gebhart/patrepeval huggingface dataset:
Conjugation of Haloalkanes by Bacterial and Mammalian Glutathione Transferases:  Mono- and Vicinal Dihaloethanes (2001)

Glutathione (GSH) transferases are generally involved in the detoxication of xenobiotic chemicals. However, conjugation can also activate compounds and result in DNA modification. Activation of 1,2-dihaloethanes (BrCH(2)CH(2)Br, BrCH(2)CH(2)Cl, and ClCH(2)CH(2)Cl) was investigated using two mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and a bacterial dichloromethane dehalogenase (DM11). Although the literature suggests that the bacterial dehalogenase does not catalyze reactions with CH(3)Cl, ClCH(2)CH(2)Cl, or CH(3)CHCl(2), we found a higher enzyme efficiency for DM11 than for the mammalian GSH transferases in conjugating CH(3)Cl, CH(3)CH(2)Cl, and CH(3)CH(2)Br. Enzymatic rates of activation of 1,2-dihaloethanes were determined in vitro by measuring S,S-ethylene-bis-GSH, the major product trapped by nonenzymatic reaction with the substrate GSH. Salmonella typhimurium TA 1535 systems expressing each of these GSH transferases were used to determine mutagenicity. Rates of formation of S,S-ethylene-bis-GSH by the GSH transferases correlated with the mutagenicity determined in the reversion assays for the three 1,2-dihaloethanes, consistent with the view that half-mustards are the mutagenic products of the GSH transferase reactions. Half-mustards [S-(2-haloethyl)GSH] containing either F, Cl, or Br (as the leaving group) were tested for their abilities to induce revertants in S. typhimurium, and rates of hydrolysis were also determined. GSH transferases do not appear to be involved in the breakdown of the half-mustard intermediates. A halide order (Br > Cl) was observed for both GSH transferase-catalyzed mutagenicity and S,S-ethylene-bis-GSH formation from 1,2-dihaloethanes, with the single exception (both assays) of BrCH(2)CH(2)Cl reaction with DM11, which was unexpectedly high. The lack of substrate saturation seen for conjugation of dihalomethanes with GSTs 5-5 and T1 was also observed with the mono- and 1,2-dihaloethanes [Wheeler, J. B., Stourman, N. V., Thier, R., Dommermuth, A., Vuilleumier, S., Rose, J. A., Armstrong, R. N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1118-1127], indicative of an inherent difference in the catalytic mechanisms of the bacterial and mammalian GSH transferases.
Potent Inhibition of Tumor Necrosis Factor-α Production by Tetrafluorothalidomide and Tetrafluorophthalimides (1996)

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTPotent Inhibition of Tumor Necrosis Factor-α Production by Tetrafluorothalidomide and TetrafluorophthalimidesSatomi Niwayama, Benjamin E. Turk, and Jun O. LiuView Author Information Departments of Biology and Chemistry, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massassachusetts 02139Cite this: J. Med. Chem. 1996, 39, 16, 3044–3045Publication Date (Web):August 2, 1996Publication History Received15 April 1996Published online2 August 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm960284rhttps://doi.org/10.1021/jm960284rrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views505Altmetric-Citations48LEARN 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 SUBJECTS:Fluorine,Hydrogen,Inhibition,Peptides and proteins,Phenyls Get e-Alerts
Substrate temperature effects on film chemistry in plasma depositions of organics. II. Polymerizable precursors (1992)

Abstract The influence of substrate temperature during plasma deposition on the chemistry of the organic films formed was examined. Plasma ionization of precursor gases that are polymerizable by conventional mechanisms was studied. Film chemistry was analyzed by x‐ray photoelectron spectroscopy (XPS). Monomers that polymerize by a free radical mechanism [2‐hydroxyethyl methacrylate (HEMA) and hexafluorobutadiene (HFB)] form more regular polymers (i.e. with less molecular rearrangement) by plasma deposition at low substrate temperatures than monomers that polymerize by ionic mechanisms [ethylene oxide (EO) and tetrahydrofuran (THF)]. In all cases, lowering the substrate temperature during deposition produces films with elemental composition virtually identical to that of the precursor gas. Comparison of high‐resolution XPS spectra of the deposited films with those for model polymers suggests that functional groups in the monomers used to generate the plasma are incorporated to a greater extent at low substrate temperatures. The effect of plasma power on the degree of precursor structure retention obtained when reduced substrate temperatures are employed was also examined. Plasma deposition of HEMA at low substrate temperatures and low plasma power produces thin films which are, by core level XPS, indistinguishable from HEMA polymerized by conventional methods. EO and THF films coated at low substrate temperatures on glass, polyethylene, or polytetrafluoroethylene varied widely in surface chemistry due to differences in film uniformity. Film quality (uniformity) is enhanced for these low reactivity precursors by pretreating substrates with an argon plasma. © 1992 John Wiley &amp; Sons, Inc.
A cost analysis of diabetic lower-extremity ulcers. (2000)

