gebhart/patrepeval huggingface dataset:
In Vitro Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor TMC435 (2010)

TMC435 is a small-molecule inhibitor of the NS3/4A serine protease of hepatitis C virus (HCV) currently in phase 2 development. The in vitro resistance profile of TMC435 was characterized by selection experiments with HCV genotype 1 replicon cells and the genotype 2a JFH-1 system. In 80% (86/109) of the sequences from genotype 1 replicon cells analyzed, a mutation at NS3 residue D168 was observed, with changes to V or A being the most frequent. Mutations at NS3 positions 43, 80, 155, and 156, alone or in combination, were also identified. A transient replicon assay confirmed the relevance of these positions for TMC435 inhibitory activity. The change in the 50% effective concentrations (EC(50)s) observed for replicons with mutations at position 168 ranged from <10-fold for those with the D168G or D168N mutation to approximately 2,000-fold for those with the D168V or D168I mutation, compared to the EC(50) for the wild type. Of the positions identified, mutations at residue Q80 had the least impact on the activity of TMC435 (<10-fold change in EC(50)s), while greater effects were observed for some replicons with mutations at positions 43, 155, and 156. TMC435 remained active against replicons with the specific mutations observed after in vitro or in vivo exposure to telaprevir or boceprevir, including most replicons with changes at positions 36, 54, and 170 (<3-fold change in EC(50)s). Replicons carrying mutations affecting the activity of TMC435 remained fully susceptible to alpha interferon and NS5A and NS5B inhibitors. Finally, combinations of TMC435 with alpha interferon and NS5B polymerase inhibitors prevented the formation of drug-resistant replicon colonies.
A No-Buff Technique to Produce Surfaces That Induce Alignment in Liquid Crystals (2002)

Alignment layers for liquid crystal cells were prepared by directional deposition of high molecular weight rigid-rod ionomers on glass and indium–tin–oxide substrates. Several deposition techniques were developed and tested. Material type, concentration, temperature, and application technique were systematically varied and the resultant alignment of the liquid crystals studied. Three different methods of applying the alignment layer were investigated: directional spray deposition, brushing, and directional deposition using a squeegee (doctor bar). The application temperature ranged from 30 to 80°C. The best results were obtained using a squeegee to perform directional deposition at temperature of less than 60°C. The alignment layers obtained in this way are robust, exhibit excellent alignment, and have pretilt angles of a few degrees. Crediting the original material http://jjap.jsap.jp/link?JJAP/41/2183/
Disabling the Gβγ-SNARE interaction disrupts GPCR-mediated presynaptic inhibition, leading to physiological and behavioral phenotypes (2019)

G protein-coupled receptors (GPCRs) that couple to G<sub>i/o</sub> proteins modulate neurotransmission presynaptically by inhibiting exocytosis. Release of Gβγ subunits from activated G proteins decreases the activity of voltage-gated Ca<sup>2+</sup> channels (VGCCs), decreasing excitability. A less understood Gβγ-mediated mechanism downstream of Ca<sup>2+</sup> entry is the binding of Gβγ to SNARE complexes, which facilitate the fusion of vesicles with the cell plasma membrane in exocytosis. Here, we generated mice expressing a form of the SNARE protein SNAP25 with premature truncation of the C terminus and that were therefore partially deficient in this interaction. SNAP25Δ3 homozygote mice exhibited normal presynaptic inhibition by GABA<sub>B</sub> receptors, which inhibit VGCCs, but defective presynaptic inhibition by receptors that work directly on the SNARE complex, such as 5-hydroxytryptamine (serotonin) 5-HT<sub>1b</sub> receptors and adrenergic α<sub>2a</sub> receptors. Simultaneously stimulating receptors that act through both mechanisms showed synergistic inhibitory effects. SNAP25Δ3 homozygote mice had various behavioral phenotypes, including increased stress-induced hyperthermia, defective spatial learning, impaired gait, and supraspinal nociception. These data suggest that the inhibition of exocytosis by G<sub>i/o</sub>-coupled GPCRs through the Gβγ-SNARE interaction is a crucial component of numerous physiological and behavioral processes.
Rate-distortion with mixed types of side information (2003)

We present the rate-distortion function and bound the rate loss for a system with some side information (s.i.) known at both the encoder and decoder, and some known only at the decoder. We extend the corresponding Wyner-Ziv rate-distortion results to give a lower bound for jointly Gaussian sources and upper and lower bounds for binary symmetric sources. Applying the construction from our binary upper bound to the Heegard and Berger (HB) problem of decoding when s.i. may be present improves the best upper bound for that problem. Applying it to the two-receiver system with different s.i. at each decoder provides a new upper bound.
Single-Core Performance is Still Relevant in the Multi-Core Era (2011)

