gebhart/patrepeval huggingface dataset:
Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy (2001)

Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. The hypertrophic process is mediated, in part, by small G proteins of the Rho family. We hypothesized that statins, inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, inhibit cardiac hypertrophy by blocking Rho isoprenylation. We treated neonatal rat cardiac myocytes with angiotensin II (AngII) with and without simvastatin (Sim) and found that Sim decreased AngII-induced protein content, [3H] leucine uptake, and atrial natriuretic factor (ANF) promoter activity. These effects were associated with decreases in cell size, membrane Rho activity, superoxide anion (O2*-) production, and intracellular oxidation, and were reversed with L-mevalonate or geranylgeranylpyrophosphate, but not with farnesylpyrophosphate or cholesterol. Treatments with the Rho inhibitor C3 exotoxin and with cell-permeable superoxide dismutase also decreased AngII-induced O2*- production and myocyte hypertrophy. Overexpression of the dominant-negative Rho mutant N17Rac1 completely inhibited AngII-induced intracellular oxidation and ANF promoter activity, while N19RhoA partially inhibited it, and N17Cdc42 had no effect. Indeed, Sim inhibited cardiac hypertrophy and decreased myocardial Rac1 activity and O2*- production in rats treated with AngII infusion or subjected to transaortic constriction. These findings suggest that statins prevent the development of cardiac hypertrophy through an antioxidant mechanism involving inhibition of Rac1.
Discovering the Genome-Wide Activity of CRISPR-Cas Nucleases (2017)

Originally discovered as part of an adaptive bacterial defense system against the invasion of foreign phages, programmable CRISPR-Cas nucleases have emerged as remarkable enzymes with transformative potential for both biological research and clinical application. CRISPR-Cas nucleases likely evolved in their natural context to tolerate imperfect specificity in order to recognize mutant bacteriophages. However, in the context of biological research and clinical applications, high specificity is generally preferred. For therapeutic applications in particular, it is important to carefully and empirically define the genome-wide activity of engineered nucleases, as hundreds of millions to billions of cells may be modified in a single therapeutic dose. Over the past several years, a number of both cell-based and in vitro sensitive and unbiased genome-scale methods to define CRISPR-Cas nuclease specificity have been developed. These methods will play important complementary roles in better understanding their global specificity profiles and identifying optimal nucleases for applications that demand high precision editing. Improving the sensitivity of mutation detection by next-generation sequencing, developing assays to define the functional consequences of unintended off-target activity nuclease activity, and understanding the consequences of individual human genetic variation on gene editing activity will be important areas for future research and development.
Low energy memory and register allocation using network flow (1997)

This paper presents for the first time low energy simultaneousmemory and register allocation. A minimum cost network flowapproach is used to efficiently solve for minimum energy dissipationsolutions in polynomial time. Results show that estimatedenergy improvements of 1.4 to 2.5 times over previous researchare obtained. This research is important for industry since energydissipation is minimized without requiring an increase in cost.
Selective priming to Toll-like receptor 4 (TLR4), not TLR2, ligands by P. acnes involves up-regulation of MD-2 in mice (2004)

Lipopolysaccharide (LPS) triggers cytokine production through Toll-like receptor 4 (TLR4), which shares downstream signaling pathways with TLR2. We investigated the roles of TLR2 and TLR4 in Propionibacterium acnes (P. acnes)-primed, LPS-induced liver damage using selective TLR ligands. Stock LPS induced interleukin 8 in both TLR4- and TLR2-expressing human embryonic kidney (HEK) 293 cells. Purified LPS (TLR4 ligand) activated HEK/TLR4 cells, while peptidoglycan and lipoteichoic acid (TLR2 ligands) activated HEK/TLR2 cells, respectively. In mice, P. acnes priming resulted in increased liver messenger RNA (mRNA) and serum levels of tumor necrosis factor alpha, interleukin 12, and interferon gamma (IFN-gamma) by both stock LPS and purified LPS challenges compared with nonprimed controls. In contrast, P. acnes failed to sensitize to TLR2 ligands (peptidoglycan + lipoteichoic acid). In the liver, P. acnes-priming was associated with up-regulation of TLR4 and MD-2 proteins, and subsequent LPS challenge further increased MD-2 and CD14 mRNA levels. The lack of sensitization to TLR2 ligands by P. acnes correlated with no increase in hepatic TLR1 or TLR6 mRNA. In vitro, P. acnes pretreatment desensitized RAW macrophages to a secondary stimulation via both TLR2 and TLR4. However, IFN-gamma could selectively prevent desensitization to TLR4 but not to TLR2 ligands. Furthermore, P. acnes induced production of IFN-gamma in vivo as well as in isolated splenocytes. In vitro, P. acnes-primed Hepa 1-6 hepatocytes but not RAW macrophages produced increased MD-2 and CD14 mRNA levels after an LPS challenge. In conclusion, P. acnes priming to selective TLR4-mediated liver injury is associated with up-regulation of TLR4 and MD-2 and is likely to involve IFN-gamma and prevent TLR4 desensitization by P. acnes.
Design of Urban Runoff Quality Controls (1988)

