gebhart/patrepeval huggingface dataset:
Signal-dependent repression of DUSP5 by class I HDACs controls nuclear ERK activity and cardiomyocyte hypertrophy (2013)

Cardiac hypertrophy is a strong predictor of morbidity and mortality in patients with heart failure. Small molecule histone deacetylase (HDAC) inhibitors have been shown to suppress cardiac hypertrophy through mechanisms that remain poorly understood. We report that class I HDACs function as signal-dependent repressors of cardiac hypertrophy via inhibition of the gene encoding dual-specificity phosphatase 5 (DUSP5) DUSP5, a nuclear phosphatase that negatively regulates prohypertrophic signaling by ERK1/2. Inhibition of DUSP5 by class I HDACs requires activity of the ERK kinase, mitogen-activated protein kinase kinase (MEK), revealing a self-reinforcing mechanism for promotion of cardiac ERK signaling. In cardiac myocytes treated with highly selective class I HDAC inhibitors, nuclear ERK1/2 signaling is suppressed in a manner that is absolutely dependent on DUSP5. In contrast, cytosolic ERK1/2 activation is maintained under these same conditions. Ectopic expression of DUSP5 in cardiomyocytes results in potent inhibition of agonist-dependent hypertrophy through a mechanism involving suppression of the gene program for hypertrophic growth. These findings define unique roles for class I HDACs and DUSP5 as integral components of a regulatory signaling circuit that controls cardiac hypertrophy.
Molecular Characterization of the Rat Insulin Enhancer-binding Complex 3b2 (1995)

Cell-specific expression of the rat insulin II gene is in part mediated through an element located in the 5'-flanking region. The element, termed RIPE3b (-126 to -101), confers beta-cell-specific expression in conjunction with an adjacent element RIPE3a (-110 to -86). Here we report the characterization of one of the RIPE3b-binding complexes, 3b2. UV cross-linking analysis demonstrated that it is composed of at least three polypeptides: p58, p62, and p110. Furthermore, a cDNA was isolated via expression screening for binding to RIPE3b. Sequence analysis reveals that the encoded protein, designated Rip-1, possessed putative helicase motifs and a potential transcription activation domain. Overexpression of Rip-1 in cells greatly enhances the 3b2 binding complex, suggesting that Rip-1 is involved in the binding of 3b2.
Calcifications, Arterial Stiffness and Atherosclerosis (2006)

Current evidence supports that medial calcification is associated with increases in arterial stiffness. The association between intimal (atherosclerotic-associated) calcification and arterial stiffness is less definitive.
Three-Dimensional Modeling of Laser Sintering of a Two-Component Metal Powder Layer on Top of Sintered Layers (2006)

A three-dimensional model of selective laser sintering of a two-component loose metal powder layer on top of previously sintered layers by a single-line laser scanning is presented. A temperature-transforming model is employed to model melting and resolidification accompanied by partial shrinkage during laser sintering. The heat losses at the top surface due to natural convection and radiation are taken into account. The liquid flow of the molten low-melting-point metal powders, which is driven by capillary and gravity forces, is also considered and formulated by using Darcy’s law. The effects of the dominant processing parameters, such as laser-beam intensity, scanning velocity, and number of the existing sintered layers underneath, are investigated.
Toward establishing an efficient and versatile gene targeting system in higher plants (2013)

