well as manufacturability, reliability and maintainability, is a huge challenge. The field of Multidisciplinary Design Optimization (MDO) provides some answers on how to integrate increasing knowledge into the design process, while reducing the design cycles. It consists in a core of key methodologies, such as multi-disciplinary problem formulation and decomposition, optimization under uncertainties and surrogate based high-fidelity tool integration, which are validated and enriched through confrontation with various kinds of design studies. The aim of this paper is, on the one hand, to give a clear view of the challenges at stake and the key difficulties that must be overcome and, on the other hand, to focus on some significant studies and achievements at Onera over the past decade, either on tools and methods, or on dedicated applications, illustrating the progress made and the challenges to come.
A Silicon Single-Electron Transistor Memory Operating at Room Temperature (1997)

A single-electron memory, in which a bit of information is stored by one electron, is demonstrated at room temperature. The memory is a floating gate metal-oxide-semiconductor transistor in silicon with a channel width ( approximately 10 nanometers) smaller than the Debye screening length of a single electron and a nanoscale polysilicon dot ( approximately 7 nanometers by 7 nanometers) as the floating gate embedded between the channel and the control gate. Storing one electron on the floating gate screens the entire channel from the potential on the control gate and leads to (i) a discrete shift in the threshold voltage, (ii) a staircase relation between the charging voltage and the shift, and (iii) a self-limiting charging process. The structure and fabrication of the memory should be compatible with future ultralarge-scale integrated circuits.
Inhibition of Translation in Eukaryotic Systems by Harringtonine (1977)

The Cephalotaxus alkaloids harringtonine, homoharringtonine and isoharringtonine inhibit protein synthesis in eukaryotic cells. The alkaloids do not inhibit, in model systems, any of the steps of the initiation process but block poly(U)-directed polyphenylalanine synthesis as well as peptide bond formation in the fragment reaction assay, the sparsomycin-induced binding of (C)U-A-C-C-A-[3H]Leu-Ac, and the enzymic and the non-enzymic binding of Phe-tRNA to ribosomes. These results suggest that the Cephalotaxus alkaloids inhibit the elongation phase of translation by preventing substrate binding to the acceptor site on the 60-S ribosome subunit and therefore block aminoacyl-tRNA binding and peptide bond formation. However, the Cephalotaxus alkaloids do not inhibit polypeptide synthesis and peptidyl[3H]puromycin formation in polysomes. Furthermore, these alkaloids strongly inhibit [14C]trichlodermin binding to free ribosomes but hardly affect the interaction of the antibiotic with yeast polysomot interact with polysomes and therefore only inhibit cycles of elongation. This explains the polysome run off that has been observed by some workers in the presence of harringtonine.
Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia (2006)

Mouse bone marrow cells transduced with retroviral vectors encoding either of two oncogenic Bcr-Abl isoforms (p210(Bcr-Abl) and p185(Bcr-Abl)) induce B cell lympholeukemias when transplanted into lethally irradiated mice. If the activity of the Arf tumor suppressor is compromised, these donor cells initiate a much more highly aggressive and rapidly fatal disease. When mouse bone marrow cells expressing Bcr-Abl are placed in short-term cultures selectively designed to support the outgrowth of pre-B cells, only those lacking one or two Arf alleles can initiate lympholeukemias when inoculated into immunocompetent, syngeneic recipient mice. Although the ABL kinase inhibitor imatinib mesylate (Gleevec) provides highly effective treatment for BCR-ABL-positive chronic myelogenous leukemia, it has proven far less efficacious in the treatment of BCR-ABL-positive acute lymphoblastic leukemias (ALLs), many of which sustain deletions of the INK4A-ARF (CDKN2A) tumor suppressor locus. Mice receiving Arf-/- or Arf+/- p210(Bcr-Abl)-positive pre-B cells do not achieve remission when maintained on high doses of oral imatinib therapy and rapidly succumb to lympholeukemia. Although cells expressing the Bcr-Abl kinase can proliferate in the absence of IL-7, they remain responsive to this cytokine, which can reduce their sensitivity to imatinib. Treatment of Arf-/-, p210(Bcr-Abl)-positive pre-B cells with imatinib together with an inhibitor of JAK kinases abrogates this resistance, suggesting that this combination may prove beneficial in the treatment of BCR-ABL-positive acute lymphoblastic leukemia.
Cellulose-binding domains promote hydrolysis of different sites on crystalline cellulose (2000)