In this study, Fe<sub>3</sub>O<sub>4</sub>@ZnO-Bru was successfully synthesized. PDT was combined with photochemotherapy, which exhibited a higher inhibitory effect on SCC. It can be inferred that Fe<sub>3</sub>O<sub>4</sub>@ZnO-Bru holds great potential for skin SCC therapy.
Parental Support Provided by Nonoffending Caregivers to Sexually Abused Children: A Comparison Between Mothers and Fathers (2014)

Parental support provided to child sexual abuse (CSA) victims is a key element in their recovery process. Yet, little is known about the extent and nature of support provided by fathers when they are not identified as the perpetrators. This study compares abuse-specific and nonspecific support provided by 92 mothers and 32 fathers after disclosure and six months later. The assessment of both types of support revealed that only the provision of nonspecific support was predicted by gender. With the exception of social support, all other dimensions increased in the months following disclosure. Implications for child protective agencies include early detection of a small group of parents who may have difficulty offering support to their child, in order to foster the development of optimal support strategies.
Abstract 992: Regulation of ABCG2 lysosomal degradation by xanthines: Role of the PI3K/AKT pathway. (2013)

Abstract ABCG2 confers multidrug resistance to a wide range of structurally unrelated chemotherapeutic drugs, often resulting in the failure of cancer chemotherapy. Accordingly, the downregulation of ABCG2 expression and/or function has been proposed as part of a regimen to improve cancer therapeutic efficacy. Previously, we have reported that a group of xanthines including caffeine, theophylline and dyphylline can dramatically decrease ABCG2 protein in drug resistant cells, causing a significant increase in the intracellular retention of ABCG2 substrates and sensitization of the cells to chemotherapeutic agents (Ding et al., Mol Pharmacol 81:328-337, 2012). This downregulation of ABCG2 is due to a selective acceleration of its lysosomal degradation by xanthines. We now show that xanthines induce the endocytosis and subsequent degradation of ABCG2. In addition, PI3K/AKT/mTORC1 signaling was found to be involved in mediating the effect of xanthines on ABCG2, since both caffeine and theophylline strongly inhibited activation of AKT and mTORC1, and inhibition of both AKT and mTORC1 mimicked the effect of xanthines on ABCG2. Furthermore, adenosine, a nucleoside vital for purine metabolism and energy homeostasis, fully reversed the downregulation effect of caffeine on ABCG2. Interestingly, this adenosine-mediated effect occurs intracellularly and independent of adenosine receptor signalling, identifying a novel mechanism whereby the xanthine-degradation of ABCG2 is influenced by intracellular levels of adenosine. Importantly, adenosine also blocked the lysosomal degradation of ABCG2 that was induced by PI3K/AKT inhibition, indicating that the adenosine-mediated intracellular events cross-talk with the PI3K/AKT pathway in regulating ABCG2 degradation. This study enhances our understanding of the regulation of ABCG2 internalization and degradation, and identifies new targets for the development of ABCG2 expression/function modulating agents for chemosensitization. Citation Format: Rui Ding, Barton A. Kamen, Jia Shi, Kathleen W. Scotto. Regulation of ABCG2 lysosomal degradation by xanthines: Role of the PI3K/AKT pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 992. doi:10.1158/1538-7445.AM2013-992
Three rapid and effective requirements definition modelling tools: evolving technology for manufacturing system investigations (1994)

Abstract Current structured analysis tools are plagued by such problems as long completion times, complex notation, high costs, and voluminous documentation. To overcome these difficulties, the authors propose three new tools for effective definition of integrated information systems for manufacturing systems: the triple diagonal, the user-concept diagram, and the concept map. The triple diagonal is used to identify and prioritize major information system modules required of the factory. The user-concept diagram plays a complementary, expansive role to the triple diagonal as it serves to model the details of the process Dow for major information system modules. The concept map is used in parallel with both of the above tools to help structure important entity/object classes making up ihc database. The tools were tested through a case study involving a startup information system design effort. This effort involved the verification of contractor software support of essential information flows within a large re-manufacturing facility for overhaul of engines and transmissions. Together, the tools aided the startup effort by decreasing the time necessary to acquire manufacturing information system requirements, lowering the costs of such an analysis, and improving consensus among the various cross-functional teams responsible for the analysis, design and startup of the facility.
Numerical modeling and validation of squeezed-film damping in vacuum-packaged industrial MEMS (2017)

