gebhart/patrepeval huggingface dataset:
Conformationally Restrained Ceramide Analogues: Effects of Lipophilic Modifications on the Antiproliferative Activity. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Insulin‐like growth factor‐1 abrogates microglial oxidative stress and <scp>TNF</scp>‐α responses to spreading depression (2013)

Spreading depression (SD), the most likely cause of migraine aura and perhaps migraine, occurs with increased oxidative stress (OS). SD increases reactive oxygen species (ROS), and ROS, in turn, can signal to increase neuronal excitability,which includes increased SD susceptibility. SD also elevates tumor necrosis factor-α (TNF-α), which increases neuronal excitability. Accordingly, we probed for the cellular origin of OS from SD and its relationship to TNF-α, which might promote SD, using rat hippocampal slice cultures. We observed significantly increased OS from SD in astrocytes and microglia but not in neurons or oligodendrocytes. Since insulin-like growth factor-1 (IGF-1) mitigates OS from SD, we determined the cell types responsible for this effect. We found that IGF-1 significantly decreased microglial but not astrocytic OS from SD. We also show that IGF-1 abrogated the SD-induced TNF-α increase. Furthermore, TNF-α application increased microglial but not astrocytic OS, an effect abrogated by IGF-1. Next,we showed that SD increased SD susceptibility, and does so via TNF-α. This work suggests that microglia promote SD via increased and interrelated ROS and TNF-α signaling. Thus, IGF-1 mitigation of microglial ROS and TNF-α responses maybe targets for novel therapeutics development to prevent SD, and perhaps migraine.
<i>EGFR</i> and <i>HER3</i> mRNA expression levels predict distant metastases in locally advanced rectal cancer (2010)

Aberrant activation of the HER signaling pathways plays a critical role in the invasive and metastatic potential of tumors. The aim of this study was to address whether, in rectal cancer, alterations of these pathways could have a value as prognostic factors to be used to identify patients who are at risk of distant metastases. Therefore, the mRNA expression of the four members of the HER family as well as the frequency of PTEN allelic loss and KRAS/BRAF mutations were determined in pretreatment biopsies from a series of 100 locally advanced rectal cancers and then their ability to predict distant metastases was evaluated. Over-expression of EGFR (p = 0.021), HER2 (p = 0.011) and HER3 (p = 0.020) was significantly associated with worse metastasis-free survival in univariate analysis. In multivariate analysis, both over-expression of EGFR (p = 0.028) and HER3 (p = 0.011) remained independent prognostic factors for distant metastasis. In conclusion, quantification of EGFR and HER3 mRNA expression in pretreatment biopsies may be useful to identify patients who are at risk of developing metastases.
Passive magnetic bearings with permanent magnets (1978)

The various geometrical dispositions which allow to realize passive magnetic bearings with permanent magnets, have been Known for several decades. Devices running by attraction were the first to be built. When new magnets, which can be used in repulsion appeared on the market (SmCo <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</inf> ), new types of passive magnetic bearings, running by repulsion, started to be made. Up to now, to our knowledge, most of the devices realized have been made with radially magnetized rings. We proved that for identically shaped bearings, strengths and stiffnesses were exactly the same in both magnetic configurations : radial and axial magnetization. The proof is only based on the rigidity of the magnetization. These results are still true for axial or radial passive bearings, and can also be used for devices in attraction. Ring shaped magnets with radial magnetization are usually made of several sectors stuck together. Axial magnetization is much easier to manufacture because large sized rings are already industrially provided.
Correlations Between the Charge of Proteins and the Number of Ionizable Groups They Incorporate:  Studies Using Protein Charge Ladders, Capillary Electrophoresis, and Debye−Hückel Theory (1999)