The cohesin-dockerin interaction in Clostridium thermocellum cellulosome mediates the tight binding of cellulolytic enzymes to the cellulosome-integrating protein CipA. Here, this interaction was used to study the effect of different cellulose-binding domains (CBDs) on the enzymatic activity of C. thermocellum endoglucanase CelD (1,4-beta-d endoglucanase, EC) toward various cellulosic substrates. The seventh cohesin domain of CipA was fused to CBDs originating from the Trichoderma reesei cellobiohydrolases I and II (CBD(CBH1) and CBD(CBH2)) (1,4-beta-d glucan-cellobiohydrolase, EC), from the Cellulomonas fimi xylanase/exoglucanase Cex (CBD(Cex)) (beta-1,4-d glucanase, EC), and from C. thermocellum CipA (CBD(CipA)). The CBD-cohesin hybrids interacted with the dockerin domain of CelD, leading to the formation of CelD-CBD complexes. Each of the CBDs increased the fraction of cellulose accessible to hydrolysis by CelD in the order CBD(CBH1) < CBD(CBH2) approximately CBD(Cex) < CBD(CipA). In all cases, the extent of hydrolysis was limited by the disappearance of sites accessible to CelD. Addition of a batch of fresh cellulose after completion of the reaction resulted in a new burst of activity, proving the reversible binding of the intact complexes despite the apparent binding irreversibility of some CBDs. Furthermore, burst of activity also was observed upon adding new batches of CelD-CBD complexes that contained a CBD differing from the first one. This complementation between different CBDs suggests that the sites made available for hydrolysis by each of the CBDs are at least partially nonoverlapping. The only exception was CBD(CipA), whose sites appeared to overlap all of the other sites.
Rational Live Oral Carrier Vaccine Design by Mutating Virulence-Associated Genes of Yersinia enterocolitica (1999)

Three different Yersinia enterocolitica serotype O8 strains harboring mutations in virulence-associated genes coding for Yersinia adhesin A (YadA), Mn-cofactored superoxide dismutase (SodA), and high-molecular-weight protein 1 were analyzed for their ability to colonize and persist in tissues after orogastric immunization of C57BL/6 mice. We demonstrated that all three Yersinia mutant strains were markedly impaired in their ability to disseminate into the spleens and livers of immunized mice but were able to colonize the Peyer's patches for at least 12 days, resulting in the induction of significant antibody titers against Yersinia outer proteins (Yops) and in the priming of Yersinia antigen-specific CD4+ Th1 cells isolated from spleens. The high level of attenuation did not diminish the immunogenic properties of the mutant strains. In fact, mice immunized with a single oral dose of any of the mutant strains were protected against a lethal oral-challenge infection with wild-type Y. enterocolitica. Moreover, adoptive transfer of Yersinia-specific antibodies from sera of mice immunized with the mutant WAP-314 sodA revealed that this protection could be mediated by Yersinia-specific immunoglobulins.
The EMBL-EBI search and sequence analysis tools APIs in 2019 (2019)

The EMBL-EBI provides free access to popular bioinformatics sequence analysis applications as well as to a full-featured text search engine with powerful cross-referencing and data retrieval capabilities. Access to these services is provided via user-friendly web interfaces and via established RESTful and SOAP Web Services APIs (https://www.ebi.ac.uk/seqdb/confluence/display/JDSAT/EMBL-EBI+Web+Services+APIs+-+Data+Retrieval). Both systems have been developed with the same core principles that allow them to integrate an ever-increasing volume of biological data, making them an integral part of many popular data resources provided at the EMBL-EBI. Here, we describe the latest improvements made to the frameworks which enhance the interconnectivity between public EMBL-EBI resources and ultimately enhance biological data discoverability, accessibility, interoperability and reusability.
Historical Review of Glasses Used for Parenteral Packaging (2017)

Glass has long been used for packaging precious liquids, in particular pharmaceuticals. Its unique combination of hermeticity, transparency, strength, and chemical durability make it the optimal material for such an important role. Today's life-saving drugs are stored in borosilicate glasses, which evolved from applications in microscope optics and thermometers. As the glass compositions improved, so did the methods used to shape them and the tests used to characterize them. While all of these advances improved the quality of the glass container and its ability to protect the contents, problems still exist such as delamination, cracks, and glass particulates. In addition to these issues, we review new developments in glass composition development, performance, and testing in the 21<sup>st</sup> century.
Role of hydrogen peroxide in cytotoxicity induction by ascorbates and other redox compounds. (1999)