Several high-performance, industrial micro-electromechanical (MEM) devices, such as gyroscopes, magnetometers, high-Q resonators and piezoelectric energy harvesters, require wafer bonding and packaging under near-vacuum conditions. One very challenging aspect of the design, verification and characterisation of these devices is to predict their performance characteristics in the presence of any residual gases post-packaging. Such gases contribute to the energy losses resulting from device surfaces squeezing or sliding against the gas films within the device cavities. In this paper, we fully expose the modelling assumptions used in commercial FEM tools to estimate the squeezed-film damping (SFD) experienced by MEM devices that are packaged under near-vacuum conditions. We also explain the various meshing options to enable the extraction of the most accurate Q factors under existing SFD assumptions. In addition, we compare the computational results across a variety of commercial FEM codes against measurements obtained under realistic vacuum conditions for an industrial high-Q magnetometer. These measurements suggest that existing computational models may deviate by as much as 25% on Q factor values for gas flow regimes under operating cavity pressures of less than 1 Torr.
Experimental dependence of resonant tunnel diode current on accumulation layer band profiles (1989)

Accurate predictive modeling and control of the negative differential conductance region of resonant tunnel diodes are important for their use in microwave circuit applications. Present ballistic transport models give much smaller currents in the negative differential conductance region than are measured for GaAs/AlAs devices. While an accumulation of charge in the cathode spacer just outside the barrier is necessary to produce a voltage drop across the structure, these models neglect the themialization of charge into this layer and its contribution to the current. We demonstrate the dependence of resonant tunnel diode characteristics on spacer accumulation layer band profiles by comparing a control sample with a sample which has an InGaAs "prewell" in the cathode spacer layer. The prewell sample has a relative valley or excess current that is reduced by 38 percent, on average, compared to the control sample.
Client and network-based dual stack mobility management (2012)

The Internet is evolving to accommodate users' demands, including mobility (users are mobile) and ubiquitous connectivity (billions of devices demand IP connectivity). The former has caused the design of IP mobility protocols aimed at enabling terminals to seamlessly roam among heterogeneous access networks, while the latter has speeded up the depletion of the IPv4 addressing space, triggering the design of a new version of IP (IPv6) and the development of transition mechanisms to enable the coexistence of IPv4- and IPv6-based networks. During the transition period, which is expected to last years, dual stack IPv4 and IPv6 mobile nodes will roam across IPv4-and-IPv6, IPv6-only and IPv4-only networks. This article presents a comprehensive tutorial of the mechanisms that have been standardized recently to support dual stack IP mobility management.
A novel ataxia-telangiectasia mutated autoregulatory feedback mechanism in murine embryonic stem cells (2009)

Ataxia-telangiectasia mutated (ATM) is known to play a central role in effecting the DNA damage response that protects somatic cells from potentially harmful mutations, and in this role it is a key anti-cancer agent. However, it also promotes repair of therapeutic damage (e.g. radiotherapy) and so frustrates the efficacy of some treatments. A better understanding of the mechanisms of ATM regulation is therefore important both in prevention and treatment of disease. While progress has been made in elucidating the key signal transduction pathways that mediate damage response in somatic cells, relatively little is known about whether these function similarly in pluripotent embryonic stem (ES) cells where ATM is also implicated in our understanding of adult stem cell ageing and in improvements in regenerative medicine. There is some evidence that different mechanisms may operate in ES cells and that our understanding of the mechanisms of ATM regulation is therefore incomplete. We investigated the behaviour of the damage response signalling pathway in mouse ES cells. We subjected the cells to the DNA-damaging agent doxorubicin, a drug that induces double-strand breaks, and measured ATM expression levels. We found that basal ATM gene expression was unaffected by doxorubicin treatment. However, following ATM kinase inhibition using a specific ATM inhibitor, we observed a significant increase in ATM and ataxia-telangiectasia and Rad3 related transcription. We demonstrate the use of a dynamical modelling approach to show that these results cannot be explained in terms of known mechanisms. Furthermore, we show that the modelling approach can be used to identify a novel feedback process that may underlie the anomalies in the data. The predictions of the model are consistent both with our in vitro experiments and with in vivo studies of ATM expression in somatic cells in mice, and we hypothesize that this feedback operates in both somatic and ES cells in vivo. The results point to a possible new target for ATM inhibition that overcomes the restorative potential of the proposed feedback.
Organolanthanide-catalyzed hydroboration of olefins (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganolanthanide-catalyzed hydroboration of olefinsKarl N. Harrison and Tobin J. MarksCite this: J. Am. Chem. Soc. 1992, 114, 23, 9220–9221Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/ja00049a083https://doi.org/10.1021/ja00049a083research-articleACS PublicationsRequest reuse permissionsArticle Views1387Altmetric-Citations174LEARN 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
Media architecture (1998)

In this paper we report a framework that makes it possible for a designer to rapidly explore the application-specific programmable processor design space under area constraints. The framework uses a production-quality compiler and simulation tools to synthesize a high performance machine for an application. Using the framework we evaluate the validity of the fundamental assumption behind the development of application-specific programmable processors. Application-specific processors are based on the idea that applications differ from each other in key architectural parameters, such as the available instruction-level parallelism, demand on various hardware components (e.g. cache memory units, register files) and the need for different number of functional units. We found that the framework introduced in this paper can be valuable in making early design decisions such as area and architectural trade-off, cache and instruction issue width trade-off under area constraint, and the number of branch units and issue width.
In vivo selection of tumor-specific antibodies (2013)

