gebhart/patrepeval huggingface dataset:
Identification of New Shikonin Derivatives as Antitumor Agents Targeting STAT3 SH2 Domain (2017)

Signal transducer and activator of transcription 3 (STAT3) is hyper-activated in diversiform human tumors and has been validated as an attractive therapeutic target. Current research showed that a natural product, shikonin, along with its synthetic analogues, is able to inhibit the activity of STAT3 potently. The potential space of shikonin in developing novel anti-cancer agents encouraged us to carry out the investigation of the probable binding mode with STAT3. From this foundation, we have designed new types of STAT3 SH2 inhibitors. Combined simulations were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. Among the entities, PMM-172 exhibited the best anti-proliferative activity against MDA-MB-231 cells with IC<sub>50</sub> value 1.98 ± 0.49 μM. Besides, it was identified to decrease luciferase activity, induce cell apoptosis and reduce mitochondrial transmembrane potential in MDA-MB-231 cells. Also, PMM-172 inhibited constitutive/inducible STAT3 activation without affecting STAT1 and STAT5 in MDA-MB-231 cells, and had no effect in non-tumorigenic MCF-10A cells. Moreover, PMM-172 suppressed STAT3 nuclear localization and STAT3 downstream target genes expression. Overall, these results indicate that the antitumor activity of PMM-172 is at least partially due to inhibition of STAT3 in breast cancer cells.
[Phosphate sorption characteristics onto sediments in the middle and lower reaches of the Yellow River]. (2008)

The equilibrium phosphate concentration (EPC0) of the Yellow River bed sediments has been measured, which was used to predict whether bed sediments are acting as a source or sink of soluble reactive phosphate (SRP). The modified Langmuir isotherm equation was used to describe phosphate (P) sorption on the Yellow River sediments. The maximum P sorption capacity (PAC) and P-binding energy constant (k) were obtained by the modified Langmuir isotherm model. Native adsorbed exchangeable phosphorus (NAP), the EPC0, and partitioning coefficients (Kp) were subsequently calculated by the corresponding formulae. The influence of pH values and ion strength were evaluated. All the EPC0 s are higher than the P concentration in the overlying water, indicating a potential source of phosphate from the sediments. PAC is linearly related to the contents of TOC of the sediment. The sorption capacity of P increased rapidly with pH below 6.0, and then reached a plateau between pH 6.0 to 9.7, and finally maintained at a slightly higher level from pH 9.7 to 12.0.The adsorption of P by the sediment decreased with the increase in Ca2+ ionic strength.
Energy-Maximizing Control of Wave-Energy Converters: The Development of Control System Technology to Optimize Their Operation (2014)

With the recent sharp increases in the price of oil, issues of security of supply, and pressure to honor greenhouse gas emission limits (e.g., the Kyoto protocol), much attention has turned to renewable energy sources to fulfill future increasing energy needs. Wind energy, now a mature technology, has had considerable proliferation, with other sources, such as biomass, solar, and tidal, enjoying somewhat less deployment. Waves provide previously untapped energy potential, and wave energy has been shown to have some favorable variability properties (a perennial issue with many renewables, especially wind), especially when combined with wind energy [1].
Molecular cloning of a 25-kDa high affinity rapamycin binding protein, FKBP25. (1992)

Two FK506 binding proteins of molecular mass 12 kDa (FKBP12) and 13 kDa (FKBP13) have been identified as common cellular receptors of the immunosuppressants FK506 and rapamycin. Here we report the molecular cloning and overexpression of a 25-kDa rapamycin and FK506 binding protein (termed FKBP25) with peptidylprolyl cis-trans-isomerase (PPIase) activity. The amino acid sequence, predicted from the FKBP25 cDNA, shares identity with FKBP12 (44%) and FKBP13 (47%) in the C-terminal 97 amino acids. Unlike either FKBP12 or FKBP13, the nucleotide sequence of FKBP25 contains a number of putative nuclear localization sequences. The PPIase activity of recombinant FKBP25 was comparable with that of FKBP12. The PPIase activity of FKBP25 was far more sensitive to inhibition by rapamycin (IC50 = 50 nM) than FK506 (IC50 = 400 nM). PPIase activity of 100 nM FKBP25 was almost completely inhibited by 150 nM rapamycin while only 90% inhibition was achieved by 4 microM FK506. These data demonstrate that FKBP25 has a higher affinity for rapamycin than for FK506 and suggest that this cellular receptor may be an important target molecule for immunosuppression by rapamycin.
Adaptive modulation and MIMO coding for broadband wireless data networks (2002)