Role of hydrogen peroxide (H2O2) in the induction of cytotoxicity by ascorbic acid derivatives was investigated. Ascorbic acid derivatives which produced radicals (sodium 5,6-benzylidene-L-ascorbate (SBA), sodium-L-ascorbate, D-isoascorbic acid) dose-dependently reduced the viable cell number of human squamous carcinoma (HSC-2, HSC-4, NA), human salivary gland tumor (HSG) and human promyelocytic leukemia (HL-60) cell lines. Conversely, L-ascorbic acid-2-phosphate magnesium which did not produce radicals, was inactive. This suggests the possible role of the ascorbate radical in apoptosis induction. The cytotoxic activity of SBA was partially reduced by catalase, and the extent of inhibition by catalase was considerably different, depending upon which target cells were used. On the other hand, the cytotoxic activity of sodium ascorbate, isoascorbic acid, hydrogen peroxide and gallic acid was more effectively inhibited by catalase. These data suggest that mechanisms other than H2O2 might be involved in the induction of cytotoxicity by SBA.
Efficacy and Safety of Inhaled Corticosteroids in Asthma (1993)

Inhaled glucocorticosteroids have now become first-line therapy for the treatment of chronic asthma in many countries. They are the most effective asthma therapy currently available, and numerous studies have documented their long-term efficacy in asthma control in adults and in children. Inhaled steroids suppress inflammation in asthmatic airways, although their precise molecular mechanism of action is not yet certain. It is likely that steroids affect the transcription of several steroid-responsive genes, and, of particular importance, they may inhibit cytokine gene transcription and cytokine effects, thereby reducing the chronic inflammation in asthmatic airways. Inhaled steroids are now used at a much earlier stage in asthma therapy, and there is a strong argument for their early introduction in both adults and children to prevent asthma morbidity and mortality and possibly the structural changes resulting from uncontrolled chronic inflammation, which may lead to irreversible airflow obstruction in some patients. Of paramount importance is the question of safety as inhaled steroids are likely to be required for a long time. Local side effects caused by oropharyngeal deposition of the inhaled steroid may be reduced by the use of spacer devices and mouthwashing. Systemic side effects caused by gastrointestinal absorption of the fraction deposited in the oropharynx may also be reduced by these devices. There are differences in the systemic bioavailability of the different inhaled steroids currently in use, and inhaled steroids with the lowest bioavailability should be chosen when high doses of inhaled steroids are required for asthma control. Systemic side effects are usually observed only when daily doses of > 800 micrograms are inhaled, and whether effects on very sensitive biochemical indices are relevant to long-term deleterious effects is not yet certain. There is now overwhelming evidence that the doses of inhaled steroids required to control asthma in the majority of adults and children are safe and without systemic side effects. It is important to control asthma with the minimum dose of inhaled steroids possible, however. In the future it may be possible to develop inhaled steroids with even fewer systemic effects if the fraction absorbed from the respiratory tract can be rapidly metabolized in the bloodstream.
One‐Pot Solution Synthesis of Cubic Cobalt Nanoskeletons (2009)

Cubic Co nanoskeletons with an edge length of 100 nm are prepared by a facile one-pot solution method. The cubic Co nanoskeletons synthesized exhibit excellent magnetic properties and mesopore structures. This work may provide an easy way to control the synthesis of hollow metal nanopolyhedra by introducing an appropriate etching agent into the synthetic process.
Characterization of the Promoter Region forflt-1Tyrosine Kinase Gene, A Receptor for Vascular Ehdothelial Growth Factor (1996)

The flt-1 gene encodes a Vascular Endothelial Growth Factor receptor, (Flt-1), whose expression is restricted to vascular endothelial cells. To characterize the cell type specificity of flt-1 gene expression, we isolated the upstream genomic DNA of the human flt-1 gene and identified a single transcription initiation site 29 bp downstream of a TATA box. DNA sequencing revealed that one TATA box, four GC boxes, nine ETS motifs and one CRE motif were present in the upstream 489 bp region of exon 1. Functional analyses using CAT plasmids in 293E1 cells, which express significant levels of the flt-1 gene, showed that the -229 to +8 region is essential for the cell type-specific expression of this gene. Deletion mutant analysis also pointed to the possible existence of negative and positive regulatory elements in the region -911 to -435, and +8 to +276, respectively. These results suggest that multiple regulatory factors are involved in the transcriptional regulation of the flt-1 gene expression in a cell type-specific, or a more ubiquitous manner.
Tissue distribution and localization of natriuretic peptide receptor subtypes in stroke-prone spontaneously hypertensive rats (1997)

These results indicated that each NPR subtype had a distinct tissue distribution pattern and that the expression of NPR-C in the kidneys of SHR-SP was greater than that in the kidneys of WKY rats.
Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on‐target ALK inhibitors in neuroblastoma (2017)

