gebhart/patrepeval huggingface dataset:
The neuroprotective pharmacology of methylprednisolone (1992)

A 24-hour intensive intravenous dosing regimen with the glucocorticoid steroid methylprednisolone has recently been shown to be effective in enhancing neurological recovery in spinal cord-injured patients when initiated within 8 hours after injury. The state of knowledge concerning the neuroprotective pharmacology of methylprednisolone, including mechanism(s) of action, dosing requirements, and time-action considerations is reviewed, as are the results of studies with high doses in experimental and clinical head injury, subarachnoid hemorrhage, and cerebral ischemia. A primary neuroprotective mechanism of action in each of these cases is hypothesized to involve the ability of high doses of methylprednisolone to inhibit oxygen free radical-induced lipid peroxidation, although additional mechanisms may contribute. Unresolved issues are also addressed, including the therapeutic window, optimum duration of treatment, and rational combination with other neuroprotective agents. A newer methylprednisolone pro-drug with improved solution stability is discussed, together with a brief consideration of novel nonglucocorticoid steroids that surpass methylprednisolone's lipid antioxidant effects without unwanted glucocorticoid properties.
Next Generation, High Relaxivity Gadolinium MRI Agents (2004)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTNext Generation, High Relaxivity Gadolinium MRI Agents†Kenneth N. Raymond and Valérie C. PierreView Author Information Department of Chemistry, University of California, Berkeley, California 94720-1460 Cite this: Bioconjugate Chem. 2005, 16, 1, 3–8Publication Date (Web):December 21, 2004Publication History Received27 July 2004Published online21 December 2004Published inissue 1 January 2005https://pubs.acs.org/doi/10.1021/bc049817yhttps://doi.org/10.1021/bc049817yreview-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views3672Altmetric-Citations281LEARN 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 SUBJECTS:Imaging agents,Ligands,Magnetic resonance imaging,Molecules,Stability Get e-Alerts
[Formaldehyde fixation in the third millennium]. (2001)

This review deals with the general principles and problems of formaldehyde fixation. After a short description of 1) formaldehyde methods of production, 2) chemical properties of formaldehyde solution, and 3) kinetic of formaldehyde binding in tissue, formaldehyde reactivity with the tissue biopolymers, proteins and cucleic acids mainly, are described. How formaldehyde fixation of tissues adversely affects the reactivity of cellular proteins with their respective specific antibody and the ways the most commonly used retrieval techniques in immunohistochemistry act are, thereafter, discussed. Finally, concerns that need to be dealt with when formalin-fixed specimens are used for genomic analysis and studies of DNA expression are highlighted.
MIF proteins are theta‐class glutathione S‐transferase homologs (1993)

MIF proteins are mammalian polypeptides of approximately 13,000 molecular weight. This class includes human macrophage migration inhibitory factor (MIF), a rat liver protein that has glutathione S-transferase (GST) activity (TRANSMIF), and the mouse delayed early response gene 6 (DER6) protein. MIF proteins were previously linked to GSTs by demonstrating transferase activity and observing N-terminal sequence homology with a mu-class GST (Blocki, F.A., Schlievert, P.M., & Wackett, L.P., 1992, Nature 360, 269-270). In this study, MIF proteins are shown to be structurally related to the theta class of GSTs. This is established in three ways. First, unique primary sequence patterns are developed for each of the GST gene classes. The patterns identify the three MIF proteins as theta-like transferase homologs. Second, pattern analysis indicates that GST members of the theta class contain a serine residue in place of the N-terminal tyrosine that is implicated in glutathione deprotonation and activation in GSTs of known structure (Liu, S., et al., 1992, J. Biol. Chem. 267, 4296-4299). The MIF proteins contain a threonine at this position. Third, polyclonal antibodies raised against recombinant human MIF cross-react on Western blots with rat theta GST but not with alpha and mu GSTs. That MIF proteins have glutathione-binding ability may provide a common structural key toward understanding the varied functions of this widely distributed emerging gene family. Because theta is thought to be the most ancient evolutionary GST class, MIF proteins may have diverged early in evolution but retained a glutathione-binding domain.
Discovery of a Highly Potent, Nonabsorbable Apical Sodium-Dependent Bile Acid Transporter Inhibitor (GSK2330672) for Treatment of Type 2 Diabetes (2013)

The apical sodium-dependent bile acid transporter (ASBT) transports bile salts from the lumen of the gastrointestinal (GI) tract to the liver via the portal vein. Multiple pharmaceutical companies have exploited the physiological link between ASBT and hepatic cholesterol metabolism, which led to the clinical investigation of ASBT inhibitors as lipid-lowering agents. While modest lipid effects were demonstrated, the potential utility of ASBT inhibitors for treatment of type 2 diabetes has been relatively unexplored. We initiated a lead optimization effort that focused on the identification of a potent, nonabsorbable ASBT inhibitor starting from the first-generation inhibitor 264W94 (1). Extensive SAR studies culminated in the discovery of GSK2330672 (56) as a highly potent, nonabsorbable ASBT inhibitor which lowers glucose in an animal model of type 2 diabetes and shows excellent developability properties for evaluating the potential therapeutic utility of a nonabsorbable ASBT inhibitor for treatment of patients with type 2 diabetes.
Octane Requirement Increase in 1971 Model Cars with Leaded and Unleaded Gasolines (Report of a Pilot Program of the Road Test Group of the Motor Vehicle Fuel, Lubricant, and Equipment Research Committee of the Coordinating Research Council, Inc.) (1971)

&lt;div class="htmlview paragraph"&gt;During the fall and winter of 1970-1971, the Coordinating Research Council (CRC) contracted with Southwest Research Institute for the latter to conduct a pilot program on 10 pairs of 1971 model cars to compare the influence of leaded and unleaded fuels on octane requirement increase (ORI). The cars were operated for 8,000-10,000 miles in the San Antonio area using a prescribed city-suburban driving schedule. One car of each pair was run on a commercially available leaded gasoline of 93 Research octane number (ON) and the other on a specially prepared unleaded fuel of similar quality. Differences in ORI for the two fuels ranged from 0-3.5 ON within car pairs. The average ORI of 4.0 ON for leaded fuel cars and 4.6 ON for unleaded fuel cars was not significantly different above the 80% confidence level.&lt;/div&gt;
Isostructural M2L4 Molecular Capsules with Anthracene Shells: Synthesis, Crystal Structures, and Fluorescent Properties (2012)

An isostructural series of M(2)L(4) molecular capsules quantitatively self-assembled from two M(II) ions (M=Zn, Cu, Pt, Pd, Ni, Co, and Mn) and four bent ligands with embedded anthracene fluorophores. X-ray crystallographic analysis (for M=Zn, Cu, Ni, and Pd) confirmed the formation of closed-shell structures in which the large interior cavities inside the molecular capsules (about 1 nm) were shielded by eight anthracene panels. Analysis of the Zn(II) and Cu(II) structures showed the inclusion of an unusual triad guest cluster; four MeCN molecules, one water molecule, and one CF(3)SO(3)(-) ion were located inside the cavities. Full characterization by NMR spectroscopy and MS (ESI-TOF) demonstrated that the molecular capsules were quite stable and persist in solution. The fluorescence properties of the isostructural capsules were strongly dependent on the identity of the metal species: the Zn(II) capsule emitted strong blue fluorescence with a high quantum yield (Φ=0.8), in sharp contrast to the weakly emissive Ni(II) and Mn(II) capsules and the completely non-emissive Pd(II), Pt(II), and Co(II) capsules. On the other hand, the Cu(II) capsule exhibited solvatochromism and solvent-dependent emission behavior; blue emission of the capsule was "on" in DMSO but "off" in MeCN.
Improved Subspace Estimation for Multivariate Observations of High Dimension: The Deterministic Signals Case (2012)

