gebhart/patrepeval huggingface dataset:
The preparation of 2,6‐diaminopyrazine, 2,6‐diazidopyrazine and some of their derivatives (1980)

Abstract A much improved synthesis of the heretofore difficultly obtainable 2,6‐diaminopyrazine (4) was afforded by the low‐pressure catalytic hydrogenation (palladium on carbon) of 2,6‐diazido‐pyrazine (2) ; reaction of 2,6‐dichloropyrazine (1) and sodium azide gave 2 in 84% yield. The outcome of the reduction was found to be solvent dependent: 1,2‐dimethoxyethane containing aqueous ammonia gave 4 in 83% yield; 1,2‐dimethoxyethane alone gave 5‐aminotetrazolo[1,5‐ a ]‐pyrazine (3) in 26% yield. Additional alternative syntheses of 3 and 4 are described. A number of acyl and azo derivatives of 4 were prepared. Reactions of 2 with dimethyl acetylenedicarboxylate and ethyl acetate (base catalyzed) leading to vic ‐triazole derivatives are also described.
Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells (2003)

Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated. We demonstrated that rare beating cells with cardiomyocyte features could be identified after culture of adipose stroma cells without addition of 5-azacytidine. The cardiomyocyte phenotype was first identified by morphological observation, confirmed with expression of specific cardiac markers, immunocytochemistry staining, and ultrastructural analysis, revealing the presence of ventricle- and atrial-like cells. Electrophysiological studies performed on early culture revealed a pacemaker activity of the cells. Finally, functional studies showed that adrenergic agonist stimulated the beating rate whereas cholinergic agonist decreased it. Taken together, this study demonstrated that functional cardiomyocyte-like cells could be directly obtained from adipose tissue. According to the large amount of this tissue in adult mammal, it could represent a useful source of cardiomyocyte progenitors.
Osteopetrosis Cured by Temporary Parabiosis (1973)

The excessive accumulations of spongiosa in the long bones of congenitally osteopetrotic mice permanently disappeared after a brief parabiotic union to normal littermates. Most of the bone removal was accomplished long after interruption of parabiosis. It is proposed that, during parabiosis, progenitors of competent osteolytic cells were recruited from the blood of the normal mouse.
Reduced cartilage proteoglycan loss during zymosan-induced gonarthritis in NOS2-deficient mice and in anti-interleukin-1-treated wild-type mice with unabated joint inflammation (1998)

IL-1 and NO play a minor role in edema and neutrophil influx, but a major role in cartilage destruction of ZIA. In this model of murine arthritis, cartilage destruction was, for the most part, caused by pronounced suppression of PG synthesis and IGF-1 unresponsiveness of the chondrocytes, which were induced by de novo-synthesized IL-1 and were mediated by NOS2 activation.
Novel Drugs and Combination Therapies for the Treatment of Metastatic Melanoma (2015)

Metastatic melanoma (MM) still remains as one of the most worrisome cancer known to mankind. In last two decades, treatment of melanoma took a dramatic turn with the discovery of targeted therapy which targets the mutations in mitogen-activated protein kinase (MAPK) pathway and immune checkpoint inhibitors. These new findings have led to emergence of many novel drugs that have been approved by FDA. Targeted therapy drugs such as vemurafenib, trametinib and dabrafenib target the MAPK pathway whereas immunotherapies such as ipilimumab, nivolumab and pembrolizumab block immune checkpoint receptors on T lymphocytes. All these drugs have shown to improve the overall survival in MM. Despite these recent discoveries, treatment of MM remains challenging because of rapid development of resistance to targeted therapy. This review will discuss recently approved drugs and their adverse effects and also shed light on combination therapy in treatment of melanoma.
Heart Rate Variability Extraction From Videos Signals: ICA vs. EVM Comparison (2017)

Medical researchers have always been interested in heart rate (HR) and heart rate variability (HRV) analysis. However, nowadays, investigators from a variety of other fields are also probing the subject. Recent advancements in non-contact HR and HRV measurement techniques will likely further boost interest in emotional estimation through HRV. Such measurement methods involve the extraction of the photoplethysmography (PPG) signal from the human's face through a camera. The latest approaches apply independent component analysis (ICA) on the color channels of video recordings to extract a PPG signal. Other investigated methods rely on Eulerian video magnification (EVM) to detect subtle changes in skin color associated with the PPG. To the best of our knowledge, EVM has not been successfully employed to extract HRV features from a video of a human face. In this paper, we present a comparison between our two approaches, one which is based on the ICA and the other is based on EVM. Final results show that the proposed ICA-based method yields better results when it comes to the high frequency (HF) and low frequency over high-frequency (LF/HF) HRV parameters [mean absolute error (MAE) of 0.57 and 0.419] when compared with the EVM-based method (MAE 0.76 and 1.69); however, the second method showed better MAE results for low frequency (LF) and higher correlation with the ground truth. Also our proposed ICA method showed better results in general by improving HF estimates, but the EVM-based method might be more appropriate when motion is involved or when the HF component is not important.
Predicting the oral bioavailability of 19-nortestosterone progestins in vivo from their metabolic stability in human liver microsomal preparations in vitro. (1998)

