gebhart/patrepeval huggingface dataset:
Fragment-Based Discovery of Bromodomain Inhibitors Part 1: Inhibitor Binding Modes and Implications for Lead Discovery (2011)

Bromodomain-containing proteins are key epigenetic regulators of gene transcription and readers of the histone code. However, the therapeutic benefits of modulating this target class are largely unexplored due to the lack of suitable chemical probes. This article describes the generation of lead molecules for the BET bromodomains through screening a fragment set chosen using structural insights and computational approaches. Analysis of 40 BRD2/fragment X-ray complexes highlights both shared and disparate interaction features that may be exploited for affinity and selectivity. Six representative crystal structures are then exemplified in detail. Two of the fragments are completely new bromodomain chemotypes, and three have never before been crystallized in a bromodomain, so our results significantly extend the limited public knowledge-base of crystallographic small molecule/bromodomain interactions. Certain fragments (including paracetamol) bind in a consistent mode to different bromodomains such as CREBBP, suggesting their potential to act as generic bromodomain templates. An important implication is that the bromodomains are not only a phylogenetic family but also a system in which chemical and structural knowledge of one bromodomain gives insights transferrable to others.
Advances in Computer-Generated Imagery for Flight Simulation (1985)

The world of aviation flight simulation is an old one as computer graphics applications go. How did it progress to its current state, and where is it going next?
Spared bone mass in rats treated with thyroid hormone receptor TRβ-selective compound GC-1 (2003)

Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. To investigate the role of thyroid hormone receptor-beta (TR beta) in mediating the osteopenic effects of triiodothyronine (T3), female adult rats were treated daily (64 days) with GC-1 (1.5 microg/100 g body wt), a TR beta-selective thyromimetic compound. Bone mass was studied by dual-energy X-ray absorptiometry of several skeletal sites and histomorphometry of distal femur, and the results were compared with T3-treated (3 microg/100 g body wt) or control animals. As expected, treatment with T3 significantly reduced bone mineral density (BMD) in the lumbar vertebrae (L2-L5), femur, and tibia by 10-15%. In contrast, GC-1 treatment did not affect the BMD in any of the skeletal sites studied. The efficacy of GC-1 treatment was verified by a reduction in serum TSH (-52% vs. control, P < 0.05) and cholesterol (-21% vs. control, P < 0.05). The histomorphometric analysis of the distal femur indicated that T3 but not GC-1 treatment reduced the trabecular volume, thickness, and number. We conclude that chronic, selective activation of the TR beta isoform does not result in bone loss typical of T3-induced thyrotoxicosis, suggesting that the TR beta isoform is not critical in this process. In addition, our findings suggest that the development of TR-selective T3 analogs that spare bone mass represents a significant improvement toward long-term TSH-suppressive therapy.
Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis (2007)

Beta-blockers appear to effectively prevent occurrence of AF in patients with systolic HF.
Activated Microglia Initiate Motor Neuron Injury by a Nitric Oxide and Glutamate-Mediated Mechanism (2004)

Recent studies suggest that motor neuron (MN) death may be non-cell autonomous, with cell injury mediated by interactions involving non-neuronal cells, such as microglia and astrocytes. To help define these interactions, we used primary MN cultures to investigate the effects of microglia activated by lipopolysaccharide or IgG immune complexes from patients with amyotrophic lateral sclerosis. Following activation, microglia induced MN injury, which was prevented by a microglial iNOS inhibitor as well as by catalase or glutathione. Glutamate was also required since inhibition of the MN AMPA/kainate receptor by CNQX prevented the toxic effects of activated microglia. Peroxynitrite and glutamate were synergistic in producing MN injury. Their toxic effects were also blocked by CNQX and prevented by calcium removal from the media. The addition of astrocytes to cocultures of MN and activated microglia prevented MN injury by removing glutamate from the media. The protective effects could be reversed by inhibiting astrocytic glutamate transport with dihydrokainic acid or pretreating astrocytes with H2O2. Astrocytic glutamate uptake was also decreased by activated microglia or by added peroxynitrite. These data suggest that free radicals released from activated microglia may initiate MN injury by increasing the susceptibility of the MN AMPA/kainate receptor to the toxic effects of glutamate.
A channel-erasing 1.8-V-only 32-Mb NOR flash EEPROM with a bitline direct sensing scheme (2000)

