gebhart/patrepeval huggingface dataset:
Dephosphorylation specificities of protein phosphatase for cardiac troponin I, troponin T, and sites within troponin T (2006)

Protein dephosphorylation by protein phosphatase 1 (PP1), acting in concert with protein kinase C (PKC) and protein kinase A (PKA), is a pivotal regulatory mechanism of protein phosphorylation. Isolated rat cardiac myofibrils phosphorylated by PKC/PKA and dephosphorylated by PP1 were used in determining dephosphorylation specificities, Ca(2+)-stimulated Mg(2+)ATPase activities, and Ca(2+) sensitivities. In reconstituted troponin (Tn) complex, PP1 displayed distinct substrate specificity in dephosphorylation of TnT preferentially to TnI, in vitro. In situ phosphorylation of cardiomyocytes with calyculin A, a protein phosphatase inhibitor, resulted in an increase in the phosphorylation stiochiometry of TnT (0.3 to 0.5 (67%)), TnI (2.6 to 3.6 (38%)), and MLC2 (0.4 to 1.7 (325%)). These results further confirmed that though MLC2 is the preferred target substrate for protein phosphatase in the thick filament, the Tn complex (TnI and TnT) from thin filament and C-protein in the thick filament are also protein phosphatase substrates. Our in vitro dephosphorylation experiments revealed that while PP1 differentially dephosphorylated within TnT at multiple sites, TnI was uniformly dephosphorylated. Phosphopeptide maps from the in vitro experiments show that TnT phosphopeptides at spots 4A and 4B are much more resistant to PP1 dephosphorylation than other TnT phosphopeptides. Mg(2+)ATPase assays of myofibrils phosphorylated by PKC/PKA and dephosphorylated by PP1 delineated that while PKC and PKA phosphorylation decreased the Ca(2+)-stimulated Mg(2+)ATPase activities, dephosphorylation antagonistically restored it. PKC and PKA phosphorylation decreased Ca(2+) sensitivity to 3.6 microM and 5.0 microM respectively. However, dephosphorylation restored the Mg(2+)ATPase activity of PKC (99%) and PKA (95%), along with the Ca(2+) sensitivities (3.3 microM and 3.0 microM, respectively).
ChemInform Abstract: Fragmentation of Optically Active (1‐Phenylethyl)‐ and (1‐Naphthylethyl)ureas in Refluxing Alcohols: Easy Preparation of Optically Active Amines of High Optical Purity. (1986)

Abstract The racemic drug mecamylamine (I) can be efficiently resolved by reaction with the optically active isocyanate (IVa) followed by refluxing the separated products (IIa) or (IIb) with ethanol [→ (IIIa), (IIIb)].
Bistatic synthetic aperture radar inversion with application in dynamic object imaging (1991)

An inversion method is presented for bistatic synthetic aperture radar imaging. The method is based on a Fourier analysis (Doppler processing) of the bistatic synthesized array's data followed by a phase modulation analysis of the Doppler data. The approach incorporates the phase information of the wavefront curvature in the transmitted waves as well as the resultant echoed signals. The Doppler data are shown to provide samples of the reflectivity function's spatial Fourier transform within a band that depends upon the bistatic angles and ranges. Associated resolution, reconstruction, and sampling constraints for the imaging problem are discussed. The bistatic SAR inversion is also utilized to formulate an inversion for multistatic measurements made along a physical linear array due to a single transmission to image a dynamic object.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Enriching Assembly CAD Models With Functional and Mechanical Informations to Ease CAE (2010)