Precise modification of plant genomes provides powerful tools for understanding gene function. Furthermore, pinpoint modification of endogenous plant genes is also an attractive method in molecular plant breeding. One of the best methods currently available to induce specific DNA sequence changes into genomes is gene targeting (GT) via homologous recombination (HR). GT can induce a variety of mutations, including substitution of several nucleotides as well as insertions and deletions. Of the various approaches taken to improve GT efficiency, utilization of engineered sequence-specific endonucleases to create targeted DNA double-strand breaks (DSBs) that stimulate HR at breaking sites is one of the most effective. As a universal selection system for GT cells, a target-gene-independent selection system such as positive–negative selection with subsequent elimination of the positive selection marker using piggyBac transposon or HR combined with mega-nuclease allows retention of the desired mutation without any trace of additional exogenous nucleotides. Furthermore, a novel GT system named in planta GT seems to have effectively overcome problems due to low transformation efficiency of the HR template into plant nuclei, and can adjust the timing of DSB induction at the target locus. In the in planta system, an HR template flanked by a nuclease recognition site is stably integrated into the plant genome; subsequent expression of nuclease simultaneously releases the HR template from the genome and induces a DSB at the target site. Here, we review recent developments in GT, giving examples of new techniques improving the efficiency of GT in plants.
Identification of Novel Small Molecule Inhibitors of Hypoxia-Inducible Factor-1 That Differentially Block Hypoxia-Inducible Factor-1 Activity and Hypoxia-Inducible Factor-1α Induction in Response to Hypoxic Stress and Growth Factors (2005)

Hypoxia-inducible factor-1 (HIF-1) is a transcriptional complex that is activated in response to hypoxia and growth factors. HIF-1 plays a central role in tumor progression, invasion, and metastasis. Overexpression of the HIF-1alpha subunit has been observed in many human cancers and is associated with a poor prognostic outcome with conventional treatments. Targeting HIF-1 using novel small molecule inhibitors is, therefore, an attractive strategy for therapeutic development. We have generated U2OS human osteosarcoma cells stably expressing a luciferase reporter construct under the control of a hypoxia response element (U2OS-HRE-luc). The U2OS-HRE-luc cells were robustly and reproducibly sensitive to hypoxic stress in a HIF-1-dependent manner. We developed an automated U2OS-HRE-luc cell-based assay that was used in a high-throughput screen to identify compounds that inhibited HIF-1 activity induced by treatment with the hypoxia mimetic, deferoxamine mesylate. We performed a pilot screen of the National Cancer Institute Diversity Set of 2,000 compounds. We identified eight hit compounds, six of these were also identified by Rapisarda et al. in an independent hypoxia screen. However, there were two novel hit compounds, NSC-134754 and NSC-643735, that did not significantly inhibit constitutive luciferase activity in U2OS cells (U2OS-luc). We showed that both NSC-134754 and NSC-643735 significantly inhibited HIF-1 activity and HIF-1alpha protein induced by deferoxamine mesylate. Interestingly, NSC-134754 but not NCS-643735 inhibited HIF-1 activity and HIF-1alpha protein induced by hypoxia and significantly inhibited Glut-1 expression. Finally, we showed that both NCS-134754 and NCS-643735 inhibited HIF-1alpha protein induced by insulin-like growth factor-1. Our cell-based assay approach has successfully identified novel compounds that differentially target hypoxia and/or growth factor-mediated induction of HIF-1alpha.
Phorbol Ester-Induced Juxtamembrane Cleavage of Angiotensin-Converting Enzyme Is Not Inhibited by a Stalk Containing Intrachain Disulfides (1998)

Specialized proteases, referred to as sheddases, secretases, or membrane-protein-solubilizing proteases (MPSPs), solubilize the extracellular domains of diverse membrane proteins by catalyzing a specific cleavage in the juxtamembrane stalk regions of such proteins. A representative MPSP (tumor necrosis factor-α convertase) was cloned recently and shown to be a disintegrin metalloprotease that is inhibited by peptide hydroxamates including the compound TAPI. Substrate determinants that specify cleavage by MPSPs remain incompletely characterized, but may include the physicochemical properties of the stalk or unidentified recognition motifs in the stalk or the extracellular domain. We constructed a mutant angiotensin-converting enzyme (ACE) in which the stalk has been replaced with an epidermal growth factor (EGF)-like domain (ACE-JMEGF), to test the hypothesis that MPSP cleavage requires an open, comparatively unfolded or extended stalk. Wild-type ACE is a type I transmembrane (TM) ectoprotein that is efficiently solubilized by a typical MPSP activity. We found that ACE-JMEGF was solubilized inefficiently and accumulated in a cell-associated form on transfected Chinese hamster ovary (CHO) cells; cleavage was stimulated by phorbol ester and inhibited by TAPI, features typical of MPSP activity. Determination of the C-terminus of soluble ACE-JMEGF revealed that, surprisingly, cleavage occurred at a Gly-Phe bond between the fifth and sixth cysteines within the third disulfide loop of the EGF-like domain. Reduction of intact CHO cells with tributylphosphine resulted in the rapid release of ACE-JMEGF (but not wild-type ACE) into the medium, suggesting that a proportion of membrane-bound ACE-JMEGF is cleaved but remains cell-associated via disulfide tethering. The mechanism for the release of ACE-JMEGF in the absence of chemical reduction is unclear. We conclude that the presence of a compact, disulfide-bridged domain does not per se inhibit cleavage by an MPSP activity, but ectodomain release is prevented by disulfide tethering to the TM domain.
An experimental analysis of classically conditioned nausea during cancer chemotherapy. (1992)