Link adaptation techniques, where the modulation, coding rate, and/or other signal transmission parameters are dynamically adapted to the changing channel conditions, have emerged as powerful tools for increasing the data rate and spectral efficiency of wireless data-centric networks. While there has been significant progress on understanding the theoretical aspects of time adaptation in LA protocols, new challenges surface when dynamic transmission techniques are employed in broadband wireless networks with multiple signaling dimensions. Those additional dimensions are mainly frequency, especially in multicarrier systems, and space in multiple-antenna systems, particularly multiarray multiple-input multiple-output communication systems. We give an overview of the challenges and promises of link adaptation in future broadband wireless networks. We suggest guidelines to help in the design of robust, complexity/cost-effective algorithms for these future wireless networks.
Roles of vaccinia virus EEV-specific proteins in intracellular actin tail formation and low pH-induced cell-cell fusion. (1998)

During vaccinia virus (VV) morphogenesis intracellular mature virus (IMV) is wrapped by two additional membranes to form intracellular enveloped virus (IEV). IEV particles can nucleate the formation of actin tails which aid movement of IEVs to the cell surface where the outer IEV membrane fuses with the plasma membrane forming cell-associated enveloped virus (CEV) which remains attached to the cell, or extracellular enveloped virus (EEV) which is shed from the cell. In this report, we have used a collection of VV mutants lacking individual EEV-specific proteins to compare the roles of these proteins in the formation of IEV and IEV-associated actin tails and fusion of infected cells after a low pH shock. Data presented here show that p45-50 (A36R) is not required for IEV formation or for acid-induced cell-cell fusion, but is required for formation of IEV-associated actin tails. In contrast, gp86 (A56R), the virus haemagglutinin, is not required for formation of either IEV or IEV-associated actin tails. Data presented also confirm that p37 (gene F13L), gp42 (B5R) and gp22-24 (A34R) are needed for formation of IEV-associated actin tails and for cell-cell fusion after low pH shock. The phenotypes of these mutants were not affected by the host cell type as similar results were obtained in a range of different cells. Lastly, comparisons of the phenotypes of VV strains Western Reserve, deltaA34R and deltaA36R demonstrate that actin tails are not required for low pH-induced cell-cell fusion.
High field gradient targeting of magnetic nanoparticle-loaded endothelial cells to the surfaces of steel stents (2008)

A cell delivery strategy was investigated that was hypothesized to enable magnetic targeting of endothelial cells to the steel surfaces of intraarterial stents because of the following mechanisms: (i) preloading cells with biodegradable polymeric superparamagnetic nanoparticles (MNPs), thereby rendering the cells magnetically responsive; and (ii) the induction of both magnetic field gradients around the wires of a steel stent and magnetic moments within MNPs because of a uniform external magnetic field, thereby targeting MNP-laden cells to the stent wires. In vitro studies demonstrated that MNP-loaded bovine aortic endothelial cells (BAECs) could be magnetically targeted to steel stent wires. In vivo MNP-loaded BAECs transduced with adenoviruses expressing luciferase (Luc) were targeted to stents deployed in rat carotid arteries in the presence of a uniform magnetic field with significantly greater Luc expression, detected by in vivo optical imaging, than nonmagnetic controls.
A soluble multimeric recombinant CD2 protein identifies CD48 as a low affinity ligand for human CD2: divergence of CD2 ligands during the evolution of humans and mice. (1993)

To search for possible ligands of CD2 distinct from CD58 (lymphocyte function-associated antigen 3), we have produced a soluble pentameric CD2-immunoglobulin (Ig) fusion protein (spCD2) linking the 182-amino acid human CD2 extracellular segment with CH2-CH3-CH4 domains of human IgM heavy chain, thus enhancing the micromolar affinity of the CD2 monomer through multimeric interaction. Using quantitative immunofluorescence and standard stringency wash conditions, we observed that the binding of spCD2 to human B lymphoblastoid JY cells and red blood cells is virtually inhibited by anti-CD58 TS2/9 monoclonal antibody, even though these cells express levels of CD48 and CD59 comparable to CD58. Consistent with these results, spCD2 did not show any binding to Chinese hamster ovary (CHO) cells transfected with human CD48 or CD59. However, binding studies on CD48-, CD58-, or CD59-transfected CHO cells with spCD2 under low stringency wash conditions revealed that human CD48 is a low affinity ligand of human CD2 compared with CD58 (Kd approximately 10(-4) vs. approximately 10(-6) M, respectively). The findings are noteworthy given that in the murine system CD48 is the major ligand for CD2. No detectable binding was observed to CD59-transfected CHO cells despite a report suggesting that CD59 may bind to the human CD2 adhesion domain. Importantly, in cell-cell adhesion assays between CD2+ Jurkat T cells and CD48- or CD59-transfected CHO cells, there was no conjugate formation, whereas binding of Jurkat T cells to CD58-transfected CHO cells was readily detected. Collectively, our findings provide evidence for a conservation of the CD2-CD48 interaction in the human species that may be of limited, if any, functional significance. Given the importance of the CD2-CD48 interaction in the murine system and CD2-CD58 interaction in humans, it would appear that there has been a divergence of functional CD2 ligands during the evolution of humans and mice.
Layout impact on the performance of a locally strained PMOSFET (2005)