Assembly models can be regarded as a kernel for product development processes where they can efficiently contribute to many product simulation behaviors. Assembly models are often containing 3D B-Rep CAD models, possibly with geometric constraints between the components and bill of materials. However, these models are often difficult to process for simulations because algorithms often face a very large diversity of configurations. One origin of such difficulties can be found in companies’ practice where components may be represented differently from one company to another and their interfaces as well. In any case, interfaces between components are not explicit, which leads to tedious model processing tasks. This paper illustrates preparation of assembly models to ease CAE through an analysis of company practices, showing that a concept of conventional representations is an important starting point to efficient treatments of assemblies. In addition, it is described how interfaces and conventional representations can be combined to derive functional and mechanical information from geometric models of components. Illustrations of the proposed approach is given throughout the paper using various standard components.
Characterization of cDNA clones for human glycophorin A (1988)

Glycophorin A is the major membrane sialoglycoprotein of human erythrocytes and represents a typical example of a transmembrane glycoprotein. The functional role of this cell-surface component is not known but it represents a receptor for viruses, bacteria and parasites like Plasmodium falciparum. 1. Two cDNA clones encoding glycophorin A have been characterized from human fetal cDNA libraries. The longer cDNA extended from the coding region of glycophorin A (residues 4-131) to the 3' untranslated region which included two polyadenylation signals and a poly(A) tail. 2. The structural gene for glycophorin A is located on chromosome 4, q28-q31 as shown by in situ hybridization, thus confirming the previous localization by genetic linkage analysis. 3. Three distinct mRNA species (1.0 kb, 1.7 kb and 2.2 kb) have been identified in erythroid spleen. Northern blot analyses with a probe directed against the 3' untranslated region of the mRNAs indicated that all these species share a homologous 3' non-coding region and that the first polyadenylation signal downstream the stop codon is not used. 4. Preliminary studies by Southern blot analysis of the genomic DNA from normal En(a+) and rare En(a-) donors suggest that the glycophorin A gene has a complex organization and is largely deleted in donors of the En(a-) phenotype (Finnish type) who lack glycophorin A on their red cells.
Is Africa suffering a leadership crisis (2010)

On Monday the 19th October 2009, the Mo Ibrahim Foundation announced the decision not to award the Ibrahim Prize for Good Governance. Established in October 2006, the Mo Ibrahim Foundation endeavours to support embedment of good governance in Africa through : stimulating debate on good governance across sub-Saharan Africa and the world; providing objective criteria by which citizens can hold their Governments accountable; recognising achievement in African leadership and providing a practical way in which African leaders can build positive legacies on the continent when they have left office; and support aspiring leaders for the African continent. Of these, the achievement of leadership award and the Ibrahim Index of African Governance which ranks African countries on governance quality have gained relatively more attention and notoriety. Since inception, the leadership award has been given two times (Joaquim Chissano of Mozambique (2007) and Festus Mogae of Botswana (2008)). Nelson Mandela was also named honorary laureate (2007).
Superconducting fiber (2013)

In this study, we demonstrated superconductivity in a fiber with a lead core and fused silica cladding. The fibers were fabricated via a melt-draw technique and maintained overall diameters ranging from 200-900 mu m and core diameters of 100-800 mu m. Superconductivity of this fiber design was validated via the traditional four probe test method in a bath of liquid helium at temperatures on the order of 4 K. The superconducting fiber paves the way for applications in power transmission, magnetic sensing, and fundamental studies in the fields of electromagnetism. (C) 2013 AIP Publishing LLC.
Cyber security analysis of state estimators in electric power systems (2010)

In this paper, we analyze the cyber security of state estimators in Supervisory Control and Data Acquisition (SCADA) systems operating in power grids. Safe and reliable operation of these critical infrastructure systems is a major concern in our society. In current state estimation algorithms there are bad data detection (BDD) schemes to detect random outliers in the measurement data. Such schemes are based on high measurement redundancy. Although such methods may detect a set of very basic cyber attacks, they may fail in the presence of a more intelligent attacker. We explore the latter by considering scenarios where deception attacks are performed, sending false information to the control center. Similar attacks have been studied before for linear state estimators, assuming the attacker has perfect model knowledge. Here we instead assume the attacker only possesses a perturbed model. Such a model may correspond to a partial model of the true system, or even an out-dated model. We characterize the attacker by a set of objectives, and propose policies to synthesize stealthy deceptions attacks, both in the case of linear and nonlinear estimators. We show that the more accurate model the attacker has access to, the larger deception attack he can perform undetected. Specifically, we quantify trade-offs between model accuracy and possible attack impact for different BDD schemes. The developed tools can be used to further strengthen and protect the critical state-estimation component in SCADA systems.
Characterization of a Stable Form of Tryptophan Hydroxylase from the Human Parasite Schistosoma mansoni (1999)

A cDNA (Schistosoma mansoni tryptophan hydroxylase; SmTPH) encoding a protein homologous to tryptophan hydroxylase, the enzyme that catalyzes the rate-limiting step in the biosynthesis of serotonin, was cloned from the human parasite Schistosoma mansoni. Bacterial expression of SmTPH as a histidine fusion protein produced soluble active enzyme, which was purified to apparent homogeneity and a final specific activity of 0.17 micromol/min/mg of protein. The purified enzyme was found to be a tetramer of approximately 240 kDa with a subunit size of 58 kDa. Several of the biochemical and kinetic properties of SmTPH were similar to those of mammalian tryptophan hydroxylase. Unlike the mammalian enzyme, however, SmTPH was found to be stable at 37 degrees C, its t((1)/(2)) being nearly 23 times higher than that of a similarly expressed rabbit tryptophan hydroxylase. A semiquantitative reverse transcription polymerase chain reaction showed that the level of SmTPH mRNA in a larval stage of the parasite (cercaria) is 2.5 times higher than in adult S. mansoni, suggesting possible differences in the level of enzyme expression between the two developmental stages. This study demonstrates for the first time the presence of a functional tryptophan hydroxylase in a parasitic helminth and further suggests that the parasites are capable of synthesizing serotonin endogenously.
A PARALLEL ARCHITECTURE FOR AI NONLINEAR PLANNING (1990)

This paper presents a resource-level conflict detection and conflict resolution scheme which is combined with a state-level backward planning algorithm and provides efficient conflict detection and global conflict resolution for nonlinear planning. The scheme keeps track of the usage of individual resources during planning, and constructs a Resource-Usage Flow (RUF) structure (based on which conflict detection and resolution is accomplished). The RUF structure allows the system to perform minimal and nonredundant operations for conflict detection and resolution. Furthermore, resource-level conflict detection and resolution facilitates problem decomposition in terms of resources, thereby providing easy implementation in a parallel and distributed processing environment. Performance analysis indicates that the proposed architecture has a speed-up factor of the average depth of a plan network, D(N a ), compared to the distributed NOAH, where N a (the total number of action nodes at the completion of planning) and D(N a ) are considerably larger than the number of resources involved in planning as well as the number of initial goal states.
IL-4 enhances expression and function of surface IgM in CLL cells (2016)

Kinase inhibitors targeting the B-cell receptor (BCR) are now prominent in the treatment of chronic lymphocytic leukemia (CLL). We have focused here on interleukin 4 (IL-4), a cytokine that protects normal and malignant B cells from apoptosis and increases surface immunoglobulin M (sIgM) expression on murine splenic B cells. First, we have demonstrated that IL-4 treatment increased sIgM expression in vitro on peripheral blood B cells obtained from healthy individuals. In CLL, IL-4 target genes are overexpressed in cells purified from the lymph nodes of patients compared with cells derived from matched blood and bone marrow samples. As for normal B cells, IL-4 increased sIgM expression on CLL cells in vitro, especially in samples expressing unmutated V-genes. IL-4-induced sIgM expression was associated with increased receptor signalling activity, measured by anti-IgM-induced calcium mobilization, and with increased expression of CD79B messenger RNA and protein, and the "mature" glycoform of sIgM. Importantly, the ability of the BCR-associated kinase inhibitors idelalisib and ibrutinib, approved for treatment of CLL and other B-cell malignancies, to inhibit anti-IgM-induced signalling was reduced following IL-4 pretreatment in samples from the majority of patients. In contrast to stimulatory effects on sIgM, IL-4 decreased CXCR4 and CXCR5 expression; therefore, CLL cells, particularly within the progressive unmutated V-gene subset, may harness the ability of IL-4 to promote BCR signalling and B-cell retention within lymph nodes. Effects of IL-4 were mediated via JAK3/STAT6 and we propose a potential role for JAK inhibitors in combination with BCR kinase inhibitors for the treatment of CLL.
Improving the length-fractionation of DNA during capillary electrophoresis (2001)