Lower-extremity ulcers cost the Medicare system $1.5 billion in 1995. Any wound care intervention that could prevent even a small percentage of wounds from progressing to the stage at which inpatient care is required may have a favorable cost effect on the Medicare system.
Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis (2009)

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.
Making the most of opportunities during a recession (2010)

The best public managers know that conventional thinking won’t get them through tough times and that a recession is a rich opportunity to reinvent their organization and to lay the groundwork for future successes. Good times are when managers experience their greatest success. But bad times provide the greatest opportunities to rethink how the organization will persist through the inevitable up and down economic cycles so as to be successful in the future. Smart managers today that I have engaged regarding this process say that they plan for both the good and bad times by continually focusing on six processes: Engaging the Outside World Managing Human Capital Recalibrating Organizational Strategy and Business Models Staying Connected with Citizens Becoming More Efficient and Productive as an Organization, and Understanding and Adapting to Changing Risks
[Benzodiazepines in geriatrics--a case report on prolonged action]. (1996)

Due to the age-dependent changes of pharmacodynamic and pharmcokinetic, the frequency of undesirable side-effects of benzodiazepines is higher in geriatric patients. An increased sensitivity to benzodiazepines and their metabolites can induce extremely prolonged duration of action leading to unconsciousness and respiratory insufficiency. Because of an assumed postoperative "psychosyndrome", a 72-year-old patient was treated with high doses of diazepam combined with single doses of tramal, clonidin and ranitidin. This treatment was followed by the development of respiratory insufficiency requiring intensive care with intubation for 8 days including assisted ventilation for 2 days. The serum concentrations of diazepam and its metabolites lay within the therapeutic range until the 7th day after the end of application. Therefore, the authors conclude that when using benzodiazepines in geriatric patients, the physiological peculiarities of this age group and possible interactions with other drugs leading to an increase in potency must be carefully considered.
Middleware to support sensor network applications (2004)

Current trends in computing include increases in both distribution and wireless connectivity, leading to highly dynamic, complex environments on top of which applications must be built. The task of designing and ensuring the correctness of applications in these environments is similarly becoming more complex. The unified goal of much of the research in distributed wireless systems is to provide higher-level abstractions of complex low-level concepts to application programmers, easing the design and implementation of applications. A new and growing class of applications for wireless sensor networks require similar complexity encapsulation. However, sensor networks have some unique characteristics, including dynamic availability of data sources and application quality of service requirements, that are not common to other types of applications. These unique features, combined with the inherent distribution of sensors, and limited energy and bandwidth resources, dictate the need for network functionality and the individual sensors to be controlled to best serve the application requirements. In this article, we describe different types of sensor network applications and discuss existing techniques for managing these types of networks. We also overview a variety of related middleware and argue that no existing approach provides all the management tools required by sensor network applications. To meet this need, we have developed a new middleware called MiLAN. MiLAN allows applications to specify a policy for managing the network and sensors, but the actual implementation of this policy is effected within MiLAN. We describe MiLAN and show its effectiveness through the design of a sensor-based personal health monitor.
Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial (2014)

The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.
The Relationship Between Multi Medium and the Sports Theory Teaching (1999)

The physical education developement deponds on the progress of advanced teaching to some extent.It is necessary for modern physical education teching to introduce multi medium teaching system into sports field.
Effect of Bunazosin Hydrochloride on Intraocular Pressure and Aqueous Humor Dynamics in Normotensive Human Eyes (1991)

