197,553 research outputs found
Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome
No full textNonsteroidal anti-inflammatory drugs interfere with the metabolism of arachidonic acid to proinflammatory prostaglandins and leukotrienes by targeting cyclooxygenases (COXs), 5-lipoxygenase (LOX), or the 5-LOX-activating protein (FLAP). These and related enzymes act in conjunction with marked crosstalk within a complex lipid mediator (LM) network where also specialized proresolving LMs (SPMs) are formed. Here, we present how prominent LM pathways can be differentially modulated in human proinflammatory M1 and proresolving M2 macrophage phenotypes that, upon exposure to Escherichia coli, produce either abundant prostaglandins and leukotrienes (M1) or SPMs (M2). Targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was applied to analyze and quantify the specific LM profiles. Besides expected on-target actions, we found that: 1) COX or 15-LOX-1 inhibitors elevate inflammatory leukotriene levels, 2) FLAP and 5-LOX inhibitors reduce leukotrienes in M1 but less so in M2 macrophages, 3) zileuton blocks resolution-initiating SPM biosynthesis, whereas FLAP inhibition increases SPM levels, and 4) that the 15-LOX-1 inhibitor 3887 suppresses SPM formation in M2 macrophages. Conclusively, interference with discrete LM biosynthetic enzymes in different macrophage phenotypes considerably affects the LM metabolomes with potential consequences for inflammation-resolution pharmacotherapy. Our data may allow better appraisal of the therapeutic potential of these drugs to intervene with inflammatory disorders.Werner, M., Jordan, P. M., Romp, E., Czapka, A., Rao, Z., Kretzer, C., Koeberle, A., Garscha, U., Pace, S., Claesson, H.-E., Serhan, C. N., Werz, O., Gerstmeier, J. Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Dr. Glendon Swarthout
No full textHosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness
Shear response of nanoconfined water on muscovite mica: role of cations
No full textBy monitoring the thermal noise of a vertically oriented micromechanical force sensor, we detect the viscoelastic response to shear for water in a subnanometer confinement. Measurements in pure water as well as under acidic and high-ionic-strength conditions relate this response to the effect of surface-adsorbed cations, which, because of their hydration, act as pinning centers restricting the mobility of the confined water molecules
Feeling the squeeze: shear viscoelasticity of nanoconfined water
No full textHow water molecules confined in nanometer gaps respond to shear: as a viscoelastic solid, viscous fluid or something in between?
This important question relevanti in biology, geochemistry, mineralogy, colloidal science and engineering continues to be debated with experimental evidence provided for conflicting point of view.
Here we show clear results obtained using innovative technique based on vertically oriented micromechanical force sensors investigating viscoelastic response of water on muscovite mica
Structural biology of carbohydrate transfer and modification in natural product biosynthesis
No full textCertain organisms, can during periods of limited resources, adapt their metabolism to enable biosynthesis of secondary metabolites, compounds that increase competitiveness and chances of survival. The subjects of this thesis are enzymes acting on carbohydrate substrates during secondary metabolism.The enzymatic attachment of carbohydrate moieties onto precursors of polyketide antibiotics such as anthracyclines, required for their biological activity, is performed by glycosyltransferases (GT). The anthracycline nogalamycin contains two carbohydrates: a nogalose moiety attached via an O-glycosidic bond to C7, and a nogalamine attached via an O-glycosidic bond to C1 and an unusual carbon-carbon bond between C2 and C5´ of the sugar. Genetic and functional data presented in this thesis established the roles of SnogE as the GT performing the C7 O-glycosyl transfer of the nogalose moiety and SnogD as the O-GT attaching the nogalamine moiety onto the C1 carbon.The activity of SnogD was verified in vitro using recombinant protein, following establishment of a transglycosylation-like assay. The three-dimensional structure of the homo-dimeric SnogD was determined to 2.6 Å and consists of a GT-B fold. Mutagenesis of two active site residues, His25 and His301, evaluated in vitro and in vivo, suggested His25 to be the catalytic base, activating the acceptor substrate by proton abstraction from the C1-hydroxyl group. His301 provides a positive charge to stabilise the negative charge formed close to the diphosphate of the leaving group during glycosyl transfer. Genetic, functional and structural data together suggest the involvement of an additional or altogether different enzyme for the C-C bond formation.The bifunctional enzyme aldos-2-ulose dehydratase (AUDH) from Phanerochaete chrysosporium catalyses the dehydration and isomerisation of the secondary metabolites glucosone and 1,5-anhydro-D-fructose (AF) into the antimicrobial compounds cortalcerone and microthecin (Mic), respectively. The threedimensional structure of the dimeric AUDH was determined to 2.0 Å. The enzyme consists of a seven bladed ß-propeller, two cupin folds and a lectin-like domain, in a novel combination. Two structural metal ions, Mg2+ and Zn2+, are bound in loop regions. Two