gebhart/patrepeval huggingface dataset:
MR Enhancement in a Current Perpendicular-to-Plane Spin Valve by Insertion of a Ferromagnetic Layer Within the Spacer Layer (2006)

In this paper, we propose an alternative method to improve magnetoresistance by inserting a thin ferromagnetic (FM) layer into the nonmagnetic (NM) spacer of a basic spin-valve (SV) trilayer (FM1-NM-FM1), thus creating a penta-layer SV structure (FM1-NM-FM2-NM-FM1). We investigated the effect of increasing the resistivity (rho <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">F2</sub> ) of the FM2 on overall magnetoresistance (MR). We performed both analytical and numerical studies on the MR of the current perpendicular-to-plane (CPP) structure using the phenomenological spin drift-diffusion models. For finite rho <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">F2 </sub> , the MR profile is dependent on the intrinsic conductance polarization (alpha <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">F2</sub> ) of FM2. We found that inserting FM2 enhances MR when alpha <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">F2</sub> exceeds a critical value of alpha <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2C</sub> . It is found that MR can be doubled by inserting a FM layer with high alpha <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">F2</sub> , such as the half-metallic Cr <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O. We have numerically calculated MR <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> and the corresponding rho <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">F20</sub> values for different alpha <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">F2 </sub> values. Finally, we studied the effect of spin relaxation on the MR of the CPP SV
Metabolic Pathways That Mediate Inhibition of Hypothalamic Neurons by Glucose (2004)

Neurons in the ventromedial hypothalamus mediate some counterregulatory responses to hypoglycemia and 2-deoxyglucose, but the mechanisms that mediate these responses to glucose are unclear. In the present study, ventromedial hypothalamus neurons were identified on the basis of their inhibition by the transition from 5 to 20 mmol/l glucose. Tolbutamide, which activates glucose-stimulated neurons, failed to inhibit or activate glucose-inhibited neurons. Inhibitors of glucose transport and glycolysis, in particular by the glucokinase inhibitor glucosamine, blocked the effect of glucose on glucose-inhibited neurons. Furthermore, the glucose-inhibited neurons were activated by 2-deoxyglucose, which also activates counterregulatory responses. Conversely, glucose-inhibited neurons were inhibited by glycolytic metabolites, including lactate, but not by pyruvate. These data indicate that hypoglycemia induces electrical activity in glucose-inhibited neurons by attenuating glycolysis in those neurons. Thus, counterregulatory failure could be due to relatively enhanced glycolysis in glucose-stimulated neurons during hypoglycemia and attenuation of glycolysis in glucose-inhibited neurons might reverse counterregulatory failure.
Synthesis of the C7-C17 Segment of Epothilones by a 10-membered Ring Closing Metathesis Reaction (1998)

The synthesis of the C7-C17 segment of epothilones employing a ring closing metathesis is described. Our approach utilizes the stereoselective methylation of the 10-membered lactone, generated by ring closing metathesis, for introducing the methyl group at C8 and provides an efficient access to strained epothilone derivatives, as well as to the C7-C17 segment of epothilones.
ACE2: A New Target for Cardiovascular Disease Therapeutics (2007)

The discovery of angiotensin-converting enzyme 2 (ACE2) in 2000 is an important event in the renin-angiotensin system (RAS) story. This enzyme, an homolog of ACE, hydrolyzes angiotensin (Ang) I to produce Ang-(1-9), which is subsequently converted into Ang-(1-7) by a neutral endopeptidase and ACE. ACE2 releases Ang-(1-7) more efficiently than its catalysis of Ang-(1-9) by cleavage of Pro(7)-Phe(8) bound in Ang II. Thus, the major biologically active product of ACE2 is Ang-(1-7), which is considered to be a beneficial peptide of the RAS cascade in the cardiovascular system. This enzyme has 42% identity with the catalytic domain of ACE, is present in most cardiovascular-relevant tissues, and is an ectoenzyme as ACE. Despite these similarities, ACE2 is distinct from ACE. Since it is a monocarboxypeptidase, it has only 1 catalytic site and is insensitive to ACE inhibitors. As a result, ACE2 is a central enzyme in balancing vasoconstrictor and proliferative actions of Ang II with vasodilatory and antiproliferative effects of Ang-(1-7). In this review, we will summarize the role of ACE2 in the cardiovascular system and discuss the importance of ACE2-Ang-(1-7) axis in the control of normal cardiovascular physiology and ACE2 as a potential target in the development of novel therapeutic agents for cardiovascular diseases.
Three-Dimensional Structure of the Tn 5 Synaptic Complex Transposition Intermediate (2000)