The present study develops a path-lengthening strategy for capillary electrophoresis of short double-stranded DNA molecules, in an aqueous solution of neutral polymer (hydroxypropylmethylcellulose). Tests of the dependence of fractionations on pulse times reveal the operation of at least one mechanism in addition to increase in effective path length. Electrophoresis is performed in the following two-stage cycles (cyclic electrophoresis): The first analysis-stage of each cycle is a constant field (forward) capillary electrophoresis. This analysis-stage reveals the length distribution of the shortest DNA molecules not previously analyzed. The second, enhancement-stage of each cycle is zero-integrated field electrophoresis (ZIFE). The enhancement-stage improves the DNA length-fractionation for the next DNA molecules to be analyzed. A slight reverse migration occurs in the enhancement-stage. Increase in both peak separation and peak sharpness contribute to improvement in the length-fractionation of DNA molecules.
Randomized Distributed Edge Coloring via an Extension of the Chernoff--Hoeffding Bounds (1997)

Certain types of routing, scheduling, and resource-allocation problems in a distributed setting can be modeled as edge-coloring problems. We present fast and simple randomized algorithms for edge coloring a graph in the synchronous distributed point-to-point model of computation. Our algorithms compute an edge coloring of a graph G with n nodes and maximum degree $\Delta$ with at most $1.6 \Delta + O(\log^{1+ \delta} n)$ colors with high probability (arbitrarily close to 1) for any fixed $\delta > 0$; they run in polylogarithmic time. The upper bound on the number of colors improves upon the $(2 \Delta - 1)$-coloring achievable by a simple reduction to vertex coloring. To analyze the performance of our algorithms, we introduce new techniques for proving upper bounds on the tail probabilities of certain random variables. The Chernoff--Hoeffding bounds are fundamental tools that are used very frequently in estimating tail probabilities. However, they assume stochastic independence among certain random variables, which may not always hold. Our results extend the Chernoff--Hoeffding bounds to certain types of random variables which are not stochastically independent. We believe that these results are of independent interest and merit further study.
A Convenient Procedure for the Preparation of Levoglucosenone and Its Conversion to Novel Chiral Derivatives (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: II. In vitro analyses of host effector mechanisms (1989)

To identify mechanisms potentially contributing to graft failure, 19 leukemic recipients of T-cell-depleted marrow transplants who failed to engraft following a transplant of HLA identical sibling marrow depleted of T cells by soybean agglutinin (SBA) and sheep erythrocytes (E) were evaluated. Peripheral blood mononuclear cells isolated at the time of failure were consistently of host origin, bearing the phenotype of suppressor T cells (CD3+, CD8+, Leu 7+). A direct cytolytic effect on 51Cr-labeled donor-derived target cells was not detected, a finding that contrasts with the donor-specific cytotoxic host T lymphocytes that have been regularly observed in patients rejecting HLA nonidentical SBA -E- BMTs. However, these host T cells did exhibit a strong and specific suppressive activity against the donor marrow CFU- GM in vitro. Furthermore, in contrast to prior findings in durably engrafted recipients of SBA -E- BMTs, the lymphocytes isolated prior to or at the time of graft failure lacked natural killer surface antigen expression and effector function.
Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells (2016)

