gebhart/patrepeval huggingface dataset:
A phase 1 study of ACE‐536, a regulator of erythroid differentiation, in healthy volunteers (2014)

ACE-536, a recombinant protein containing a modified activin receptor type IIB, is being developed for the treatment of anemias caused by ineffective erythropoiesis, such as thalassemias and myelodysplastic syndromes. ACE-536 acts through a mechanism distinct from erythropoiesis-stimulating agents to promote late-stage erythroid differentiation by binding to transforming growth factor-β superfamily ligands and inhibiting signaling through transcription factors Smad 2/3. The goal of this Phase 1 study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of ascending dose levels of ACE-536 in healthy volunteers. Thirty-two postmenopausal women were randomized in sequential cohorts of eight subjects each to receive up to two doses of either ACE-536 (0.0625-0.25 mg/kg) or placebo (3:1 randomization) given subcutaneously every 2 weeks. Mean baseline age was 59.4 years, and hemoglobin was 13.2 g/dL. ACE-536 was well tolerated at dose levels up to 0.25 mg/kg over the 1-month treatment period. There were no serious or severe adverse events, nor clinically meaningful changes in safety laboratory measures or vital signs. Mean ACE-536 AUC0-14d and Cmax increased proportionally after first dose; mean t½ was 15-16 days. Dose-dependent increases in hemoglobin concentration were observed, beginning 7 days after initiation of treatment and maintained for several weeks following treatment. The proportion of subjects with a hemoglobin increase ≥1.0 g/dL increased in a dose-dependent manner to 83.3% of subjects in the highest dose group, 0.25 mg/kg. ACE-536 was well tolerated and resulted in sustained increases in hemoglobin levels in healthy postmenopausal women.
Driver Monitors: Improving Transportation Safety and Enhancing Performance Through Behavioral Change (2004)

Proposal Driving presents the greatest risk to human life in the oil and gas industry. While short-term changes in driving habits may be hard to achieve, they can be modified or improved with regular, positive influence. In 1997, Schlumberger adopted a plan to monitor, evaluate, and improve driver behavior and performance using vehicle-data monitoring systems. When compiled in a database, vehicle monitor information enables an objective evaluation of the operator's driving habits. The intent is to use data to identify unsafe behaviors, and subsequently train, coach, and mentor individuals to reduce or eliminate these behaviors. Emphasis is placed on identifying habits or tendencies known to be high-risk factors. As an operator's performance is evaluated on an ongoing basis, their performance improves through positive reinforcement. Previously published papers have described the concept of this behavior modification approach to driver performance improvement. In this paper, we present the results of 3 years of data collected from a fleet of more than 2,000 vehicles that drove more than 50 million miles a year in the continental U.S.A. Following complete system implementation and vehicle hardware installation, from 2000 to 2003 we have seen a more than 50% reduction in automotive incidents (per million miles driven), and a more than 70% reduction in high-potential automotive incidents, per year. This paper includes details of the driver performance report evaluation process, and describes how data are used in the coaching and remedial process. Examples of using monitor data in an incident investigation and analysis are also provided. We also demonstrate how the program has helped improve regulatory compliance, and has increased regulatory report preparation efficiency.
The North American Operations Research Societies (2011)

Abstract This short article describes the two major societies that make up the North American Operations Research Societies and lists a collection of other societies that are affiliated with the field of operations research within North America.
Adenoviruses in Fecal Samples from Asymptomatic Rhesus Macaques, United States (2012)

Adenoviruses can cause infectious diarrheal disease or respiratory infections in humans; 2 recent reports have indicated probable human infection with simian adenoviruses (SAdVs). To assess the possibility of animal-to-human transmission of SAdVs, we tested fecal samples from asymptomatic rhesus macaques housed in 5 primate facilities in the United States and cultured 23 SAdV isolates. Of these, 9 were purified and completely sequenced; 3 SAdV samples from the American Type Culture Collection (SAdV-6, SAdV-18, and SAdV-20) were also completely sequenced. The sequence of SAdV-18 was closely related to that of human adenovirus F across the whole genome, and the new isolates were found to harbor 2 fiber genes similar to those of human adenovirus (HAdV) strains HAdV-40 and HAdV-41, which can cause infectious diarrhea. The high prevalence of adenoviruses in fecal samples from asymptomatic rhesus macaques and the similarity of the isolates to human strains indicates the possibility of animal-to-human transmission of SAdVs.
The effects of nicotine on Parkinson's disease. (2000)

