gebhart/patrepeval huggingface dataset:
Prediction of PPAR-α ligand-mediated physiological changes using gene expression profiles (2004)

Peroxisome proliferator-activated receptor (PPAR)-alpha controls the transcription of a variety of genes involved in lipid metabolism and is the target receptor for the hypolipidemic drug class of fibrates. In the present study, the molecular and physiological effects of seven different PPAR-activating drugs have been examined in a rodent model of dyslipidemia. The drugs examined were selected to display varying potencies and efficacies toward PPAR-alpha. To help elucidate the link between the gene regulation elicited by PPAR-alpha ligands and the concomitant physiological changes, we have used cDNA microarray analysis to identify smaller gene sets that are predictive of the function of these ligands. A number of genes showed strong correlations to the relative PPAR-alpha efficacy of the drugs. Furthermore, using multivariate analysis, a strong relationship between the drug-induced triglyceride lowering and the transcriptional profiles of the different drugs could be found.
Epidemiology of Preterm Birth (1993)

Journal Article Epidemiology of Preterm Birth Get access Gertrud S. Berkowitz, Gertrud S. Berkowitz 1Department of Obstetrics, Gynecology and Reproductive Science and Community Medicine, The Mount Sinai School of MedicineOne Gustave L. Levy Place, New York, NY Dr. Gertrud S. Berkowitz, Department of Obstetrics, Gynecology and Reproductive Science, Box 1172, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029 Search for other works by this author on: Oxford Academic PubMed Google Scholar Emile Papiernik Emile Papiernik 2Université René Descartes, Gynecologie Obstetrique de la clinique Universitaire Baudelocque123 Boulevard de Port-Royal, 75014 Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Epidemiologic Reviews, Volume 15, Issue 2, 1993, Pages 414–443, https://doi.org/10.1093/oxfordjournals.epirev.a036128 Published: 01 July 1993
A Terminal Access Control System for FLEETSAT (1976)

Abstract : Lincoln Laboratory's Terminal Access Control System (TACS) provides demand assigned time division multiple access TDMA to GAPSAT or FLEETSAT 25 kHz channels. TACS is centrally controlled by a multiple access controller (MAC), nominally located at a shore station. Users of TACS who can be on shorebased or mobile platforms, enter requests for service via a Terminal Access Controller (TAC). The TAC provides error control and data buffering functions in addition to demand assignment control. The MAC automatically responds to the user request with an assignment or busy indication. TACS initially will utilize WSC-3 radios and modems, modified for 19,200 symbol per second operation and for rapid turn around time. TDMA frame formats are designed to maximize system efficiency and utility. For example, a mobile platform equipped with one half duplex WSC-3 has use of two 2.4 kbps circuits simultaneously. A platform with a full duplex radio has use of four such circuits.
Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled γ-phosphate-linked GTP analogs (2004)

Regulated guanosine nucleotide exchange and hydrolysis constitute the fundamental activities of low molecular weight GTPases. We show that three guanosine 5'-triphosphate analogs with BODIPY fluorophores coupled via the gamma phosphate bind to the GTPases Cdc42, Rac1, RhoA, and Ras and displace guanosine 5'-diphosphate with high intrinsic exchange rates in the presence of Mg(2+) ions, thereby acting as synthetic, low molecular weight guanine nucleotide exchange factors. The accompanying large fluorescence enhancements (as high as 12-fold), caused by a reduction in guanine quenching of the environmentally sensitive BODIPY dye fluorescence on protein binding, allow for real-time monitoring of this spontaneous nucleotide exchange in the visible spectrum with high signal-to-noise ratios. Binding affinities increased with longer aliphatic linkers connecting the nucleotide and BODIPY fluorophore and were in the 10-100 nM range. Steady-state and time-resolved fluorescence spectroscopy showed an inverse relationship between linker length and fluorescence enhancement factors and differences in protein-bound fluorophore mobilities, providing optimization criteria for future applications of such compounds as efficient elicitors and reporters of nucleotide exchange. EDTA markedly enhanced nucleotide exchange, enabling rapid loading of GTPases with these probes. Differences in active site geometries, in the absence of Mg(2+), caused qualitatively different reporting of the bound state by the different analogs. The BODIPY analogs also prevented the interaction of Cdc42 with p21 activated kinase. Together, these results validate the use of these analogs as valuable tools for studying GTPase functions and for developing potent synthetic nucleotide exchange factors for this important class of signaling molecules.
The development of phenylethylene dendrons for blue phosphorescent emitters (2009)

