gebhart/patrepeval huggingface dataset:
The novel elastase inhibitor BAY 85-8501: First-in-man study to evaluate safety, tolerability and pharmacokinetics in healthy male subjects (2014)

Human neutrophil elastase (HNE) is a key mediator of tissue remodeling and inflammation. An excess of HNE activity has been implicated in the pathogenesis of inflammatory pulmonary diseases, e.g. bronchiectasis (BE), COPD, and pulmonary hypertension. HNE inhibitors could potentially restore the protease/anti-protease balance in these diseases providing a new therapeutic target. BAY 85-8501 is a novel, selective and reversible HNE inhibitor with activity in the picomolar concentration range, which reveals target inhibition in the lung and ameliorates pulmonary inflammation in preclinical models. This First-in-Man study evaluated BAY 85-8501 in a Single-Dose-Escalation (SDE) design with 0.05, 0.1, 0.2, 0.5 or 1.0 mg as oral liquid formulation in 37 healthy male subjects (27 active, 10 placebo). The single dose treatments were safe and well tolerated without serious or severe adverse events and without any hints for mode of action or drug substance related adverse effects. All clinical safety parameters (BP, HR, ECG) and clinical laboratory parameters were in the normal range for single doses up to 1 mg. Drug absorption was fast, max. concentration (C) reached after 1 h, mean drug half-life was up to 145 - 175 h, allowing once daily dosing. Max. C and Area under Curve (0-24) increased in a dose-proportional way. Renal elimination of the unchanged drug is a minor pathway of elimination ( 4%). SDE up to 1 mg BAY 85-8501 was safe and well tolerated with pharmacokinetics that allow once daily dosing. Drug candidate is adequate for further clinical evaluation in studies in chronic anti-inflammatory treatment of lung diseases.
A Mirror Predistortion linear power amplifier (2011)

We propose a new type of predistortion linearization technique: “Mirror Predistortion”. In a regular predistortion power amplifier (PA), the AM-AM and AM-PM distortion (Or IMD3, Third Order Inter-modulation Distortion, and IMD5) of the PA are not known before measurement. In the Mirror Predistortion technique, we choose a PA with identical design as, but smaller than the main PA, as a Mirror Predistorter (PD). Since this Mirror PD's nonlinear characteristics tracks the main PA, there is no need for nonlinear characterization for the PD or the PA. We have reduced this concept to practice and have built a mirror predistortion linear PA having 23 dB improvement in IMD3, at a 2-tone total output power of 34 dBm, with 7.5 dB back off from P1dB of 41.5dBm.
Viscoelastic Warpage Analysis of Surface Mount Package (2001)

The reduction of the warpage of LSI package is a critical issue to ensure good solder joint connection in surface mount. In this study, different combinations of finite element and calculating methods were used to investigate the best method for predicting the thin small outline packages (TSOP) warpage. The results indicate that viscoelastic-GK calculation with relaxation of shear modulus and of bulk modulus using the multilayer shell element is the most appropriate method for predicting the warpage. All calculations confirm that a compound thickness ratio of 1.2 results in minimal warpage for a large chip TSOP. In this case, the warpage is reduced to near zero and the compound properties have little influence on warpage. However, for a small chip TSOP, a compound thickness ratio of 2.0–2.9 reduces the warpage. The warpage of small chip TSOP shows a severe saddle shape. The ratio and the magnitude of warpage depend on the compound properties. Also, the elastic method may result in a false simulation.
Fragile X gene instability: anchoring AGGs and linked microsatellites. (1995)

Interspersed AGGs within the FMR1 gene CGG repeat region may anchor the sequence and prevent slippage during replication. In order to detect the AGG position variations, we developed a method employing partial MnlI restriction analysis and analyzed X chromosomes from 187 males, including 133 normal controls (117 with 20-34 and 16 with 35-52 repeats), plus 54 fragile X premutations with 56-180 repeats. Among controls, the interspersed AGG positions were highly polymorphic, with a heterozygosity of 91%. Among the control samples, 1.5% had no AGG positions, 25% had one, 71% had two, and 3% had three. Among the fragile X premutation samples, 63% had no AGG, while 37% had only one AGG. Analysis of premutation samples within fragile X families showed that variation occurred only within the 3' end of the region. Thus, the instability was polar. Controls with > or = 15 pure CGG repeats were associated with the longest alleles of two nearby microsatellites, FRAXAC1 with 20-21 repeats and DXS548 with 202-206 bp and with increased microsatellite heterozygosity. The association of long pure CGG regions, as with fragile X chromosomes, with the longer and more heterozygous microsatellite alleles suggests they may be related mechanistically. Further, our results do not support a recent suggestion that the frequency of fragile X alleles may be increasing. Finally, analysis of a set of nonhuman primate samples showed that long pure CGG tracks are variable in size and are located within the 3' region, which suggests that polar instability within FMR1 is evolutionarily quite old.
A pair of chiral flavonolignans as novel anti‐cyanobacterial allelochemicals derived from barley straw ( <i> <scp>H</scp> ordeum vulgare </i> ): characterization and comparison of their anti‐cyanobacterial activities (2013)