We investigated the effects of topical administration of bunazosin hydrochloride, a new selective alpha 1-adrenergic antagonist, on intraocular pressure and aqueous humor dynamics in normal human eyes. In the single-dose study, all concentrations of bunazosin (0.025%, 0.05%, 0.1%, and 0.2%) significantly lowered intraocular pressure in a concentration-dependent manner. Administration of multiple doses of 0.1% bunazosin revealed no occurrence of tachyphylaxis after 1 week. Single application of 0.1% bunazosin had no significant influence on aqueous flow rate, tonographic outflow facility, or episcleral venous pressure, suggesting that bunazosin reduces intraocular pressure by increasing uveoscleral outflow. Aqueous protein concentration was found to be unaltered by bunazosin, indicating that blood-aqueous barrier permeability to protein molecules remained unchanged. We conclude that bunazosin may be a possible new antiglaucoma agent with a mechanism of action different from those currently in use for treating ocular hypertension.
Infectivity of Moloney Murine Leukemia Virus Defective in Late Assembly Events Is Restored by Late Assembly Domains of Other Retroviruses (2000)

The p12 region of the Moloney murine leukemia virus (M-MuLV) Gag protein contains a PPPY motif important for efficient virion assembly and release. To probe the function of the PPPY motif, a series of insertions of homologous and heterologous motifs from other retroviruses were introduced at various positions in a mutant gag gene lacking the PPPY motif. The assembly defects of the PPPY deletion mutant could be rescued by insertion of a wild-type PPPY motif and flanking sequences at several ectopic positions in the Gag protein. The late assembly domain (L-domain) of Rous sarcoma virus (RSV) or human immunodeficiency virus type 1 (HIV-1) could also fully or partially restore M-MuLV assembly when introduced into matrix, p12, or nucleocapsid domains of the mutant M-MuLV Gag protein lacking the PPPY motif. Strikingly, mutant viruses carrying the RSV or the HIV-1 L-domain at the original location of the deleted PPPY motif were replication competent in rodent cells. These data suggest that the PPPY motif of M-MuLV acts in a partially position-independent manner and is functionally interchangeable with L-domains of other retroviruses. Electron microscopy studies revealed that deletion of the entire p12 region resulted in the formation of tube-like rather than spherical particles. Remarkably, the PPPY deletion mutant formed chain structures composed of multiple viral particles linked on the cell surface. Many of the mutants with heterologous L-domains released virions with wild-type morphology.
Mg2+-Induced Thermal Enediyne Cyclization at Ambient Temperature (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTMg2+-Induced Thermal Enediyne Cyclization at Ambient TemperatureDiwan S. Rawat and Jeffrey M. ZaleskiView Author Information Contribution from the Department of Chemistry Indiana University, Bloomington, Indiana 47405 Cite this: J. Am. Chem. Soc. 2001, 123, 39, 9675–9676Publication Date (Web):September 8, 2001Publication History Received17 May 2001Published online8 September 2001Published inissue 1 October 2001https://pubs.acs.org/doi/10.1021/ja011215rhttps://doi.org/10.1021/ja011215rrapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views844Altmetric-Citations47LEARN 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:Cyclization,Hydrocarbons,Ligands,Metals,Reactivity Get e-Alerts
Characterization of arbitrary femtosecond pulses using frequency-resolved optical gating (1993)

The frequency-resolved optical gating (FROG) technique for characterizing and displaying arbitrary femtosecond pulses is presented. The method is simple, general, broadband, and does not require a reference pulse. Using virtually any instantaneous nonlinear-optical effect, FROG involves measuring the spectrum of the signal pulse as a function of the delay between two input pulses. The resulting trace of intensity versus frequency and delay is related to the pulse's spectrogram a visually intuitive transform containing time and frequency information. It is proven using phase retrieval concepts that the FROG trace yields the full intensity I(t) and phase phi (t) of an arbitrary ultrashort pulse with no physically significant ambiguities. FROG appears to have temporal resolution limited only by the response of the nonlinear medium. The method is demonstrated by using self-diffraction through the electronic Kerr effect in BK-7 glass and 620-nm, linearly chirped, approximately 200-fs pulses of a few microjoules.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Environmental Policy Reform in the Post-communist Czech Republic: The Case of Air Pollution (2001)