Genomic evolution has been profoundly influenced by DNA transposition, a process whereby defined DNA segments move freely about the genome. Transposition is mediated by transposases, and similar events are catalyzed by retroviral integrases such as human immunodeficiency virus-1 (HIV-1) integrase. Understanding how these proteins interact with DNA is central to understanding the molecular basis of transposition. We report the three-dimensional structure of prokaryotic Tn5 transposase complexed with Tn5 transposon end DNA determined to 2.3 angstrom resolution. The molecular assembly is dimeric, where each double-stranded DNA molecule is bound by both protein subunits, orienting the transposon ends into the active sites. This structure provides a molecular framework for understanding many aspects of transposition, including the binding of transposon end DNA by one subunit and cleavage by a second, cleavage of two strands of DNA by a single active site via a hairpin intermediate, and strand transfer into target DNA.
Nucleotide sequence of a cyanobacterial nifH gene coding for nitrogenase reductase (1980)

The nucleotide sequence of nifH, the structural gene for nitrogenase reductase (component II or Fe protein of nitrogenase) from the cyanobacterium Anabaena 7120 has been determined. Also reported are 194 bases of the 5'-flanking sequence and 170 bases of the 3'-flanking sequence. The predicted amino acid sequence was compared with that determined for the complete nitrogenase reductase of Clostridium pasteurianum and the cysteine-containing peptides of the protein from Azotobacter vinelandii. Amino acid sequences around five cysteines, located in the NH(2)-terminal two-thirds of the protein, are highly conserved in all three species. Codon usage in the first gene from a cyanobacterium to be sequenced shows striking asymmetries for eight amino acids.
Improvement of Plasma Confinement on a Field-Reversed Configuration with Strong Mirror Field by Neutral Beam Injection (2001)

The first experiments of neutral beam (NB) injection into a field-reversed configuration (FRC) plasma have been performed at FIX (FRC Injection Experiment) device.1 The experimental results show that the configuration lifetime of a FRC have been expanded by about 200% compared with no NB injection case. These results indicate that several hundred kilo watts of NB injection saves several mega watts of global energy losses. For understanding these experimental phenomena, some numerical calculations have been performed. Numerically calculated ionization degree vs. distance along beam injection axis and beam trajectories show that the injected beam ions form dense regions around minimum │B│. These formed hot beam ions walls would play a role in improving these confinements on the edge layer. Some previous theoretical studies pointed out the existence of electrostatic effects in the FRC edge plasma confinements.6, 7 Since only several kilo watts NB injection improves FRC confinement, it seems that the injected hot beam ions encourage electrostatic effects on the edge layer.
Measurement of high piezoelectric response of strontium-doped lead zirconate titanate thin films using a nanoindenter (2007)

Strontium-doped lead zirconate titanate (PSZT) is reported to have a high piezoelectric coefficient (d33) in the range of 200−600 pm∕V, when in the form of ceramic disks or pellets. This article reports piezoelectric response results for PSZT thin films deposited by rf magnetron sputtering on gold-coated silicon substrates. The compositions of the deposited thin films have been found to be uniform with depth, using secondary ion mass spectroscopy. The surfaces of the deposited thin films have been studied using an atomic force microscope and observed to be regular and nanostructured in nature. The piezoelectric response of the thin films, using the inverse piezoelectric effect, has been measured using a nanoindenter. Values of thin film d33 up to 608 pm∕V were obtained, which is much higher than previously reported values of d33 for any thin film. The high values can be attributed to optimized deposition conditions and the low stress measured for the thin film arrangement on the substrate. The technique has been verified by obtaining a null response for silicon dioxide and by measuring d33 values of similar magnitude for PSZT thin films using an atomic force microscope in the same testing arrangement. The piezoelectric response has been mapped to study variations across the thin film and with distance from the top electrode.
Antineoplastic agents 389. New syntheses of the combretastatin A-4 prodrug. (1998)