New high triplet energy dendrons based on 1,2-diphenylethylene with and without 2-ethylhexyloxy surface groups have been developed for deep blue phosphorescent iridium(III) dendrimers. The fac-tris[1-methyl-5-(4-fluoro)phenyl-3-n-propyl-1H-[1,2,4]triazolyl]iridium(III)-cored dendrimers, bearing first generation 1,2-diphenylethylene dendrons on the ligand triazolyl and phenyl rings, were prepared in excellent yields, employing Sonogashira cross-couplings and palladium catalysed hydrogenation as the key synthetic steps. Both dendrimers showed good thermal stability although the flexible nature of the dendrons led to the materials having low glass transition temperatures. Dendrimer 15 (without the surface groups) emitted good blue phosphorescence with a solution photoluminescence quantum yield (PLQY) of 46%, Commission Internationale de l'Eclairage (CIE) co-ordinates of (0.15, 0.14) and photoluminescence peaks at 441 and 468 nm. The solution PLQY was 50% higher than the parent iridium(III) complex showing that the high triplet energy of the diphenylethylene dendrons does not quench the luminescence of the iridium(III) complex core. Dendrimer 34, which has the surface groups, had a film PLQY of 49% and CIE co-ordinates of (0.16, 0.19) with PL peaks at 441 and 469 nm.
Bitterness of Leucine-containing Peptides (1987)

Journal Article Bitterness of Leucine-containing Peptides Get access Norio Ishibashi, Norio Ishibashi Morinaga Milk Industry Co., Ltd., Nutritional Science Laboratory, 4-22, Meguro 4-chome, Meguro-ku, Tokyo 153, Japan Search for other works by this author on: Oxford Academic Google Scholar Yasuhiro Arita, Yasuhiro Arita Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, Shitami, Saijo-cho, Higashihiroshima 724, Japan Search for other works by this author on: Oxford Academic Google Scholar Hidenori Kanehisa, Hidenori Kanehisa Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, Shitami, Saijo-cho, Higashihiroshima 724, Japan Search for other works by this author on: Oxford Academic Google Scholar Katsushige Kouge, Katsushige Kouge Sanshin Chemical Industrial Co., Ltd., 531 Nagahama, Hirao-cho, Kumage-gun, Yamaguchi 724–11, Japan Search for other works by this author on: Oxford Academic Google Scholar Hideo Okai, Hideo Okai Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, Shitami, Saijo-cho, Higashihiroshima 724, Japan To whom enquiries should be addressed. Search for other works by this author on: Oxford Academic Google Scholar Sakuzo Fukui Sakuzo Fukui Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, Shitami, Saijo-cho, Higashihiroshima 724, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 51, Issue 9, 1 September 1987, Pages 2389–2394, https://doi.org/10.1080/00021369.1987.10868411 Published: 01 September 1987 Article history Received: 12 March 1987 Published: 01 September 1987
Solid solubility limit in alloying nanoparticles (2006)

In order to gain a better thermodynamic understanding of the phase diagram of alloying nanoparticles, we establish a size-dependent solid solubility model of binary metallic systems to elucidate the anomalous solid solubility in nanometre-sized alloying particles. It is found that a diameter of 20 nm seems a threshold value of the size of alloying nanoparticles for the unusual solid solubility, i.e. the solubility is greatly promoted with decreasing grain size when the size of alloying nanoparticles is less than 20 nm. Taking the Pb-Sn system as an example, we show that the theoretical predictions are consistent with experimental data.
A versatile multichannel direct-synthesized electrical stimulator for FES applications (2002)