Post-mortem studies have demonstrated a substantial loss of nicotinic receptors in Parkinson's disease (PD), which may be at least partially responsible for some of the cognitive, motoric, and behavioral deficits seen in this disorder. Epidemiologic studies have suggested that cigarette smoking is a strong negative risk factor for the development of PD. We have previously shown that blockade of central nicotinic receptors produces cognitive impairment in areas of new learning, short-term memory, and psychomotor slowing with increasing dose sensitivity with age and disease. Studies of acute stimulation of nicotinic receptors in Alzheimer's disease with nicotine and the novel agonist ABT-418 in our laboratory and others have shown improvements in several measures of cognitive function. Prior studies of the effects of nicotine in PD have suggested some improvements in clinical symptomatology. We have begun quantitative studies of both acute and chronic nicotine in PD to assess both cognitive and motor effects. Fifteen (15) nondemented subjects (age 66 +/- 5.3; M/F = 11/4) with early to moderate PD (mean Hoehn-Yahr stage = 1.77; MMSE = 28.6) received a dose-ranging study of intravenous nicotine up to 1.25 microg/kg/min, followed by chronic administration of nicotine by transdermal patch with doses ranging up to 14 mg per day for 2 weeks. Testing occurred both during drug administration and up to 2 months after drug cessation to look for prolonged effects. Preliminary analysis shows improvements after acute nicotine in several areas of cognitive performance, particularly measures such as reaction time, central processing speed, and decreased tracking error. Improvements in attention and semantic retrieval were not seen. After chronic nicotine, improvements were seen in several motor measures suggesting improved extrapyramidal functioning. This appeared to be sustained for up to 1 month after drug. The treatment was well tolerated. Nicotinic stimulation may have promise for improving both cognitive and motor aspects of Parkinson's disease.
Di- and triester prodrugs of the varicella-zoster antiviral agent 6-methoxypurine arabinoside (1992)

6-Methoxypurine arabinoside (9-beta-D-arabinofuranosyl-6-methoxy-9H-purine, 1) has potent and selective activity against varicella-zoster virus in vitro. An unfavourable metabolic profile observed with oral dosing in the rat led to the preparation of a variety of 2',3',5'-triesters (2a-n) and several 2',3'-, 2',5'-, and 3',5'-diesters of this arabinoside (3a-n, 4a-f, and 5a-j, respectively). The compounds were evaluated as prodrugs by measuring the urinary levels of 1 in rat urine after oral dosing. With the exception of triacetate 2a, the triesters failed to significantly enhance bioavailability. Administration of compound 2a resulted in a 3-fold increase in systemic availability of 1, possibly because of its increased water solubility (1.6 times more soluble than 1) and only slightly increased relative log P value (1.93 vs 0.50 for 1). The longer chain aliphatic triesters and aromatic triesters had lower water solubilities and increased lipophilic partitioning. These factors might account for the lower systemic bioavailability of these compounds. In contrast, the diesters, especially the aliphatic diesters, showed significantly improved systemic availability. This might be a consequence of the higher aqueous solubilities and enhanced partition coefficients seen with these compounds. 2',3'-Diacetate 3a showed the best combination of high systemic availability and water solubility of all the prodrugs of 1.
Electrical resistance of a capillary endothelium. (1981)

The electrical resistance of consecutive segments of capillaries has been determined by a method in which the microvessels were treated as a leaky, infinite cable. A two-dimensional analytical model to describe the potential field in response to intracapillary current injection was formulated. The model allowed determination of the electrical resistance from four sets of data: the capillary radius, the capillary length constant, the length constant in the mesentery perpendicular to the capillary, and the relative potential drop across the capillary wall. Of particular importance were the mesothelial membranes covering the mesenteric capillaries with resistances several times higher than that of the capillary endothelium. 27 frog mesenteric capillaries were characterized. The average resistance of the endothelium was 1.85 omega cm2, which compares well with earlier determinations of the ionic permeability of such capillaries. However, heterogeneity with respect to resistance was observed, that of 10 arterial capillaries being 3.0 omega cm2 as compared with 0.95 omega cm2 for 17 mid- and venous capillaries. The average in situ length constant was 99 micrometers for the arterial capillaries and 57 micrometers for the mid- and venous capillaries. It is likely that the ions that carry the current must move paracellularly, through junctions that are leaky to small solutes.
Polysialyltransferase ST8Sia II (STX) polysialylates all of the major isoforms of NCAM and facilitates neurite outgrowth (2001)