THE DEVELOPMENT OF ENVIRONMENTAL POLICY in Western countries during the past three decades is a remarkable story of policy change driven by public concern. Environmental activists and Green parties have pushed environmental issues onto national government agendas in the face of stiff opposition from economic interests. In 1989 the world witnessed a new wave of environmental protest in East Central Europe (ECE). As environmental groups rallied public opposition to the region's failing communist regimes, many Western analysts predicted that grassroots activism would drive environmental policy reform in post-communist countries.2 This prediction turned out to be unfounded. Across the region, public concern about the environment plummeted after 1989 as the hardships of transition to a market economy took centre stage. Environmental policy came to be developed largely in isolation from societal pressures. In this article I examine the dynamics and results of environmental policy reform in the Czech Republic between 1989 and 1998. The first section analyses the changing nature of the driving forces behind environmental policy reform in the post-communist Czech Republic. In the late 1980s the Czech lands (then part of the former Czechoslovakia) had some of the most severe environmental problems in ECE, as well as one of the region's most significant grassroots environmental opposition movements. The prominence of environmental themes during the 'Velvet Revolution' of November 1989 resulted in the creation of a powerful Czech Environment Ministry headed by former 'green dissidents'. Yet the ministry's efforts to forge a more inclusive environmental policy process were soon undermined by a rapid and sustained decline in popular concern with the environment, attributable chiefly to the function of environmental protest in 1989 as an outlet for broader
Thrombin and Antithrombotics (1998)

From injury through healing, thrombin has several important functions in blood clotting, subsequent clot lysis, and tissue repair. These include edema, inflammation, cell recruitment, cellular releases, transformations, mitogenesis, and angiogenesis. Thrombin also participates in disease states, such as venous thrombosis, coronary thrombosis, stroke, and pulmonary emboli, among others and is implicated in atherosclerosis, the growth and metastasis of certain cancers, Alzheimer's disease, and perhaps other conditions.
EIE: Efficient Inference Engine on Compressed Deep Neural Network (2016)

State-of-the-art deep neural networks (DNNs) have hundreds of millions of connections and are both computationally and memory intensive, making them difficult to deploy on embedded systems with limited hardware resources and power budgets. While custom hardware helps the computation, fetching weights from DRAM is two orders of magnitude more expensive than ALU operations, and dominates the required power. Previously proposed 'Deep Compression' makes it possible to fit large DNNs (AlexNet and VGGNet) fully in on-chip SRAM. This compression is achieved by pruning the redundant connections and having multiple connections share the same weight. We propose an energy efficient inference engine (EIE) that performs inference on this compressed network model and accelerates the resulting sparse matrix-vector multiplication with weight sharing. Going from DRAM to SRAM gives EIE 120x energy saving, Exploiting sparsity saves 10x, Weight sharing gives 8x, Skipping zero activations from ReLU saves another 3x. Evaluated on nine DNN benchmarks, EIE is 189x and 13x faster when compared to CPU and GPU implementations of the same DNN without compression. EIE has a processing power of 102 GOPS working directly on a compressed network, corresponding to 3 TOPS on an uncompressed network, and processes FC layers of AlexNet at 1.88x104 frames/sec with a power dissipation of only 600mW. It is 24,000x and 3,400x more energy efficient than a CPU and GPU respectively. Compared with DaDianNao, EIE has 2.9x, 19x and 3x better throughput, energy efficiency and area efficiency.
Molecular predictors of response to a humanized anti–insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer (2009)

The insulin-like growth factor-I receptor (IGF-IR) pathway is required for the maintenance of the transformed phenotype in neoplastic cells and hence has been the subject of intensive drug discovery efforts. A key aspect of successful clinical development of targeted therapies directed against IGF-IR will be identification of responsive patient populations. Toward that end, we have endeavored to identify predictive biomarkers of response to an anti-IGF-IR-targeting monoclonal antibody in preclinical models of breast and colorectal cancer. We find that levels of the IGF-IR itself may have predictive value in these tumor types and identify other gene expression predictors of in vitro response. Studies in breast cancer models suggest that IGF-IR expression is both correlated and functionally linked with estrogen receptor signaling and provide a basis for both patient stratification and rational combination therapy with antiestrogen-targeting agents. In addition, we find that levels of other components of the signaling pathway such as the adaptor proteins IRS1 and IRS2, as well as the ligand IGF-II, have predictive value and report on the development of a pathway-focused panel of diagnostic biomarkers that could be used to test these hypotheses during clinical development of IGF-IR-targeting therapies.