gebhart/patrepeval huggingface dataset:
Naloxone-inaccessible sigma receptor in rat central nervous system. (1983)

It has been postulated that the psychotomimetic effects of opiates of the benzomorphan series are due to their activity at the sigma receptor. Therefore, the binding of (+/-)-[3H]ethylketocyclazocine ( [3H]EKC), a benzomorphan, to synaptosomal membranes of rat central nervous tissue was studied. Surprisingly, high concentrations of naloxone, a mu, delta, and kappa receptor antagonist, only inhibited about 80% of the specifically bound [3H]EKC in the spinal cord. This suggested that the remaining 20% of the binding sites were not mu, delta, or kappa. The Scatchard plot of the binding of [3H]EKC was nonlinear but became linear in the presence of naloxone (1 microM), suggesting a single class of naloxone-inaccessible receptor sites. This biochemically readily distinguishable receptor type bound the dextrorotatory isomer of EKC stereoselectively. The sigma agonist N-allylnormetazocine [(+)-SKF 10,047] stereoselectively competed with the binding of [3H]EKC to this naloxone-inaccessible binding site. A number of opiates that have psychotomimetic activity also competed for binding to this binding site. This binding site is designated as sigma binding site according to the nomenclature originally suggested by Martin et al. [Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E. & Gilbert, P. E. (1976) J. Pharmacol. Exp. Ther. 197, 517-532]. The drug selectivity and regional distribution of this sigma binding site in the rat central nervous system are different from that of the mu and delta opioid receptors and phencyclidine receptors. The concentration of the sigma binding site is highest in the spinal cord, pons and medulla, and cerebellum.
Decreased BMD and Limb Deformities in Mice Carrying Mutations in Both <i>Lrp5</i> and <i>Lrp6</i> (2004)

Lrp6 and Lrp5 genetically interact in limb development in mice. Furthermore, heterozygosity for an inactivating mutation in Lrp6 further reduces BMD in both male and female mice lacking Lrp5.
Growth Hormone and Insulin Reverse Net Whole Body and Skeletal Muscle Protein Catabolism in Cancer Patients (1992)

The authors examined the effect of recombinant-human growth hormone (r-hGH) and insulin (INS) administration on protein kinetics in cancer patients. Twenty-eight cancer patients either received r-hGH for 3 days (GH group, n = 12, weight loss = 6 +/- 2%) or were not treated (control [CTL] group, n = 16, weight loss = 11 +/- 2%) before metabolic study. Recombinant-human growth hormone dose was 0.1 mg/kg/day (n = 6) or 0.2 mg/kg/day (n = 6). Patients then underwent measurement of baseline protein kinetics (GH/B, CTL/B) followed by a 2-hour euglycemic insulin infusion (1 mU/kg/minute) and repeat kinetic measurements (GH/INS,CTL/INS). Whole-body protein net balance (mumol leucine/kg/minute) was higher (p less than 0.05) in GH/INS (0.20 +/- 0.06) than in CTL/INS (0.06 +/- 0.03) or GH/B (-0.19 +/- 0.03). Skeletal muscle protein net balance (nmol phenylalanine/100 g/minute) in GH/INS (25 +/- 6) and CTL/INS (19 +/- 5) was higher than CTL/B (-18 +/- 3). Recombinant-human growth hormone and insulin reduce whole-body and skeletal muscle protein loss in cancer patients. Simultaneous use of these agents during nutritional therapy may benefit the cancer patient.
Link between drug absorption solubility and permeability measurements in Caco-2 cells (1998)