Functional electrical stimulation (FES) has been applied to restore or maintain the muscle activity of paralyzed patients who suffer from spinal cord injuries and related neural impairments for several decades. In this paper, a direct-synthesized arbitrary waveform stimulator for multichannel FES applications is described. A novel element-envelope method is proposed for flexible waveform generation and implemented by a digital signal processor based system. We also designed an output circuit that can provide bi-phasic, voltage-controlled, constant-current outputs while keeping high-voltage compliance and wide signal bandwidth. High time-resolution and arbitrary stimulating waveforms can thus be synthesized, and more flexible closed-loop feedback controllers can be achieved. The proposed stimulator can be considered as a full-featured electrical stimulator for various FES applications with its flexibility in pattern generation and feedback processing capabilities.
Voriconazole versus Amphotericin B for Primary Therapy of Invasive Aspergillosis (2002)

In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.
PIISignal Transduction Proteins, Pivotal Players in Microbial Nitrogen Control (2001)

The P(II) family of signal transduction proteins are among the most widely distributed signal proteins in the bacterial world. First identified in 1969 as a component of the glutamine synthetase regulatory apparatus, P(II) proteins have since been recognized as playing a pivotal role in control of prokaryotic nitrogen metabolism. More recently, members of the family have been found in higher plants, where they also potentially play a role in nitrogen control. The P(II) proteins can function in the regulation of both gene transcription, by modulating the activity of regulatory proteins, and the catalytic activity of enzymes involved in nitrogen metabolism. There is also emerging evidence that they may regulate the activity of proteins required for transport of nitrogen compounds into the cell. In this review we discuss the history of the P(II) proteins, their structures and biochemistry, and their distribution and functions in prokaryotes. We survey data emerging from bacterial genome sequences and consider other likely or potential targets for control by P(II) proteins.
Effects of anti-peptide antibodies against human M2 muscarinic receptors on the cAMP generating system in guinea pig ventricles. (1996)

The effects of anti-peptide antibodies (Ab) against the second extracellular loop of human muscarinic receptor-2 on the cAMP generating system in guinea pig ventricles were studied. These effects were compared with those of the muscarinic receptor agonist carbachol (Carb). It was shown that: (1) both Carb and Ab were able to inhibit the isoproterenol (Iso)-stimulated cAMP production of ventricles in a dose-dependent manner. Carb at 2 microM, 10 microM and 50 microM decreased Iso-stimulated cAMP production by 8.0 +/- 1.1, 15.8 +/- 1.2 and 28.4 +/- 1.7%, respectively; whereas Ab at 50 nM, 100 nM and 400 nM decreased it by 5.8 +/- 0.4, 16.8 +/- 1.4 and 30.6 +/- 2.5%, respectively. (2) Both Carb and Ab could also inhibit the basal cAMP content of ventricles significantly. Carb at 10 microM and Ab at 100 nM decreased it by 46.9 +/- 4.2% and 60.2 +/- 4.6%, respectively. (3) The inhibitory effects of both Ab and Carb on Iso-stimulated cAMP production were significantly prevented by atropine at 1.5 microM. (4) The inhibitory effect of Ab at 100 nM was almost completely abolished by the peptide (700 nM) used as immunogen. These findings suggest that the antibodies exhibit a stimulatory muscarinic activity similar to carbachol in the inhibitory modulation of cAMP production.
Resistance of human leukemic CEM-C1 cells is overcome by synergism between glucocorticoid and protein kinase A pathways: correlation with c-Myc suppression. (1998)