We consider the problem of subspace estimation in situations where the number of available snapshots and the observation dimension are comparable in magnitude. In this context, traditional subspace methods tend to fail because the eigenvectors of the sample correlation matrix are heavily biased with respect to the true ones. It has recently been suggested that this situation (where the sample size is small compared to the observation dimension) can be very accurately modeled by considering the asymptotic regime where the observation dimension <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> and the number of snapshots <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</i> converge to +∞ at the same rate. Using large random matrix theory results, it can be shown that traditional subspace estimates are not consistent in this asymptotic regime. Furthermore, new consistent subspace estimate can be proposed, which outperform the standard subspace methods for realistic values of <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</i> . The work carried out so far in this area has always been based on the assumption that the observations are random, independent and identically distributed in the time domain. The goal of this paper is to propose new consistent subspace estimators for the case where the source signals are modelled as unknown deterministic signals. In practice, this allows to use the proposed approach regardless of the statistical properties of the source signals. In order to construct the proposed estimators, new technical results concerning the almost sure location of the eigenvalues of sample covariance matrices of Information plus Noise complex Gaussian models are established. These results are believed to be of independent interest.
Mouse interleukin‐12 (IL‐12) p40 homodimer: a potent IL‐12 antagonist (1995)

Interleukin-12 (IL-12) is a cytokine that has regulatory effects on T and natural killer (NK) cells and is composed of two disulfide-bonded subunits, p40 and p35. It was recently reported that supernatants from cultures of mouse IL-12 (moIL-12) p40-transfected COS cells could inhibit IL-12-dependent responses in vitro (Mattner, F., et al., Eur. J. Immunol. 1993. 23: 2202). We have further characterized the nature of the inhibitory substance. Purified mouse p40 produced in a baculovirus expression system was found to consist of two species: the p40 monomer and a disulfide-linked p40 dimer [(p40)2]. The (p40)2 was 25- to 50-fold more active than the p40 monomer in causing specific, dose-dependent inhibition of IL-12-induced mouse concanavalin A (Con A) blast proliferation and could also inhibit IL-12-induced interferon-gamma (IFN-gamma) secretion by mouse splenocytes and IL-12-dependent activation of mouse NK cells. Competitive binding studies on mouse Con A blasts showed that (p40)2 was equally effective as moIL-12 in competing with 125I-labeled moIL-12 ([125I]moIL-12) for binding to mouse Con A blasts. However, in contrast to moIL-12, mouse (p40)2 displayed little ability to compete with 125I-labeled human IL-12 (huIL-12) for binding to high-affinity IL-12 receptors (IL-12R) on human phytohemagglutinin (PHA) blasts and caused little or no inhibition of huIL-12-induced human PHA blast proliferation. Nonetheless, mouse (p40)2 was equally effective as moIL-12 in competing with [125I] huIL-12 for binding to COS cells transfected with the human IL-12R beta subunit and expressing low-affinity IL-12 binding sites. These results suggest that (i) the majority of the structural determinants required for binding of IL-12 to its receptor are contained within the p40 subunit, but p35 is required for signaling, (ii) the p40 subunit of IL-12 interacts with the beta subunit of IL-12R, and (iii) (p40)2 may be a suitable IL-12 antagonist for studying the role of IL-12 in various immune responses in vivo as well as in vitro. Further studies are required to determine whether or not (p40)2 is produced by normal lymphoid cells and is a physiologic regulator of IL-12 activity.
Conjugation of High-Molecular Weight Poly(ethylene glycol) to Cytokines: Granulocyte-Macrophage Colony-Stimulating Factors as Model Substrates (1997)

The ability of the small receptor-binding protein, recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF), to increase the abundance of certain blood cell types in mice was enhanced markedly by covalent attachment of a single long strand of PEG (30-40 kDa). Potency was not increased further by coupling a second strand. Such conjugates can be synthesized efficiently by reaction of protein amino groups with PEG propionaldehydes in the presence of NaBH3CN or with PEG p-nitrophenyl carbonates. Both methods have been used to prepare recombinant human GM-CSF conjugates of predetermined composition, e.g. PEG1GM-CSF and PEG2GM-CSF, in high yield. These compounds, or analogous derivatives of other cytokines, purified by ion-exchange and size-exclusion chromatography, may be suitable candidates for pharmaceutical development.
Adeno‐Associated Virus RNA Transcription in vivo (1981)