This book describes current practice in the design of pollution controls for urban runoff. The contents comprise the proceedings of an Engineering Foundation Conference held in July 1988, titled “Current Practice and Design Criteria for Urban Runoff Water Quality Control.” The papers are concerned with the pragmatic, functional design and maintenance of devices that have been demonstrated to work in the field. These include: wet and dry detention ponds, infiltration devices, sedimentation tanks, swirl concentrators, wetlands, and source controls. Three related sessions address receiving water responses to urban runoff, the Water Quality Act of 1987, and institutional issues related to implementation of urban runoff quality control. These proceedings bring together much of the collective knowledge of American and European technology in the subject area. Many of the authors are internationally recognized in their field.
Grazing Angle Metal-Overlayer Infrared ATR Spectroscopy (1988)

The most sensitive reflection spectroscopic technique has been developed for studying the structure of thin films between a semiconductor and a metallic film. In this study, a metal-overlayer ATR technique was applied to measure the infrared spectra of interfacial layers. According to optical theory, this technique requires a high angle of incidence near the grazing angle in order to obtain optimum sensitivity. On the basis of the theoretical prediction, an optimized prism was designed. Our prism/thin film/ metal configuration yields an S/N ratio 5 times better than that achieved by the conventional reflection-absorption spectroscopy. This enhancement is not due to the so-called metal island effect, but is due instead to the high refractive index of the semiconductor prism.
Comparative study of maximum power point tracking algorithms (2002)

Abstract Maximum power point trackers (MPPTs) play an important role in photovoltaic (PV) power systems because they maximize the power output from a PV system for a given set of conditions, and therefore maximize the array efficiency. Thus, an MPPT can minimize the overall system cost. MPPTs find and maintain operation at the maximum power point, using an MPPT algorithm. Many such algorithms have been proposed. However, one particular algorithm, the perturb‐and‐observe (P&O) method, claimed by many in the literature to be inferior to others, continues to be by far the most widely used method in commercial PV MPPTs. Part of the reason for this is that the published comparisons between methods do not include an experimental comparison between multiple algorithms with all algorithms optimized and a standardized MPPT hardware. This paper provides such a comparison. MPPT algorithm performance is quantified through the MPPT efficiency. In this work, results are obtained for three optimized algorithms, using a microprocessor‐controlled MPPT operating from a PV array and also a PV array simulator. It is found that the P&O method, when properly optimized, can have MPPT efficiencies well in excess of 97%, and is highly competitive against other MPPT algorithms. Copyright © 2002 John Wiley & Sons, Ltd.
The factor V-activating enzyme (RVV-V) from Russell's viper venom. Identification of isoproteins RVV-V alpha, -V beta, and -V gamma and their complete amino acid sequences. (1988)

The complete amino acid sequences of two isoproteins of the factor V-activating enzyme (RVV-V) isolated from Vipera russelli (Russell's viper) venom were determined by sequencing S-pyridylethylated derivatives of the proteins and their peptide fragments generated by either chemical (cyanogen bromide and 2-(2-nitrophenylsulfenyl)-3-methyl-3-bromoindolenine) or enzymatic (trypsin, alpha-chymotrypsin, and lysyl endopeptidase) cleavages. Both enzymes, designated RVV-V alpha and RVV-V gamma, consist of 236 amino acid residues and have a N-linked oligosaccharide chain at Asn229. The six amino acid substitutions between RVV-V alpha and -V gamma are: Thr22(alpha)-Ala22(gamma), Gly29(alpha)-Ala29(gamma), Gln191(alpha)-Glu191(gamma), Ile192(alpha)-Met192(gamma), Gln193(alpha)-His193(gamma), and Asn224(alpha)-Ser224(gamma). The molecular weights were calculated as 26,182 for RVV-V alpha and 26,167 for RVV-V gamma. The sequences of the RVV-V isoproteins exhibited 62% identity with that of batroxobin, a thrombin-like enzyme present in Bothrops atrox venom, and 33% identity with that of human thrombin B chain. The most interesting difference between the structures of RVV-V and other trypsin-type serine proteases is that the conservative Ser214-Trp215-Gly216 sequence (chymotrypsinogen numbering), considered as the site of antiparallel beta-sheet formation between the protein substrate and most serine proteases, has been replaced by the corresponding sequence Ala-Gly-Gly.
Pushing ASIC performance in a power envelope (2004)