The values of electrophoretic mobility, μelectro, of bovine carbonic anhydrase II, human carbonic anhydrase II, cytochrome c, lysozyme, superoxide dismutase, ovalbumin, and derivatives of these proteins produced by partial neutralization of Lys ε-NH3+ and/or Asp and Glu carboxyl groups were measured using capillary electrophoresis (CE). For derivatives of these proteins with the lowest overall values of net charge (either positive or negative), the values of μelectro and the values of charge measured by CE, ZCE, demonstrate a linear correlation with the number of charged groups, n, converted to neutral derivatives. For derivatives of these proteins with larger values of net charge, the values of μelectro and ZCE demonstrate a nonlinear correlation with n. Several observations made in this work suggest that shifts in the values of pka of the ionizable groups on these proteins likely contribute to the observed nonlinear correlation. Debye−Hückel theory was used to calculate values of electrostatic potential at the surface of the derivatives of all six proteins from the measured values of μelectro. These values were plotted against the values of electrostatic potential calculated by assigning a charge to each protein in direct proportion to n. The data for all six proteins fell along a single common curve, regardless of the concentration of monovalent cations in the electrophoresis buffer.
Sold Downstream: Free Speech, Fair Use, and Anti-Circumvention Law (2007)

[Excerpt] “Here’s a hypo. Living in Asia, I purchased a shameful amount of music and movies, all legit purchases through reputable stores, HMV and Tower Records, but little of which will get reissued. I wanted to preserve my collection but software in the discs prevented me from ripping backup copies to my computer. Lacking the technological savvy to get around this software myself, I purchased and used a product to help me circumvent these controls. Discuss. Courts agree that copying the music and movies here is infringement but that fair use may provide a defense. However, courts do not agree as to whether or not fair use provides a defense when determining the liability of selling products that enable me to access and copy my CDs to my computer. This article examines a line of cases in the Ninth Circuit that hold that fair use or lawfulness of copying is irrelevant in calculating liability under the Digital Millennium Copyright Act (DMCA) and another line of cases in the Federal Circuit which hold that fair use should be relevant. In particular, this article argues that calculating fair use into the analysis is crucial in maintaining the balance between the First Amendment’s protection of free speech rights and copyright’s regulation of speech. Part I will outline the relationship between free speech rights and copyrights, noting the important role that fair use plays in keeping this relationship harmonious. Part II will outline the anti-circumvention provisions in the Digital Millennium Copyright Act and argue that these broad brush provisions chill speech. Part III will discuss two streams in the current law: first, the Ninth Circuit’s decisions 321 Studios v. Metro Goldwyn Mayer Studios, Inc.1 and Sony Computer Entertainment America, Inc. v. Divineo; 2 and, second, the Federal Circuit’s decisions in The Chamberlain Group, Inc. v. Skylink Technologies, Inc.3 and Storage Technology Corporation v. Custom Hardware Engineering & Consulting, Inc.4 Part IV will argue that the Federal Circuit’s approach to fair use is favored. However, an alternate analysis toward their conclusion would have more constitutional integrity. Namely, the DMCA, as applied to software, should be seen as a content-based restriction on speech and should not be read to prohibit circumvention of access controls where the circumvention would not constitute a copyright violation.”
Exploring a 2-Naphthoic Acid Template for the Structure-Based Design of P2Y<sub>14</sub>Receptor Antagonist Molecular Probes (2014)

The P2Y14 receptor (P2Y14R), one of eight P2Y G protein-coupled receptors (GPCR), is involved in inflammatory, endocrine, and hypoxic processes and is an attractive pharmaceutical target. The goal of this research is to develop high-affinity P2Y14R fluorescent probes based on the potent and highly selective antagonist 4-(4-(piperidin-4-yl)-phenyl)-7-(4-(trifluoromethyl)-phenyl)-2-naphthoic acid (6, PPTN). A model of hP2Y14R based on recent hP2Y12R X-ray structures together with simulated antagonist docking suggested that the piperidine ring is suitable for fluorophore conjugation while preserving affinity. Chain-elongated alkynyl or amino derivatives of 6 for click or amide coupling were synthesized, and their antagonist activities were measured in hP2Y14R-expressing CHO cells. Moreover, a new Alexa Fluor 488 (AF488) containing derivative 30 (MRS4174, Ki = 80 pM) exhibited exceptionally high affinity, as compared to 13 nM for the alkyne precursor 22. A flow cytometry assay employing 30 as a fluorescent probe was used to quantify specific binding to P2Y14R. Known P2Y receptor ligands inhibited binding of 30 with properties consistent with their previously established receptor selectivities and affinities. These results illustrate that potency in this series of 2-naphthoic acid derivatives can be preserved by chain functionalization, leading to highly potent fluorescent molecular probes for P2Y14R. Such conjugates will be useful tools in expanding the SAR of this receptor, which still lacks chemical diversity in its collective ligands. This approach demonstrates the predictive power of GPCR homology modeling and the relevance of newly determined X-ray structures to GPCR medicinal chemistry.
Polymer electrolyte membranes prepared by blending of poly(vinyl alcohol)-poly(ethylene oxide) for lithium battery application (2015)