Targeted inhibition of anaplastic lymphoma kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies; however, the presence of resistant mutations necessitates both the development of more potent compounds and pharmacodynamic methods with which to determine their efficacy. We describe immunoassays designed to quantitate phosphorylation of ALK, and their use in preclinical models of neuroblastoma, a pediatric malignancy in which gain-of-function ALK mutations predict a poor overall outcome to conventional treatment. Validation of the immunoassays is presented using a panel of neuroblastoma cell lines and evidence of on-target ALK inhibition provided by treatment of a genetically engineered murine model of neuroblastoma with two clinical ALK inhibitors, crizotinib and ceritinib, highlighting the superior efficacy of ceritinib.
Using Workflow Technology to Manage Flexible e-Learning Services (2002)

Workflow technology provides a suitable platform to define and manage the coordination of business process activities. We introduce a flexible e-learning environment – called Flex-eL – that has been built upon workflow technology. The workflow functionality of Flex-eL manages the coordination of learning and assessment activities of the course process between students and teaching staff. It provides a unique environment for teachers to design and develop process-centric courses and to monitor student progress. It allows students to learn at their own pace while observing the learning guidelines and checkpoints modeled into the course process by teaching staff. We also report on the successful deployment of the concept and system for university courses and our experiences from the implementation.
Highly Efficient Solar Cells using TiO2 Nanotube Arrays Sensitized with a Donor-Antenna Dye (2008)

Donor antenna dyes provide an exciting route to improving the efficiency of dye sensitized solar cells owing to their high molar extinction coefficients and the effective spatial separation of charges in the charge-separated state, which decelerates the recombination of photogenerated charges. Vertically oriented TiO(2) nanotube arrays provide an optimal material architecture for photoelectrochemical devices because of their large internal surface area, lower recombination losses, and vectorial charge transport along the nanotube axis. In this study, the results obtained by sensitizing TiO(2) nanotube arrays with the donor antenna dye Ru-TPA-NCS are presented. Solar cells fabricated using an antenna dye-sensitized array of 14.4 microm long TiO(2) nanotubes on Ti foil subjected to AM 1.5 one sun illumination in the backside geometry exhibited an overall conversion efficiency of 6.1%. An efficiency of 4.1% was obtained in the frontside illumination geometry using a 1 microm long array of transparent TiO(2) nanotubes subjected to a TiCl(4) treatment and then sensitized with the Ru-TPA-NCS dye. Open circuit voltage decay measurements give insight into the recombination behavior in antenna-dye sensitized nanotube photoelectrodes, demonstrating outstanding properties likely due to a reduction in the influence of the surface traps and reduced electron transfer from TiO(2) to ions in solution.
The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma (2010)

Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.
Interleukin‐17‐producing γδ+ T cells protect NOD mice from type 1 diabetes through a mechanism involving transforming growth factor‐β (2009)

Whether interleukin (IL)-17 promotes a diabetogenic response remains unclear. Here we examined the effects of neutralization of IL-17 on the progress of adoptively transferred diabetes. IL-17-producing cells in non-obese diabetic (NOD) mice were identified and their role in the pathogenesis of diabetes examined using transfer and co-transfer assays. Unexpectedly, we found that in vivo neutralization of IL-17 did not protect NOD-severe combined immunodeficiency (SCID) mice against diabetes transferred by diabetic splenocytes. In NOD mice, gammadelta(+) T cells were dominated by IL-17-producing cells and were found to be the major source of IL-17. Interestingly, these IL-17-producing gammadelta T cells did not exacerbate diabetes in an adoptive transfer model, but had a regulatory effect, protecting NOD mice from diabetes by up-regulating transforming growth factor (TGF)-beta production. Our data suggest that the presence of IL-17 did not increase the chance of the development of diabetes; gammadelta T cells protected NOD mice from diabetes in a TGF-beta-dependent manner, irrespective of their role as major IL-17 producers.
Considerations for the Clinical Development of Cytokine Gene-Transduced Tumor Cell Vaccines (1997)

In preclinical models, tumor cells genetically altered to secrete cytokines or express costimulatory molecules can generate systemic antitumor immunity. In some studies, these tumor vaccines have been shown to eradicate micrometastases. These results have led to the initiation of numerous phase I clinical trials employing either genetically modified or allogenic tumor vaccines. This article addresses a number of issues related to the clinical development of cytokine gene-transduced tumor cell vaccines including: (1) the production of cytokine-secreting tumor vaccines; and (2) the preclinical feasibility and toxicity studies required for testing these vaccines in patients with cancer.