Power dissipation is becoming the most challenging design constraint in nanometer technologies. Among various design implementation schemes, standard cell ASICs offer the best power efficiency for high-performance applications. The flexibility of ASICs allow for the use of multiple voltages and multiple thresholds to match the performance of critical regions to their timing constraints, and minimize the power everywhere else. We explore the trade-off between multiple supply voltages and multiple threshold voltages in the optimization of dynamic and static power. The use of multiple supply voltages presents some unique physical and electrical challenges. Level shifters need to be introduced between the various voltage regions. Several level shifter implementations will be shown. The physical layout needs to be designed to ensure the efficient delivery of the correct voltage to various voltage regions. More flexibility can be gained by using appropriate level shifters. We will discuss optimization techniques such as clock skew scheduling which can be effectively used to push performance in a power neutral way.
Bovine Activin Receptor Type IIB Messenger Ribonucleic Acid Displays Alternative Splicing Involving a Sequence Homologous to Src-Homology 3 domain Binding Sites (1997)

Activins are implicated in a variety of biological effects, particularly in reproductive processes such as embryonic development and folliculogenesis. Breakthroughs in the elucidation of the activin signal transduction mechanism were achieved with the characterization of the activin receptors, and the recent identification of cytoplasmic factors apparently involved in the signaling process. The present studies were undertaken to further analyze the activin signaling pathway. The complementary DNA coding for the bovine activin receptor type IIB (bActRIIB) was amplified by RT-PCR from corpus luteum and pituitary RNA, and cloned to characterize its role in activin signal transduction. Two complementary DNA isoforms (bAct-RIIB2 and bActRIIB5) were detected, coding for 512 amino acids and 498 amino acids, respectively. The shortest isoform lacked a sequence encoding a 14-amino acid stretch very rich in proline residues, located between the transmembrane region and the intracellular kinase domain. Intron sequencing and ribonuclease protection assay demonstrated that alternative splicing is responsible for the generation of these bActRIIB isoforms. This alternative splicing event is unique in that it has not been observed in other species, including the mouse, in which extensive alternative splicing of the ActRIIB messenger RNA is described. Comparison of this alternative sequence with other known proline-rich sequences showed that it has characteristics of a Src-homology 3 domain (SH3) binding site. Coprecipitation experiments have identified two proteins of 69 kDa and 71 kDa from an uterine endometrial cell line, specifically interacting with the short bActRIIB alternative proline-rich sequence. These results suggest that bActRIIB could have a protein-protein interaction, through its putative SH3 binding site, with at least two intracellular SH3-containing proteins.
A combined electron beam/optical lithography process step for the fabrication of sub-half-micron-gate-length MMIC chips (1994)

Advanced radar and communication systems rely heavily on state-of-the-art microelectronics. Systems such as the phased-array radar require many transmit/receive (T/R) modules which are made up of many millimeter wave - microwave integrated circuits (MMIC's). The heart of a MMIC chip is the Gallium Arsenide (GaAs) field-effect transistor (FET). The transistor gate length is the critical feature that determines the operating frequency of the radar system. A smaller gate length will typically result in a higher frequency. In order to make a phased array radar system economically feasible, manufacturers must be capable of producing very large quantities of small-gate-length MMIC chips at a relatively low cost per chip. This requires the processing of a large number of wafers with a large number of chips per wafer, minimum processing time, and a very high chip yield. One of the bottlenecks in the fabrication of MIMIC chips is the transistor gate definition. The definition of sub-half-micron gates for GaAs-based field-effect transistors is generally performed by direct-write electron beam lithography (EBL). Because of the throughput limitations of EBL, the gate-layer fabrication is conventionally divided into two lithographic processes where EBL is used to generate the gate fingers and optical lithography is used to generate the large-area gate pads and interconnects. As a result, two complete sequences of resist application, exposure, development, metallization and lift-off are required for the entire gate structure. We have baselined a hybrid process, referred to as EBOL (electron beam/optical lithography), in which a single application of a multi-level resist is used for both exposures. The entire gate structure, (gate fingers, interconnects and pads), is then formed with a single metallization and lift-off process. The EBOL process thus retains the advantages of the high-resolution E-beam lithography and the high throughput of optical lithography while essentially eliminating an entire lithography/metallization/lift-off process sequence. This technique has been proven to be reliable for both trapezoidal and mushroom gates and has been successfully applied to metal-semiconductor and high-electron-mobility field-effect transistor (MESFET and HEMT) wafers containing devices with gate lengths down to 0.10 micron and 75 x 75 micron gate pads. The yields and throughput of these wafers have been very high with no loss in device performance. We will discuss the entire EBOL process technology including the multilayer resist structure, exposure conditions, process sensitivities, metal edge definition, device results, comparison to the standard gate-layer process, and its suitability for manufacturing.
The Chemistry of Hortiamine and 6-Methoxyrhetsinine<sup>1</sup> (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry of Hortiamine and 6-Methoxyrhetsinine1Irwin J. Pachter, Richard J. Mohrbacher, and David E. ZachariasCite this: J. Am. Chem. Soc. 1961, 83, 3, 635–642Publication Date (Print):February 1, 1961Publication History Published online1 May 2002Published inissue 1 February 1961https://pubs.acs.org/doi/10.1021/ja01464a032https://doi.org/10.1021/ja01464a032research-articleACS PublicationsRequest reuse permissionsArticle Views207Altmetric-Citations24LEARN 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
Animal Models of Human Prostate Cancer: The Consensus Report of the New York Meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee (2013)

