gebhart/patrepeval huggingface dataset:
Mechanism of tumor resistance to cisplatin mediated by the copper transporter ATP7BThis paper is one of a selection of papers published in a Special Issue entitled CSBMCB 53rd Annual Meeting — Membrane Proteins in Health and Disease, and has undergone the Journal’s usual peer review process. (2011)

The Wilson disease protein (ATP7B) is a copper-transporting ATPase that is responsible for regulating copper homeostasis in human tissues. ATP7B is associated with cancer resistance to cisplatin, one of the most widely used anticancer drugs. This minireview discusses the possible mechanisms of tumor resistance to cisplatin mediated by ATP7B. Cisplatin binds to the N-terminal cytosolic domain of ATP7B, which contains multiple copper-binding sites. Active platinum efflux catalyzed by ATP7B is unlikely to significantly contribute to cisplatin resistance in vivo. Transient platinum sequestration in the metal-binding domain followed by transfer to an acceptor protein or a low molecular weight compound is proposed as an alternative mechanism of cisplatin detoxification in the cell.
Synthesizing natural textures (2001)

Article Share on Synthesizing natural textures Author: Michael Ashikhmin Univ. of Utah, Salt Lake City Univ. of Utah, Salt Lake CityView Profile Authors Info & Claims I3D '01: Proceedings of the 2001 symposium on Interactive 3D graphicsMarch 2001Pages 217–226https://doi.org/10.1145/364338.364405Published:01 March 2001Publication History 501citation2,408DownloadsMetricsTotal Citations501Total Downloads2,408Last 12 Months84Last 6 weeks8 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Inhibition of protein synthesis in CHO cells by actinomycin D: lesion occurs after 40S initiation complex formation (1983)

Inhibitors of RNA synthesis such as actinomycin D, 2-mercapto-1-(beta-4-pyridylethyl)benzimidazole, and cordycepin progressively inhibit the initiation of protein synthesis in intact nucleated mammalian cells independent of their effect on mRNA synthesis. The mechanism of this effect is unknown. The activity of cell-free lysates is not directly affected by these inhibitors, suggesting that their effect is indirect and requires an intact cell. However, lysates prepared from L-cells or CHO cells treated with the inhibitors do exhibit a decrease in initiation activity corresponding in magnitude to the effect seen in intact cells. Mixing experiments with lysates isolated from untreated or treated cells provide no evidence for a translational inhibitor. However, experiments analyzing the incorporation of [35S]methionine and [35S]Met-tRNAf into initiation complexes showed that while the level of labeled 40S initiation complex in lysates from treated cells was the same or higher than in control lysates, the rate or efficiency of formation of the 80S initiation complex was inhibited. These results imply that the transcriptional inhibitors do not affect the level or charging of the initiation tRNAMet, the activity of the eIF-2 initiation factor needed for ternary complex formation, and the availability of active 40S ribosomal subunits. Thus, this site of action is different from that observed in other translational control systems such as the hemin response in reticulocytes and the interferon-induced translation inhibition in virally infected cells. This effect may reflect the cell's coordination of nuclear transcription and cytoplasmic translation.
Influence of the calcium-sensitizer UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy. Comparison with nitroprusside (1989)

UDCG-115 is a new cardiotonic agent which in vitro increases the sensitivity of the contractile proteins to calcium ions, inhibits the activity of phosphodiesterase, and prolongs the duration of the action potential. The influence of UDCG-115 (i.v.) on hemodynamics and myocardial energetics was investigated in patients with idiopathic dilated cardiomyopathy (NYHA II—III) and compared to the effects of the pure vasodilator nitroprusside. UDCG-115 increased cardiac index from 3.2 ± 0.4 to 4.2 ± 0.8 1/min/m2 (p < 0.01) and decreased left ventricular end-diastolic wall stress (preload) from 52 ± 21 to 28 ± 18 103 dyn/cm2 (p < 0.01) and end-systolic wall stress (afterload) from 201 ± 61 to 129±43 103 dyn/cm2 (p < 0.01) compared to control conditions. Compared to nitroprusside, for a similar decrease in preload and afterload, UDCG-115 increased cardiac index by 40% (p < 0.01), stroke volume index by 37% (p < 0.01) and maximum rate of left ventricular pressure rise by 23% (p < 0.05). Heart rate did not significantly change with either drug. Myocardial oxygen consumption per beat decreased by 33% (p < 0.05) with UDCG-115 and by 30% (p < 0.01) with nitroprusside. With both drugs, the decrease of myocardial oxygen consumption correlated significantly with the decrease of left ventricular systolic stress-time integral. The slopes of the respective linear regression lines were not significantly different. Thus, UDCG-115 given intravenously in patients with idiopathic dilated cardiomyopathy and moderate congestive heart failure exhibits significant inotropic and vasodilating properties. The systemic hemodynamic actions are associated with favorable effects on myocardial energetics.
A Mild and Efficient Sonochemicaltert-Butoxycarbonylation of Amines from Their Salts (1991)

