gebhart/patrepeval huggingface dataset:
Design and Synthesis of 2-Naphthoate Esters as Selective Dopamine D<sub>4</sub>Antagonists (1996)

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTDesign and Synthesis of 2-Naphthoate Esters as Selective Dopamine D4 AntagonistsIzzy Boyfield, Thomas H. Brown, Martyn C. Coldwell, David G. Cooper, Michael S. Hadley, Jim J. Hagan, Maureen A. Healy, Amanda Johns, Ron J. King, Derek N. Middlemiss, David J. Nash, Graham J. Riley, Emma E. Scott, Stephen A. Smith, and Geoffrey StempView Author Information SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, U.K. Cite this: J. Med. Chem. 1996, 39, 10, 1946–1948Publication Date (Web):May 10, 1996Publication History Received5 January 1996Published online10 May 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm960017lhttps://doi.org/10.1021/jm960017lrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views335Altmetric-Citations42LEARN 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 (1)»Supporting Information Supporting Information SUBJECTS:Amides,Ketones,Organic compounds,Receptors,Selectivity Get e-Alerts
Microtubule‐associated Protein 1B Light Chain (MAP1B‐LC1) negatively regulates the activity of tumor suppressor p53 in neuroblastoma cells (2008)

The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses and can trigger apoptosis in many cell types, including neurons. In this study, we have shown that the Microtubule-Associated Protein 1B (MAP1B) light chain can interact with the tumor suppressor p53. We also demonstrate that both p53 and the MAP1B light chain (MAP1B-LC1) alter their localization from the cytoplasm to the nucleus when neuroblastoma cells, SH-SY5Y, are treated with doxorubicin. Additionally, we demonstrate that the MAP1B-LC1 negatively regulates p53-dependent transcriptional activity of a reporter construct driven by the p21 promoter. Consequently, MAP1B-LC1 binds to p53 and this interaction leads to the inhibition of doxorubicin-induced apoptosis in SH-SY5Y cells.
Continuous-membrane surface-micromachined silicon deformable mirror (1997)

The authors describe the development of a new type of micromachined device designed for use in correcting optical aberrations. A nine-element continuous deformable mirror was fabricated using surface micromachining. The electromechanical behavior of the deformable mirror was measured. A finite-difference model for predicting the mirror deflections was developed. In addition, novel fabrication techniques were developed to permit the production of nearly planar mirror surfaces.
[Effects of signal transducers and activators of transcription 4 and 6 on development of worms and granuloma formation in mice infected with Schistosoma japonicum]. (2011)

STAT4 or STAT6 deficiency has no conspicuous effect on the development and fecundity of S. japonicum. STAT6 plays an important role for the granuloma formation and liver fibrosis.
ATP/GTP Hydrolysis Is Required for Oxazole and Thiazole Biosynthesis in the Peptide Antibiotic Microcin B17 (1998)

In the maturation of the Escherichia coli antibiotic Microcin B17, the product of the mcbA gene is modified posttranslationally by the multimeric Microcin synthetase complex (composed of McbB, C, and D) to cyclize four Cys and four Ser residues to four thiazoles and four oxazoles, respectively. The purified synthetase shows an absolute requirement for ATP or GTP in peptide substrate heterocyclization, with GTP one-third as effective as ATP in initial rate studies. The ATPase/GTPase activity of the synthetase complex is conditional in that ADP or GDP formation requires the presence of substrate; noncyclizable versions of McbA bind to synthetase, but do not induce the NTPase activity. The stoichiometry of ATP hydrolysis and heterocycle formation is 5:1 for a substrate that contains two potential sites of modification. However, at high substrate concentrations (>50Km) heterocycle formation is inhibited, while ATPase activity occurs undiminished, consistent with uncoupling of NTP hydrolysis and heterocycle formation at high substrate concentrations. Sequence homology reveals that the McbD subunit has motifs reminiscent of the Walker B box in ATP utilizing enzymes and of motifs found in small G protein GTPases. Mutagenesis of three aspartates to alanine in these motifs (D132, D147, and D199) reduced Microcin B17 production in vivo and heterocycle formation in vitro, suggesting that the 45 kDa McbD has a regulated ATPase/GTPase domain in its N-terminal region necessary for peptide heterocyclization.
High-efficiency thin-film AlGaAs-GaAs double heterostructure solar cells (1988)