Glucocorticoids (GCs) induce apoptosis in lymphoid cells that contain functional GC receptors (GRs). However, GC resistance often is seen in cells with demonstrable GRs; one such line is CEM-C1. We have tested the hypothesis that positive interactions between GC and cyclic AMP (cAMP) regulate GC actions in CEM clones. Treatment of both GC-resistant CEM-C1 [resistant to 1 microM dexamethasone (Dex)] and the sensitive sister clone, CEM-C7 (approximately 65% cell death with 20 nM Dex, approximately 99% death with 1 microM Dex), with a < or = 20 microM concentration of the protein kinase A activator, forskolin, had no significant effect on cell viability. Cotreatment with Dex and forskolin resulted in a strong synergistic death response, with only approximately 10% CEM-C1 cells surviving treatment with 1 microM Dex and 20 microM forskolin. This death was blocked by the GR antagonist RU 38486. However, the extent of apoptosis did not correlate with the amount of GR protein or binding activity in either C7 or C1 cells. As reported previously, Dex-evoked cell death was associated with suppression of c-Myc in C7 cells. In CEM-C1 cells, Dex alone did not affect c-Myc; however, Dex plus forskolin suppressed c-Myc levels. To evaluate mechanisms of Dex-forskolin synergism, fresh subclones of CEM-C7 (clone 14) and CEM-C1 (clone 15) were isolated, to ensure purity of phenotype. In these, forskolin (with or without Dex) caused a similar increase in cAMP (approximately 300-fold) and phospho-cAMP-responsive element binding protein (approximately 4-5-fold) levels, whereas total cAMP-responsive element binding protein expression was not affected. GR transcription function, as tested from a GR-responsive 330-bp mouse mammary tumor virus promoter-luciferase reporter construct, was induced 8- and 4-fold by 1 microM Dex treatment of CEM-C7-14 and CEM-C1-15 cells, respectively. Forskolin (10 microM) significantly potentiated Dex response in CEM-C1-15 cells (13.5-fold) but had only a modest effect (1.5-fold) in CEM-C7-14 cells. These studies suggest that sensitization of CEM-C1 cells by cross-talk between GR and protein kinase A pathways may occur via cooperative effects on GR-mediated gene transcription.
Evidence for Possible Involvement of 5-HT2BReceptors in the Cardiac Valvulopathy Associated With Fenfluramine and Other Serotonergic Medications (2000)

Our data imply that activation of 5-HT(2B) receptors is necessary to produce VHD and that serotonergic medications that do not activate 5-HT(2B) receptors are unlikely to produce VHD. We suggest that all clinically available medications with serotonergic activity and their active metabolites be screened for agonist activity at 5-HT(2B) receptors and that clinicians should consider suspending their use of medications with significant activity at 5-HT(2B) receptors.
Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? I. Characterization of pharmacological probes with different receptor binding affinities and catechol oestrogen formation rates (1986)

In an attempt to define pharmacological probes with which to test the role of catechol oestrogen formation in the central nervous system, five oestrogens (oestradiol-17 beta, oestradiol-17 alpha, 4-fluoro-oestradiol, 2-fluoro-oestradiol and moxestrol (11 beta-methoxy-17 alpha-ethynyloestradiol) were studied for binding to oestrogen receptors and conversion to catechol metabolites. Binding to cytosol oestrogen receptors was measured in the hypothalamus-preoptic area-amygdala (HPA), pituitary gland and uterus of ovariectomized rats. Conversion to catechol oestrogens was tested in microsomes from the HPA, pituitary gland and liver, using a catechol-O-methyltransferase-coupled radioenzymatic assay. Oestradiol-17 alpha was the only weak oestrogen receptor ligand. Binding affinities of the other compounds tested were much higher and comparable to those of oestradiol-17 beta. In contrast, oestradiol-17 alpha was rapidly converted to catechol metabolites, while moxestrol was a relatively poor substrate for catechol oestrogen formation. 4-Fluoro-oestradiol could be 2-hydroxylated but not 4-hydroxylated. 2-Fluoro-oestradiol exhibited impaired 2-hydroxylation but normal 4-hydroxylation.
Spatial imaging of luciferase gene expression in transgenic fish (1990)

Journal Article Spatial imaging of luciferase gene expression in transgenic fish Get access Eiichi Tamiya, Eiichi Tamiya Search for other works by this author on: Oxford Academic PubMed Google Scholar Tomoyasu Sugiyama, Tomoyasu Sugiyama Search for other works by this author on: Oxford Academic PubMed Google Scholar Kazuyoshi Masaki, Kazuyoshi Masaki 1Toyo Suisan Kaisha Ltd2-13-40 Kounan, Minato-ku, Tokyo 108, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Akira Hirose, Akira Hirose Search for other works by this author on: Oxford Academic PubMed Google Scholar Takanori Okoshi, Takanori Okoshi Search for other works by this author on: Oxford Academic PubMed Google Scholar Isao Karube Isao Karube Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 4, 25 February 1990, Page 1072, https://doi.org/10.1093/nar/18.4.1072 Published: 25 February 1990 Article history Received: 09 January 1990 Published: 25 February 1990
Valproic Acid Activates Notch-1 Signaling and Regulates the Neuroendocrine Phenotype in Carcinoid Cancer Cells (2007)