The objective of this investigation was to establish a relationship between drug permeability and solubility in vitro and the extent of drug absorption in humans. We selected drugs with varying permeabilities and solubilities with the aim of establishing a relationship between permeability and solubility measurements in vitro and the extent of absorption in vivo. Effective permeability coefficients of the model drugs (naproxen, phenytoin, propranolol, diltiazem, salicylic acid, ephedrine, cimetidine, chlorothiazide, and furosemide) at 37 degrees C and pH 7.2 were estimated using the Caco-2 cell line. Saturation solubilities of the model drugs were estimated at pH 7.2 and at 37 degrees C. Data obtained from the permeability and solubility experiments were employed in classifying the drugs into high and low permeability-solubility groups. The permeability coefficients ranged from 1x10(-7) to 4x10(-5) cm/s, and a good correlation was observed between the permeability coefficients in Caco-2 cells and percent absorbed in humans. Drugs in the high permeability, high solubility class are completely absorbed (90% or higher). The study results indicate that there is a strong link between permeability measured in Caco-2 cells, solubility, and fraction of drug absorbed in humans.
Perceptual and acoustic analysis of brazilian actresses' voices (2015)

Purpose: The present study aimed to compare actresses’ and non-actresses’ voices through perceptual and acoustic analysis and also to determine possible correlations between variables. Special attention was given to the identi­fication of the actor’s formant (AF). Method: Thirty actresses and thirty non-actresses participated as subjects. All participants were recorded reading at their habitual loudness level from a 200-word reading task. The acoustical variables obtained through the Longer Term Average Spectrum (LTAS) analysis included: (1) equivalent sound level (Leq), (2) speaking fundamental frequency (SFF), (3) alpha ratio, (4) level difference between the F1 and F0 regions (L1 - L0) and (5) energy level of 30 spectral points separated by 160 Hz. Voice samples from both groups were perceptually assessed by ­ve external raters. A total of 70 voice samples were evaluated: 30 actresses, 30 non-actresses and 10 repeated samples in order to assess the intra-rater concordance. Perceptual variables were: (1) pitch, (2) vocal extension, (3) loudness, (4) sonority, (5) breathiness, (6) hyper and hypofunctional voice production, (7) articulation and (8) overall voice quality. Results: Actresses’ voices were perceived to be lower, louder and more sonorous, with more vocal extention, better articulation, and better overall quality. There were no signifi­cant differences for hypofunction and breathiness. With the exception of SFF, which was signifi­cantly lower for actresses, no differences between groups were demonstrated for acoustic parameters. Furthermore, acoustic parameters did not correlate with perceptual variables. No evidence of the AF in actresses’ spectrums was found. Conclusion: While Perceptual analysis depicted differences in voice quality between actresses and non-actresses, there were no differences between these groups demonstrated for acoustic variables, including no evidence of the AF in actresses’ spectrums. Perceptual and acoustic parameter correlations were also not found.
Bandwidth-Variable Transceivers based on Four-Dimensional Modulation Formats (2014)

In this invited contribution, we discuss technology options for bandwidth-variable transceivers which are key components for the realization of flexible software-defined optical networking. Bandwidth-variable transceivers enable the software-controlled adaptation of physical layer parameters such as transmitted bit rate, spectral efficiency and transparent reach according to the traffic demands at hand. In particular, we focus on recent advances in four-dimensional modulation formats and in modulation format transparent data-aided digital signal processing. It is argued that four-dimensional modulation formats present an attractive complement to conventional polarization-multiplexed formats in the context of bandwidth-variable transceivers, where they enable a smooth transition with respect to spectral efficiency while requiring marginal additional hardware effort. Results of numerical simulations and experiments supporting this statement are presented. For the cost-efficient hardware implementation of bandwidth-variable transceivers supporting several polarization-multiplexed and four-dimensional modulation formats, digital signal processing algorithms are required which operate format transparent and consume little hardware resources. We discuss data-aided signal processing as one possible option, in particular with respect to carrier frequency recovery and channel estimation in combination with frequency domain equalization.
Effect of Cry-consensus Peptide, a Novel Recombinant Peptide for Immunotherapy of Japanese Cedar Pollinosis, on an Experimental Allergic Rhinitis Model in B10.S Mice (2007)

It was concluded that Cry-consensus peptide effectively controlled allergic responses, which results from shifting from a Th2-dominated to a Th1-dominated immune response.
Two-dimensional optical scanner with large angular rotation realized by self-assembled micro-elevator (2002)