AlGaAs-GaAs double-heterostructure solar cells were fabricated in 10 mu m-thick films and exhibited one-sun, total-area conversion efficiencies up to 19.5% AM0, and 22.4% AM1.5. The cell structure consisted on an n-doped GaAs emitter and p-doped GaAs base interposed between AlGaAs layers. The cell structure was deposited by organometallic vapor-phase epitaxy on a GaAs CLEFT substrate, and later mechanically separated from the substrate during cell fabrication. A single-layer antireflection coating was used without a coverglass. The cells, fabricated on 2 in diameter wafers, had areas of either 1 or 4 cm/sup 2/. Reuse of the substrate was successfully demonstrated. For comparison, cells fabricated with a conventional process from double heterostructures deposited on bulk GaAs substrates exhibited one-sun AM1.5 efficiencies as high as 23.7%. The impact of these high efficiencies on space and terrestrial applications is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Preparation and properties of superconducting Y(<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">Ba</mml:mi></mml:mrow><mml:mrow><mml:mn>1</mml:mn><mml:mi mathvariant="normal">−</mml:mi><mml:mi mathvariant="italic">x</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">Sr</mml:mi></mml:mrow><mml:mrow><mml:mi mathvariant="italic">x</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mo>)</mml:mo></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">Cu</mml:mi></mml:mrow><mml:mrow><mml:mn>4</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">O</mml:mi></mml:mrow><mml:mrow><mml:mn>8</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math> (1990)

We have prepared single-phase or near-single-phase Y(${\mathrm{Ba}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${)}_{2}$${\mathrm{Cu}}_{4}$${\mathrm{O}}_{8}$ (0\ensuremath{\le}x\ensuremath{\le}0.4) samples by means of a high-oxygen-pressure technique using an ${\mathrm{O}}_{2}$ hot isostatic pressing. All the lattice constants, a, b, and c, of Y(${\mathrm{Ba}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${)}_{2}$${\mathrm{Cu}}_{4}$${\mathrm{O}}_{8}$ monotonically decreased with increasing Sr content. The superconducting transition temperatures of these samples were nearly constant, being around 80 K, while the ${\mathit{T}}_{\mathit{c}}$'s of Y(${\mathrm{Ba}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${)}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{\mathit{z}}$ (z\ensuremath{\sim}7) samples decreased with increasing Sr content. When Y in Y(${\mathrm{Ba}}_{0.8}$${\mathrm{Sr}}_{0.2}$${)}_{2}$${\mathrm{Cu}}_{4}$${\mathrm{O}}_{8}$ was partially substituted by Ca, the superconducting critical temperature increased to near 90 K.
A Small, Fast and Low-Power Register File by Bit-Partitioning (2005)

A large multi-ported register file is indispensable for exploiting instruction level parallelism (ILP) in today's dynamically scheduled superscalar processors. The number of ports and the size of the register file must be enlarged as the issue width and instruction window size increase. However, a larger register file causes longer access delays and more power consumption. To tackle these problems, we propose bit-partitioned register file which reduces the area, access time, and energy consumption of the register file. The proposed method relies on the fact that many operands do not need the full-bit width (typically a 32-bit or 64-bit width) of a register entry. Because the effective bit-width of most register operands is narrower than the full-bit width of a register entry, the upper bits of the register entries assigned to such narrow-width operands are useless. Thus, we propose to use of these useless upper bits for other operands by partitioning the register entries. In this paper, we show the mechanism of the proposed register file and evaluate its performance and power consumption. The evaluation results reveal that the proposed register file achieves higher instruction per cycle (IPC) in a smaller physical area, and consequently with shorter access time and less power consumption.
Experience in critical path selection for deep sub-micron delay test and timing validation (2003)

Critical path selection is an indispensable step for AC delay test and timing validation. Traditionally, this step relies on the construction of a set of worse-case paths based upon discrete timing models. However, the assumption of discrete timing models can be invalidated by timing defects and process variation in the deep sub-micron domain, which are often continuous in nature. As a result, critical paths defined in a traditional timing analysis approach may not be truly critical in reality. In this paper, we propose using a statistical delay evaluation framework for estimating the quality of a path set. Based upon the new framework, we demonstrate how the traditional definition of a critical path set may deviate from the true critical path set in the deep sub-micron domain. To remedy the problem, we discuss improvements to the existing path selection strategies by including new objectives. We then compare statistical approaches with traditional approaches based upon experimental analysis of both defect-free and defect-injected cases.
High strain biocompatible polydimethylsiloxane-based conductive graphene and multiwalled carbon nanotube nanocomposite strain sensors (2013)

High performance strain sensors were achieved featuring simple, low-cost construction involving the screen printing of combinations of multi-walled carbon nanotube and graphene nano-platelet nanocomposites on biocompatible and flexible polymer substrates. Conductivity and thermal coefficients of resistance of different conductive nanocomposite sensor materials were measured. The zero current resistance and gauge factor of printed sensors was characterized. The combination of high strain operation (up to 40%), high gauge factor (GF &amp;gt; 100), and biocompatible construction pave the way for applications such as minimally invasive in vivo strain measurements.
The molecular mechanism of osteoclastogenesis in rheumatoid arthritis. (2002)