The neural cell adhesion molecule (NCAM) has different isoforms due to different sizes in its polypeptide and plays a significant role in neural development. In neural development, the function of NCAM is modified by polysialylation catalyzed by two polysialyltransferases, ST8Sia II and ST8Sia IV. Previously, it was reported by others that ST8Sia II polysialylates only transmembrane isoforms of the NCAM, such as NCAM-140 and NCAM-180, but not NCAM-120 and NCAM-125 anchored by a glycosylphosphotidylinositol. In the present study, we first discovered that ST8Sia II polysialylates all isoforms of the NCAM examined, and we demonstrated that polysialylation of NCAM expressed on 3T3 cells facilitates neurite outgrowth regardless of isoforms of NCAM, where polysialic acid is attached. We then show that neurite outgrowth is significantly facilitated only when polysialylated NCAM is present in cell membranes. Moreover, the soluble NCAM coated on plates did not have an effect on neurite outgrowth exerted by soluble L1 adhesion molecule coated on plates. These results, taken together, indicate that ST8Sia II plays critical roles in modulating the function of all major isoforms of NCAM. The results also support previous studies showing that a signal cascade initiated by NCAM differs from that initiated by L1 molecule.
Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. (1980)

Abstract A murine hybridoma secreting monoclonal IgE antibodies of anti-2,4-dinitrophenyl (DNP) specificity was generated by fusion of SP2/0 tumor cells and spleen cells from DNP-Ascaris-hyperimmunized mice. Hybridomas secreting anti-DNP antibodies of other heavy chain classes, i.e., μ, γ1 and γ2b, were also obtained from the same fusion experiment. Large quantities of IgE antibodies were obtained from ascites of mice in which the IgE-secreting hybridoma was propagated in vivo. The IgE antibodies were isolated by precipitation with ammonium sulfate followed by afinity chromatography on DNP-bovine serum albumin (BSA)-Sepharose-4B and further purified by ion-exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-200. The isolated IgE has an approximate m.w. of 184,000, a total carbohydrate content of 13.3%, and its amino acid composition has been determined. The antibody has an association constant with DNP-lysine of 1.4 × 108 M-1 at 25°C and 7.1 × 107 M-1 at 37°C. Rabbit and goat antibodies against the hybridoma IgE were prepared and the antisera were made specific for IgE by adsorption on normal mouse serum protein-Sepharose-4B. Solid phase radioimmunoassays for measuring murine antigen-specific and total IgE were developed and were shown to have high specificity and sensitivity. Finally, the isolated hybridoma IgE can mediate antigen (DNP-BSA)-induced release of mediator (serotonin) from rat basophilic leukemia cells.
Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4 (1993)

The product (pRb) of the retinoblastoma gene (RB-1) prevents S-phase entry during the cell cycle, and inactivation of this growth-suppressive function is presumed to result from pRb hyperphosphorylation during late G1 phase. Complexes of the cyclin-dependent kinase, cdk4, and each of three different D-type cyclins, assembled in insect Sf9 cells, phosphorylated a pRb fusion protein in vitro at sites identical to those phosphorylated in human T cells. Only D-type cyclins activated cdk4 enzyme activity, whereas cyclins A, B1, and E did not. When Sf9 cells were coinfected with baculovirus vectors encoding human pRb and murine D-type cyclins, cyclins D2 and D3, but not D1, bound pRb with high stoichiometry in intact cells. Introduction of a vector encoding cdk4, together with those expressing pRb and D-type cyclins, induced pRb hyperphosphorylation and dissociation of cyclins D2 and D3, whereas expression of a kinase-defective cdk4 mutant in lieu of the wild-type catalytic subunit yielded ternary complexes. The transcription factor E2F-1 also bound to pRb in insect cells, and coexpression of cyclin D-cdk4 complexes, but neither subunit alone, triggered pRb phosphorylation and prevented its interaction with E2F-1. The D-type cyclins may play dual roles as cdk4 regulatory subunits and as adaptor proteins that physically target active enzyme complexes to particular substrates.
Effects of SCH 32651 on resting and stimulated acid secretion in guinea‐pig isolated fundic mucosa (1984)