A 1.8-V-only 32-Mb NOR flash EEPROM has been developed based on the 0.25-/spl mu/m triple-well double-metal CMOS process. A channel-erasing scheme has been implemented to realize a cell size of 0.49 /spl mu/m/sup 2/, the smallest yet reported for 0.25-/spl mu/m CMOS technology. A block decoder circuit with a novel erase-reset sequence has been designed for the channel-erasing operation. A bitline direct sensing scheme and a wordline boosted voltage pooling method have been developed to obtain high-speed reading operation at low voltage. An access time of 90 ns at 1.8 V has been realized.
Abstracts.12 th lnternational Symposium Chemistry and Biology of Pteridines and Folates (2001)

DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.
Differential regulation of IgG1 and IgE synthesis by interleukin 4. (1988)

IL-4/B cell stimulatory factor-1 is a T cell-derived lymphokine that has been shown to enhance IgG1 and IgE and to suppress IgG3 and IgG2b secretion by B cells stimulated with bacterial LPS. We show here that the stimulation of IgG1 and IgE secretion in response to rIL-4 is differentially regulated. The dose-response curve for IgG1 production is bimodal with peaks at 100 and 10,000 U/ml. IgE production is modest at 100 U/ml and exhibits a progressive enhancement as the IL-4 concentration is increased to 10,000 U/ml, reaching approximately 1 microgram of IgE from an initial cell number of 2 X 10(4). Both of these effects are reversed by monoclonal anti-IL-4 antibody. Neither the enhancing nor suppressing effects of IL-4 can be explained by changes in viable cell yields or [3H]thymidine incorporation. The production of both IgG1 and IgE is controlled by IL-4 in a two-phase manner. During the initial 2 d of culture with LPS, IL-4 action for both IgG1 and IgE production is relatively concentration independent at doses greater than 600 U/ml. This 2-d treatment leads to maximal IgG1 production at day 6 with no further addition of IL-4. Addition of IL-4 during the final 4 d of culture has no effect at concentrations under 100 U/ml. At higher concentrations, IL-4 is strikingly suppressive for IgG1 production. By contrast, little IgE is produced unless IL-4 is present after 2 d of culture and the response is directly dependent on the concentration of IL-4 during this second phase of culture with maximal responses observed at 10,000 U/ml. These differences in IL-4 requirements for IgG1 and IgE production, respectively, may have an important role in the regulation of the synthesis of these isotypes in responses to microbial antigens.
Adherence of Ureaplasma urealyticum to human epithelial cells (1994)

Adherence of Ureaplasma urealyticum cells to eukaryotic cell monolayers was quantified using the Bertholet assay to monitor ammonia produced from urea by ureaplasma urease. Adherence was abolished by pre-treatment of ureaplasmas with HeLa cell extracts and inhibited to varying degrees by pretreatment of the ureaplasmas with N-acetylneuraminic acid, specific antisera and monoclonal antibodies. The data suggest the presence of several ureaplasma adhesins, some of which are species- or serotype-specific and some of which are proteinaceous and antigenic. The serotype-8-specific 96 kDa surface-expressed antigen may be one adhesin. Pre-treatment of HeLa cell monolayers with neuraminidase significantly reduced ureaplasma adherence and, using a novel 'immunoblot adherence assay', ureaplasmas were shown to bind to a number of HeLa cell components, three of which appear to terminate in sialic acid.
Repression of a herpes simplex virus immediate-early promoter by the Oct-2 transcription factor is dependent on an inhibitory region at the N terminus of the protein. (1994)

The B-cell form of the Oct-2 transcription factor Oct 2.1 can activate the herpes simplex virus immediate-early gene 3 (IE3) promoter, whereas the neuronally expressed Oct 2.4 and 2.5 forms of the protein, which contain a different C terminus, can repress this promoter. Here we show that partial or full deletion of the C terminus of Oct 2.1 in the presence of an intact N terminus results in a protein which can strongly repress the IE3 promoter. In contrast, deletion of the entire N terminus or a short region within it leaving the C terminus intact results in a very strong activator. Deletion of both N and C termini leaving only the isolated POU domain generates only a very weak repressor. The N-terminal region defined in this way can repress a heterologous promoter when linked to the DNA-binding domain of the GAL4 factor, indicating that it can function as an independent inhibitory domain. These results indicate that a specific region within the N terminus common to Oct 2.1, 2.4, and 2.5 plays a critical role in the ability of neuronally expressed forms of Oct-2 to repress the IE3 promoter but can do so only when the C-terminal region of Oct 2.1 is altered or deleted.
Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes (2004)