Bone-resorbing osteoclasts are formed from hemopoietic cells of the monocyte-macrophage lineage under the control of bone-forming osteoblasts. We have cloned an osteoblast-derived factor essential for osteoclastogenesis, the receptor activator of NF-kappaB ligand (RANKL). Synovial fibroblasts and activated T lymphocytes from patients with rheumatoid arthritis also express RANKL, which appears to trigger bone destruction in rheumatoid arthritis as well. Recent studies have shown that T lymphocytes produce cytokines other than RANKL such as IL-17, granulocyte-macrophage colony-stimulating factor and IFN-gamma, which have powerful regulatory effects on osteoclastogenesis. The possible roles of RANKL and other cytokines produced by T lymphocytes in bone destruction are described.
Regulated Human Erythropoietin Receptor Expression in Mouse Brain (1997)

Erythropoietin (Epo) is known for its role in erythropoiesis and acts by binding to its receptor (EpoR) on the surface of erythroid progenitors. EpoR activity follows the site of hematopoiesis from the embryonic yolk sac to the fetal liver and then the adult spleen and bone marrow. Expression of EpoR has also been observed in selected cells of non-hematopoietic origin, such as the embryonic mouse brain during mid-gestation, at levels comparable to adult bone marrow. EpoR transcripts in brain decrease during development falling by birth to less than 1-3% of the level in hematopoietic tissue. We have now recapitulated this pattern of expression using a human EpoR transgene consisting of an 80-kb human EpoR genomic fragment. The highest level of expression was observed in the embryonic yolk sac and fetal liver, analogous to the endogenous gene, in addition to expression in adult spleen and bone marrow. Although activity of this transgene in brain is initially lower than the endogenous gene, it does exhibit the down-regulation observed for the endogenous gene in adult brain. The expression pattern of hybrid transgenes of an hEpoR promoter fused to beta-galactosidase in 9. 5-day embryos suggested that the hEpoR promoter region between -1778 and -150 bp 5' of the transcription start site is necessary to direct EpoR expression in the neural tube. EpoR expression in the neural tube may be the origin of the EpoR transcripts detected in brain during development. These data demonstrate that both the mouse and human EpoR genes contain regulatory elements to direct significant levels of expression in a developmentally controlled manner in brain and suggest that in addition to its function during erythropoiesis, EpoR may play a role in the development of selected non-hematopoietic tissue.
Processing of the phosphorylated recognition marker in lysosomal enzymes. Characterization and partial purification of a microsomal alpha-N-acetylglucosaminyl phosphodiesterase. (1981)

N-Acetylglucosamine(1)phospho(6)mannose groups recently identified in lysosomal enzymes were proposed to be precursors of the recognition markers terminating with mannose 6-phosphate (Tabas, I., and Kornfeld, S. (1980) J. Biol. Chem. 225, 6633-6639; Hasilik, A., Klein, U., Waheed, A., Strecker, G., and von Figura, K. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 7074-7078). To study the presumptive enzyme removing N-acetylglucosamine from the diester, an assay was developed using a radioactive oligosaccharide containing diester groups of the above structure. An alpha-N-acetylglucosaminyl phosphodiesterase cleaving this substrate in vitro was found in human placenta and in rat liver. The enzyme was solubilized from the microsomal fraction of human placenta and more than 800-fold purified with 75% yield. It is distinct from the lysosomal alpha-N-acetylglucosaminidase by the criteria of immunological cross-reactivity, substrate specificity, and heat stability. The partially purified enzyme cleaves alpha-N-acetylglucosamine phosphodiester bonds in oligosaccharides from lysosomal enzymes, in lysosomal enzymes, and in UDP-N-acetylglucosamine. We propose that the microsomal alpha-N-acetylglucosaminyl phosphodiesterase is involved in the processing of the phosphorylated recognition marker in lysosomal enzymes.
Effect of Fatty Acid Conjugation on Antimicrobial Peptide Activity (2004)

Two peptides, YGAAKKAAKAA2 (AKK), and YGAKAKAAKA2 (KAK) were conjugated to fatty acids and tested for the effect on their structure, antibacterial activity, and eukaryotic cell toxicity. In the presence of bacteria-mimicking phospholipid vesicles fatty acid conjugates of the amphipathic peptide, AKK, show a larger change in helical structure than either of the unmodified peptides or the conjugate of the nonamphipathic peptide, KAK. The induction of helicity corresponds to a significant improvement in antimicrobial activity as measured by a minimum bactericidal concentration test. Lengthening the fatty acid conjugate improves the antimicrobial activity of AKK as long as the peptide has less than 16 carbons. Peptide AKK conjugated to fatty acids with more than 16 carbons show no antimicrobial activity. Investigation of peptide and peptide amphiphile structure in the presence of red blood cell-mimicking phospholipid vesicles shows that neither the peptides, nor the fatty acid conjugated peptides have any significant helical structure. Neither the peptides nor their lauric acid conjugates showed significant hemolytic activity.
Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells (2012)