The inhibitory effect of barley straw (Hordeum vulgare) on cyanobacteria has been observed in many field and laboratory studies for over 30 years, although the compounds responsible for this anti-cyanobacterial effect have remained unknown. In this study, a pair of chiral flavonolignans were isolated from barley straw extract using a bioassay-guided isolation procedure against Microcystis sp. The structures of the allelopathic compounds were elucidated by NMR (nuclear magnetic resonance) and HPLC-MS (high performance liquid chromatography-mass spectrometry), and turned out to be salcolin A and B. The enantiomers differ in their anti-cyanobacterial abilities. Both enantiomers exhibited inhibitory effects on Microcystis sp., and the EC50 (concentration for 50% of maximal effect) of salcolin A and B were 6.02 × 10(-5) and 9.60 × 10(-5 ) mol l(-1) , respectively. Furthermore, the modes of actions of the enantiomers were investigated and compared at a single cell level by flow cytometry. Salcolin A was found to induce an increase on cyanobacterial intracellular ROS (reactive oxygen species) levels and to inhibit esterase activity, whereas salcolin B caused leakages of cyanobacterial cytoplasms. Thus, salcolin A was more 'algistatic', and salcolin B was more 'algicidal'. This study suggests that salcolin is the key allelochemical in barley straw's inhibitory effect on cyanobacteria and could be used as an agent in the future control of cyanobacterial harmful algae blooms.
LETTERS (1991)

RETURN TO ISSUEPREVLetterNEXTLETTERSCite this: Chem. Eng. News 1991, 69, 9, 2–3Publication Date (Print):March 4, 1991Publication History Published online10 November 2010Published inissue 4 March 1991https://doi.org/10.1021/cen-v069n009.p002Copyright © 1991 AMERICAN CHEMICAL SOCIETYArticle Views14Altmetric-Citations-LEARN 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 InReddit PDF (456 KB) Get e-Alerts
Plastic Instability in Irradiated Zr-Sn and Zr-Nb Alloys (1974)

Factors affecting the plastic instability of irradiated zirconium alloys in tensile deformation have been studied. The materials used were pure zirconium, commercial Zircaloy-2 and Zr-2.5Nb, and a series of alloys based on pure zirconium containing either niobium or tin. The materials were rolled into thick sheet which enabled different crystallographic textures and deformation modes to be studied. Niobium alloy additions delay the onset of plastic instability and in some circumstances reverse the textural effects found in commercial Zircaloy-2 and Zr-2.5Nb. The merits of Zr-Nb alloys for use as fuel sheathing are outlined.
Preparation and in Vitro Evaluation of Novel Lipopeptide Transfection Agents for Efficient Gene Delivery (2008)

Gene therapy by delivery of nonviral expression vectors is highly desirable, due to their safety, stability, and suitability for production as bulk pharmaceuticals. However, low transfection efficiency remains a limiting factor in application on nonviral gene delivery. Despite recent advances in the field, there are still major obstacles to overcome. In an attempt to construct more efficient nonviral gene delivery vectors, we have designed a series of novel lipopeptide transfection agents, consisting of an alkyl chain, one cysteine, 1 to 4 histidine and 1 to 3 lysine residues. The lipopeptides were designed to facilitate dimerization (by way of the cysteine residues), DNA binding at neutral pH (making use of charged lysine residues), and endosomal escape (by way of weakly basic histidine residues). DNA/lipopeptide complexes were evaluated for their biophysical properties and transfection efficiencies. The number and identity of amino acids incorporated in the lipopeptide construct affected their DNA/lipopeptide complex forming capacity. As the number of lysine residues in the lipopeptide increased, the DNA complexes formed became more stable, had higher zeta potential (particle surface charge), and produced smaller mean particle sizes (typically 110 nm at a charge ratio of 5.0 and 240 nm at a charge ratio of 1.0). The effect of inclusion of histidines in the lipopeptide moiety had the opposite effect on complex formation to lysine, but was necessary for high transfection efficiency. In vitro transfection studies in COS-7 cells revealed that the efficiency of gene delivery of the luciferase encoding plasmid, pCMV-Luc, mediated by all the lipopeptides, was much higher than poly(L-lysine) (PLL), which has no endosomal escape system, and in two cases was slightly higher than that of branched polyethylenimine (PEI). Lipopeptides with at least two lysine residues and at least one histidine residue produced spontaneous transfection complexes with plasmid DNA, indicating that endosomal escape was achieved by incorporation of histidine residues. These low molecular weight peptides can be readily synthesized and purified and offer new insights into the mechanism of action of transfection complexes.
Pulmonary intravascular macrophages in horses and ponies (1994)