We present a study on the layout dependence of a SiGe S/D PMOSFET technology. While 65% increase in drive current is obtained for 45nm gate length transistors with large active areas, measurements and simulations show that this improvement may be seriously degraded when transistor dimensions, such as the source-drain length (L/sub s/d/) and the device width are further scaled. TDDB and NBTI measurements show that the oxide reliability is not degraded for this technology.
Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases (2007)

Human BSEP (ABCB11) mutations are the molecular basis for at least three clinical forms of liver disease, progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), and intrahepatic cholestasis of pregnancy (ICP). To better understand the pathobiology of these disease phenotypes, we hypothesized that different mutations may cause significant differences in protein defects. Therefore we compared the effect of two PFIC2 mutations (D482G, E297G) with two BRIC2 mutations (A570T and R1050C) and one ICP mutation (N591S) with regard to the subcellular localization, maturation, and function of the rat Bsep protein. Bile salt transport was retained in all but the E297G mutant. Mutant proteins were expressed at reduced levels on the plasma membrane of transfected HEK293 cells compared with wild-type (WT) Bsep in the following order: WT > N591S > R1050C approximately A570T approximately E297G >> D482G. Total cell protein and surface protein expression were reduced to the same extent, suggesting that trafficking of these mutants to the plasma membrane is not impaired. All Bsep mutants accumulate in perinuclear aggresome-like structures in the presence of the proteasome inhibitor MG-132, suggesting that mutations are associated with protein instability and ubiquitin-dependent degradation. Reduced temperature, sodium butyrate, and sodium 4-phenylbutyrate enhanced the expression of the mature and cell surface D482G protein in HEK293 cells. These results suggest that the clinical phenotypes of PFIC2, BRIC2, and ICP may directly correlate with the amount of mature protein that is expressed at the cell surface and that strategies to stabilize cell surface mutant protein may be therapeutic.
Site-specific phosphorylation of the middle molecular weight human neurofilament protein in transfected non-neuronal cells (1990)

We expressed the human midsized neurofilament subunit (NF-M) using genomic DNA in mouse L cells and showed that it is transcribed and translated into a protein capable of assembly into the cytoskeleton and of forming a filamentous network that colocalizes with the endogenous vimentin filaments. Moreover, human NF-M expressed in L cells is phosphorylated at sites within the multiphosphorylation repeat (MPR), i.e., the major sites of phosphorylation of NF-M in vivo. We also expressed a genomic construct lacking the MPR domain in the native molecule and showed that this MPR(-) protein also was expressed and formed a filamentous network despite diminished incorporation of radiolabeled phosphate. Two major conclusions emerged from the work described in this paper: human NF-M is translated, assembled, and phosphorylated at physiological sites without the need of any other specific neuronal proteins; phosphorylation sites other than the MPR are present within NF-M which may play a role in synthesis, assembly, and degradation of NF protein in humans.
Receptor-mediated Transcytosis of Lactoferrin through the Blood-Brain Barrier (1999)