A novel 2D scanner with large mirror area and large angular rotation has been proposed and demonstrated. The mirror is supported by the surface-micromachined micro-elevators by self-assembly. Maximum optical deflection angles of of /spl plusmn/14/spl deg/ and a resonant frequency of 1.5 kHz have been achieved.
Optimization and characterization of an opioid kappa receptor (OPRK1) antagonist (2014)

The opioid receptors are a subfamily of the family A G protein-coupled opioid receptor superfamily and consist of mu (OPRM1), delta (OPRD1), and kappa (OPRK1), all of which activate inhibitory G proteins. The dynorphins act as endogenous agonists of OPRK to activate a variety of signaling transduction pathways including those involving mitogen activated protein kinases (MAPK). Activation of OPRK leads to a number of physiological effects implicating a role for these receptors in addiction, dysphoria and reward. Hence, OPRK antagonists are being explored for their effects in the treatment of cocaine addiction, depression, and feeding behavior and have been proposed as a treatment for psychosis and schizophrenia. While a number of OPRK1 antagonists have been identified, all of the prototypic antagonists are very long-acting, exhibit unusual pharmacology, exhibit delayed onset of action, and are associated with serious safety concerns. Very few drug-like OPRK antagonists have been developed. New OPRK antagonists possessing novel scaffolds and improved selectivity are needed as pharmacological tools to better understand the OPRK- dynorphin system and as potential pharmacotherapies. The Scripps Research Institute Molecular Screening Center (SRIMSC), part of the Molecular Libraries Probe Production Centers Network (MLPCN), reports ML350 as a highly potent OPRK1 antagonist with an IC50 of 9-16 nM, with high selectivity (selectivities vs. OPRD1 and OPRM1 of 219-382–fold and 20-35–fold, respectively). ML350 was identified by high-throughput screening using a cell-based Tango™-format assay. A set of pharmacokinetic analyses show that ML350 has high passive membrane permeability, good brain penetration, no significant activity at three of four human cytochrome P450 subtypes, high binding for rodent plasma protein and modest binding for human plasma protein, and an encouraging in vivo pharmacokinetic profile in rats. ML350 was submitted to CEREP for broad panel screening against a panel of receptors, transporters, and ion channels; the data suggest that ML350 is generally inactive against a broad array of off targets and does not likely exert unwanted effects. Importantly, ML350 was shown to have a reversible analgesic effect when challenged with an OPRK agonist in a tail flick assay in mice. ML350 serves as a novel OPRK antagonist that can be developed as a therapeutic for the treatment of a variety of disorders involving the OPRK1-dynorphin system.
The pH as a Control Parameter for Oxidation-Reduction Potential on the Denitrification by Ochrobactrum anthropi SY 509 (2004)

The pH as a control parameter for oxidation-reduction potential (ORP) was investigated through the denitrification by Ochrobactrum anthropi SY509 under non-growing condition. The optimal pH of nitrate reductase was 7.0, and the minimal ORP level was -250 mV for the denitrification under aerobic condition. In the case of anaerobic condition, the optimal pHs of nitrate and nitrite reductase were shifted to 10.0 and 9.0, respectively, and the minimal ORP levels of nitrate and nitrite reductase were decreased to - 370 mV and - 340 mV, respectively. In the case of alkaline pH and anaerobic condition, the denitrification efficiency of nitrate was increased up to about 2-fold over that of neutral pH and anaerobic condition. Therefore, the combined control of pH and ORP in the anaerobic condition is shown to be an important parameter in the biological denitrification process.
Solid phase synthesis of polynucleotides. VI. Farther studies on polystyrene copolymers for the solid support (1982)

A simple solid phase method for the synthesis of oligodeoxyribonucleotides has been developed using the phosphotriester approach. Mononucleotide coupling units are sequentially added to the polystyrene copolymer with 1% divinylbenzene and two kinds of oligonucleotides, d(CACGACCCCTCCACGT) and d(AACTGGTATTACTGGGCG), are synthesized in a relatively high yield. One cycle of the mononucleotide addition is about 70 minutes, and this method is particularly suitable for the automation of the synthesis upon availability of an automatic synthesizer.
Highly Sensitive and Broadly Reactive Quantitative Reverse Transcription-PCR Assay for High-Throughput Detection of Rift Valley Fever Virus (2007)