We have studied RNA transcripts of the defective parvovirus, adeno-associated virus (AAV) present in poly(A)rich and poly-(A)free fractions of nuclear and cytoplasmic RNA prepared from cells infected together with a helper adenovirus. Cytoplasmic poly-(A)rich RNA contains three overlapping spliced AAV RNAs having sizes of 3.9 X 10(3), 3.3 X 10(3) and 2.3 X 10(3) bases respectively. The nuclear precursors of these RNAs appear to be the coterminal unspliced poly(A)-rich RNAs containing 4.2 X 10(3), 3.6 X 10(3) and 2.6 X 10(3) bases respectively. These unspliced RNAs were also found in the cytoplasm. The nuclear poly(A)-free RNA contained a heterogenous population of AAV RNAs that were generally smaller than 2.3 X 10(3) bases. In addition, the Hirt pellet fraction of the nuclear RNA contained two discrete AAV poly(A)-free RNAs having sizes of 2.5 X 10(3) and 2.8 X 10(3) bases. The 4.2 X 10(3) and 3.6 X 10(3)-base unspliced RNAs are more abundant than the coterminal 3.9 X 10(3) and 3.3 X 10(3)-base spliced RNAs whereas the 2.3 X 10(3)-base spliced RNA is much more abundant than the 2.6 X 10(3)-base unspliced RNA. Thus, the cytoplasmic abundance of the AAV spliced RNAs appears to be controlled in part by the post-transcriptional events of splicing or message stability. We also analysed the effects of AAV defective-interfering genomes upon AAV transcription. These studies showed that when synthesis of standard AAV genomes was inhibited more than 10-fold by defective-interfering genomes there was no significant effect on the types or amounts of AAV RNA transcripts which accumulated. These observations indicate that interference by defective-interfering genomes occurs mostly at the level of DNA replication rather than transcription.
Soft-starting procedure for dual active bridge converter (2015)

Dual Active Bridge converter is extensively used to manage the power flow in high power and high density applications, as energy storage systems, renewable sources integration and electrical vehicles. This paper focuses on a digital starting process - suitable for all operating conditions - aiming at minimizing the inrush current at the turn on. The output voltage is initially built up by the secondary side body diodes, then phase-shift control is enabled and the reference is smoothly increased till the nominal value. A FPGA controlled 1.2kW 270V/28V converter is developed and experimental results are provided to assess the proposed method.
Clusters and superclusters of phased small RNAs in the developing inflorescence of rice (2009)

To address the role of small regulatory RNAs in rice development, we generated a large data set of small RNAs from mature leaves and developing roots, shoots, and inflorescences. Using a spatial clustering algorithm, we identified 36,780 genomic groups of small RNAs. Most consisted of 24-nt RNAs that are expressed in all four tissues and enriched in repeat regions of the genome; 1029 clusters were composed primarily of 21-nt small RNAs and, strikingly, 831 of these contained phased RNAs and were preferentially expressed in developing inflorescences. Thirty-eight of the 24-mer clusters were also phased and preferentially expressed in inflorescences. The phased 21-mer clusters derive from nonprotein coding, nonrepeat regions of the genome and are grouped together into superclusters containing 10-46 clusters. The majority of these 21-mer clusters (705/831) are flanked by a degenerate 22-nt motif that is offset by 12 nt from the main phase of the cluster. Small RNAs complementary to these flanking 22-nt motifs define a new miRNA family, which is conserved in maize and expressed in developing reproductive tissues in both plants. These results suggest that the biogenesis of phased inflorescence RNAs resembles that of tasiRNAs and raise the possibility that these novel small RNAs function in early reproductive development in rice and other monocots.
Repression of the HIV-1 5′ LTR promoter and inhibition of HIV-1 replication by using engineered zinc-finger transcription factors (2003)