Lactoferrin (Lf) is an iron-binding protein involved in host defense against infection and severe inflammation; it accumulates in the brain during neurodegenerative disorders. Before determining Lf function in brain tissue, we investigated its origin and demonstrate here that it crosses the blood-brain barrier. An in vitro model of the blood-brain barrier was used to examine the mechanism of Lf transport to the brain. We report that differentiated bovine brain capillary endothelial cells exhibited specific high (Kd = 37.5 nM; n = 90,000/cell) and low (Kd = 2 microM; n = 900,000 sites/cell) affinity binding sites. Only the latter were present on nondifferentiated cells. The surface-bound Lf was internalized only by the differentiated cell population leading to the conclusion that Lf receptors were acquired during cell differentiation. A specific unidirectional transport then occurred via a receptor-mediated process with no apparent intraendothelial degradation. We further report that iron may cross the bovine brain capillary endothelial cells as a complex with Lf. Finally, we show that the low density lipoprotein receptor-related protein might be involved in this process because its specific antagonist, the receptor-associated protein, inhibits 70% of Lf transport.
CATALYTIC REDUCTION OF NITRILES AND OXIMES (1928)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCATALYTIC REDUCTION OF NITRILES AND OXIMESWalter H. HartungCite this: J. Am. Chem. Soc. 1928, 50, 12, 3370–3374Publication Date (Print):December 1, 1928Publication History Published online1 May 2002Published inissue 1 December 1928https://pubs.acs.org/doi/10.1021/ja01399a033https://doi.org/10.1021/ja01399a033research-articleACS PublicationsRequest reuse permissionsArticle Views1498Altmetric-Citations79LEARN 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
Histopathologic characteristics of a chronic arteriovenous malformation in a swine model: preliminary study. (2000)

Nidus vessels in this chronic swine AVM model exhibited striking histologic changes similar to those seen in cerebral AVMs. The induced vessel growth seen angiographically and histologically in components of the chronic AVMs was consistent with the presence of persistently raised intravascular hemodynamic loads. This preliminary feasibility study suggests that the realistic histologic characteristics of this chronic AVM model are an attractive feature, and if confirmed in future, more comprehensive, studies would be of benefit in accurate histopathologic interpretation of the effects of superimposed experimental embolotherapy or radiosurgery. This model may provide a useful experimental tool to study the dynamic cellular and tissue events that dictate the development and natural history of AVMs.
Heme Protein Assemblies (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHeme Protein AssembliesCharles J. Reedy and Brian R. GibneyView Author Information Department of Chemistry, Columbia University, 3000 Broadway, MC 3121, New York, New York 10027 Cite this: Chem. Rev. 2004, 104, 2, 617–650Publication Date (Web):January 24, 2004Publication History Received20 June 2003Published online24 January 2004Published inissue 1 February 2004https://doi.org/10.1021/cr0206115Copyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views4848Altmetric-Citations318LEARN 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 InReddit Read OnlinePDF (1 MB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Bioinorganic chemistry,Ligands,Monomers,Peptides and proteins,Redox reactions Get e-Alerts
A prediction- and cost function-based algorithm for robust autonomous freeway driving (2010)

In this paper, a prediction- and cost function-based algorithm (PCB) is proposed to implement robust freeway driving in autonomous vehicles. A prediction engine is built to predict the future microscopic traffic scenarios. With the help of a human-understandable and representative cost function library, the predicted traffic scenarios are evaluated and the best control strategy is selected based on the lowest cost. The prediction- and cost function-based algorithm is verified using the simulator of the autonomous vehicle Boss from the DARPA Urban Challenge 2007. The results of both case tests and statistical tests using PCB show enhanced performance of the autonomous vehicle in performing distance keeping, lane selecting and merging on freeways.
Competitive interactions in Escherichia coli populations: the role of bacteriocins (2010)

Explaining the coexistence of competing species is a major challenge in community ecology. In bacterial systems, competition is often driven by the production of bacteriocins, which are narrow-spectrum proteinaceous toxins that serve to kill closely related species, providing the producer better access to limited resources. Bacteriocin producers have been shown to competitively exclude sensitive, nonproducing strains. However, the dynamics between bacteriocin producers, each lethal to its competitor, are largely unknown. In this study, we used in vitro, in vivo and in silico models to study competitive interactions between bacteriocin producers. Two Escherichia coli strains were generated, each carrying a DNA-degrading bacteriocin (colicins E2 and E7). Using reporter-gene assays, we showed that each DNase bacteriocin is not only lethal to its opponent but, at lower doses, can also induce the expression of its opponent's toxin. In a well-mixed habitat, the E2 producer outcompeted its adversary; however, in structured environments (on plates or in mice colons), the two producers coexisted in a spatially 'frozen' pattern. Coexistence occurred when the producers were initiated with a clumped spatial distribution. This suggests that a 'clump' of each producer can block invasion of the other producer. Agent-based simulation of bacteriocin-mediated competition further showed that mutual exclusion in a structured environment is a relatively robust result. These models imply that colicin-mediated colicin induction enables producers to successfully compete and defend their niche against invaders. This suggests that localized interactions between producers of DNA-degrading toxins can lead to stable coexistence of heterogeneously distributed strains within the bacterial community and to the maintenance of diversity.