Seven horses (4 anesthetized and 3 awake) and 2 ponies (anesthetized) were studied to evaluate the high sensitivity of the pulmonary circulation of the horse to various blood-borne particles, and to establish the presence of intravascular macrophages in the lung. Pulmonary and systemic pressures and cardiac output before and during particle injection were measured in some animals. An anesthetized foal had a large increase in pulmonary arterial pressure (32 and 34 mm of Hg) within 1 minute of IV administration of small test doses of radioactively labeled liposomes (2.5 mumol/kg of body weight) or a 1% suspension of blue pigment (0.3 ml/kg), respectively. Quantitative real-time gamma camera imaging of the foal revealed high retention of the labeled liposomes during the first pass through the lungs; retention persisted throughout the experiment. Postmortem analysis revealed 55 and 47% lung retention of liposomes and blue pigment, respectively. The 2 anesthetized ponies had increased pulmonary artery pressure of 34 +/- 7 mm of Hg, decreased cardiac output, and 42% lung retention after administration of 1% blue pigment (0.2 ml/kg), whereas 3 awake horses had increased pressure of 28 +/- 9 mm of Hg after 1.8 x 10(8) (1.8-microns-diameter) latex microspheres/kg. None of the injected particles caused vascular obstruction, and they do not cause pulmonary vascular reactivity in species that lack pulmonary intravascular macrophages. Finally, 3 horses (1 anesthetized and 2 awake) were infused IV with small doses of the blue pigment, and their lungs were perfusion-fixed to identify specific labeling of the pulmonary intravascular macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Reactions of sodium borohydride. IV. Reduction of aromatic sulfonyl chlorides with sodium borohydride. (1987)

Aromatic sulfonyl chlorides were reduced with sodium borohydride in tetrahydrofuran at 0 C to the corresponding sulfinic acids in good yields. Further reduction proceeded when the reaction was carried out under reflux in tetrahydrofuran to give disulfide and thiophenol derivatives via sulfinic acid. Furthermore, sulfonamides were reduced with sodium borohydride by heating directly to give sulfide, disulfide and thiophenol derivatives, and diphenyl sulfone was reduced under similar conditions to give thiophenol and biphenyl
Selective Peripheral Denervation in Patients with Spasmodic Torticollis (1991)

The results of selective peripheral denervation of the involved muscles in 35 patients with spasmodic torticollis are reported. We modified the operation first described by Bertrand. Follow-up was 3 months to 2.5 years in 34/35 patients. 73% noticed a significant improvement or disappearance of dystonia and pain following surgery and physiotherapy for 3 months postoperatively. Selective peripheral denervation is recommended for patients with spasmodic torticollis of at least 1-2 years duration which is resistant to conservative treatment. It may also be used in patients who do not respond to injection of botulinum A toxin or who develop resistance to this kind of therapy.
A Wall of Funnels Concentrates Swimming Bacteria (2007)

Randomly moving but self-propelled agents, such as Escherichia coli bacteria, are expected to fill a volume homogeneously. However, we show that when a population of bacteria is exposed to a microfabricated wall of funnel-shaped openings, the random motion of bacteria through the openings is rectified by tracking (trapping) of the swimming bacteria along the funnel wall. This leads to a buildup of the concentration of swimming cells on the narrow opening side of the funnel wall but no concentration of nonswimming cells. Similarly, we show that a series of such funnel walls functions as a multistage pump and can increase the concentration of motile bacteria exponentially with the number of walls. The funnel wall can be arranged along arbitrary shapes and cause the bacteria to form well-defined patterns. The funnel effect may also have implications on the transport and distribution of motile microorganisms in irregular confined environments, such as porous media, wet soil, or biological tissue, or act as a selection pressure in evolution experiments.
Flameless atomic absorption spectrometry employing a wire loop atomizer (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFlameless atomic absorption spectrometry employing a wire loop atomizerM. P. Newton and D. G. DavisCite this: Anal. Chem. 1975, 47, 12, 2003–2009Publication Date (Print):October 1, 1975Publication History Published online1 May 2002Published inissue 1 October 1975https://pubs.acs.org/doi/10.1021/ac60362a006https://doi.org/10.1021/ac60362a006research-articleACS PublicationsRequest reuse permissionsArticle Views55Altmetric-Citations26LEARN 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
AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action <i>in vivo</i> , pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models (2007)