Recently, the battery industry has represented one important and growing sector where the use of non-toxic and non-hazardous substitute materials has not rapidly developed. The environmentally friendly polymer electrolyte is required to decrease the risk of environmental pollution caused by toxic materials of battery components. Therefore, in this study was focused on the preparation of the environmentally friendly low cost polymer electrolyte membrane for lithium-ion battery applications. The preparation of polymer electrolyte membrane was done by casting of polymer solution. Polymer electrolyte membrane was prepared by mixing poly(vinyl alcohol) (PVA), poly(ethylene oxide) (PEO), and LiClO4 with various compositions, and each component of was separately dissolved in demineralized water. Polymer solution was stirred until homogeneous, the solution was then poured onto a petri dish, and the solvent was evaporated to form the film/membrane. The characterizations of polymer electrolyte membranes were carried out by using FTIR for functional group, Impedance Spectroscopy (IS) used for ionic conductivity, Autograph for mechanical strength, and Optical microscope for surfaces morphology. The optimal ionic conductivity was obtained on the membrane with PVA/PEO composition of 7/3 (w/w). By addition of PEO on the blending of LiClO4-PVA can increase the mechanical stress and modulus at break of the membranes, and the optimal mechanical stress and modulus at break of membranes were obtained in the membrane with PVA/PEO ratio of 8/2. In addition, the increase LiClO4 content in membranes can improve the ionic conductivity of the polymer electrolyte membranes, but the mechanical strength of membranes decreases.
ANALYSIS OF THE AUXILIARY RESONANT COMMUTATED POLE INVERTER (1995)

A study of the Auxiliary Resonant Commutated Pole (ARCP) converter and a comparison with standard hard-switched inverters is presented. A thorough description of the AELCP circuit topology is made with three switching scenarios discussed: commutation from a diode, commutation from a switch with low current, and commutation from a switch with high current. The efficiency of the ARCP inverter is attributed to the fact that switching losses are eliminated by switching under zero voltage or zero current conditions. To accomplish this task, addition circuitry is introduced which colntributes to additional conduction losses. An example H-bridge is presented using both ARCP phase legs and hard-switched phase legs. Losses for each case are calculated and a comparison is made. From simulations, it is shown that the additional conduction losses introduced by the ARCP circuit are small in comparison with the switching losses found in a standard hard-switched circuit. A simulation of a three-phase example ARCP inverter is briefly discussed.
RADIATION GRAFTING OF SYNTHETIC HYDROGELS TO INERT POLYMER SURFACES. I. HYDROXYETHYL METHACRYLATE. (1972)

level after a maximum is reached. The difference in behavior was interpreted in terms of partitioning of monomers into the polyethlene substrate. The surface topography of the grafted films was studied by means of scanning electron microscopy. A mechanism based on osmotic cell formation was suggested for the HEMA graft system. The copolymer systems investigated showed that the graft reaction is faster in the initial stages for higher percentages of EMA in the monomer mixtures; as grafting proceeds the trend is reversed. 24 references, 16 figures, 2 tables.
Characterization of silicon micro-oscillators by scanning laser vibrometry (2002)