Prostate cancer is currently the most commonly diagnosed noncutaneous malignancy in American men. When metastatic, usually to the bone, the disease is no longer curable and is usually treated palliatively with androgen ablation. However, after conversion to androgen-independent disease, there is no effective therapy currently available. The “T body” approach, which uses genetically reprogrammed lymphocytes derived from the patient and expressing chimeric receptor genes, combines the effector functions of T lymphocytes and NK cells with the ability of antibodies to recognize predefined surface antigens with high specificity and in a non–MHC-restricted manner. We show here the therapeutic efficacy of human lymphocytes bearing erbB2-specific chimeric receptors on human prostate cancer BM lesions in a SCID mouse model after conditioning of the recipient to allow homing and persistent functioning of the adoptively transferred cells. Induction of stromal cell–derived factor-1 production within the BM using low-dose irradiation or cyclophosphamide combined with IL-2 administration enhanced the homing of systemically delivered T bodies, resulting in decreased tumor growth and prostate-specific antigen secretion, prolongation of survival, and even cure of the treated mice. These preclinical studies strongly support the idea that the T body approach has therapeutic potential in disseminated prostate cancer.
Usefulness of Plasma Vascular Endothelial Growth Factor in the Diagnosis of Pancreatic Carcinoma (2005)

p-VEGF proved useful in differentiating between PC and CP, and in patients with PC, a high level of p-VEGF may be a predictor of distant metastases and poor prognosis.
The HBV Drug Entecavir — Effects on HIV-1 Replication and Resistance (2007)

Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log(10) decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1-resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.
Smirk Wipes Golden Smiles with Pessimistic Predictions (2009)

Justin Smirk, Westpac senior economist has said that anyone looking for a long-term investment would do good to steer clear of gold. Gold will continue to remain bullish and does have a very good future, however, in terms of a good investment, other commodities are probably going to outperform it.
Residential Customer Response to Real-time Pricing: The Anaheim Critical Peak Pricing Experiment (2007)

This paper analyzes the results of a critical peak pricing (CPP) experiment involving 123 residential customers of the City of Anaheim Public Utilities (APU) over the period June 1, 2005 to October 14, 2005. Using a nonparametric condition mean estimation framework that allows for customer-specific fixed effects and day-of-sample fixed effects, I find that customers in the treatment group consumed an average of 12 percent less electricity during the peak hours of the day on CPP days than customers in the control group. There is also evidence that this reduction in consumption for customers in the treatment group relative to customers in the control group is larger on higher temperature CPP days. The impact of CPP events is confined to the peak periods of CPP days. Mean electricity consumption by customers in the treatment group is not significantly different from that of customers in the control group during the peak or off-peak periods of the day before or day after a CPP event. Much of the estimated consumption reduction of treatment consumers relative to control group consumers during peak periods of CPP days is due to reductions from a higher level of consumption by treatment group customers in non-CPP days. The consumption reductions paid rebates during CPP days are almost 7 times the reduction in consumption due to CPP events predicted by the treatment effects estimate, which provides strong evidence of an overly generous method for setting the reference level for peak period consumption relative to which customers are issued refunds during CPP days. The paper closes with a discussion of the challenges associated with implementing a CPP rate with a rebate mechanism as the default rate for residential customers.
Use of [3H]tetrahydrocerulenin to assay condensing enzyme activity in Streptomyces erythreus (1984)

Conference Article| August 01 1984 Use of [3H]tetrahydrocerulenin to assay condensing enzyme activity in Streptomyces erythreus GRAHAM ROBERTS; GRAHAM ROBERTS 1Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar PETER F. LEADLAY PETER F. LEADLAY 1Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1984) 12 (4): 642–643. https://doi.org/10.1042/bst0120642 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation GRAHAM ROBERTS, PETER F. LEADLAY; Use of [3H]tetrahydrocerulenin to assay condensing enzyme activity in Streptomyces erythreus. Biochem Soc Trans 1 August 1984; 12 (4): 642–643. doi: https://doi.org/10.1042/bst0120642 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: ACP, acyl carrier protein This content is only available as a PDF. © 1984 Biochemical Society1984 Article PDF first page preview Close Modal You do not currently have access to this content.
Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis (2020)

PROSPERO CRD42020179452.
Adsorption of alkanenitriles and alkanedinitriles on gold and copper (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdsorption of alkanenitriles and alkanedinitriles on gold and copperUlrich B. Steiner, Walter R. Caseri, and Ulrich W. SuterCite this: Langmuir 1992, 8, 11, 2771–2777Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/la00047a031https://doi.org/10.1021/la00047a031research-articleACS PublicationsRequest reuse permissionsArticle Views392Altmetric-Citations31LEARN 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
Atomically Resolved Single-Walled Carbon Nanotube Intramolecular Junctions (2001)