Constitutive activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signaling pathway in human cancers is often associated with mutational activation of BRAF or RAS. MAPK/ERK kinase 1/2 kinases lie downstream of RAS and BRAF and are the only acknowledged activators of ERK1/2, making them attractive targets for therapeutic intervention. AZD6244 (ARRY-142886) is a potent, selective, and ATP-uncompetitive inhibitor of MAPK/ERK kinase 1/2. In vitro cell viability inhibition screening of a tumor cell line panel found that lines harboring BRAF or RAS mutations were more likely to be sensitive to AZD6244. The in vivo mechanisms by which AZD6244 inhibits tumor growth were investigated. Chronic dosing with 25 mg/kg AZD6244 bd resulted in suppression of growth of Colo-205, Calu-6, and SW-620 xenografts, whereas an acute dose resulted in significant inhibition of ERK1/2 phosphorylation. Increased cleaved caspase-3, a marker of apoptosis, was detected in Colo-205 and Calu-6 but not in SW-620 tumors where a significant decrease in cell proliferation was detected. Chronic dosing of AZD6244 induced a morphologic change in SW-620 tumors to a more differentiated phenotype. The potential of AZD6244 in combination with cytotoxic drugs was evaluated in mice bearing SW-620 xenografts. Treatment with tolerated doses of AZD6244 and either irinotecan or docetaxel resulted in significantly enhanced antitumor efficacy relative to that of either agent alone. These results indicate that AZD6244 has potential to inhibit proliferation and induce apoptosis and differentiation, but the response varies between different xenografts. Moreover, enhanced antitumor efficacy can be obtained by combining AZD6244 with the cytotoxic drugs irinotecan or docetaxel.
Adaptive suppression of skywave interference in HF surface wave radar using auxiliary horizontal dipole antennas (2003)

This paper presents the results of a study to evaluate the effectiveness of an adaptive technique using horizontal dipoles to suppress the skywave interference in HF surface wave radar (HFSWR). Four auxiliary horizontal dipole antennas, configured in the form of two separate crosses, are used to form an adaptive system with the vertically polarized antennas (VPA) of a HFSWR system. The outputs of the horizontal dipoles are correlated with the summed output of the VPAs to cancel the interference component in the output of the VPAs. Two slightly different methods are used in the estimation of the correlation coefficients. The first method uses the samples at the far ranges of the radar. The second method uses the samples in the nearby range bins. The results of using the first method have been presented by Leong (see RADAR'97, IEE Conf., Edinburgh, Scotland, p.26-30, 1997). Here we present the results of using the second method. With the first method, the interference-plus-noise power (INP) is reduced by more than 13 dB, and the Bragg-to-interference-plus-noise-ratio (BINR) increases by up to 21 dB. With the second method, the INP is reduced by more than 17 dB, and the BINR increases by up to 25 dB. Both sets of the results show that the adaptive techniques are effective in suppressing the skywave interference.
Analysis of bacteriophage N protein and peptide binding to boxB RNA using polyacrylamide gel coelectrophoresis (PACE). (1997)

The antitermination protein N from bacteriophage lambda (Nlambda) interacts with the nut site in its own mRNA, as well as host factors, to facilitate formation of a termination-resistant transcription complex. The conserved, amino-terminal arginine-rich domain of Nlambda protein is known to interact with a small RNA hairpin (boxB) derived from the nut site RNA. We have examined the binding of Nlambda protein, peptides derived from the amino terminus of Nlambda, and the related phage P22 N protein to lambda boxB RNAs. To facilitate the study of complexes that are not amenable to gel retardation assays, a new polyacrylamide affinity coelectrophoresis technique (PACE) was developed. Using the PACE assay, we have demonstrated that a 19-amino acid peptide from the amino terminus of Nlambda protein binds lambda boxB RNA with a Kd,app of 5.2 nM. PACE was also used to study the binding affinity of a number of Nlambda peptide and lambda boxB RNA mutants. The PACE technique is complementary to the traditional gel retardation assay for direct measurement of binding interactions, and will be useful for any procedure that requires a pool of RNAs to be resolved based on their relative affinities for proteins or peptides.
Reduction of 2-substituted 3-oxoglutarates mediated by baker's yeast. Variation in enantioselectivity without corresponding variation in diastereoselectivity (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of 2-substituted 3-oxoglutarates mediated by baker's yeast. Variation in enantioselectivity without corresponding variation in diastereoselectivityTuncer Arslan and Steven A. BennerCite this: J. Org. Chem. 1993, 58, 8, 2260–2264Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/jo00060a048https://doi.org/10.1021/jo00060a048research-articleACS PublicationsRequest reuse permissionsArticle Views197Altmetric-Citations6LEARN 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