It was the aim of this study to investigate whether assessment of the metabolic stability of selected progestins of the 19-nortestosterone type in human microsomal liver preparations was a suitable approach to predict the oral bioavailability of these drugs in humans. The Michaelis-Menten parameters Vmax and KM,app for norethisterone, levonorgestrel, gestodene, desogestrel, 3-keto-desogestrel, norgestimate, and dienogest were determined in in vitro incubations with human liver microsomes. Using these data, both the in vitro intrinsic clearance (CLint) and, after application of a suitable scaling factor, the scaled in vivo CLint were calculated. For progestins for which human in vivo data were available, the in vitro results were correlated with in vivo CLint values and oral bioavailability. A comparison of the scaled in vivo CLint values with the corresponding in vivo CLint values showed a reasonable correlation, although the latter values were generally approximately 2-fold higher than the former. Excluding desogestrel, which is subject to substantial intestinal metabolism in vivo, there was a linear relationship (r = -0.986) between increasing in vitro CLint values for the progestins and decreasing bioavailability in vivo. Other methods of assessing the metabolic stability of the progestins in vitro, such as evaluation of metabolic half-lives at single initial concentrations, showed either no correlation or a less satisfactory correlation with bioavailability data.
Phosphoenolpyruvate- and ATP-Dependent Dihydroxyacetone Kinases:  Covalent Substrate-Binding and Kinetic Mechanism, (2004)

Dihydroxyacetone (Dha) kinases are a sequence-conserved family of enzymes, which utilize two different phosphoryldonors, ATP in animals, plants, and some bacteria, and a multiphosphoprotein of the phosphoenolpyruvate carbohydrate phosphotransferase system (PTS) in most bacteria. Here, we compare the PTS-dependent kinase of Escherichia coli and the ATP-dependent kinase of Citrobacter freundii. They display 30% sequence identity. The binding constants of the E. coli kinase for eleven short-chain carbonyl compounds were determined by acetone precipitation of the enzyme-substrate complexes. They are 3.4 microM for Dha, 780 microM for Dha-phosphate (DhaP), 50 microM for D,L-glyceraldehyde (GA), and 90 microM for D,L-glyceraldehyde-3-phosphate. The k(cat) for Dha of the PTS-dependent kinase is 290 min(-1), and that of the ATP-dependent kinase is 1050 min(-1). The Km for Dha of both kinases is <6 microM. The X-ray structures of the enzyme-GA and the enzyme-DhaP complex show that substrates as well as products are bound in hemiaminal linkage to an active-site histidine. Quantum-mechanical calculations offer no indication for activation of the reacting hydroxyl group by the formation of the hemiaminal. However, the formation of the hemiaminal bond allows selection for short-chain carbonyl compounds and discrimination against structurally similar polyols. The Dha kinase remains fully active in the presence of 2 M glycerol, and phosphorylates trace impurities of carbonyl compounds present in glycerol.
Digital Image Processing, Third Edition (2009)

The <i>Journal of Biomedical Optics</i> (JBO) is a Gold Open Access journal that publishes peer-reviewed papers on the use of novel optical systems and techniques for improved health care and biomedical research.
Interaction of a 1 psec laser pulse with solid matter (1991)

Absorption and x-ray emission results obtained with a 1 psec pulse incident on solid targets with an intensity between 1011 and 1016 W/cm2 are presented and discussed. For I&amp;lt;5×1014 W/cm2, submicron density gradient scale lengths (L/λ≤0.2) are measured and the comparison of calculated and experimental values of absorption for aluminum indicates a relatively good agreement for p polarization and noticeable differences for s polarization. X-ray conversion efficiencies have been obtained in the sub-keV and keV range. At high intensities (I&amp;gt;1015 W/cm2) an evaluation of the plasma parameters is obtained from high resolution keV spectra. Finally, the results are discussed in the light of 1-D hydrodynamic simulations with time-dependent atomic physics.
Effect of Texture of Plastic and Elastic Model Foods on the Parameters of Mastication (2006)