This study investigated classical conditioning in women undergoing outpatient adjuvant chemotherapy for breast cancer. Breast cancer chemotherapy outpatients were randomly assigned either to an Experimental Group (exposed to a distinctive stimulus before each infusion of chemotherapy) or to a Control Group. After repeated infusions of chemotherapy, patients' responses to the experimental stimulus were assessed in a location not associated with chemotherapy. Experimental Group patients had increased nausea (self-reported on a visual analog scale) following the presentation of the experimental stimulus at this test trial, whereas Control Group patients did not. Two other measures of nausea corroborated these results. Post hoc statistical analyses confirmed predictions based on conditioning theory. This conditioning model of anticipatory nausea bears witness to the relevance of classical conditioning in clinical medicine.
Hydrolytic Stability of Hydrazones and Oximes (2008)

Watching C 'n' N: Hydrazones and oximes are common conjugates but are labile to hydrolysis. The hydrolytic stabilities of isostructural hydrazones and one oxime were determined at pD 5.0–9.0. The rate constant for the acid-catalyzed hydrolysis of the oxime was nearly 103-fold lower than those for simple hydrazones, and a trialkylhydrazonium ion (formed after condensation) was even more stable than the oxime. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z802651_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Conjugated Fluorene and Silole Copolymers:  Synthesis, Characterization, Electronic Transition, Light Emission, Photovoltaic Cell, and Field Effect Hole Mobility (2005)

A novel series of soluble conjugated random and alternating copolymers (PFO-TST) derived from 9,9-dioctylfluorene (FO) and 1,1-dimethyl-3,4-diphenyl-2,5-bis(2'-thienyl)silole (TST) were synthesized by palladium(0)-catalyzed Suzuki coupling reactions. The feed ratios of FO to TST were 99:1, 95:5, 90:10, 80:20, and 50:50. Chemical structures and optoelectronic properties of the copolymers were characterized by elemental analysis, NMR, UV absorption, cyclic voltammetry, photoluminescence (PL), electroluminescence (EL), a photovoltaic cell, and a field effect transistor. The elemental analyses of the copolymers indicated that FO and TST contents in the copolymers were very close to the feed compositions. The random copolymers exhibited a PFO-segment-dominated UV absorption peak at ∼385 nm and a narrow band gap TST absorption at ∼490 nm. For the alternating copolymer, only a broad absorption band was found, demonstrating a mixed and TST-dominated electronic configuration. Compared with the solution PL, complete PL excitation energy transfer from the PFO segment to the TST unit could be achieved by film PL at lower TST content. It was found that the EL spectra of the copolymers with a device configuration of indium−tin oxide/poly(3,4-ethylenedioxythiophene)/poly(vinylcarbazole) (PVK)/copolymer/Ba/Al were red shifted and had better red light CIE coordinates with improved external quantum efficiency, compared with corresponding device performances without the PVK layer. With the alternating copolymer as the electron donor and methanofullerene [6,6]-phenyl C61-butyric acid methyl ester as the electron acceptor, an energy conversion efficiency of 2.01% was achieved under an AM1.5 simulated solar light at 100 mW/cm2, which is among the highest values so far reported for bulk-heterojunction photovoltaic cells. The field effect hole mobility of the alternating copolymer is 4.5 × 10-5 cm2/(V s) using polyacrylonitrile as an organic insulator on a gate electrode.
Formation of an optically active 2-phenyl[1,2,4]triazolo[1,5-a]pyrimidine derivative in the reaction of (+)-3-carene-derived β-chlorovinylketone with benzylidene aminoguanidine (2002)