One of the most promising strategies for the development of effective cancer therapies relies on the targeted delivery of antibody-based therapeutics.Effective tumor targeting with antibodies depends on the identification of new targets, and the optimization of antibody structure [1,2]; however, the discovery and validation of novel tumor-associated antigens remains challenging [1].Indeed, the FDA-approved antibodies for cancer indications are directed against a limited number of targets.Often, novel antibodies are raised against well-known antigens, trying to surpass pre-existing ones in favorable properties.This approach can be helpful; for example, the upcoming obinutuzumab seems to outperform the blockbuster rituximab [3], but it doesn't necessarily imply an advance in our understanding of the disease.In contrast, using a functional approach, it is possible to select monoclonal antibodies with a defined biological effect that can lead to the identification of new or less well studied proteins potentially involved in the pathogeny of diseases [4].This strategy has greater potential for innovation and can be used to address the unmet need in oncology of discovering systemically accessible antigens preferentially overexpressed in the tumor microenvironment.We have recently used a functional approach to identify antibodies able to deliver a payload to the primary tumor in a xenograft mouse model [5].Using a highly diverse (~3 × 10 9 ) combinatorial library of single domain antibodies ensures the presence of antibodies against any potentially relevant target.We performed the selection in vivo -letting the antibody library circulate in the mouse-and selected only those antibodies that met the defined biological effect, without previous knowledge of the target.This unbiased approach can yield new antigens, discriminates against antibodies with unexpected off-target effects; and emphasizes the availability of the epitope in vivo.This latter aspect is sometimes overlooked when selecting antibodies for therapy, as antibodies selected using functional screens in vitro can fail in the clinic because of the in vivo environment is different.One of the antibodies selected with our new strategy recognizes the proteasome activator complex PA28.We found that the expression of the α subunit of PA28 is elevated in primary and metastatic human prostate cancer and used anti-PA28α antibodies to show that PA28 is accessible in mouse xenograft tumors.These results support the use of PA28 as a tumor marker, and potentially, as a target for therapeutic intervention in prostate cancer.We have focused on antibody discovery in tumor-bearing mice; however, this procedure is applicable to any disease for which an animal model exists (be it cancer, neurodegenerative diseases, etc.).Furthermore, the phage display technology can be used to study not only antibodies, but also to investigate any other extracellular protein-protein interactions [6,7] in vivo, and to map such interaction in the organism where they occur.
Predictors and Sequelae of Distal Embolization During Saphenous Vein Graft Intervention From the CAVEAT-II Trial (1995)

In this first prospective multicenter trial of saphenous vein graft intervention, distal embolization was more common after DCA than PTCA and in lesions containing thrombus. It also was associated with worse in-hospital and 12-month outcomes. The risk and sequelae of distal embolization should be considered when choosing a treatment strategy for vein graft disease.
Comparison of the Effect of Standard and Novel Immunosuppressive Drugs on CMV-Specific T-Cell Cytokine Profiling (2012)

Immunosuppression-specific and dose-dependent reductions in CMV-specific cytokine release were observed with significant differences in Th1 versus Th2 profiles and in relative potency of the drugs.
Development of two real-time polymerase chain reaction assays to detect Actinobacillus pleuropneumoniae serovars 1-9-11 and serovar 2 (2014)

Two real-time, or quantitative, polymerase chain reaction (qPCR) assays were developed to detect Actinobacillus pleuropneumoniae serovars 1-9-11 (highly related serovars with similar virulence potential) and serovar 2, respectively. The specificity of these assays was verified on a collection of 294 strains, which included all 16 reference A. pleuropneumoniae strains (including serovars 5a and 5b), 263 A. pleuropneumoniae field strains isolated between 1992 and 2009 in different countries, and 15 bacterial strains other than A. pleuropneumoniae. The detection levels of both qPCR tests were evaluated using 10-fold dilutions of chromosomal DNA from reference strains of A. pleuropneumoniae serovars 1 and 2, and the detection limit for both assays was 50 fg per assay. The analytical sensitivities of the qPCR tests were also estimated by using pure cultures and tonsils experimentally spiked with A. pleuropneumoniae. The detection threshold was 2.5 × 10(4) colony forming units (CFU)/ml and 2.9 × 10(5) CFU/0.1 g of tonsil, respectively, for both assays. These specific and sensitive tests can be used for the serotyping of A. pleuropneumoniae in diagnostic laboratories to control porcine pleuropneumonia.
ChemInform Abstract: Measurement of the Absolute Rate of 1,2‐Hydrogen Migration in Benzylchlorocarbene (1989)

Abstract (II).