Mastication is continually modified throughout the chewing sequence in response to the texture of the food. The aim of this work was to compare the effects of an increase in hardness of two model food types, presenting either elastic or plastic rheological properties, on mastication. Each model food type consisted of four products of different hardness. Sensory testing experiments conducted with one group of 14 subjects showed significant perceived differences between products in terms of their increasing hardness. Fifteen other volunteers were asked to chew three replicates of each elastic and plastic product during two sessions. EMGs of masseter and temporalis muscles were recorded simultaneously with jaw movement during chewing. Numerous variables were analyzed from these masticatory recordings. Multiple linear regression analyses were used to assess the respective effects of food hardness and rheological properties on variables characterizing either the whole masticatory sequence or different stages of the sequence. Muscle activities were significantly affected by an increase in hardness regardless of the food type, whereas the shape of the cycles depended on the rheological properties. The masticatory frequency was affected by hardness at the initial stage of the sequence but overall frequency adaptation was better explained by a change in rheological behavior, with plastic products being chewed at a slower frequency. A dual hypothesis was proposed, implicating first a cortical-brain stem preprogrammed mechanism to adapt the shape of the jaw movements to the rheological properties of the food, and second, a brain stem mechanism with mainly sensory feedback from the mouth to adapt muscle force to the food hardness.
An investigation of the airflow in mushroom growing structures, the development of an improved, three-dimensional solution technique for fluid flow and its evaluation for the modelling of mushroom growing structures (2002)

This thesis is an examination of the airflows in mushroom growing rooms. An experimental investigation of the nature of the flows in Irish tunnels showed them to be of low magnitude at the crop but controllable in principle for single layer growing. It was found that stratification of the airflow in growing tunnels could cause severe reductions in cropping surface airspeed and the operation of the heating system was identified as the main source of this. An alternative air distribution system was shown to have the potential to overcome the effects of heating. Airflow for three level growing systems in tunnels was found to be non-uniform and the use of wall-mounted deflecting plates was shown to have the potential to correct this.&#13;\n&#13;\nThe provision of air flow solutions for the wide range of new growing systems would be difficult using empirical methods alone and therefore a modelling approach was sought to complement and aid the experimental work.&#13;\n&#13;\nThe initial modelling work was carried out in two dimensions with TEACH-T code (SIMPLE flow solver) to calculate the turbulent flow. The code was extended to three dimensions because it was not possible to model usefully in a two-dimensional approximation.&#13;\n&#13;\nConvergence times for the SIMPLE solver were found to be excessively long. Trial applications of multi-level acceleration produced approximately 15% savings in computational effort so a new solver was investigated. The CELS (Coupled Equation Line Solver) method had been reported as superior to SIMPLE in two dimensions and already has a multi-level technique to accelerate convergence, i.e. Additive Correction Multigrid (ACM).&#13;\n&#13;\nCELS was first applied in two dimensions in order to test its usefulness with the turbulence model in the equation set. Improvements in the time to convergence, relative to SIMPLE, justified its extension to three dimensions. The Additive Correction Multi grid technique also produced significant improvements and this was extended to three dimensions.&#13;\n&#13;\nCELS3D is essentially a plane solver applied to a three-dimensional grid and a number of procedures for its application were investigated. All produced savings relative to the SIMPLE solver. The QUICK differencing scheme was incorporated in the TEACH-based code and CELS3D was tested with various geometries and values of the Reynolds number. The best results gave a 79% reduction in the time to convergence of the solver. The ACM technique in three dimensions was investigated but no useful savings in computational effort were made.&#13;\n&#13;\nIn the application to mushroom growing structures, the principles of the application of CELS3D to flows around obstructions in the flow domain were examined and the difficulties identified. A solution was found but its implementation proved impractical for all but the simplest cases.
Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis (2014)

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.
Electric Field Tuning of Plasmonic Response of Nanodot Array in Liquid Crystal Matrix (2005)

In this work we demonstrate the feasibility of electric-field tuning of the plasmonic spectrum of a novel gold nanodot array in a liquid crystal matrix. As opposed to previously reported microscopically observed near-field spectral tuning of individual gold nanoparticles, this system exhibits macroscopic far-field spectral tuning. The nanodot-liquid crystal matrix also displays strong anisotropic absorption characteristics, which can be effectively described as a collective ensemble within a composite matrix in the lateral dimension and a group of noninteracting individual particles in the normal direction. The effective medium model and the Mie theory are employed to describe the experimental results.
Genetic Control of Hydroxamate-Mediated Iron Uptake in Escherichia coli (1980)