The treatment of a seco-carane-type β-chlorovinyl ketone with benzylidene aminoguanidine in boiling methanol in the presence of sodium bicarbonate results in the formation of a substituted 2-phenyl[1,2,4]triazolo[1,5-a]pyrimidine.
Prostatic intraepithelial neoplasia: Animal models 2000 (2000)

Numerous animal models of preinvasive prostate cancer have been described in the past decade. Differences among models account for their variable applicability for answering specific research questions. The dog is the only known nonhuman spontaneous animal model of prostate cancer, but numerous transgenic and therapy-induced models have been generated in mice and rats. This report summarizes existing models of prostatic intraepithelial neoplasia and their relevance for the study of human prostate cancer.
Heterogeneity of drug resistance in human breast and ovarian cancers. (1998)

Heterogeneity of drug resistance for ovarian and breast cancer is a serious clinical problem encountered in administering chemotherapy for overt metastatic or recurrent cancers. The first step in managing this problem is to recognize that heterogeneity of drug resistance exists. Drug resistance tests may then help the physician avoid administering certain chemotherapeutic agents when a patient's metastatic or recurrent tumor is found to be resistant to those agents.
Giant Intrinsic Carrier Mobilities in Graphene and Its Bilayer (2008)

We have studied temperature dependences of electron transport in graphene and its bilayer and found extremely low electron-phonon scattering rates that set the fundamental limit on possible charge carrier mobilities at room temperature. Our measurements show that mobilities higher than 200 000 cm2/V s are achievable, if extrinsic disorder is eliminated. A sharp (thresholdlike) increase in resistivity observed above approximately 200 K is unexpected but can qualitatively be understood within a model of a rippled graphene sheet in which scattering occurs on intraripple flexural phonons.
Melanoma-Reactive CD8 + T Cells Recognize a Novel Tumor Antigen Expressed in a Wide Variety of Tumor Types (2001)

An autologous melanoma cell line selected for loss of expression of the immunodominant MART-1 and gp100 antigens was initially used to carry out a mixed lymphocyte tumor culture (MLTC) in a patient who expressed the human leukocyte antigen (HLA)-AI and HLA-A2 class I major histocompatibility complex alleles. Ten clones identified from this MLTC seemed to recognize melanoma in an HLA-A1-restricted manner but failed to recognize a panel of previously described melanoma antigens. The screening of an autologous melanoma cDNA library with one HLA-Al-restricted melanoma-reactive T-cell clone resulted in the isolation of a cDNA clone called AIM-2 (antigen isolated from immunoselected melanoma-2). The AIM-2 transcript seemed to have retained an intronic sequence based on its alignment with genomic sequences as well as expressed sequence tags. This transcript was not readily detected after Northern blot analysis of melanoma mRNA, indicating that only low levels of this product may be expressed in tumor cells. Quantitative reverse transcriptase-polymerase chain reaction analysis, however, demonstrated a correlation between T-cell recognition and expression in HLA-A1-expressing tumor cell lines. A peptide that was encoded within a short open reading frame of 23 amino acids and conformed to the HLA-A1 binding motif RSDSGQQARY was found to represent the T-cell epitope. The AIM-2-reactive T-cell clone recognized a number of neuroectodermal tumors as well as breast, ovarian, and colon carcinomas that expressed HLA-A1, indicating that this represents a widely expressed tumor antigen. Thus, AIM-2 may represent a potential target for the development of vaccines in patients bearing tumors of a variety of histologies.
Do minocycline and other tetracyclines have a place in rheumatology? (1997)