Recent reports on direct reprogramming of cancer cells (iPCs) which results in reduced tumorigenic potential has attributed the importance of epigenetics in tumorigenesis, but lacked genome-wide analysis. Here we describe successful generation of iPCs from non-small cell lung cancer (NSCLC) cell lines. Following reprogramming, they resembled embryonic stem and induced pluripotent stem cells in pluripotency markers expression, gene expression patterns and in vitro differentiation ability. Genome-wide methylation analysis revealed that aberrantly methylated promoters which were mostly developmental-associated genes and tumor suppressors; as well as commonly upregulated genes in NSCLC i.e. KRT19 and S100P were reversed in iPCs upon reprogramming. Also, the reversal of oncogenes and tumor suppressors status were partially explainable by DNA methylation. These findings suggest that DNA methylation patterns explain the downstream transcriptional effects, which potentially caused the reduced tumorigenicity in iPCs, thus providing evidence that reprogramming reverses the aberrantly dysregulated genes in NSCLC both epigenetically and transcriptionally.
Optimization of Long Anisotropic Laminated Fiber Composite Panels with T-Shaped Stiffeners (2007)

A method to optimise long anisotropic laminated fibre composite panels with T-shape stiffeners is presented. The technique splits the optimisation problem into two steps. At the first step, composite optimisation is performed using Mathematical Programming (MP) where the skin and the stiffeners are characterised by lamination parameters accounting for their membrane and flexural anisotropy. Skin and stiffener laminates are assumed to be symmetric, or mid-plane symmetric laminates, with 0, 90, 45, or -45 degree ply angles. The stiffened panel consists of a series of skin-stiffener assemblies or super-stiffeners. Each super-stiffener is further idealised as a group of flat laminated plates that are rigidly connected. The stiffened panel is subjected to a combined loading under strength, buckling and practical design constraints. At the second step, the actual skin and stiffener lay-ups are obtained using a Genetic Algorithm (GA) and considering the ease of manufacture. This approach offers the advantage of introducing numerical analysis methods such as Finite Elements (FE) at the first step, without significant increases in processing time. Furthermore modelling the laminate anisotropy enables the designer to explore and potentially use elastic tailoring in a beneficial manner.
GC Points in a Threaded Environment (1998)

: Many garbage-collected systems, including most that involve a stop-the-world phase, restrict GC to socalled GC points. In single-threaded environments, GC points carry no overhead: when a GC must be done, the single thread is already at a GC point. In multi-threaded environments, however, only the thread that triggers the GC by failing an allocation will be at a GC point. Other threads must be rolled forward to their next GC point before the GC can take place. We compare, in the context of a high-performance Java^TM virtual machine, two approaches to advancing threads to a GC point, polling and code patching, while keeping all other factors constant. Code patching outperforms polling by an average of 4.7% and sometimes by as much as 11.2%, while costing only slightly more compiled code space. Put differently, since most programs spend less than 1/5 of the time in GC, a 4.7% bottom-line speedup amounts to more than a 20% reduction in the GC-related costs. Patching is, however, more di...
Effects of the diluent mixing ratio and conditions of the thermally induced phase‐separation process on the pore size of microporous polyethylene membranes (2008)

Abstract Microporous polyethylene (PE) membranes having a controlled pore size were produced via the thermally induced phase separation process by manipulation of the phase boundary of the PE/diluent blend and process conditions. The phase boundary of the PE blend, caused by upper critical solution temperature type phase behavior, was controlled by the use of a diluent mixture, that is, an isoparaffin/soybean oil mixture. The phase‐separation temperature of the PE/soybean oil blend was always higher than that of the PE/isoparaffin blend. In PE/(isoparaffin/soybean oil) ternary blends, the phase‐separation temperature of the ternary blend rapidly increased with increasing soybean oil content in the diluent mixture. Furthermore, the phase‐separation temperatures of ternary blends were always higher than that of the PE/soybean oil blend, regardless of the blend compositions, when the diluent mixture contained more than 50 wt % soybean oil. The observed phase behavior of the ternary blends was analyzed with interaction energy densities calculated with the Flory–Huggins theory and ternary stability conditions. The growth of droplets caused by both coalescence and the Oswald ripening process was observed after the onset of phase separation. As the blends became less stable, the droplet growth rate increased, and larger equilibrium droplets were formed. Microporous membranes with the desired pore structure could be prepared by control of the phase boundary and the variation of processing conditions such as the quenching depth, annealing time, and cooling rate. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008