Combretastatin A-4 (1) as the phosphate ester prodrug (3d) is a potent antineoplastic and antiangiogenesis substance and is in advanced preclinical development. For the purpose of improving the phosphorylation synthetic sequence from combretastatin A-4, new routes were investigated. The phosphorylation step was found to be considerably improved using in situ-generated dibenzyl chlorophosphite. Cleavage of the benzyl esters employing a trimethylchlorosilane/sodium iodide procedure, followed by treatment with sodium methoxide, led to the water-soluble prodrug (3d) in high yield.
ΔFosB: A sustained molecular switch for addiction (2001)

The longevity of some of the behavioral abnormalities that characterize drug addiction has suggested that regulation of neural gene expression may be involved in the process by which drugs of abuse cause a state of addiction. Increasing evidence suggests that the transcription factor DeltaFosB represents one mechanism by which drugs of abuse produce relatively stable changes in the brain that contribute to the addiction phenotype. DeltaFosB, a member of the Fos family of transcription factors, accumulates within a subset of neurons of the nucleus accumbens and dorsal striatum (brain regions important for addiction) after repeated administration of many kinds of drugs of abuse. Similar accumulation of DeltaFosB occurs after compulsive running, which suggests that DeltaFosB may accumulate in response to many types of compulsive behaviors. Importantly, DeltaFosB persists in neurons for relatively long periods of time because of its extraordinary stability. Therefore, DeltaFosB represents a molecular mechanism that could initiate and then sustain changes in gene expression that persist long after drug exposure ceases. Studies in inducible transgenic mice that overexpress either DeltaFosB or a dominant negative inhibitor of the protein provide direct evidence that DeltaFosB causes increased sensitivity to the behavioral effects of drugs of abuse and, possibly, increased drug seeking behavior. This work supports the view that DeltaFosB functions as a type of sustained "molecular switch" that gradually converts acute drug responses into relatively stable adaptations that contribute to the long-term neural and behavioral plasticity that underlies addiction.
Remodeling of the Myocardium and Potential Targets in the Collagen Degradation and Synthesis Pathways (2003)

Remodeling of the myocardium is the major mechanism for disability and death in prevalent cardiovascular diseases such as hypertension, heart failure and myocardial infarction (MI). It is a complex process that involves changes in structure, shape and topography at the global level and changes in myocytes and non-myocytes at cellular and subcellular levels that impact negatively on function. Although the myocytes subserve the heart's pump function, the predominant cell type in the heart is the fibroblast (not the myocyte). The fibroblast's major role is deposition of the extracellular matrix (ECM) of which collagen is the principal component. The cardiac extracellular collagen matrix (ECCM) maintains structural and functional integrity, and contributes to coordinated mechanical action with every systole during life. Excessive collagen deposition or pathological fibrosis is an important contributor to left ventricular (LV) dysfunction and poor outcome in hypertension, MI and heart failure. It is also an important problem in the aging heart. Antifibrotic agents that target steps in the collagen synthesis and degradation pathways therefore represent promising strategies for these diseases. Because reparative fibrosis is an essential component of healing of the infarct zone (IZ) after MI, the design of approaches that separately target the IZ and non-infarct zone (NIZ) is challenging. It may be possible in future to target the collagen pathways in the heart or regions of the heart, and not other areas or organs, by delivering drugs or genes locally to specific regions.
Sequential scalar quantization of color images (1994)