Cells of Escherichia coli can derive iron from a variety of chelators (siderophores) in addition to enterochelin, the catechol derivative excreted by many enteric bacteria. The genetic control of hydroxamate siderophore utilization was investigated in mutants of E. coli K-12 selected for resistance to lethal agents which adsorb to the tonA protein of the outer membrane (albomycin, colicin M, and phages T5 and phi80). Many of the mutants were unable to utilize hydroxamate siderophores as an iron source. This phenotype was termed Fhu, for ferric hydroxamate uptake. Mutants carrying lesions in the tonA region of the chromosome were studied and fell into several types. Members of one class had lost some or all of the tonA receptor protein's functions in that they were resistant to the lethal agents and unable to utilize ferrichrome and its analogs, although able to respond to the hydroxamate rhodotorulic acid (FhuA phenotype). Other mutants were unable to utilize any of the hydroxamate siderophores tested and were resistant to albomycin, althogh many were sensitive to the other lethal agents (FhuB phenotype). Members of these classes lacked ferrichrome-mediated iron uptake. Strains carrying transposon Tn10 insertions in fhuA (previously termed tonA) lacked the 78,000-molecular-weight outer membrane protein previously described; insertions in fhuB retained this protein and had no detectable change in outer membrane composition. Three-point transduction crosses revealed the gene order to be pan-fhuA-fhuB-metD in the min 3.5 region of the chromosome map. Complementation analyses with F' merodiploid strains showed that fhuA and fhuB comprise separate transcription units which are both required for utilization of ferrichrome. Response of diploid strains to rhodotorulic acid suggested the existence of a third gene, fhuC, required for utilization of this siderophore, but not ferrichrome. It is suggested that fhuB encodes a transport component in the cytoplasmic membrane that is necessary for the uptake of all hydroxamate siderophores following their receptor-mediated passage across the outer membrane.
Preparation of Some Arylchlorosilanes with Arylmagnesium Chlorides1 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of Some Arylchlorosilanes with Arylmagnesium Chlorides1SANDERS D. ROSENBERGSANDERS D. ROSENBERGMore by SANDERS D. ROSENBERG, JOHN J. WALBURNJOHN J. WALBURNMore by JOHN J. WALBURN, and HUGH E. RAMSDENHUGH E. RAMSDENMore by HUGH E. RAMSDENCite this: J. Org. Chem. 1957, 22, 12, 1606–1607Publication Date (Print):December 1, 1957Publication History Published online1 May 2002Published inissue 1 December 1957https://pubs.acs.org/doi/10.1021/jo01363a019https://doi.org/10.1021/jo01363a019research-articleACS PublicationsRequest reuse permissionsArticle Views469Altmetric-Citations60LEARN 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
Determination of the human cytochrome P450 isoforms involved in the metabolism of zolmitriptan (1999)

1. Zolmitriptan was extensively metabolized by freshly isolated human hepatocytes to a number of components including the three main metabolites observed in vivo (N-desmethyl-zolmitriptan, zolmitriptan N-oxide and the indole acetic acid derivative). In contrast, metabolism of zolmitriptan by human hepatic microsomes was extremely limited with only small amounts of the N-desmethyl and indole ethyl alcohol metabolites being produced. 2. Furafylline, a selective inhibitor of CYP1A2, almost completely abolished the hepatocellular metabolism of zolmitriptan and markedly inhibited formation of the N-desmethyl metabolite in microsomes. Chemical inhibitors, selective against other major human cytochrome P450 (CYP2C9, 2C19, 2D6 and 3A4), had no obvious effects. In addition, expressed human CYP1A2 was the only cytochrome P450 to form the N-desmethyl metabolite. 3. N-desmethyl-zolmitriptan was extensively metabolized by both human hepatocytes and microsomes. The indole acetic acid and ethyl alcohol derivatives were the major metabolites formed by hepatocytes, whereas only the indole ethyl alcohol derivative was produced by microsomes. Metabolism of N-desmethyl-zolmitriptan was not inhibited by cytochrome P450-selective chemical inhibitors nor was it observed following incubation with expressed human cytochrome P450. Clorgyline, a selective inhibitor of monoamine oxidase A (MAO-A), markedly inhibited the microsomal formation of the indole ethyl alcohol derivative. 4. Primary metabolism of zolmitriptan is dependent mainly on CYP1A2, whereas MAO-A is responsible for further metabolism of N-desmethyl-zolmitriptan, the active metabolite. Since the in vivo clearance of zolmitriptan is primarily dependent on metabolism, interactions with drugs that induce or inhibit CYP1A2 or MAO-A may be anticipated.
Tumour sidedness and intrinsic subtypes in patients with stage II/III colon cancer: analysis of NSABP C-07 (NRG Oncology) (2017)

Sidedness was associated with molecular subtypes and was predictive of OS in stage III colon cancer but was not predictive of RFS or oxaliplatin benefit in C-07. Molecular subtypes may provide more predictive value for oxaliplatin benefit than tumour sidedness.