Intramolecular junctions in single-walled carbon nanotubes are potentially ideal structures for building robust, molecular-scale electronics but have only been studied theoretically at the atomic level. Scanning tunneling microscopy was used to determine the atomic structure and electronic properties of such junctions in single-walled nanotube samples. Metal-semiconductor junctions are found to exhibit an electronically sharp interface without localized junction states, whereas a more diffuse interface and low-energy states are found in metal-metal junctions. Tight-binding calculations for models based on observed atomic structures show good agreement with spectroscopy and provide insight into the topological defects forming intramolecular junctions. These studies have important implications for applications of present materials and provide a means for assessing efforts designed to tailor intramolecular junctions for nanoelectronics.
GoQBot: a caterpillar-inspired soft-bodied rolling robot (2011)

Rolling locomotion using an external force such as gravity has evolved many times. However, some caterpillars can curl into a wheel and generate their own rolling momentum as part of an escape repertoire. This change in body conformation occurs well within 100 ms and generates a linear velocity over 0.2 m s(-1), making it one of the fastest self-propelled wheeling behaviors in nature. Inspired by this behavior, we construct a soft-bodied robot to explore the dynamics and control issues of ballistic rolling. This robot, called GoQBot, closely mimics caterpillar rolling. Analyzing the whole body kinematics and 2D ground reaction forces at the robot ground anchor reveals about 1G of acceleration and more than 200 rpm of angular velocity. As a novel rolling robot, GoQBot demonstrates how morphing can produce new modes of locomotion. Furthermore, mechanical coupling of the actuators improves body coordination without sensory feedback. Such coupling is intrinsic to soft-bodied animals because there are no joints to isolate muscle-generated movements. Finally, GoQBot provides an estimate of the mechanical power for caterpillar rolling that is comparable to that of a locust jump. How caterpillar musculature produces such power in such a short time is yet to be discovered.
An artificial fingerprint device (AFD): a study of identification number applications utilizing characteristics variation of polycrystalline silicon TFTs (2003)

An idea for obtaining unique identification (ID) numbers using polycrystalline silicon (poly-Si) thin-film transistors (TFTs) with a logic LSI compatible process is proposed. Like an actual human fingerprint, the characteristic variations of poly-Si TFTs are utilized for ID numbers in LSIs. The variation of poly-Si TFT characteristics is random, and this method offers unique, nonalterable, and nonduplicable numbers without any special processes, unlike other methods such as flash memory and mask ROM. These characteristics are highly suitable for ID number applications. The device physics of poly-Si TFTs for realizing the stable recognition of ID numbers was studied and a recognition circuit is proposed. The design guidelines for the grain size of poly-Si and AFD applications are also discussed.
Single-Engine Firefighting Air Tanker Human Factors (2009)

This paper describes the unique environment and safety challenges for pilots who fly singleengine air tanker (SEAT) firefighting aircraft, and the highlights from a human factors (HF) analysis of SEAT operations conducted in 2009. The HF analysis used the FAA’s Human Factors Analysis and Classification System (HFACS) because of its broad examination of HF issues and prior use in aviation. We examined operations, training, and the applicable safety reports, and we interviewed or received anonymous surveys from 71 stakeholders – pilots, supervisors, and managers. The analysis yielded 63 recommendations, many of which were adopted for the 2010 fire season. Despite a busier fire season in 2010 compared with 2009, SEAT safety improved. The Bureau of Land Management (BLM) attributes this improvement, in part, to the adopted recommendations.
The HSP90 Inhibitor Ganetespib Synergizes with the MET Kinase Inhibitor Crizotinib in both Crizotinib-Sensitive and -Resistant MET-Driven Tumor Models (2013)

The proto-oncogene MET is aberrantly activated via overexpression or mutation in numerous cancers, making it a prime anticancer molecular target. However, the clinical success of MET-directed tyrosine kinase inhibitors (TKI) has been limited due, in part, to mutations in the MET kinase domain that confer therapeutic resistance. Circumventing this problem remains a key challenge to improving durable responses in patients receiving MET-targeted therapy. MET is an HSP90-dependent kinase, and in this report we show that HSP90 preferentially interacts with and stabilizes activated MET, regardless of whether the activation is ligand-dependent or is a consequence of kinase domain mutation. In contrast, many MET-TKI show a preference for the inactive form of the kinase, and activating mutations in MET can confer resistance. Combining the HSP90 inhibitor ganetespib with the MET-TKI crizotinib achieves synergistic inhibition of MET, its downstream signaling pathways, and tumor growth in both TKI-sensitive and -resistant MET-driven tumor models. These data suggest that inclusion of an HSP90 inhibitor can partially restore TKI sensitivity to previously resistant MET mutants, and they provide the foundation for clinical evaluation of this therapeutic combination in patients with MET-driven cancers.