The dynamics of single-crystal silicon ∼100 μm size rectangular paddle oscillators at room temperature have been studied using a recently developed high-resolution scanning laser vibrometer. The dynamic mechanical behavior is determined by scans of the entire device, providing both amplitude and phase spatial maps of the vibratory response. These reveal more than 16 normal modes below 500 kHz. In addition to simple translation and torsional motion, flexural modes of the paddle plate are observed. Quality factors ranging from 1×103 to 2×104 are measured and are found to be significantly lower than those expected from well-known intrinsic absorption mechanisms. The measurements reveal that there exists significant modification of the expected eigenfrequencies and mode shapes. It is speculated that this is caused by excessive undercutting of the support structure, and that the resulting energy flow into the support leads to increased oscillator loss. Indeed, some correlation is found between observed loss and energy levels resident in the supports. At frequencies where there is relatively little support motion, three-dimensional finite-element modeling accurately predicts the paddle modal behavior.
Near edge X-ray absorption fine structure spectroscopy as a tool to probe electronic and structural properties of thin organic films and liquids (2006)

Synchrotron-based spectroscopic techniques have contributed significantly to a better understanding of the properties of materials on the macroscopic and microscopic scale over the last decades. They can be applied to samples from a diversity of fields, including Biology, Life Sciences, Chemistry and Materials. One of these techniques is Near Edge X-Ray Absorption Fine Structure (NEXAFS) spectroscopy, revealing electronic structure and information on the orientation of adsorbed molecules. The present article describes the basics of the technique and the progress it has made over the last three decades, and summarizes some of its more recent developments and applications. This tutorial review article should be accessible for novices to the field from Physics, Chemistry, Biology, Materials, and the Life Sciences, interested in thin organic films and liquid systems.
Genetic Variability in CLU and Its Association with Alzheimer's Disease (2010)

We conclude that common coding variability at this locus does not explain the association, and that there is no large effect of common genetic variability on expression in brain tissue. We surmise that the most likely mechanism underpinning the association is either small effects of genetic variability on resting gene expression, or effects on damage induced expression of the protein.
Cloned genomic DNA sequences from Mycoplasma hyorhinis encoding antigens expressed in Escherichia coli. (1983)

A library of cloned Mycoplasma hyorhinis genomic sequences was constructed by incorporation of EcoRI digestion fragments of mycoplasma DNA into the lambda Charon 4A bacteriophage vector. Immunological screening of recombinant phage plaques identified clones containing genes encoding mycoplasma antigenic structures expressed in an Escherichia coli host. Two such recombinant phage isolates, lambda Ch4A-MhrG1 and lambda Ch4A-MhrG28, were defined and found to contain distinct genomic sequences by analysis of restriction endonuclease fragments. Inoculation of mice with recombinant gene products from lambda Ch4A-MhrG1 yielded antiserum selectively recognizing a Mr 29,500 trypsin-sensitive mycoplasma constituent. This established a means for producing selected immunogenic mycoplasma component in a bacterial host. The cloned genomic sequences of M. hyorhinis encoding expressed mycoplasma antigens represent molecular probes that can be characterized both by specific DNA sequences and by the antigenic structure of corresponding gene products. These genomic fragments define initial physical markers of the M. hyorhinis genome and may be useful in assessing antigenic and molecular genetic relationships within the genus Mycoplasma and among other members of the class Mollicutes.
Functional Roles of Otx2 Transcription Factor in Postnatal Mouse Retinal Development (2007)

We previously reported that Otx2 is essential for photoreceptor cell fate determination; however, the functional role of Otx2 in postnatal retinal development is still unclear although it has been reported to be expressed in retinal bipolar cells and photoreceptors at postnatal stages. In this study, we first examined the roles of Otx2 in the terminal differentiation of photoreceptors by analyzing Otx2; Crx double-knockout mice. In Otx2+/-; Crx-/- retinas, photoreceptor degeneration and downregulation of photoreceptor-specific genes were much more prominent than in Crx-/- retinas, suggesting that Otx2 has a role in the terminal differentiation of the photoreceptors. Moreover, bipolar cells decreased in the Otx2+/-; Crx-/- retina, suggesting that Otx2 is also involved in retinal bipolar-cell development. To further investigate the role of Otx2 in bipolar-cell development, we generated a postnatal bipolar-cell-specific Otx2 conditional-knockout mouse line. Immunohistochemical analysis of this line showed that the expression of protein kinase C, a marker of mature bipolar cells, was significantly downregulated in the retina. Electroretinograms revealed that the electrophysiological function of retinal bipolar cells was impaired as a result of Otx2 ablation. These data suggest that Otx2 plays a functional role in the maturation of retinal photoreceptor and bipolar cells.
Impaired Inhibition by Dexamethasone of Cytokine Release by Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease (2002)