Zinc finger domains are small DNA-binding modules that can be engineered to bind desired target sequences. Functional transcription factors can be made from these DNA-binding modules, by fusion with an appropriate effector domain. In this study, eight three-zinc-finger proteins (ZFPs) that bound HIV-1 sequences in vitro were engineered into transcription repressors by linking them to the Krüppel-associated box (KRAB) repressor domain (KOX1). One protein, ZFP HIVB-KOX, which bound to a 9-bp region overlapping two Sp1 sites, was found to repress a Tat-activated 5' LTR cellular HIV-reporter assay to almost basal levels. A related six-finger protein, HIVBA'-KOX, was made to target all three Sp1 sites in the 5' LTR promoter and efficiently inhibited both basal and Tat-activated transcription in unstimulated and mitogen-stimulated T cells. In contrast, a combination of two unlinked three-finger ZFPs, HIVA'-KOX and HIVB-KOX, which bind over the same region of DNA, resulted in less effective repression. Finally, HIVBA'-KOX was tested for its capacity to block viral replication in a cellular infection assay using the HIV-1 HXB2 strain. This ZFP was found to inhibit HIV-1 replication by 75% compared with control constructs, thus demonstrating the potential of this approach for antiviral therapy.
An Improved Tetrodotoxin Analyzer (1989)

Journal Article An Improved Tetrodotoxin Analyzer Get access Mari Yotsu, Mari Yotsu Department of Food Chemistry, Faculty of Agriculture, Tohoku University, Tsutsumidori, Sendai 981, Japan Search for other works by this author on: Oxford Academic Google Scholar Amane Endo, Amane Endo Department of Food Chemistry, Faculty of Agriculture, Tohoku University, Tsutsumidori, Sendai 981, Japan Search for other works by this author on: Oxford Academic Google Scholar Takeshi Yasumoto Takeshi Yasumoto Department of Food Chemistry, Faculty of Agriculture, Tohoku University, Tsutsumidori, Sendai 981, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 53, Issue 3, 1 March 1989, Pages 893–895, https://doi.org/10.1080/00021369.1989.10869337 Published: 01 March 1989 Article history Received: 28 November 1988 Published: 01 March 1989
Neural differentiation regulated by biomimetic surfaces presenting motifs of extracellular matrix proteins (2009)

The interaction between cells and the extracellular matrix (ECM) is essential during development. To elucidate the function of ECM proteins on cell differentiation, we developed biomimetic surfaces that display specific ECM peptide motifs in a controlled manner. Presentation of ECM domains for collagen, fibronectin, and laminin influenced the formation of neurites by differentiating PC12 cells. The effect of these peptide sequences was also tested on the development of adult neural stem/progenitor cells. In this system, collagen I and fibronectin induced the formation of beta-III-tubulin positive cells, whereas collagen IV reduced such differentiation. Biomimetic surfaces composed of multiple peptide types enabled the combinatorial effects of various ECM motifs to be studied. Surfaces displaying combined motifs were often predictable as a result of the synergistic effects of ECM peptides studied in isolation. For example, the additive effects of fibronectin and laminin resulted in greater expression of beta-III-tubulin positive cells, whereas the negative effect of the collagen IV domain was canceled out by coexpression of collagen I. However, simultaneous expression of certain ECM domains was less predictable. These data highlight the complexity of the cellular response to combined ECM signals and the need to study the function of ECM domains individually and in combination.
Regulation of Adenylyl Cyclase by Protein Kinase A (1995)

The changing relationship between stimuli and responses after prolonged receptor stimulation is a general feature of hormonal signaling systems, termed desensitization. This phenomenon has been best exemplified in the covalent modification of the G protein-linked catecholamine receptors. However, other components within this signaling pathway can be involved in desensitization. Here we present evidence that desensitization occurs at the level of the effector enzyme itself through phosphorylation. Type V adenylyl cyclase (AC) is the major isoform expressed in the heart. Using purified enzymes, we demonstrate that protein kinase A (PKA) directly phosphorylates and thereby inhibits type V AC catalytic activity. This inhibition was negated in the presence of PKA inhibitor. Analysis of enzyme kinetics revealed that this inhibition was due to a decrease in the catalytic rate, not to a decrease in the affinity for the substrate ATP. Our results indicate that AC catalytic activity can be regulated through PKA-mediated phosphorylation, suggesting another mechanism of desensitization for receptor pathways which signal via increases in intracellular cAMP.