additional zinc ions are present at the base of two putative active sites, located in the ß-propeller and the second cupin fold. The specific removal of these zinc ions eliminated catalytic activity, proving the metal dependency of the overall reaction. The structure of AUDH in complex with the reaction intermediate ascopyrone M bound at both putative active sites, and a complex of zinc-depleted enzyme with AF bound in the cupin fold have been determined by X-ray crystallography to 2.6 and 2.8 Å resolution, respectively.These observations support the presence of two distinct active sites located 60 Å apart, partly connected by an intra-dimeric channel. The dehydration reaction most likely follows an elimination reaction with the zinc ion acting as a Lewis acid to polarise the C2 keto group of AF. Abstraction of the C3 proton by the suitably located residue His155 would generate an enol intermediate, which is stabilised by the zinc ion. Return of the proton to the C4 hydroxyl group would generate a favourable leaving group.List of scientific papersI. Vilja Siitonen, Magnus Claesson, Pekka Patrikainen, Maria Aromaa, Pekka Mäntsälä, Gunter Schneider and Mikko Metsä‐Ketelä. Identification of late‐stage glycosylation steps in the biosynthetic pathway of the anthracycline nogalamycin. ChemBioChem. 2012, 13, 120‐128. https://doi.org/10.1002/cbic.201100637 II. Magnus Claesson, Ylva Lindqvist, Susan Madrid, Tatyana Sandalova, Roland Fiskesund, Shukun Yu and Gunter Schneider. Crystal Structure of Bifunctional Aldos‐2‐Ulose Dehydratase/Isomerase from Phanerochaete chrysosporium with the Reaction Intermediate Ascopyrone M. J Mol Biol. 2012; 417, 279‐293. https://doi.org/10.1016/j.jmb.2012.02.001 III. Magnus Claesson, Vilja Siitonen, Doreen Dobritzsch, Mikko Metsä‐Ketelä and Gunter Schneider. Crystal structure of the glycosyltransferase SnogD from the biosynthetic pathway of nogalamycin in Streptomyces nogalater. FEBS J. 2012; 279, 3251‐3263. https://doi.org/10.1111/j.1742-4658.2012.08711.x </p
Simulation of thermal plant optimization and hydraulic aspects of thermal distribution loops for large campuses
No full textFollowing an introduction, the author describes Texas A&M University and its utilities system. After that, the author presents how to construct simulation models for chilled water and heating hot water distribution systems. The simulation model was used in a $2.3 million Ross Street chilled water pipe replacement project at Texas A&M University. A second project conducted at the University of Texas at San Antonio was used as an example to demonstrate how to identify and design an optimal distribution system by using a simulation model. The author found that the minor losses of these closed loop thermal distribution systems are significantly higher than potable water distribution systems. In the second part of the report, the author presents the latest development of software called the Plant Optimization Program, which can simulate cogeneration plant operation, estimate its operation cost and provide optimized operation suggestions. The author also developed detailed simulation models for a gas turbine and heat recovery steam generator and identified significant potential savings. Finally, the author also used a steam turbine as an example to present a multi-regression method on constructing simulation models by using basic statistics and optimization algorithms. This report presents a survey of the author??s working experience at the Energy Systems Laboratory (ESL) at Texas A&M University during the period of January 2002 through March 2004. The purpose of the above work was to allow the author to become familiar with the practice of engineering. The result is that the author knows how to complete a project from start to finish and understands how both technical and nontechnical aspects of a project need to be considered in order to ensure a quality deliverable and bring a project to successful completion. This report concludes that the objectives of the internship were successfully accomplished and that the requirements for the degree of Degree of Engineering have been satisfied
n! matchings, n! posets
No full textWe show that there are matchings on points without, so called, left (neighbor) nestings. We also define a set of naturally labeled -free posets, and show that there are such posets on elements. Our work was inspired by Bousquet-M\'elou, Claesson, Dukes and Kitaev [J. Combin. Theory Ser. A. 117 (2010) 884--909]. They gave bijections between four classes of combinatorial objects: matchings with no neighbor nestings (due to Stoimenow), unlabeled -free posets, permutations avoiding a specific pattern, and so called ascent sequences. We believe that certain statistics on our matchings and posets could generalize the work of Bousquet-M\'elou et al.\ and we make a conjecture to that effect. We also identify natural subsets of matchings and posets that are equinumerous to the class of unlabeled -free posets. We give bijections that show the equivalence of (neighbor) restrictions on nesting arcs with (neighbor) restrictions on crossing arcs. These bijections are thought to be of independent interest. One of the bijections maps via certain upper-triangular integer matrices that have recently been studied by Dukes and Parviainen [Electron. J. Combin. 17 (2010) \#R53
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