Chronic obstructive pulmonary disease (COPD) is characterized by inflammation of the respiratory tract in which macrophages are the predominant inflammatory cell and for which the efficacy of treatment with corticosteroids is controversial. We investigated the effect of dexamethasone on basal and interleukin (IL)-1beta or cigarette smoke media (CSM)-stimulated release of IL-8 and granulocyte macrophage-colony stimulating factor (GM-CSF) by bronchoalveolar lavage macrophages from cigarette smokers and patients with COPD (n = 15). Basal release of IL-8 was approximately fivefold greater in patients with COPD than smokers, whereas GM-CSF was similar for each group. IL-1beta and CSM increased IL-8 and GM-CSF release by macrophages from both smokers and patients with COPD. Dexamethasone did not inhibit basal or stimulated IL-8 release from macrophages from patients with COPD but inhibited release in smokers. In contrast, basal and IL-1beta-stimulated GM-CSF release, but not CSM-stimulated release, was inhibited by dexamethasone. We conclude that the lack of efficacy of corticosteroids in COPD might be due to the relative steroid insensitivity of macrophages in the respiratory tract.
Trifluoperazine-Induced Suicidal Erythrocyte Death and S-Nitrosylation Inhibition, Reversed by the Nitric Oxide Donor Sodium Nitroprusside (2017)

TFP induces eryptosis and decreases protein S-nitrosylation, effects blunted by nitroprusside. The effect of nitroprusside is attenuated in the presence of extracellular Ca2+.
Evaluation of Wheat (<i>Triticum aestivum</i> L.) Phenolic Acids during Grain Development and Their Contribution to <i>Fusarium</i> Resistance (1999)

The phenolic acid profiles of six cultivars of wheat with known tolerance to Fusarium head blight were evaluated during plant development from anthesis through maturity. Analysis by HPLC of grain at anthesis revealed that p-coumaric and ferulic acid were the two principal phenolic compounds present. The effect of these two phenolic acids on Fusarium species was evaluated in vitro. Both phenolic acids demonstrated significant reductions (p < 0.05) of Fusarium species growth at all concentrations tested. Ferulic acid is the primary phenolic acid in grain at all stages of development, and its concentration increased steadily during grain development prior to a 50% decrease during grain ripening. The accumulation of ferulic acid synthesis from anthesis until approximately 20 days after anthesis appears related with cultivar resistance to Fusarium. Concentrations of ferulic acid in the grain were similar at maturity, implying that the end-use quality would be similar for both resistant and susceptible cultivars.
Generation of Free Radicals during the Death of Saccharomyces cerevisiae Caused by Lipid Hydroperoxide (1999)

The exposure of Saccharomyces cerevisiae cells to 13-L-hydroperoxylinoleic acid (LOOH) caused their death, the degree of which was dependent on the growth phase of the cells. Pre-application of ethanol, hydrogen peroxide (H2O2) and LOOH to S. cerevisiae cells reduced the effect of LOOH on the cells, showing the transient cross adaptation to LOOH. Antioxidants such as N,N',-diphenyl-p-phenylenediamine (DPPD), melatonin and vitamin E, and inhibitors of permeability transition of mitochondria, cyclosporin A and trifluoperazine, inhibited the LOOH-triggered cell death, while an inhibitor of glutathione synthetase, buthionine sulfoximine (BSO), enhanced the cell death by LOOH. Reactive oxygen species (ROS) were detected by flow cytometry, using the ROS-specific fluorescent indicator. A ferric iron chelator, deferoxamine, inhibited the LOOH-triggered cell death, and peroxyl radicals (LOO.) were detected by a spin trapping method. These reactive radicals possibly induced the death of S. cerevisiae cells. However, the DNA fragmentation characteristic of apoptosis was not observed in S. cerevisiae cells after exposure to LOOH, staurosporine, dexamethasone or etoposide, which have been reported to cause apoptosis in mammalian cells.