Most breast cancer-related deaths from triple-negative breast cancer (TNBC) occur following metastasis of cancer cells and development of tumors at secondary sites. Because TNBCs lack the three receptors targeted by current chemotherapeutic regimens, they are typically treated with extremely aggressive and highly toxic non-targeted treatment strategies. Women with TNBC frequently develop metastatic lesions originating from drug-resistant residual cells and have poor prognosis. For this reason, novel therapeutic strategies that are safer and more effective are sought. Luteolin (LU) is a naturally occurring, non-toxic plant compound that has proven effective against several types of cancer. With this in mind, we conducted in vivo and in vitro studies to determine whether LU might suppress metastasis of TNBC. In an in vivo mouse metastasis model, LU suppressed metastasis of human MDA-MB-435 and MDA-MB-231 (4175) LM2 TNBC cells to the lungs. In in vitro assays, LU inhibited cell migration and viability of MDA-MB-435 and MDA-MB-231 (4175) LM2 cells. Further, LU induced apoptosis in MDA-MB-231 (4175) LM2 cells. Relatively low levels (10 µM) of LU significantly inhibited vascular endothelial growth factor (VEGF) secretion in MDA-MB-231 (4175) LM2 cells, suggesting that it has the ability to suppress a potent angiogenic and cell survival factor. In addition, migration of MDA-MB-231 (4175) LM2 cells was inhibited upon exposure to an antibody against the VEGF receptor, KDR, but not by exposure to a VEGF<sub>165</sub> antibody. Collectively, these data suggest that the anti-metastatic properties of LU may, in part, be due to its ability to block VEGF production and KDR-mediated activity, thereby inhibiting tumor cell migration. These studies suggest that LU deserves further investigation as a potential treatment option for women with TNBC.
Introduction to Photoelectron Spectroscopy (1983)

Experimental Techniques. Core Electron Spectra. Valence Electron Spectra. Spectra From Solids and Surfaces. Photo Ionization Cross Sections and Quantitative Analytical Applications. Angular Distribution of Photoelectrons. References and Notes. Index.
Discovery of 1-{4-[1-(2,6-Difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3- <i>d</i> ]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a Potent, Orally Active, Non-Peptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor (2011)

We previously discovered an orally active human gonadotropin-releasing hormone (GnRH) receptor antagonist, thieno[2,3-d]pyrimidine-2,4-dione derivative 1 (sufugolix). To reduce the cytochrome P450 (CYP) inhibitory activity and improve in vivo GnRH antagonistic activity, further optimization of this scaffold was carried out. We focused our synthetic efforts on chemical modification at the 5 and 3 positions of the thieno[2,3-d]pyrimidine-2,4-dione ring based on computational modeling, which resulted in the discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (16b) as a highly potent and orally active GnRH antagonist. Compound 16b showed potent in vitro GnRH antagonistic activity in the presence of fetal bovine serum (FBS) without CYP inhibition. Oral administration of 16b maintained the suppressive effect of the plasma luteinizing hormone levels in castrated cynomolgus monkeys at a 3 mg/kg dose for more than 24 h. Compound 16b is currently under clinical development with the code name of TAK-385.
A Conceptual Basis for Defibrillation Waveforms (1996)

A model is developed for defibrillation that treats the heart as a first order time constant. Such a model allows ready evaluation of different monophasic waveforms. For implantable devices where the voltage is provided by the discharge of a capacitor, it can be seen that the effective voltage within the heart rises rapidly to a peak and then decays to zero. The time interval at which this peak occurs is defined as the optimal duration, and there is no advantage in extending the pulse beyond this point. Characteristics are presented that show how the time course of this voltage within the heart changes with different device capacitors and load impedances. The effect of different heart time constant are also examined. For biphasic waveforms, a contour plot of threshold voltage is presented with phase 1 and phase 2 durations on the two axes. It is seen that there is a region of reliable low threshold defibrillation from 3.5/1.5 ms to 9/6 ms.