Rift Valley fever (RVF) virus is a mosquito-borne virus associated with large-scale epizootics/epidemics throughout Africa and the Arabian peninsula. Virus infection can result in economically disastrous "abortion storms" and high newborn mortality in livestock. Human infections result in a flu-like illness, with 1 to 2% of patients developing severe complications, including encephalitis or hemorrhagic fever with high fatality rates. There is a critical need for a highly sensitive and specific molecular diagnostic assay capable of detecting the natural genetic spectrum of RVF viruses. We report here the establishment of a pan-RVF virus quantitative real-time reverse transcription-PCR assay with high analytical sensitivity (approximately 5 RNA copies of in vitro-transcribed RNA/reaction or approximately 0.1 PFU of infectious virus/reaction) and efficiency (standard curve slope = -3.66). Based on the alignments of the complete genome sequences of 40 ecologically and biologically diverse virus isolates collected over 56 years (1944 to 2000), the primer and probe annealing sites targeted in this assay are known to be located in highly conserved genomic regions. The performance of this assay relative to serologic assays is illustrated by testing of known RVF case materials obtained during the Saudi Arabia outbreak in 2000. Furthermore, analysis of acute-phase blood samples collected from human patients (25 nonfatal, 8 fatal) during that outbreak revealed that patient viremia at time of presentation at hospital may be a useful prognostic tool in determining patient outcome.
Femtosecond pulse shaping as analytic tool in mass spectrometry of complex polyatomic systems (2008)

An additional dimension to mass spectrometric studies on building blocks of proteins is discussed in this paper. The present approach is based on tailored femtosecond laser pulses, using the concept of strong-field pulse shaping in an adaptive feedback loop. We show that control strategies making use of coherent properties of the electromagnetic wave allow one to break pre-selected backbone bonds in amino acid complexes that may be regarded as peptide model systems. Studies on different chromophores, such as phenylalanine and alanine, while keeping the backbone structure unchanged elucidates the effect of the excitation dynamics on the relaxation pathways. The observation of protonated species in the corresponding mass spectra indicates that optimal control of ultrafast laser pulses may even be useful to study intramolecular reactions such as hydrogen- or proton-transfer in particular cases. This opens new perspectives for biophysical and biochemical research, since these photochemical reactions are suggested to explain, e.g. photostability of DNA.
Achievement of insulin independence in three consecutive type-1 diabetic patients via pancreatic islet transplantation using islets isolated at a remote islet isolation center (2002)

These early data demonstrate that (1) pancreatic islets remain viable after shipment to remote transplant sites; (2) pancreatic islet isolation techniques and experience can be concentrated at a small number of regional facilities that could supply islets to remote transplant centers; and (3) insulin independence via PIT can be achieved using a remote pancreatic islet isolation center.
Comparative evaluation of the protective effect of immune spleen cells and immune RNA against<i>Plasmodium berghei</i> (1988)

Earlier studies from this laboratory indicated that passive transfer of viable or frozen-thawed cells from spleens and lymph nodes of immune mice resulted in a significant protective immunity against Plasmodium berghei in syngeneic recipients. To assess whether immune RNA played a role in conferring such protection, experiments were designed wherein immune RNA was isolated from immune monkeys, rats and mice and transferred to normal mice. The effect of transfer was assessed by challenging RNA-primed animals with Plasmodium berghei. Results indicated that immune RNA failed to confer resistance against P. berghei both in syngeneic and in heterologous systems.
Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo (1998)