The introduction of the tert-butoxycarbonyl protecting group onto amines, as free bases or as salts, can be effected under mild conditions with ultrasonic irradiation. This method permits easy work-up and gives the protected compounds in high yield.
Density Fluctuations in the Etude Stellarator (1964)

Density fluctuations of the Ohmically heated plasma of the Étude stellarator can be resolved into azimuthally propagating waves by means of narrow-band correlation measurements. At frequencies below roughly 100 kHz, propagation velocities are comparable to macroscopic plasma velocities, but increase with frequency and azimuthal mode number. Kink or field degeneracy modes, such as those found on B-1, dominate the spectrum of azimuthal modes at appropriate plasma currents. At frequencies above 100 kHz, the wave propagation velocity tends to become constant at a value nearly an order of magnitude larger than either the ion diamagnetic drift or the mean column rotation velocity, but remains in the same direction.
Anaerobic growth of a Rhodopseudomonas species in the dark with carbon monoxide as sole carbon and energy substrate. (1976)

A species of Rhodopseudomonas that grows under strict anaerobic conditions in the dark and requires CO was isolated from lake and pond sediments. Although anaerobic growth in the dark occurs in a chemically defined mineral medium with CO as the only carbon and energy source, growth is stimulated by adding trypticase. Under these conditions, cells exhibit a generation time of 6.7 hr and reach a final concentration of 1 to 3 X 10(9) cells per ml of liquid medium. Resting suspensions of CO-grown cells metabolize about 6.7 mumol of CO per mg of protein in 1 hr and produce equimolar amounts of CO2 and H2 according to the equation CO + H2O leads to CO2 + H2. As predicted by this equation, when cells were suspended in tritium-labeled water containing potassium phosphate buffer at pH 7.0 and incubated with pure CO, 3H2 gas was produced at linear rate with a constant specific activity.
Nitric oxide. A novel signal transduction mechanism for transcellular communication. (1990)

Nitric oxide first captured the interest of biologists when this inorganic molecule was found to activate cytosolic guanylate cyclase and stimulate cyclic guanosine monophosphate (GMP) formation in mammalian cells. Further studies led to the finding that nitric oxide causes vascular smooth muscle relaxation and inhibition of platelet aggregation by mechanisms involving cyclic GMP and that several clinically used nitrovasodilators owe their biological actions to nitric oxide. Nitric oxide possesses physicochemical and pharmacological properties that make it an ideal candidate for a short-term regulator or modulator of vascular smooth muscle tone and platelet function. Nitric oxide is synthesized by various mammalian tissues including vascular endothelium, macrophages, neutrophils, hepatic Kupffer cells, adrenal tissue, cerebellum, and other tissues. Nitric oxide is synthesized from endogenous L-arginine by a nitric oxide synthase system that possesses different cofactor requirements in different cell types. The nitric oxide formed diffuses out of its cells of origin and into nearby target cells, where it binds to the heme group of cytosolic guanylate cyclase and thereby causes enzyme activation. This interaction represents a novel and widespread signal transduction mechanism that links extracellular stimuli to the biosynthesis of cyclic GMP in nearby target cells. The small molecular size and lipophilic nature of nitric oxide enable communication with nearby cells containing cytosolic guanylate cyclase. The extent of transcellular communication is limited by the short half-life of nitric oxide, thereby ensuring a localized response. Labile nitric oxide-generating molecules such as S-nitrosothiols may be involved as precursors or effectors. Further research will provide a deeper understanding of the biology of nitric oxide and the nature of associated pathophysiological states.
Robust Micromachined Gyroscopes for Automotive Applications (2005)

This paper reports a micromachined gyroscope with a 2-DoF sense-mode oscillator that provides a flat region in the sense-mode frequency response curve, where the amplitude and phase of the response are insensitive to parameter fluctuations. The sensitivity is also improved by utilizing dynamical amplification of oscillations in the 2-DoF sense-mode oscillator. Thus, improved long-term stability and robustness to fabrication variations, structural and thermal parameter fluctuations and vacuum degradations are achieved, solely by the mechanical system design. Bulk micromachined prototype gyroscopes exhibited a measured noise-floor of 0.64 0 /s/ √ Hz over a 50Hz bandwidth at atmospheric pressure. The sensemode response in the flat operating region was also experimentally demonstrated to be inherently insensitive to pressure, temperature and DC bias variations.
Intermediate and long-acting insulins: a review of NPH insulin, insulin glargine and insulin detemir (2006)