Animal models, particularly mouse models, play a central role in the study of the etiology, prevention, and treatment of human prostate cancer. While tissue culture models are extremely useful in understanding the biology of prostate cancer, they cannot recapitulate the complex cellular interactions within the tumor microenvironment that play a key role in cancer initiation and progression. The National Cancer Institute (NCI) Mouse Models of Human Cancers Consortium convened a group of human and veterinary pathologists to review the current animal models of prostate cancer and make recommendations about the pathologic analysis of these models. More than 40 different models with 439 samples were reviewed, including genetically engineered mouse models, xenograft, rat, and canine models. Numerous relevant models have been developed over the past 15 years, and each approach has strengths and weaknesses. Analysis of multiple genetically engineered models has shown that reactive stroma formation is present in all the models developing invasive carcinomas. In addition, numerous models with multiple genetic alterations display aggressive phenotypes characterized by sarcomatoid carcinomas and metastases, which is presumably a histologic manifestation of epithelial-mesenchymal transition. The significant progress in development of improved models of prostate cancer has already accelerated our understanding of the complex biology of prostate cancer and promises to enhance development of new approaches to prevention, detection, and treatment of this common malignancy.
Human interleukin-2 production in insect (Trichoplusia ni) larvae: Effects and partial control of proteolysis (1999)

Many eukaryotic proteins have been successfully expressed in insect cells infected with a baculovirus in which the foreign gene has been placed under the control of a viral promoter. This system can be costly at large scale due to the quality of virus stock, problems of oxygen transfer, and severity of large-scale contamination. To circumvent this problem, we have investigated the expression of a foreign protein, human interleukin-2 (IL-2), in insect larvae, Trichoplusia ni, infected with the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV). The IL-2 gene was placed under control of the p10 promoter so that the polyhedra remained intact for efficient primary infection. From our results, it was clear that early infection limited larval growth and late infection delayed product production until near pupation, hence infection timing was important. Also, the harvest time was crucial for obtaining high yield, because IL-2 production had a sharp optimal peak with a time of occurrence dependent on both temperature and the initial amount of infection virus. Specifically, we found that, by raising the infection temperature to 30 degrees C, we more than doubled the protein productivity. Furthermore, a significant concern of the larvae/baculovirus expression system has been the large amount of protease produced by the larvae, which adversely affects the protein yield. Therefore, we screened several protease inhibitors and characterized the larval protease specificity and timing to attenuate their impact. This report elucidates and delineates the factors that most directly impact protein yield in the larvae expression system, using IL-2 as a model.
Polymer-based actuators for virtual reality devices (2004)

Virtual Reality (VR) is gaining more importance in our society. For many years, VR has been limited to the entertainment applications. Today, practical applications such as training and prototyping find a promising future in VR. Therefore there is an increasing demand for low-cost, lightweight haptic devices in virtual reality (VR) environment. Electroactive polymers seem to be a potential actuation technology that could satisfy these requirements. Dielectric polymers developed the past few years have shown large displacements (more than 300%). This feature makes them quite interesting for integration in haptic devices due to their muscle-like behaviour. Polymer actuators are flexible and lightweight as compared to traditional actuators. Using stacks with several layers of elatomeric film increase the force without limiting the output displacement. The paper discusses some design methods for a linear dielectric polymer actuator for VR devices. Experimental results of the actuator performance is presented.
Physical exercise and the lactating woman: a qualitative pilot study of mothers' perceptions and experiences. (2004)

This study aimed to explore the lactating woman's perceptions and experiences of physical exercise. Utilising quantitative and qualitative measures, six lactating women (average age = 31.6 years) who had recently given birth and were engaging in regular exercise, took part in open-ended, semi-structured interviews and questionnaires which focused on their individual experiences. The mothers also completed inventories measuring self-esteem, the presence of postnatal depression, and a retrospective survey gauging their preconception, prenatal and current participation in physical activity. The main themes to emerge from teh content analysis of the qualitative data included perceived well-being from improved energy and stress levels, and weight control. Some of the mothers stated that exercise affected their breastfeeding in a negative way by possibly reducing their breastmilk supply. All mothers confirmed exercise as enhancing the maternal-infant relationship. It is recommended that future research be conducted into the exercise prescription guidelines for women to enhance breastfeeding success.