An efficient algorithm for color image quantization is proposed based on a new vector quantization technique that we call sequential scalar quantization. The scalar components of the 3-D color vector are individually quantized in a predetermined sequence. With this technique, the color palette is designed very efficiently, while pixel mapping is performed with no computation. To obtain an optimal allocation of quantization levels along each color coordinate, we appeal to the asymptotic quantization theory, where the number of quantization levels is assumed to be very large. We modify this theory to suit our application, where the number of quantization 1evels is typically small. To utilize the properties of the human visual system (HVS), the quantization is performed in a luminance-chrominance color space. A luminance-chrominance weighting is introduced to account for the greater sensitivity of the HVS to luminance than to chrominance errors. A spatial activity measure is also incorporated to reflect the increased sensitivity of the HVS to quantization errors in smooth image regions. The algorithm yields high-quality images and is significantly faster than existing quantization algorithms.
Involvement of Calcineurin in Transforming Growth Factor-β-mediated Regulation of Extracellular Matrix Accumulation (2004)

Calcineurin is a calcium-dependent, serine/threonine phosphatase that functions as a signaling intermediate. In this study, we investigated the role of calcineurin in transforming growth factor-beta (TGF-beta)-mediated cellular effects and examined the signaling pathway involved in activation of calcineurin. Calcineurin is activated by TGF-beta in a time- and dose-dependent manner. Consistent with increased phosphatase activity, the calcineurin substrate, NFATc1, is dephosphorylated and transported to the nucleus. Inhibition of calcineurin prior to the addition of TGF-beta revealed that calcineurin is required for TGF-beta-mediated accumulation of extracellular matrix (ECM) proteins but not cell hypertrophy. Conversely, overexpression of constitutively active calcineurin was sufficient to induce ECM protein expression. The mechanism of calcineurin activation by TGF-beta was found to be induction of a low, sustained increase of intracellular calcium. Chelation of extracellular calcium blocked both TGF-beta-mediated calcium influx and calcineurin activity. Finally, calcium entry was found to be dependent upon generation of reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide. Accordingly, inhibition of ROS generation also blocked TGF-beta-mediated calcineurin phosphatase activity and decreased ECM accumulation. In conclusion, this study describes a new pathway for TGF-beta-mediated regulation of ECM via generation of ROS, calcium influx, and activation of calcineurin.
Expression of Integrin αvβ3 in Gliomas Correlates with Tumor Grade and Is not Restricted to Tumor Vasculature (2008)

In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of alpha(v)beta(3) integrin caused by malignancy. The aim of our study was to assess the extent and pattern of alpha(v)beta(3) integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of alpha(v)beta(3) integrin and quantified by an imaging software. The expression of alpha(v)beta(3) was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of alpha(v)beta(3) integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the beta(3) integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of alpha(v)beta(3) integrin in gliomas and are of relevance for the inhibition of alpha(v)beta(3) integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth.
Preparation and Characterization of LiNi0.5Co0.5O2 and LiNi0.5Co0.4Al0.1O2 by Molten Salt Synthesis for Li Ion Batteries (2007)

The layer compounds LiNi0.5Co0.5O2 and LiNi0.5Co0.4Al0.1O2 were prepared by using the molten salt of the eutectic mixture LiNO3−LiCl at temperatures of 750 and 850 °C in air. They were characterized by X-ray diffraction, Rietveld refinement, SEM, EDAX, chemical analysis, surface area, and density techniques. Cathodic behavior was examined at ambient temperature by cyclic voltammetry, charge−discharge cycling, and impedance spectra in cells with Li−metal as the counter electrode at a current rate of 30 mAg-1 with a lower cutoff voltage of 2.5 V up to 120 cycles. The upper cutoff voltages ranged from 4.2 to 4.5 V. The 10th cycle reversible capacities for LiNi0.5Co0.5O2 varied from 131 to 186(±3) mAhg-1 depending on the upper cutoff voltage, but capacity fading occurred ranging from 5 to 18% at the end of 50 or 80 cycles. The Al-doped compound showed a 20th cycle reversible capacity of 146 (±3) mAhg-1 (4.3 V cutoff) which was stable up to 120 cycles. Good rate capability was also observed. Thus, LiNi0.5Co0.4Al0.1O2 with only 0.4 mol of cobalt is a cheaper and viable alternative to the presently used cathode, LiCoO2. Impedance spectra on cells cycled up to 60 cycles with 4.3 V cutoff have been analyzed and interpreted.
A Dual PIM 1/3 Kinase Inhibitor Demonstrates Efficacy in Murine Models of Lupus and Multiple Sclerosis (119.9) (2012)