The newer long-acting insulin analogs, insulin detemir and glargine, appear to provide better glycemic control than NPH insulin without increasing the risk of hypoglycemia.
Sputter deposition and annealing of Ta, TaSix and TaBx composite films and their application in next generation lithography masks (2000)

Ta and Ta composites with other elements have been developed as low stress absorbers for x-ray mask technology. These thin films are often produced in small quantities by sputter deposition from targets of pure Ta with chips of the minor elements placed on the target to create the composites. For membrane-mask manufacturing it is important that absorber films have uniform composition, thickness, and low, uniform stress to assure that image size and pattern placement errors are minimal. Since sputtered films containing Ta often have highly compressive stress, several methods have been used to reduce the final stress, including careful control of sputtering conditions, deposition of layered films with different stresses, and thermal annealing. Much data has been reported regarding the effects of thermal annealing of Ta films but less information is available on multiple element films such as TaSix and TaBx. Previous reports on these materials have generally not discussed the behavior of these films under long term, higher volume manufacturing conditions. During the last several years IBM has been engaged in development and fabrication of refractory x-ray membrane masks using Ta composites as absorber materials. Films were sputter deposited from hot isostatically pressed powder targets of Ta, Si, and B using an S-gun magnetron cluster deposition system. This article reports on the deposition and annealing of these films and their application to membrane-mask fabrication in a manufacturing environment. The effects of deposition parameters such as dc power, argon gas pressure, and substrate composition on film stress, composition, and density are discussed. The results of nitrogen annealing on TaSix and TaBx films are presented. Absorber film quality data and its impact on image size, image placement, and defect density of some x-ray masks is presented.
Development of PF-06671008, a Highly Potent Anti-P-cadherin/Anti-CD3 Bispecific DART Molecule with Extended Half-Life for the Treatment of Cancer (2016)

Bispecific antibodies offer a promising approach for the treatment of cancer but can be challenging to engineer and manufacture. Here we report the development of PF-06671008, an extended-half-life dual-affinity re-targeting (DART<sup>®</sup>) bispecific molecule against P-cadherin and CD3 that demonstrates antibody-like properties. Using phage display, we identified anti-P-cadherin single chain Fv (scFv) that were subsequently affinity-optimized to picomolar affinity using stringent phage selection strategies, resulting in low picomolar potency in cytotoxic T lymphocyte (CTL) killing assays in the DART format. The crystal structure of this disulfide-constrained diabody shows that it forms a novel compact structure with the two antigen binding sites separated from each other by approximately 30 Å and facing approximately 90° apart. We show here that introduction of the human Fc domain in PF-06671008 has produced a molecule with an extended half-life (-4.4 days in human FcRn knock-in mice), high stability (T<sub>m</sub>1 > 68 °C), high expression (>1 g/L), and robust purification properties (highly pure heterodimer), all with minimal impact on potency. Finally, we demonstrate <i>in vivo</i> anti-tumor efficacy in a human colorectal/human peripheral blood mononuclear cell (PBMC) co-mix xenograft mouse model. These results suggest PF-06671008 is a promising new bispecific for the treatment of patients with solid tumors expressing P-cadherin.
Synthesis of Gold Hexagonal Bipyramids Directed by Planar-Twinned Silver Triangular Nanoprisms (2013)

The direct growth of planar-twinned Au nanoparticles (NPs) in high yield remains a challenge in shape-controlled NP synthesis largely because suitable planar-twinned seeds for Au NP growth have not been identified to date. Herein we describe the use of planar-twinned Ag triangular nanoprisms as a means to dictate Au NP twin structure. In a one-pot process, the Ag triangular nanoprisms first undergo oxidative Au replacement, forming Ag-Au alloy nanoframes and concomitantly releasing Ag(+) into solution, which then directs subsequent Au NP growth through an underpotential deposition process. The planar-twinned structure of the initial Ag nanoprism is maintained throughout particle growth. Using this method, we have successfully synthesized Au hexagonal bipyramids in high yield for the first time.
Evolutionary Optimization of Computationally Expensive Problems via Surrogate Modeling (2003)