Effects of SCH 32651, a novel antisecretory and cytoprotective agent, on resting and stimulated acid secretion by the guinea-pig isolated fundic mucosa were studied. SCH 32651 inhibited resting acid secretion in proportion to concentrations in serosal solution (0.1-10 microM), the IC50 being 4.4 microM. Cimetidine and atropine at concentrations up to 100 microM were inactive. Serosal application of SCH 32651 inhibited acid secretory responses to histamine (10 microM), methacholine (1 microM) or dibutyryl cyclic AMP (0.5 mM) plus theophylline (1 mM) in a concentration-dependent manner. The IC50S against histamine, methacholine and db cyclic AMP plus theophylline were 4.2 microM, 0.71 microM and 2.9 microM, respectively. In contrast, atropine and cimetidine each at 100 microM, a concentration that entirely abolished responses to methacholine and histamine, respectively, did not affect acid responses to db cyclic AMP plus theophylline. The inhibitory effects of SCH 32651 on resting and histamine-stimulated acid secretion were readily reversible upon washing. SCH 32651 0.1 mM in the mucosal solution also greatly suppressed the resting and stimulated acid secretion. In the presence of histamine treatment, SCH 32651 concomitantly caused a marked rise in K+ entry into the mucosal solution in parallel to a decline in the appearance of H+ in the same solution. The various events demonstrated by SCH 32651 in the present study are shared by omeprazole, a potent antisecretory agent working through inhibition of gastric H+/K+-ATPase. We conclude that SCH 32651 as a potent antisecretory agent seems to act directly on the parietal cell, near or at the site of H+/K+-ATPase which is a final step in the acid secretory process triggered by various stimuli.
Mammary tumorigenesis in feral mice: identification of a new int locus in mouse mammary tumor virus (Czech II)-induced mammary tumors (1987)

A population of Mus musculus subsp. musculus (Czech II), recently isolated from the wild, lack endogenous mouse mammary tumor virus (MMTV) proviral genomes. Some of these mice carry an infectious MMTV [designated MMTV (Czech II)] that is transmitted in the milk and is associated with mammary tumor development. This virus is distinct from laboratory strains of MMTV present in inbred mice. An MMTV (Czech II) genome was found within a 0.5-kilobase region of the cellular genome in five of 16 Czech II mammary tumors. MMTV insertion at this site activates expression of a 2.4-kilobase species of RNA from a previously silent cellular gene. This region of the cellular genome was designated int-3 since it is unrelated to the int-1 and int-2 loci. The int-3 locus does not appear to correspond to other proto-oncogenes but is well conserved among mammalian species.
SHEDDING LIGHT ON HYBRID OPTICS: A Tutorial in Coupling (1999)

In most fiber optic systems, optical fiber and waveguides are coupled to and from bulk optical devices, creating hybrid optical devices. In this tutorial article, the authors explain in detail how to successfully collimate, focus, and align hybrid optics, including polarizing and polarization maintaining optics.
The extrinsic nature of nonlinear behavior observed in lead zirconate titanate ferroelectric ceramic (1991)

The nonlinear electric and electromechanical responses of lead zirconate titanate Pb(ZrxTi1−x)O3 ceramics to an external ac electric field have been measured under different driving levels. The onset of measurable nonlinearity is observed to be accompanied by the appearance of hysteresis loops. This lossy nature suggests that the nonlinearities in a ferroelectric ceramic are generated by the domain-wall motion. In addition, aging experiments and the bias field dependence of the threshold field (onset of nonlinearity) all indicate the extrinsic nature of the nonlinear behavior of ferroelectric ceramics. A phenomenological theory of Arlt, Dederichs, and Herbiet [Ferroelectrics 74, 34 (1987)] has been extended to include the nonlinear contributions. With only 90° wall vibration being considered, the theory leads to some basic understanding of the experimental results.
The subtilin gene of Bacillus subtilis ATCC 6633 is encoded in an operon that contains a homolog of the hemolysin B transport protein (1992)