Uric acid is a well-known natural antioxidant present in fluids and tissues throughout the body. Oxyradical production and cellular calcium overload are believed to contribute to the damage and death of neurons that occurs following cerebral ischemia in victims of stroke. We now report that uric acid protects cultured rat hippocampal neurons against cell death induced by insults relevant to the pathogenesis of cerebral ischemia, including exposure to the excitatory amino acid glutamate and the metabolic poison cyanide. Confocal laser scanning microscope analyses showed that uric acid suppresses the accumulation of reactive oxygen species (hydrogen peroxide and peroxynitrite), and lipid peroxidation, associated with each insult. Mitochondrial function was compromised by the excitotoxic and metabolic insults, and was preserved in neurons treated with uric acid. Delayed elevations of intracellular free calcium levels induced by glutamate and cyanide were significantly attenuated in neurons treated with uric acid. These data demonstrate a neuroprotective action of uric acid that involves suppression of oxyradical accumulation, stabilization of calcium homeostasis, and preservation of mitochondrial function. Administration of uric acid to adult rats either 24 hr prior to middle cerebral artery occlusion (62.5 mg uric acid/kg, intraperitoneally) or 1 hr following reperfusion (16 mg uric acid/kg, intravenously) resulted in a highly significant reduction in ischemic damage to cerebral cortex and striatum, and improved behavioral outcome. These findings support a central role for oxyradicals in excitotoxic and ischemic neuronal injury, and suggest a potential therapeutic use for uric acid in ischemic stroke and related neurodegenerative conditions.
Studies relating to the synthesis of the immunosuppressive agent FK-506: synthesis of the cyclohexyl moiety via a group-selective epoxidation (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies relating to the synthesis of the immunosuppressive agent FK-506: synthesis of the cyclohexyl moiety via a group-selective epoxidationStuart L. Schreiber and David B. SmithCite this: J. Org. Chem. 1989, 54, 1, 9–10Publication Date (Print):January 1, 1989Publication History Published online1 May 2002Published inissue 1 January 1989https://pubs.acs.org/doi/10.1021/jo00262a004https://doi.org/10.1021/jo00262a004research-articleACS PublicationsRequest reuse permissionsArticle Views786Altmetric-Citations38LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Natural History and Treatment of Low and High Risk Superficial Bladder Tumors (1988)

Since 1979 a prospective randomized trial was done to examine the efficacy of intravesical doxorubicin as prophylaxis against recurrence. After complete transurethral resection of the tumor, patients were divided into 3 groups at random: group 1-no further treatment after transurethral resection, group 2-doxorubicin twice weekly for 6 weeks and group 3-doxorubicin for 1 year. A total of 268 patients entered the study. Neither frequency of recurrences, tumor progression nor survival rate was improved significantly by the adjuvant treatment, so that only a limited number of patients will profit by instillation therapy. Analysis of previously reported data suggests that patients with superficial bladder tumors can be stratified into groups with appreciable differences in risk of progression. With regard to these results a differentiated use of a "wait and see" adjuvant intravesical therapy and more aggressive treatment after transurethral resection of superficial bladder tumors seems to be indicated rather than a general practice of chemoprophylaxis.
Clinical features predicting failure of pathogen identification in patients with community acquired pneumonia (2008)

Community acquired pneumonia (CAP) is caused by a variety of microorganisms. By identifying patients at risk for failure of pathogen identification, it is possible to make an early decision on the extent of diagnostic procedures to be performed. This is especially important in patients with severe CAP. The aim of this study was to identify these patients by using clinical and laboratory features. In 201 patients hospitalized for CAP, clinical and laboratory variables were collected. Pathogen identification was performed by culture of sputum and blood, urine antigen tests, polymerase chain reaction of sputum, serological testing and viral culture of the pharynx. In 128 patients a respiratory microorganism was identified. In both univariate and multivariate analysis, failure of pathogen identification was predicted by pre-hospital antibiotic therapy, a medical history of hypertension and a low C-reactive protein. We conclude that patients with pre-hospital antibiotic therapy, a medical history of hypertension and a relatively low C-reactive protein are at risk for failure of pathogen identification. These predictors should be confirmed in a larger population. Invasive testing in high-risk patients with CAP in the presence of these predictors should be considered at an early phase of hospitalization.