Abstract PIM kinases are a family of 3 intracellular serine/threonine kinases, and have been shown to be uniquely regulated at the level of expression rather than by upstream phosphorylation. The PIMs are STAT-induced proteins and function as a key signaling node downstream of multiple cytokine, growth factor and oncogene pathways. Here we report the in vivo efficacy in mice of a small molecule PIM kinase inhibitor, AR317, in NZB/NZW Lupus, MOG EAE, and relapsing remitting EAE models. AR317 is a selective and potent inhibitor of PIM-1 and PIM-3 kinases in both the enzyme (IC50 = 0.2 nM PIM-1 and 0.5 nM PIM-3) and cellular setting (EC50 = 21 nM). Administered orally twice daily at 3, 10, and 30 mg/kg to NZB/NZW mice, AR317 afforded dose-responsive improvements in proteinuria, with normalization to base line at 30 mg/kg. Improvements in disease indices were also observed including reductions in spleen and kidney weights, increase in hematocrit, decreases in lymphocyte and neutrophil counts. In a mouse SJL MOG (35-55) EAE model, AR317 (70 mg/kg, BID) produced a significant reduction in ataxia over the course of the study. When dosed in the SJL/J PLP(139-151) mouse model of relapsing remitting EAE, AR317 exhibited marked efficacy vs. ataxia, with reductions in cumulative relapse scores at both 30 mg/kg and 90 mg/kg. These data support the hypothesis that a small molecule PIM 1/3 kinase inhibitor may provide efficacy for patients suffering from lupus or multiple sclerosis.
Mechanism of action of adenosylcobalamin: glycerol and other substrate analogs as substrates and inactivators for propanediol dehydratase - kinetics, stereospecificity, and mechanism (1977)

A number of vicinal diols were found to react with&#13;\npropanediol dehydratase, typically resulting in the conversion&#13;\nof enzyme-bound adenosylcobalamin to cob(Il)alamin and&#13;\nformation of aldehyde or ketone derived from substrate.&#13;\nMoreover, all are capable of effecting the irreversible inactivation&#13;\nof the enzyme. The kinetics and mechanism of product&#13;\nformation and inactivation were investigated. Glycerol, found&#13;\nto be a very good substrate for diol dehydratase as well as a&#13;\npotent inactivator, atypically, did not induce cob(II)alamin&#13;\nformation to any detectable extent. With glycerol, the inactivation&#13;\nprocess was accompanied by conversion of enzymebound&#13;\nadenosylcobalamin to an alkyl or thiol cobalamin,&#13;\nprobably by substitution of an amino acid side chain near the&#13;\nactive site for the 5'-deoxy-5'-adenosyl ligand on the cobala-min. The inactivation reaction with glycerol as the inactivator&#13;\nexhibits a deuterium isotope effect of 14, strongly implicating&#13;\nhydrogen transfer as an important step in the mechanism of&#13;\ninactivation. The isotope effect on the rate of product formation&#13;\nwas found to be 8.0. Experiments with isotopically substituted&#13;\nglycerols indicate that diol dehydrase distinguishes between&#13;\n"R" and "S" binding conformations, the enzyme-(R)-glycerol&#13;\ncomplex being predominately responsible for the productforming&#13;\nreaction, while the enzyme-(S)-glycerol complex&#13;\nresults primarily in the inactivation reaction. Mechanistic&#13;\nimplications are discussed. A method for removing enzymebound&#13;\nhydroxycobalamin that is nondestructive to the enzyme&#13;\nand a technique for measuring the binding constants of (R) and&#13;\n(S)-1,2-propanediols are presented.