Carcinoid tumors are neuroendocrine malignancies that frequently metastasize and secrete hormones that cause debilitating symptoms in patients. In this study we report the effects of valproic acid (VPA), a drug long used for the treatment of epilepsy, on the growth and neuroendocrine phenotype of human carcinoid cancer cells. VPA treatment of gastrointestinal and pulmonary carcinoid cells resulted in a dose-dependent inhibition of cancer cell growth. Western blot analysis revealed degradation of cyclin D1 and an increase in cyclin-dependent kinases p21 and p27 with VPA treatment. Flow cytometry confirmed that the mechanism of VPA-induced growth inhibition is G(1) phase cell cycle arrest. Furthermore, VPA suppressed expression of the neuroendocrine tumor marker chromogranin A. In addition to these effects, VPA also increased levels of full-length Notch-1 and the active Notch-1 intracellular domain. Luciferase reporter assays incorporating the centromere-binding factor 1 (CBF-1) binding site and the achaete-scute complex-like 1 (ASCL-1) promoter confirmed the functional activity of VPA-induced Notch-1. Transfection of Notch-1 small-interfering RNA into carcinoid tumor cells blocked the effects of VPA on Notch-1 activation, ASCL-1 suppression, p21 induction, and cell growth inhibition. VPA also suppressed growth of carcinoid tumors in vivo in a mouse tumor xenograft experiment. These findings confirm the important role of Notch-1 in regulating the growth and neuroendocrine phenotype of carcinoid tumor cells. On the basis of this study, a clinical trial of VPA for patients with advanced carcinoid cancer will be conducted. Disclosure of potential conflicts of interest is found at the end of this article.
Quantification of human atherosclerotic plaques using spatially enhanced cluster analysis of multicontrast‐weighted magnetic resonance images (2004)

One of the current limitations of magnetic resonance imaging (MRI) is the lack of an objective method to classify plaque components. Here we present a cluster analysis technique that can objectively quantify and classify MR images of atherosclerotic plaques. We obtained three-dimensional (3D) images from 12 human coronary artery specimens on a 9.4T imaging system using multicontrast-weighted fast spin-echo (T1-, proton density-, and T2-weighted) imaging with an isotropic voxel size of 39 micro. Spatially enhanced cluster analysis (SECA) was performed on multicontrast MR images, and the resulting segmentation was evaluated against histological tracings. To visualize the overall structure of plaques, the MR images were rendered in 3D. The specimens exhibited lesions of American Heart Association (AHA) plaque classification types I-VI. Both MR images and histological sections were independently reviewed, categorized, and compared. Overall, the classification obtained from the cluster-analyzed MR and histopathology images showed very good agreement for all AHA types (92%, Cohen's kappa = 0.89, P < 0.0001). All plaque types were identified and quantified by SECA with a high degree of correlation between cluster-analyzed MR and manually traced histopathology data. MRI combined with SECA provides an objective method for atherosclerotic plaque component characterization and quantification.
RESPONSE OF EXTERNAL URETHRAL SPHINCTER TO HIGH FREQUENCY BIPHASIC ELECTRICAL STIMULATION OF PUDENDAL NERVE (2005)

Reversible block of EUS contractions by high frequency, biphasic stimulation of pudendal nerves is a potential method for suppressing detrusor-sphincter dyssynergia and improving voiding in spinal cord injured patients.
Trajectory Planning for Autonomous Ground Vehicles Driving in Structured Environments (2017)

To solve the problem of trajectory planning for Autonomous Ground Vehicles (AGVs) in structured environments, a kinematically-feasible trajectory planning approach based on road models is proposed. In order to cope with obstacle avoidance on roads, we develop an efficient path generation method, using the piecewise spiral curve to generate a set of continuous curvature paths which satisfy the constraints of the start and end point boundaries. Based on the proposed optimization function, the optimal path is selected. Compared with the model-based predictive trajectory planner, the method proposed in this paper can effectively avoid the problem of slow convergence or no feasible solution. The experimental results show that: The proposed method not only retains most of the advantages of model-based predictive trajectory planning, but also reduces the computational complexity to meet the real-time requirements. The curvature of the generated path is continuous and is suitable for the actual control of the vehicle. Simulation results show that the proposed method can track the reference path smoothly and avoid static obstacles successfully.