Sequence analysis upstream from the subtilin structural gene (spaS) in Bacillus subtilis ATCC 6633 revealed several open reading frames, SpaB, SpaC, and SpaD. SpaB, consisting of 599 amino acid residues, shows excellent homology with a variety of membrane translocator proteins, such as HlyB from Escherichia coli and some mammalian multidrug resistance proteins. When the spaB gene was interrupted by integration of a chloramphenicol acetyltransferase gene, the ability of the cell to produce subtilin, as determined by a halo assay, was lost. The homology of SpaB to translocator proteins, including transmembrane and ATP-binding regions, suggests that SpaB may play a role in subtilin secretion. The SpaB open reading frame overlaps with another open reading frame called SpaC, and the possibility that the SpaB and SpaC proteins become fused by frameshifting is considered. Regions of homology between SpaD (177 residues) and HlyD were also found, suggesting that SpaD may participate with SpaB in translocation of subtilin through the membrane. Although no readily interpretable homologies to SpaC (442 residues) were found, its sequence suggests that it is membrane associated. The absence of rho-independent transcription terminators between these open reading frames suggests that they are all part of the same operon.
Sustainable Treatment and Detoxification of1-Chloro-2,4-Dinitrobenzene-containing Industrial Wastewater (2004)

In 1-chloro-2,4-dinitrobenzene (CDNB) manufacture, the washing process discharges a large amount of CDNB-rich acidic effluent: a very aggressive and toxic wastewater. The concentration of CDNB reaches up to 332.2mg/L. CDNB has been known as an intracellular glutathione-depleting agent and shown to have an adverse effect on erythrocyte membrane integrity and caused aemolysis of human red blood cell. 1 Its removal from wastewater is necessary for health and environmental reason.Two main techniques have been used for the decontamination of CDNB-containing wastewater:activate-carbon adsorption and biodegradation. Biodegradation method works well in summer.However in winter, the activity of animalcules decreases dramatically with the dropping of temperature. Adsorption of CDNB on fresh active-carbon is quick and efficient. However once saturated, active-carbon loses adsorption capacity sharply. The revival of active-carbon by flash steam blowing or sweeping proves to be sluggish and inefficient. Therefore frequent change and replenish of active-carbon is necessary which results in significant operating cost.In this study, we disclose an easy-operating and sustainable method for the treatment of CDNB-contaminated wastewater, which not only removes the toxic CDNB from wastewater and readily revives the active-carbon, but also produces another useful chemical 2,4-dinitrophenol(DNP). Our method is based upon the physical adsorption of CDNB on active-carbon and the chemical conversion of CDNB to SDNP and then to DNP. As a well known nucleophilic substitution example, chlorobenzene with one/two/three NO2, a very strong electron-withdrawing group, at its ortho- and/or para- positions can be readily hydrolysed to give the corresponding phenols under basic condition (Scheme 1).First, the CDNB-contaminated wastewater was treated with active-carbon at room temperature.CDNB was thus adsorbed on to active-carbon physically. The CDNB-loaded active-carbon was filtered off. The acidic filtrate was neutralised by aqueous Ca(OH)2 to gi
Synthesis, Fungicidal and Antibacterial Activity of New Pyridazine Derivatives (2009)

Compounds 1 -3 were obtained in the reaction of 3,6-dichloropyridazines with phenylacetonitriles in the biphasic system -DMSO / 50% NaOH.The chlorine atom was replaced with cycloalkylamino (4 -13) and hydrazinyl (23, 24) moiety.These last compounds were condensed with aldehydes (25 -34).Pyridazynylphenylacetonitriles were converted into amides 14 -18 and thioamides 19 -22.In compounds 2, 3 the chlorine atom was replaced with thiophenyl (37, 38) and in compound 1 with thioethyl and thiophenyl (35, 36) functional groups.In the reactions of compounds 1, 2 with ammonium polysulfide thioamides with thiol group (39, 40) and chlorine atom (41, 42) were obtained.Compounds 1 -17, 19 -43 were screened for antibacterial and fungicidal activities.