We present a parallel evolutionary optimization algorithm that leverages surrogate models for solving computationally expensive design problems with general constraints, on a limited computational budget. The essential backbone of our framework is an evolutionary algorithm coupled with a feasible sequential quadratic programming solver in the spirit of Lamarckian learning. We employ a trust-region approach for interleaving use of exact modelsfortheobjectiveandconstraintfunctionswithcomputationallycheapsurrogatemodelsduringlocalsearch. In contrastto earlier work, we construct local surrogatemodels using radial basis functionsmotivated by theprinciple of transductive inference. Further, the present approach retains the intrinsic parallelism of evolutionary algorithms and can hence be readily implemented on grid computing infrastructures. Experimental results are presented for some benchmark test functions and an aerodynamic wing design problem to demonstrate that our algorithm converges to good designs on a limited computational budget.
Total synthesis of (+-)-6,7-didehydroaspidospermine (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of (+-)-6,7-didehydroaspidospermineSol S. Klioze and Frank P. DarmoryCite this: J. Org. Chem. 1975, 40, 11, 1588–1592Publication Date (Print):May 1, 1975Publication History Published online1 May 2002Published inissue 1 May 1975https://pubs.acs.org/doi/10.1021/jo00899a015https://doi.org/10.1021/jo00899a015research-articleACS PublicationsRequest reuse permissionsArticle Views471Altmetric-Citations15LEARN 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
Identification of Substrate Binding Site of Cyclin-dependent Kinase 5 (1999)

Cyclin-dependent kinase 5 (CDK5), unlike other CDKs, is active only in neuronal cells where its neuron-specific activator p35 is present. However, it phosphorylates serines/threonines in S/TPXK/R-type motifs like other CDKs. The tail portion of neurofilament-H contains more than 50 KSP repeats, and CDK5 has been shown to phosphorylate S/T specifically only in KS/TPXK motifs, indicating highly specific interactions in substrate recognition. CDKs have been shown to have a high preference for a basic residue (lysine or arginine) as the n+3 residue, n being the location in the primary sequence of a phosphoacceptor serine or threonine. Because of the lack of a crystal structure of a CDK-substrate complex, the structural basis for this specific interaction is unknown. We have used site-directed mutagenesis ("charged to alanine") and molecular modeling techniques to probe the recognition interactions for substrate peptide (PKTPKKAKKL) derived from histone H1 docked in the active site of CDK5. The experimental data and computer simulations suggest that Asp86 and Asp91 are key residues that interact with the lysines at positions n+2 and/or n+3 of the substrates.
Reversal of radiation resistance in LNCaP cells by targeting apoptosis through ceramide synthase. (1999)

Cell lines derived from human prostate cancer are regarded as relatively resistant to both radiation-induced clonogenic death and apoptosis. Here we attempted to modulate the response of LNCaP prostate cancer cells to radiation therapy (XRT) by pretreatment with 12-O-tetradecanoylphorbol acetate (TPA), a known apoptogenic agent in LNCaP cells. Using plateau-phase cultures, we investigated the response of these cells to XRT, TPA, and a combination of XRT and TPA. LNCaP irradiation did not result in ceramide generation or apoptosis. However, pretreatment with TPA enabled XRT to generate ceramide via activation of the enzyme ceramide synthase and signal apoptosis. Apoptosis was abrogated by the competitive inhibitor of ceramide synthase, fumonisin B1. Furthermore, when transplanted orthotopically into the prostate of nude mice, LNCaP cells produced tumors that recapitulated the responses of LNCaP cells in vitro. XRT or TPA failed to signal apoptosis in LNCaP tumors, whereas a combination of the two resulted in substantial (20-25%) apoptosis within 24 h. There was an additional benefit associated with this regimen because TPA pretreatment protected the adjacent rectum from radiation-induced apoptosis. This represents the first description of signaling-based therapy designed to overcome one form of radiation resistance expressed preferentially in LNCaP human prostate cancer cells.
Discretely tunable multi cavity FFP filter for standard WDM frequency grid (2002)

In this paper, we present theoretical results of research on a new discretely tunable multi cavity fiber Fabry-Perot (DTFFP) filter. The structure we propose assumes using at least two F-P filters with different length of resonance cavities, tuned by a shared piezoelectric transducer, e.g: the changes of all filter lengths are equal. Different speed of cavity tuning creates a set of separate frequencies of the common resonances. In this paper, we derive basic equations describing properties and allowing a design of DTFFP filter. We also carry out calculations for a standard frequency grid used in optical fiber WDM systems. The research done proves that, for the examined filters, it is possible to obtain both high selectivity and high value of tuning range at the same time.