Tetracyclines are a family of antimicrobials with activity against a broad range of organisms including those that develop intracellularly. Links have been reported between some infections and some inflammatory joint diseases, with the most notable example involving mycoplasmas and rheumatoid arthritis. Reactive arthritides are known to be triggered by organisms found in the gastrointestinal or genitourinary tract, and antigenic material from these organisms has recently been demonstrated in synovial tissue from patients with reactive arthritis. These facts led to the hypothesis that tetracyclines may be useful in rheumatoid arthritis and reactive arthritis. Two controlled studies found that minocycline benefited rheumatoid arthritis patients when it was given either as an adjunct to another second-line treatment or as the only slow-acting drug. Lymecycline has been found to expedite recovery from reactive arthritis due to Chlamydia trachomatis, and tetracycline to decrease the incidence of reactive arthritis due to sexually-transmitted diseases. The safety profiles of these treatments were acceptable in all available studies but require further investigation during long-term administration. The benefits may be related to the immunomodulating effects of tetracyclines and/or to their ability to inhibit metalloproteases such as collagenases. Whether tetracycline therapy influences the course of radiologic lesions in rheumatoid arthritis remains unknown. However, minocycline therapy has given sufficient proof of its efficacy to make it an attractive alternative in rheumatoid arthritis.
A Fully Projective Formulation for Lowe's Tracking Algorithm (1996)

David Lowe's influential and classic algorithm for tracking objects with known geometry is formulated with certain simplifying assumptions. A version implemented by Ishii et al. makes different simplifying assumptions. We formulate a full projective solution and apply the same algorithm (Newton's method). We report results of extensive testing of these three algorithms. We compute two image--space and six pose--space error metrics to quantify the effects of object pose, errors in initial solutions, and image noise levels. We consider several scenaria, from relatively unconstrained conditions to those that mirror real--world and real--time constraints. The conclusion is that the full projective formulation makes the algorithm orders of magnitude more accurate and gives it super--exponential convergence properties with arguably better computation--time properties.
Neuron Protection as a Therapeutic Target in Acute Ischemic Stroke (2009)

Involvement of various neurotransmitters and neuromodulators have been shown to contribute to the ischemic injury and neuronal death associated with stroke Role of excitatory amino acid receptor activation, calcium overload, nitric oxide, and oxidative stress in the pathogenesis of ischemic brain damage is well established. Several new strategies are currently emerging, based on recent advances in our understanding of molecular pathways that could be considered as potential therapeutic targets. For example reactive oxygen species (ROS) are important contributors to the secondary injury cascade following traumatic brain injury (TBI), and ROS inhibition has consistently been shown to be neuroprotective following experimental TBI and brain ischemia. Furthermore, more recently, some authors concluded that nonanticoagulant 3K3A-APC exhibits greater neuroprotective efficacy with no risk for bleeding compared with drotrecogin-alfa activated, a hyperanticoagulant form of APC. Excessive calcium entry into depolarized neurons contributes significantly to cerebral tissue damage after ischemia. Included in the sequence of events leading to neuronal death in ischemic tissue following stroke is an excessive and toxic rise in the intracellular Ca(2+)-concentration, predominantly due to an influx of Ca2+ through nonselective cation-channels as well as Ca(2+)-channels.. Some authros conducted a study to investigate whether the enhancement of GABA receptor activity could inhibit NMDA receptor-mediated nitric oxide (NO) production by neuronal NO synthase (nNOS) in brain ischemic injury. The results showed that both the GABA(A) receptor agonist muscimol and the GABA(B) receptor agonist baclofen had neuroprotective effect, and the combination of two agonists could significantly protect neurons against death induced by ischemia/reperfusion. On this basis we conclude that neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection.
Glycobiology: an expanding research area in carbohydrate chemistry (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGlycobiology: an expanding research area in carbohydrate chemistryAkira KobataCite this: Acc. Chem. Res. 1993, 26, 6, 319–324Publication Date (Print):June 1, 1993Publication History Published online1 May 2002Published inissue 1 June 1993https://pubs.acs.org/doi/10.1021/ar00030a004https://doi.org/10.1021/ar00030a004research-articleACS PublicationsRequest reuse permissionsArticle Views442Altmetric-Citations125LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts