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Sample records for acid sites evolving

  1. Hemicrania continua evolving from cluster headache responsive to valproic acid.

    Science.gov (United States)

    Lambru, Giorgio; Castellini, Paola; Bini, Annamaria; Evangelista, Andrea; Manzoni, Gian Camillo; Torelli, Paola

    2008-10-01

    Hemicrania continua (HC) is a rare type of primary headache characterized by a prompt and enduring response to indomethacin. We describe a patient who suffered from cluster headache evolving into ipsilateral HC, who does not tolerate a long-term indomethacin therapy. The case was complex in terms of diagnosis, associated comorbidity, and choice of treatment; after several trials with different therapeutic regimens, we started the patient on a therapy with valproic acid and obtained an improvement of her HC.

  2. EVOLVE

    CERN Document Server

    Deutz, André; Schütze, Oliver; Legrand, Pierrick; Tantar, Emilia; Tantar, Alexandru-Adrian

    2017-01-01

    This book comprises nine selected works on numerical and computational methods for solving multiobjective optimization, game theory, and machine learning problems. It provides extended versions of selected papers from various fields of science such as computer science, mathematics and engineering that were presented at EVOLVE 2013 held in July 2013 at Leiden University in the Netherlands. The internationally peer-reviewed papers include original work on important topics in both theory and applications, such as the role of diversity in optimization, statistical approaches to combinatorial optimization, computational game theory, and cell mapping techniques for numerical landscape exploration. Applications focus on aspects including robustness, handling multiple objectives, and complex search spaces in engineering design and computational biology.

  3. Evolving issues in the prevention of surgical site infections.

    LENUS (Irish Health Repository)

    Quinn, A

    2009-06-01

    Surgical site infection is one of the more common causes of post-operative morbidity. Such infections contribute to prolonged recovery, delayed discharge and increasing costs to both patients and the health service. In the current climate increased emphasis is being placed on minimising the risks of acquiring or transmitting these nosocomial infections. This article reviews the current literature obtained from a Pubmed database search in relation to three specific aspects of surgical site infection: compliance with prophylactic antibiotics, post-discharge surveillance and novel methods for preventing surgical site infections. These topics represent areas where many institutions will find room for improvement in the prevention of surgical site infections. Tight adherence to prophylactic antibiotic guidelines, close followup of surgical wounds during and after hospital discharge, and attention to oxygenation status and the body temperature of patients may all prove to be useful adjuncts in significantly decreasing surgical site infections.

  4. The evolution of evolvability in microRNA target sites in vertebrates

    Science.gov (United States)

    Xu, Jin; Zhang, Rui; Shen, Yang; Liu, Guojing; Lu, Xuemei; Wu, Chung-I

    2013-01-01

    The lack of long-term evolutionary conservation of microRNA (miRNA) target sites appears to contradict many analyses of their functions. Several hypotheses have been offered, but an attractive one—that the conservation may be a function of taxonomic hierarchy (vertebrates, mammals, primates, etc.)—has rarely been discussed. For such an analysis, we cannot use evolutionary conservation as a criterion of target identification, and hence, have used high confidence target sites in the cross-linking immunoprecipitation (CLIP) data. Assuming that a proportion, p, of target sites in the CLIP data are conserved, we define the evolvability of miRNA targets as 1-p. Genomic data from vertebrate species show that the evolvability between human and fish is very high, at more than 90%. The evolvability decreases to 50% between birds and mammals, 20% among mammalian orders, and only 6% between human and chimpanzee. Within each taxonomic hierarchy, there is a set of targets that are conserved only at that level of evolution. Extrapolating the evolutionary trend, we find the evolvability in any single species to be close to 0%. Thus, all miRNA target sites identified by the CLIP method are evolutionarily conserved in one species, but the conservation is lost step by step in larger taxonomic groups. The changing evolvability of miRNA targets suggests that miRNA-target interactions may play a role in the evolution of organismal diversity. PMID:24077390

  5. Renal Transport of Uric Acid: Evolving Concepts and Uncertainties

    OpenAIRE

    Bobulescu, Ion Alexandru; Moe, Orson W.

    2012-01-01

    In addition to its role as a metabolic waste product, uric acid has been proposed to be an important molecule with multiple functions in human physiology and pathophysiology and may be linked to human diseases beyond nephrolithiasis and gout. Uric acid homeostasis is determined by the balance between production, intestinal secretion, and renal excretion. The kidney is an important regulator of circulating uric acid levels, by reabsorbing around 90% of filtered urate, while being responsible f...

  6. Aquatic snails from mining sites have evolved to detect and avoid heavy metals.

    Science.gov (United States)

    Lefcort, H; Abbott, D P; Cleary, D A; Howell, E; Keller, N C; Smith, M M

    2004-05-01

    Toxicants in polluted environments are often patchily distributed. Hence, rather than being passive absorbers of pollution, some organisms have evolved the ability to detect and avoid toxicants. We studied the avoidance behavior of Physella columbiana, an aquatic pulmonate snail, in a pond that has been polluted with heavy metals for more than 120 years. Populations of this snail are rare at reference sites and are only robust at heavy-metal-polluted sites. We hypothesized that the snails are able to persist because they have evolved the ability to minimize their exposure to metals by actively avoiding metals in their environment. Using a Y-maze flow tank, we tested the avoidance behavior of snails to heavy-metal-polluted sediments and single-metal solutions of cadmium, zinc, or lead. We also tested the avoidance behaviors of the snails' laboratory-reared offspring raised in nonpolluted conditions. In addition, we tested the avoidance behavior of a small population of snails from a reference pond. Although all the snails we tested were able to detect low concentrations of heavy metals, we found that snails from the polluted site were the most sensitive, that their offspring were somewhat less sensitive, and that snails from the reference site were the least sensitive. This suggests that the ability of polluted-site snails to avoid heavy metals is both genetic and environmental. The concentrations of metals avoided by the snails from the polluted site were below the levels found at hot spots within their natal pond. The snails may be able to persist at this site because they decrease their exposure by moving to less-polluted sections of the pond. One application of our findings is the use of aquatic snails and our Y-maze design as an inexpensive pollution detector. Environmental pollutants such as lead, zinc, and arsenic are a problem throughout the world. People in underdeveloped countries often lack sophisticated pollution detection devices. We have developed a

  7. How Stakeholder Engagement is Evolving at the Caldas Uranium Mining Site in Minas Gerais, Brazil - 13223

    Energy Technology Data Exchange (ETDEWEB)

    Booth, Peter M. [WSP Environment and Energy, Manchester (United Kingdom); Da Silva, Nivaldo Carlos [CNEN, Pocos de Caldas (Brazil); Pereira de Oliveira, Alexandre; Cioffi Batagini, Regina Maria [CMPC, Pocos de Caldas (Brazil); Rangel, Heraldo Junior [INB, Pocos de Caldas (Brazil); Da Conceicao Estrella Abad, Maria [IBAMA, Brasilia (Brazil)

    2013-07-01

    The Caldas site is located in the Federal State of Minas Gerais in Brazil about 25 km from the city of Pocos de Caldas. While the city itself has 150,000 inhabitants there is a total population of around 0.5 million people living in an area that could potentially be influenced by the site. Uranium ore was mined and milled here between the years of 1982 and 1995, with ore extraction taking place from an open pit. Of the material removed, aside from that extracted for uranium, some was used on-site for road construction and building embankments while the remainder was disposed of onto two major rock piles. There are a number of potential historical and current environmental impacts to groundwater as a consequence of discharges into streams which then flow off site. The site is now undergoing a phase of decommissioning which includes the formulation and substantiation of a site remediation strategy. As part of a wider International Atomic Energy Agency (IAEA) Technical Cooperation Project aimed at providing practical guidance for implementing a decommissioning and remediation plan at the site, WSP E and E were invited to lead a mission in order to provide advice on the importance and merits of stakeholder engagement and how to ultimately build an engagement program. In November 2011, WSP E and E met with personnel from the site operators, the Brazilian regulatory bodies and representatives from the local stakeholder community and explained the principles of stakeholder engagement and how the process had internationally evolved principally from a decide-announce-defend approach to a more formal two way mechanism of engagement. Historically there had been insufficient liaison between the site operator, the nuclear regulator and the environmental regulator. All parties had recognized that greater interaction was necessary. There had also been very little engagement with local stakeholders about the various activities on the site and the potential implications of these

  8. Perturbations at the chloride site during the photosynthetic oxygen-evolving cycle.

    Science.gov (United States)

    Cooper, Ian B; Barry, Bridgette A

    2007-06-01

    Photosystem II (PSII) catalyzes the oxidation of water to O2 at the manganese-containing, oxygen-evolving complex (OEC). Photoexcitation of PSII results in the oxidation of the OEC; four sequential oxidation reactions are required for the generation and release of molecular oxygen. Therefore, with flash illumination, the OEC cycles among five Sn states. Chloride depletion inhibits O2 evolution. However, the binding site of chloride in the OEC is not known, and the role of chloride in oxygen evolution has not as yet been elucidated. We have employed reaction-induced FT-IR spectroscopy and selective flash excitation, which cycles PSII samples through the S state transitions. On the time scale employed, these FT-IR difference spectra reflect long-lived structural changes in the OEC. Bromide substitution supports oxygen evolution and was used to identify vibrational bands arising from structural changes at the chloride-binding site. Contributions to the vibrational spectrum from bromide-sensitive bands were observed on each flash. Sulfate treatment led to an elimination of oxygen evolution activity and of the FT-IR spectra assigned to the S3 to S0 (third flash) and S0 to S1 transitions (fourth flash). However, sulfate treatment changed, but did not eliminate, the FT-IR spectra obtained with the first and second flashes. Solvent isotope exchange in chloride-exchanged samples suggests flash-dependent structural changes, which alter protein dynamics during the S state cycle.

  9. Primordial soup or vinaigrette: did the RNA world evolve at acidic pH?

    Directory of Open Access Journals (Sweden)

    Bernhardt Harold S

    2012-01-01

    Full Text Available Abstract Background The RNA world concept has wide, though certainly not unanimous, support within the origin-of-life scientific community. One view is that life may have emerged as early as the Hadean Eon 4.3-3.8 billion years ago with an atmosphere of high CO2 producing an acidic ocean of the order of pH 3.5-6. Compatible with this scenario is the intriguing proposal that life arose within alkaline (pH 9-11 deep-sea hydrothermal vents like those of the 'Lost City', with the interface with the acidic ocean creating a proton gradient sufficient to drive the first metabolism. However, RNA is most stable at pH 4-5 and is unstable at alkaline pH, raising the possibility that RNA may have first arisen in the acidic ocean itself (possibly near an acidic hydrothermal vent, acidic volcanic lake or comet pond. As the Hadean Eon progressed, the ocean pH is inferred to have gradually risen to near neutral as atmospheric CO2 levels decreased. Presentation of the hypothesis We propose that RNA is well suited for a world evolving at acidic pH. This is supported by the enhanced stability at acidic pH of not only the RNA phosphodiester bond but also of the aminoacyl-(tRNA and peptide bonds. Examples of in vitro-selected ribozymes with activities at acid pH have recently been documented. The subsequent transition to a DNA genome could have been partly driven by the gradual rise in ocean pH, since DNA has greater stability than RNA at alkaline pH, but not at acidic pH. Testing the hypothesis We have proposed mechanisms for two key RNA world activities that are compatible with an acidic milieu: (i non-enzymatic RNA replication of a hemi-protonated cytosine-rich oligonucleotide, and (ii specific aminoacylation of tRNA/hairpins through triple helix interactions between the helical aminoacyl stem and a single-stranded aminoacylating ribozyme. Implications of the hypothesis Our hypothesis casts doubt on the hypothesis that RNA evolved in the vicinity of alkaline

  10. Thermal and Evolved Gas Analysis of Magnesium Perchlorate: Implications for Perchlorates in Soils at the Mars Phoenix Landing Site

    Science.gov (United States)

    Ming, Douglas W.; Morris, R.V.; Lauer, H. V.; Sutter, B.; Golden, D.C.; Boynton, W.V.

    2009-01-01

    Perchlorate salts were discovered in the soils around the Phoenix landing site on the northern plains of Mars [1]. Perchlorate was detected by an ion selective electrode that is part of the MECA Wet Chemistry Laboratory (WCL). The discovery of a mass 32 fragment (likely 02) by the Thermal and Evolved-Gas Analyzer (TEGA) provided additional confirmation of a strong oxidizer in the soils around the landing site. The purpose of this paper is to evaluate the thermal and evolved gas behavior of perchlorate salts using TEGA-like laboratory testbed instruments. TEGA ovens were fabricated from high purity Ni. Hence, an additional objective of this paper is to determine the effects that Ni might have on the evolved gas behavior of perchlorate salts.

  11. Two citizen task forces and the challenge of the evolving nuclear waste siting process

    Energy Technology Data Exchange (ETDEWEB)

    Peelle, E.B.

    1990-01-01

    Siting any nuclear waste facility is problematic in today's climate of distrust toward nuclear agencies and fear of nuclear waste. This study compares and contrasts the siting and public participation processes as two citizen task forces dealt with their difficult responsibilities. 10 refs., 3 tabs.

  12. Evolving Techniques of Documentation of a World Heritage Site in Lahore

    Science.gov (United States)

    Arif, R.; Essa, K.

    2017-08-01

    Lahore is an ancient, culturally rich city amidst which are embedded two world heritage sites. The state of historic preservation in the country is impoverished with a dearth of training and poor documentation skills, thus these monuments are decaying and in dire need of attention. The Aga Khan Cultural Service - Pakistan is one of the first working in heritage conservation in the country. AKCSP is currently subjecting the UNESCO World Heritage site of the Mughal era Lahore Fort to an intensive and multi-faceted architectural documentation process. This is presented here as a case study to chart the evolution of documentation techniques and enunciate the spectrum of challenges faced in the documentation of an intricate Mughal heritage site for conservation in the Pakistani context. 3D - laser scanning is used for the purpose of heritage conservation for the first time, and since has been utilised on heritage buildings and urban fabric in ongoing projects. These include Lahore Fort, Walled city of Lahore as well as the Baltit Fort, a project restored in the past, assisting in the maintenance of conserved buildings. The documentation team is currently discovering the full potential of this technology especially its use in heritage conservation simultaneously overcoming challenges faced. Moreover negotiating solutions to auto-generate 2D architectural drawings from the 3D pointcloud output. The historic architecture is juxtaposed with contemporary technology in a region where such a combination is rarely found. The goal is to continually develop the documentation methodologies whilst investigating other technologies in the future.

  13. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids.

    Science.gov (United States)

    Fan, Chenguang; Xiong, Hai; Reynolds, Noah M; Söll, Dieter

    2015-12-15

    Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNA(Pyl) to create tRNA(Pyl-opt) with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (N(ϵ)-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNA(Pyl-opt) facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNA(Pyl-opt) with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNA(Pyl-opt) had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNA(Pyl-opt) should be an excellent replacement of wild-type tRNA(Pyl) for future ncAA incorporation by PylRS enzymes.

  14. Rationally evolving tRNAPyl for efficient incorporation of noncanonical amino acids

    Science.gov (United States)

    Fan, Chenguang; Xiong, Hai; Reynolds, Noah M.; Söll, Dieter

    2015-01-01

    Genetic encoding of noncanonical amino acids (ncAAs) into proteins is a powerful approach to study protein functions. Pyrrolysyl-tRNA synthetase (PylRS), a polyspecific aminoacyl-tRNA synthetase in wide use, has facilitated incorporation of a large number of different ncAAs into proteins to date. To make this process more efficient, we rationally evolved tRNAPyl to create tRNAPyl-opt with six nucleotide changes. This improved tRNA was tested as substrate for wild-type PylRS as well as three characterized PylRS variants (Nϵ-acetyllysyl-tRNA synthetase [AcKRS], 3-iodo-phenylalanyl-tRNA synthetase [IFRS], a broad specific PylRS variant [PylRS-AA]) to incorporate ncAAs at UAG codons in super-folder green fluorescence protein (sfGFP). tRNAPyl-opt facilitated a 5-fold increase in AcK incorporation into two positions of sfGFP simultaneously. In addition, AcK incorporation into two target proteins (Escherichia coli malate dehydrogenase and human histone H3) caused homogenous acetylation at multiple lysine residues in high yield. Using tRNAPyl-opt with PylRS and various PylRS variants facilitated efficient incorporation of six other ncAAs into sfGFP. Kinetic analyses revealed that the mutations in tRNAPyl-opt had no significant effect on the catalytic efficiency and substrate binding of PylRS enzymes. Thus tRNAPyl-opt should be an excellent replacement of wild-type tRNAPyl for future ncAA incorporation by PylRS enzymes. PMID:26250114

  15. The Caulobacter crescentus chromosome replication origin evolved two classes of weak DnaA binding sites.

    Science.gov (United States)

    Taylor, James A; Ouimet, Marie-Claude; Wargachuk, Richard; Marczynski, Gregory T

    2011-10-01

    The Caulobacter crescentus replication initiator DnaA and essential response regulator CtrA compete to control chromosome replication. The C. crescentus replication origin (Cori) contains five strong CtrA binding sites but only two apparent DnaA boxes, termed G-boxes (with a conserved second position G, TGATCCACA). Since clusters of DnaA boxes typify bacterial replication origins, this discrepancy suggested that C. crescentus DnaA recognizes different DNA sequences or compensates with novel DNA-binding proteins. We searched for novel DNA sites by scanning mutagenesis of the most conserved Cori DNA. Autonomous replication assays showed that G-boxes and novel W-boxes (TCCCCA) are essential for replication. Further analyses showed that C. crescentus DnaA binds G-boxes with moderate and W-boxes with very weak affinities significantly below DnaA's capacity for high-affinity Escherichia coli-boxes (TTATCCACA). Cori has five conserved W-boxes. Increasing W-box affinities increases or decreases autonomous replication depending on their strategic positions between the G-boxes. In vitro, CtrA binding displaces DnaA from proximal G-boxes and from distal W-boxes implying CtrA-DnaA competition and DnaA-DnaA cooperation between G-boxes and W-boxes. Similarly, during cell cycle progression, CtrA proteolysis coincides with DnaA binding to Cori. We also observe highly conserved W-boxes in other replication origins lacking E. coli-boxes. Therefore, strategically weak DnaA binding can be a general means of replication control. © 2011 Blackwell Publishing Ltd.

  16. Reevaluating NIMBY: Evolving Public Fear and Acceptance in Siting a Nuclear Waste Facility

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins-Smith, Hank C.; Silva, Carol L.; Nowlin, Matthew C.; deLozier, Grant (Dept. of Political Science, Univ. of Oklahoma, Norman, OK (United States))

    2010-09-15

    The not-in-my-backyard (NIMBY) syndrome has long been the focus of academic and policy research. We test several competing hypothesis concerning the sources of NIMBY sentiments, including demographics, proximity, political ideology and partisanship, and the unfolding policy process over time. To test these hypotheses we use survey data collected in New Mexico dealing with risk perceptions and acceptance related to the Waste Isolation Pilot Project (WIPP), a permanent storage site for radioactive waste located near Carlsbad, New Mexico. WIPP became operational and received its first shipment of waste on March 26, 1999. This study tracks the changes of risk perception and acceptance over a decade, using measures taken from 35 statewide surveys of New Mexico citizens spanning the 11-year period from fall 1990 to summer 2001. This time span includes periods before and after WIPP became operational. We find that acceptance of WIPP is greater among those in the most proximate counties to WIPP. Surprisingly, and contrary to expectations drawn from the broader literature, acceptance is also greater among those who live closest to the nuclear waste transportation route. We also find that ideology, partisanship, government approval and broader environmental concerns influence support for WIPP acceptance. Finally, the sequence of procedural steps taken toward formal approval of WIPP by government agencies proved to be important to public acceptance, the most significant being the opening of the WIPP facility itself

  17. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinghe; Kang, Byong H.; Ishida, Elise; Zhou, Tongqing; Griesman, Trevor; Sheng, Zizhang; Wu, Fan; Doria-Rose, Nicole A.; Zhang, Baoshan; McKee, Krisha; O’Dell, Sijy; Chuang, Gwo-Yu; Druz, Aliaksandr; Georgiev, Ivelin S.; Schramm, Chaim A.; Zheng, Anqi; Joyce, M.  Gordon; Asokan, Mangaiarkarasi; Ransier, Amy; Darko, Sam; Migueles, Stephen A.; Bailer, Robert T.; Louder, Mark K.; Alam, S.  Munir; Parks, Robert; Kelsoe, Garnett; Von Holle, Tarra; Haynes, Barton F.; Douek, Daniel C.; Hirsch, Vanessa; Seaman, Michael S.; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.; Connors, Mark

    2016-11-01

    Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.

  18. Improving evolutionary models for mitochondrial protein data with site-class specific amino acid exchangeability matrices.

    Directory of Open Access Journals (Sweden)

    Katherine A Dunn

    Full Text Available Adequate modeling of mitochondrial sequence evolution is an essential component of mitochondrial phylogenomics (comparative mitogenomics. There is wide recognition within the field that lineage-specific aspects of mitochondrial evolution should be accommodated through lineage-specific amino-acid exchangeability matrices (e.g., mtMam for mammalian data. However, such a matrix must be applied to all sites and this implies that all sites are subject to the same, or largely similar, evolutionary constraints. This assumption is unjustified. Indeed, substantial differences are expected to arise from three-dimensional structures that impose different physiochemical environments on individual amino acid residues. The objectives of this paper are (1 to investigate the extent to which amino acid evolution varies among sites of mitochondrial proteins, and (2 to assess the potential benefits of explicitly modeling such variability. To achieve this, we developed a novel method for partitioning sites based on amino acid physiochemical properties. We apply this method to two datasets derived from complete mitochondrial genomes of mammals and fish, and use maximum likelihood to estimate amino acid exchangeabilities for the different groups of sites. Using this approach we identified large groups of sites evolving under unique physiochemical constraints. Estimates of amino acid exchangeabilities differed significantly among such groups. Moreover, we found that joint estimates of amino acid exchangeabilities do not adequately represent the natural variability in evolutionary processes among sites of mitochondrial proteins. Significant improvements in likelihood are obtained when the new matrices are employed. We also find that maximum likelihood estimates of branch lengths can be strongly impacted. We provide sets of matrices suitable for groups of sites subject to similar physiochemical constraints, and discuss how they might be used to analyze real data. We

  19. Improving Evolutionary Models for Mitochondrial Protein Data with Site-Class Specific Amino Acid Exchangeability Matrices

    Science.gov (United States)

    Dunn, Katherine A.; Jiang, Wenyi; Field, Christopher; Bielawski, Joseph P.

    2013-01-01

    Adequate modeling of mitochondrial sequence evolution is an essential component of mitochondrial phylogenomics (comparative mitogenomics). There is wide recognition within the field that lineage-specific aspects of mitochondrial evolution should be accommodated through lineage-specific amino-acid exchangeability matrices (e.g., mtMam for mammalian data). However, such a matrix must be applied to all sites and this implies that all sites are subject to the same, or largely similar, evolutionary constraints. This assumption is unjustified. Indeed, substantial differences are expected to arise from three-dimensional structures that impose different physiochemical environments on individual amino acid residues. The objectives of this paper are (1) to investigate the extent to which amino acid evolution varies among sites of mitochondrial proteins, and (2) to assess the potential benefits of explicitly modeling such variability. To achieve this, we developed a novel method for partitioning sites based on amino acid physiochemical properties. We apply this method to two datasets derived from complete mitochondrial genomes of mammals and fish, and use maximum likelihood to estimate amino acid exchangeabilities for the different groups of sites. Using this approach we identified large groups of sites evolving under unique physiochemical constraints. Estimates of amino acid exchangeabilities differed significantly among such groups. Moreover, we found that joint estimates of amino acid exchangeabilities do not adequately represent the natural variability in evolutionary processes among sites of mitochondrial proteins. Significant improvements in likelihood are obtained when the new matrices are employed. We also find that maximum likelihood estimates of branch lengths can be strongly impacted. We provide sets of matrices suitable for groups of sites subject to similar physiochemical constraints, and discuss how they might be used to analyze real data. We also discuss how

  20. Adverse experiences with nitric acid at the Savannah River Site

    Energy Technology Data Exchange (ETDEWEB)

    Durant, W.S.; Craig, D.K.; Vitacco, M.J.; McCormick, J.A.

    1991-06-01

    Nitric acid is used routinely at the Savannah River Site (SRS) in many processes. However, the site has experienced a number of adverse situations in handling nitric acid. These have ranged from minor injuries to personnel to significant explosions. This document compiles many of these events and includes discussions of process upsets, fires, injuries, and toxic effects of nitric acid and its decomposition products. The purpose of the publication is to apprise those using the acid that it is a potentially dangerous material and can react in many ways as demonstrated by SRS experience. 10 refs.

  1. Long lifespans have evolved with long and monounsaturated fatty acids in birds.

    Science.gov (United States)

    Galván, Ismael; Naudí, Alba; Erritzøe, Johannes; Møller, Anders P; Barja, Gustavo; Pamplona, Reinald

    2015-10-01

    The evolution of lifespan is a central question in evolutionary biology, begging the question why there is so large variation among taxa. Specifically, a central quest is to unravel proximate causes of ageing. Here, we show that the degree of unsaturation of liver fatty acids predicts maximum lifespan in 107 bird species. In these birds, the degree of fatty acid unsaturation is positively related to maximum lifespan across species. This is due to a positive effect of monounsaturated fatty acid content, while polyunsaturated fatty acid content negatively correlates with maximum lifespan. Furthermore, fatty acid chain length unsuspectedly increases with maximum lifespan independently of degree of unsaturation. These findings tune theories on the proximate causes of ageing while providing evidence that the evolution of lifespan in birds occurs in association with fatty acid profiles. This suggests that studies of proximate and ultimate questions may facilitate our understanding of these central evolutionary questions.

  2. Investigation of the calcium-binding site of the oxygen evolving complex of photosystem II using 87Sr ESEEM spectroscopy.

    Science.gov (United States)

    Kim, Sun Hee; Gregor, Wolfgang; Peloquin, Jeffrey M; Brynda, Marcin; Britt, R David

    2004-06-16

    The proximity of the calcium/strontium binding site of the oxygen evolving complex (OEC) of photosystem II (PSII) to the paramagnetic Mn cluster is explored with (87)Sr three-pulse electron spin-echo envelope modulation (ESEEM) spectroscopy. CW-EPR spectra of Sr(2+)-substituted Ca(2+)-depleted PSII membranes show the modified g = 2 multiline EPR signal as previously reported. We performed three-pulse ESEEM on this modified multiline signal of the Mn cluster using natural abundance Sr and (87)Sr, respectively. Three-pulse ESEEM of the natural abundance Sr sample exhibits no detectable modulation by the 7% abundance (87)Sr. On the other hand, that of the (87)Sr enriched (93%) sample clearly reveals modulation arising from the I = (9)/(2) (87)Sr nucleus weakly magnetically coupled to the Mn cluster. Using a simple point dipole approximation for the electron spin, analysis of the (87)Sr ESEEM modulation depth via an analytic expression suggests a Mn-Ca (Sr) distance of 4.5 A. Simulation of three-pulse ESEEM with a numerical matrix diagonalization procedure gave good agreement with this analytical result. A more appropriate tetranuclear magnetic/structural model for the Mn cluster converts the 4.5 A point dipole distance to a 3.8-5.0 A range of distances. DFT calculations of (43)Ca and (87)Sr quadrupolar interactions on Ca (and Sr substituted) binding sites in various proteins suggest that the lack of the nuclear quadrupole induced splitting in the ESEEM spectrum of (87)Sr enriched PSII samples is related to a very high degree of symmetry of the ligands surrounding the Sr(2+) ion in the substituted Ca site. Numerical simulations show that moderate (87)Sr quadrupolar couplings decrease the envelope modulation relative to the zero quadrupole case, and therefore we consider that the 3.8-5.0 A range obtained without quadrupolar coupling included in the simulation represents an upper limit to the actual manganese-calcium distance. This (87)Sr pulsed EPR spectroscopy provides

  3. Genomic analysis of parallel-evolved cyanobacterium Synechocystis sp. PCC 6803 under acid stress.

    Science.gov (United States)

    Uchiyama, Junji; Kanesaki, Yu; Iwata, Naoya; Asakura, Ryousuke; Funamizu, Kento; Tasaki, Rizumu; Agatsuma, Mina; Tahara, Hiroko; Matsuhashi, Ayumi; Yoshikawa, Hirofumi; Ogawa, Satoru; Ohta, Hisataka

    2015-08-01

    Experimental evolution is a powerful tool for clarifying phenotypic and genotypic changes responsible for adaptive evolution. In this study, we isolated acid-adapted Synechocystis sp. PCC 6803 (Synechocystis 6803) strains to identify genes involved in acid tolerance. Synechocystis 6803 is rarely found in habitants with pH 6803.

  4. Systematic investigation of the catalytic cycle of a single site ruthenium oxygen evolving complex using density functional theory.

    Science.gov (United States)

    Hughes, Thomas F; Friesner, Richard A

    2011-07-28

    The mechanism of water oxidation by a single site ruthenium oxygen evolving complex is investigated using fully unrestricted pseudospectral B3LYP with the effective core potential LACV3P in continuum solvent with some quantum mechanical waters. Guess wave functions have been used that allow greater flexibility in sampling different electronic configurations of the complex. Systematic comparison with experiment is improved using these guesses because they provide a complete analysis of the low energy manifold and help to alleviate the formal disconnect between theory and experiment in assigning Lewis structures for transition metal complexes. In agreement with results from the literature, the challenging 4e(-)and 4H(+) oxidation of water is accomplished using a mechanism that features three proton coupled electron transfers, one electron transfer, one atom proton transfer (APT), and one ligand exchange (LE). Calculations on a large database of ruthenium complexes allows us to benchmark the computation of reduction half potentials and free energies of activation and to investigate systematic ligand variations and their effect on the reaction mechanism. Mean unsigned errors of reduction half potentials in comparison to experiment are generally small (100-200 mV). The APT and LE steps are found to be rate limiting with free energy barriers of 19.27 and 19.53 kcal/mol respectively, which is in excellent agreement with the ∼20 kcal/mol barrier obtained from experimental rate constants using classical transition state theory.

  5. Ultraviolet pigments in birds evolved from violet pigments by a single amino acid change

    Science.gov (United States)

    Yokoyama, Shozo; Radlwimmer, F. Bernhard; Blow, Nathan S.

    2000-01-01

    UV vision has profound effects on the evolution of organisms by affecting such behaviors as mating preference and foraging strategies. Despite its importance, the molecular basis of UV vision is not known. Here, we have transformed the zebra finch UV pigment into a violet pigment by incorporating one amino acid change, C84S. By incorporating the reverse mutations, we have also constructed UV pigments from the orthologous violet pigments of the pigeon and chicken. These results and comparative amino acid sequence analyses of the pigments in vertebrates demonstrate that many avian species have achieved their UV vision by S84C. PMID:10861005

  6. Ultraviolet pigments in birds evolved from violet pigments by a single amino acid change

    OpenAIRE

    Yokoyama, Shozo; Radlwimmer, F. Bernhard; Blow, Nathan S.

    2000-01-01

    UV vision has profound effects on the evolution of organisms by affecting such behaviors as mating preference and foraging strategies. Despite its importance, the molecular basis of UV vision is not known. Here, we have transformed the zebra finch UV pigment into a violet pigment by incorporating one amino acid change, C84S. By incorporating the reverse mutations, we have also constructed UV pigments from the orthologous violet pigments of the pigeon and chicken. These results and comparative...

  7. The evolving role of hyaluronic acid fillers for facial volume restoration and contouring: a Canadian overview

    Directory of Open Access Journals (Sweden)

    Muhn C

    2012-10-01

    Full Text Available Channy Muhn,1 Nathan Rosen,1 Nowell Solish,2 Vince Bertucci,2 Mark Lupin,3 Alain Dansereau,4 Fred Weksberg,5 B Kent Remington,6 Arthur Swift71Division of Dermatology, McMaster University, Hamilton, Ontario, 2Division of Dermatology, New Women's College Hospital, Toronto, Ontario, 3Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, 4Private Practice, Repentigny, Québec, 5Department of Medicine, University of Toronto, Toronto, Ontario, 6Private Practice, Calgary, Alberta, Canada; 7St Mary's Hospital, McGill University, Montréal, Québec, CanadaAbstract: Recent advancements, including more versatile facial fillers, refined injection techniques and the adoption of a global facial approach, have contributed to improved patient outcome and increased patient satisfaction. Nine Canadian specialists (eight dermatologists, one plastic surgeon collaborated to develop an overview on volume restoration and contouring based on published literature and their collective clinical experience. The specialists concurred that optimal results in volume restoration and contouring depend on correcting deficiencies at various layers of the facial envelope. This includes creating a foundation for deep structural support in the supraperiosteal or submuscular plane; volume repletion of subcutaneous fat compartments; and the reestablishment of dermal and subdermal support to minimize cutaneous rhytids, grooves and furrows. It was also agreed that volume restoration and contouring using a global facial approach is essential to create a natural, youthful appearance in facial aesthetics. A comprehensive non-surgical approach should therefore incorporate combining fillers such as high-viscosity, low-molecular-weight hyaluronic acid (LMWHA for structural support and hyaluronic acid (HA for lines, grooves and furrows with neuromodulators, lasers and energy devices.Keywords: hyaluronic acid filler, volumizing, facial

  8. Accumulation of acid sites on natural clinoptilolite under recurring dehydration

    Science.gov (United States)

    Moroz, N. K.; Afanassyev, I. S.; Paukshtis, E. A.; Valueva, G. P.

    A new 1H NMR approach was applied to study the influence of recurring dehydration on the acidity of a natural Ca-rich zeolite clinoptilolite. It has been found that thermal cycling progressively increases the rate of the proton exchange between water molecules in the rehydrated state. The observed effect is interpreted as a result of the irreversible accumulation of specific structural defects represented by Brønsted acid sites: each dehydration at 720 K adds to the acid sites in an amount of the order of 10-3 per unit cell. The number of these defects, detected by NMR in hydrated mineral, is in reasonable agreement with their amount estimated for the dehydrated state with an IR-spectroscopy CO-probe method. A comparison of the results obtained for two distinct zeolite samples shows that the Ca2+ ions are of first importance in the dehydration-induced formation of the active acid sites. The barrier for the proton-transfer reaction between the acid sites and H2O molecules in hydrated clinoptilolite is found to be 46 kJ mol-1, which is not too different from the value of 54 kJ mol-1 reported recently for natural chabazite.

  9. Modeling lanthanide series binding sites on humic acid.

    Science.gov (United States)

    Pourret, Olivier; Martinez, Raul E

    2009-02-01

    Lanthanide (Ln) binding to humic acid (HA) has been investigated by combining ultrafiltration and ICP-MS techniques. A Langmuir-sorption-isotherm metal-complexation model was used in conjunction with a linear programming method (LPM) to fit experimental data representing various experimental conditions both in HA/Ln ratio (varying between 5 and 20) and in pH range (from 2 to 10) with an ionic strength of 10(-3) mol L(-1). The LPM approach, not requiring prior knowledge of surface complexation parameters, was used to solve the existing discrepancies in LnHA binding constants and site densities. The application of the LPM to experimental data revealed the presence of two discrete metal binding sites at low humic acid concentrations (5 mg L(-1)), with log metal complexation constants (logK(S,j)) of 2.65+/-0.05 and 7.00 (depending on Ln). The corresponding site densities were 2.71+/-0.57x10(-8) and 0.58+/-0.32x10(-8) mol of Ln(3+)/mg of HA (depending on Ln). Total site densities of 3.28+/-0.28x10(-8), 4.99+/-0.02x10(-8), and 5.01+/-0.01x10(-8) mol mg(-1) were obtained by LPM for humic acid, for humic acid concentrations of 5, 10, and 20 mg L(-1), respectively. These results confirm that lanthanide binding occurs mainly at weak sites (i.e., ca. 80%) and second at strong sites (i.e., ca. 20%). The first group of discrete metal binding sites may be attributed to carboxylic groups (known to be the main binding sites of Ln in HA), and the second metal binding group to phenolic moieties. Moreover, this study evidences heterogeneity in the distribution of the binding sites among Ln. Eventually, the LPM approach produced feasible and reasonable results, but it was less sensitive to error and did not require an a priori assumption of the number and concentration of binding sites.

  10. Composite active site of chondroitin lyase ABC accepting both epimers of uronic acid

    Energy Technology Data Exchange (ETDEWEB)

    Shaya, D.; Hahn, Bum-Soo; Bjerkan, Tonje Marita; Kim, Wan Seok; Park, Nam Young; Sim, Joon-Soo; Kim, Yeong-Shik; Cygler, M. (Catholic Univ of Korea); (NUST); (McGill); (Nat); (Natural Products Res Inst, Korea)

    2008-03-19

    Enzymes have evolved as catalysts with high degrees of stereospecificity. When both enantiomers are biologically important, enzymes with two different folds usually catalyze reactions with the individual enantiomers. In rare cases a single enzyme can process both enantiomers efficiently, but no molecular basis for such catalysis has been established. The family of bacterial chondroitin lyases ABC comprises such enzymes. They can degrade both chondroitin sulfate (CS) and dermatan sulfate (DS) glycosaminoglycans at the nonreducing end of either glucuronic acid (CS) or its epimer iduronic acid (DS) by a {beta}-elimination mechanism, which commences with the removal of the C-5 proton from the uronic acid. Two other structural folds evolved to perform these reactions in an epimer-specific fashion: ({alpha}/{alpha}){sub 5} for CS (chondroitin lyases AC) and {beta}-helix for DS (chondroitin lyases B); their catalytic mechanisms have been established at the molecular level. The structure of chondroitinase ABC from Proteus vulgaris showed surprising similarity to chondroitinase AC, including the presence of a Tyr-His-Glu-Arg catalytic tetrad, which provided a possible mechanism for CS degradation but not for DS degradation. We determined the structure of a distantly related Bacteroides thetaiotaomicron chondroitinase ABC to identify additional structurally conserved residues potentially involved in catalysis. We found a conserved cluster located {approx}12 {angstrom} from the catalytic tetrad. We demonstrate that a histidine in this cluster is essential for catalysis of DS but not CS. The enzyme utilizes a single substrate-binding site while having two partially overlapping active sites catalyzing the respective reactions. The spatial separation of the two sets of residues suggests a substrate-induced conformational change that brings all catalytically essential residues close together.

  11. Dehydration of lactic acid to acrylic acid over lanthanum phosphate catalysts: the role of Lewis acid sites.

    Science.gov (United States)

    Guo, Zhen; Theng, De Sheng; Tang, Karen Yuanting; Zhang, Lili; Huang, Lin; Borgna, Armando; Wang, Chuan

    2016-09-14

    Lanthanum phosphate (LaP) nano-rods were synthesized using n-butylamine as a shape-directing agent (SDA). The resulting catalysts were applied in the dehydration of lactic acid to acrylic acid. Aiming to understand the nature of the active sites, the chemical and physical properties of LaP materials were studied using a variety of characterization techniques. This study showed that the SDA not only affected the porosity of the LaP materials but also modified the acid-base properties. Clearly, the modification of the acid-base properties played a more critical role in determining the catalytic performance than porosity. An optimized catalytic performance was obtained on the LaP catalyst with a higher concentration of Lewis acid sites. Basic sites showed negative effects on the stability of the catalysts. Good stability was achieved when the catalyst was prepared using the appropriate SDA/La ratio.

  12. Detecting coevolving amino acid sites using Bayesian mutational mapping

    DEFF Research Database (Denmark)

    Dimmic, Matthew W.; Hubisz, Melissa J.; Bustamente, Carlos D.

    2005-01-01

    Motivation: The evolution of protein sequences is constrained by complex interactions between amino acid residues. Because harmful substitutions may be compensated for by other substitutions at neighboring sites, residues can coevolve. We describe a Bayesian phylogenetic approach to the detection...... of coevolving residues in protein families. This method, Bayesian mutational mapping (BMM), assigns mutations to the branches of the evolutionary tree stochastically, and then test statistics are calculated to determine whether a coevolutionary signal exists in the mapping. Posterior predictive P-values provide...... of eukaryotic proteins from the phosphoglycerate kinase (PGK) family, interdomain site contacts yield a significantly greater coevolutionary signal than interdomain non-contacts, an indication that the method provides information about interacting sites. Failure to account for the heterogeneity in rates across...

  13. Structural characterization of the manganese sites in the photosynthetic oxygen-evolving complex using x-ray absorption spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Penner-Hahn, J.E.; Fronko, R.M.; Pecoraro, V.L.; Yocum, C.F.; Betts, S.D.; Bowlby, N.R. (Univ. of Michigan, Ann Arbor (USA))

    1990-03-28

    Manganese x-ray absorption spectra (XAS) are reported for the S{sub 1} state of highly purified, highly concentrated preparations of the oxygen-evolving complex (OEC) from photosystem II (PSII). Improvements in concentration (ca. 1.5 mM Mn) and detection efficiency (13-element solid-state detector array) have permitted a substantial improvement in data quality relative to previous solution XAS studies of PSII. Principal findings are that there is no need to include a shell of oxygens at ca. 1.75 {angstrom} in order to account for the Mn EXAFS, that there are 2-3 Mn-Mn distances of ca. 2.7 {angstrom}, and that there are one and possibly two shells of additional scatterers at longer distance (ca. 3.3 and 4.2 {angstrom}) from the Mn. Even with this higher quality data, it is not possible to use EXAFS to determine whether chloride is coordinated to the Mn. The structure consequences of these results are discussed in the context of proposed structural models. It is concluded that neither a cubane nor previously prepared butterfly type clusters can account for the observed features.

  14. Nucleic acid constructs containing orthogonal site selective recombinases (OSSRs)

    Energy Technology Data Exchange (ETDEWEB)

    Gilmore, Joshua M.; Anderson, J. Christopher; Dueber, John E.

    2017-08-29

    The present invention provides for a recombinant nucleic acid comprising a nucleotide sequence comprising a plurality of constructs, wherein each construct independently comprises a nucleotide sequence of interest flanked by a pair of recombinase recognition sequences. Each pair of recombinase recognition sequences is recognized by a distinct recombinase. Optionally, each construct can, independently, further comprise one or more genes encoding a recombinase capable of recognizing the pair of recombinase recognition sequences of the construct. The recombinase can be an orthogonal (non-cross reacting), site-selective recombinase (OSSR).

  15. Metabolic engineering for the production of shikimic acid in an evolved Escherichia coli strain lacking the phosphoenolpyruvate: carbohydrate phosphotransferase system

    Directory of Open Access Journals (Sweden)

    Bolívar Francisco

    2010-04-01

    Full Text Available Abstract Background Shikimic acid (SA is utilized in the synthesis of oseltamivir-phosphate, an anti-influenza drug. In this work, metabolic engineering approaches were employed to produce SA in Escherichia coli strains derived from an evolved strain (PB12 lacking the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS- but with capacity to grow on glucose. Derivatives of PB12 strain were constructed to determine the effects of inactivating aroK, aroL, pykF or pykA and the expression of plasmid-coded genes aroGfbr, tktA, aroB and aroE, on SA synthesis. Results Batch cultures were performed to evaluate the effects of genetic modifications on growth, glucose consumption, and aromatic intermediate production. All derivatives showed a two-phase growth behavior with initial high specific growth rate (μ and specific glucose consumption rate (qs, but low level production of aromatic intermediates. During the second growth phase the μ decreased, whereas aromatic intermediate production reached its maximum. The double aroK- aroL- mutant expressing plasmid-coded genes (strain PB12.SA22 accumulated SA up to 7 g/L with a yield of SA on glucose of 0.29 mol/mol and a total aromatic compound yield (TACY of 0.38 mol/mol. Single inactivation of pykF or pykA was performed in PB12.SA22 strain. Inactivation of pykF caused a decrease in μ, qs, SA production, and yield; whereas TACY increased by 33% (0.5 mol/mol. Conclusions The effect of increased availability of carbon metabolites, their channeling into the synthesis of aromatic intermediates, and disruption of the SA pathway on SA production was studied. Inactivation of both aroK and aroL, and transformation with plasmid-coded genes resulted in the accumulation of SA up to 7 g/L with a yield on glucose of 0.29 mol/mol PB12.SA22, which represents the highest reported yield. The pykF and pykA genes were inactivated in strain PB12.SA22 to increase the production of aromatic compounds in the PTS

  16. (Ca,Mg)-Carbonate and Mg-Carbonate at the Phoenix Landing Site: Evaluation of the Phoenix Lander's Thermal Evolved Gas Analyzer (TEGA) Data Using Laboratory Simulations

    Science.gov (United States)

    Sutter, B.; Ming, D. W.; Boynton, W. V.; Niles, P. B.; Morris, R. V.

    2011-01-01

    Calcium carbonate (4.5 wt. %) was detected in the soil at the Phoenix Landing site by the Phoenix Lander s The Thermal and Evolved Gas Analyzer [1]. TEGA operated at 12 mbar pressure, yet the detection of calcium carbonate is based on interpretations derived from thermal analysis literature of carbonates measured under ambient (1000 mbar) and vacuum (10(exp -3) mbar) conditions [2,3] as well as at 100 and 30 mbar [4,5] and one analysis at 12 mbar by the TEGA engineering qualification model (TEGA-EQM). Thermodynamics (Te = H/ S) dictate that pressure affects entropy ( S) which causes the temperature (Te) of mineral decomposition at one pressure to differ from Te obtained at another pressure. Thermal decomposition analyses of Fe-, Mg-, and Ca-bearing carbonates at 12 mbar is required to enhance the understanding of the TEGA results at TEGA operating pressures. The objectives of this work are to (1) evaluate the thermal and evolved gas behavior of a suite of Fe-, Mg-, Ca-carbonate minerals at 1000 and 12 mbar and (2) discuss possible emplacement mechanisms for the Phoenix carbonate.

  17. Post-duplication charge evolution of phosphoglucose isomerases in teleost fishes through weak selection on many amino acid sites

    Directory of Open Access Journals (Sweden)

    Sato Yukuto

    2007-10-01

    Full Text Available Abstract Background The partitioning of ancestral functions among duplicated genes by neutral evolution, or subfunctionalization, has been considered the primary process for the evolution of novel proteins (neofunctionalization. Nonetheless, how a subfunctionalized protein can evolve into a more adaptive protein is poorly understood, mainly due to the limitations of current analytical methods, which can detect only strong selection for amino acid substitutions involved in adaptive molecular evolution. In this study, we employed a comparative evolutionary approach to this question, focusing on differences in the structural properties of a protein, specifically the electric charge, encoded by fish-specific duplicated phosphoglucose isomerase (Pgi genes. Results Full-length cDNA cloning, RT-PCR based gene expression analyses, and comparative sequence analyses showed that after subfunctionalization with respect to the expression organ of duplicate Pgi genes, the net electric charge of the PGI-1 protein expressed mainly in internal tissues became more negative, and that of PGI-2 expressed mainly in muscular tissues became more positive. The difference in net protein charge was attributable not to specific amino acid sites but to the sum of various amino acid sites located on the surface of the PGI molecule. Conclusion This finding suggests that the surface charge evolution of PGI proteins was not driven by strong selection on individual amino acid sites leading to permanent fixation of a particular residue, but rather was driven by weak selection on a large number of amino acid sites and consequently by steady directional and/or purifying selection on the overall structural properties of the protein, which is derived from many modifiable sites. The mode of molecular evolution presented here may be relevant to various cases of adaptive modification in proteins, such as hydrophobic properties, molecular size, and electric charge.

  18. In situ characterization of cofacial Co(IV) centers in Co4O4 cubane: Modeling the high-valent active site in oxygen-evolving catalysts.

    Science.gov (United States)

    Brodsky, Casey N; Hadt, Ryan G; Hayes, Dugan; Reinhart, Benjamin J; Li, Nancy; Chen, Lin X; Nocera, Daniel G

    2017-03-27

    The Co4O4 cubane is a representative structural model of oxidic cobalt oxygen-evolving catalysts (Co-OECs). The Co-OECs are active when residing at two oxidation levels above an all-Co(III) resting state. This doubly oxidized Co(IV)2 state may be captured in a Co(III)2(IV)2 cubane. We demonstrate that the Co(III)2(IV)2 cubane may be electrochemically generated and the electronic properties of this unique high-valent state may be probed by in situ spectroscopy. Intervalence charge-transfer (IVCT) bands in the near-IR are observed for the Co(III)2(IV)2 cubane, and spectroscopic analysis together with electrochemical kinetics measurements reveal a larger reorganization energy and a smaller electron transfer rate constant for the doubly versus singly oxidized cubane. Spectroelectrochemical X-ray absorption data further reveal systematic spectral changes with successive oxidations from the cubane resting state. Electronic structure calculations correlated to experimental data suggest that this state is best represented as a localized, antiferromagnetically coupled Co(IV)2 dimer. The exchange coupling in the cofacial Co(IV)2 site allows for parallels to be drawn between the electronic structure of the Co4O4 cubane model system and the high-valent active site of the Co-OEC, with specific emphasis on the manifestation of a doubly oxidized Co(IV)2 center on O-O bond formation.

  19. Acidity of edge surface sites of montmorillonite and kaolinite

    NARCIS (Netherlands)

    Liu, X.; Lu, X.; Sprik, M.; Cheng, J.; Meijer, E.J.; Wang, R.

    2013-01-01

    Acid-base chemistry of clay minerals is central to their interfacial properties, but up to now a quantitative understanding on the surface acidity is still lacking. In this study, with first principles molecular dynamics (FPMD) based vertical energy gap technique, we calculate the acidity constants

  20. Layered materials with coexisting acidic and basic sites for catalytic one-pot reaction sequences.

    Science.gov (United States)

    Motokura, Ken; Tada, Mizuki; Iwasawa, Yasuhiro

    2009-06-17

    Acidic montmorillonite-immobilized primary amines (H-mont-NH(2)) were found to be excellent acid-base bifunctional catalysts for one-pot reaction sequences, which are the first materials with coexisting acid and base sites active for acid-base tamdem reactions. For example, tandem deacetalization-Knoevenagel condensation proceeded successfully with the H-mont-NH(2), affording the corresponding condensation product in a quantitative yield. The acidity of the H-mont-NH(2) was strongly influenced by the preparation solvent, and the base-catalyzed reactions were enhanced by interlayer acid sites.

  1. High-Temperature Decomposition of Brønsted Acid Sites in Gallium-Substituted Zeolites

    Energy Technology Data Exchange (ETDEWEB)

    K Al-majnouni; N Hould; W Lonergan; D Vlachos; R Lobo

    2011-12-31

    The dehydroxylation of Broensted acid sites (BAS) in Ga-substituted zeolites was investigated at temperatures up to 850 C using X-ray absorption spectroscopy (XAS), Fourier transform infrared spectroscopy (FTIR), and mass spectrometry-temperature programmed desorption (MS-TPD). X-ray absorption near-edge spectroscopy (XANES) revealed that the majority of gallium has tetrahedral coordination even after complete dehydroxylation. The interatomic gallium-oxygen distance and gallium coordination number determined by extended X-ray absorption fine structure (EXAFS) are consistent with gallium in tetrahedral coordination at low T (< 550 C). Upon heating Ga-Beta and Ga-ZSM5 to 850 C, analysis of the EXAFS showed that 70 and 80% of the gallium was still in tetrahedral coordination. The remainder of the gallium was found to be in octahedral coordination. No trigonal Ga atoms were observed. FTIR measurements carried out at similar temperatures show that the intensity of the OH vibration due to BAS has been eliminated. MS-TPD revealed that hydrogen in addition to water evolved from the samples during dehydroxylation. This shows that dehydrogenation in addition to dehydration is a mechanism that contributes to BAS decomposition. Dehydrogenation was further confirmed by exposing the sample to hydrogen to regenerate some of the BAS as monitored by FTIR and MS-TPD.

  2. Highly selective Lewis acid sites in desilicated MFI zeolites for dihydroxyacetone isomerization to lactic acid.

    Science.gov (United States)

    Dapsens, Pierre Y; Mondelli, Cecilia; Pérez-Ramírez, Javier

    2013-05-01

    Desilication of commercial MFI-type (ZSM-5) zeolites in solutions of alkali metal hydroxides is demonstrated to generate highly selective heterogeneous catalysts for the aqueous-phase isomerization of biobased dihydroxyacetone (DHA) to lactic acid (LA). The best hierarchical ZSM-5 sample attains a LA selectivity exceeding 90 %, which is comparable to that of the state-of-the-art catalyst (i.e., the Sn-beta zeolite); this optimized hierarchical catalyst is recyclable over three runs. The Lewis acid sites, which are created through desilication along with the introduction of mesoporosity, are shown to play a crucial role in the formation of the desired product; these cannot be achieved by using other post-synthetic methods, such as steaming or impregnation of aluminum species. Desilication of other metallosilicates, such as Ga-MFI, also leads to high LA selectivity. In the presence of a soluble aluminum source, such as aluminum nitrate, alkaline-assisted alumination can introduce these unique Lewis acid centers in all-silica MFI zeolites. These findings highlight the potential of zeolites in the field of biomass-to-chemical conversion, and expand the applicability of desilication for the generation of selective catalytic centers. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Characterization of the binding sites for dicarboxylic acids on bovine serum albumin.

    Science.gov (United States)

    Tonsgard, J H; Meredith, S C

    1991-06-15

    Dicarboxylic acids are prominent features of several diseases, including Reye's syndrome and inborn errors of mitochondrial and peroxisomal fatty acid oxidation. Moreover, dicarboxylic acids are potentially toxic to cellular processes. Previous studies [Tonsgard, Mendelson & Meredith (1988) J. Clin. Invest. 82, 1567-1573] demonstrated that long-chain dicarboxylic acids have a single high-affinity binding site and between one and three lower-affinity sites on albumin. Medium-chain-length dicarboxylic acids have a single low-affinity site. We further characterized dicarboxylic acid binding to albumin in order to understand the potential effects of drugs and other ligands on dicarboxylic acid binding and toxicity. Progesterone and oleate competitively inhibit octadecanedioic acid binding to the single high-affinity site. Octanoate inhibits binding to the low-affinity sites. Dansylated probes for subdomain 2AB inhibit dodecanedioic acid binding whereas probes for subdomain 3AB do not. In contrast, low concentrations of octadecanedioic acid inhibit the binding of dansylated probes to subdomain 3AB and 2AB. L-Tryptophan, which binds in subdomain 3AB, inhibits hexadecanedioic acid binding but has no effect on dodecanedioic acid. Bilirubin and acetylsalicylic acid, which bind in subdomain 2AB, inhibit the binding of medium-chain and long-chain dicarboxylic acids. Our results suggest that long-chain dicarboxylic acids bind in subdomains 2C, 3AB and 2AB. The single low-affinity binding site for medium-chain dicarboxylic acids is in subdomain 2AB. These studies suggest that dicarboxylic acids are likely to be unbound in disease states and may be potentially toxic.

  4. Site specific incorporation of keto amino acids into proteins

    Science.gov (United States)

    Schultz, Peter G [La Jolla, CA; Wang, Lei [San Diego, CA

    2012-02-14

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate keto amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with keto amino acids using these orthogonal pairs.

  5. Modeling acidic sites in zeolites and aluminosilicates by aluminosilsesquioxanes

    NARCIS (Netherlands)

    Duchateau, R; Harmsen, RJ; Abbenhuis, HCL; van Santen, RA; Meetsma, A; Thiele, SKH; Kranenburg, M

    1999-01-01

    Protolysis of alkylaluminum compounds with silsesquioxanes is an efficient procedure to synthesize both Lewis and Bronsted acidic aluminosilsesquioxanes. Treatment of AlEt3 with (c-C5H9)(7)Si7O9(OH)(3) and (c-C5H9)(7)Si7O9(OSiMe3)(OH)(2) gives the corresponding Lewis acidic aluminosilsesquioxanes, {

  6. Site specific incorporation of keto amino acids into proteins

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter G [La Jolla, CA; Wang, Lei [San Diego, CA

    2012-02-14

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate keto amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with keto amino acids using these orthogonal pairs.

  7. Site specific incorporation of keto amino acids into proteins

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter G. (La Jolla, CA); Wang, Lei (San Diego, CA)

    2011-03-22

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate keto amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with keto amino acids using these orthogonal pairs.

  8. Site specific incorporation of keto amino acids into proteins

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter G [La Jolla, CA; Wang, Lei [San Diego, CA

    2011-12-06

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate keto amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with keto amino acids using these orthogonal pairs.

  9. Naturally evolved enhanced Cd tolerance of Dianthus carthusianorum L. is not related to accumulation of thiol peptides and organic acids.

    Science.gov (United States)

    Wójcik, Małgorzata; Dresler, Sławomir; Plak, Andrzej; Tukiendorf, Anna

    2015-05-01

    Two contrasting ecotypes of Dianthus carthusianorum L., metallicolous (M) and nonmetallicolous (NM), were cultivated in hydroponics at 0-50 μM Cd for 14 days to compare their Cd accumulation, sensitivity and tolerance mechanisms. While both ecotypes contained similar concentrations of Cd in the shoots and roots, the M ecotype was more Cd-tolerant (as measured by fresh weight production and root and leaf viability). Both ecotypes accumulated phytochelatins (PCs) in response to Cd with a higher amount thereof found in the NM ecotype. Concentrations of PCs remained unchanged with increasing Cd concentrations in the root tissues, but their content in the shoots increased. The addition of L-buthionine-sulfoximine (BSO) diminished glutathione (GSH) accumulation and arrested PC production, which increased the sensitivity to Cd of the NM, but not M ecotype. Organic acids (malate and citrate) as well as proline accumulation did not change significantly after Cd exposition and was at the same level in both ecotypes. The enhanced Cd tolerance of the M ecotype of D. carthusianorum cannot be explained in terms of restricted Cd uptake and differential production of PCs, organic acids or proline; some other mechanisms must be involved in its adaptation to the high Cd content in the environment.

  10. A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs

    OpenAIRE

    Miao, Zhichao; Westhof, Eric

    2015-01-01

    Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i) the definition of nucleic acid binding sites; ii) the training and test datasets; iii) the algorithmic methods for the prediction strategies; iv) the performance measures and v) the distribution and avail...

  11. A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs.

    OpenAIRE

    Zhichao Miao; Eric Westhof

    2015-01-01

    Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i) the definition of nucleic acid binding sites; ii) the training and test datasets; iii) the algorithmic methods for the prediction strategies; iv) the performance measures and v) the distribution and avail...

  12. Trimethylamine as a probe molecule to differentiate acid sites in Y-FAU zeolite: FTIR study.

    Science.gov (United States)

    Sarria, Francisca Romero; Blasin-Aubé, Vanessa; Saussey, Jacques; Marie, Olivier; Daturi, Marco

    2006-07-06

    In heterogeneous catalysis acidity has a very important influence on activity and selectivity: correct determination of acidic properties is a base to improve industrial processes. The aim of this work was to study trimethylamine (TMA) as a probe molecule able to distinguish between the different Brønsted acid sites in zeolitic frameworks. Our work mainly focused on faujasite-type zeolites because the HY zeolite is one of the most used acidic catalysts in industrial processes. In this paper, typical IR bands assigned to TMA-protonated species (formed in supercages) are detected in the HY zeolite. TMA interacting by hydrogen bonding with the acid sites located in the sodalite units is also observed. The wavenumbers of some typical IR bands assigned to TMA-protonated species appear to depend on the acidic strength, and a complementary study with ZSM-5 and X-FAU samples confirms this proposition.

  13. Organic acids in cloud water and rainwater at a mountain site in acid rain areas of South China.

    Science.gov (United States)

    Sun, Xiao; Wang, Yan; Li, Haiyan; Yang, Xueqiao; Sun, Lei; Wang, Xinfeng; Wang, Tao; Wang, Wenxing

    2016-05-01

    To investigate the chemical characteristics of organic acids and to identify their source, cloud water and rainwater samples were collected at Mount Lu, a mountain site located in the acid rain-affected area of south China, from August to September of 2011 and March to May of 2012. The volume-weighted mean (VWM) concentration of organic acids in cloud water was 38.42 μeq/L, ranging from 7.45 to 111.46 μeq/L, contributing to 2.50 % of acidity. In rainwater samples, organic acid concentrations varied from 12.39 to 68.97 μeq/L (VWM of 33.39 μeq/L). Organic acids contributed significant acidity to rainwater, with a value of 17.66 %. Formic acid, acetic acid, and oxalic acid were the most common organic acids in both cloud water and rainwater. Organic acids had an obviously higher concentration in summer than in spring in cloud water, whereas there was much less discrimination in rainwater between the two seasons. The contribution of organic acids to acidity was lower during summer than during spring in both cloud water (2.20 % in summer vs 2.83 % in spring) and rainwater (12.24 % in summer vs 19.89 % in spring). The formic-to-acetic acid ratio (F/A) showed that organic acids were dominated by primary emissions in 71.31 % of the cloud water samples and whole rainwater samples. Positive matrix factorization (PMF) analysis determined four factors as the sources of organic acids in cloud water, including biogenic emissions (61.8 %), anthropogenic emissions (15.28 %), marine emissions (15.07 %) and soil emissions (7.85 %). The findings from this study imply an indispensable role of organic acids in wet deposition, but organic acids may have a limited capacity to increase ecological risks in local environments.

  14. The Detection of Evolved Oxygen from the Rocknest Eolian Bedform Material by the Sample Analysis at Mars(SAM) instrument at the Mars Curiosity Landing Site

    Science.gov (United States)

    Sutter, B.; Archer, D.; Ming, D.; Eigenbrode, J. L.; Franz, H.; Glavin, D. P.; McAdam, A.; Mahaffy, P.; Stern, J.; Navarro-Gonzalex, R.; McKay, C.

    2013-01-01

    The Sample Analysis at Mars (SAM) instrument onboard the Curiosity rover detected an O2 gas release from the Rocknest eolain bedform (Fig. 1). The detection of perchlorate (ClO4-) by the Mars Phoenix Lander s Wet Chemistry Laboratory (WCL) [1] suggests that perchlorate is a possible candidate for evolved O2 release detected by SAM. The perchlorate would also serve as a source of chlorine in the chlorinated hydrocarbons detected by the SAM quadrupole mass spectrometer (QMS) and gas chromatography/mass spectrometer (GCMS) [2,3]. Chlorates (ClO3-) [4,5] and/or superoxides [6] may also be sources of evolved O2 from the Rocknest materials. The work objectives are to 1) evaluate the O2 release temperatures from Rocknest materials, 2) compare these O2 release temperatures with a series of perchlorates and chlorates, and 3) evaluate superoxide O2- sources and possible perchlorate interactions with other Rocknest phases during QMS analysis.

  15. Fatty acid composition differences between adipose depot sites in dairy and beef steer breeds.

    Science.gov (United States)

    Liu, T; Lei, Z M; Wu, J P; Brown, M A

    2015-03-01

    The objective of the study was to compare fatty acid composition of longissimus dorsi (LD) and kidney fat (KF) in Holstein steers (HS), Simmental steers (SS) and Chinese LongDong Yellow Cattle steers (CLD). All steers received the same nutrition and management but in different locations. Cattle were harvested at approximately 550 kg and fatty acid composition of longissimus dorsi and kidney fat was analyzed in samples taken after 3 days of aging. There was evidence (P fatty acids were greater in LD than KF for all breeds (P fatty acids (PUFA), monounsaturated fatty acids (MUFA), and a greater ratio of n6:n3 PUFAs compared to the KF in each breed (P fatty acid percentages generally differed between longissimus dorsi fat and kidney fat. Further, there was some indication that some of these differences between fatty acid deposition sites were not consistent across breed group.

  16. Review of Evolving Planet [game

    Directory of Open Access Journals (Sweden)

    Shawn Graham

    2016-11-01

    Full Text Available A review of Evolving Planet is an agent-based model situated in the archaeology of hominin dispersal, wrapped in the trappings of a casual video game. In Evolving Planet, a terrestrial world has been discovered, replete with artefacts and sites from a now-extinct intelligent species, dubbed the 'Lovans'. You (the player are the distinguished archaeologist sent from Earth to oversee a project trying to work out why the 'Lovans' became extinct.

  17. Review of Evolving Planet [game

    OpenAIRE

    Shawn Graham

    2016-01-01

    A review of Evolving Planet is an agent-based model situated in the archaeology of hominin dispersal, wrapped in the trappings of a casual video game. In Evolving Planet, a terrestrial world has been discovered, replete with artefacts and sites from a now-extinct intelligent species, dubbed the 'Lovans'. You (the player) are the distinguished archaeologist sent from Earth to oversee a project trying to work out why the 'Lovans' became extinct.

  18. Phylogenetic distribution of [3H]kainic acid receptor binding sites in neuronal tissue.

    Science.gov (United States)

    London, E D; Klemm, N; Coyle, J T

    1980-06-23

    The phylogenetic distribution of specific binding sites for kainic acid was determined in 14 species including invertebrates and vertebrates. The highest level of binding was observed in brains of the frog (Xenopus laevis), followed by the spiny dogfish (Heterodontus francisci), the goldfish (Carasius auratus) and the chick (Gallus domesticus). Although significant specific binding was noted in some of the lowest forms tested (e.g. Hydra littoralis), this was not a consistent observation in the invertebrates. In most cases, specific binding to both high and low affinity sites was detected; notable exceptions were the cockroach brain (Periplaneta americana), which had negligible high affinity binding, and the crayfish brain (Procambarus) which had negligible low affinity binding. In the spiny dogfish, the smooth dogfish and the chick, the highest level of binding occurred in cerebellum with less in the forebrain and the least in the medulla; in the mammalian species, the highest level of binding occurred in the forebrain structures with less in the cerebellum and least in the medulla. Eadie plots of the saturation isotherms for [3H]kainic acid revealed similar kinetics of binding for frog whole brain, rat forebrain and human parietal cortex with two apparent populations of binding sites: KD1 = 25--50 nM and KD2 = 3--14 nM. While binding in the spiny dogfish forebrain and human caudate nucleus occurred exclusively at a high affinity component, the cerebella of chick, rat and man exhibited only a low affinity binding site. In the 3 species studied most extensively, frog, rat and man, unlabeled kainic acid was the most potent inhibitor of the specific binding of [3H]-kainic acid. L-Glutamic acid was 20--20-fold less potent than kainic acid, and D-glutamic acid was 4--2500-fold less potent than its L-isomer. Reduction of the isopropylene side chain of kainic acid to form dihydrokainic acid decreased the affinity of the derivative 115--30,000-fold. Hill coefficients

  19. Site specific incorporation of heavy atom-containing unnatural amino acids into proteins for structure determination

    Science.gov (United States)

    Xie, Jianming; Wang, Lei; Wu, Ning; Schultz, Peter G.

    2008-07-15

    Translation systems and other compositions including orthogonal aminoacyl tRNA-synthetases that preferentially charge an orthogonal tRNA with an iodinated or brominated amino acid are provided. Nucleic acids encoding such synthetases are also described, as are methods and kits for producing proteins including heavy atom-containing amino acids, e.g., brominated or iodinated amino acids. Methods of determining the structure of a protein, e.g., a protein into which a heavy atom has been site-specifically incorporated through use of an orthogonal tRNA/aminoacyl tRNA-synthetase pair, are also described.

  20. Quantitative measurement of the Brönsted acid sites in solid acids: toward a single-site design of Mo-modified ZSM-5 zeolite.

    Science.gov (United States)

    Tessonnier, Jean-Philippe; Louis, Benoît; Walspurger, Stephane; Sommer, Jean; Ledoux, Marc-Jacques; Pham-Huu, Cuong

    2006-06-01

    On the basis of our previous H/D exchange studies devoted to the quantification of the number of Brönsted acid sites in solid acids, we report here an innovative approach to determine both the amount and the localization of Mo atoms inside the Mo/ZSM-5 catalyst, commonly used for the methane dehydroaromatization reaction. The influence of Mo introduction in the MFI framework was studied by means of BET, X-ray diffraction, 27Al magic angle spinning NMR, NH3 temperature-programmed desorption, and H/D isotopic exchange techniques. A dependence was found between the decrease of acidic OH groups and the Mo content. Depending on the Si/Al ratio of the zeolite, i.e., the proximity of two Brönsted acid sites, the Mo atoms substitute a different number of OH groups. Consequently, a chemical structure was proposed to describe the geometry of the Mo complex in the channels of the ZSM-5 zeolite.

  1. Site directed mutagenesis of amino acid residues at the active site of mouse aldehyde oxidase AOX1.

    Directory of Open Access Journals (Sweden)

    Silvia Schumann

    Full Text Available Mouse aldehyde oxidase (mAOX1 forms a homodimer and belongs to the xanthine oxidase family of molybdoenzymes which are characterized by an essential equatorial sulfur ligand coordinated to the molybdenum atom. In general, mammalian AOs are characterized by broad substrate specificity and an yet obscure physiological function. To define the physiological substrates and the enzymatic characteristics of mAOX1, we established a system for the heterologous expression of the enzyme in Escherichia coli. The recombinant protein showed spectral features and a range of substrate specificity similar to the native protein purified from mouse liver. The EPR data of recombinant mAOX1 were similar to those of AO from rabbit liver, but differed from the homologous xanthine oxidoreductase enzymes. Site-directed mutagenesis of amino acids Val806, Met884 and Glu1265 at the active site resulted in a drastic decrease in the oxidation of aldehydes with no increase in the oxidation of purine substrates. The double mutant V806E/M884R and the single mutant E1265Q were catalytically inactive enzymes regardless of the aldehyde or purine substrates tested. Our results show that only Glu1265 is essential for the catalytic activity by initiating the base-catalyzed mechanism of substrate oxidation. In addition, it is concluded that the substrate specificity of molybdo-flavoenzymes is more complex and not only defined by the three characterized amino acids in the active site.

  2. Atmospheric geochemistry of formic and acetic acids at a mid-latitude temperate site

    Science.gov (United States)

    Talbot, R. W.; Beecher, K. M.; Harriss, R. C.; Cofer, R. W., III

    1988-01-01

    Tropospheric concentrations of formic and acetic acids in the gas, the aerosol, and the rainwater phases were determined in samples collected 1-2 m above ground level at an open field site in eastern Virginia. These acids were found to occur principally (98 percent or above) in the gas phase, with a marked annual seasonality, averaging 1890 ppt for formate and 1310 ppt for acetate during the growing season, as compared to 695 ppt and 700 ppt, respectively, over the nongrowing season. The data support the hypothesis that biogenic emissions from vegatation are important sources of atmospheric formic and acetic acid during the local growing season. The same time trends were observed for precipitation, although with less defined seasonality. The relative increase of the acetic acid/formic acid ratio during the nongrowing season points to the dominance of anthropogenic inputs of acetic acid from motor vehicles and biomass combustion in the wintertime.

  3. Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

    Directory of Open Access Journals (Sweden)

    Mashiur Rahman

    2014-12-01

    Full Text Available Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA was studied by equilibrium dialysis method (ED at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Results: Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 105 M-1 with low capacity (n1 = 2 and low affinity association (k2 = 4.0×105 M-1 constant with high capacity (n2 = 8 at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10-5 M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. Conclusion: This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

  4. Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites

    OpenAIRE

    Zahid, Henna; Miah, Layeque; Lau, Andy; Brochard, Lea; Hati, Debolina; Bui, T. T.; Drake, A. F.; Gor, Jayesh; Perkins, Stephen J.; McDermott, Lindsay C.

    2016-01-01

    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigate...

  5. Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

    OpenAIRE

    Mashiur Rahman; Farzana Prianka; Mohammad Shohel; Md. Abdul Mazid

    2014-01-01

    Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA) was studied by equilibrium dialysis method (ED) at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 a...

  6. Role of Lewis acid sites of ZSM-5 zeolite on gaseous ozone abatement

    OpenAIRE

    Brodu, Nicolas; Manero, Marie-Hélène; Andriantsiferana, Caroline; Pic, Jean-Stéphane; Valdés, Héctor

    2013-01-01

    International audience; In this work, chemical interactions between ozone and zeolite surface active sites are studied in order to propose a process for gaseous ozone removal. Synthetic ZSM-5 zeolites with three different Si/Al2 ratios and similar specific surface areas and microporous volumes were used in this study. Zeolite samples were characterised using Fourier Transform InfraRed spectroscopy (FTIR) and pyridine sorption IR studies in order to determine acidic site concentrations and str...

  7. Effect of sun elevation upon remote sensing of ocean color over an acid waste dump site

    Science.gov (United States)

    Bressette, W. E.

    1978-01-01

    Photographic flights were made over an ocean acid waste dump site while dumping was in progress. The flights resulted in wide angle, broadband, spectral radiance film exposure data between the wavelengths of 500 to 900 nanometers for sun elevation angles ranging from 26 to 42 degrees. It is shown from densitometer data that the spectral signature of acid waste discharged into ocean water can be observed photographically, the influence of sun elevation upon remotely sensed apparent color can be normalized by using a single spectral band ratioing technique, and photographic quantification and mapping of acid waste through its suspended iron precipitate appears possible.

  8. A general method for site-specific incorporation of unnatural amino acids into proteins

    Energy Technology Data Exchange (ETDEWEB)

    Noren, C.J.; Anthony-Cahill, S.J; Griffith, M.C.; Schultz, P.G. (Lawrence Berkeley Lab., CA (USA))

    1989-04-14

    A new method has been developed that makes it possible to site-specifically incorporate unnatural amino acids into proteins. Synthetic amino acids were incorporated into the enzyme {beta}-lactamase by the use of a chemically acylated suppressor transfer RNA that inserted the amino acid in response to a stop codon substituted for the codon encoding residue of interest. Peptide mapping localized the inserted amino acid to a single peptide, and enough enzyme could be generated for purification to homogeneity. The catalytic properties of several mutants at the conserved Phe{sup 66} were characterized. The ability to selectively replace amino acids in a protein with a wide variety of structural and electronic variants should provide a more detailed understanding of protein structure and function. 45 refs., 7 figs., 1 tab.

  9. Dissolution of Simulated and Radioactive Savannah River Site High-Level Waste Sludges with Oxalic Acid & Citric Acid Solutions

    Energy Technology Data Exchange (ETDEWEB)

    STALLINGS, MARY

    2004-07-08

    This report presents findings from tests investigating the dissolution of simulated and radioactive Savannah River Site sludges with 4 per cent oxalic acid and mixtures of oxalic and citric acid previously recommended by a Russian team from the Khlopin Radium Institute and the Mining and Chemical Combine (MCC). Testing also included characterization of the simulated and radioactive waste sludges. Testing results showed the following: Dissolution of simulated HM and PUREX sludges with oxalic and citric acid mixtures at SRTC confirmed general trends reported previously by Russian testing. Unlike the previous Russian testing six sequential contacts of a mixture of oxalic acid citric acids at a 2:1 ratio (v/w) of acid to sludge did not produce complete dissolution of simulated HM and PUREX sludges. We observed that increased sludge dissolution occurred at a higher acid to sludge ratio, 50:1 (v/w), compared to the recommended ratio of 2:1 (v/w). We observed much lower dissolution of aluminum in a simulated HM sludge by sodium hydroxide leaching. We attribute the low aluminum dissolution in caustic to the high fraction of boehmite present in the simulated sludge. Dissolution of HLW sludges with 4 per cent oxalic acid and oxalic/citric acid followed general trends observed with simulated sludges. The limited testing suggests that a mixture of oxalic and citric acids is more efficient for dissolving HM and PUREX sludges and provides a more homogeneous dissolution of HM sludge than oxalic acid alone. Dissolution of HLW sludges in oxalic and oxalic/citric acid mixtures produced residual sludge solids that measured at higher neutron poison to equivalent 235U weight ratios than that in the untreated sludge solids. This finding suggests that residual solids do not present an increased nuclear criticality safety risk. Generally the neutron poison to equivalent 235U weight ratios of the acid solutions containing dissolved sludge components are lower than those in the untreated

  10. Are carboxyl groups the most acidic sites in amino acids? Gas-phase acidities, photoelectron spectra, and computations on tyrosine, p-hydroxybenzoic acid, and their conjugate bases.

    Science.gov (United States)

    Tian, Zhixin; Wang, Xue-Bin; Wang, Lai-Sheng; Kass, Steven R

    2009-01-28

    Deprotonation of tyrosine in the gas phase was found to occur preferentially at the phenolic site, and the conjugate base consists of a 70:30 mixture of phenoxide and carboxylate anions at equilibrium. This result was established by developing a chemical probe for differentiating these two isomers, and the presence of both ions was confirmed by photoelectron spectroscopy. Equilibrium acidity measurements on tyrosine indicated that deltaG(acid)(o) = 332.5 +/- 1.5 kcal mol(-1) and deltaH(acid)(o) = 340.7 +/- 1.5 kcal mol(-1). Photoelectron spectra yielded adiabatic electron detachment energies of 2.70 +/- 0.05 and 3.55 +/- 0.10 eV for the phenoxide and carboxylate anions, respectively. The H/D exchange behavior of deprotonated tyrosine was examined using three different alcohols (CF3CH2OD, C6H5CH2OD, and CH3CH2OD), and incorporation of up to three deuterium atoms was observed. Two pathways are proposed to account for these results, and all of the experimental findings are supplemented with B3LYP/aug-cc-pVDZ and G3B3 calculations. In addition, it was found that electrospray ionization of tyrosine from a 3:1 (v/v) CH3OH/H2O solution using a commercial source produces a deprotonated [M-H]- anion with the gas-phase equilibrium composition rather than the structure of the ion that exists in aqueous media. Electrospray ionization from acetonitrile, however, leads largely to the liquid-phase (carboxylate) structure. A control molecule, p-hydroxybenzoic acid, was found to behave in a similar manner. Thus, the electrospray conditions that are employed for the analysis of a compound can alter the isomeric composition of the resulting anion.

  11. Bayes Empirical Bayes Inference of Amino Acid Sites Under Positive Selection

    DEFF Research Database (Denmark)

    Yang, Ziheng; Wong, Wendy Shuk Wan; Nielsen, Rasmus

    2005-01-01

    Codon-based substitution models have been widely used to identify amino acid sites under positive selection in comparative analysis of protein-coding DNA sequences. The nonsynonymous-synonymous substitution rate ratio (dN/dS, denoted ) is used as a measure of selective pressure at the protein level...

  12. Spontaneous dispersion of PdO onto acid sites of zeolites studied by in situ DXAFS

    CERN Document Server

    Okumura, K; Niwa, M; Yokota, S; Kato, K; Tanida, H; Uruga, T

    2003-01-01

    The generation of highly dispersed PdO over zeolite supports was studied using in situ energy-dispersive XAFS (DXAFS) technique. From the comparison with the Na-ZSM-5, it was found that the oxidation as well as the spontaneous dispersion of Pd was promoted through the interaction between PdO and acid sites of H-form zeolites. (author)

  13. PHYSICAL SOLUTIONS FOR ACID ROCK DRAINAGE AT REMOTE SITES DEMONSTRATION PROJECT

    Science.gov (United States)

    This report summarizes the results of Mine Waste Technology Program, Activity III, Project 42, Physical Solutions for Acid Rock Drainage at Remote Sites, funded by the U.S. Environmental Protection Agency (EPA) and jointly administered by EPA and the U.S. Department of Energy. A...

  14. Brønsted acid sites based on penta-coordinated aluminum species

    Science.gov (United States)

    Wang, Zichun; Jiang, Yijiao; Lafon, Olivier; Trébosc, Julien; Duk Kim, Kyung; Stampfl, Catherine; Baiker, Alfons; Amoureux, Jean-Paul; Huang, Jun

    2016-12-01

    Zeolites and amorphous silica-alumina (ASA), which both provide Brønsted acid sites (BASs), are the most extensively used solid acid catalysts in the chemical industry. It is widely believed that BASs consist only of tetra-coordinated aluminum sites (AlIV) with bridging OH groups in zeolites or nearby silanols on ASA surfaces. Here we report the direct observation in ASA of a new type of BAS based on penta-coordinated aluminum species (AlV) by 27Al-{1H} dipolar-mediated correlation two-dimensional NMR experiments at high magnetic field under magic-angle spinning. Both BAS-AlIV and -AlV show a similar acidity to protonate probe molecular ammonia. The quantitative evaluation of 1H and 27Al sites demonstrates that BAS-AlV co-exists with BAS-AlIV rather than replaces it, which opens new avenues for strongly enhancing the acidity of these popular solid acids.

  15. Theoretical study on OH{sup −} site and electronic spin state of oxygen-evolving complex in photosystem II at the dark S{sub 1} state

    Energy Technology Data Exchange (ETDEWEB)

    Hatakeyama, Makoto; Ogata, Koji; Nakamura, Shinichiro [RIKEN Research Cluster for Innovation, Nakamura Laboratory, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Uchida, Waka [Department of Biomolecular Engineering, Tokyo Institute of Technology, B-70, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan)

    2013-12-10

    Possible protonation and electronic-spin states of oxygen-evolving complex (OEC) in photosystem II have been investigated by using QM(DFT-UB3LYP)/MM(Amber) calculation, in order to elucidate which OEC state satisfies the known experimental results at the dark stable state (S{sub 1}), i.e. OEC involves Mn{sub 4}(III{sub 2},IV{sub 4})-cluster and a S=0 state as the lowest energy electronic-spin state at S{sub 1}. The configuration of Mn oxidation numbers and the lowest energy spin state within the Mn{sub 4}-cluster depend on the protonation state of one oxo-anion bridging three Mn ions. When all water-ligands and oxo-bridges form H{sub 2}O and O{sup 2−}, respectively, the resulting OEC model involved Mn{sub 4}(III{sub 2},IV{sub 2})-cluster and one S=0 state as the lowest energy spin state. To rationalize the O{sup 2−}-bridge model at S{sub 1} state, a new H{sup +}-release scheme during the H{sub 2}O-splitting reaction is proposed.

  16. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    Energy Technology Data Exchange (ETDEWEB)

    Gangi Setty, Thanuja [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Cho, Christine [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Govindappa, Sowmya [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Apicella, Michael A. [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Ramaswamy, S., E-mail: ramas@instem.res.in [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India)

    2014-07-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

  17. Detection of Evolved Carbon Dioxide in the Rocknest Eolian Bedform by the Sample Analysis at Mars(SAM) Instrument at the Mars Curiosity Landing Site

    Science.gov (United States)

    Sutter, B.; Archer, D.; McAdam, A.; Franz, H.; Ming, D. W.; Eigenbrode, J. L.; Glavin, D. P.; Mahaffy, P.; Stern, J.; Navarro-Gonzalez, R.

    2013-01-01

    The Sample Analysis at Mars (SAM) instrument detected four releases of carbon dioxide (CO2) that ranged from 100 to 700 C from the Rocknest eolian bedform material (Fig. 1). Candidate sources of CO2 include adsorbed CO2, carbonate(s), combusted organics that are either derived from terrestrial contamination and/or of martian origin, occluded or trapped CO2, and other sources that have yet to be determined. The Phoenix Lander s Thermal Evolved Gas Analyzer (TEGA) detected two CO2 releases (400-600, 700-840 C) [1,2]. The low temperature release was attributed to Fe- and/or Mg carbonates [1,2], per-chlorate interactions with carbonates [3], nanophase carbonates [4] and/or combusted organics [1]. The high temperature CO2 release was attributed to a calcium bearing carbonate [1,2]. No evidence of a high temperature CO2 release similar to the Phoenix material was detected in the Rocknest materials by SAM. The objectives of this work are to evaluate the temperature and total contribution of each Rocknest CO2 release and their possible sources. Four CO2 releases from the Rocknest material were detected by SAM. Potential sources of CO2 are adsorbed CO2, (peak 1) and Fe/Mg carbonates (peak 4). Only a fraction of peaks 2 and 3 (0.01 C wt.%) may be partially attributed to combustion of organic contamination. Meteoritic organics mixed in the Rocknest bedform could be present, but the peak 2 and 3 C concentration (approx.0.21 C wt. %) is likely too high to be attributed solely to meteoritic organic C. Other inorganic sources of C such as interactions of perchlorates and carbonates and sources yet to be identified will be evaluated to account for CO2 released from the thermal decomposition of Rocknest material.

  18. Lipid Classes and Fatty Acids in Ophryotrocha cyclops, a Dorvilleid from Newfoundland Aquaculture Sites.

    Science.gov (United States)

    Salvo, Flora; Dufour, Suzanne C; Hamoutene, Dounia; Parrish, Christopher C

    2015-01-01

    A new opportunistic annelid (Ophryotrocha cyclops) discovered on benthic substrates underneath finfish aquaculture sites in Newfoundland (NL) may be involved in the remediation of organic wastes. At those aquaculture sites, bacterial mats and O. cyclops often coexist and are used as indicators of organic enrichment. Little is known on the trophic strategies used by these annelids, including whether they might consume bacteria or other aquaculture-derived wastes. We studied the lipid and fatty acid composition of the annelids and their potential food sources (degraded flocculent organic matter, fresh fish pellets and bacterial mats) to investigate feeding relationships in these habitats and compared the lipid and fatty acid composition of annelids before and after starvation. Fish pellets were rich in lipids, mainly terrestrially derived C18 fatty acids (18:1ω9, 18:2ω6, 18:3ω3), while bacterial samples were mainly composed of ω7 fatty acids, and flocculent matter appeared to be a mixture of fresh and degrading fish pellets, feces and bacteria. Ophryotrocha cyclops did not appear to store excessive amounts of lipids (13%) but showed a high concentration of ω3 and ω6 fatty acids, as well as a high proportion of the main fatty acids contained in fresh fish pellets and bacterial mats. The dorvilleids and all potential food sources differed significantly in their lipid and fatty acid composition. Interestingly, while all food sources contained low proportions of 20:5ω3 and 20:2ω6, the annelids showed high concentrations of these two fatty acids, along with 20:4ω6. A starvation period of 13 days did not result in a major decrease in total lipid content; however, microscopic observations revealed that very few visible lipid droplets remained in the gut epithelium after three months of starvation. Ophryotrocha cyclops appears well adapted to extreme environments and may rely on lipid-rich organic matter for survival and dispersal in cold environments.

  19. Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites.

    Science.gov (United States)

    Zahid, Henna; Miah, Layeque; Lau, Andy M; Brochard, Lea; Hati, Debolina; Bui, Tam T T; Drake, Alex F; Gor, Jayesh; Perkins, Stephen J; McDermott, Lindsay C

    2016-01-01

    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigated. Analytical ultracentrifugation (AUC) and CD showed that zinc, but not other divalent metals, causes ZAG to oligomerize in solution. Thus ZAG dimers and trimers were observed in the presence of 1 and 2 mM zinc. Molecular modelling of X-ray scattering curves and sedimentation coefficients indicated a progressive stacking of ZAG monomers, suggesting that the ZAG groove may be occluded in these. Using fluorescence-detected sedimentation velocity, these ZAG-zinc oligomers were again observed in the presence of the fluorescent boron dipyrromethene fatty acid C16-BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-hexadecanoic acid). Fluorescence spectroscopy confirmed that ZAG binds C16-BODIPY. ZAG binding to C16-BODIPY, but not to DAUDA, was reduced by increased zinc concentrations. We conclude that the lipid-binding groove in ZAG contains at least two distinct fatty acid-binding sites for DAUDA and C16-BODIPY, similar to the multiple lipid binding seen in the structurally related immune protein CD1c. In addition, because high concentrations of zinc occur in the pancreas, the perturbation of these multiple lipid-binding sites by zinc may be significant in Type 2 diabetes where dysregulation of ZAG and zinc homoeostasis occurs.

  20. Analyzing Evolving Social Network 2 (EVOLVE2)

    Science.gov (United States)

    2015-04-01

    COVERED (From - To) JUN 2012 – OCT 2014 4. TITLE AND SUBTITLE ANALYZING EVOLVING SOCIAL NETWORKS 2 (EVOLVE2) 5a. CONTRACT NUMBER FA8750-12-2-0186... jazz 198 2742 274 0.14 connect 1095 7825 783 0.014 hep-th 8710 14254 1425 0.0003 netscience 1461 2742 274 0.0013 imdb 6260 98235 9824 0.005 technological

  1. Novel Ionic Liquid with Both Lewis and Brønsted Acid Sites for Michael Addition

    Directory of Open Access Journals (Sweden)

    Runpu Shen

    2011-10-01

    Full Text Available Ionic liquid with both Lewis and Brønsted acid sites has been synthesized and its catalytic activities for Michael addition were carefully studied. The novel ionic liquid was stable to water and could be used in aqueous solution. The molar ratio of the Lewis and Brønsted acid sites could be adjusted to match different reactions. The results showed that the novel ionic liquid was very efficient for Michael addition with good to excellent yields within several min. Operational simplicity, high stability to water and air, small amount used, low cost of the catalyst used, high yields, chemoselectivity, applicability to large-scale reactions and reusability are the key features of this methodology, which indicated that this novel ionic liquid also holds great potential for environmentally friendly processes.

  2. Comparative site-directed mutagenesis in the catalytic amino acid triad in calicivirus proteases.

    Science.gov (United States)

    Oka, Tomoichiro; Murakami, Kosuke; Wakita, Takaji; Katayama, Kazuhiko

    2011-02-01

    Calicivirus proteases cleave the viral precursor polyprotein encoded by open reading frame 1 (ORF1) into multiple intermediate and mature proteins. These proteases have conserved histidine (His), glutamic acid (Glu) or aspartic acid (Asp), and cysteine (Cys) residues that are thought to act as a catalytic triad (i.e. general base, acid and nucleophile, respectively). However, is the triad critical for processing the polyprotein? In the present study, we examined these amino acids in viruses representing the four major genera of Caliciviridae: Norwalk virus (NoV), Rabbit hemorrhagic disease virus (RHDV), Sapporo virus (SaV) and Feline calicivirus (FCV). Using single amino-acid substitutions, we found that an acidic amino acid (Glu or Asp), as well as the His and Cys in the putative catalytic triad, cannot be replaced by Ala for normal processing activity of the ORF1 polyprotein in vitro. Similarly, normal activity is not retained if the nucleophile Cys is replaced with Ser. These results showed the calicivirus protease is a Cys protease and the catalytic triad formation is important for protease activity. Our study is the first to directly compare the proteases of the four representative calicivirus genera. Interestingly, we found that RHDV and SaV proteases critically need the acidic residues during catalysis, whereas proteolytic cleavage occurs normally at several cleavage sites in the ORF1 polyprotein without a functional acid residue in the NoV and FCV proteases. Thus, the substrate recognition mechanism may be different between the SaV and RHDV proteases and the NoV and FCV proteases. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

  3. Irreversible loss of ice nucleation active sites in mineral dust particles caused by sulphuric acid condensation

    Directory of Open Access Journals (Sweden)

    R. C. Sullivan

    2010-07-01

    Full Text Available During the FROST-2 (FReezing Of duST measurement campaign conducted at the Leipzig Aerosol Cloud Interaction Simulator (LACIS, we investigated changes in the ice nucleation properties of 300 nm Arizona test dust mineral particles following thermochemical processing by varying amounts and combinations of exposure to sulphuric acid vapour, ammonia gas, water vapour, and heat. The processed aerosol's heterogeneous ice nucleation properties were determined in both the water subsaturated and supersaturated humidity regimes at −30 °C and −25 °C using Colorado State University's continuous flow diffusion chamber. The amount of sulphuric acid coating material was estimated by an aerosol mass spectrometer and from CCN-derived hygroscopicity measurements. The condensation of sulphuric acid decreased the dust particles' ice nucleation ability in proportion to the amount of sulphuric acid added. Heating the coated particles in a thermodenuder at 250 °C – intended to evaporate the sulphuric acid coating – reduced their freezing ability even further. We attribute this behaviour to accelerated acid digestion of ice active surface sites by heat. Exposing sulphuric acid coated dust to ammonia gas produced particles with similarly poor freezing potential; however a portion of their ice nucleation ability could be restored after heating in the thermodenuder. In no case did any combination of thermochemical treatments increase the ice nucleation ability of the coated mineral dust particles compared to unprocessed dust. These first measurements of the effect of identical chemical processing of dust particles on their ice nucleation ability in both water subsaturated and mixed-phase supersaturated cloud conditions revealed that ice nucleation was more sensitive to all coating treatments in the water subsaturated regime. The results clearly indicate irreversible impairment of ice nucleation activity in both regimes after condensation of concentrated

  4. Natural heterogeneity and evolving geochemistry of Lower Tuscaloosa Formation brine in response to continuing CO2 injection at Cranfield EOR site, Mississippi, USA

    Science.gov (United States)

    Thordsen, J. J.; Kharaka, Y. K.; Thomas, B.; Abedini, A. A.; Conaway, C. H.; Manning, M. A.; Lu, J.

    2012-12-01

    Geochemical monitoring of Lower Tuscaloosa Formation (LTF) brine continues at the Cranfield CO2-enhanced oil recovery (EOR) and sequestration site to investigate the potential for the geologic storage of large volumes of CO2 in saline aquifers and depleted reservoirs. Cranfield oil field is a domal depleted oil and gas reservoir in the Mississippi Interior Salt Basin, with production in heterogeneous fluvial sandstones of the LTF (depth ~3000 m). CO2 flood began in July 2008. Brine samples were collected from selected production wells in March and December 2009, April 2010, and November 2011. Intensive sampling also was conducted for the first 18 days of a CO2 injection experiment below the oil-water contact (December 2009) at the Detailed Area of Study (DAS) 3-well array. The sampling objectives are to define the geochemical composition of the pre-injection brine, and to understand the geochemical changes resulting from interactions between the injected CO2, brine, and reservoir minerals. Results show that Tuscaloosa brine is Na-Ca-Cl type with total salinity ranging from ~140 to 160 g/L TDS (50 samples). Relatively large variations are observed in major divalent cations (Ca ~7,500-14,000 mg/L, Mg ~800-1,250 mg/L, Sr ~475-750 mg/L). Significant positive correlations are noted amongst Ca, Mg, Sr, Ba, and Br, whereas these solutes all trend negatively with Na and Cl. These results may be interpreted as possible binary mixing between two end-member waters: (1) high Na-Cl (51 and 97 g/L, respectively), low Ca, Mg, Sr, and Br (~7500, 800, 475, 280 mg/L, respectively); and (2) low Na-Cl (40 and 86 g/L), high Ca, Mg, Sr, and Br (~14,000, 1250, 750, 480 mg/L). This apparent binary mixing has no obvious correlation to CO2 injection, which suggests that observed variations are due to natural heterogeneities in LTF brine within the Cranfield dome. The variations may indicate vertical and/or lateral proximity to a halite source (i.e. salt dome), with the high Na-Cl, low Br

  5. Intramolecular Lewis pairs with two acid sites - reactivity differences between P- and N-based systems.

    Science.gov (United States)

    Körte, Leif A; Blomeyer, Sebastian; Heidemeyer, Shari; Nissen, Jan Hendrick; Mix, Andreas; Neumann, Beate; Stammler, Hans-Georg; Mitzel, Norbert W

    2016-11-01

    The doubly acid-functionalised aniline PhN[(CH2)3B(C6F5)2]2 shows rapidly exchanging boron acid groups at the central base function and is an active frustrated Lewis pair due to cooperative hydride binding by both Lewis acids. Here we report investigations on the effect of different substituents at the central nitrogen atom and on the effect of exchanging nitrogen by phosphorus. Treatment of diallyl-tert-butylaniline with one equivalent of HB(C6F5)2 led to formation of a seven-membered iminium hydridoborate ring; after mono-hydroboration the intermediately formed frustrated Lewis pair reacts with the second allylamine function under ring closure. Phosphorus based Lewis pairs with two acid sites were prepared by hydroboration of diallylphenylphosphane and diallyl-tert-butylphosphane. Unlike the aniline PhN[(CH2)3B(C6F5)2]2 the doubly hydroborated species ((t)Bu/Ph)P[(CH2)3B(C6F5)2]2 show no dynamic exchange of the boron Lewis acid functions in solution and are not catalytically active in terms of H/D-scrambling as well as hydrogenation reactions. Quantum-chemical investigations revealed the B-P bond dissociation Gibbs free energy to be much larger than those of the nitrogen analogue. The absence of an active open form in solution prevents an activity in heterolytic hydrogen splitting.

  6. A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs.

    Directory of Open Access Journals (Sweden)

    Zhichao Miao

    2015-12-01

    Full Text Available Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i the definition of nucleic acid binding sites; ii the training and test datasets; iii the algorithmic methods for the prediction strategies; iv the performance measures and v the distribution and availability of the prediction programs. Here we report a large-scale assessment of 19 web servers and 3 stand-alone programs on 41 datasets including more than 5000 proteins derived from 3D structures of protein-nucleic acid complexes. Well-defined binary assessment criteria (specificity, sensitivity, precision, accuracy… are applied. We found that i the tools have been greatly improved over the years; ii some of the approaches suffer from theoretical defects and there is still room for sorting out the essential mechanisms of binding; iii RNA binding and DNA binding appear to follow similar driving forces and iv dataset bias may exist in some methods.

  7. Backward Evolving Quantum States

    CERN Document Server

    Vaidman, L

    2006-01-01

    The basic concept of the two-state vector formalism, which is the time symmetric approach to quantum mechanics, is the backward evolving quantum state. However, due to the time asymmetry of the memory's arrow of time, the possible ways to manipulate a backward evolving quantum state differ from those for a standard, forward evolving quantum state. The similarities and the differences between forward and backward evolving quantum states regarding the no-cloning theorem, nonlocal measurements, and teleportation are discussed. The results are relevant not only in the framework of the two-state vector formalism, but also in the framework of retrodictive quantum theory.

  8. Modelling metal centres, acid sites and reaction mechanisms in microporous catalysts.

    Science.gov (United States)

    O'Malley, Alexander J; Logsdail, A J; Sokol, A A; Catlow, C R A

    2016-07-04

    We discuss the role of QM/MM (embedded cluster) computational techniques in catalytic science, in particular their application to microporous catalysis. We describe the methodologies employed and illustrate their utility by briefly summarising work on metal centres in zeolites. We then report a detailed investigation into the behaviour of methanol at acidic sites in zeolites H-ZSM-5 and H-Y in the context of the methanol-to-hydrocarbons/olefins process. Studying key initial steps of the reaction (the adsorption and subsequent methoxylation), we probe the effect of framework topology and Brønsted acid site location on the energetics of these initial processes. We find that although methoxylation is endothermic with respect to the adsorbed system (by 17-56 kJ mol(-1) depending on the location), there are intriguing correlations between the adsorption/reaction energies and the geometries of the adsorbed species, of particular significance being the coordination of methyl hydrogens. These observations emphasise the importance of adsorbate coordination with the framework in zeolite catalysed conversions, and how this may vary with framework topology and site location, particularly suited to investigation by QM/MM techniques.

  9. Site-specific estimates of water yield applied in regional acid sensitivity surveys across western Canada

    Directory of Open Access Journals (Sweden)

    Patrick D. SHAW

    2010-08-01

    Full Text Available Runoff or water yield is an important input to the Steady-State Water Chemistry (SSWC model for estimating critical loads of acidity. Herein, we present site-specific water yield estimates for a large number of lakes (779 across three provinces of western Canada (Manitoba, Saskatchewan, and British Columbia using an isotope mass balance (IMB approach. We explore the impact of applying site-specific hydrology as compared to use of regional runoff estimates derived from gridded datasets in assessing critical loads of acidity to these lakes. In general, the average water yield derived from IMB is similar to the long-term average runoff; however, IMB results suggest a much larger range in hydrological settings of the lakes, attributed to spatial heterogeneity in watershed characteristics and landcover. The comparison of critical loads estimates from the two methods suggests that use of average regional runoff data in the SSWC model may overestimate critical loads for the majority of lakes due to systematic skewness in the actual runoff distributions. Implications for use of site-specific hydrology in regional critical loads assessments across western Canada are discussed.

  10. Mutational Studies on Resurrected Ancestral Proteins Reveal Conservation of Site-Specific Amino Acid Preferences throughout Evolutionary History

    Science.gov (United States)

    Risso, Valeria A.; Manssour-Triedo, Fadia; Delgado-Delgado, Asunción; Arco, Rocio; Barroso-delJesus, Alicia; Ingles-Prieto, Alvaro; Godoy-Ruiz, Raquel; Gavira, Jose A.; Gaucher, Eric A.; Ibarra-Molero, Beatriz; Sanchez-Ruiz, Jose M.

    2015-01-01

    Local protein interactions (“molecular context” effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to coevolution of sites, they change strongly. Such research highlights an unresolved and fundamental issue with far-reaching implications for phylogenetic analysis and molecular evolution modeling. Here, we take advantage of the recent availability of phenotypically supported laboratory resurrections of Precambrian thioredoxins and β-lactamases to experimentally address the change of site-specific amino acid preferences over long geological timescales. Extensive mutational analyses support the notion that evolutionary adjustment to a new amino acid may occur, but to a large extent this is insufficient to erase the primitive preference for amino acid replacements. Generally, site-specific amino acid preferences appear to remain conserved throughout evolutionary history despite local sequence divergence. We show such preference conservation to be readily understandable in molecular terms and we provide crystallographic evidence for an intriguing structural-switch mechanism: Energetic preference for an ancestral amino acid in a modern protein can be linked to reorganization upon mutation to the ancestral local structure around the mutated site. Finally, we point out that site-specific preference conservation naturally leads to one plausible evolutionary explanation for the existence of intragenic global suppressor mutations. PMID:25392342

  11. A novel acidophile community populating waste ore deposits at an acid mine drainage site

    Institute of Scientific and Technical Information of China (English)

    HAO Chun-bo; ZHANG Hong-xun; BAI Zhi-hui; HU Qing; ZHANG Bao-guo

    2007-01-01

    Waste ore samples (pH 3.0) were collected at an acid mine drainage site in Anhui, China. The present acidophilic microbial community in the waste ore was studied with 16S rRNA gene clone library and denaturing gradient gel electrophoresis (DGGE). Eighteen different clones were identified and affiliated with Actinobacteria, low G + C Gram-positives, Thermomicrobia, Acidobacteria, Proteobacteria, Candidate division TM7, and Planctomycetes. Phylogenetic analysis of 16S rRNA gene sequences revealed a diversity of acidophiles in the samples that were mostly novel. It is unexpected that the moderately thermophilic acidophiles were abundant in the acidic ecosystem and may play a great role in the generation of AMD. The result of DGGE was consistent with that of clone library analysis. These findings help in the better understanding of the generation mechanism of AMD and in developing a more efficient method to control AMD.

  12. Probing the orthosteric binding site of GABAA receptors with heterocyclic GABA carboxylic acid bioisosteres

    DEFF Research Database (Denmark)

    Petersen, Jette G; Bergmann, Rikke; Krogsgaard-Larsen, Povl;

    2013-01-01

    selective and potent GABAAR agonists. This review investigates the use of heterocyclic carboxylic acid bioisosteres within the GABAAR area. Several heterocycles including 3-hydroxyisoxazole, 3-hydroxyisoxazoline, 3-hydroxyisothiazole, and the 1- and 3-hydroxypyrazole rings have been employed in order to map...... the orthosteric binding site. The physicochemical properties of the heterocyclic moieties making them suitable for bioisosteric replacement of the carboxylic acid in the molecule of GABA are discussed. A variety of synthetic strategies for synthesis of the heterocyclic scaffolds are available. Likewise, methods...... for introduction of substituents into specific positions of the heterocyclic scaffolds facilitate the investigation of different regions in the orthosteric binding pocket in close vicinity of the core scaffolds of muscimol/GABA. The development of structural models, from pharmacophore models to receptor homology...

  13. Interim policy for acid rock drainage at mine sites: Issued for comment and discussion

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The Reclamation Advisory Committee (RAC) has developed a series of working policies and technical initiatives to deal with acid rock drainage (ARD) from previous project reviews and research. This document is an attempt to present those rules and guidelines as a comprehensive working policy. As better ARD control methods are developed the RAC will endeavor to incorporate them into the ARD policy. This interim policy reflects the RAC's current philosophy of preventing ARD generation through prediction and design, avoiding long term treatment where possible. It deals with proposed mine developments, prediction, prevention, collection and treatment, permitting, bonding, monitoring, historic sites, existing mines, comercial leaching, and exploration.

  14. REMOVING SLUDGE HEELS FROM SAVANNAH RIVER SITE WASTE TANKS BY OXALIC ACID DISSOLUTION

    Energy Technology Data Exchange (ETDEWEB)

    Poirier, M; David Herman, D; Fernando Fondeur, F; John Pareizs, J; Michael Hay, M; Bruce Wiersma, B; Kim Crapse, K; Thomas Peters, T; Samuel Fink, S; Donald Thaxton, D

    2009-03-01

    The Savannah River Site (SRS) will remove sludge as part of waste tank closure operations. Typically the bulk sludge is removed by mixing it with supernate to produce a slurry, and transporting the slurry to a downstream tank for processing. Experience shows that a residual heel may remain in the tank that cannot be removed by this conventional technique. In the past, SRS used oxalic acid solutions to disperse or dissolve the sludge heel to complete the waste removal. To better understand the actual conditions of oxalic acid cleaning of waste from carbon steel tanks, the authors developed and conducted an experimental program to determine its effectiveness in dissolving sludge, the hydrogen generation rate, the generation rate of other gases, the carbon steel corrosion rate, the impact of mixing on chemical cleaning, the impact of temperature, and the types of precipitates formed during the neutralization process. The test samples included actual SRS sludge and simulated SRS sludge. The authors performed the simulated waste tests at 25, 50, and 75 C by adding 8 wt % oxalic acid to the sludge over seven days. They conducted the actual waste tests at 50 and 75 C by adding 8 wt % oxalic acid to the sludge as a single batch. Following the testing, SRS conducted chemical cleaning with oxalic acid in two waste tanks. In Tank 5F, the oxalic acid (8 wt %) addition occurred over seven days, followed by inhibited water to ensure the tank contained enough liquid to operate the mixer pumps. The tank temperature during oxalic acid addition and dissolution was approximately 45 C. The authors analyzed samples from the chemical cleaning process and compared it with test data. The conclusions from the work are: (1) Oxalic acid addition proved effective in dissolving sludge heels in the simulant demonstration, the actual waste demonstration, and in SRS Tank 5F. (2) The oxalic acid dissolved {approx} 100% of the uranium, {approx} 100% of the iron, and {approx} 40% of the manganese

  15. Thermal and evolved gas analyzer

    Science.gov (United States)

    Williams, M. S.; Boynton, W. V.; James, R. L.; Verts, W. T.; Bailey, S. H.; Hamara, D. K.

    1998-01-01

    The Thermal and Evolved Gas Analyzer (TEGA) instrument will perform calorimetry and evolved gas analysis on soil samples collected from the Martian surface. TEGA is one of three instruments, along with a robotic arm, that form the Mars Volatile and Climate Survey (MVACS) payload. The other instruments are a stereo surface imager, built by Peter Smith of the University of Arizona and a meteorological station, built by JPL. The MVACS lander will investigate a Martian landing site at approximately 70 deg south latitude. Launch will take place from Kennedy Space Center in January, 1999. The TEGA project started in February, 1996. In the intervening 24 months, a flight instrument concept has been designed, prototyped, built as an engineering model and flight model, and tested. The instrument performs laboratory-quality differential-scanning calorimetry (DSC) over the temperature range of Mars ambient to 1400K. Low-temperature volatiles (water and carbon dioxide ices) and the carbonates will be analyzed in this temperature range. Carbonates melt and evolve carbon dioxide at temperatures above 600 C. Evolved oxygen (down to a concentration of 1 ppm) is detected, and C02 and water vapor and the isotopic variations of C02 and water vapor are detected and their concentrations measured. The isotopic composition provides important tests of the theory of solar system formation.

  16. SAVANNAH RIVER SITE TANK CLEANING: CORROSION RATE FOR ONE VERSUS EIGHT PERCENT OXALIC ACID SOLUTION

    Energy Technology Data Exchange (ETDEWEB)

    Ketusky, E.; Subramanian, K.

    2011-01-20

    Until recently, the use of oxalic acid for chemically cleaning the Savannah River Site (SRS) radioactive waste tanks focused on using concentrated 4 and 8-wt% solutions. Recent testing and research on applicable dissolution mechanisms have concluded that under appropriate conditions, dilute solutions of oxalic acid (i.e., 1-wt%) may be more effective. Based on the need to maximize cleaning effectiveness, coupled with the need to minimize downstream impacts, SRS is now developing plans for using a 1-wt% oxalic acid solution. A technology gap associated with using a 1-wt% oxalic acid solution was a dearth of suitable corrosion data. Assuming oxalic acid's passivation of carbon steel was proportional to the free oxalate concentration, the general corrosion rate (CR) from a 1-wt% solution may not be bound by those from 8-wt%. Therefore, after developing the test strategy and plan, the corrosion testing was performed. Starting with the envisioned process specific baseline solvent, a 1-wt% oxalic acid solution, with sludge (limited to Purex type sludge-simulant for this initial effort) at 75 C and agitated, the corrosion rate (CR) was determined from the measured weight loss of the exposed coupon. Environmental variations tested were: (a) Inclusion of sludge in the test vessel or assuming a pure oxalic acid solution; (b) acid solution temperature maintained at 75 or 45 C; and (c) agitation of the acid solution or stagnant. Application of select electrochemical testing (EC) explored the impact of each variation on the passivation mechanisms and confirmed the CR. The 1-wt% results were then compared to those from the 8-wt%. The immersion coupons showed that the maximum time averaged CR for a 1-wt% solution with sludge was less than 25-mils/yr for all conditions. For an agitated 8-wt% solution with sludge, the maximum time averaged CR was about 30-mils/yr at 50 C, and 86-mils/yr at 75 C. Both the 1-wt% and the 8-wt% testing demonstrated that if the sludge was removed

  17. Enhanced concentrations of citric acid in spring aerosols collected at the Gosan background site in East Asia

    Science.gov (United States)

    Jung, Jinsang; Kawamura, Kimitaka

    2011-09-01

    In order to investigate water-soluble dicarboxylic acids and related compounds in the aerosol samples under the Asian continent outflow, total suspended particle (TSP) samples ( n = 32) were collected at the Gosan site in Jeju Island over 2-5 days integration during 23 March-1 June 2007 and 16-24 April 2008. The samples were analyzed for water-soluble dicarboxylic acids, ketocarboxylic acids, and α-dicarbonyls using a capillary gas chromatography technique. We found elevated concentrations of atmospheric citric acid (range: 20-320 ng m -3) in the TSP samples during mid- to late April of 2007 and 2008. To specify the sources of citric acid, dicarboxylic acids and related compounds were measured in the pollen sample collected at the Gosan site (Pollen_Gosan), authentic pollen samples from Japanese cedar ( Cryptomeria) (Pollen_cedar) and Japanese cypress ( Chamaecyparis obtusa) (Pollen_cypress), and tangerine fruit produced from Jeju Island. Citric acid (2790 ng in unit mg of pollen mass) was found as most abundant species in the Pollen_Gosan, followed by oxalic acid (2390 ng mg -1). Although citric acid was not detected in the Pollen_cedar and Pollen_cypress as major species, it was found as a dominant species in the tangerine juice while malic acid was detected as major species in the tangerine peel, followed by oxalic and citric acids. Since Japanese cedar trees are planted around tangerine farms to prevent strong winds from the Pacific Ocean, citric acid that may be directly emitted from tangerine is likely adsorbed on pollens emitted from Japanese cedar and then transported to the Gosan site. Much lower malic/citric acid ratios obtained under cloudy condition than clear condition suggest that malic acid may rapidly decompose to lower molecular weight compounds such as oxalic and malonic acids (

  18. Promotion of viral internal ribosomal entry site-mediated translation under amino acid starvation.

    Science.gov (United States)

    Licursi, Maria; Komatsu, Yumiko; Pongnopparat, Theerawat; Hirasawa, Kensuke

    2012-05-01

    Cap-dependent and internal ribosomal entry site (IRES)-mediated translation are regulated differently within cells. Viral IRES-mediated translation often remains active when cellular cap-dependent translation is severely impaired under cellular stresses induced by virus infection. To investigate how cellular stresses influence the efficiency of viral IRES-mediated translation, we used a bicistronic luciferase reporter construct harbouring IRES elements from the following viruses: encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), hepatitis C virus (HCV) or human rhinovirus (HRV). NIH3T3 cells transfected with these bicistronic reporter constructs were subjected to different cellular stresses. Increased translation initiation was only observed under amino acid starvation when EMCV or FMDV IRES elements were present. To identify cellular mechanisms that promoted viral IRES-mediated translation, we tested the involvement of eukaryotic initiation factor 4E-binding protein (4E-BP), general control non-depressed 2 (GCN2) and eukaryotic initiation factor 2B (eIF2B), as these are known to be modulated under amino acid starvation. Knockdown of 4E-BP1 impaired the promotion of EMCV and FMDV IRES-mediated translation under amino acid starvation, whereas GCN2 and eIF2B were not involved. To further investigate how 4E-BP1 regulates translation initiated by EMCV and FMDV IRES elements, we used a phosphoinositide kinase-3 inhibitor (LY294002), an mTOR inhibitor (Torin1) or leucine starvation to mimic 4E-BP1 dephosphorylation induced by amino acid starvation. 4E-BP1 dephosphorylation induced by the treatments was not sufficient to promote viral IRES-mediated translation. These results suggest that 4E-BP1 regulates EMCV and FMDV IRES-mediated translation under amino acid starvation, but not via its dephosphorylation.

  19. Effects of Multiple Soil Conditioners on a Mine Site Acid Sulfate Soil for Vetiver Growth

    Institute of Scientific and Technical Information of China (English)

    LIN Chu-Xia; LONG Xin-Xian; XU Song-Jun; CHU Cheng-Xing; MAI Shao-Zhi; JIANG Dian

    2004-01-01

    A pot experiment was conducted to investigate the effects of various soil treatments on the growth of vetiver grass ( Vetiveria zizanioides (L.) Nash) with the objective of formulating appropriate soil media for use in sulfide-bearing mined areas. An acidic mine site acid sulfate soil (pH 2.8) was treated with different soil conditioner formula including hydrated lime, red mud (bauxite residues), zeolitic rock powder, biosolids and a compound fertilizer. Soils treated with red mud and hydrated lime corrected soil acidity and reduced or eliminated metal toxicity enabling the establishment of vetiver grass.Although over-liming affected growth, some seedlings of vetiver survived the initial strong alkaline conditions. Addition of appropriate amounts of zeolitic rock powder also enhanced growth, but over-application caused detrimental effects. In this experiment, soil medium with the best growth performance of vetiver was 50 g of red mud, 10 g of lime, 30 g of zeolitic rock powder and 30 g of biosolids with 2000 g of mine soils (100% survival rate with the greatest biomass and number of new shoots), but adding a chemical fertilizer to this media adversely impacted plant growth. In addition, a high application rate of biosolids resulted in poorer growth of vetiver, compared to a moderate application rate.

  20. Evaluation Of Sludge Heel Dissolution Efficiency With Oxalic Acid Cleaning At Savannah River Site

    Energy Technology Data Exchange (ETDEWEB)

    Sudduth, Christie; Vitali, Jason; Keefer, Mark

    2014-01-08

    The chemical cleaning process baseline strategy at the Savannah River Site was revised to improve efficiency during future execution of the process based on lessons learned during previous bulk oxalic acid cleaning activities and to account for operational constraints imposed by safety basis requirements. These improvements were also intended to transcend the difficulties that arise from waste removal in higher rheological yield stress sludge tanks. Tank 12 implemented this improved strategy and the bulk oxalic acid cleaning efforts concluded in July 2013. The Tank 12 radiological removal results were similar to previous bulk oxalic acid cleaning campaigns despite the fact that Tank 12 contained higher rheological yield stress sludge that would make removal more difficult than the sludge treated in previous cleaning campaigns. No appreciable oxalate precipitation occurred during the cleaning process in Tank 12 compared to previous campaigns, which aided in the net volume reduction of 75-80%. Overall, the controls established for Tank 12 provide a template for an improved cleaning process.

  1. Site directed mutagenesis of StSUT1 reveals target amino acids of regulation and stability.

    Science.gov (United States)

    Krügel, Undine; Wiederhold, Elena; Pustogowa, Jelena; Hackel, Aleksandra; Grimm, Bernhard; Kühn, Christina

    2013-11-01

    Plant sucrose transporters (SUTs) are functional as sucrose-proton-cotransporters with an optimal transport activity in the acidic pH range. Recently, the pH optimum of the Solanum tuberosum sucrose transporter StSUT1 was experimentally determined to range at an unexpectedly low pH of 3 or even below. Various research groups have confirmed these surprising findings independently and in different organisms. Here we provide further experimental evidence for a pH optimum at physiological extrema. Site directed mutagenesis provides information about functional amino acids, which are highly conserved and responsible for this extraordinary increase in transport capacity under extreme pH conditions. Redox-dependent dimerization of the StSUT1 protein was described earlier. Here the ability of StSUT1 to form homodimers was demonstrated by heterologous expression in Lactococcus lactis and Xenopus leavis using Western blots, and in plants by bimolecular fluorescence complementation. Mutagenesis of highly conserved cysteine residues revealed their importance in protein stability. The accessibility of regulatory amino acid residues in the light of StSUT1's compartmentalization in membrane microdomains is discussed.

  2. Modification and characterization of sites giving acid cracking on aluminium oxide supports; Modification et caracterisation des sites responsables du craquage acide sur des supports a base d`alumine

    Energy Technology Data Exchange (ETDEWEB)

    Guillaume, D.

    1997-10-23

    The aim of this work is to characterize the surface acid properties of {gamma} alumina, especially the nature, the amount, the strength and the environment of acid sites. The techniques that have been used are: the thermo-desorption of trimethyl-phosphine followed by {sup 31}P MAS NMR, the infrared spectroscopy, the n-heptane cracking, the modification of {gamma} alumina by the addition of chlorine, silicon and alkali (K{sup +}, Na{sup +}), alkaline-earths (Mg{sup 2+}, Ca{sup 2+}), lanthanum (La{sup 3+}) cations. The combination of these techniques has allowed to identify the surface acid properties of {gamma} alumina through the n-heptane transformation reactions under reforming conditions. We have shown that Lewis acidity is responsible for cracking reactions leading to C{sub 1}-C{sub 6} and C{sub 2}-C{sub 5} whereas the cracking of n-heptane producing C{sub 3}-C{sub 4} is due to Broensted acid sites. The isomerization and cyclization reactions both require weaker Broensted acid sites than cracking leading to C{sub 3}-C{sub 4}. The mechanisms involved in the formation of products of these reactions have been identified. Despite the complexity of surface acid properties of {gamma} alumina, this study has determined the environment of catalytically active sites, considering the presence of cation vacancies. (author) 206 refs.

  3. Characteristics of fluoride in pore-water at accidental hydrofluoric acid spillage site, Gumi, Korea

    Science.gov (United States)

    Kwon, E. H.; Lee, H. A.; Lee, J.; Kim, D.; Lee, S.; Yoon, H. O.

    2015-12-01

    A leakage accident of hydrofluoric acid (HF) occurred in Gumi, South Korea at Sep. 2012. The study site is located in the borderline between a large-scale industrial complex and a rural area. The HF plume was made immediately, and moved toward the rural area through air. After the accident, 212 ha of farm land were influenced and most of crops were withered. To recover the soil, CaO was applied after six months. Although several studies have done to estimate the extension and movement of HF plume in the air and to assess the impact on human health or plant after the incident, the long-term fate of fluoride (F) in the affected soils is not identified clearly. Thus, this study aimed to understand the behavior of F in the soil after HF releasing from accident site through chemical analysis and geochemical modeling. Within the radius of 1 km of accident site, 16 pore-water and soil samples were collected. The semi-quantitative soil composition (i.e., Al, Ca, Fe, K, Mg, Mn, Na, P, Si, Ti), total F, total P, OM contents in soil, and soil pH have already been measured, and pore-water compositions are also identified. From these experimental and modeling data, we could be evaluate if impact of accident exists until now, and also could be select and identify existing form of fluoride in soil and pore-water.

  4. Modeling Evolving Innovation Networks

    OpenAIRE

    Koenig, Michael D.; Battiston, Stefano; Schweitzer, Frank

    2007-01-01

    We develop a new framework for modeling innovation networks which evolve over time. The nodes in the network represent firms, whereas the directed links represent unilateral interactions between the firms. Both nodes and links evolve according to their own dynamics and on different time scales. The model assumes that firms produce knowledge based on the knowledge exchange with other firms, which involves both costs and benefits for the participating firms. In order to increase their knowledge...

  5. High mature grain phytase activity in the Triticeae has evolved by duplication followed by neofunctionalization of the purple acid phosphatase phytase (PAPhy) gene

    DEFF Research Database (Denmark)

    Madsen, Claus Krogh; Dionisio, Giuseppe; Holme, Inger

    2013-01-01

    The phytase activity in food and feedstuffs is an important nutritional parameter. Members of the Triticeae tribe accumulate purple acid phosphatase phytases (PAPhy) during grain filling. This accumulation elevates mature grain phytase activities (MGPA) up to levels between ~650 FTU/kg for barley...

  6. Evolving digital ecological networks.

    Science.gov (United States)

    Fortuna, Miguel A; Zaman, Luis; Wagner, Aaron P; Ofria, Charles

    2013-01-01

    "It is hard to realize that the living world as we know it is just one among many possibilities" [1]. Evolving digital ecological networks are webs of interacting, self-replicating, and evolving computer programs (i.e., digital organisms) that experience the same major ecological interactions as biological organisms (e.g., competition, predation, parasitism, and mutualism). Despite being computational, these programs evolve quickly in an open-ended way, and starting from only one or two ancestral organisms, the formation of ecological networks can be observed in real-time by tracking interactions between the constantly evolving organism phenotypes. These phenotypes may be defined by combinations of logical computations (hereafter tasks) that digital organisms perform and by expressed behaviors that have evolved. The types and outcomes of interactions between phenotypes are determined by task overlap for logic-defined phenotypes and by responses to encounters in the case of behavioral phenotypes. Biologists use these evolving networks to study active and fundamental topics within evolutionary ecology (e.g., the extent to which the architecture of multispecies networks shape coevolutionary outcomes, and the processes involved).

  7. Evolving digital ecological networks.

    Directory of Open Access Journals (Sweden)

    Miguel A Fortuna

    Full Text Available "It is hard to realize that the living world as we know it is just one among many possibilities" [1]. Evolving digital ecological networks are webs of interacting, self-replicating, and evolving computer programs (i.e., digital organisms that experience the same major ecological interactions as biological organisms (e.g., competition, predation, parasitism, and mutualism. Despite being computational, these programs evolve quickly in an open-ended way, and starting from only one or two ancestral organisms, the formation of ecological networks can be observed in real-time by tracking interactions between the constantly evolving organism phenotypes. These phenotypes may be defined by combinations of logical computations (hereafter tasks that digital organisms perform and by expressed behaviors that have evolved. The types and outcomes of interactions between phenotypes are determined by task overlap for logic-defined phenotypes and by responses to encounters in the case of behavioral phenotypes. Biologists use these evolving networks to study active and fundamental topics within evolutionary ecology (e.g., the extent to which the architecture of multispecies networks shape coevolutionary outcomes, and the processes involved.

  8. Visualization of abscisic acid-perception sites on the plasma membrane of stomatal guard cells.

    Science.gov (United States)

    Yamazaki, Daiki; Yoshida, Shigeo; Asami, Tadao; Kuchitsu, Kazuyuki

    2003-07-01

    Abscisic acid (ABA) is a phytohormone that plays a key role as a stress signal, regulating water relations during drought conditions, by inducing stomatal closure. However, to date, no putative ABA receptor(s) has been reported at the protein sequence, gene family, or cellular localization levels. We used biotinylated ABA (bioABA) to characterize the ABA-perception sites in the stomatal guard cells of Vicia faba. Treatment with bioABA induced stomatal closure and shrinkage of guard cell protoplasts (GCPs). The ABA-perception sites were visualized by fluorescence microscopy and confocal laser scanning microscopy (CLSM), using bioABA and fluorescence-labeled avidin. Fluorescent particles were observed in patches on the surface of the GCPs. Fluorescence intensity was quantified by flow cytometry (FCM) as well as by CLSM. Binding of bioABA was inhibited by ABA in a dose-dependent manner. Pre-treatment of GCPs with proteinase K also blocked the binding of bioABA. Binding of bioABA was inhibited by RCA-7a, an ABA analog that induces stomatal closure, but not by RCA-16, which has no effect on stomatal aperture. Another ABA analog, PBI-51, inhibited ABA-induced stomatal closure. This ABA antagonist also inhibited binding of bioABA to the GCPs. These results suggest that ABA is perceived on the plasma membrane of stomatal guard cells, and that the present experimental methods constitute valuable tools for characterizing the nature of the ABA receptor(s) that perceives physiological ABA signals. These imaging studies allow us to demonstrate the spatial distribution of the ABA-perception sites. Visualization of the ABA-perception sites provides new insights into the nature of membrane-associated ABA receptor(s).

  9. Fabrication of hydrophobic polymer foams with double acid sites on surface of macropore for conversion of carbohydrate.

    Science.gov (United States)

    Pan, Jianming; Mao, Yanli; Gao, Heping; Xiong, Qingang; Qiu, Fengxian; Zhang, Tao; Niu, Xiangheng

    2016-06-05

    Herein we reported a simple and novel synthetic strategy for the fabrication of two kinds of hydrophobic polymer foam catalysts (i.e. Cr(3+)-HPFs-1-H(+) and HPFs-1-H(+)) with hierarchical porous structure, inhomogeneous acidic composition and Lewis-Brønsted double acid sites distributed on the surface, which was used to one-pot conversion of carbohydrate (such as cellulose, glucose and fructose) to a key chemical platform (i.e. 5-hydroxymethylfurfural, HMF). The water-in-oil (W/O) high internal phase emulsions (HIPEs), stabilized by both Span 80 and acidic prepolymers as analogous particles offered the acidic actives, were used as the template for simultaneous polymerization of oil phase in the presence of divinylbenzene (DVB) and styrene (St). After subsequent ion-exchange process, Lewis and Brønsted acid sites derived from exchanged Cr(3+) and H(+) ion were both fixed on the surface of cell of the catalysts. The HPFs-1-H(+) and Cr(3+)-HPFs-1-H(+) had similar hierarchical porous, hydrophobic surface and acid sites (HPFs-1-H(+) with macropores ranging from 0.1 μm to 20 μm, uniform mesopores in 14.4 nm, water contact angle of 122° and 0.614 mmolg(-1) of Brønsted acid sites, as well as Cr(3+)-HPFs-1-H(+) with macropores ranging from 0.1 μm to 20 μm, uniform mesopores in 13.3 nm, water contact angle of 136° and 0.638 mmolg(-1) of Lewis-Brønsted acid sites). It was confirmed that Lewis acid sites of catalyst had a slight influence on the HMF yield of fructose came from the function of Brønsted acid sites, and Lewis acid sites were in favor of improving the HMF yield from cellulose and glucose. This work opens up a simple and novel route to synthesize multifunctional polymeric catalysts for efficient one-pot conversion of carbohydrate to HMF.

  10. Methane to acetic acid over Cu-exchanged zeolites: mechanistic insights from a site-specific carbonylation reaction.

    Science.gov (United States)

    Narsimhan, Karthik; Michaelis, Vladimir K; Mathies, Guinevere; Gunther, William R; Griffin, Robert G; Román-Leshkov, Yuriy

    2015-02-11

    The selective low temperature oxidation of methane is an attractive yet challenging pathway to convert abundant natural gas into value added chemicals. Copper-exchanged ZSM-5 and mordenite (MOR) zeolites have received attention due to their ability to oxidize methane into methanol using molecular oxygen. In this work, the conversion of methane into acetic acid is demonstrated using Cu-MOR by coupling oxidation with carbonylation reactions. The carbonylation reaction, known to occur predominantly in the 8-membered ring (8MR) pockets of MOR, is used as a site-specific probe to gain insight into important mechanistic differences existing between Cu-MOR and Cu-ZSM-5 during methane oxidation. For the tandem reaction sequence, Cu-MOR generated drastically higher amounts of acetic acid when compared to Cu-ZSM-5 (22 vs 4 μmol/g). Preferential titration with sodium showed a direct correlation between the number of acid sites in the 8MR pockets in MOR and acetic acid yield, indicating that methoxy species present in the MOR side pockets undergo carbonylation. Coupled spectroscopic and reactivity measurements were used to identify the genesis of the oxidation sites and to validate the migration of methoxy species from the oxidation site to the carbonylation site. Our results indicate that the Cu(II)-O-Cu(II) sites previously associated with methane oxidation in both Cu-MOR and Cu-ZSM-5 are oxidation active but carbonylation inactive. In turn, combined UV-vis and EPR spectroscopic studies showed that a novel Cu(2+) site is formed at Cu/Al <0.2 in MOR. These sites oxidize methane and promote the migration of the product to a Brønsted acid site in the 8MR to undergo carbonylation.

  11. Repetitive sequence based polymerase chain reaction to differentiate close bacteria strains in acidic sites

    Institute of Scientific and Technical Information of China (English)

    XIE Ming; YIN Hua-qun; LIU Yi; LIU Jie; LIU Xue-duan

    2008-01-01

    To study the diversity of bacteria strains newly isolated from several acid mine drainage(AMD) sites in China,repetitive sequence based polymerase chain reaction (rep-PCR),a well established technology for diversity analysis of closely related bacteria strains,was conducted on 30 strains of bacteria Leptospirillum ferriphilium,8 strains of bacteria Acidithiobacillus ferrooxidans,as well as the Acidithiobacillus ferrooxidans type strain ATCC (American Type Culture Collection) 23270.The results showed that,using ERIC and BOX primer sets,rep-PCR produced highly discriminatory banding patterns.Phylogenetic analysis based on ERIC-PCR banding types was made and the results indicated that rep-PCR could be used as a rapid and highly discriminatory screening technique in studying bacterial diversity,especially in differentiating bacteria within one species in AMD.

  12. Site-Specific Pyrolysis Induced Cleavage at Aspartic Acid Residue in Peptides and Proteins

    Science.gov (United States)

    Zhang, Shaofeng; Basile, Franco

    2011-01-01

    A simple and site-specific non-enzymatic method based on pyrolysis has been developed to cleave peptides and proteins. Pyrolytic cleavage was found to be specific and rapid as it induced a cleavage at the C-terminal side of aspartic acid in the temperature range of 220–250 °C in 10 seconds. Electrospray Ionization (ESI) mass spectrometry (MS) and tandem-MS (MS/MS) were used to characterize and identify pyrolysis cleavage products, confirming that sequence information is conserved after the pyrolysis process in both peptides and protein tested. This suggests that pyrolysis-induced cleavage at aspartyl residues can be used as a rapid protein digestion procedure for the generation of sequence specific protein biomarkers. PMID:17388620

  13. On the characterization of acidic and basic surface sites on carbons by various techniques

    OpenAIRE

    2009-01-01

    Active carbons of different origins have been oxidized with H2O2 and (NH4)2S2O8 and their oxygen surface complexes have been characterized by TPD, classical titration following Boehm's method and by neutralization calorimetry. The net enthalpies of neutralization, determined by immersion calorimetry into NaOH and HCl 2 N lead to −41.1±1.8 and −52.3±2.0 kJ eq−1 for the acidic and basic sites on the surface. Experiments with NaHCO3 lead to −39.7±1.7 kJ eq−1 for the carboxylic groups alone. Thes...

  14. Site-specific acid-base properties of pholcodine and related compounds.

    Science.gov (United States)

    Kovács, Z; Hosztafi, S; Noszál, B

    2006-11-01

    The acid-base properties of pholcodine, a cough-depressant agent, and related compounds including metabolites were studied by 1H NMR-pH titrations, and are characterised in terms of macroscopic and microscopic protonation constants. New N-methylated derivatives were also synthesized in order to quantitate site- and nucleus-specific protonation shifts and to unravel microscopic acid-base equilibria. The piperidine nitrogen was found to be 38 and 400 times more basic than its morpholine counterpart in pholcodine and norpholcodine, respectively. The protonation data show that the molecule of pholcodine bears an average of positive charge of 1.07 at physiological pH, preventing it from entering the central nervous system, a plausible reason for its lack of analgesic or addictive properties. The protonation constants of pholcodine and its derivatives are interpreted by comparing with related molecules of pharmaceutical interest. The pH-dependent relative concentrations of the variously protonated forms of pholcodine and morphine are depicted in distribution diagrams.

  15. Radiosynthesis and Evaluation of [(11)C]3-Hydroxycyclopent-1-enecarboxylic Acid as Potential PET Ligand for the High-Affinity γ-Hydroxybutyric Acid Binding Sites

    DEFF Research Database (Denmark)

    Jensen, Claus H; Hansen, Hanne D; Bay, Tina

    2017-01-01

    the (11)C-labeling and subsequent evaluation of [(11)C]HOCPCA in a domestic pig, as a PET-radioligand for visualization of the high-affinity GHB binding sites in the live pig brain. To investigate the regional binding of HOCPCA in pig brain prior to in vivo PET studies, in vitro quantitative......γ-Hydroxybutyric acid (GHB) is an endogenous neuroactive substance and proposed neurotransmitter with affinity for both low- and high-affinity binding sites. A radioligand with high and specific affinity toward the high-affinity GHB binding site would be a unique tool toward a more complete...... understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate. Here, we report...

  16. Diversity of acidophilic prokaryotes at two acid mine drainage sites in Turkey.

    Science.gov (United States)

    Aytar, Pınar; Kay, Catherine Melanie; Mutlu, Mehmet Burçin; Çabuk, Ahmet; Johnson, David Barrie

    2015-04-01

    The biodiversity of acidophilic prokaryotes in two acidic (pH 2.8-3.05) mine drainage (AMD) sites (Balya and Çan) in Turkey was examined using a combined cultivation-based and cultivation-independent approach. The latter included analyzing microbial diversity using fluorescent in situ hybridization (FISH), terminal restriction enzyme fragment length polymorphism (`T-RFLP), and quantitative PCR (qPCR). Numbers of cultivatable heterotrophic acidophilic bacteria were over an order of magnitude greater than those of chemolithotrophic acidophiles in both AMD ponds examined. Isolates identified as strains of Acidithiobacillus ferrivorans, Acidiphilium organovorum, and Ferrimicrobium acidiphilum were isolated from the Balya AMD pond, and others identified as strains of Leptospirillum ferriphilum, Acidicapsa ligni, and Acidiphilium rubrum from Çan AMD. Other isolates were too distantly related (from analysis of their 16S rRNA genes) to be identified at the species level. Archaeal diversity in the two ponds appeared to be far more limited. T-RFLP and qPCR confirmed the presence of Ferroplasma-like prokaryotes, but no archaea were isolated from the two sites. qPCR generated semiquantitative data for genera of some of the iron-oxidizing acidophiles isolated and/or detected, suggesting the order of abundance was Leptospirillum > Ferroplasma > Acidithiobacillus (Balya AMD) and Ferroplasma > Leptospirillum > Acidithiobacillus (Çan AMD).

  17. Oncologic doses of zoledronic acid induce site specific suppression of bone modelling in rice rats.

    Science.gov (United States)

    Exposto, C R; Oz, U; Callard, J S; Allen, M J; Khurana, H; Atri, A D'; Mo, X; Fernandez, S A; Tatakis, D N; Edmonds, K; Westgate, P M; Huja, S S

    2017-06-01

    To examine the effect of zoledronic acid (ZOL) on cortical bone modelling and healing of extraction sockets in the jaw bones of a rodent model. We hypothesized ZOL suppresses both the bone formation in the modelling mode in the jaw bones and alters the extraction site healing. Rice rats were administered saline solution and two dose regimens of ZOL: 0.1 mg/kg, twice a week, for 4 weeks (n=17, saline=8 & ZOL=9) and a higher dose of 0.4 mg/kg, weekly, for 9 weeks (n=30, saline=15 & ZOL=15). Two pairs of fluorochrome bone labels were administered. Extraction of maxillary teeth was performed in maxilla. Mineral apposition rate, mineralizing surface and bone formation rate (BFR) were quantified on periodontal (PDL), alveolar and basal bone surfaces, and in the trabecular bone of proximal tibia. Bone volume (BV) was evaluated at extraction sockets. Multivariate Gaussian models were used to account for repeated measurements, and analyzes were conducted in SAS V9.3. ZOL suppressed bone modelling (BFR/BS) at the PDL surfaces in the mandible (Pmodelling mode in the jaws demonstrates the site specific effects of ZOL in rice rats. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Purification, enzymatic properties, and active site environment of a novel manganese(III)-containing acid phosphatase.

    Science.gov (United States)

    Sugiura, Y; Kawabe, H; Tanaka, H; Fujimoto, S; Ohara, A

    1981-10-25

    A new manganese-containing acid phosphatase has been isolated and crystallized from sweet potato tubers. The pure enzyme contains one atom of manganese per Mr = 110,000 polypeptide and shows phosphatase activity toward various phosphate substrates. The pH optimum of the enzyme was 5.8 and the enzyme activity was inhibited by Cu2+, Zn2+, Hg2+, AsO43-, and MoO42-. This stable metalloenzyme is red-violet in color with an intense absorption band at 515 nm (epsilon - 2460). Our electronic, circular dichroism, and electron spin resonance findings strongly indicate that the Mn-valence state of the native enzyme is trivalent. When the Mn-enzyme is excited by the 5145 A line of Ar+ laser, prominent Raman lines at 1230, 1298, 1508, and 1620 cm-1 were detected. This Raman spectrum can probably be interpreted in terms of internal vibration of a coordinated tyrosine phenolate anion. The tryptophan-modified enzyme showed a positive Raman band at 370 cm-1, which is preferentially assigned to a Mn(III)-S streching mode. The modification of the Mn-enzyme by N-bromosuccinimide led to a large decrease in the fluorescence intensity of 335 nm which was dominated by its tryptophan residues within a considerable hydrophobic environment. The acid phosphatase activity was significantly decreased by the tryptophan modification. With respect to the active site donor sets, the Mn(III)-containing acid phosphatase is distinctly different from the Zn(II)-containing alkaline phosphatase. Of interest is also the appreciable similarity of some enzymatic and spectroscopic properties between the present enzyme and uteroferrin.

  19. Volatile aromatic hydrocarbons and dicarboxylic acid concentrations in air at an urban site in the Southwestern US

    Science.gov (United States)

    Tran, Ngoc K.; Steinberg, Spencer M.; Johnson, Brian J.

    Concentrations of benzene, toluene, ethylbenzene, o-xylene, and m- and p-xylene were measured at an urban sampling site in Las Vegas, NV by sorbent sampling followed by thermal desorption and determination by GC-PID. Simultaneously, measurements of oxalic, malonic, succinic, and adipic acids were made at the same site by collection on quartz filters, extraction, esterification, and determination by GC-FID. For the period from April 7, 1997 to June 11, 1997, 201 sets of hydrocarbon measurements and 99 sets of acid measurements were made. Additional measurements of dicarboxylic acids were made on samples that represented potential direct sources, e.g. green plants and road dust. Correlations between the hydrocarbon and CO concentrations (measured by the Clark County Health District at a nearby site) were highly significant and a strong negative correlation of hydrocarbon concentration with ozone concentration (also from the county site) was observed under quiescent atmospheric conditions. In general, dicarboxylic acid concentrations were well correlated with one another (with the exception of adipic acid) but not well correlated with hydrocarbon, CO, and ozone concentrations. Multiple sources and complex formation processes are indicated for the dicarboxylic acids.

  20. Prediction of protein modification sites of pyrrolidone carboxylic acid using mRMR feature selection and analysis.

    Directory of Open Access Journals (Sweden)

    Lu-Lu Zheng

    Full Text Available Pyrrolidone carboxylic acid (PCA is formed during a common post-translational modification (PTM of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR and incremental feature selection (IFS. We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations.

  1. iNitro-Tyr: prediction of nitrotyrosine sites in proteins with general pseudo amino acid composition.

    Directory of Open Access Journals (Sweden)

    Yan Xu

    Full Text Available Nitrotyrosine is one of the post-translational modifications (PTMs in proteins that occurs when their tyrosine residue is nitrated. Compared with healthy people, a remarkably increased level of nitrotyrosine is detected in those suffering from rheumatoid arthritis, septic shock, and coeliac disease. Given an uncharacterized protein sequence that contains many tyrosine residues, which one of them can be nitrated and which one cannot? This is a challenging problem, not only directly related to in-depth understanding the PTM's mechanism but also to the nitrotyrosine-based drug development. Particularly, with the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop a high throughput tool in this regard. Here, a new predictor called "iNitro-Tyr" was developed by incorporating the position-specific dipeptide propensity into the general pseudo amino acid composition for discriminating the nitrotyrosine sites from non-nitrotyrosine sites in proteins. It was demonstrated via the rigorous jackknife tests that the new predictor not only can yield higher success rate but also is much more stable and less noisy. A web-server for iNitro-Tyr is accessible to the public at http://app.aporc.org/iNitro-Tyr/. For the convenience of most experimental scientists, we have further provided a protocol of step-by-step guide, by which users can easily get their desired results without the need to follow the complicated mathematics that were presented in this paper just for the integrity of its development process. It has not escaped our notice that the approach presented here can be also used to deal with the other PTM sites in proteins.

  2. A class frequency mixture model that adjusts for site-specific amino acid frequencies and improves inference of protein phylogeny

    Directory of Open Access Journals (Sweden)

    Li Karen

    2008-12-01

    Full Text Available Abstract Background Widely used substitution models for proteins, such as the Jones-Taylor-Thornton (JTT or Whelan and Goldman (WAG models, are based on empirical amino acid interchange matrices estimated from databases of protein alignments that incorporate the average amino acid frequencies of the data set under examination (e.g JTT + F. Variation in the evolutionary process between sites is typically modelled by a rates-across-sites distribution such as the gamma (Γ distribution. However, sites in proteins also vary in the kinds of amino acid interchanges that are favoured, a feature that is ignored by standard empirical substitution matrices. Here we examine the degree to which the pattern of evolution at sites differs from that expected based on empirical amino acid substitution models and evaluate the impact of these deviations on phylogenetic estimation. Results We analyzed 21 large protein alignments with two statistical tests designed to detect deviation of site-specific amino acid distributions from data simulated under the standard empirical substitution model: JTT+ F + Γ. We found that the number of states at a given site is, on average, smaller and the frequencies of these states are less uniform than expected based on a JTT + F + Γ substitution model. With a four-taxon example, we show that phylogenetic estimation under the JTT + F + Γ model is seriously biased by a long-branch attraction artefact if the data are simulated under a model utilizing the observed site-specific amino acid frequencies from an alignment. Principal components analyses indicate the existence of at least four major site-specific frequency classes in these 21 protein alignments. Using a mixture model with these four separate classes of site-specific state frequencies plus a fifth class of global frequencies (the JTT + cF + Γ model, significant improvements in model fit for real data sets can be achieved. This simple mixture model also reduces the long

  3. Methods Evolved by Observation

    Science.gov (United States)

    Montessori, Maria

    2016-01-01

    Montessori's idea of the child's nature and the teacher's perceptiveness begins with amazing simplicity, and when she speaks of "methods evolved," she is unveiling a methodological system for observation. She begins with the early childhood explosion into writing, which is a familiar child phenomenon that Montessori has written about…

  4. Investigation of prototypal MOFs consisting of polyhedral cages with accessible Lewis-acid sites for quinoline synthesis.

    Science.gov (United States)

    Gao, Wen-Yang; Leng, Kunyue; Cash, Lindsay; Chrzanowski, Matthew; Stackhouse, Chavis A; Sun, Yinyong; Ma, Shengqian

    2015-03-21

    A series of prototypal metal-organic frameworks (MOFs) consisting of polyhedral cages with accessible Lewis-acid sites, have been systematically investigated for Friedländer annulation reaction, a straightforward approach to synthesizing quinoline and its derivatives. Amongst them MMCF-2 demonstrates significantly enhanced catalytic activity compared with the benchmark MOFs, HKUST-1 and MOF-505, as a result of a high-density of accessible Cu(II) Lewis acid sites and large window size in the cuboctahedral cage-based nanoreactor of MMCF-2.

  5. Site and extent of amino acid digestion in dairy cattle fed with corn and its byproducts

    Directory of Open Access Journals (Sweden)

    Reginaldo Nassar Ferreira

    2015-02-01

    Full Text Available The study was conducted to evaluated the site and extent of dry matter (DM, crude protein (CP, methionine (Met, lysine (Lys, and threonine (Thr digestion of corn and byproducts obtained from corn germ mixed with different amounts of extruded or non-extruded ether extract (EE in dairy cattle. Treatments consisted in eight types of feed and two processing in a 4 × 2 factorial design. There were four feeds: corn grain cracked (Corn, corn germ meal with 1% EE (CG1, corn germ meal with 7% EE (CG7, and corn germ meal with 10% EE (CG10. The feeds were processed in one of two ways: extruded (Ex and not extruded. In situ techniques were used to determine DM, CP, Met, Lys, and Thr partial and total tract digestion. A basic diet was compounded of corn germ meal, soybean meal and coastcross hay in a 70:30 roughage to concentrate ratio. There was no interaction (P>0.05 between feeds and processing method. Extrusion improved (P0.05 for corn and corn germ meal mixed with 7 and 10% EE, regardless of EE processing method. The CP total tract digestibility of corn germ meal with 1% nonextruded EE was 16.62% higher (P<0.05 than that of the extruded form. The best total CP digestibility was obtained for corn germ meal with 7% EE, independently of the processing method. The effects of EE processing method on partial and total digestibility differed between amino acid. Corn and corn byproduct extrusion may improve dry matter digestibility, but do not necessarily influence crude protein digestion. Ruminal and intestinal digestibility of Met, Lys, and Thr depends on both feed type and processing method. Therefore, amino acid availability should be considered individually.

  6. Atmospheric oxalic acid and related secondary organic aerosols in Qinghai Lake, a continental background site in Tibet Plateau

    Science.gov (United States)

    Meng, Jingjing; Wang, Gehui; Li, Jianjun; Cheng, Chunlei; Cao, Junji

    2013-11-01

    Summertime PM2.5 aerosols collected from Qinghai Lake (3200 m a.s.l.), a remote continental site in the northeastern part of Tibetan Plateau, were analyzed for dicarboxylic acids (C2-C11), ketocarboxylic acids and α-dicarbonyals. Oxalic acid (C2) is the dominant dicarboxylic acid in the samples, followed by malonic, succinic and azelaic acids. Total dicarboxylic acids (231 ± 119 ng m-3), ketocarboxylic acids (8.4 ± 4.3 ng m-3), and α-dicarbonyls (2.7 ± 2.1 ng m-3) at the Tibetan background site are 2-5 times less than those detected in lowland areas such as 14 Chinese megacities. Compared to those in other urban and marine areas enhancements in relative abundances of C2/total diacids and diacids-C/WSOC of the PM2.5 samples suggest that organic aerosols in the region are more oxidized due to strong solar radiation. Molecular compositions and air mass trajectories demonstrate that the above secondary organic aerosols in the Qinghai Lake atmosphere are largely derived from long-range transport. Ratios of oxalic acid, glyoxal and methylglyoxal to levoglucosan in PM2.5 aerosols emitted from household burning of yak dung, a major energy source for Tibetan in the region, are 30-400 times lower than those in the ambient air, which further indicates that primary emission from biomass burning is a negligible source of atmospheric oxalic acid and α-dicarbonyls at this background site.

  7. Vitamin B12, folic acid, ferritin and haematological variables among Thai construction site workers in urban Bangkok.

    Science.gov (United States)

    Tungtrongchitr, R; Pongpaew, P; Phonrat, B; Chanjanakitskul, S; Paksanont, S; Migasena, P; Schelp, F P

    1995-01-01

    Serum vitamin B12, folic acid, ferritin and haematological variables were investigated in eighty-seven male and nineteen female construction site workers in Bangkok. Haemoglobin concentration, haematocrit and MCHC were found to be higher in male than in female workers. Serum ferritin was slightly higher in males than in females. Serum B12 was found to be higher in male than in female workers and serum folic acid level were significantly higher in female than in male workers. Vitamin B12 deficiency was found in 2.3 per cent and folic acid deficiency in 6.9 per cent of the male workers. Serum vitamin B12 and folic acid levels were normal for female workers. The adequate serum levels of vitamin B12 and folic acid might be the result of the habit of the workers to consume tonic drinks which contain glucose, caffeine, and vitamins especially vitamins B6, and B12.

  8. Identification of gamma-aminobutyric acid and its binding sites in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Schaeffer, J.M.; Bergstrom, A.R.

    1988-01-01

    Gamma-aminobutyric acid (GABA), glutamate decarboxylase and GABA-transaminase were identified in the nematode Caenorhabditis elegans. The concentration of GABA in C. elegans is approximately 10-fold lower than the concentration of GABA in rat brain. Glutamate decarboxylase and GABA-transaminase, the GABA anabolic and catabolic enzymes, are also present in C. elegans. Crude membrane fractions were prepared from C. elegans and used to study specific (/sup 3/H) GABA binding sites. GABA binds to C. elegans membranes with high affinity and low capacity. Muscimol is a competitive inhibitor of specific GABA binding with a K/sub I/ value of 120 nM. None of the other GABA agonists or antagonists inhibited greater than 40% of the specific GABA binding at concentrations up to 10/sup -4/M. Thirteen spider venoms were examined as possible GABA agonists or antagonists, the venom from Calilena agelenidae inhibits specific GABA binding with a K/sub I/ value of 6 nl/ml. These results suggest that GABA has a physiological role as a neurotransmitter in C. elegans.

  9. EVOLVE 2014 International Conference

    CERN Document Server

    Tantar, Emilia; Sun, Jian-Qiao; Zhang, Wei; Ding, Qian; Schütze, Oliver; Emmerich, Michael; Legrand, Pierrick; Moral, Pierre; Coello, Carlos

    2014-01-01

    This volume encloses research articles that were presented at the EVOLVE 2014 International Conference in Beijing, China, July 1–4, 2014.The book gathers contributions that emerged from the conference tracks, ranging from probability to set oriented numerics and evolutionary computation; all complemented by the bridging purpose of the conference, e.g. Complex Networks and Landscape Analysis, or by the more application oriented perspective. The novelty of the volume, when considering the EVOLVE series, comes from targeting also the practitioner’s view. This is supported by the Machine Learning Applied to Networks and Practical Aspects of Evolutionary Algorithms tracks, providing surveys on new application areas, as in the networking area and useful insights in the development of evolutionary techniques, from a practitioner’s perspective. Complementary to these directions, the conference tracks supporting the volume, follow on the individual advancements of the subareas constituting the scope of the confe...

  10. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  11. Enzyme active site mimics based on TriAzaCyclophane (TAC)-scaffolded peptides and amino acid residues

    NARCIS (Netherlands)

    Albada, H.B.

    2009-01-01

    This thesis describes the scope and limitations of the application of TriAzaCyclophane (TAC)-scaffolded peptides or amino acid residues as enzyme active site mimics, as ligands in asymmetric catalysis and as hydrolysis catalysts attached to vancomycin. For the mimicry of functional group enzymes, of

  12. Triazacyclophane (TAC)-scaffolded histidine and aspartic acid residues as mimics of non-heme metalloenzyme active sites

    NARCIS (Netherlands)

    Albada, H.B.; Soulimani, F.; Jacobs, H.J.F.; Versluis, C.; Weckhuysen, B.M.; Liskamp, R.M.J.

    2012-01-01

    We describe the synthesis and coordination behaviour to copper(II) of two close structural triazacyclophane-based mimics of two often encountered aspartic acid and histidine containing metalloenzyme active sites. Coordination of these mimics to copper(I) and their reaction with molecular oxygen lead

  13. Dynamic HypA zinc site is essential for acid viability and proper urease maturation in Helicobacter pylori

    Science.gov (United States)

    Johnson, Ryan C.; Hu, Heidi Q.; Merrell, D. Scott; Maroney, Michael J.

    2015-01-01

    Helicobacter pylori requires urease activity in order to survive in the acid environment of the human stomach. Urease is regulated in part by nickelation, a process that requires the HypA protein, which is a putative nickel metallochaperone that is generally associated with hydrogenase maturation. However, in H. pylori, HypA plays a dual role. In addition to an N-terminal nickel binding site, HypA proteins also contain a structural zinc site that is coordinated by two rigorously conserved CXXC sequences, which in H. pylori are flanked by His residues. These structural Zn sites are known to be dynamic, converting from Zn(Cys)4 centers at pH 7.2 to Zn(Cys)2(His)2 centers at pH 6.3 in the presence of Ni(II) ions. In this study, mutant strains of H. pylori that express zinc site variants of the HypA protein are used to show that the structural changes in the zinc site are important for the acid viability of the bacterium, and that a reduction in acid viability in these variants can be traced in large measure to deficient urease activity. This in turn leads to a model that connects the Zn(Cys)4 coordination to urease maturation. PMID:25608738

  14. Amino acid sequences of neuropeptides in the sinus gland of the land crab Cardisoma carnifex: a novel neuropeptide proteolysis site.

    Science.gov (United States)

    Newcomb, R W

    1987-08-01

    The sinus gland is a major neurosecretory structure in Crustacea. Five peptides, labeled C, D, E, F, and I, isolated from the sinus gland of the land crab have been hypothesized to arise from the incomplete proteolysis at two internal sites on a single biosynthetic intermediate peptide "H", based on amino acid composition additivities and pulse-chase radiolabeling studies. The presence of only a single major precursor for the sinus gland peptides implies that peptide H may be synthesized on a common precursor with crustacean hyperglycemic hormone forms, "J" and "L," and a peptide, "K," similar to peptides with molt inhibiting activity. Here I report amino acid sequences of these peptides. The amino terminal sequence of the parent peptide, H, (and the homologous fragments) proved refractory to Edman degradation. Data from amino acid analysis and carboxypeptidase digestion of the naturally occurring fragments and of fragments produced by endopeptidase digestion were used together with Edman degradation to obtain the sequences. Amino acid analysis of fragments of the naturally occurring "overlap" peptides (those produced by internal cleavage at one site on H) was used to obtain the sequences across the cleavage sites. The amino acid sequence of the land crab peptide H is Arg-Ser-Ala-Asp-Gly-Phe-Gly-Arg-Met-Glu-Ser-Leu-Leu-Thr-Ser-Leu-Arg-Gly- Ser-Ala-Glu- Ser-Pro-Ala-Ala-Leu-Gly-Glu-Ala-Ser-Ala-Ala-His-Pro-Leu-Glu. In vivo cleavage at one site involves excision of arginine from the sequence Leu-Arg-Gly, whereas cleavage at the other site involves excision of serine from the sequence Glu-Ser-Leu. Proteolysis at the latter sequence has not been previously reported in intact secretory granules. The aspartate at position 4 is possibly covalently modified.

  15. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue

    Directory of Open Access Journals (Sweden)

    Sofía Arriarán

    2015-11-01

    Full Text Available Background and Objectives. White adipose tissue (WAT shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism.Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities.Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males’ subcutaneous WAT.Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole.

  16. Uptake of gamma-aminobutyric acid and L-glutamic acid by synaptosomes from postmortem human cerebral cortex: multiple sites, sodium dependence and effect of tissue preparation.

    Science.gov (United States)

    Dodd, P R; Watson, W E; Morrison, M M; Johnston, G A; Bird, E D; Cowburn, R F; Hardy, J A

    1989-06-26

    The uptake of gamma-aminobutyric acid (GABA) and L-glutamic acid by synaptosomes prepared from frozen postmortem human brain was shown to be effected via distinct high and low affinity sites. At approximately 17 h postmortem delay, the kinetic parameters for GABA uptake were: high affinity site, Km 7.1 +/- 2.5 microM, Vmax 18.7 +/- 4.8 nmol.min-1 per 100 mg protein; low affinity site, Km 2 +/- 1 mM, Vmax 425 +/- 250 nmol.min-1 per 100 mg protein (means +/- S.E.M., n = 13). Kinetic parameters for L-glutamate uptake were: high affinity site, Km 7.5 +/- 1.0 microM, Vmax 85 +/- 8 nmol.min-1 per 100 mg protein; low affinity site, Km 1.8 +/- 1.2 mM. Vmax 780 +/- 175 nmol.min-1 per 100 mg protein (n = 11). A detailed kinetic analysis of high affinity GABA uptake was performed over a range of sodium ion concentrations. The results were consistent with a coupling ratio of one Na+ ion to one GABA molecule; a similar result was found with rat brain synaptosomes. However, rat and human synaptosomes differed in the degree to which the substrate affinity of the high affinity GABA uptake site varied with decreasing Na+ ion concentration. High affinity GABA uptake was markedly affected by the method used to freeze and divide the tissue, but did not vary greatly in different cortical regions. There was some decline of high affinity GABA uptake activity with postmortem delay, apparently due to a loss of sites rather than a change in site affinity.

  17. Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Lummis, S.C.R.; Johnston, G.A.R. (Univ. of Sydney, New South Wales (Australia)); Nicoletti, G. (Royal Melbourne Inst. of Tech. (Australia)); Holan, G. (CSIRO, Melbourne (Australia))

    1991-01-01

    Benzodiazepine binding sites, which were once considered to exist only in higher vertebrates, are here demonstrated in the bacteria E. coli. The bacterial ({sup 3}H)diazepam binding sites are modulated by GABA; the modulation is dose dependent and is reduced at high concentrations. The most potent competitors of E.Coli ({sup 3}H)diazepam binding are those that are active in displacing ({sup 3}H)benzodiazepines from vertebrate peripheral benzodiazepine binding sites. These vertebrate sites are not modulated by GABA, in contrast to vertebrate neuronal benzodiazepine binding sites. The E.coli benzodiazepine binding sites therefore differ from both classes of vertebrate benzodiazepine binding sites; however the ligand spectrum and GABA-modulatory properties of the E.coli sites are similar to those found in insects. This intermediate type of receptor in lower species suggests a precursor for at least one class of vertebrate benzodiazepine binding sites may have existed.

  18. Original tandem duplication in FXIIIA gene with splicing site modification and four amino acids insertion causes factor XIII deficiency.

    Science.gov (United States)

    Louhichi, Nacim; Haj Salem, Ikhlass; Medhaffar, Moez; Miled, Nabil; Hadji, Ahmad F; Keskes, Leila; Fakhfakh, Faiza

    2017-04-01

    : Recessive mutations of F13A gene are reported to be responsible of FXIIIA subunit deficiency (FXIIIA). In all, some intronic nucleotide changes identified in this gene were investigated by in-silico analysis and occasionally supported by experimental data or reported in some cases as a polymorphism. To determine the molecular defects responsible of congenital factor XIII deficiency in Libyan patient, molecular analysis was performed by direct DNA sequencing of the coding regions and splice junctions of the FXIIIA subunit gene (F13A). A splicing minigene assay was used to study the effect of this mutation. Bioinformatics exploration was fulfilled to conceive consequences on protein. A 12-bp duplication straddling the border of intron 9 and exon 10 leads to two 3' acceptor splice sites, resulting in silencing of the downstream wild 3' splice site. It caused an in-frame insertion of 12 nucleotides into mRNA and four amino acids into protein. Bioinformatic analysis predicts that the insertion of four amino acids affects the site 3 of calcium binding site, which disturbs the smooth function of the FXIIIA peptide causing the factor XIII deficiency. This study showed that a small duplication seems to weaken the original 3' splice site and enhance the activation of a new splice site responsible for an alternative splicing. It would be interesting to examine the underlying molecular mechanism involved in this rearrangement.

  19. Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites.

    Science.gov (United States)

    Xiong, S; Chirala, S S; Wakil, S J

    2000-04-11

    To understand cholesterol-mediated regulation of human fatty acid synthase promoter I, we tested various 5'-deletion constructs of promoter I-luciferase reporter gene constructs in HepG2 cells. The reporter gene constructs that contained only the Sp-1-binding site (nucleotides -82 to -74) and the two tandem sterol regulatory elements (SREs; nucleotides -63 to -46) did not respond to cholesterol. Only the reporter gene constructs containing a nuclear factor-Y (NF-Y) sequence, the CCAAT sequence (nucleotides -90 to -86), an Sp-1 sequence, and the two tandem SREs responded to cholesterol. The NF-Y-binding site, therefore, is essential for cholesterol response. Mutating the SREs or the NF-Y site and inserting 4 bp between the Sp-1- and NF-Y-binding sites both resulted in a minimal cholesterol response of the reporter genes. Electrophoretic mobility-shift assays using anti-SRE-binding protein (SREBP) and anti-NF-Ya antibodies confirmed that these SREs and the NF-Y site bind the respective factors. We also identified a second Sp-1 site located between nucleotides -40 and -30 that can substitute for the mutated Sp-1 site located between nucleotides -82 and -74. The reporter gene expression of the wild-type promoter and the Sp-1 site (nucleotides -82 to -74) mutant promoter was similar when SREBP1a [the N-terminal domain of SREBP (amino acids 1-520)] was constitutively overexpressed, suggesting that Sp-1 recruits SREBP to the SREs. Under the same conditions, an NF-Y site mutation resulted in significant loss of reporter gene expression, suggesting that NF-Y is required to activate the cholesterol response.

  20. Effects of acidic recharge on groundwater at the St. Kevin Gulch site, Leadville, Colorado

    Science.gov (United States)

    Paschke, S.S.; Harrison, W.J.; Walton-Day, K.

    2001-01-01

    The acid rock drainage-affected stream of St. Kevin Gulch recharges the Quaternary sand and gravel aquifer of Tennessee Park, near Leadville, Colorado, lowering pH and contributing iron, cadmium, copper, zinc and sulphate to the ground-water system. Dissolved metal mobility is controlled by the seasonal spring runoff as well as oxidation/reduction (redox) reactions in the aquifer. Oxidizing conditions occur in the unconfined portions of the aquifer whilst sulphate-reducing conditions are found down gradient where semi-confined groundwater flow occurs beneath a natural wetland. Iron-reducing conditions occur in the transition from unconfined to semi-confined groundwater flow. Dissolved iron concentrations are low to not detectable in the alluvial fan recharge zone and increase in a down gradient direction. The effects of low-pH, metal-rich recharge are pronounced during low-flow in the fall when there is a defined area of low pH groundwater with elevated concentrations of dissolved zinc, cadmium, copper and sulphate adjacent to St. Kevin Gulch. Dissolved metal and sulphate concentrations in the recharge zone are diluted during spring runoff, although the maximum concentrations of dissolved zinc, cadmium, copper and sulphate occur at selected down gradient locations during high flow. Dissolved zinc, cadmium and copper concentrations are low to not detectable, whereas dissolved iron concentrations are greatest, in groundwater samples from the sulphate-reducing zone. Attenuation of zinc, cadmium and copper beneath the wetland suggests sulphide mineral precipitation is occurring in the semi-confined aquifer, in agreement with previous site investigations and saturation index calculations. Adsorption of dissolved zinc, cadmium and copper onto iron hydroxides is a minor attenuation process due to the low pH of the groundwater system.

  1. The Involvement of Amino Acid Side Chains in Shielding the Nickel Coordination Site: An NMR Study

    Directory of Open Access Journals (Sweden)

    Serenella Medici

    2013-10-01

    Full Text Available Coordination of proteins and peptides to metal ions is known to affect their properties, often by a change in their structural organization. Side chains of the residues directly involved in metal binding or very close to the coordination centre may arrange themselves around it, in such a way that they can, for instance, disrupt the protein functions or stabilize a metal complex by shielding it from the attack of water or other small molecules. The conformation of these side chains may be crucial to different biological or toxic processes. In our research we have encountered such behaviour in several cases, leading to interesting results for our purposes. Here we give an overview on the structural changes involving peptide side chains induced by Ni(II coordination. In this paper we deal with a number of peptides, deriving from proteins containing one or more metal coordinating sites, which have been studied through a series of NMR experiments in their structural changes caused by Ni(II complexation. Several peptides have been included in the study: short sequences from serum albumin (HSA, Des-Angiotensinogen, the 30-amino acid tail of histone H4, some fragments from histone H2A and H2B, the initial fragment of human protamine HP2 and selected fragments from prion and Cap43 proteins. NMR was the election technique for gathering structural information. Experiments performed for this purpose included 1D 1H and 13C, and 2D HSQC, COSY, TOCSY, NOESY and ROESY acquisitions, which allowed the calculation of the Ni(II complexes structural models.

  2. Measurably evolving populations

    DEFF Research Database (Denmark)

    Drummond, Alexei James; Pybus, Oliver George; Rambaut, Andrew

    2003-01-01

    processes through time. Populations for which such studies are possible � measurably evolving populations (MEPs) � are characterized by sufficiently long or numerous sampled sequences and a fast mutation rate relative to the available range of sequence sampling times. The impact of sequences sampled through...... time has been most apparent in the disciplines of RNA viral evolution and ancient DNA, where they enable us to estimate divergence times without paleontological calibrations, and to analyze temporal changes in population size, population structure and substitution rates. Thus, MEPs could increase our...

  3. Evolving XSLT stylesheets

    CERN Document Server

    Zorzano, Nestor; Laredo, J L J; Sevilla, J P; Garcia, Pablo; Merelo, J J

    2007-01-01

    This paper introduces a procedure based on genetic programming to evolve XSLT programs (usually called stylesheets or logicsheets). XSLT is a general purpose, document-oriented functional language, generally used to transform XML documents (or, in general, solve any problem that can be coded as an XML document). The proposed solution uses a tree representation for the stylesheets as well as diverse specific operators in order to obtain, in the studied cases and a reasonable time, a XSLT stylesheet that performs the transformation. Several types of representation have been compared, resulting in different performance and degree of success.

  4. Trace metal biogeochemistry in mangrove ecosystems: a comparative assessment of acidified (by acid sulfate soils) and non-acidified sites.

    Science.gov (United States)

    Nath, Bibhash; Birch, Gavin; Chaudhuri, Punarbasu

    2013-10-01

    The generation of acidity and subsequent mobilization of toxic metals induced by acid sulfate soils (ASSs) are known to cause severe environmental damage to many coastal wetlands and estuaries of Australia and worldwide. Mangrove ecosystems serve to protect coastal environments, but are increasingly threatened from such ASS-induced acidification due to variable hydrological conditions (i.e., inundation-desiccation cycles). However, the impact of such behaviors on trace metal distribution, bio-availability and accumulation in mangrove tissues, i.e., leaves and pneumatophores, are largely unknown. In this study, we examined how ASS-induced acidifications controlled trace metal distribution and bio-availability in gray mangrove (Avicennia marina) soils and in tissues in the Kooragang wetland, New South Wales, Australia. We collected mangrove soils, leaves and pneumatophores from a part of the wetland acidified from ASS (i.e., an affected site) for detailed biogeochemical studies. The results were compared with samples collected from a natural intertidal mangrove forest (i.e., a control site) located within the same wetland. Soil pH (mean: 5.90) indicated acidic conditions in the affected site, whereas pH was near-neutral (mean: 7.17) in the control site. The results did not show statistically significant differences in near-total and bio-available metal concentrations, except for Fe and Mn, between affected and control sites. Iron concentrations were significantly (p values≤0.001) greater in the affected site, whereas Mn concentrations were significantly (p values≤0.001) greater in the control site. However, large proportions of near-total metals were potentially bio-available in control sites. Concentrations of Fe and Ni were significantly (p values≤0.001) greater in leaves and pneumatophores of the affected sites, whereas Mn, Cu, Pb and Zn were greater in control sites. The degree of metal bio-accumulation in leaves and pneumatophores suggest contrasting

  5. Distribution and integrated assessment of lead in an abandoned lead-acid battery site in Southwest China before redevelopment.

    Science.gov (United States)

    Wang, Mei; Zhang, Chao; Zhang, Zhuo; Li, Fasheng; Guo, Guanlin

    2016-06-01

    Lead-acid battery sites have contributed enormous amounts of lead to the environment, significantly affecting its global biogeochemical cycle and leaving the potential risks to human health. An abandoned lead-acid battery site prepared for redevelopment was selected in order to study the distribution of lead in soils, plants, rhizosphere soils and soil solutions. In total, 197 samples from 77 boreholes were collected and analyzed. Single extractions by acetic acid (HOAc) were conducted to assess the bioavailability and speciation of lead in soils for comparison with the parts of the plants that are aboveground. Health risks for future residential development were evaluated by the integrated exposure uptake biokinetic (IEUBK) model. The results indicated that lead concentrations in 83% of the soil samples exceeded the Chinese Environmental Quality Standard for soil (350 mg/kg for Pb) and mainly occurred at depths between 0 and 1.5 m while accumulating at the surface of demolished construction waste and miscellaneous fill. Lead concentrations in soil solutions and HOAc extraction leachates were linked closely to the contents of aboveground Broussonetia papyrifera and Artemisia annua, two main types of local plants that were found at the site. The probability density of lead in blood (PbB) in excess of 10 µg/dL could overtake the 99% mark in the residential scenario. The findings provided a relatively integrated method to illustrate the onsite investigations and assessment for similar sites before remediation and future development from more comprehensive aspects.

  6. Unexpected tricovalent binding mode of boronic acids within the active site of a penicillin-binding protein.

    Science.gov (United States)

    Zervosen, Astrid; Herman, Raphael; Kerff, Frédéric; Herman, Alexandre; Bouillez, André; Prati, Fabio; Pratt, R F; Frère, Jean-Marie; Joris, Bernard; Luxen, André; Charlier, Paulette; Sauvage, Eric

    2011-07-20

    Boronic acids bearing appropriate side chains are good inhibitors of serine amidohydrolases. The boron usually adopts a tetrahedral conformation, bound to the nucleophilic serine of the active site and mimicking the transition state of the enzymatic reaction. We have solved the structures of complexes of a penicillin-binding protein, the DD-peptidase from Actinomadura sp. R39, with four amidomethylboronic acids (2,6-dimethoxybenzamidomethylboronic acid, phenylacetamidomethylboronic acid, 2-chlorobenzamidomethylboronic acid, and 2-nitrobenzamidomethylboronic acid) and the pinacol ester derived from phenylacetamidomethylboronic acid. We found that, in each case, the boron forms a tricovalent adduct with Oγ of Ser49, Ser298, and the terminal amine group of Lys410, three key residues involved in the catalytic mechanism of penicillin-binding proteins. This represents the first tricovalent enzyme-inhibitor adducts observed by crystallography. In two of the five R39-boronate structures, the boronic acid is found as a tricovalent adduct in two monomers of the asymmetric unit and as a monocovalent adduct with the active serine in the two remaining monomers of the asymmetric unit. Formation of the tricovalent complex from a classical monocovalent complex may involve rotation around the Ser49 Cα-Cβ bond to place the boron in a position to interact with Ser298 and Lys410, and a twisting of the side-chain amide such that its carbonyl oxygen is able to hydrogen bond to the oxyanion hole NH of Thr413. Biphasic kinetics were observed in three of the five cases, and details of the reaction between R39 and 2,6-dimethoxybenzamidomethylboronic acid were studied. Observation of biphasic kinetics was not, however, thought to be correlated to formation of tricovalent complexes, assuming that the latter do form in solution. On the basis of the crystallographic and kinetic results, a reaction scheme for this unexpected inhibition by boronic acids is proposed.

  7. A comparison of copper and acid site zeolites for the production of nitric oxide for biomedical applications.

    Science.gov (United States)

    Russell, Samantha E; González Carballo, Juan María; Orellana-Tavra, Claudia; Fairen-Jimenez, David; Morris, Russell E

    2017-03-21

    Copper-exchanged and acidic zeolites are shown to produce nitric oxide (NO) from a nitrite source in biologically active (nanomolar) concentrations. Four zeolites were studied; mordenite, ferrierite, ZSM-5 and SSZ-13, which had varying pore size, channel systems and Si/Al ratios. ZSM-5 and SSZ-13 produced the highest amounts of NO in both the copper and acid form. The high activity and regeneration of the copper active sites makes them good candidates for long-term NO production. Initial cytotoxicity tests have shown at least one of the copper zeolites (Cu-SSZ-13) to be biocompatible, highlighting the potential usage within biomedical applications.

  8. Application of variable anti-connectivity index to active sites. Modelling pK(a) values of aliphatic monocarboxylic acids.

    Science.gov (United States)

    Sčavničar, A; Balaban, A T; Pompe, M

    2013-01-01

    A partial distance-weighted variable anti-connectivity topological index was introduced for modelling pK(a) values of 31 aliphatic carboxylic acids and haloalkyl-carboxylic acids. The partial distance-weighted variable anti-connectivity index showed superior modelling capabilities compared with the index calculated from the complete graph, because it is capable of accounting correctly for the intramolecular interactions of unconnected vertices to specific bond strengths (active site), thereby improving the RMS(CV) error by about 30% (0.221 pK(a) units).

  9. Novel radioiodinated {gamma}-hydroxybutyric acid analogues for radiolabeling and Photolinking of high-affinity {gamma}-hydroxybutyric acid binding sites

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Høg, Signe; Sabbatini, Paola;

    2010-01-01

    ¿-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse, and an endogenous substance that binds to low- and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a (125)I-labeled GHB analog and characterized its binding in rat brain...... homogenate and slices. Our data show that [(125)I]4-hydroxy-4-[4-(2-iodobenzyloxy)phenyl]butanoate ([(125)I]BnOPh-GHB) binds to one site in rat brain cortical membranes with low nanomolar affinity (K(d), 7 nM; B(max), 61 pmol/mg protein). The binding is inhibited by GHB and selected analogs......, but not by ¿-aminobutyric acid. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether, the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites...

  10. Novel Radioiodinated γ-Hydroxybutyric Acid Analogues for Radiolabeling and Photolinking of High-Affinity γ-Hydroxybutyric Acid Binding Sites

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Høg, Signe; Sabbatini, Paola;

    2010-01-01

    γ-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse, and an endogenous substance that binds to low- and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a 125I-labeled GHB analog and characterized its binding in rat brain...... homogenate and slices. Our data show that [125I]4-hydroxy-4-[4-(2-iodobenzyloxy)phenyl]butanoate ([125I]BnOPh-GHB) binds to one site in rat brain cortical membranes with low nanomolar affinity (Kd, 7 nM; Bmax, 61 pmol/mg protein). The binding is inhibited by GHB and selected analogs, but not by γ......-aminobutyric acid. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether, the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites or [3H...

  11. Radiosynthesis and Evaluation of [(11)C]3-Hydroxycyclopent-1-enecarboxylic Acid as Potential PET Ligand for the High-Affinity γ-Hydroxybutyric Acid Binding Sites.

    Science.gov (United States)

    Jensen, Claus H; Hansen, Hanne D; Bay, Tina; Vogensen, Stine B; Lehel, Szabolcs; Thiesen, Louise; Bundgaard, Christoffer; Clausen, Rasmus P; Knudsen, Gitte M; Herth, Matthias M; Wellendorph, Petrine; Frølund, Bente

    2017-01-18

    γ-Hydroxybutyric acid (GHB) is an endogenous neuroactive substance and proposed neurotransmitter with affinity for both low- and high-affinity binding sites. A radioligand with high and specific affinity toward the high-affinity GHB binding site would be a unique tool toward a more complete understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate. Here, we report the (11)C-labeling and subsequent evaluation of [(11)C]HOCPCA in a domestic pig, as a PET-radioligand for visualization of the high-affinity GHB binding sites in the live pig brain. To investigate the regional binding of HOCPCA in pig brain prior to in vivo PET studies, in vitro quantitative autoradiography on sections of pig brain was performed using [(3)H]HOCPCA. In vivo evaluation of [(11)C]HOCPCA showed no brain uptake, possibly due to a limited uptake of HOCPCA by the MCT1 transporter at tracer doses of [(11)C]HOCPCA.

  12. Sequence and structural features of binding site residues in protein-protein complexes: comparison with protein-nucleic acid complexes

    Directory of Open Access Journals (Sweden)

    Selvaraj S

    2011-10-01

    Full Text Available Abstract Background Protein-protein interactions are important for several cellular processes. Understanding the mechanism of protein-protein recognition and predicting the binding sites in protein-protein complexes are long standing goals in molecular and computational biology. Methods We have developed an energy based approach for identifying the binding site residues in protein–protein complexes. The binding site residues have been analyzed with sequence and structure based parameters such as binding propensity, neighboring residues in the vicinity of binding sites, conservation score and conformational switching. Results We observed that the binding propensities of amino acid residues are specific for protein-protein complexes. Further, typical dipeptides and tripeptides showed high preference for binding, which is unique to protein-protein complexes. Most of the binding site residues are highly conserved among homologous sequences. Our analysis showed that 7% of residues changed their conformations upon protein-protein complex formation and it is 9.2% and 6.6% in the binding and non-binding sites, respectively. Specifically, the residues Glu, Lys, Leu and Ser changed their conformation from coil to helix/strand and from helix to coil/strand. Leu, Ser, Thr and Val prefer to change their conformation from strand to coil/helix. Conclusions The results obtained in this study will be helpful for understanding and predicting the binding sites in protein-protein complexes.

  13. Evolving Procurement Organizations

    DEFF Research Database (Denmark)

    Bals, Lydia; Laine, Jari; Mugurusi, Godfrey

    Procurement has to find further levers and advance its contribution to corporate goals continuously. This places pressure on its organization in order to facilitate its performance. Therefore, procurement organizations constantly have to evolve in order to match these demands. A conceptual model...... putting the structural elements in focus is derived from the analysis of two case companies, which extends the existing literature and opens new avenues for future research. The findings highlight the importance of taking a contingency perspective on procurement organization, understanding the internal...... and external contingency factors and having a more detailed look at the structural dimensions chosen, beyond the well-known characteristics of centralization, formalization, participation, specialization, standardization and size. From a theoretical perspective, it opens up insights that can be leveraged...

  14. New insights into Cu/SSZ-13 SCR catalyst acidity. Part I: Nature of acidic sites probed by NH 3 titration

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Jinyong; Gao, Feng; Kamasamudram, Krishna; Currier, Neal; Peden, Charles H. F.; Yezerets, Aleksey

    2017-04-01

    In this work we investigated an unusual acidity feature of a Cu/SSZ-13 catalyst used in selective catalytic reduction of NOx with NH3 (NH3-SCR). In particular, this catalyst showed two distinct NH3 desorption peaks in NH3-TPD measurements, in contrast to single, unresolved desorption peaks observed for other Cu-exchanged zeolites conventionally used in the SCR studies, including its isostructural but chemically different analogue Cu/SAPO-34. We further observed that the intensities of the two TPD peaks, which represented the amount of stored NH3, changed in opposite directions in response to progressive mild hydrothermal aging, while the total storage capacity was preserved. We proposed an explanation for this remarkable behavior, by using model reference samples and additional characterization techniques. At least three NH3 storage sites were identified: two distinct populations of Cu sites responsible for low-temperature NH3 storage, and Brønsted acid sites responsible for high-temperature NH3 storage. Contrary to the commonly accepted mechanism that Brønsted acid site loss during hydrothermal aging is driven by dealumination, we concluded that the decline in the number of Brønsted acid sites upon mild hydrothermal aging for Cu/SSZ-13 was not due to dealumination, but rather transformation of Cu sites, i.e., gradual conversion of ZCuOH (Cu2+ singly coordinated with Zeolite) to Z2Cu (Cu2+ doubly coordinated with Zeolite). This transformation was responsible for the increased low-temperature desorption peak in NH3-TPD since each ZCuOH adsorbed ~1 NH3 molecule while each Z2Cu adsorbed ~2 NH3 molecules under the conditions used here. These findings were used in Part II of this series of studies to develop a method for quantifying hydrothermal ageing of industrial Cu/SSZ-13 SCR catalysts. Authors would like to thank Randall Jines for his help with collecting the reactor data, Nancy W. Washton for measuring the NMR data and Tamas Varga for in-situ XRD measurements

  15. Improved dating of the human/chimpanzee separation in the mitochondrial DNA tree: heterogeneity among amino acid sites.

    Science.gov (United States)

    Adachi, J; Hasegawa, M

    1995-06-01

    The internal branch lengths estimated by distance methods such as neighbor-joining are shown to be biased to be short when the evolutionary rate differs among sites. The variable-invariable model for site heterogeneity fits the amino acid sequence data encoded by the mitochondrial DNA from Hominoidea remarkably well. By assuming the orangutan separation to be 13 or 16 Myr old, a maximum-likelihood analysis estimates a young date of 3.6 +/- 0.6 or 4.4 +/- 0.7 Myr (+/- 1 SE) for the human/chimpanzee separation, and these estimates turn out to be robust against differences in the assumed model for amino acid substitutions. Although some uncertainties still exist in our estimates, this analysis suggests that humans separated from chimpanzees some 4-5 Myr ago.

  16. Identification of protein SUMOylation sites by mass spectrometry using combined microwave-assisted aspartic acid cleavage and tryptic digestion

    Science.gov (United States)

    Osula, Omoruyi; Swatkoski, Stephen; Cotter, Robert J.

    2012-01-01

    SUMO (Small-Ubiquitin-like MOdifier) is a post-translational modifier of protein substrates at lysine residues that conjugates to proteins in response to various changes in the cell. As a result of SUMO modification, marked changes in transcription regulation, DNA repair, subcellular localization, and mitosis, among other cellular processes, are known to occur. However, while the identification of ubiquitylation sites by mass spectrometry is aided in part by the presence of a small di-amino acid GlyGly “tag” that remains on lysine residues following tryptic digestion, SUMOylation poses a particular challenge as the absence of a basic residue near to the SUMO C-terminus results in a significant 27 or 32 amino acid sequence branch conjugated to the substrate peptide. MS/MS analyses of these branch peptides generally reveal abundant fragment ions resulting from cleavage of the SUMO tail, but which obscure those needed for characterizing the target peptide sequence. Other approaches for identifying SUMO substrates exist and include overexpression of the SUMO isoforms using an N-terminal histidine tag, as well as site-directed mutagenesis of the C-terminal end of the SUMO sequence. Here, we employ combined enzymatic/chemical approaches which serve to shorten the SUMO tag, and thus help to simplify SUMO spectra, making interpretation of mass spectra and location of the SUMOylation site easier. As described in this report, we demonstrate a method for identifying SUMOylation sites using three commercially available SUMO- modified isoforms, and by employing acid-only and acid/trypsin cleavage strategies. These approaches were carried out using MALDI-TOF and LC/MS instrumentation, along with CID and ETD fragmentation. PMID:22576878

  17. Site-specific incorporation of redox active amino acids into proteins

    Science.gov (United States)

    Alfonta; Lital , Schultz; Peter G. , Zhang; Zhiwen

    2010-10-12

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate redox active amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with redox active amino acids using these orthogonal pairs.

  18. Site-specific incorporation of redox active amino acids into proteins

    Science.gov (United States)

    Alfonta, Lital; Schultz, Peter G.; Zhang, Zhiwen

    2009-02-24

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate redox active amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with redox active amino acids using these orthogonal pairs.

  19. Site-specific incorporation of redox active amino acids into proteins

    Energy Technology Data Exchange (ETDEWEB)

    Alfonta, Lital [San Diego, CA; Schultz, Peter G [La Jolla, CA; Zhang, Zhiwen [San Diego, CA

    2012-02-14

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate redox active amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with redox active amino acids using these orthogonal pairs.

  20. Site-specific incorporation of redox active amino acids into proteins

    Energy Technology Data Exchange (ETDEWEB)

    Alfonta; Lital (San Diego, CA), Schultz; Peter G. (La Jolla, CA), Zhang; Zhiwen (San Diego, CA)

    2010-10-12

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate redox active amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with redox active amino acids using these orthogonal pairs.

  1. Site-specific incorporation of redox active amino acids into proteins

    Energy Technology Data Exchange (ETDEWEB)

    Alfonta, Lital (San Diego, CA); Schultz, Peter G. (La Jolla, CA); Zhang, Zhiwen (Austin, TX)

    2011-08-30

    Compositions and methods of producing components of protein biosynthetic machinery that include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, and orthogonal pairs of tRNAs/synthetases, which incorporate redox active amino acids into proteins are provided. Methods for identifying these orthogonal pairs are also provided along with methods of producing proteins with redox active amino acids using these orthogonal pairs.

  2. Ordered cleavage of myeloperoxidase ester bonds releases active site heme leading to inactivation of myeloperoxidase by benzoic acid hydrazide analogs.

    Science.gov (United States)

    Huang, Jiansheng; Smith, Forrest; Panizzi, Peter

    2014-04-15

    Myeloperoxidase (MPO) catalyzes the breakdown of hydrogen peroxide and the formation of the potent oxidant hypochlorous acid. We present the application of the fluorogenic peroxidase substrate 10-acetyl-3,7-dihydroxyphenoxazine (ADHP) in steady-state and transient kinetic studies of MPO function. Using initial kinetic parameters for the MPO system, we characterized under the same conditions a number of gold standards for MPO inhibition, namely 4-amino benzoic acid hydrazide (4-ABAH), isoniazid and NaN3 before expanding our focus to isomers of 4-ABAH and benzoic acid hydrazide analogs. We determined that in the presence of hydrogen peroxide that 4-ABAH and its isomer 2-ABAH are both slow-tight binding inhibitors of MPO requiring at least two steps, whereas NaN3 and isoniazid-based inhibition has a single observable step. We also determined that MPO inhibition by benzoic acid hydrazide and 4-(trifluoromethyl) benzoic acid hydrazide was due to hydrolysis of the ester bond between MPO heavy chain Glu 242 residue and the heme pyrrole A ring, freeing the light chain and heme b fragment from the larger remaining MPO heavy chain. This new mechanism would essentially indicate that the benzoic acid hydrazide analogs impart inhibition through initial ejection of the heme catalytic moiety without prior loss of the active site iron.

  3. Evolving production network structures

    DEFF Research Database (Denmark)

    Grunow, Martin; Gunther, H.O.; Burdenik, H.

    2007-01-01

    When deciding about future production network configurations, the current structures have to be taken into account. Further, core issues such as the maturity of the products and the capacity requirements for test runs and ramp-ups must be incorporated. Our approach is based on optimization...... modelling and assigns products and capacity expansions to production sites under the above constraints. It also considers the production complexity at the individual sites and the flexibility of the network. Our implementation results for a large manufacturing network reveal substantial possible cost...

  4. Fluorescent amino acid undergoing excited state intramolecular proton transfer for site-specific probing and imaging of peptide interactions.

    Science.gov (United States)

    Sholokh, Marianna; Zamotaiev, Oleksandr M; Das, Ranjan; Postupalenko, Viktoriia Y; Richert, Ludovic; Dujardin, Denis; Zaporozhets, Olga A; Pivovarenko, Vasyl G; Klymchenko, Andrey S; Mély, Yves

    2015-02-12

    Fluorescent amino acids bearing environment-sensitive fluorophores are highly valuable tools for site-selective probing of peptide/ligand interactions. Herein, we synthesized a fluorescent l-amino acid bearing the 4'-methoxy-3-hydroxyflavone fluorophore (M3HFaa) that shows dual emission, as a result of an excited state intramolecular proton transfer (ESIPT). The dual emission of M3HFaa was found to be substantially more sensitive to hydration as compared to previous analogues. By replacing the Ala30 and Trp37 residues of a HIV-1 nucleocapsid peptide, M3HFaa was observed to preserve the peptide structure and functions. Interaction of the labeled peptides with nucleic acids and lipid vesicles produced a strong switch in their dual emission, favoring the emission of the ESIPT product. This switch was associated with the appearance of long-lived fluorescence lifetimes for the ESIPT product, as a consequence of the rigid environment in the complexes that restricted the relative motions of the M3HFaa aromatic moieties. The strongest restriction and thus the longest fluorescence lifetimes were observed at position 37 in complexes with nucleic acids, where the probe likely stacks with the nucleobases. Based on the dependence of the lifetime values on the nature of the ligand and the labeled position, two-photon fluorescence lifetime imaging was used to identify the binding partners of the labeled peptides microinjected into living cells. Thus, M3HFaa appears as a sensitive tool for monitoring site selectively peptide interactions in solution and living cells.

  5. Complexation of trivalent lanthanide cations by different chelation sites of malic and tartric acid (composition, stability and probable structure

    Directory of Open Access Journals (Sweden)

    Mohammed Riri

    2016-11-01

    Full Text Available The formation of colorless gadolinium complexes (x,y,z between x gadolinium ions, y ligands and z protons of some organic acids has been studied in aqueous solution. In this work we shall present the results of investigations on the interaction of the gadolinium ion (Gd3+ with different chelation sites of malic and tartric acid formed in dilute solution for pH values between 5.50 and 7.50. The structures of these new organometallic complexes are Gd3(C4H4O52·(NO33·nH2O and Gd3(C4H4O62·(NO33·nH2O (C4H4O52-: malate ions and C4H4O62-: tartrate ions. These colorless gadolinium complexes of malate and tartrate ions have no absorption band UV–visible, the indirect photometry detection (IPD study; have identified major tri-nuclear complexes of these dicarboxylic acids, giving for these colorless complexes a (3,2,2 and (3,2,3, respectively. Composition and apparent stability constant depends on the acidity of the medium. To complement previous results and to propose probable structures for these new complexes detected in solution FT-IR and FT-Raman spectroscopy have been conducted to identify the different chelation sites for both ligands.

  6. Conceptual Model of Uranium in the Vadose Zone for Acidic and Alkaline Wastes Discharged at the Hanford Site Central Plateau

    Energy Technology Data Exchange (ETDEWEB)

    Truex, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Szecsody, James E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Qafoku, Nikolla [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Serne, R. Jeffrey [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-09-01

    Historically, uranium was disposed in waste solutions of varying waste chemistry at the Hanford Site Central Plateau. The character of how uranium was distributed in the vadose zone during disposal, how it has continued to migrate through the vadose zone, and the magnitude of potential impacts on groundwater are strongly influenced by geochemical reactions in the vadose zone. These geochemical reactions can be significantly influenced by the disposed-waste chemistry near the disposal location. This report provides conceptual models and supporting information to describe uranium fate and transport in the vadose zone for both acidic and alkaline wastes discharged at a substantial number of waste sites in the Hanford Site Central Plateau. The conceptual models include consideration of how co-disposed acidic or alkaline fluids influence uranium mobility in terms of induced dissolution/precipitation reactions and changes in uranium sorption with a focus on the conditions near the disposal site. This information, when combined with the extensive information describing uranium fate and transport at near background pH conditions, enables focused characterization to support effective fate and transport estimates for uranium in the subsurface.

  7. Binding of lipoic acid induces conformational change and appearance of a new binding site in methylglyoxal modified serum albumin.

    Science.gov (United States)

    Suji, George; Khedkar, Santosh A; Singh, Sreelekha K; Kishore, Nand; Coutinho, Evans C; Bhor, Vikrant M; Sivakami, S

    2008-06-01

    The binding of lipoic acid (LA), to methylglyoxal (MG) modified BSA was studied using isothermal titration calorimetry in combination with enzyme kinetics and molecular modelling. The binding of LA to BSA was sequential with two sites, one with higher binding constant and another comparatively lower. In contrast the modified protein showed three sequential binding sites with a reduction in affinity at the high affinity binding site by a factor of 10. CD results show appreciable changes in conformation of the modified protein as a result of binding to LA. The inhibition of esterase like activity of BSA by LA revealed that it binds to site II in domain III of BSA. The pH dependence of esterase activity of native BSA indicated a catalytic group with a pK(a) = 7.9 +/- 0.1, assigned to Tyr411 with the conjugate base stabilised by interaction with Arg410. Upon modification by MG, this pK(a) increased to 8.13. A complex obtained by docking of LA to BSA and BSA in which Arg410 is modified to hydroimidazolone showed that the long hydrocarbon chain of lipoic acid sits in a cavity different from the one observed for unmodified BSA. The molecular electrostatic potential showed that the modification of Arg410 reduced the positive electrostatic potential around the protein-binding site. Thus it can be concluded that the modification of BSA by MG resulted in altered ligand binding characteristics due to changes in the internal geometry and electrostatic potential at the binding site.

  8. Rapidly Evolving Giant Dermatofibroma

    Directory of Open Access Journals (Sweden)

    K. J. Lang

    2010-01-01

    Full Text Available Dermatofibroma, also known as “fibrous histiocytoma”, is a benign dermal or subcutaneous poorly circumscribed proliferation of spindle-shaped fibroblasts and macrophages in the dermis. Although it is commonly present as a brownish nodule the legs of females, it may also arise on the upper extremities, trunk, and rarely on the head. The exact pathogenesis is unclear. However, it is widely believed that the originating insult to the dermis is a folliculitis, an arthropod bite, or an unspecified initial inflammatory condition. Giant dermatofibromas of greater than 5 cm in diameter are rare, with only 22 cases reported in the literature. We present a case of a rapidly evolving pedunculated mass in the groin of a male patient. Histological examination confirmed this to be a giant dermatofibroma. Though this specimen cannot is not confirmed as such, the cellular subtype is sometimes present as a larger lesion with anecdotal reports of local recurrence and distant metastases. The clinical and radiological features which were somewhat suspicious of malignancy are considered in the context of the definitive pathological diagnosis of a benign lesion.

  9. Communicability across evolving networks.

    Science.gov (United States)

    Grindrod, Peter; Parsons, Mark C; Higham, Desmond J; Estrada, Ernesto

    2011-04-01

    Many natural and technological applications generate time-ordered sequences of networks, defined over a fixed set of nodes; for example, time-stamped information about "who phoned who" or "who came into contact with who" arise naturally in studies of communication and the spread of disease. Concepts and algorithms for static networks do not immediately carry through to this dynamic setting. For example, suppose A and B interact in the morning, and then B and C interact in the afternoon. Information, or disease, may then pass from A to C, but not vice versa. This subtlety is lost if we simply summarize using the daily aggregate network given by the chain A-B-C. However, using a natural definition of a walk on an evolving network, we show that classic centrality measures from the static setting can be extended in a computationally convenient manner. In particular, communicability indices can be computed to summarize the ability of each node to broadcast and receive information. The computations involve basic operations in linear algebra, and the asymmetry caused by time's arrow is captured naturally through the noncommutativity of matrix-matrix multiplication. Illustrative examples are given for both synthetic and real-world communication data sets. We also discuss the use of the new centrality measures for real-time monitoring and prediction.

  10. Evolving a photosynthetic organelle

    Directory of Open Access Journals (Sweden)

    Nakayama Takuro

    2012-04-01

    Full Text Available Abstract The evolution of plastids from cyanobacteria is believed to represent a singularity in the history of life. The enigmatic amoeba Paulinella and its 'recently' acquired photosynthetic inclusions provide a fascinating system through which to gain fresh insight into how endosymbionts become organelles. The plastids, or chloroplasts, of algae and plants evolved from cyanobacteria by endosymbiosis. This landmark event conferred on eukaryotes the benefits of photosynthesis - the conversion of solar energy into chemical energy - and in so doing had a huge impact on the course of evolution and the climate of Earth 1. From the present state of plastids, however, it is difficult to trace the evolutionary steps involved in this momentous development, because all modern-day plastids have fully integrated into their hosts. Paulinella chromatophora is a unicellular eukaryote that bears photosynthetic entities called chromatophores that are derived from cyanobacteria and has thus received much attention as a possible example of an organism in the early stages of organellogenesis. Recent studies have unlocked the genomic secrets of its chromatophore 23 and provided concrete evidence that the Paulinella chromatophore is a bona fide photosynthetic organelle 4. The question is how Paulinella can help us to understand the process by which an endosymbiont is converted into an organelle.

  11. Fat: an evolving issue

    Directory of Open Access Journals (Sweden)

    John R. Speakman

    2012-09-01

    Work on obesity is evolving, and obesity is a consequence of our evolutionary history. In the space of 50 years, we have become an obese species. The reasons why can be addressed at a number of different levels. These include separating between whether the primary cause lies on the food intake or energy expenditure side of the energy balance equation, and determining how genetic and environmental effects contribute to weight variation between individuals. Opinion on whether increased food intake or decreased energy expenditure drives the obesity epidemic is still divided, but recent evidence favours the idea that food intake, rather than altered expenditure, is most important. There is more of a consensus that genetics explains most (probably around 65% of weight variation between individuals. Recent advances in genome-wide association studies have identified many polymorphisms that are linked to obesity, yet much of the genetic variance remains unexplained. Finding the causes of this unexplained variation will be an impetus of genetic and epigenetic research on obesity over the next decade. Many environmental factors – including gut microbiota, stress and endocrine disruptors – have been linked to the risk of developing obesity. A better understanding of gene-by-environment interactions will also be key to understanding obesity in the years to come.

  12. Evolving paradigms in pharmacovigilance.

    Science.gov (United States)

    Brewster, Wendy; Gibbs, Trevor; Lacroix, Karol; Murray, Alison; Tydeman, Michael; Almenoff, June

    2006-05-01

    All medicines have adverse effects as well as benefits. The aim of pharmacovigilance is to protect public health by monitoring medicines to identify and evaluate issues and ensure that the overall benefits outweigh the potential risks. The tools and processes used in pharmacovigilance are continually evolving. Increasingly sophisticated tools are being designed to evaluate safety data from clinical trials to enhance the likelihood of detecting safety signals ahead of product registration. Methods include integration of safety data throughout development, meta-analytical techniques, quantitative and qualitative methods for evaluation of adverse event data and graphical tools to explore laboratory and biometric data. Electronic data capture facilitates monitoring of ongoing studies so that it is possible to promptly identify potential issues and manage patient safety. In addition, GSK employs a number of proactive methods for post-marketing signal detection and knowledge management using state-of-the-art statistical and analytical tools. Using these tools, together with safety data collected through pharmacoepidemiologic studies, literature and spontaneous reporting, potential adverse drug reactions can be better identified in marketed products. In summary, the information outlined in this paper provides a valuable benchmark for risk management and pharmacovigilance in pharmaceutical development.

  13. [Identification of rat and human hemoglobin acetilation sites after its interaction with acetylsalicylic acid].

    Science.gov (United States)

    Shreĭner, E V; Murashko, E A; Dubrovskiĭ, Ia D; Krasnov, N V; Podol'skaia, E P; Babakov, V N

    2012-01-01

    The possibility of interaction of 0.1 mg/mL acetylsalicylic acid with purified human and rat globin in vitro during 24 h at 37 degrees C was investigated. The rat globin can be modified with acetylsalicylic acid on aminoacid residues K-17, K-57, K-91, K-140 in alpha subunit as well as on K-18, K-77 in beta subunit. The human globin can be modified with acetylsalicylic acid on aminoacid residues K-17, K-41, K-57 and K-91 in alpha subunit as well as on K-18, K-96 and K- 133 in beta subunit. We identified of acetetylated lysines K-17 and K-57 in alpha subunit of human hemoglobin after incubation whole blood with 0.1 mg/mL acetylsalicylic acid during 3 h.

  14. Determination of solvation and binding site profile within electropolymerised poly(pyrrole-N-propionic acid)

    DEFF Research Database (Denmark)

    Glidle, A.; Swann, M.J.; Gadegaard, Nikolaj

    2000-01-01

    Specular neutron reflectivity measurements were performed on electropolymerised films of poly(pyrrole-N-propionic acid) to determine the degree to which the solvents are capable of supporting biological macromolecules can penetrate the polymer film. The permeation profile of Ni2+ ions which chela...... to the polymer's carboxylic acid moieties for subsequent modified protein binding was also determined. (C) 2000 Elsevier Science B.V. All rights reserved....

  15. In vivo reshaping the catalytic site of nucleoside 2'-deoxyribosyltransferase for dideoxy- and didehydronucleosides via a single amino acid substitution.

    Science.gov (United States)

    Kaminski, Pierre Alexandre; Dacher, Priscilla; Dugué, Laurence; Pochet, Sylvie

    2008-07-18

    Nucleoside 2'-deoxyribosyltransferases catalyze the transfer of 2-deoxyribose between bases and have been widely used as biocatalysts to synthesize a variety of nucleoside analogs. The genes encoding nucleoside 2'-deoxyribosyltransferase (ndt) from Lactobacillus leichmannii and Lactobacillus fermentum underwent random mutagenesis to select variants specialized for the synthesis of 2',3'-dideoxynucleosides. An Escherichia coli strain, auxotrophic for uracil and unable to use 2',3'-dideoxyuridine, cytosine, and 2',3'-dideoxycytidine as a source of uracil was constructed. Randomly mutated lactobacilli ndt libraries from two species, L. leichmannii and L. fermentum, were screened for the production of uracil with 2',3'-dideoxyuridine as a source of uracil. Several mutants suitable for the synthesis of 2',3'-dideoxynucleosides were isolated. The nucleotide sequence of the corresponding genes revealed a single mutation (G --> A transition) leading to the substitution of a small aliphatic amino acid by a nucleophilic one, A15T (L. fermentum) or G9S (L. leichmannii), respectively. We concluded that the "adaptation" of the nucleoside 2'-deoxyribosyltransferase activity to 2,3-dideoxyribosyl transfer requires an additional hydroxyl group on a key amino acid side chain of the protein to overcome the absence of such a group in the corresponding substrate. The evolved proteins also display significantly improved nucleoside 2',3'-didehydro-2',3'-dideoxyribosyltransferase activity.

  16. New amino acid changes in drug resistance sites and HBsAg in hepatitis B virus genotype H.

    Science.gov (United States)

    Fernández-Galindo, D A; Sánchez-Ávila, F; Bobadilla-Morales, L; Gómez-Quiróz, P; Bueno-Topete, M; Armendáriz-Borunda, J; Sánchez-Orozco, L V

    2015-06-01

    Long-term treatment with retrotranscriptase (RT) inhibitors eventually leads to the development of drug resistance. Drug-related mutations occur naturally and these can be found in hepatitis B virus (HBV) carriers who have never received antiviral therapy. HBsAg are overlapped with RT domain, thus nucleot(s)ide analogues (NAs) resistance mutations and naturally-occurring mutations can cause amino acid changes in the HBsAg. Twenty-two patients with chronic hepatitis B were enrolled; three of them were previously treated with NAs and 19 were NAs-naïve treated. HBV reverse transcriptase region was sequenced; genotyping and analysis of missense mutations were performed in both RT domain and HBsAg. There was predominance of genotype H. Drug mutations were present in 18.2% of patients. Classical lamivudine resistance mutations (rtM204V/rtL180M) were present in one naïve-treatment patient infected with genotype G. New amino acid changes were identified in drug resistance sites in HBV strains from patients infected with genotype H; rtQ215E was present in two naïve-NAs treatment patients and rtI169M was identified in a patient previously treated with lamivudine. Mutations at sites rt169, rt204, and rt215 resulted in the Y161C, I195M, and C206W mutations at HBsAg. Also, new amino acid changes were identified in B-cell and T-cell epitopes and were more frequent in HBsAg compared to RT domain. In conclusion, new amino acid changes at antiviral resistance sites, B-cell and T-cell epitopes in HBV genotype H were identified in Mexican patients.

  17. A study of the source-receptor relationships influencing the acidity of precipitation collected at a rural site in France

    Science.gov (United States)

    Charron, Aurélie; Plaisance, Hervé; Sauvage, Stéphane; Coddeville, Patrice; Galloo, Jean-Claude; Guillermo, René

    In order to examine the qualitative and quantitative source-receptor relationships responsible for acid rains at a background site in France, a receptor-oriented model was applied to the precipitation data collected from 1992 to 1995. Origins of acidic and alkaline species in precipitations have been investigated. The methodology combines precipitation chemical data with air parcel backward trajectories to establish concentration field maps of likely contributing sources. Highest acidities and concentrations of sulfate and nitrate in precipitation were associated with transport from the high emission areas of central Europe. Alkaline events were associated with air masses originating from Mediterranean basin or northern Africa. The quantitative relationships between the maps of potential sources and the European emissions of SO 2 and NO x were examined performing a correlation analysis. Good correlations were found between computed concentrations of acidic species and emissions of SO 2 and NO x. Substantial seasonal variations of acidic species were revealed. The highest concentrations occurred during the warm season. These seasonal variations are the effect of change of meteorological conditions and of the strength atmospheric processes according to the season.

  18. Phenylacetic acids and the structurally related non-steroidal anti-inflammatory drug diclofenac bind to specific gamma-hydroxybutyric acid sites in rat brain

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Høg, Signe; Skonberg, Christian

    2009-01-01

    with a twofold higher affinity than GHB. Measuring the affinities of structurally related NSAIDs for the [(3)H]NCS-382 site identified diclofenac, a clinically relevant NSAID (Voltaren, Diclon) of the phenylacetic acid (PAA) type, as a GHB ligand (K(i) value of 5.1 microM). Other non-NSAID PAAs also exhibited...... affinities similar to GHB. Our data raise the interesting possibility that the widely used over-the-counter drug compound, diclofenac, might affect GHB binding at relevant clinical dosages. Furthermore, the identification of PAAs as GHB ligands supplies new information about the structural preferences...

  19. [Contents of tannins and oxalic acid in the selected forest fruits depending on the harvest site].

    Science.gov (United States)

    Sembratowicz, Iwona; Ognik, Katarzyna; Rusinek, Elzbieta; Truchliński, Jerzy

    2008-01-01

    Contents of anti-nutritional components (tannins and oxalic acid) were determined in samples of forest fruits: blueberry, raspberry and wild strawberry harvested in Lublin region from areas considered as potentially not exposed to pollution (Skierbieszów Landscape Park) and potentially polluted areas (Cement Factory Rejowiec S.A.). Study revealed that blueberry and raspberry fruits collected on potentially polluted area were characterized by higher tannins contents than those harvested on potentially not polluted area. Oxalic acid level in studied material indicated its significantly higher concentration in wild strawberry fruits collected both from not exposed and polluted areas as compared to raspberry and blueberry. Tannins and oxalic acid contents in analyzed berries may be accepted as low and safe for human's health.

  20. CERN internal communication is evolving

    CERN Multimedia

    2016-01-01

    CERN news will now be regularly updated on the CERN People page (see here).      Dear readers, All over the world, communication is becoming increasingly instantaneous, with news published in real time on websites and social networks. In order to keep pace with these changes, CERN's internal communication is evolving too. From now on, you will be informed of what’s happening at CERN more often via the “CERN people” page, which will frequently be updated with news. The Bulletin is following this trend too: twice a month, we will compile the most important articles published on the CERN site, with a brand-new layout. You will receive an e-mail every two weeks as soon as this new form of the Bulletin is available. If you have interesting news or stories to share, tell us about them through the form at: https://communications.web.cern.ch/got-story-cern-website​. You can also find out about news from CERN in real time...

  1. Chromatographic analysis of the effects of fatty acids and glycation on binding by probes for Sudlow sites I and II to human serum albumin.

    Science.gov (United States)

    Anguizola, Jeanethe; Debolt, Erin; Suresh, D; Hage, David S

    2016-05-15

    The primary endogenous ligands of human serum albumin (HSA) are non-esterified fatty acids, with 0.1-2mol of fatty acids normally being bound to HSA. In type II diabetes, fatty acid levels in serum are often elevated, and the presence of high glucose results in an increase in the non-enzymatic glycation of HSA. High-performance affinity chromatography (HPAC) was used to examine the combined effects of glycation and the presence of long chain fatty acids on the binding of HSA with R-warfarin and l-tryptophan (i.e., probes for Sudlow sites I and II, the major sites for drugs on this protein). Zonal elution competition studies were used to examine the interactions of myristic acid, palmitic acid and stearic acid with these probes on HSA. It was found that all these fatty acids had direct competition with R-warfarin at Sudlow site I of normal HSA and glycated HSA, with the glycated HSA typically having stronger binding for the fatty acids at this site. At Sudlow site II, direct competition was observed for all the fatty acids with l-tryptophan when using normal HSA, while glycated HSA gave no competition or positive allosteric interactions between these fatty acids and l-tryptophan. These data indicated that glycation can alter the interactions of drugs and fatty acids at specific binding sites on HSA. The results of this study should lead to a better understanding of how these interactions may change during diabetes and demonstrate how HPAC can be used to examine drug/solute-protein interactions in complex systems.

  2. eVolver: an optimization engine for evolving protein sequences to stabilize the respective structures.

    Science.gov (United States)

    Brylinski, Michal

    2013-07-31

    Many structural bioinformatics approaches employ sequence profile-based threading techniques. To improve fold recognition rates, homology searching may include artificially evolved amino acid sequences, which were demonstrated to enhance the sensitivity of protein threading in targeting midnight zone templates. We describe implementation details of eVolver, an optimization algorithm that evolves protein sequences to stabilize the respective structures by a variety of potentials, which are compatible with those commonly used in protein threading. In a case study focusing on LARG PDZ domain, we show that artificially evolved sequences have quite high capabilities to recognize the correct protein structures using standard sequence profile-based fold recognition. Computationally design protein sequences can be incorporated in existing sequence profile-based threading approaches to increase their sensitivity. They also provide a desired linkage between protein structure and function in in silico experiments that relate to e.g. the completeness of protein structure space, the origin of folds and protein universe. eVolver is freely available as a user-friendly webserver and a well-documented stand-alone software distribution at http://www.brylinski.org/evolver.

  3. Site-specific critical acid load estimates for forest soils in the Osborn Creek watershed, Michigan

    Science.gov (United States)

    Trevor Hobbs; Jason Lynch; Randy. Kolka

    2017-01-01

    Anthropogenic acid deposition has the potential to accelerate leaching of soil cations, and in turn, deplete nutrients essential to forest vegetation. The critical load concept, employing a simple mass balance (SMB) approach, is often used to model this process. In an evaluation under the U.S. Forest Service Watershed Condition Framework program, soils in all 6th level...

  4. An active site mutant of Escherichia coli cyclopropane fatty acid synthase forms new non-natural fatty acids providing insights on the mechanism of the enzymatic reaction.

    Science.gov (United States)

    E, Guangqi; Drujon, Thierry; Correia, Isabelle; Ploux, Olivier; Guianvarc'h, Dominique

    2013-12-01

    We have produced and purified an active site mutant of the Escherichia coli cyclopropane fatty acid synthase (CFAS) by replacing the strictly conserved G236 within cyclopropane synthases, by a glutamate residue, which corresponds to E146 of the homologous mycolic acid methyltransferase, Hma, producing hydroxymethyl mycolic acids. The G236E CFAS mutant had less than 1% of the in vitro activity of the wild type enzyme. We expressed the G236E CFAS mutant in an E. coli (DE3) strain in which the chromosomal cfa gene had been deleted. After extraction of phospholipids and conversion into the corresponding fatty acid methyl esters (FAMEs), we observed the formation of cyclopropanated FAMEs suggesting that the mutant retained some of the normal activity in vivo. However, we also observed the formation of new C17 methyl-branched unsaturated FAMEs whose structures were determined using GC/MS and NMR analyses. The double bond was located at different positions 8, 9 or 10, and the methyl group at position 10 or 9. Thus, this new FAMEs are likely arising from a 16:1 acyl chain of a phospholipid that had been transformed by the G236E CFAS mutant in vivo. The reaction catalyzed by this G236E CFAS mutant thus starts by the methylation of the unsaturated acyl chain at position 10 or 9 yielding a carbocation at position 9 or 10 respectively. It follows then two competing steps, a normal cyclopropanation or hydride shift/elimination events giving different combinations of alkenes. This study not only provides further evidence that cyclopropane synthases (CSs) form a carbocationic intermediate but also opens the way to CSs engineering for the synthesis of non-natural fatty acids.

  5. Prediction of posttranslational modification sites from amino acid sequences with kernel methods.

    Science.gov (United States)

    Xu, Yan; Wang, Xiaobo; Wang, Yongcui; Tian, Yingjie; Shao, Xiaojian; Wu, Ling-Yun; Deng, Naiyang

    2014-03-07

    Post-translational modification (PTM) is the chemical modification of a protein after its translation and one of the later steps in protein biosynthesis for many proteins. It plays an important role which modifies the end product of gene expression and contributes to biological processes and diseased conditions. However, the experimental methods for identifying PTM sites are both costly and time-consuming. Hence computational methods are highly desired. In this work, a novel encoding method PSPM (position-specific propensity matrices) is developed. Then a support vector machine (SVM) with the kernel matrix computed by PSPM is applied to predict the PTM sites. The experimental results indicate that the performance of new method is better or comparable with the existing methods. Therefore, the new method is a useful computational resource for the identification of PTM sites. A unified standalone software PTMPred is developed. It can be used to predict all types of PTM sites if the user provides the training datasets. The software can be freely downloaded from http://www.aporc.org/doc/wiki/PTMPred.

  6. Technology development for phosphoric acid fuel cell powerplant (phase 2). [on site integrated energy systems

    Science.gov (United States)

    Christner, L.

    1980-01-01

    Progress is reported in the development of material, cell components, and reformers for on site integrated energy systems. Internal resistance and contact resistance were improved. Dissolved gases (O2, N2, and CO2) were found to have no effect on the electrochemical corrosion of phenolic composites. Stack performance was increased by 100 mV over the average 1979 level.

  7. Hydrogenation of biofuels with formic acid over a palladium-based ternary catalyst with two types of active sites.

    Science.gov (United States)

    Wang, Liang; Zhang, Bingsen; Meng, Xiangju; Su, Dang Sheng; Xiao, Feng-Shou

    2014-06-01

    A composite catalyst including palladium nanoparticles on titania (TiO2) and on nitrogen-modified porous carbon (Pd/TiO2@N-C) is synthesized from palladium salts, tetrabutyl titanate, and chitosan. N2 sorption isotherms show that the catalyst has a high BET surface area (229 m(2)  g(-1)) and large porosity. XPS and TEM characterization of the catalyst shows that palladium species with different chemical states are well dispersed across the TiO2 and nitrogen-modified porous carbon, respectively. The Pd/TiO2@N-C catalyst is very active and shows excellent stability towards hydrogenation of vanillin to 2-methoxy-4-methylphenol using formic acid as hydrogen source. This activity can be attributed to a synergistic effect between the Pd/TiO2 (a catalyst for dehydrogenation of formic acid) and Pd/N-C (a catalyst for hydrogenation of vanillin) sites.

  8. Application of the Nutrient Cycling Model NuCM to a Forest Monitoring Site Exposed to Acidic Precipitation in China

    Institute of Scientific and Technical Information of China (English)

    ZHU Jian-Hua; YU Peng-Tao; T. A. SOGN; WANG Yan-Hui; J.MULDER

    2008-01-01

    The nutrient cycling model NuCM is one of the most detailed models for simulating processes that influence nutrient cycling in forest ecosystems. A field study was conducted at Tieshanping, a Masson pine (Pinus massoniana Lamb.) forest site, in hongqing, China, to monitor the impacts of acidic precipitation on nutrient cycling. NuCM simulations were compared with observed data from the study site. The model produced an approximate fit with the observed data. It simulated the mean annual soil solution concentrations in the two simulation years, whereas it sometimes failed to reproduce seasonal variation. Even though some of the parameters required by modcl running were measured in the field,some others were still highly uncertain and the uncertainties were analyzed. Some of the uncertain parameters necessary for model running should be measured and calibrated to produce a better fit between modeled results and field data.

  9. Irreversible Oxidation of the Active-site Cysteine of Peroxiredoxin to Cysteine Sulfonic Acid for Enhanced Molecular Chaperone Activity*

    OpenAIRE

    2008-01-01

    The thiol (–SH) of the active cysteine residue in peroxiredoxin (Prx) is known to be reversibly hyperoxidized to cysteine sulfinic acid (–SO2H), which can be reduced back to thiol by sulfiredoxin/sestrin. However, hyperoxidized Prx of an irreversible nature has not been reported yet. Using an antibody developed against the sulfonylated (–SO3H) yeast Prx (Tsa1p) active-site peptide (AFTFVCPTEI), we observed an increase in the immunoblot intensity in proportion to the ...

  10. EFFECTS OF SP1 SITE TO hTERT PROMOTER ACTIVITY AND ITS RESPONSE TO RETINOID ACID

    Institute of Scientific and Technical Information of China (English)

    应磊; 戴冰冰; 王楚; 卢健; 钱关祥

    2005-01-01

    Objective To investigate the function of Sp1 consensus sites to human telomerase reverse transcriptase (hTERT) promoter in different cell lines and in TRA-treated Held cell. Methods Different length of hTERT promoter was cloned and inserted into pGL3/basic reporter plasmid. The last four Sp1 sites were deleted by PCR and pGL3 B/TRTP413 A reporter plasmid was constructed. All reporter plasmids were transiently transfected into 293, A549, Hela and HepG2 cell lines. 48 h after transfection, luciferase activity was analyzed. hTERT promoter activity of Held cell which was treated with trans-retinoid acid (TRA) was tested too. Total RNA of these cells were extracted and reverse transcript. hTERT mRNA level was analyzed in all tested cells. c-Myc and Sp1 expression were examined in Hela cell before and after TRA treatment. U937 was used as a positive control in TRA treatment.Results hTERT was expressed at different level in all tested cell lines. 207bp promoter upstream of transcription start site maintained complete activity. Deletion of last 4 Sp1 sites greatly decreased activity of hTERT promoter, and almost eliminated its activity in HepG2. TRA increased the activity of different length hTERT promoters in Hela cell,but the activity of Sp1 site-deleted promoter decreased by 3 times. Unlike U937 cell, hTERT expression of Held cell increased after TRA treatment, and c-Myc and Sp1 mRNA level were relatively stable. Conclusion Sp1 site was required for transactivation of hTERT promoter and played an important role during TRA treatment.

  11. Relationship between environmental parameters and Pinus sylvestris L. site index in forest plantations in northern Spain acidic plateau

    Directory of Open Access Journals (Sweden)

    Bueis T

    2016-06-01

    Full Text Available The assessment of forest productivity at early stages of stand development may help to define the most appropriate silviculture treatment to be applied for each stand. Site index (dominant height at a reference age is a useful tool for forest productivity estimation. The aim of this study was to develop a model to predict site index for Scots pine (Pinus sylvestris L. plantations in northern Spain acidic plateau by using soil (physical, chemical and biochemical, climatic and physiographic parameters. To meet this objective, data from 35 stands classified into three different site quality classes and 63 soil, climatic and physiographic parameters were examined in order to develop a discriminant model. After selecting 12 discriminant models which were biologically consistent and presented the higher cross-validated rate of correct classification, a model including four parameters (latitude, inorganic Al, porosity and microbial biomass carbon as predictors was chosen. The discriminant model classified 71% of cases correctly and no inferior-quality stands were misassigned to the highest quality class. Soil and physiographic parameters included in the above model are easily obtainable in the field or by simple laboratory analysis, thus our results can be easily integrated in operational forestry to determine site quality.

  12. Structure and Mutagenesis of Neural Cell Adhesion Molecule Domains Evidence for Flexibility in the Placement of Polysialic Acid Attachment Sites

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Deirdre A.; Swartzentruber, Kristin G.; Lavie, Arnon; Colley, Karen J. (UICM)

    2010-11-09

    The addition of {alpha}2,8-polysialic acid to the N-glycans of the neural cell adhesion molecule, NCAM, is critical for brain development and plays roles in synaptic plasticity, learning and memory, neuronal regeneration, and the growth and invasiveness of cancer cells. Our previous work indicates that the polysialylation of two N-glycans located on the fifth immunoglobulin domain (Ig5) of NCAM requires the presence of specific sequences in the adjacent fibronectin type III repeat (FN1). To understand the relationship of these two domains, we have solved the crystal structure of the NCAM Ig5-FN1 tandem. Unexpectedly, the structure reveals that the sites of Ig5 polysialylation are on the opposite face from the FN1 residues previously found to be critical for N-glycan polysialylation, suggesting that the Ig5-FN1 domain relationship may be flexible and/or that there is flexibility in the placement of Ig5 glycosylation sites for polysialylation. To test the latter possibility, new Ig5 glycosylation sites were engineered and their polysialylation tested. We observed some flexibility in glycosylation site location for polysialylation and demonstrate that the lack of polysialylation of a glycan attached to Asn-423 may be in part related to a lack of terminal processing. The data also suggest that, although the polysialyltransferases do not require the Ig5 domain for NCAM recognition, their ability to engage with this domain is necessary for polysialylation to occur on Ig5 N-glycans.

  13. The Significance of Lewis Acid Sites for the Selective Catalytic Reduction of Nitric Oxide on Vanadium-Based Catalysts.

    Science.gov (United States)

    Marberger, Adrian; Ferri, Davide; Elsener, Martin; Kröcher, Oliver

    2016-09-19

    The long debated reaction mechanisms of the selective catalytic reduction (SCR) of nitric oxide with ammonia (NH3 ) on vanadium-based catalysts rely on the involvement of Brønsted or Lewis acid sites. This issue has been clearly elucidated using a combination of transient perturbations of the catalyst environment with operando time-resolved spectroscopy to obtain unique molecular level insights. Nitric oxide reacts predominantly with NH3 coordinated to Lewis sites on vanadia on tungsta-titania (V2 O5 -WO3 -TiO2 ), while Brønsted sites are not involved in the catalytic cycle. The Lewis site is a mono-oxo vanadyl group that reduces only in the presence of both nitric oxide and NH3 . We were also able to verify the formation of the nitrosamide (NH2 NO) intermediate, which forms in tandem with vanadium reduction, and thus the entire mechanism of SCR. Our experimental approach, demonstrated in the specific case of SCR, promises to progress the understanding of chemical reactions of technological relevance.

  14. Remediation of acid mine drainage at the friendship hill national historic site with a pulsed limestone bed process

    Science.gov (United States)

    Sibrell, P.L.; Watten, B.; Boone, T.; ,

    2003-01-01

    A new process utilizing pulsed fluidized limestone beds was tested for the remediation of acid mine drainage at the Friendship Hill National Historic Site, in southwestern Pennsylvania. A 230 liter-per-minute treatment system was constructed and operated over a fourteen-month period from June 2000 through September 2001. Over this period of time, 50,000 metric tons of limestone were used to treat 50 million liters of water. The influent water pH was 2.5 and acidity was 1000 mg/L as CaCO3. Despite the high potential for armoring at the site, effluent pH during normal plant operation ranged from 5.7 to 7.8 and averaged 6.8. As a result of the high influent acidity, sufficient CO2 was generated and recycled to provide a net alkaline discharge with about 50 mg/L as CaCO3 alkalinity. Additions of commercial CO2 increased effluent alkalinity to as high as 300 mg/L, and could be a useful process management tool for transient high flows or acidities. Metal removal rates were 95% for aluminum (60 mg/L in influent), 50 to 90% for iron (Fe), depending on the ratio of ferrous to ferric iron, which varied seasonally (200 mg/L in influent), and iron and Mn removal was incomplete because of the high pH required for precipitation of these species. Iron removal could be improved by increased aeration following neutralization, and Mn removal could be effected by a post treatment passive settling/oxidation pond. Metal hydroxide sludges were settled in settling tanks, and then hauled from the site for aesthetic purposes. Over 450 metric tons of sludge were removed from the water over the life of the project. The dried sludge was tested by the Toxicity Characteristics Leaching Protocol (TCLP) and was found to be non-hazardous. Treatment costs were $43,000 per year and $1.08 per m 3, but could be decreased to $22,000 and $0.51 per m3 by decreasing labor use and by onsite sludge handling. These results confirm the utility of the new process in treatment of acid impaired waters that were

  15. Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias.

    OpenAIRE

    1990-01-01

    Quantitative receptor autoradiography was used to measure muscarinic cholinergic, benzodiazepine, kainate, phencyclidine (PCP), N-methyl-D-aspartate (NMDA) (measured in Tris acetate), quisqualate-sensitive, non-quisqualate-sensitive and total glutamate (measured in Tris chloride buffer) binding sites in adjacent sections of the hippocampal region of 10 Alzheimer's disease, nine control, and six demented, non-Alzheimer's disease postmortem human brains. The measurements were compared to the nu...

  16. Probing the acidic residue within the integrin binding site of laminin-511 that interacts with the metal ion-dependent adhesion site of α6β1 integrin.

    Science.gov (United States)

    Taniguchi, Yukimasa; Li, Shaoliang; Takizawa, Mamoru; Oonishi, Eriko; Toga, Junko; Yagi, Emiko; Sekiguchi, Kiyotoshi

    2017-06-03

    Laminins are major cell-adhesive proteins of basement membranes that interact with integrins in a divalent cation-dependent manner. Laminin-511 consists of α5, β1, and γ1 chains, of which three laminin globular domains of the α5 chain (α5/LG1-3) and a Glu residue in the C-terminal tail of chain γ1 (γ1-Glu1607) are required for binding to integrins. However, it remains unsettled whether the Glu residue in the γ1 tail is involved in integrin binding by coordinating the metal ion in the metal ion-dependent adhesion site of β1 integrin (β1-MIDAS), or by stabilizing the conformation of α5/LG1-3. To address this issue, we examined whether α5/LG1-3 contain an acidic residue required for integrin binding that is as critical as the Glu residue in the γ1 tail; to achieve this, we undertook exhaustive alanine substitutions of the 54 acidic residues present in α5/LG1-3 of the E8 fragment of laminin-511 (LM511E8). Most of the alanine mutants possessed α6β1 integrin binding activities comparable with wild-type LM511E8. Alanine substitution for α5-Asp3198 and Asp3219 caused mild reduction in integrin binding activity, and that for α5-Asp3218 caused severe reduction, possibly resulting from conformational perturbation of α5/LG1-3. When α5-Asp3218 was substituted with asparagine, the resulting mutant possessed significant binding activity to α6β1 integrin, indicating that α5-Asp3218 is not directly involved in integrin binding through coordination with the metal ion in β1-MIDAS. Given that substitution of γ1-Glu1607 with glutamine nullified the binding activity to α6β1 integrin, these results, taken together, support the possibility that the critical acidic residue coordinating the metal ion in β1-MIDAS is Glu1607 in the γ1 tail, but no such residue is present in α5/LG1-3. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Impact of acid mine drainages on surficial waters of an abandoned mining site.

    Science.gov (United States)

    García-Lorenzo, M L; Marimón, J; Navarro-Hervás, M C; Pérez-Sirvent, C; Martínez-Sánchez, M J; Molina-Ruiz, José

    2016-04-01

    Weathering of sulphide minerals produces a great variety of efflorescences of soluble sulphate salts. These minerals play an important role for environmental pollution, since they can be either a sink or a source for acidity and trace elements. This paper aims to characterise surface waters affected by mining activities in the Sierra Minera of Cartagena-La Union (SE, Spain). Water samples were analysed for trace metals (Zn, Cd, Pb, Cu, As and Fe), major ions (Na(+), K(+), Ca(2+) and Mg(2+)) and anions (F(-), Cl(-), NO3 (-), CO3 (2-), SO4 (2-)) concentrations and were submitted to an "evaporation-precipitation" experiment that consisted in identifying the salts resulting from the evaporation of the water aliquots sampled onsite. Mineralogy of the salts was studied using X-ray diffraction and compared with the results of calculations using VISUAL MINTEQ. The study area is heavily polluted as a result of historical mining and processing activities that has produced large amount of wastes characterised by a high trace elements content, acidic pH and containing minerals resulting from the supergene alteration of the raw materials. The mineralogical study of the efflorescences obtained from waters shows that magnesium, zinc, iron and aluminium sulphates predominate in the acid mine drainage precipitates. Minerals of the hexahydrite group have been quantified together with minerals of the rozenite group, alunogen and other phases such as coquimbite and copiapite. Calcium sulphates correspond exclusively to gypsum. In a semiarid climate, such as that of the study area, these minerals contribute to understand the response of the system to episodic rainfall events. MINTEQ model could be used for the analysis of waters affected by mining activities but simulation of evaporation gives more realistic results considering that MINTEQ does not consider soluble hydrated salts.

  18. Session 4: Role of the Broensted acid sites for Pd/Pt catalysts in the hydrotreating of LCO fractions

    Energy Technology Data Exchange (ETDEWEB)

    Albertazzi, S.; Faraone, C.; Vaccari, A. [Bologna Univ., Dipt. di Chimica Industriale e dei Materiali, INSTM-UdR (Italy); Lenarda, M.; Storaro, L.; Talon, A. [Venezia, Univ., Dipt. di Chimica, INSTM-UdR di Venezia, VE (Italy)

    2004-07-01

    The aim of this work was to investigate the catalytic activity and thio-tolerance of the Pd-Pt metallic pair supported on porous systems almost or totally lacking of Broensted acid sites. For this purpose an Al/Ce/Mg pillared montmorillonite clay (PILC), containing almost exclusively Lewis acid sites, and a basic Mg/Al mixed oxide, obtained by calcination of a hydrotalcite-type, were used as supports for Pt/Pd and tested in the hydrogenation of naphthalene in vapour phase, chosen as model molecule of LCO fractions. All the catalysts were activated in situ under a H{sub 2} flow, using a programmed increase of the temperature from room temperature up to 450 C. The catalytic tests were performed in a micro-reactor at 6.0 MPa, investigating a wide range of reaction conditions (temperature, contact time and H{sub 2}/naphthalene feed ratio). Finally, the catalyst thio-resistance was tested, feeding increasing amounts of dibenzothiophene (DBT). The experimental results are given. (O.M.)

  19. Incorporating significant amino acid pairs to identify O-linked glycosylation sites on transmembrane proteins and non-transmembrane proteins

    Directory of Open Access Journals (Sweden)

    Lee Tzong-Yi

    2010-10-01

    Full Text Available Abstract Background While occurring enzymatically in biological systems, O-linked glycosylation affects protein folding, localization and trafficking, protein solubility, antigenicity, biological activity, as well as cell-cell interactions on membrane proteins. Catalytic enzymes involve glycotransferases, sugar-transferring enzymes and glycosidases which trim specific monosaccharides from precursors to form intermediate structures. Due to the difficulty of experimental identification, several works have used computational methods to identify glycosylation sites. Results By investigating glycosylated sites that contain various motifs between Transmembrane (TM and non-Transmembrane (non-TM proteins, this work presents a novel method, GlycoRBF, that implements radial basis function (RBF networks with significant amino acid pairs (SAAPs for identifying O-linked glycosylated serine and threonine on TM proteins and non-TM proteins. Additionally, a membrane topology is considered for reducing the false positives on glycosylated TM proteins. Based on an evaluation using five-fold cross-validation, the consideration of a membrane topology can reduce 31.4% of the false positives when identifying O-linked glycosylation sites on TM proteins. Via an independent test, GlycoRBF outperforms previous O-linked glycosylation site prediction schemes. Conclusion A case study of Cyclic AMP-dependent transcription factor ATF-6 alpha was presented to demonstrate the effectiveness of GlycoRBF. Web-based GlycoRBF, which can be accessed at http://GlycoRBF.bioinfo.tw, can identify O-linked glycosylated serine and threonine effectively and efficiently. Moreover, the structural topology of Transmembrane (TM proteins with glycosylation sites is provided to users. The stand-alone version of GlycoRBF is also available for high throughput data analysis.

  20. Interaction of aspartic acid-104 and proline-287 with the active site of m-calpain.

    Science.gov (United States)

    Arthur, J S; Elce, J S

    1996-01-01

    In an ongoing study of the mechanisms of calpain catalysis and Ca(2+)-induced activation, the effects of Asp-104-->Ser and Pro-287-->Ser large subunit mutations on m-calpain activity, the pH-activity profile, Ca(2+)-sensitivity, and autolysis were measured. The importance of these positions was suggested by sequence comparisons between the calpain and papain families of cysteine proteinases. Asp-104 is adjacent to the active-site Cys-105, and Pro-287 is adjacent to the active-site Asn-286 and probably to the active-site His-262; both Asp-104 and Pro-287 are absolutely conserved in the known calpains, but are replaced by highly conserved serine residues in the papains. The single mutants had approx. 10-15% of wild-type activity, due mainly to a decrease in kcat, since Km was only slightly increased. The Pro-287-->Ser mutation appeared to cause a local perturbation of the catalytic Cys-105/His-262 catalytic ion pair, reducing its efficiency without major effect on the conformation and stability of the enzyme. The Asp-104-->Ser mutation caused a marked narrowing of the pH-activity curve, a 9-fold increase in Ca2+ requirement, and an acceleration of autolysis, when compared with the wild-type enzyme. The results indicated that Asp-104 alters the nature of its interaction with the catalytic ion pair during Ca(2+)-induced conformational change in calpain. This interaction may be direct or indirect, but is important in activation of the enzyme. PMID:8912692

  1. Genetic Incorporation of the Unnatural Amino Acid p-Acetyl Phenylalanine into Proteins for Site-Directed Spin Labeling

    Science.gov (United States)

    Evans, Eric G.B.; Millhauser, Glenn L.

    2016-01-01

    Site-directed spin labeling (SDSL) is a powerful tool for the characterization of protein structure and dynamics; however, its application in many systems is hampered by the reliance on unique and benign cysteine substitutions for the site-specific attachment of the spin label. An elegant solution to this problem involves the use of genetically encoded unnatural amino acids (UAAs) containing reactive functional groups that are chemically orthogonal to those of the 20 amino acids found naturally in proteins. These unique functional groups can then be selectively reacted with an appropriately functionalized spin probe. In this chapter, we detail the genetic incorporation of the ketone-bearing amino acid p-acetyl phenylalanine (pAcPhe) into recombinant proteins expressed in E. coli. Incorporation of pAcPhe is followed by chemoselective reaction of the ketone side chain with a hydroxylamine-functionalized nitroxide to afford the spin-labeled side chain “K1,” and we present two protocols for successful K1 labeling of proteins bearing site-specific pAcPhe. We outline the basic requirements for pAcPhe incorporation and labeling, with an emphasis on practical aspects that must be considered by the researcher if high yields of UAA incorporation and efficient labeling reactions are to be achieved. To this end, we highlight recent advances that have led to increased yields of pAcPhe incorporation, and discuss the use of aniline-based catalysts allowing for facile conjugation of the hydroxylamine spin label under mild reaction conditions. To illustrate the utility of K1 labeling in proteins where traditional cysteine-based SDSL methods are problematic, we site-specifically K1 label the cellular prion protein at two positions in the C-terminal domain and determine the interspin distance using double electron–electron resonance EPR. Recent advances in UAA incorporation and ketone-based bioconjugation, in combination with the commercial availability of all requisite

  2. Genetic Incorporation of the Unnatural Amino Acid p-Acetyl Phenylalanine into Proteins for Site-Directed Spin Labeling.

    Science.gov (United States)

    Evans, Eric G B; Millhauser, Glenn L

    2015-01-01

    Site-directed spin labeling (SDSL) is a powerful tool for the characterization of protein structure and dynamics; however, its application in many systems is hampered by the reliance on unique and benign cysteine substitutions for the site-specific attachment of the spin label. An elegant solution to this problem involves the use of genetically encoded unnatural amino acids (UAAs) containing reactive functional groups that are chemically orthogonal to those of the 20 amino acids found naturally in proteins. These unique functional groups can then be selectively reacted with an appropriately functionalized spin probe. In this chapter, we detail the genetic incorporation of the ketone-bearing amino acid p-acetyl phenylalanine (pAcPhe) into recombinant proteins expressed in E. coli. Incorporation of pAcPhe is followed by chemoselective reaction of the ketone side chain with a hydroxylamine-functionalized nitroxide to afford the spin-labeled side chain "K1," and we present two protocols for successful K1 labeling of proteins bearing site-specific pAcPhe. We outline the basic requirements for pAcPhe incorporation and labeling, with an emphasis on practical aspects that must be considered by the researcher if high yields of UAA incorporation and efficient labeling reactions are to be achieved. To this end, we highlight recent advances that have led to increased yields of pAcPhe incorporation, and discuss the use of aniline-based catalysts allowing for facile conjugation of the hydroxylamine spin label under mild reaction conditions. To illustrate the utility of K1 labeling in proteins where traditional cysteine-based SDSL methods are problematic, we site-specifically K1 label the cellular prion protein at two positions in the C-terminal domain and determine the interspin distance using double electron-electron resonance EPR. Recent advances in UAA incorporation and ketone-based bioconjugation, in combination with the commercial availability of all requisite reagents

  3. Direct evidence for active site-dependent formic acid electro-oxidation by topmost-surface atomic redistribution in a ternary PtPdCu electrocatalyst.

    Science.gov (United States)

    Cui, Chun-Hua; Li, Hui-Hui; Cong, Huai-Ping; Yu, Shu-Hong; Tao, Franklin Feng

    2012-12-25

    The active site-dependent electrochemical formic acid oxidation was evidenced by the increased coverage of Pt in the topmost mixed PtPd alloy layer of ternary PtPdCu upon potential cycling, which demonstrated two catalytic pathways only in one catalyst owing to surface atomic redistribution in an acidic electrolyte environment.

  4. Element mobility during pyrite weathering: implications for acid and heavy metal pollution at mining-impacted sites

    Science.gov (United States)

    Lu, Long; Wang, Rucheng; Chen, Fanrong; Xue, Jiyue; Zhang, Peihua; Lu, Jianjun

    2005-11-01

    Based on back scattered electron images and electron micro-probe analysis results, four alteration layers, including a transition layer, a reticulated ferric oxide layer, a nubby ferric oxide layer and a cellular ferric oxide layer, were identified in the naturally weathering products of pyrite. These layers represent a progressive alteration sequence of pyrite under weathering conditions. The cellular ferric oxide layer correlates with the strongest weathering phase and results from the dissolution of nubby ferric oxide by acidic porewater. Leaching coefficient was introduced to better express the response of element mobility to the degree of pyrite weathering. Its variation shows that the mobility of S, Co and Bi is stronger than As, Cu and Zn. Sulfur in pyrite is oxidized to sulfuric acid and sulfate that are basically released into to porewater, and heavy metals Co and Bi are evidently released by acid dissolution. As, Cu and Zn are enriched in ferric oxide by adsorption and by co-precipitation, but they would re-release to the environment via desorption or dissolution when porewater pH becomes low enough. Consequently, Co, Bi, As, Cu and Zn may pose a substantial impact on water quality. Considering that metal mobility and its concentration in mine waste are two important factors influencing heavy metal pollution at mining-impacted sites, Bi and Co are more important pollutants in this case.

  5. The role of amino acid residues in the active site of L-methionine γ-lyase from Pseudomonas putida.

    Science.gov (United States)

    Fukumoto, Mitsuki; Kudou, Daizou; Murano, Shouko; Shiba, Tomoo; Sato, Dan; Tamura, Takashi; Harada, Shigeharu; Inagaki, Kenji

    2012-01-01

    Cys116, Lys240*, and Asp241* (asterisks indicate residues from the second subunit of the active dimer) at the active site of L-methionine γ-lyase of Pseudomonas putida (MGL_Pp) are highly conserved among heterologous MGLs. In a previous study, we found that substitution of Cys116 for His led to a drastic increase in activity toward L-cysteine and a decrease in that toward L-methionine. In this study, we examined some properties of the C116H mutant by kinetic analysis and 3D structural analysis. We assumed that substitution of Cys116 for His broke the original hydrogen-bond network and that this induced a significant effect of Tyr114 as a general acid catalyst, possibly due to the narrow space in the active site. The C116H mutant acquired a novel β-elimination activity and lead a drastic conformation change in the histidine residue at position 116 by binding the substrate, suggesting that this His residue affects the reaction specificity of C116H. Furthermore, we suggest that Lys240* is important for substrate recognition and structural stability and that Asp241* is also involved in substrate specificity in the elimination reaction. Based on this, we suggest that the hydrogen-bond network among Cys116, Lys240*, and Asp241* contributes to substrate specificity that is, to L-methionine recognition at the active site in MGL_Pp.

  6. Spectroscopic insights into the nature of active sites in iron–nitrogen–carbon electrocatalysts for oxygen reduction in acid

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Qingying; Ramaswamy, Nagappan; Tylus, Urszula; Strickland, Kara; Li, Jingkun; Serov, Alexey; Artyushkova, Kateryna; Atanassov, Plamen; Anibal, Jacob; Gumeci, Cenk; Barton, Scott Calabrese; Sougrati, Moulay-Tahar; Jaouen, Frederic; Halevi, Barr; Mukerjee, Sanjeev (NEU); (UNM); (CNRS-UMR); (General Motors); (Pajarito); (MSU)

    2016-11-01

    Developing efficient and inexpensive catalysts for the sluggish oxygen reduction reaction (ORR) constitutes one of the grand challenges in the fabrication of commercially viable fuel cell devices and metal–air batteries for future energy applications. Despite recent achievements in designing advanced Pt-based and Pt-free catalysts, current progress primarily involves an empirical approach of trial-and-error combination of precursors and synthesis conditions, which limits further progress. Rational design of catalyst materials requires proper understanding of the mechanistic origin of the ORR and the underlying surface properties under operating conditions that govern catalytic activity. Herein, several different groups of iron-based catalysts synthesized via different methods and/or precursors were systematically studied by combining multiple spectroscopic techniques under ex situ and in situ conditions in an effort to obtain a comprehensive understanding of the synthesis-products correlations, nature of active sites, and the reaction mechanisms. These catalysts include original macrocycles, macrocycle-pyrolyzed catalysts, and Fe-N–C catalysts synthesized from individual Fe, N, and C precursors including polymer-based catalysts, metal organic framework (MOF)-based catalysts, and sacrificial support method (SSM)-based catalysts. The latter group of catalysts is most promising as not only they exhibit exceptional ORR activity and/or durability, but also the final products are controllable. We show that the high activity observed for most pyrolyzed Fe-based catalysts can mainly be attributed to a single active site: non-planar Fe–N4 moiety embedded in distorted carbon matrix characterized by a high potential for the Fe2+/3+ redox transition in acidic electrolyte/environment. The high intrinsic ORR activity, or turnover frequency (TOF), of this site is shown to be accounted for by redox catalysis mechanism that highlights the dominant role

  7. Evolvability Is an Evolved Ability: The Coding Concept as the Arch-Unit of Natural Selection.

    Science.gov (United States)

    Janković, Srdja; Ćirković, Milan M

    2016-03-01

    Physical processes that characterize living matter are qualitatively distinct in that they involve encoding and transfer of specific types of information. Such information plays an active part in the control of events that are ultimately linked to the capacity of the system to persist and multiply. This algorithmicity of life is a key prerequisite for its Darwinian evolution, driven by natural selection acting upon stochastically arising variations of the encoded information. The concept of evolvability attempts to define the total capacity of a system to evolve new encoded traits under appropriate conditions, i.e., the accessible section of total morphological space. Since this is dependent on previously evolved regulatory networks that govern information flow in the system, evolvability itself may be regarded as an evolved ability. The way information is physically written, read and modified in living cells (the "coding concept") has not changed substantially during the whole history of the Earth's biosphere. This biosphere, be it alone or one of many, is, accordingly, itself a product of natural selection, since the overall evolvability conferred by its coding concept (nucleic acids as information carriers with the "rulebook of meanings" provided by codons, as well as all the subsystems that regulate various conditional information-reading modes) certainly played a key role in enabling this biosphere to survive up to the present, through alterations of planetary conditions, including at least five catastrophic events linked to major mass extinctions. We submit that, whatever the actual prebiotic physical and chemical processes may have been on our home planet, or may, in principle, occur at some time and place in the Universe, a particular coding concept, with its respective potential to give rise to a biosphere, or class of biospheres, of a certain evolvability, may itself be regarded as a unit (indeed the arch-unit) of natural selection.

  8. Evolvability Is an Evolved Ability: The Coding Concept as the Arch-Unit of Natural Selection

    Science.gov (United States)

    Janković, Srdja; Ćirković, Milan M.

    2016-03-01

    Physical processes that characterize living matter are qualitatively distinct in that they involve encoding and transfer of specific types of information. Such information plays an active part in the control of events that are ultimately linked to the capacity of the system to persist and multiply. This algorithmicity of life is a key prerequisite for its Darwinian evolution, driven by natural selection acting upon stochastically arising variations of the encoded information. The concept of evolvability attempts to define the total capacity of a system to evolve new encoded traits under appropriate conditions, i.e., the accessible section of total morphological space. Since this is dependent on previously evolved regulatory networks that govern information flow in the system, evolvability itself may be regarded as an evolved ability. The way information is physically written, read and modified in living cells (the "coding concept") has not changed substantially during the whole history of the Earth's biosphere. This biosphere, be it alone or one of many, is, accordingly, itself a product of natural selection, since the overall evolvability conferred by its coding concept (nucleic acids as information carriers with the "rulebook of meanings" provided by codons, as well as all the subsystems that regulate various conditional information-reading modes) certainly played a key role in enabling this biosphere to survive up to the present, through alterations of planetary conditions, including at least five catastrophic events linked to major mass extinctions. We submit that, whatever the actual prebiotic physical and chemical processes may have been on our home planet, or may, in principle, occur at some time and place in the Universe, a particular coding concept, with its respective potential to give rise to a biosphere, or class of biospheres, of a certain evolvability, may itself be regarded as a unit (indeed the arch-unit) of natural selection.

  9. Anethole Isomerization and Dimerization Induced by Acid Sites or UV Irradiation

    Directory of Open Access Journals (Sweden)

    Elena Stashenko

    2010-07-01

    Full Text Available The formation of cis-anethole and various dimers as a result of the exposure of trans-anethole to microporous solid acids (dealuminated HY zeolites, or UV-Vis irradiation was established by means of high resolution gas chromatography coupled to mass spectrometry. 3,4-bis-(4-Methoxyphenyl-(E-hex-2-ene was the most abundant compound among eight different methoxyphenyl-disubstituted hexenes produced by electrophilic addition and elimination reactions induced by HY zeolites. (1a,2a,3b,4b-1,2-bis(4-Methoxyphenyl-3,4-dimethylcyclobutane was the principal component in the mixture of 5 methoxyphenyl-disubstituted cyclobutanes found, together with cis-anethole, after UV-Vis irradiation of a trans-anethole solution in toluene.

  10. Synthesis and Site-Specific Incorporation of Red-Shifted Azobenzene Amino Acids into Proteins.

    Science.gov (United States)

    John, Alford A; Ramil, Carlo P; Tian, Yulin; Cheng, Gang; Lin, Qing

    2015-12-18

    A series of red-shifted azobenzene amino acids were synthesized in moderate-to-excellent yields via a two-step procedure in which tyrosine derivatives were first oxidized to the corresponding quinonoidal spirolactones followed by ceric ammonium nitrate-catalyzed azo formation with the substituted phenylhydrazines. The resulting azobenzene-alanine derivatives exhibited efficient trans/cis photoswitching upon irradiation with a blue (448 nm) or green (530 nm) LED light. Moreover, nine superfolder green fluorescent protein (sfGFP) mutants carrying the azobenzene-alanine analogues were expressed in E. coli in good yields via amber codon suppression with an orthogonal tRNA/PylRS pair, and one of the mutants showed durable photoswitching with the LED light.

  11. Site-Selective Binding of Nanoparticles to Double-Stranded DNA via Peptide Nucleic Acid "Invasion"

    Energy Technology Data Exchange (ETDEWEB)

    Stadler, A.L.; van der Lelie, D.; Sun, D.; Maye, M. M.; Gang, O.

    2011-04-01

    We demonstrate a novel method for by-design placement of nano-objects along double-stranded (ds) DNA. A molecular intercalator, designed as a peptide nucleic acid (PNA)-DNA chimera, is able to invade dsDNA at the PNA-side due to the hybridization specificity between PNA and one of the duplex strands. At the same time, the single-stranded (ss) DNA tail of the chimera, allows for anchoring of nano-objects that have been functionalized with complementary ssDNA. The developed method is applied for interparticle attachment and for the fabrication of particle clusters using a dsDNA template. This method significantly broadens the molecular toolbox for constructing nanoscale systems by including the most conventional not yet utilized DNA motif, double helix DNA.

  12. Policy for metal leaching and acid rock drainage at mine sites in British Columbia

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-07-01

    One of the major environmental issues facing the provincial government of British Columbia is the prevention of environmental impacts from metal leaching and acid rock drainage (ML/ARD). The government`s major challenge in regulating ML/ARD is to ensure that all mines are planned and operated in a manner that allows for effective problem detection and mitigation, and that the mines emphasize problem prevention at the outset. This paper reviews the legislated requirements regarding ML/ARD prevention and lists guiding principles for the regulation of ML/ARD in the province. Some of the measures to predict and to mitigate ML/ARD include underwater storage of problematic materials, engineered covers, blending of wastes and drainage collection and treatment. Requirements applicable to construction materials, backfill, geotechnical and hydrological considerations, and security of funds for ML/ARD measures are also discussed.

  13. Effects of jasmonic acid signalling on the wheat microbiome differ between body sites

    Science.gov (United States)

    Liu, Hongwei; Carvalhais, Lilia C.; Schenk, Peer M.; Dennis, Paul G.

    2017-01-01

    Jasmonic acid (JA) signalling helps plants to defend themselves against necrotrophic pathogens and herbivorous insects and has been shown to influence the root microbiome of Arabidopsis thaliana. In this study, we determined whether JA signalling influences the diversity and functioning of the wheat (Triticum aestivum) microbiome and whether these effects are specific to particular parts of the plant. Activation of the JA pathway was achieved via exogenous application of methyl jasmonate and was confirmed by significant increases in the abundance of 10 JA-signalling-related gene transcripts. Phylogenetic marker gene sequencing revealed that JA signalling reduced the diversity and changed the composition of root endophytic but not shoot endophytic or rhizosphere bacterial communities. The total enzymatic activity and substrate utilisation profiles of rhizosphere bacterial communities were not affected by JA signalling. Our findings indicate that the effects of JA signalling on the wheat microbiome are specific to individual plant compartments. PMID:28134326

  14. Complete amino acid sequence of Mytilus anterior byssus retractor paramyosin and its putative phosphorylation site.

    Science.gov (United States)

    Watabe, S; Iwasaki, K; Funabara, D; Hirayama, Y; Nakaya, M; Kikuchi, K

    2000-01-01

    A cDNA encoding the full-length paramyosin molecule was cloned from the mussel Mytilus galloprovincialis, a species closely related to Mytilus edulis. It contained 3,497 nucleotides (nt), with 79 and 826 nt for the 5' and 3' non-coding regions, respectively. The coding region was composed of 2,592 nt for 864 amino acid residues, a size typical of paramyosin. While genomic DNA digests with either HindIII or PstI exhibited a single band when hybridized with a SacI fragment of paramyosin cDNA, the digests with either EcoRV or EcoRI showed two bands, suggesting that the mussel has at least two genes encoding paramyosin. The mRNAs encoding paramyosin were most abundant in muscle tissues from byssus retractor and adductor muscles. Only traces of paramyosin transcripts were found in the tissue of foot, gill, inner mantle, and outer mantle. The same phosphorylatable peptide previously reported for paramyosin from the bivalve Mercenaria mercenaria, Ser-Arg-Ser-Met-Ser(P)-Val-Ser-Arg (Watabe et al. 1989. Comp Biochem Physiol 94B:813-821) was found in the C-terminal non-helical part of this Mytilus paramyosin. We predict that this particular paramyosin has a coiled-coil structure composed of two alpha-helices that show the heptad repeats (a-b-c-d-e-f-g) with further 28-amino acid repeat zones, where a and d tend to be occupied by nonpolar residues.

  15. Binding site of ribosomal proteins on prokaryotic 5S ribonucleic acids: a study with ribonucleases

    DEFF Research Database (Denmark)

    Douthwaite, S; Christensen, A; Garrett, R A

    1982-01-01

    The binding sites of ribosomal proteins L18 and L25 on 5S RNA from Escherichia coli were probed with ribonucleases A, T1, and T2 and a double helix specific cobra venom endonuclease. The results for the protein-RNA complexes, which were compared with those for the free RNA [Douthwaite, S...... stearothermophilus 5S RNA. Several protein-induced changes in the RNA structures were identified; some are possibly allosteric in nature. The two prokaryotic 5S RNAs were also incubated with total 50S subunit proteins from E. coli and B. stearothermophilus ribosomes. Homologous and heterologous reconstitution....... stearothermophilus 5S RNA, which may have been due to a third ribosomal protein L5....

  16. A Wood-Waste Cover Prevents Sulphide Oxidation and Treats Acid Effluents at the East-Sullivan Mine Site

    Science.gov (United States)

    Germain, D.; Tassé, N.; Cyr, J.

    2004-05-01

    At the East Sullivan site, wood wastes covering the abandoned mine tailings impoundment prevent sulphide oxidation by creating an anoxic environment. The addition of coarse ligneous wastes favours infiltration, resulting in a water table rise. This maintains most tailings saturated and thus provides an additional protection against sulphide oxidation. Moreover, high infiltration allows a more rapid flushing of acid prone groundwater generated prior to the cover placement. Finally, the pore-waters under the cover are characterized by a strong reducing potential and high alkalinity. These conditions favour sulphate reduction and base metal precipitation as sulphides and carbonates. The restoration strategy capitalized on the alkaline and reductive properties of the waters underlying the wood-waste cover. An original treatment of acid effluents, based on the recirculation of water discharging around the impoundment through the organic cover, was implemented in 1998. In 2003, the total volume of water treated was 725 000 m3. Data gathered near the dispersal zone show that despite dispersing acid water, the groundwater pH decreases by only one unit from 7 to 6, during the recirculation period: May to October. However, alkalinity decreases from 800 to 100 mg/L-CaCO3. But it is back up to 800 mg/L the following spring, thanks to sulphate reduction. Fe2+ concentrations near the dispersal zone are maintained below 2 mg/L. Evolution of the iron mass in the surface waters suggests that the contaminated groundwater flush is completed in the north and west sectors of the impoundment; the east and south ones are expected to be recovered within 3 to 4 years. A wood-waste cover, besides limiting sulphide oxidation, can fill the role of alkaline reducing barrier for the treatment of these acidogenic waters, until a balance between acidity and alkalinity in the effluent is reached.

  17. Marshal: Maintaining Evolving Models Project

    Data.gov (United States)

    National Aeronautics and Space Administration — SIFT proposes to design and develop the Marshal system, a mixed-initiative tool for maintaining task models over the course of evolving missions. Marshal-enabled...

  18. Exploring the atmospheric chemistry of nitrous acid (HONO at a rural site in Southern China

    Directory of Open Access Journals (Sweden)

    X. Li

    2012-02-01

    Full Text Available We performed measurements of nitrous acid (HONO during the PRIDE-PRD2006 campaign in the Pearl River Delta region 60 km north of Guangzhou, China, for 4 weeks in June 2006. HONO was measured by a LOPAP in-situ instrument which was setup in one of the campaign supersites along with a variety of instruments measuring hydroxyl radicals, trace gases, aerosols, and meteorological parameters. Maximum diurnal HONO mixing ratios of 1–5 ppb were observed during the nights. We found that the nighttime build-up of HONO can be attributed to the heterogeneous NO2 to HONO conversion on ground surfaces and the OH + NO reaction. In addition to elevated nighttime mixing ratios, measured noontime values of ≈200 ppt indicate the existence of a daytime source higher than the OH + NO→HONO reaction. Using the simultaneously recorded OH, NO, and HONO photolysis frequency, a daytime additional source strength of HONO (PM was calculated to be 0.77 ppb h−1 on average. This value compares well to previous measurements in other environments. Our analysis of PM provides evidence that the photolysis of HNO3 adsorbed on ground surfaces contributes to the HONO formation.

  19. Acid mine drainage risks - A modeling approach to siting mine facilities in Northern Minnesota USA

    Science.gov (United States)

    Myers, Tom

    2016-02-01

    Most watershed-scale planning for mine-caused contamination concerns remediation of past problems while future planning relies heavily on engineering controls. As an alternative, a watershed scale groundwater fate and transport model for the Rainy Headwaters, a northeastern Minnesota watershed, has been developed to examine the risks of leaks or spills to a pristine downstream watershed. The model shows that the risk depends on the location and whether the source of the leak is on the surface or from deeper underground facilities. Underground sources cause loads that last longer but arrive at rivers after a longer travel time and have lower concentrations due to dilution and attenuation. Surface contaminant sources could cause much more short-term damage to the resource. Because groundwater dominates baseflow, mine contaminant seepage would cause the most damage during low flow periods. Groundwater flow and transport modeling is a useful tool for decreasing the risk to downgradient sources by aiding in the placement of mine facilities. Although mines are located based on the minerals, advance planning and analysis could avoid siting mine facilities where failure or leaks would cause too much natural resource damage. Watershed scale transport modeling could help locate the facilities or decide in advance that the mine should not be constructed due to the risk to downstream resources.

  20. Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T

    1997-01-01

    Full Text Available Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

  1. Multi-component reactive transport modeling of natural attenuation of an acid groundwater plume at a uranium mill tailings site

    Science.gov (United States)

    Zhu, Chen; Hu, Fang Q.; Burden, David S.

    2001-11-01

    Natural attenuation of an acidic plume in the aquifer underneath a uranium mill tailings pond in Wyoming, USA was simulated using the multi-component reactive transport code PHREEQC. A one-dimensional model was constructed for the site and the model included advective-dispersive transport, aqueous speciation of 11 components, and precipitation-dissolution of six minerals. Transport simulation was performed for a reclamation scenario in which the source of acidic seepage will be terminated after 5 years and the plume will then be flushed by uncontaminated upgradient groundwater. Simulations show that successive pH buffer reactions with calcite, Al(OH) 3(a), and Fe(OH) 3(a) create distinct geochemical zones and most reactions occur at the boundaries of geochemical zones. The complex interplay of physical transport processes and chemical reactions produce multiple concentration waves. For SO 42- transport, the concentration waves are related to advection-dispersion, and gypsum precipitation and dissolution. Wave speeds from numerical simulations compare well to an analytical solution for wave propagation.

  2. Succinic acid production from fruit and vegetable wastes hydrolyzed by on-site enzyme mixtures through solid state fermentation.

    Science.gov (United States)

    Dessie, Wubliker; Zhang, Wenming; Xin, Fengxue; Dong, Weiliang; Zhang, Min; Ma, Jiangfeng; Jiang, Min

    2017-09-01

    In this study, a novel biorefinery concept of succinic acid (SA) production from fruit and vegetable wastes (FVWs) hydrolyzed by crude enzyme mixtures through solid state fermentation was designed. Enzyme complex solid mashes from various types of FVWs were on-site produced through solid-state fermentation by Aspergillus niger and Rhizopus oryzae. This solid was then added to FVW suspensions and undergo hydrolysis reaction to generate fermentable sugars and other essential nutrients for bacterial growth and product formation. The subsequent fungal hydrolysis produced 12.00g/L glucose and 13.83g/L fructose using 10% mass ratio (w/v) of FVW. Actinobacillus succinogenes used this FVW hydrolysate as the sole feedstock and produced 27.03g/L of succinic acid with high yield and productivity of 1.18gSA/g sugar and 1.28gL(-1)h(-1), respectively. This work demonstrated that FVWs can be biotransformed to value added products which have considerable potential economics and environmental meaning. Copyright © 2017. Published by Elsevier Ltd.

  3. The Evolving Demographic and Health Transition in Four Low- and Middle-Income Countries: Evidence from Four Sites in the INDEPTH Network of Longitudinal Health and Demographic Surveillance Systems.

    Directory of Open Access Journals (Sweden)

    Ayaga Bawah

    Full Text Available This paper contributes evidence documenting the continued decline in all-cause mortality and changes in the cause of death distribution over time in four developing country populations in Africa and Asia. We present levels and trends in age-specific mortality (all-cause and cause-specific from four demographic surveillance sites: Agincourt (South Africa, Navrongo (Ghana in Africa; Filabavi (Vietnam, Matlab (Bangladesh in Asia. We model mortality using discrete time event history analysis. This study illustrates how data from INDEPTH Network centers can provide a comparative, longitudinal examination of mortality patterns and the epidemiological transition. Health care systems need to be reconfigured to deal simultaneously with continuing challenges of communicable disease and increasing incidence of non-communicable diseases that require long-term care. In populations with endemic HIV, long-term care of HIV patients on ART will add to the chronic care needs of the community.

  4. iMethyl-PseAAC: Identification of Protein Methylation Sites via a Pseudo Amino Acid Composition Approach

    Directory of Open Access Journals (Sweden)

    Wang-Ren Qiu

    2014-01-01

    Full Text Available Before becoming the native proteins during the biosynthesis, their polypeptide chains created by ribosome’s translating mRNA will undergo a series of “product-forming” steps, such as cutting, folding, and posttranslational modification (PTM. Knowledge of PTMs in proteins is crucial for dynamic proteome analysis of various human diseases and epigenetic inheritance. One of the most important PTMs is the Arg- or Lys-methylation that occurs on arginine or lysine, respectively. Given a protein, which site of its Arg (or Lys can be methylated, and which site cannot? This is the first important problem for understanding the methylation mechanism and drug development in depth. With the avalanche of protein sequences generated in the postgenomic age, its urgency has become self-evident. To address this problem, we proposed a new predictor, called iMethyl-PseAAC. In the prediction system, a peptide sample was formulated by a 346-dimensional vector, formed by incorporating its physicochemical, sequence evolution, biochemical, and structural disorder information into the general form of pseudo amino acid composition. It was observed by the rigorous jackknife test and independent dataset test that iMethyl-PseAAC was superior to any of the existing predictors in this area.

  5. A two-helix motif positions the lysophosphatidic acid acyltransferase active site for catalysis within the membrane bilayer.

    Science.gov (United States)

    Robertson, Rosanna M; Yao, Jiangwei; Gajewski, Stefan; Kumar, Gyanendra; Martin, Erik W; Rock, Charles O; White, Stephen W

    2017-08-01

    Phosphatidic acid (PA), the central intermediate in membrane phospholipid synthesis, is generated by two acyltransferases in a pathway conserved in all life forms. The second step in this pathway is catalyzed by 1-acyl-sn-glycerol-3-phosphate acyltransferase, called PlsC in bacteria. Here we present the crystal structure of PlsC from Thermotoga maritima, revealing an unusual hydrophobic/aromatic N-terminal two-helix motif linked to an acyltransferase αβ-domain that contains the catalytic HX4D motif. PlsC dictates the acyl chain composition of the 2-position of phospholipids, and the acyl chain selectivity 'ruler' is an appropriately placed and closed hydrophobic tunnel. We confirmed this by site-directed mutagenesis and membrane composition analysis of Escherichia coli cells that expressed mutant PlsC. Molecular dynamics (MD) simulations showed that the two-helix motif represents a novel substructure that firmly anchors the protein to one leaflet of the membrane. This binding mode allows the PlsC active site to acylate lysophospholipids within the membrane bilayer by using soluble acyl donors.

  6. Encapsulating Metal Clusters and Acid Sites within Small Voids: Synthetic Strategies and Catalytic Consequences

    Science.gov (United States)

    Goel, Sarika

    The selective encapsulation of metal clusters within zeolites can be used to prepare clusters that are uniform in diameter and to protect them against sintering and contact with feed impurities, while concurrently allowing active sites to select reactants based on their molecular size, thus conferring enzyme-like specificity to chemical catalysis. The apertures in small and medium-pore zeolites preclude the use of post-synthetic protocols to encapsulate the relevant metal precursors because cationic or anionic precursors with their charge-balancing double layer and gaseous complexes cannot diffuse through their windows or channels. We have developed general strategies to encapsulate metal clusters within small-pore zeolites by using metal precursors stabilized by ammonia or organic amine ligands, which stabilize metal precursors against their premature precipitation at the high temperature and pH conditions required for the hydrothermal synthesis of the target zeolite structures and favor interactions between metal precursors and incipient aluminosilicate nuclei during the self-assembly of microporous frameworks. When synthesis temperatures were higher than 400 K, available ligands were unable to prevent the premature precipitation of the metal precursors. In such cases, encapsulation was achieved instead via interzeolite transformations after successfully encapsulating metal precursors or clusters via post-synthesis exchange or ligand protection into parent zeolites and subsequently converting them into the target structures while retaining the encapsulated clusters or precursors. Such strategies led to the successful selective encapsulation of a wide range of metal clusters (Pt, Pd, Ru, Rh, Ir, Re, and Ag) within small-pore (SOD (sodalite), LTA (Linde type A (zeolite A)), GIS (gismondine), and ANA (analcime)) and medium-pore (MFI (ZSM-5)) zeolites. These protocols provide novel and diverse mechanism-based strategies for the design of catalysts with protected

  7. Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1∙Nup98)

    Energy Technology Data Exchange (ETDEWEB)

    Quan, Beili; Seo, Hyuk-Soo; Blobel, Günter; Ren, Yi [Rockefeller

    2014-07-01

    mRNA export factor 1 (Rae1) and nucleoporin 98 (Nup98) are host cell targets for the matrix (M) protein of vesicular stomatitis virus (VSV). How Rae1 functions in mRNA export and how M protein targets both Rae1 and Nup98 are not understood at the molecular level. To obtain structural insights, we assembled a 1:1:1 complex of M•Rae1•Nup98 and established a crystal structure at 3.15-Å resolution. We found that the M protein contacts the Rae1•Nup98 heterodimer principally by two protrusions projecting from the globular domain of M like a finger and thumb. Both projections clamp to the side of the β-propeller of Rae1, with the finger also contacting Nup98. The most prominent feature of the finger is highly conserved Methionine 51 (Met51) with upstream and downstream acidic residues. The complementary surface on Rae1 displays a deep hydrophobic pocket, into which Met51 fastens like a bolt, and a groove of basic residues on either side, which bond to the acidic residues of the finger. Notably, the M protein competed for in vitro binding of various oligonucleotides to Rae1•Nup98. We localized this competing activity of M to its finger using a synthetic peptide. Collectively, our data suggest that Rae1 serves as a binding protein for the phosphate backbone of any nucleic acid and that the finger of M mimics this ligand. In the context of mRNA export, we propose that a given mRNA segment, after having been deproteinated by helicase, is transiently reproteinated by Nup98-tethered Rae1. We suggest that such repetitive cycles provide cytoplasmic stopover sites required for ratcheting mRNA across the nuclear pore.

  8. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

    1994-07-01

    Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).

  9. Structural model for gamma-aminobutyric acid receptor noncompetitive antagonist binding: widely diverse structures fit the same site.

    Science.gov (United States)

    Chen, Ligong; Durkin, Kathleen A; Casida, John E

    2006-03-28

    Several major insecticides, including alpha-endosulfan, lindane, and fipronil, and the botanical picrotoxinin are noncompetitive antagonists (NCAs) for the GABA receptor. We showed earlier that human beta(3) homopentameric GABA(A) receptor recognizes all of the important GABAergic insecticides and reproduces the high insecticide sensitivity and structure-activity relationships of the native insect receptor. Despite large structural diversity, the NCAs are proposed to fit a single binding site in the chloride channel lumen lined by five transmembrane 2 segments. This hypothesis is examined with the beta(3) homopentamer by mutagenesis, pore structure studies, NCA binding, and molecular modeling. The 15 amino acids in the cytoplasmic half of the pore were mutated to cysteine, serine, or other residue for 22 mutants overall. Localization of A-1'C, A2'C, T6'C, and L9'C (index numbers for the transmembrane 2 region) in the channel lumen was established by disulfide cross-linking. Binding of two NCA radioligands [(3)H]1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane and [(3)H] 3,3-bis-trifluoromethyl-bicyclo[2,2,1]heptane-2,2-dicarbonitrile was dramatically reduced with 8 of the 15 mutated positions, focusing attention on A2', T6', and L9' as proposed binding sites, consistent with earlier mutagenesis studies. The cytoplasmic half of the beta3 homopentamer pore was modeled as an alpha-helix. The six NCAs listed above plus t-butylbicyclophosphorothionate fit the 2' to 9' pore region forming hydrogen bonds with the T6' hydroxyl and hydrophobic interactions with A2', T6', and L9' alkyl substituents, thereby blocking the channel. Thus, widely diverse NCA structures fit the same GABA receptor beta subunit site with important implications for insecticide cross-resistance and selective toxicity between insects and mammals.

  10. Jack bean (Canavalia ensiformis) urease. Probing acid-base groups of the active site by pH variation.

    Science.gov (United States)

    Krajewska, Barbara; Ciurli, Stefano

    2005-07-01

    A pH-variation study of jack bean (Canavalia ensiformis) urease steady-state kinetic parameters and of the inhibition constant of boric acid, a urease competitive inhibitor, was performed using both noninhibitory organic (MES, HEPES and CHES) and inhibitory inorganic (phosphate) buffers, in an effort to elucidate the functions exercised in the catalysis by the ionizable groups of the enzyme active site. The results obtained are consistent with the requirement for three groups utilized by urease with pK(a)s equal to 5.3+/-0.2, 6.6+/-0.2 and 9.1+/-0.4. Based on the appearance of the ionization step with pK(a)=5.3 in v(max)-pH, K(M)-pH and K(i)-pH profiles, we assigned this group as participating both in the substrate binding and catalytic reaction. As shown by its presence in v(max)-pH and K(M)-pH curves, the obvious role of the group with pK(a)=9.1 is the participation in the catalytic reaction. One function of the group featuring pK(a)=6.6, which was derived from a two-maxima v(max)-pH profile obtained upon increasing phosphate buffer concentration, an effect the first time observed for urease-phosphate systems, is the substrate binding, another possible function being modulation of the active site structure controlled by the ionic strength. It is also possible that the pK(a)=6.6 is a merger of two pK(a)s close in value. The study establishes that regular bell-shaped activity-pH profiles, commonly reported for urease, entail more complex pH-dependent behavior of the urease active site ionizable groups, which could be experimentally derived using species interacting with the enzyme, in addition to changing solution pH and ionic strength.

  11. A mass-spectrometric method for the estimation of the ratio of gamma-carboxyglutamic acid to glutamic acid at specific sites in proteins. Application to the N-terminal region of bovine prothrombin.

    Science.gov (United States)

    Rose, K; Priddle, J D; Offord, R E; Esnouf, M P

    1980-04-01

    When a polypeptide containing gamma-carboxyglutamic acid is decarboxylated in 2H2O, residue of (gamma gamma-2H2)glutamic acid are formed. Subsequent proteolytic digestion produces peptides which contain at each site 2H2-substituted and unsubstituted glutamic acid in the same ratio as existed for gramma-carboxy-substitution. The peptides may be identified and this ratio determined by combined gas chromatography--mass spectrometry. We also discuss decarboxylation in 3H2O followed by amino-acid analysis and Edman degradation.

  12. Novel cooperation experimentally evolved between species.

    Science.gov (United States)

    Harcombe, William

    2010-07-01

    Cooperation violates the view of "nature red in tooth and claw" that prevails in our understanding of evolution, yet examples of cooperation abound. Most work has focused on maintenance of cooperation within a single species through mechanisms such as kin selection. The factors necessary for the evolutionary origin of aiding unrelated individuals such as members of another species have not been experimentally tested. Here, I demonstrate that cooperation between species can be evolved in the laboratory if (1) there is preexisting reciprocation or feedback for cooperation, and (2) reciprocation is preferentially received by cooperative genotypes. I used a two species system involving Salmonella enterica ser. Typhimurium and an Escherichia coli mutant unable to synthesize an essential amino acid. In lactose media Salmonella consumes metabolic waste from E. coli, thus creating a mechanism of reciprocation for cooperation. Growth in a spatially structured environment assured that the benefits of cooperation were preferentially received by cooperative genotypes. Salmonella evolved to aid E. coli by excreting a costly amino acid, however this novel cooperation disappeared if the waste consumption or spatial structure were removed. This study builds on previous work to demonstrate an experimental origin of interspecific cooperation, and to test the factors necessary for such interactions to arise.

  13. Determination of the positions of aluminum atoms introduced into SSZ-35 and the catalytic properties of the generated Brønsted acid sites.

    Science.gov (United States)

    Miyaji, Akimitsu; Kimura, Nobuhiro; Shiga, Akinobu; Hayashi, Yoshihiro; Nishitoba, Toshiki; Motokura, Ken; Baba, Toshihide

    2017-03-01

    The positions of aluminum (Al) atoms in SSZ-35 together with the characteristics of the generated protons were investigated by (27)Al multiple quantum magic-angle spinning (MQ-MAS), (29)Si MAS, and (1)H MAS NMR data analyses accompanied by a variable temperature (1)H MAS NMR analysis. The origin of the acidic -OH groups (Brønsted acid sites) generated by introducing Al atoms into the T sites was investigated and the T sites introduced into the Al atoms were revealed. To further determine the catalytic properties of the acidic protons generated in SSZ-35, the influence of the concentration of the Al atoms on the catalytic activity and selectivity during the transformation of toluene was examined.

  14. Hydrogeology and ground-water quality of the Chromic Acid Pit site, US Army Air Defense Artillery Center and Fort Bliss, El Paso, Texas

    Science.gov (United States)

    Abeyta, Cynthia G.; Thomas, C.L.

    1996-01-01

    The Chromic Acid Pit site is an inactive waste disposal site that is regulated by the Resource Conservation and Recovery Act of 1976. The 2.2-cubic-yard cement-lined pit was operated from 1980 to 1983 by a contractor to the U.S. Army Air Defense Artillery Center and Fort Bliss. The pit, located on the Fort Bliss military reservation, in El Paso, Texas, was used for disposal and evaporation of chromic acid waste generated from chrome plating operations. The site was certified closed in 1989 and the Texas Natural Resources Conservation Commission issued Permit Number HW-50296 (U.S. Environmental Protection Agency Permit Number TX4213720101), which approved and implemented post-closure care for the Chromic Acid Pit site. In accordance with an approved post-closure plan, the U.S. Geological Survey is cooperating with the U.S. Army in evaluating hydrogeologic conditions and ground- water quality at the site. One upgradient and two downgradient ground-water monitoring wells were installed adjacent to the chromic acid pit by a private contractor. Quarterly ground-water sampling of these wells by the U.S. Geological Survey began in December 1993. The Chromic Acid Pit site is situated in the Hueco Bolson intermontane valley. The Hueco Bolson is a primary source of ground water in the El Paso area. City of El Paso and U.S. Army water-supply wells are located on all sides of the study area and are completed 600 to more than 1,200 feet below land surface. The ground-water level in the area of the Chromic Acid Pit site has declined about 25 feet from 1982 to 1993. Depth to water at the Chromic Acid Pit site in September 1994 was about 284 feet below land surface; ground-water flow is to the southeast. Ground-water samples collected from monitoring wells at the Chromic Acid Pit site contained dissolved-solids concentrations of 442 to 564 milligrams per liter. Nitrate as nitrogen concentrations ranged from 2.1 to 2.7 milligrams per liter; nitrite plus nitrate as nitrogen

  15. The role of outer surface/inner bulk Brønsted acidic sites in the adsorption of a large basic molecule (simazine) on H-Y zeolite.

    Science.gov (United States)

    Sannino, Filomena; Pansini, Michele; Marocco, Antonello; Bonelli, Barbara; Garrone, Edoardo; Esposito, Serena

    2015-11-21

    The simple means adopted for investigating H-Y zeolite acidity in water is the pH-dependence of the amount of a basic molecule adsorbed under isochoric conditions, a technique capable of yielding, under equilibrium conditions, an estimate of the pKa value of the involved acidic centres: the behaviour with temperature of adsorbed amounts yields instead some information on thermodynamics. Simazine (Sim, 2-chloro-4,6-bis(ethylamino)-s-triazine) was chosen as an adsorbate because its transverse dimension (7.5 Å) is close to the opening of the supercage in the faujasite structure of H-Y (7.4 Å). In short term measurements, Sim adsorption at 25 °C occurs only at the outer surface of H-Y particles. Two types of mildly acidic centres are present (with pKaca. 7 and ca. 8, respectively) and no strong one is observed. Previous adsorption of ammonia from the gas phase discriminates between the two. The former survives, and shows features common with the silanols of amorphous silica. The latter is suppressed: because of this and other features distinguishing this site from silanol species (e.g. the formation of dimeric Sim2H(+) species, favoured by coverage and unfavoured by temperatures of adsorption higher than ambient temperature) a candidate is an Al based site. We propose a Lewis centre coordinating a water molecule, exhibiting acidic properties. This acidic water molecule can be replaced by the stronger base ammonia, also depleting inner strong Brønsted sites. A mechanism for the generation of the two sites from surface Brønsted species is proposed. Long term adsorption measurements at 25 °C already show the onset of the interaction with inner strongly acidic Brønsted sites: because of its size, activation is required for Sim to pass the supercage openings and reach inner acidic sites. When adsorption is run at 40-50 °C, uptake is much larger and increases with temperature. Isochoric measurements suggest a pKa value of ca. 3 compatible with its marked acidic

  16. Evolving sensitivity balances Boolean Networks.

    Directory of Open Access Journals (Sweden)

    Jamie X Luo

    Full Text Available We investigate the sensitivity of Boolean Networks (BNs to mutations. We are interested in Boolean Networks as a model of Gene Regulatory Networks (GRNs. We adopt Ribeiro and Kauffman's Ergodic Set and use it to study the long term dynamics of a BN. We define the sensitivity of a BN to be the mean change in its Ergodic Set structure under all possible loss of interaction mutations. In silico experiments were used to selectively evolve BNs for sensitivity to losing interactions. We find that maximum sensitivity was often achievable and resulted in the BNs becoming topologically balanced, i.e. they evolve towards network structures in which they have a similar number of inhibitory and excitatory interactions. In terms of the dynamics, the dominant sensitivity strategy that evolved was to build BNs with Ergodic Sets dominated by a single long limit cycle which is easily destabilised by mutations. We discuss the relevance of our findings in the context of Stem Cell Differentiation and propose a relationship between pluripotent stem cells and our evolved sensitive networks.

  17. Evolving Objects for Software Engineering

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper is concerned with evolving objects method for softwaredesign that can adapt to the changing environments and requirements automatically. We presen t system architecture with objects library, where there are objects based on dom ain ontologies. We define some genetic operators for objects, and discuss how to apply these genetic operators on objects to get new objects, which can satisfy new requirements.

  18. Active site modification of the β-ketoacyl-ACP synthase FabF3 of Streptomyces coelicolor affects the fatty acid chain length of the CDA lipopeptides.

    Science.gov (United States)

    Lewis, Richard A; Nunns, Laura; Thirlway, Jenny; Carroll, Kathleen; Smith, Colin P; Micklefield, Jason

    2011-02-14

    Using site directed mutagenesis we altered an active site residue (Phe107) of the enzyme encoded by fabF3 (SCO3248) in the Streptomyces coelicolor gene cluster required for biosynthesis of the calcium dependent antibiotics (CDAs), successfully generating two novel CDA derivatives comprising truncated (C4) lipid side chains and confirming that fabF3 encodes a KAS-II homologue that is involved in determining CDA fatty acid chain length.

  19. Rapid, transient, and highly localized induction of plastidial omega-3 fatty acid desaturase mRNA at fungal infection sites in Petroselinum crispum.

    Science.gov (United States)

    Kirsch, C; Takamiya-Wik, M; Reinold, S; Hahlbrock, K; Somssich, I E

    1997-03-04

    Parsley (Petroselinum crispum) plants and suspension-cultured cells have been used extensively for studies of non-host-resistance mechanisms in plant/pathogen interactions. We now show that treatment of cultured parsley cells with a defined peptide elicitor of fungal origin causes rapid and large changes in the levels of various unsaturated fatty acids. While linoleic acid decreased and linolenic acid increased steadily for several hours, comparatively sharp increases in oleic acid followed a biphasic time course. In contrast, the overall level of stearic acid remained unaffected. Using a PCR-based approach, a parsley cDNA was isolated sharing high sequence similarity with omega-3 fatty acid desaturases. Subsequent isolation and characterization of a full-length cDNA enabled its functional identification as a plastid-localized omega-3 fatty acid desaturase by complementation of the Arabidopsis thaliana fad7/8 double mutant which is low in trienoic fatty acids. omega-3 Fatty acid desaturase mRNA accumulated rapidly and transiently in elicitor-treated cultured parsley cells, protoplasts, and leaves, as well as highly localized around fungal infection sites in parsley leaf buds. These results indicate that unsaturated fatty acid metabolism is yet another component of the highly complex, transcriptionally regulated pathogen defense response in plants.

  20. Site-directed mutagenesis of HgcA and HgcB reveals amino acid residues important for mercury methylation.

    Science.gov (United States)

    Smith, Steven D; Bridou, Romain; Johs, Alexander; Parks, Jerry M; Elias, Dwayne A; Hurt, Richard A; Brown, Steven D; Podar, Mircea; Wall, Judy D

    2015-05-01

    Methylmercury is a potent neurotoxin that is produced by anaerobic microorganisms from inorganic mercury by a recently discovered pathway. A two-gene cluster, consisting of hgcA and hgcB, encodes two of the proteins essential for this activity. hgcA encodes a corrinoid protein with a strictly conserved cysteine proposed to be the ligand for cobalt in the corrinoid cofactor, whereas hgcB encodes a ferredoxin-like protein thought to be an electron donor to HgcA. Deletion of either gene eliminates mercury methylation by the methylator Desulfovibrio desulfuricans ND132. Here, site-directed mutants of HgcA and HgcB were constructed to determine amino acid residues essential for mercury methylation. Mutations of the strictly conserved residue Cys93 in HgcA, the proposed ligand for the corrinoid cobalt, to Ala or Thr completely abolished the methylation capacity, but a His substitution produced measurable methylmercury. Mutations of conserved amino acids near Cys93 had various impacts on the methylation capacity but showed that the structure of the putative "cap helix" region harboring Cys93 is crucial for methylation function. In the ferredoxin-like protein HgcB, only one of two conserved cysteines found at the C terminus was necessary for methylation, but either cysteine sufficed. An additional, strictly conserved cysteine, Cys73, was also determined to be essential for methylation. This study supports the previously predicted importance of Cys93 in HgcA for methylation of mercury and reveals additional residues in HgcA and HgcB that facilitate the production of this neurotoxin.

  1. The linoleic acid derivative DCP-LA selectively activates PKC-epsilon, possibly binding to the phosphatidylserine binding site.

    Science.gov (United States)

    Kanno, Takeshi; Yamamoto, Hideyuki; Yaguchi, Takahiro; Hi, Rika; Mukasa, Takeshi; Fujikawa, Hirokazu; Nagata, Tetsu; Yamamoto, Satoshi; Tanaka, Akito; Nishizaki, Tomoyuki

    2006-06-01

    This study examined the effect of 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a newly synthesized linoleic acid derivative with cyclopropane rings instead of cis-double bonds, on protein kinase C (PKC) activity. In the in situ PKC assay with reverse-phase high-performance liquid chromatography, DCP-LA significantly activated PKC in PC-12 cells in a concentration-dependent (10 nM-100 microM) manner, with the maximal effect at 100 nM, and the DCP-LA effect was blocked by GF109203X, a PKC inhibitor, or a selective inhibitor peptide of the novel PKC isozyme PKC-epsilon. Furthermore, DCP-LA activated PKC in HEK-293 cells that was inhibited by the small, interfering RNA against PKC-epsilon. In the cell-free PKC assay, of the nine isozymes examined here, DCP-LA most strongly activated PKC-epsilon, with >7-fold potency over other PKC isozymes, in the absence of dioleoyl-phosphatidylserine and 1,2-dioleoyl-sn-glycerol; instead, the DCP-LA action was inhibited by dioleoyl-phosphatidylserine. DCP-LA also activated PKC-gamma, a conventional PKC, but to a much lesser extent compared with that for PKC-epsilon, by a mechanism distinct from PKC-epsilon activation. Thus, DCP-LA serves as a selective activator of PKC-epsilon, possibly by binding to the phosphatidylserine binding site on PKC-epsilon. These results may provide fresh insight into lipid signaling in PKC activation.

  2. In Silico Structure Prediction of Human Fatty Acid Synthase-Dehydratase: A Plausible Model for Understanding Active Site Interactions.

    Science.gov (United States)

    John, Arun; Umashankar, Vetrivel; Samdani, A; Sangeetha, Manoharan; Krishnakumar, Subramanian; Deepa, Perinkulam Ravi

    2016-01-01

    Fatty acid synthase (FASN, UniProt ID: P49327) is a multienzyme dimer complex that plays a critical role in lipogenesis. Consequently, this lipogenic enzyme has gained tremendous biomedical importance. The role of FASN and its inhibition is being extensively researched in several clinical conditions, such as cancers, obesity, and diabetes. X-ray crystallographic structures of some of its domains, such as β-ketoacyl synthase, acetyl transacylase, malonyl transacylase, enoyl reductase, β-ketoacyl reductase, and thioesterase, (TE) are already reported. Here, we have attempted an in silico elucidation of the uncrystallized dehydratase (DH) catalytic domain of human FASN. This theoretical model for DH domain was predicted using comparative modeling methods. Different stand-alone tools and servers were used to validate and check the reliability of the predicted models, which suggested it to be a highly plausible model. The stereochemical analysis showed 92.0% residues in favorable region of Ramachandran plot. The initial physiological substrate β-hydroxybutyryl group was docked into active site of DH domain using Glide. The molecular dynamics simulations carried out for 20 ns in apo and holo states indicated the stability and accuracy of the predicted structure in solvated condition. The predicted model provided useful biochemical insights into the substrate-active site binding mechanisms. This model was then used for identifying potential FASN inhibitors using high-throughput virtual screening of the National Cancer Institute database of chemical ligands. The inhibitory efficacy of the top hit ligands was validated by performing molecular dynamics simulation for 20 ns, where in the ligand NSC71039 exhibited good enzyme inhibition characteristics and exhibited dose-dependent anticancer cytotoxicity in retinoblastoma cancer cells in vitro.

  3. [Preliminary application of injectable calcium phosphate cement/poly (lactic-co-glycolic acid) microspheres for extraction site preservation].

    Science.gov (United States)

    Mai, Yuying; Wu, Huihuang; Mai, Zhisong; Li, Xinghong; Huang, Linhui; Liao, Hongbing

    2014-03-01

    To investigate the feasibility of extraction site preservation using injectable calcium phosphate cement (CPC) combine with poly (lactic-co-glycolic acid) (PLGA) microspheres. Immediate extraction defects models were created in canine mandibles, and the defects were filled with CPC/PLGA (experimental group, E) , Bio-Oss (positive control, P), non-treatment (blank control, B) respectively. Dogs were sacrificed after 4, 8, 12 weeks post operation. Statistical analysis were conducted using SPSS 19. of radiological observation showed that there were not significantly different between groups in 4 and 8 week (P > 0.05). After 12 week,E (114.9 ± 8.4) were not significantly different compared with P (117.4 ± 12.1) (P > 0.05) , both were significantly higher than B (95.0 ± 12.6) (P B[(78.7 ± 2.7)%] > E[(69.2 ± 1.8)%] (P < 0.05). At 8, 12 week, results of P[(94.0 ± 2.3)% and (93.5 ± 1.9) %] and E[ (94.7 ± 1.1) % and (96.0 ± 0.9) %] were better than those of B[ (76.8 ± 3.0)% and (87.0 ± 2.4)%] (P < 0.05). The effect of CPC/PLGA repair immediate alveolar ridge defects is the same as that of Bio-Oss, and CPC/PLGA can be used as a material in extraction site preservation.

  4. Nucleic Acid-Dependent Conformational Changes in CRISPR-Cas9 Revealed by Site-Directed Spin Labeling.

    Science.gov (United States)

    Vazquez Reyes, Carolina; Tangprasertchai, Narin S; Yogesha, S D; Nguyen, Richard H; Zhang, Xiaojun; Rajan, Rakhi; Qin, Peter Z

    2017-06-01

    In a type II clustered regularly interspaced short palindromic repeats (CRISPR) system, RNAs that are encoded at the CRISPR locus complex with the CRISPR-associated (Cas) protein Cas9 to form an RNA-guided nuclease that cleaves double-stranded DNAs at specific sites. In recent years, the CRISPR-Cas9 system has been successfully adapted for genome engineering in a wide range of organisms. Studies have indicated that a series of conformational changes in Cas9, coordinated by the RNA and the target DNA, direct the protein into its active conformation, yet details on these conformational changes, as well as their roles in the mechanism of function of Cas9, remain to be elucidated. Here, nucleic acid-dependent conformational changes in Streptococcus pyogenes Cas9 (SpyCas9) were investigated using the method of site-directed spin labeling (SDSL). Single nitroxide spin labels were attached, one at a time, at one of the two native cysteine residues (Cys80 and Cys574) of SpyCas9, and the spin-labeled proteins were shown to maintain their function. X-band continuous-wave electron paramagnetic resonance spectra of the nitroxide attached at Cys80 revealed conformational changes of SpyCas9 that are consistent with a large-scale domain re-arrangement upon binding to its RNA partner. The results demonstrate the use of SDSL to monitor conformational changes in CRISPR-Cas9, which will provide key information for understanding the mechanism of CRISPR function.

  5. TmiRUSite and TmiROSite scripts: searching for mRNA fragments with miRNA binding sites with encoded amino acid residues

    OpenAIRE

    Berillo, Olga; Régnier, Mireille; Ivashchenko, Anatoly

    2014-01-01

    microRNAs are small RNA molecules that inhibit the translation of target genes. microRNA binding sites are located in the untranslated regions as well as in the coding domains. We describe TmiRUSite and TmiROSite scripts developed using python as tools for the extraction of nucleotide sequences for miRNA binding sites with their encoded amino acid residue sequences. The scripts allow for retrieving a set of additional sequences at left and at right from the binding site. The scripts presents ...

  6. TmiRUSite and TmiROSite scripts: searching for mRNA fragments with miRNA binding sites with encoded amino acid residues

    OpenAIRE

    Berillo, Olga; Régnier, Mireille; Ivashchenko, Anatoly

    2014-01-01

    microRNAs are small RNA molecules that inhibit the translation of target genes. microRNA binding sites are located in the untranslated regions as well as in the coding domains. We describe TmiRUSite and TmiROSite scripts developed using python as tools for the extraction of nucleotide sequences for miRNA binding sites with their encoded amino acid residue sequences. The scripts allow for retrieving a set of additional sequences at left and at right from the binding site. The scripts presents ...

  7. Conformational transition of FGFR kinase activation revealed by site-specific unnatural amino acid reporter and single molecule FRET

    Science.gov (United States)

    Perdios, Louis; Lowe, Alan R.; Saladino, Giorgio; Bunney, Tom D.; Thiyagarajan, Nethaji; Alexandrov, Yuriy; Dunsby, Christopher; French, Paul M. W.; Chin, Jason W.; Gervasio, Francesco Luigi; Tate, Edward W.; Katan, Matilda

    2017-01-01

    Protein kinases share significant structural similarity; however, structural features alone are insufficient to explain their diverse functions. Thus, bridging the gap between static structure and function requires a more detailed understanding of their dynamic properties. For example, kinase activation may occur via a switch-like mechanism or by shifting a dynamic equilibrium between inactive and active states. Here, we utilize a combination of FRET and molecular dynamics (MD) simulations to probe the activation mechanism of the kinase domain of Fibroblast Growth Factor Receptor (FGFR). Using genetically-encoded, site-specific incorporation of unnatural amino acids in regions essential for activation, followed by specific labeling with fluorescent moieties, we generated a novel class of FRET-based reporter to monitor conformational differences corresponding to states sampled by non phosphorylated/inactive and phosphorylated/active forms of the kinase. Single molecule FRET analysis in vitro, combined with MD simulations, shows that for FGFR kinase, there are populations of inactive and active states separated by a high free energy barrier resulting in switch-like activation. Compared to recent studies, these findings support diversity in features of kinases that impact on their activation mechanisms. The properties of these FRET-based constructs will also allow further studies of kinase dynamics as well as applications in vivo.

  8. Scanning mutagenesis of the amino acid sequences flanking phosphorylation site 1 of the mitochondrial pyruvate dehydrogenase complex

    Directory of Open Access Journals (Sweden)

    Nagib eAhsan

    2012-07-01

    Full Text Available The mitochondrial pyruvate dehydrogenase complex is regulated by reversible seryl-phosphorylation of the E1α subunit by a dedicated, intrinsic kinase. The phospho-complex is reactivated when dephosphorylated by an intrinsic PP2C-type protein phosphatase. Both the position of the phosphorylated Ser-residue and the sequences of the flanking amino acids are highly conserved. We have used the synthetic peptide-based kinase client assay plus recombinant pyruvate dehydrogenase E1α and E1α-kinase to perform scanning mutagenesis of the residues flanking the site of phosphorylation. Consistent with the results from phylogenetic analysis of the flanking sequences, the direct peptide-based kinase assays tolerated very few changes. Even conservative changes such as Leu, Ile, or Val for Met, or Glu for Asp, gave very marked reductions in phosphorylation. Overall the results indicate that regulation of the mitochondrial pyruvate dehydrogenase complex by reversible phosphorylation is an extreme example of multiple, interdependent instances of co-evolution.

  9. Conformational transition of FGFR kinase activation revealed by site-specific unnatural amino acid reporter and single molecule FRET

    Science.gov (United States)

    Perdios, Louis; Lowe, Alan R.; Saladino, Giorgio; Bunney, Tom D.; Thiyagarajan, Nethaji; Alexandrov, Yuriy; Dunsby, Christopher; French, Paul M. W.; Chin, Jason W.; Gervasio, Francesco Luigi; Tate, Edward W.; Katan, Matilda

    2017-01-01

    Protein kinases share significant structural similarity; however, structural features alone are insufficient to explain their diverse functions. Thus, bridging the gap between static structure and function requires a more detailed understanding of their dynamic properties. For example, kinase activation may occur via a switch-like mechanism or by shifting a dynamic equilibrium between inactive and active states. Here, we utilize a combination of FRET and molecular dynamics (MD) simulations to probe the activation mechanism of the kinase domain of Fibroblast Growth Factor Receptor (FGFR). Using genetically-encoded, site-specific incorporation of unnatural amino acids in regions essential for activation, followed by specific labeling with fluorescent moieties, we generated a novel class of FRET-based reporter to monitor conformational differences corresponding to states sampled by non phosphorylated/inactive and phosphorylated/active forms of the kinase. Single molecule FRET analysis in vitro, combined with MD simulations, shows that for FGFR kinase, there are populations of inactive and active states separated by a high free energy barrier resulting in switch-like activation. Compared to recent studies, these findings support diversity in features of kinases that impact on their activation mechanisms. The properties of these FRET-based constructs will also allow further studies of kinase dynamics as well as applications in vivo. PMID:28045057

  10. Exploring the mechanism of DNA polymerases by analyzing the effect of mutations of active site acidic groups in Polymerase β.

    Science.gov (United States)

    Matute, Ricardo A; Yoon, Hanwool; Warshel, Arieh

    2016-11-01

    Elucidating the catalytic mechanism of DNA polymerase is crucial for a progress in the understanding of the control of replication fidelity. This work tries to advance the mechanistic understanding by analyzing the observed effect of mutations of the acidic groups in the active site of Polymerase β as well as the pH effect on the rate constant. The analysis involves both empirical valence bond (EVB) free energy calculations and considerations of the observed pH dependence of the reaction. The combined analysis indicates that the proton transfer (PT) from the nucleophilic O3' has two possible pathways, one to D256 and the second to the bulk. We concluded based on calculations and the experimental pH profile that the most likely path for the wild-type (WT) and the D256E and D256A mutants is a PT to the bulk, although the WT may also use a PT to Asp 256. Our analysis highlights the need for very extensive sampling in the calculations of the activation barrier and also clearly shows that ab initio QM/MM calculations that do not involve extensive sampling are unlikely to give a clear quantitative picture of the reaction mechanism. Proteins 2016; 84:1644-1657. © 2016 Wiley Periodicals, Inc.

  11. Site-specific influence of polyunsaturated fatty acids on atherosclerosis in immune incompetent LDL receptor deficient mice.

    Science.gov (United States)

    Reardon, Catherine A; Blachowicz, Lydia; Gupta, Gaorav; Lukens, John; Nissenbaum, Michael; Getz, Godfrey S

    2006-08-01

    Polyunsaturated fatty acids (PUFA) are thought to influence plasma lipid levels, atherosclerosis, and the immune system. In this study, we fed male LDL receptor deficient (LDLR(-/-)) mice and immune incompetent LDLR(-/-) RAG2(-/-) mice diets containing predominantly saturated fats (milk fat) or PUFA (safflower oil) to determine if the response to diet was influenced by immune status. Relative to milk fat diet, plasma lipid and VLDL levels in both the LDLR(-/-) and LDLR(-/-) RAG2(-/-) mice fed safflower oil diet were lower, suggesting that the primary effect of PUFA on plasma lipids was not due to its inhibition of the immune system. Neither diet nor immune status influenced hepatic triglyceride production and post-heparin lipase activity, suggesting that the differences in triglyceride levels are due to differences in rates of catabolism of triglyceride-rich lipoproteins. While both diets promoted atherogenesis, both aortic root and innominate artery atherosclerosis in LDLR(-/-) mice was less in safflower oil fed animals. In contrast, a site-specific effect of PUFA was observed in the immune incompetent LDLR(-/-) RAG2(-/-). In these mice, aortic root atherosclerosis, but not innominate artery atherosclerosis, was less in PUFA fed animal. These results suggest that PUFA and the immune system may influence innominate artery atherosclerosis by some overlapping mechanisms.

  12. Design, Synthesis, and in Vitro Pharmacology of New Radiolabeled γ-Hydroxybutyric Acid Analogues Including Photolabile Analogues with Irreversible Binding to the High-Affinity γ-Hydroxybutyric Acid Binding Sites

    DEFF Research Database (Denmark)

    Sabbatini, Paola; Wellendorph, Petrine; Høg, Signe;

    2010-01-01

    γ-Hydroxybutyric acid (GHB) is a psychotropic compound endogenous to the brain. Despite its potential physiological significance, the complete molecular mechanisms of action remain unexplained. To facilitate the isolation and identification of the high-affinity GHB binding site, we herein report...... the design and synthesis of the first 125I-labeled radioligands in the field, one of which contains a photoaffinity label which enables it to bind irreversibly to the high-affinity GHB binding sites....

  13. Coupled oscillators on evolving networks

    Science.gov (United States)

    Singh, R. K.; Bagarti, Trilochan

    2016-12-01

    In this work we study coupled oscillators on evolving networks. We find that the steady state behavior of the system is governed by the relative values of the spread in natural frequencies and the global coupling strength. For coupling strong in comparison to the spread in frequencies, the system of oscillators synchronize and when coupling strength and spread in frequencies are large, a phenomenon similar to amplitude death is observed. The network evolution provides a mechanism to build inter-oscillator connections and once a dynamic equilibrium is achieved, oscillators evolve according to their local interactions. We also find that the steady state properties change by the presence of additional time scales. We demonstrate these results based on numerical calculations studying dynamical evolution of limit-cycle and van der Pol oscillators.

  14. Identification of the catalytic residues of alpha-amino acid ester hydrolase from Acetobacter turbidans by labeling and site-directed mutagenesis

    NARCIS (Netherlands)

    Polderman - Tijmes, Jolanda j.; Jekel, Peter A.; Jeronimus-Stratingh, CM; Bruins, Andries P.; van der Laan, Jan-Metske; Sonke, Theo; Janssen, Dick B.

    2002-01-01

    The alpha-amino acid ester hydrolase from Acetobacter turbidans ATCC 9325 is capable of hydrolyzing and synthesizing the side chain peptide bond in beta-lactam antibiotics. Data base searches revealed that the enzyme contains an active site serine consensus sequence Gly-X-Ser-Tyr-X-Gly that is also

  15. Mandelbrot Law of Evolving Networks

    Institute of Scientific and Technical Information of China (English)

    REN Xue-Zao; YANG Zi-Mo; WANG Bing-Hong; ZHOU Tao

    2012-01-01

    We show that the degree distribution of a growing network with linear preferential attachment approximately follows the Mandelbrot law,and propose an analytical method based on a recursive formula that can be used to obtain a more accurate expression of the shifting coefficient.Simulations demonstrate the advantages of our method. This work provides a possible mechanism leading to the Mandelbrot law of evolving networks,and refines the mainstream analytical methods for the shifting coefficient.

  16. A Calculus of Evolving Objects

    Directory of Open Access Journals (Sweden)

    M. Dezani-Ciancaglini

    2008-01-01

    Full Text Available The demands of developing modern, highly dynamic applications have led to an increasing interest in dynamic programming languages and mechanisms. Not only must applications evolve over time, but the object models themselves may need to be adapted to the requirements of different run-time contexts. Class-based models and prototype-based models, for example, may need to co-exist to meet the demands of dynamically evolving applications. Multi-dimensional dispatch, fine-grained and dynamic software composition, and run-time evolution of behaviour are further examples of diverse mechanisms which may need to co-exist in a dynamically evolving run-time environment. How can we model the semantics of these highly dynamic features, yet still offer some reasonable safety guarantees?To this end we present an original calculus in which objects can adapt their behaviour at run-time. Both objects and environments are represented by first-class mappings between variables and values. Message sends are dynamically resolved to method calls. Variables may be dynamically bound, making it possible to model a variety of dynamic mechanisms within the same calculus. Despite the highly dynamic nature of the calculus, safety properties are assured by a type assignment system.

  17. Ranking in evolving complex networks

    Science.gov (United States)

    Liao, Hao; Mariani, Manuel Sebastian; Medo, Matúš; Zhang, Yi-Cheng; Zhou, Ming-Yang

    2017-05-01

    Complex networks have emerged as a simple yet powerful framework to represent and analyze a wide range of complex systems. The problem of ranking the nodes and the edges in complex networks is critical for a broad range of real-world problems because it affects how we access online information and products, how success and talent are evaluated in human activities, and how scarce resources are allocated by companies and policymakers, among others. This calls for a deep understanding of how existing ranking algorithms perform, and which are their possible biases that may impair their effectiveness. Many popular ranking algorithms (such as Google's PageRank) are static in nature and, as a consequence, they exhibit important shortcomings when applied to real networks that rapidly evolve in time. At the same time, recent advances in the understanding and modeling of evolving networks have enabled the development of a wide and diverse range of ranking algorithms that take the temporal dimension into account. The aim of this review is to survey the existing ranking algorithms, both static and time-aware, and their applications to evolving networks. We emphasize both the impact of network evolution on well-established static algorithms and the benefits from including the temporal dimension for tasks such as prediction of network traffic, prediction of future links, and identification of significant nodes.

  18. Evolving Systems and Adaptive Key Component Control

    Science.gov (United States)

    Frost, Susan A.; Balas, Mark J.

    2009-01-01

    We propose a new framework called Evolving Systems to describe the self-assembly, or autonomous assembly, of actively controlled dynamical subsystems into an Evolved System with a higher purpose. An introduction to Evolving Systems and exploration of the essential topics of the control and stability properties of Evolving Systems is provided. This chapter defines a framework for Evolving Systems, develops theory and control solutions for fundamental characteristics of Evolving Systems, and provides illustrative examples of Evolving Systems and their control with adaptive key component controllers.

  19. Secondary structural analysis of the mRNA regions encoding the hemagglutinin cleavage site basic amino acids of the avian influenza virus H5N1 subtype samples

    Institute of Scientific and Technical Information of China (English)

    ZHANG SuXia; WANG Xin; CHEN XueFeng; CAO Huai; ZHANG Wen; LIU CiQuan

    2008-01-01

    Here we report the codon bias and the mRNA secondary structural features of the hemagglutinin (HA) cleavage site basic amino acid regions of avian influenza virus H5N1 subtypes. We have developed a dynamic extended folding strategy to predict RNA secondary structure with RNAstructure 4.1 program in an iterative extension process. Statistical analysis of the sequences showed that the HA cleavage site basic amino acids favor the adenine-rich codons, and the corresponding mRNA fragments are mainly in the folding states of single-stranded loops. Our sequential and structural analyses showed that to prevent and control these highly pathogenic viruses, that is, to inhibit the gene expression of avian influenza virus H5N1 subtypes, we should consider the single-stranded loop regions of the HA cleavage site-coding sequences as the targets of RNA interference.

  20. Influence of ionic strength and pH on the limitation of latex microsphere deposition sites on iron-oxide coated sand by humic acid

    Energy Technology Data Exchange (ETDEWEB)

    Yang, X. [School of Planning, Architecture and Civil Engineering, Queen' s University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, N. Ireland (United Kingdom); Flynn, R., E-mail: r.flynn@qub.ac.uk [School of Planning, Architecture and Civil Engineering, Queen' s University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, N. Ireland (United Kingdom); Kammer, F. von der, E-mail: frank.von.der.kammer@univie.ac.at [Department of Environmental Geosciences, University of Vienna, Althanstrasse 14, 1090 Vienna (Austria); Hofmann, T. [Department of Environmental Geosciences, University of Vienna, Althanstrasse 14, 1090 Vienna (Austria)

    2011-07-15

    This study, for the first time, investigates and quantifies the influence of slight changes in solution pH and ionic strength (IS) on colloidal microsphere deposition site coverage by Suwannee River Humic Acid (SRHA) in a column matrix packed with saturated iron-oxide coated sand. Triple pulse experimental (TPE) results show adsorbed SRHA enhances microsphere mobility more at higher pH and lower IS and covers more sites than at higher IS and lower pH. Random sequential adsorption (RSA) modelling of experimental data suggests 1 {mu}g of adsorbed SRHA occupied 9.28 {+-} 0.03 x 10{sup 9} sites at pH7.6 and IS of 1.6 mMol but covered 2.75 {+-} 0.2 x 10{sup 9} sites at pH6.3 and IS of 20 mMol. Experimental responses are suspected to arise from molecular conformation changes whereby SRHA extends more at higher pH and lower ionic strength but is more compact at lower pH and higher IS. Results suggest effects of pH and IS on regulating SRHA conformation were additive. - Highlights: > We quantified the coupled role of pH and IS and humic acid on colloid deposition. > Humic acid enhances microsphere mobility more at higher pH and lower IS. > pH and IS may control the behaviour of humic acid by regulating its conformation. > The effect of pH and IS on regulating humic acid conformation is additive. - This paper quantifies the impact of pH and ionic strength on the transient deposition behaviour of colloids in porous medium in the presence of humic acid.

  1. Site-Directed Spin-Labeling of Nucleic Acids by Click Chemistry. Detection of Abasic Sites in Duplex DNA by EPR Spectroscopy

    DEFF Research Database (Denmark)

    Sigurdsson, Snorri; Vogel, Stefan; Shelke, Sandip

    2010-01-01

    This paper describes a spin label that can detect and identify local structural deformations in duplex DNA, in particular abasic sites. The spin label was incorporated into DNA by a new postsynthetic approach using click-chemistry on a solid support, which simplified both the synthesis and purifi......This paper describes a spin label that can detect and identify local structural deformations in duplex DNA, in particular abasic sites. The spin label was incorporated into DNA by a new postsynthetic approach using click-chemistry on a solid support, which simplified both the synthesis...

  2. Enhancement of the catalytic activity of ferulic acid decarboxylase from Enterobacter sp. Px6-4 through random and site-directed mutagenesis.

    Science.gov (United States)

    Lee, Hyunji; Park, Jiyoung; Jung, Chaewon; Han, Dongfei; Seo, Jiyoung; Ahn, Joong-Hoon; Chong, Youhoon; Hur, Hor-Gil

    2015-11-01

    The enzyme ferulic acid decarboxylase (FADase) from Enterobacter sp. Px6-4 catalyzes the decarboxylation reaction of lignin monomers and phenolic compounds such as p-coumaric acid, caffeic acid, and ferulic acid into their corresponding 4-vinyl derivatives, that is, 4-vinylphenol, 4-vinylcatechol, and 4-vinylguaiacol, respectively. Among various ferulic acid decarboxylase enzymes, we chose the FADase from Enterobacter sp. Px6-4, whose crystal structure is known, and produced mutants to enhance its catalytic activity by random and site-directed mutagenesis. After three rounds of sequential mutations, FADase(F95L/D112N/V151I) showed approximately 34-fold higher catalytic activity than wild-type for the production of 4-vinylguaiacol from ferulic acid. Docking analyses suggested that the increased activity of FADase(F95L/D112N/V151I) could be due to formation of compact active site compared with that of the wild-type FADase. Considering the amount of phenolic compounds such as lignin monomers in the biomass components, successfully bioengineered FADase(F95L/D112N/V151I) from Enterobacter sp. Px6-4 could provide an ecofriendly biocatalytic tool for producing diverse styrene derivatives from biomass.

  3. Applications of site-specific labeling to study HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

    Directory of Open Access Journals (Sweden)

    Natalia Mercer

    Full Text Available BACKGROUND: Alpha-lactalbumin (α-LA is a calcium-bound mammary gland-specific protein that is found in milk. This protein is a modulator of β1,4-galactosyltransferase enzyme, changing its acceptor specificity from N-acetyl-glucosamine to glucose, to produce lactose, milk's main carbohydrate. When calcium is removed from α-LA, it adopts a molten globule form, and this form, interestingly, when complexed with oleic acid (OA acquires tumoricidal activity. Such a complex made from human α-LA (hLA is known as HAMLET (Human A-lactalbumin Made Lethal to Tumor cells, and its tumoricidal activity has been well established. METHODOLOGY/PRINCIPAL FINDINGS: In the present work, we have used site-specific labeling, a technique previously developed in our laboratory, to label HAMLET with biotin, or a fluoroprobe for confocal microscopy studies. In addition to full length hLA, the α-domain of hLA (αD-hLA alone is also included in the present study. We have engineered these proteins with a 17-amino acid C-terminal extension (hLA-ext and αD-hLA-ext. A single Thr residue in this extension is glycosylated with 2-acetonyl-galactose (C2-keto-galactose using polypeptide-α-N-acetylgalactosaminyltransferase II (ppGalNAc-T2 and further conjugated with aminooxy-derivatives of fluoroprobe or biotin molecules. CONCLUSIONS/SIGNIFICANCE: We found that the molten globule form of hLA and αD-hLA proteins, with or without C-terminal extension, and with and without the conjugated fluoroprobe or biotin molecule, readily form a complex with OA and exhibits tumoricidal activity similar to HAMLET made with full-length hLA protein. The confocal microscopy studies with fluoroprobe-labeled samples show that these proteins are internalized into the cells and found even in the nucleus only when they are complexed with OA. The HAMLET conjugated with a single biotin molecule will be a useful tool to identify the cellular components that are involved with it in the tumoricidal

  4. Applications of site-specific labeling to study HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

    Science.gov (United States)

    Mercer, Natalia; Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Qasba, Pradman K

    2011-01-01

    Alpha-lactalbumin (α-LA) is a calcium-bound mammary gland-specific protein that is found in milk. This protein is a modulator of β1,4-galactosyltransferase enzyme, changing its acceptor specificity from N-acetyl-glucosamine to glucose, to produce lactose, milk's main carbohydrate. When calcium is removed from α-LA, it adopts a molten globule form, and this form, interestingly, when complexed with oleic acid (OA) acquires tumoricidal activity. Such a complex made from human α-LA (hLA) is known as HAMLET (Human A-lactalbumin Made Lethal to Tumor cells), and its tumoricidal activity has been well established. In the present work, we have used site-specific labeling, a technique previously developed in our laboratory, to label HAMLET with biotin, or a fluoroprobe for confocal microscopy studies. In addition to full length hLA, the α-domain of hLA (αD-hLA) alone is also included in the present study. We have engineered these proteins with a 17-amino acid C-terminal extension (hLA-ext and αD-hLA-ext). A single Thr residue in this extension is glycosylated with 2-acetonyl-galactose (C2-keto-galactose) using polypeptide-α-N-acetylgalactosaminyltransferase II (ppGalNAc-T2) and further conjugated with aminooxy-derivatives of fluoroprobe or biotin molecules. We found that the molten globule form of hLA and αD-hLA proteins, with or without C-terminal extension, and with and without the conjugated fluoroprobe or biotin molecule, readily form a complex with OA and exhibits tumoricidal activity similar to HAMLET made with full-length hLA protein. The confocal microscopy studies with fluoroprobe-labeled samples show that these proteins are internalized into the cells and found even in the nucleus only when they are complexed with OA. The HAMLET conjugated with a single biotin molecule will be a useful tool to identify the cellular components that are involved with it in the tumoricidal activity.

  5. Identification of glutamic acid 78 as the active site nucleophile in Bacillus subtilis xylanase using electrospray tandem mass spectrometry.

    Science.gov (United States)

    Miao, S; Ziser, L; Aebersold, R; Withers, S G

    1994-06-14

    A new mechanism-based inactivator of beta-1,4-xylanases, 2',4'-dinitrophenyl 2-deoxy-2-fluoro-beta-xylobioside, has been synthesized and used to trap the covalent intermediate formed during catalysis by Bacillus subtilis xylanase. Electrospray mass spectrometry confirmed the 1:1 stoichiometry of the incorporation of inactivator into the enzyme. Inactivation of xylanase followed the expected pseudo-first-order kinetic behavior, and kinetic parameters were determined. The intermediate trapped was relatively stable toward hydrolytic turnover (t1/2 = 350 min). However, turnover could be facilitated by transglycosylation following the addition of the acceptor benzyl thio-beta-xylobioside, thus demonstrating the catalytic competence of the trapped intermediate. Reactivation kinetic parameters for this process of kre = 0.03 min-1 and Kre = 46 mM were determined. The nucleophilic amino acid was identified as Glu78 by a tandem mass spectrometric technique which does not require the use of radiolabels. The peptic digest of the labeled enzyme was separated by high-performance liquid chromatography and the eluent fed into a tandem mass spectrometer via an electrospray ionization device. The labeled peptide was identified as one of m/z = 826 (doubly charged) which fragmented in the collision chamber between the mass analyzers with loss of the mass of a 2-fluoroxylobiosyl unit. Confirmation of the peptide identity was obtained both by tandem mass spectrometric sequencing and by Edman degradation of the purified peptide. Glu78 is completely conserved in all members of this xylanase family and indeed is shown to be located in the active site in the recently determined X-ray crystal structure.

  6. Guest dynamics in solid acetone-d/sub 6/-DOCA and acetone-d/sub 6/-APA inclusion compounds: correlation between the symmetry of the motion and the site symmetry. [Deoxycholic acid; Apocholic acid

    Energy Technology Data Exchange (ETDEWEB)

    Meirovitch, E.

    1986-10-23

    The molecular motion of acetone-d/sub 6/ acting as guest in deoxycholic acid and apocholic acid host lattices in the solid state is interpreted in light of a broader concept assessing that very often the motion of the guest proceeds through discrete jumps rather than diffusively and its symmetry is congenial with the site symmetry of the host lattice. In particular, the acetone molecules are engaged in threefold jumps about a unique axis, compatible with the 32 site symmetry of the host lattice. The entire dynamic range of this process is investigated in terms of spectral consequences brought about by variations in jump rates, in the relative population of the three symmetry related sites, and in instrumental parameters such as the time interval between the two 90/sup 0/ pulses in the quadrupole echo sequence and the length of the 90/sup 0/ pulses.

  7. The 'E' factor -- evolving endodontics.

    Science.gov (United States)

    Hunter, M J

    2013-03-01

    Endodontics is a constantly developing field, with new instruments, preparation techniques and sealants competing with trusted and traditional approaches to tooth restoration. Thus general dental practitioners must question and understand the significance of these developments before adopting new practices. In view of this, the aim of this article, and the associated presentation at the 2013 British Dental Conference & Exhibition, is to provide an overview of endodontic methods and constantly evolving best practice. The presentation will review current preparation techniques, comparing rotary versus reciprocation, and question current trends in restoration of the endodontically treated tooth.

  8. Synchronization in an evolving network

    CERN Document Server

    Singh, R K

    2015-01-01

    In this work we study the dynamics of Kuramoto oscillators on a stochastically evolving network whose evolution is governed by the phases of the individual oscillators and degree distribution. Synchronization is achieved after a threshold connection density is reached. This cumulative effect of topology and dynamics has many real-world implications, where synchronization in a system emerges as a collective property of its components in a self-organizing manner. The synchronous state remains stable as long as the connection density remains above the threshold value, with additional links providing resilience against network fluctuations.

  9. How did 'biopolymers' evolve before life began?

    Science.gov (United States)

    Scott, J E

    1988-12-01

    The very reactive products of ionizing radiations acting on water (e(aq)(-), OH·, H·, etc.) probably had a very potent effect in selecting prebiopolymers from the polymers of the primordial soup. e(aq)(-), in particular, has properties that give considerable insight into the survival of nucleic acids, secondary structures in DNA and polypeptides, lipid membranes and electron transport systems. OH· could have played an important part in selecting specific binding sites ('specifity selection'). Experimental evidence is available for these proposals.

  10. Characterization of the N-Acetyl-5-neuraminic Acid-binding Site of the Extracytoplasmic Solute Receptor (SiaP) of Nontypeable Haemophilus influenzae Strain 2019

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, Jason W.; Coussens, Nathan P.; Allen, Simon; Houtman, Jon C.D.; Turner, Keith H.; Zaleski, Anthony; Ramaswamy, S.; Gibson, Bradford W.; Apicella, Michael A. (Iowa); (Buck Inst.)

    2012-11-14

    Nontypeable Haemophilus influenzae is an opportunistic human pathogen causing otitis media in children and chronic bronchitis and pneumonia in patients with chronic obstructive pulmonary disease. The outer membrane of nontypeable H. influenzae is dominated by lipooligosaccharides (LOS), many of which incorporate sialic acid as a terminal nonreducing sugar. Sialic acid has been demonstrated to be an important factor in the survival of the bacteria within the host environment. H. influenzae is incapable of synthesizing sialic acid and is dependent on scavenging free sialic acid from the host environment. To achieve this, H. influenzae utilizes a tripartite ATP-independent periplasmic transporter. In this study, we characterize the binding site of the extracytoplasmic solute receptor (SiaP) from nontypeable H. influenzae strain 2019. A crystal structure of N-acetyl-5-neuraminic acid (Neu5Ac)-bound SiaP was determined to 1.4 {angstrom} resolution. Thermodynamic characterization of Neu5Ac binding shows this interaction is enthalpically driven with a substantial unfavorable contribution from entropy. This is expected because the binding of SiaP to Neu5Ac is mediated by numerous hydrogen bonds and has several buried water molecules. Point mutations targeting specific amino acids were introduced in the putative binding site. Complementation with the mutated siaP constructs resulted either in full, partial, or no complementation, depending on the role of specific residues. Mass spectrometry analysis of the O-deacylated LOS of the R127K point mutation confirmed the observation of reduced incorporation of Neu5Ac into the LOS. The decreased ability of H. influenzae to import sialic acid had negative effects on resistance to complement-mediated killing and viability of biofilms in vitro, confirming the importance of sialic acid transport to the bacterium.

  11. Characterization of the N-acetyl-5-neuraminic acid-binding site of the extracytoplasmic solute receptor (SiaP) of nontypeable Haemophilus influenzae strain 2019.

    Science.gov (United States)

    Johnston, Jason W; Coussens, Nathan P; Allen, Simon; Houtman, Jon C D; Turner, Keith H; Zaleski, Anthony; Ramaswamy, S; Gibson, Bradford W; Apicella, Michael A

    2008-01-11

    Nontypeable Haemophilus influenzae is an opportunistic human pathogen causing otitis media in children and chronic bronchitis and pneumonia in patients with chronic obstructive pulmonary disease. The outer membrane of nontypeable H. influenzae is dominated by lipooligosaccharides (LOS), many of which incorporate sialic acid as a terminal nonreducing sugar. Sialic acid has been demonstrated to be an important factor in the survival of the bacteria within the host environment. H. influenzae is incapable of synthesizing sialic acid and is dependent on scavenging free sialic acid from the host environment. To achieve this, H. influenzae utilizes a tripartite ATP-independent periplasmic transporter. In this study, we characterize the binding site of the extracytoplasmic solute receptor (SiaP) from nontypeable H. influenzae strain 2019. A crystal structure of N-acetyl-5-neuraminic acid (Neu5Ac)-bound SiaP was determined to 1.4A resolution. Thermodynamic characterization of Neu5Ac binding shows this interaction is enthalpically driven with a substantial unfavorable contribution from entropy. This is expected because the binding of SiaP to Neu5Ac is mediated by numerous hydrogen bonds and has several buried water molecules. Point mutations targeting specific amino acids were introduced in the putative binding site. Complementation with the mutated siaP constructs resulted either in full, partial, or no complementation, depending on the role of specific residues. Mass spectrometry analysis of the O-deacylated LOS of the R127K point mutation confirmed the observation of reduced incorporation of Neu5Ac into the LOS. The decreased ability of H. influenzae to import sialic acid had negative effects on resistance to complement-mediated killing and viability of biofilms in vitro, confirming the importance of sialic acid transport to the bacterium.

  12. Evolving understanding of the evolution of herbicide resistance.

    Science.gov (United States)

    Gressel, Jonathan

    2009-11-01

    A greater number of, and more varied, modes of resistance have evolved in weeds than in other pests because the usage of herbicides is far more extensive than the usage of other pesticides, and because weed seed output is so great. The discovery and development of selective herbicides are more problematic than those of insecticides and fungicides, as these must only differentiate between plant and insect or pathogen. Herbicides are typically selective between plants, meaning that before deployment there are already some crops possessing natural herbicide resistance that weeds could evolve. The concepts of the evolution of resistance and the mechanisms of delaying resistance have evolved as nature has continually evolved new types of resistance. Major gene target-site mutations were the first types to evolve, with initial consideration devoted mainly to them, but slowly 'creeping' resistance, gradually accruing increasing levels of resistance, has become a major force owing to an incremental accumulation of genetic changes in weed populations. Weeds have evolved mechanisms unknown even in antibiotic as well as other drug and pesticide resistances. It is even possible that cases of epigenetic 'remembered' resistances may have appeared.

  13. Stability of Evolving Multiagent Systems.

    Science.gov (United States)

    De Wilde, P; Briscoe, G

    2011-08-01

    A multiagent system is a distributed system where the agents or nodes perform complex functions that cannot be written down in analytic form. Multiagent systems are highly connected, and the information they contain is mostly stored in the connections. When agents update their state, they take into account the state of the other agents, and they have access to those states via the connections. There is also external user-generated input into the multiagent system. As so much information is stored in the connections, agents are often memory less. This memory-less property, together with the randomness of the external input, has allowed us to model multiagent systems using Markov chains. In this paper, we look at multiagent systems that evolve, i.e., the number of agents varies according to the fitness of the individual agents. We extend our Markov chain model and define stability. This is the start of a methodology to control multiagent systems. We then build upon this to construct an entropy-based definition for the degree of instability (entropy of the limit probabilities), which we used to perform a stability analysis. We then investigated the stability of evolving agent populations through simulation and show that the results are consistent with the original definition of stability in nonevolving multiagent systems, proposed by Chli and De Wilde. This paper forms the theoretical basis for the construction of digital business ecosystems, and applications have been reported elsewhere.

  14. Convergently Evolved Toxic Secondary Metabolites in Plants Drive the Parallel Molecular Evolution of Insect Resistance.

    Science.gov (United States)

    Petschenka, Georg; Wagschal, Vera; von Tschirnhaus, Michael; Donath, Alexander; Dobler, Susanne

    2017-08-01

    Natural selection imposed by natural toxins has led to striking levels of convergent evolution at the molecular level. Cardiac glycosides represent a group of plant toxins that block the Na,K-ATPase, a vital membrane protein in animals. Several herbivorous insects have convergently evolved resistant Na,K-ATPases, and in some species, convergent gene duplications have also arisen, likely to cope with pleiotropic costs of resistance. To understand the genetic basis and predictability of these adaptations, we studied five independent lineages of leaf-mining flies (Diptera: Agromyzidae). These flies have colonized host plants in four botanical families that convergently evolved cardiac glycosides of two structural types: cardenolides and bufadienolides. We compared each of six fly species feeding on such plants to a phylogenetically related but nonadapted species. Irrespective of the type of cardiac glycoside in the host plant, five out of six exposed species displayed substitutions in the cardiac glycoside-binding site of the Na,K-ATPase that were previously described in other insect orders; in only one species was the gene duplicated. In vitro assays of nervous tissue extractions confirmed that the substitutions lead to increased resistance of the Na,K-ATPase. Our results demonstrate that target site insensitivity of Na,K-ATPase is a common response to dietary cardiac glycosides leading to highly predictable amino acid changes; nonetheless, convergent evolution of gene duplication for this multifunctional enzyme appears more constrained.

  15. Influences of Bronsted Acidic Sites in H[Al] ZSM-5 on Polarization and Electronegativity of Ethene Studied by Molecular Dynamics

    Institute of Scientific and Technical Information of China (English)

    FAN,Jian-Fen(樊建芬); XIAO,He-Ming(肖鹤鸣); van de GRAAF,B; WANG,Qiu-Xia(王秋霞); NJO,S.L; XIA,Qi-Ying(夏其英)

    2002-01-01

    Molecular dynamics simulation has been performed for studying the polarization and electronegativity of ethene molecules near Bronsted acidic sites in H[Al]ZSM-5. The result shows that the molecules are polarized most at the edges of intersections and least at the segments of channels. On the contrary, the highest global molecular electronegativity is fotund at the centers of channel segments. Al substitution slightly increases the molecular dipole moment, but hardly affects the molecular electronegativity. Bronsted acidic proton decreases the dipole moment of guest molecule, but increases the molecular electronegativity.

  16. An acidic loop and cognate phosphorylation sites define a molecular switch that modulates ubiquitin charging activity in Cdc34-like enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Ranzani, Valeria; Tripodi, Farida;

    2011-01-01

    elements in one of the larger families of E2 enzymes: an acidic insertion in β4α2 loop in the proximity of the catalytic cysteine and two conserved key serine residues within the catalytic domain, which are phosphorylated by CK2. Our investigations, using yeast Cdc34 as a model, through 2.5 µs molecular......E2 ubiquitin-conjugating enzymes are crucial mediators of protein ubiquitination, which strongly influence the ultimate fate of the target substrates. Recently, it has been shown that the activity of several enzymes of the ubiquitination pathway is finely tuned by phosphorylation, an ubiquitous...... mechanism for cellular regulation, which modulates protein conformation. In this contribution, we provide the first rationale, at the molecular level, of the regulatory mechanism mediated by casein kinase 2 (CK2) phosphorylation of E2 Cdc34-like enzymes. In particular, we identify two co-evolving signature...

  17. Correction of a splice-site mutation in the beta-globin gene stimulated by triplex-forming peptide nucleic acids

    DEFF Research Database (Denmark)

    Chin, Joanna Y; Kuan, Jean Y; Lonkar, Pallavi S

    2008-01-01

    Splice-site mutations in the beta-globin gene can lead to aberrant transcripts and decreased functional beta-globin, causing beta-thalassemia. Triplex-forming DNA oligonucleotides (TFOs) and peptide nucleic acids (PNAs) have been shown to stimulate recombination in reporter gene loci in mammalian...... DNA fragments, can promote single base-pair modification at the start of the second intron of the beta-globin gene, the site of a common thalassemia-associated mutation. This single base pair change was detected by the restoration of proper splicing of transcripts produced from a green fluorescent...

  18. Semivolatile behaviour of dicarboxylic acids and other polar organic species at a rural background site (Nylsvley, RSA)

    CSIR Research Space (South Africa)

    Limbeck, A

    2001-01-01

    Full Text Available esters and monocarboxylic acids is available (Cautreels and Van Cauwenberghe, 1978). Here we report about the observa- tion of a semivolatile behavior of oxalic acid and related polar organic compounds. Sample collection was per- formed at a biogenically...}propanol complex to obtain the propyl-esters. After the addition of a saturated aqueous NaCl solution the dicarboxylic acid esters were extracted with cyclohexane and analyzed by GC/MS. The adsor- bed compounds like monocarboxylic acids, aromatic compounds...

  19. Developing palaeolimnological records of organic content (DOC and POC) using the UK Acid Water Monitoring Network sites

    Science.gov (United States)

    Russell, Fiona; Chiverrell, Richard; Boyle, John

    2016-04-01

    Monitoring programmes have shown increases in concentrations of dissolved organic matter (DOM) in the surface waters of northern and central Europe (Monteith et al. 2007), and negative impacts of the browning of river waters have been reported for fish populations (Jonsson et al. 2012; Ranaker et al. 2012) and for ecosystem services such as water treatment (Tuvendal and Elmqvist 2011). Still the exact causes of the recent browning remain uncertain, the main contenders being climate change (Evans et al. 2005) and reduced ionic strength in surface water resulting from declines in anthropogenic sulphur and sea salt deposition (Monteith et al. 2007). There is a need to better understand the pattern, drivers and trajectory of these increases in DOC and POC in both recent and longer-term (Holocene) contexts to improve the understanding of carbon cycling within lakes and their catchments. In Britain there are some ideal sites for testing whether these trends are preserved and developing methods for reconstructing organic fluxes from lake sedimentary archives. There is a suite of lakes distributed across the country, the UK Acid Waters Monitoring Network (UKAWMN) sites, which have been monitored monthly for dissolved organic carbon and other aqueous species since 1988. These 12 lakes have well studied recent and in some case whole Holocene sediment records. Here four of those lakes (Grannoch, Chon, Scoat Tarn and Cwm Mynach) are revisited, with sampling focused on the sediment-water interface and very recent sediments (approx.150 years). At Scoat Tarn (approx. 1000 years) and Llyn Mynach (11.5k years) longer records have been obtained to assess equivalent patterns through the Holocene. Analyses of the gravity cores have focused on measuring and characterising the organic content for comparison with recorded surface water DOC measurements (UKAWMN). Data from pyrolysis measurements (TGA/DSC) in an N atmosphere show that the mass loss between 330-415°C correlates well with

  20. CHARACTERIZATION OF SORBENT PRODUCED THROUGH IMMOBILIZATION OF HUMIC ACID ON CHITOSAN USING GLUTARALDEHYDE AS CROSS-LINKING AGENT AND Pb(II ION AS ACTIVE SITE PROTECTOR

    Directory of Open Access Journals (Sweden)

    Uripto Trisno Santoso

    2010-12-01

    Full Text Available Sorbent produced through immobilization of humic acid (HA on chitosan using glutaraldehyde as cross-linking agent and Pb(II ions as active site protector has been characterized. Active sorption site of HA was protected by reacting HA with Pb(II ion, and the protected-HA was then activated by glutaraldehyde, crosslinked onto chitosan, and deprotected by 0.1 M disodium ethylenediamine tetra-acetic acid (Na2EDTA. The protected-crosslinking method enhanced the content of immobilized-HA and its chemical stability. Based on the FTIR spectra, crosslinking of HA on chitosan probably occurred through a chemical reaction. The sorption capacity of sorbent still remains unchanged after the second regeneration, but some of HA start to be soluble. The latter shows that cross-linking reaction between HA and chitosan is through formation an unstable product. The effectiveness of sorbent regeneration can also be identified by the XRD pattern.

  1. Distribution bias analysis of germline and somatic single-nucleotide variations that impact protein functional site and neighboring amino acids

    Science.gov (United States)

    Pan, Yang; Yan, Cheng; Hu, Yu; Fan, Yu; Pan, Qing; Wan, Quan; Torcivia-Rodriguez, John; Mazumder, Raja

    2017-01-01

    Single nucleotide variations (SNVs) can result in loss or gain of protein functional sites. We analyzed the effects of SNVs on enzyme active sites, ligand binding sites, and various types of post translational modification (PTM) sites. We found that, for most types of protein functional sites, the SNV pattern differs between germline and somatic mutations as well as between synonymous and non-synonymous mutations. From a total of 51,138 protein functional site affecting SNVs (pfsSNVs), a pan-cancer analysis revealed 142 somatic pfsSNVs in five or more cancer types. By leveraging patient information for somatic pfsSNVs, we identified 17 loss of functional site SNVs and 60 gain of functional site SNVs which are significantly enriched in patients with specific cancer types. Of the key pfsSNVs identified in our analysis above, we highlight 132 key pfsSNVs within 17 genes that are found in well-established cancer associated gene lists. For illustrating how key pfsSNVs can be prioritized further, we provide a use case where we performed survival analysis showing that a loss of phosphorylation site pfsSNV at position 105 in MEF2A is significantly associated with decreased pancreatic cancer patient survival rate. These 132 pfsSNVs can be used in developing genetic testing pipelines. PMID:28176830

  2. Evolving networks by merging cliques

    Science.gov (United States)

    Takemoto, Kazuhiro; Oosawa, Chikoo

    2005-10-01

    We propose a model for evolving networks by merging building blocks represented as complete graphs, reminiscent of modules in biological system or communities in sociology. The model shows power-law degree distributions, power-law clustering spectra, and high average clustering coefficients independent of network size. The analytical solutions indicate that a degree exponent is determined by the ratio of the number of merging nodes to that of all nodes in the blocks, demonstrating that the exponent is tunable, and are also applicable when the blocks are classical networks such as Erdös-Rényi or regular graphs. Our model becomes the same model as the Barabási-Albert model under a specific condition.

  3. Peripartum hysterectomy: an evolving picture.

    LENUS (Irish Health Repository)

    Turner, Michael J

    2012-02-01

    Peripartum hysterectomy (PH) is one of the obstetric catastrophes. Evidence is emerging that the role of PH in modern obstetrics is evolving. Improving management of postpartum hemorrhage and newer surgical techniques should decrease PH for uterine atony. Rising levels of repeat elective cesarean deliveries should decrease PH following uterine scar rupture in labor. Increasing cesarean rates, however, have led to an increase in the number of PHs for morbidly adherent placenta. In the case of uterine atony or rupture where PH is required, a subtotal PH is often sufficient. In the case of pathological placental localization involving the cervix, however, a total hysterectomy is required. Furthermore, the involvement of other pelvic structures may prospectively make the diagnosis difficult and the surgery challenging. If resources permit, PH for pathological placental localization merits a multidisciplinary approach. Despite advances in clinical practice, it is likely that peripartum hysterectomy will be more challenging for obstetricians in the future.

  4. Axial Spondyloarthritis: An Evolving Concept

    Directory of Open Access Journals (Sweden)

    Nelly Ziadé

    2015-07-01

    Full Text Available Axial spondyloarthritis (AxSpA is the prototype of a family of inter-related yet heterogeneous diseases sharing common clinical and genetic manifestations: the spondyloarthritides (SpAs. The condition mainly affects the sacroiliac joints and axial skeleton, and has a clear classification scheme, wider epidemiological data, and distinct therapeutic guidelines when compared with other SpAs. However, the concept of AxSpA has not been immutable over time and has evolved tremendously on many levels over the past decades. This review identifies the evolution of the AxSpA concept at two levels. First, at the level of classification, the old classifications and rationales leading to the current Assessment of SpondyloArthritis international Society (ASAS classification are reviewed, and the advantages and drawbacks are discussed. Second, at the therapeutic level, current and future treatments are described and treatment strategies are discussed.

  5. The evolving Gleason grading system.

    Science.gov (United States)

    Chen, Ni; Zhou, Qiao

    2016-02-01

    The Gleason grading system for prostate adenocarcinoma has evolved from its original scheme established in the 1960s-1970s, to a significantly modified system after two major consensus meetings conducted by the International Society of Urologic Pathology (ISUP) in 2005 and 2014, respectively. The Gleason grading system has been incorporated into the WHO classification of prostate cancer, the AJCC/UICC staging system, and the NCCN guidelines as one of the key factors in treatment decision. Both pathologists and clinicians need to fully understand the principles and practice of this grading system. We here briefly review the historical aspects of the original scheme and the recent developments of Gleason grading system, focusing on major changes over the years that resulted in the modern Gleason grading system, which has led to a new "Grade Group" system proposed by the 2014 ISUP consensus, and adopted by the 2016 WHO classification of tumours of the prostate.

  6. Mandelbrot Law of Evolving Networks

    CERN Document Server

    Ren, Xue-Zao; Wang, Bing-Hong; Zhou, Tao

    2011-01-01

    Degree distributions of many real networks are known to follow the Mandelbrot law, which can be considered as an extension of the power law that determined by not only the power-law exponent, but also the shifting coefficient. Although the shifting coefficient highly affect the shape of distribution, it receives less attention in the literature and in fact, mainstream analytical method based on backward or forward difference will lead to considerable deviation to its value. In this article, we show that the degree distribution of a growing network with linear preferential attachment approximately follows the Mandelbrot law. We propose an analytical method based on a recursive formula that can obtain a more accurate expression of the shifting coefficient than the previous methods. Simulations demonstrate the advantages of our method. This work provides a possible mechanism leading to the Mandelbrot law of evolving networks, and refines the mainstream analytical methods for the shifting coefficient.

  7. Directing Group in Decarboxylative Cross-Coupling: Copper-Catalyzed Site-Selective C-N Bond Formation from Nonactivated Aliphatic Carboxylic Acids.

    Science.gov (United States)

    Liu, Zhao-Jing; Lu, Xi; Wang, Guan; Li, Lei; Jiang, Wei-Tao; Wang, Yu-Dong; Xiao, Bin; Fu, Yao

    2016-08-03

    Copper-catalyzed directed decarboxylative amination of nonactivated aliphatic carboxylic acids is described. This intramolecular C-N bond formation reaction provides efficient access to the synthesis of pyrrolidine and piperidine derivatives as well as the modification of complex natural products. Moreover, this reaction presents excellent site-selectivity in the C-N bond formation step through the use of directing group. Our work can be considered as a big step toward controllable radical decarboxylative carbon-heteroatom cross-coupling.

  8. The reaction mechanism for the SCR process on monomer V(5+) sites and the effect of modified Brønsted acidity.

    Science.gov (United States)

    Arnarson, Logi; Falsig, Hanne; Rasmussen, Søren B; Lauritsen, Jeppe V; Moses, Poul Georg

    2016-06-22

    The energetics, structures and activity of a monomeric VO3H/TiO2(001) catalyst are investigated for the selective catalytic reduction (SCR) reaction by the use of density functional theory (DFT). Furthermore we study the influences of a dopant substitute in the TiO2 support and its effects on the known properties of the SCR system such as Brønsted acidity and reducibility of vanadium. We find for the reduction part of the SCR mechanism that it involves two Ti-O-V oxygen sites. One is a hydroxyl possessing Brønsted acidity which contributes to the formation of NH4(+), while the other accepts a proton which charge stabilizes the reduced active site. In the reduction the proton is donated to the latter due to a reaction between NH3 and NO that forms a H2NNO molecule which decomposes into N2(g) and H2O(g). A dopant substitution of 10 different dopants: Si, Ge, Se, Zr, Sn, Te, Hf, V, Mo and W at each of the sites, which participate in the reaction, modifies the energetics and therefore the SCR activity. We find that Brønsted acidity is a descriptor for the SCR activity at low temperatures. Based on this descriptor we find that Zr, Hf and Sn have a positive effect as they decrease the activation energy for the SCR reaction.

  9. Aspartic Acid 397 in Subunit B of the Na+-pumping NADH:Quinone Oxidoreductase from Vibrio cholerae Forms Part of a Sodium-binding Site, Is Involved in Cation Selectivity, and Affects Cation-binding Site Cooperativity

    Science.gov (United States)

    Shea, Michael E.; Juárez, Oscar; Cho, Jonathan; Barquera, Blanca

    2013-01-01

    The Na+-pumping NADH:quinone complex is found in Vibrio cholerae and other marine and pathogenic bacteria. NADH:ubiquinone oxidoreductase oxidizes NADH and reduces ubiquinone, using the free energy released by this reaction to pump sodium ions across the cell membrane. In a previous report, a conserved aspartic acid residue in the NqrB subunit at position 397, located in the cytosolic face of this protein, was proposed to be involved in the capture of sodium. Here, we studied the role of this residue through the characterization of mutant enzymes in which this aspartic acid was substituted by other residues that change charge and size, such as arginine, serine, lysine, glutamic acid, and cysteine. Our results indicate that NqrB-Asp-397 forms part of one of the at least two sodium-binding sites and that both size and charge at this position are critical for the function of the enzyme. Moreover, we demonstrate that this residue is involved in cation selectivity, has a critical role in the communication between sodium-binding sites, by promoting cooperativity, and controls the electron transfer step involved in sodium uptake (2Fe-2S → FMNC). PMID:24030824

  10. Conserved amino acid motifs from the novel Piv/MooV family of transposases and site-specific recombinases are required for catalysis of DNA inversion by Piv.

    Science.gov (United States)

    Tobiason, D M; Buchner, J M; Thiel, W H; Gernert, K M; Karls, A C

    2001-02-01

    Piv, a site-specific invertase from Moraxella lacunata, exhibits amino acid homology with the transposases of the IS110/IS492 family of insertion elements. The functions of conserved amino acid motifs that define this novel family of both transposases and site-specific recombinases (Piv/MooV family) were examined by mutagenesis of fully conserved amino acids within each motif in Piv. All Piv mutants altered in conserved residues were defective for in vivo inversion of the M. lacunata invertible DNA segment, but competent for in vivo binding to Piv DNA recognition sequences. Although the primary amino acid sequences of the Piv/MooV recombinases do not contain a conserved DDE motif, which defines the retroviral integrase/transposase (IN/Tnps) family, the predicted secondary structural elements of Piv align well with those of the IN/Tnps for which crystal structures have been determined. Molecular modelling of Piv based on these alignments predicts that E59, conserved as either E or D in the Piv/MooV family, forms a catalytic pocket with the conserved D9 and D101 residues. Analysis of Piv E59G confirms a role for E59 in catalysis of inversion. These results suggest that Piv and the related IS110/IS492 transposases mediate DNA recombination by a common mechanism involving a catalytic DED or DDD motif.

  11. Multiple Propofol-binding Sites in a γ-Aminobutyric Acid Type A Receptor (GABAAR) Identified Using a Photoreactive Propofol Analog*♦

    Science.gov (United States)

    Jayakar, Selwyn S.; Zhou, Xiaojuan; Chiara, David C.; Dostalova, Zuzana; Savechenkov, Pavel Y.; Bruzik, Karol S.; Dailey, William P.; Miller, Keith W.; Eckenhoff, Roderic G.; Cohen, Jonathan B.

    2014-01-01

    Propofol acts as a positive allosteric modulator of γ-aminobutyric acid type A receptors (GABAARs), an interaction necessary for its anesthetic potency in vivo as a general anesthetic. Identifying the location of propofol-binding sites is necessary to understand its mechanism of GABAAR modulation. [3H]2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate (azietomidate) and R-[3H]5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (mTFD-MPAB), photoreactive analogs of 2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate (etomidate) and mephobarbital, respectively, have identified two homologous but pharmacologically distinct classes of intersubunit-binding sites for general anesthetics in the GABAAR transmembrane domain. Here, we use a photoreactive analog of propofol (2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol ([3H]AziPm)) to identify propofol-binding sites in heterologously expressed human α1β3 GABAARs. Propofol, AziPm, etomidate, and R-mTFD-MPAB each inhibited [3H]AziPm photoincorporation into GABAAR subunits maximally by ∼50%. When the amino acids photolabeled by [3H]AziPm were identified by protein microsequencing, we found propofol-inhibitable photolabeling of amino acids in the β3-α1 subunit interface (β3Met-286 in β3M3 and α1Met-236 in α1M1), previously photolabeled by [3H]azietomidate, and α1Ile-239, located one helical turn below α1Met-236. There was also propofol-inhibitable [3H]AziPm photolabeling of β3Met-227 in βM1, the amino acid in the α1-β3 subunit interface photolabeled by R-[3H]mTFD-MPAB. The propofol-inhibitable [3H]AziPm photolabeling in the GABAAR β3 subunit in conjunction with the concentration dependence of inhibition of that photolabeling by etomidate or R-mTFD-MPAB also establish that each anesthetic binds to the homologous site at the β3-β3 subunit interface. These results establish that AziPm as well as propofol bind to the homologous intersubunit sites in the

  12. A human fatty acid synthase inhibitor binds β-ketoacyl reductase in the keto-substrate site.

    Science.gov (United States)

    Hardwicke, Mary Ann; Rendina, Alan R; Williams, Shawn P; Moore, Michael L; Wang, Liping; Krueger, Julie A; Plant, Ramona N; Totoritis, Rachel D; Zhang, Guofeng; Briand, Jacques; Burkhart, William A; Brown, Kristin K; Parrish, Cynthia A

    2014-09-01

    Human fatty acid synthase (hFAS) is a complex, multifunctional enzyme that is solely responsible for the de novo synthesis of long chain fatty acids. hFAS is highly expressed in a number of cancers, with low expression observed in most normal tissues. Although normal tissues tend to obtain fatty acids from the diet, tumor tissues rely on de novo fatty acid synthesis, making hFAS an attractive metabolic target for the treatment of cancer. We describe here the identification of GSK2194069, a potent and specific inhibitor of the β-ketoacyl reductase (KR) activity of hFAS; the characterization of its enzymatic and cellular mechanism of action; and its inhibition of human tumor cell growth. We also present the design of a new protein construct suitable for crystallography, which resulted in what is to our knowledge the first co-crystal structure of the human KR domain and includes a bound inhibitor.

  13. Recommendation in evolving online networks

    Science.gov (United States)

    Hu, Xiao; Zeng, An; Shang, Ming-Sheng

    2016-02-01

    Recommender system is an effective tool to find the most relevant information for online users. By analyzing the historical selection records of users, recommender system predicts the most likely future links in the user-item network and accordingly constructs a personalized recommendation list for each user. So far, the recommendation process is mostly investigated in static user-item networks. In this paper, we propose a model which allows us to examine the performance of the state-of-the-art recommendation algorithms in evolving networks. We find that the recommendation accuracy in general decreases with time if the evolution of the online network fully depends on the recommendation. Interestingly, some randomness in users' choice can significantly improve the long-term accuracy of the recommendation algorithm. When a hybrid recommendation algorithm is applied, we find that the optimal parameter gradually shifts towards the diversity-favoring recommendation algorithm, indicating that recommendation diversity is essential to keep a high long-term recommendation accuracy. Finally, we confirm our conclusions by studying the recommendation on networks with the real evolution data.

  14. Multiscale modelling of evolving foams

    Science.gov (United States)

    Saye, R. I.; Sethian, J. A.

    2016-06-01

    We present a set of multi-scale interlinked algorithms to model the dynamics of evolving foams. These algorithms couple the key effects of macroscopic bubble rearrangement, thin film drainage, and membrane rupture. For each of the mechanisms, we construct consistent and accurate algorithms, and couple them together to work across the wide range of space and time scales that occur in foam dynamics. These algorithms include second order finite difference projection methods for computing incompressible fluid flow on the macroscale, second order finite element methods to solve thin film drainage equations in the lamellae and Plateau borders, multiphase Voronoi Implicit Interface Methods to track interconnected membrane boundaries and capture topological changes, and Lagrangian particle methods for conservative liquid redistribution during rearrangement and rupture. We derive a full set of numerical approximations that are coupled via interface jump conditions and flux boundary conditions, and show convergence for the individual mechanisms. We demonstrate our approach by computing a variety of foam dynamics, including coupled evolution of three-dimensional bubble clusters attached to an anchored membrane and collapse of a foam cluster.

  15. OH-PRED: prediction of protein hydroxylation sites by incorporating adapted normal distribution bi-profile Bayes feature extraction and physicochemical properties of amino acids.

    Science.gov (United States)

    Jia, Cang-Zhi; He, Wen-Ying; Yao, Yu-Hua

    2017-03-01

    Hydroxylation of proline or lysine residues in proteins is a common post-translational modification event, and such modifications are found in many physiological and pathological processes. Nonetheless, the exact molecular mechanism of hydroxylation remains under investigation. Because experimental identification of hydroxylation is time-consuming and expensive, bioinformatics tools with high accuracy represent desirable alternatives for large-scale rapid identification of protein hydroxylation sites. In view of this, we developed a supporter vector machine-based tool, OH-PRED, for the prediction of protein hydroxylation sites using the adapted normal distribution bi-profile Bayes feature extraction in combination with the physicochemical property indexes of the amino acids. In a jackknife cross validation, OH-PRED yields an accuracy of 91.88% and a Matthew's correlation coefficient (MCC) of 0.838 for the prediction of hydroxyproline sites, and yields an accuracy of 97.42% and a MCC of 0.949 for the prediction of hydroxylysine sites. These results demonstrate that OH-PRED increased significantly the prediction accuracy of hydroxyproline and hydroxylysine sites by 7.37 and 14.09%, respectively, when compared with the latest predictor PredHydroxy. In independent tests, OH-PRED also outperforms previously published methods.

  16. Site-specific solvent exposure analysis of a membrane protein using unnatural amino acids and {sup 19}F nuclear magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Pan; Li, Dong [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Chen, Hongwei [High Magnetic Field Laboratory, Chinese Academy of Science, Hefei, Anhui 230031 (China); Xiong, Ying [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Tian, Changlin, E-mail: cltian@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); High Magnetic Field Laboratory, Chinese Academy of Science, Hefei, Anhui 230031 (China)

    2011-10-22

    Highlights: {yields} Solvent isotope shift analysis of {sup 19}F-tfmF in different H{sub 2}O/D{sub 2}O molar ratio. {yields} Correlation between solvent isotope shift of {sup 19}F-spins and solvent exposure analysis. {yields} Solvent exposure analysis of membrane proteins. -- Abstract: Membrane proteins play an essential role in cellular metabolism, transportation and signal transduction across cell membranes. The scarcity of membrane protein structures has thus far prevented a full understanding of their molecular mechanisms. Preliminary topology studies and residue solvent exposure analysis have the potential to provide valuable information on membrane proteins of unknown structure. Here, a {sup 19}F-containing unnatural amino acid (trimethylfluoro-phenylalanine, tfmF) was applied to accomplish site-specific {sup 19}F spin incorporation at different sites in diacylglycerol kinase (DAGK, an Escherichia coli membrane protein) for site-specific solvent exposure analysis. Due to isotope effect on {sup 19}F spins, a standard curve for {sup 19}F-tfmF chemical shifts was drawn for varying solvent H{sub 2}O/D{sub 2}O ratios. Further site-specific {sup 19}F solvent isotope shift analysis was conducted for DAGK to distinguish residues in water-soluble loops, interfacial areas or hydrophobic membrane regions. This site-specific solvent exposure analysis method could be applied for further topological analysis of other membrane proteins.

  17. Modulation of the enzymatic efficiency of ferredoxin-NADP(H) reductase by the amino acid volume around the catalytic site.

    Science.gov (United States)

    Musumeci, Matías A; Arakaki, Adrián K; Rial, Daniela V; Catalano-Dupuy, Daniela L; Ceccarelli, Eduardo A

    2008-03-01

    Ferredoxin (flavodoxin)-NADP(H) reductases (FNRs) are ubiquitous flavoenzymes that deliver NADPH or low-potential one-electron donors (ferredoxin, flavodoxin, adrenodoxin) to redox-based metabolic reactions in plastids, mitochondria and bacteria. Plastidic FNRs are quite efficient reductases. In contrast, FNRs from organisms possessing a heterotrophic metabolism or anoxygenic photosynthesis display turnover numbers 20- to 100-fold lower than those of their plastidic and cyanobacterial counterparts. Several structural features of these enzymes have yet to be explained. The residue Y308 in pea FNR is stacked nearly parallel to the re-face of the flavin and is highly conserved amongst members of the family. By computing the relative free energy for the lumiflavin-phenol pair at different angles with the relative position found for Y308 in pea FNR, it can be concluded that this amino acid is constrained against the isoalloxazine. This effect is probably caused by amino acids C266 and L268, which face the other side of this tyrosine. Simple and double FNR mutants of these amino acids were obtained and characterized. It was observed that a decrease or increase in the amino acid volume resulted in a decrease in the catalytic efficiency of the enzyme without altering the protein structure. Our results provide experimental evidence that the volume of these amino acids participates in the fine-tuning of the catalytic efficiency of the enzyme.

  18. Evolvability Search: Directly Selecting for Evolvability in order to Study and Produce It

    OpenAIRE

    Mengistu, Henok; Lehman, Joel Anthony; Clune, Jeff

    2016-01-01

    One hallmark of natural organisms is their significant evolvability, i.e.,their increased potential for further evolution. However, reproducing such evolvability in artificial evolution remains a challenge, which both reduces the performance of evolutionary algorithms and inhibits the study of evolvable digital phenotypes. Although some types of selection in evolutionary computation indirectly encourage evolvability, one unexplored possibility is to directly select for evolvability. To do so,...

  19. Voyages Through Time: Everything Evolves

    Science.gov (United States)

    Pendleton, Y. J.; Tarter, J. C.; DeVore, E. K.; O'Sullivan, K. A.; Taylor, S. M.

    2001-12-01

    Evolutionary change is a powerful framework for studying our world and our place therein. It is a recurring theme in every realm of science: over time, the universe, the planet Earth, life, and human technologies all change, albeit on vastly different scales. Evolution offers scientific explanations for the age-old question, "Where did we come from?" In addition, historical perspectives of science show how our understanding has evolved over time. The complexities of all of these systems will never reveal a "finished" story. But it is a story of epic size, capable of inspiring awe and of expanding our sense of time and place, and eminently worthy of investigating. This story is the basis of Voyages Through Time. Voyages Through Time (VTT), provides teachers with not only background science content and pedagogy, but also with materials and resources for the teaching of evolution. The six modules, Cosmic Evolution, Planetary Evolution, Origin of Life, Evolution of Life, Hominid Evolution, and Evolution of Technology, emphasize student inquiry, and promote the nature of science, as recommended in the NSES and BSL. The modules are unified by the overarching theme of evolution and the meta questions: "What is changing?" "What is the rate of change?" and "What is the mechanism of change?" Determination of student outcomes for the project required effective collaboration of scientists, teachers, students and media specialists. The broadest curricula students outcomes are 1) an enjoyment of science, 2) an understanding of the nature of science, especially the understanding of evidence and re-evaluation, and 3) key science content. The curriculum is being developed by the SETI Institute, NASA Ames Research Center, California Academy of Sciences, and San Francisco State University, and is funded by the NSF (IMD 9730693), with support form Hewlett-Packard Company, The Foundation for Microbiology, Combined Federated Charities, NASA Astrobiology Institute, and NASA Fundamental

  20. An investigation of folic acid-protein association sites and the effect of this association on folic acid self-assembly.

    Science.gov (United States)

    Gupta, Rajat; Kalita, Prasanta; Patil, Omkar; Mohanty, Sanat

    2015-12-01

    The contribution of folic acid (FA)-tryptophan interactions to FA-protein association was investigated in the context of using FA as a drug carrier in protein delivery systems. Bovine serum albumin (BSA) and indolicidin were used as model proteins in the study. The FA-BSA complex was characterized by using the Bradford reagent to identify the impact of FA-BSA association on BSA-dye reagent interactions. UV-visible spectroscopic analysis of the FA-BSA mixture showed that the absorbance maximum of BSA-dye reagent occurred at 595 nm, even after the association of FA with BSA. This confirms that protonated amino acid groups of the protein are not involved in FA-BSA association. Moreover, molecular dynamics (MD) simulation confirmed the presence of an associative interaction between aromatic moieties in FA and tryptophan moieties in the indolicidin molecule, which disrupted FA self-assembly. An X-ray diffraction (XRD) study showed that there was limited disruption of FA self-assembly after the addition of BSA or tryptophan. This suggests that FA and BSA are compatible and associate with each other. Graphical Abstract Mechanism of folic acid and protein association.

  1. Accurate Three States Model for Amino Acids with Two Chemically Coupled Titrating Sites in Explicit Solvent Atomistic Constant pH Simulations and pKa Calculations.

    Science.gov (United States)

    Dobrev, Plamen; Donnini, Serena; Groenhof, Gerrit; Grubmüller, Helmut

    2017-01-10

    Correct protonation of titratable groups in biomolecules is crucial for their accurate description by molecular dynamics simulations. In the context of constant pH simulations, an additional protonation degree of freedom is introduced for each titratable site, allowing the protonation state to change dynamically with changing structure or electrostatics. Here, we extend previous approaches for an accurate description of chemically coupled titrating sites. A second reaction coordinate is used to switch between two tautomeric states of an amino acid with chemically coupled titratable sites, such as aspartate (Asp), glutamate (Glu), and histidine (His). To this aim, we test a scheme involving three protonation states. To facilitate charge neutrality as required for periodic boundary conditions and Particle Mesh Ewald (PME) electrostatics, titration of each respective amino acid is coupled to a "water" molecule that is charged in the opposite direction. Additionally, a force field modification for Amber99sb is introduced and tested for the description of carboxyl group protonation. Our three states model is tested by titration simulations of Asp, Glu, and His, yielding a good agreement, reproducing the correct geometry of the groups in their different protonation forms. We further show that the ion concentration change due to the neutralizing "water" molecules does not significantly affect the protonation free energies of the titratable groups, suggesting that the three states model provides a good description of biomolecular dynamics at constant pH.

  2. Effects of neonatal. gamma. -ray irradiation on rat hippocampus: Pt. 2; Development of excitatory amino acid binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Dessi, F.; Represa, A.; Ben-Ari, Y. (Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France))

    1991-01-01

    In the rat, neonatal irradiation produces a destruction of denate granule cells and prevents the development of the mossy fibre-CA3 pyramidal cell synapse. The developmental increase of high affinity kainate binding sites in the stratum lucidum was reduced on the irradiated side as compared with the control side. This suggests that a proportion of high affinity kainate binding sites is associated with mossy fibres. In contrast, the development profile of N-methyl-D-aspartate binding sites, which are associated with associational and commissural synapses in CA3, was not affected by irradiation. The role that afferent fibres may play in the development of pyramidal cells is discussed in connection with the modulatory effects of glutamate receptors on the development of neurons. (author).

  3. A counting renaissance: combining stochastic mapping and empirical Bayes to quickly detect amino acid sites under positive selection

    Science.gov (United States)

    Lemey, Philippe; Suchard, Marc A.

    2012-01-01

    Motivation: Statistical methods for comparing relative rates of synonymous and non-synonymous substitutions maintain a central role in detecting positive selection. To identify selection, researchers often estimate the ratio of these relative rates () at individual alignment sites. Fitting a codon substitution model that captures heterogeneity in across sites provides a reliable way to perform such estimation, but it remains computationally prohibitive for massive datasets. By using crude estimates of the numbers of synonymous and non-synonymous substitutions at each site, counting approaches scale well to large datasets, but they fail to account for ancestral state reconstruction uncertainty and to provide site-specific estimates. Results: We propose a hybrid solution that borrows the computational strength of counting methods, but augments these methods with empirical Bayes modeling to produce a relatively fast and reliable method capable of estimating site-specific values in large datasets. Importantly, our hybrid approach, set in a Bayesian framework, integrates over the posterior distribution of phylogenies and ancestral reconstructions to quantify uncertainty about site-specific estimates. Simulations demonstrate that this method competes well with more-principled statistical procedures and, in some cases, even outperforms them. We illustrate the utility of our method using human immunodeficiency virus, feline panleukopenia and canine parvovirus evolution examples. Availability: Renaissance counting is implemented in the development branch of BEAST, freely available at http://code.google.com/p/beast-mcmc/. The method will be made available in the next public release of the package, including support to set up analyses in BEAUti. Contact: philippe.lemey@rega.kuleuven.be or msuchard@ucla.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23064000

  4. Evolving evolutionary algorithms using linear genetic programming.

    Science.gov (United States)

    Oltean, Mihai

    2005-01-01

    A new model for evolving Evolutionary Algorithms is proposed in this paper. The model is based on the Linear Genetic Programming (LGP) technique. Every LGP chromosome encodes an EA which is used for solving a particular problem. Several Evolutionary Algorithms for function optimization, the Traveling Salesman Problem and the Quadratic Assignment Problem are evolved by using the considered model. Numerical experiments show that the evolved Evolutionary Algorithms perform similarly and sometimes even better than standard approaches for several well-known benchmarking problems.

  5. Particle-facilitated lead and arsenic transport in abandoned mine sites soil influenced by simulated acid rain.

    Science.gov (United States)

    Shaoping, Hu; Xincai, Chen; Jiyan, Shi; Yingxu, Chen; Qi, Lin

    2008-05-01

    The role of acid rain in affecting Pb and As transport from mine tailings was investigated by pumping simulated acid rain at a infiltration rate of 10.2 cm/h through soil columns. Simulated acid rain with pH of 3.0, 4.5 and 5.6 were used as leaching solutions. Results showed that 86.9-95.9% of Pb and 90-91.8% of As eluted from the columns were adsorbed by particles in the leachates. Scanning electron microscopy (SEM) analysis showed that particles released from the columns were mainly composed of flocculated aggregates and plate or rod shaped discrete grains. Transmission electron microscopy (TEM) coupled with energy dispersive X-ray analysis (EDX) showed that these particles were predominantly silicate minerals. Results from our experiments demonstrated that when rapid infiltration conditions or a rainstorm exist, particle-facilitated transport of contaminants is likely to the dominant metal transport pathway influenced by acid rain.

  6. One-Tube-Only Standardized Site-Directed Mutagenesis: An Alternative Approach to Generate Amino Acid Substitution Collections

    NARCIS (Netherlands)

    Mingo, J.; Erramuzpe, A.; Luna, S.; Aurtenetxe, O.; Amo, L.; Diez, I.; Schepens, J.T.G.; Hendriks, W.J.A.J.; Cortes, J.M.; Pulido, R.

    2016-01-01

    Site-directed mutagenesis (SDM) is a powerful tool to create defined collections of protein variants for experimental and clinical purposes, but effectiveness is compromised when a large number of mutations is required. We present here a one-tube-only standardized SDM approach that generates compreh

  7. Waste sulphuric acid regeneration plants and on-site services%废硫酸再生装置与现场服务

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Waste sulphuric acid regeneration has matured to provide a robust and reliable way for recycling the waste sulphuric acid using a variety of sources. Design features of MECS waste sulphuric acid regeneration plants and on-site service for sulphuric users provided by Rhodia are described. Rhodia's service includes a patented storage tank cleaning technology, which can not only clean out and recover acid sludge from storage tanks, but also avoid confined space entry.%废硫酸再生技术已经成熟,为回收利用各种来源的废硫酸提供了一条稳健、可靠的途径。主要阐述了MECS废酸再生装置的设计特点和罗地亚为硫酸用户提供的现场服务。罗地亚的现场服务包括一种专利储罐清洗技术,该技术不但可清除并回收罐底酸泥,而且可避免受限空间的进入。

  8. Assessment of acid rock drainage pollutants release in the uranium mining site of Poços de Caldas--Brazil.

    Science.gov (United States)

    Fernandes, H M; Franklin, M R

    2001-01-01

    We compared three different techniques to assess acid drainage occurrence connected to pyritic waste rock piles at a uranium mining and milling site in Poços de Caldas--Brazil: (1) mass balance calculations, (2) column leaching experiments and (3) geochemical modelling. The study site was chosen because all the drainage coming from the pile is collected in one holding pond and a huge database (monitoring program) was available. The three independent methods predicted similar values for the intrinsic oxidation rate (IOR) (about 10(-9) kg m-3 s-1). We estimate the total time for consumption of all oxidizable material in the dump to be greater than 500 years. Geochemical model results showed a good agreement between predicted sulphate concentrations in relation to those found in the waste pile drainage, although the Al values were overestimated and pH values were underestimated.

  9. Adsorptive denitrogenation of model fuels with porous metal-organic framework (MOF) MIL-101 impregnated with phosphotungstic acid: effect of acid site inclusion.

    Science.gov (United States)

    Ahmed, Imteaz; Khan, Nazmul Abedin; Hasan, Zubair; Jhung, Sung Hwa

    2013-04-15

    A metal-organic framework (MOF) MIL-101 was impregnated with phosphotungstic acid (PWA) and used as an adsorbent in liquid phase adsorption of nitrogen-containing compounds (NCCs) from a model fuel. The model fuel contained one sulfur-containing compound (SCC), benzothiophene (BT); one basic NCC, quinoline (QUI); and one neutral NCC, indole (IND). In both MIL-101 and PWA-impregnated MIL-101s, NCC adsorption selectivity was very high compared to the SCC selectivity. Additionally, the adsorption capacity of basic QUI increased by 20% with only 1% PWA impregnation in MIL-101. The adsorption of a neutral compound, IND, was slightly reduced with PWA impregnation in the MOF. The adsorption capacity/selectivity can be remarkably improved by a slight modification of MOFs, for example, to impart acidity. The MOF impregnated with PWA may be very interesting in commercial denitrogenation, especially for coal-derived fuels which contain mainly basic NCCs, by adsorption since the selectivity for NCCs (compared to SCCs) over the adsorbent is very high and the adsorbent can be reused many times. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. A prospective, randomized, double-blinded single-site control study comparing blood loss prevention of tranexamic acid (TXA to epsilon aminocaproic acid (EACA for corrective spinal surgery

    Directory of Open Access Journals (Sweden)

    Vaz Kenneth M

    2010-04-01

    Full Text Available Abstract Background Multilevel spinal fusion surgery has typically been associated with significant blood loss. To limit both the need for transfusions and co-morbidities associated with blood loss, the use of anti-fibrinolytic agents has been proposed. While there is some literature comparing the effectiveness of tranexamic acid (TXA to epsilon aminocaproic acid (EACA in cardiac procedures, there is currently no literature directly comparing TXA to EACA in orthopedic surgery. Methods/Design Here we propose a prospective, randomized, double-blinded control study evaluating the effects of TXA, EACA, and placebo for treatment of adolescent idiopathic scoliosis (AIS, neuromuscular scoliosis (NMS, and adult deformity (AD via corrective spinal surgery. Efficacy will be determined by intraoperative and postoperative blood loss. Other clinical outcomes that will be compared include transfusion rates, preoperative and postoperative hemodynamic values, and length of hospital stay after the procedure. Discussion The primary goal of the study is to determine perioperative blood loss as a measure of the efficacy of TXA, EACA, and placebo. Based on current literature and the mechanism by which the medications act, we hypothesize that TXA will be more effective at reducing blood loss than EACA or placebo and result in improved patient outcomes. Trial Registration ClinicalTrials.gov ID: NCT00958581

  11. Structure of a highly acidic β-lactamase from the moderate halophile Chromohalobacter sp. 560 and the discovery of a Cs{sup +}-selective binding site

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Shigeki; Yonezawa, Yasushi; Okazaki, Nobuo; Matsumoto, Fumiko; Shibazaki, Chie; Shimizu, Rumi; Yamada, Mitsugu; Adachi, Motoyasu; Tamada, Taro [Japan Atomic Energy Agency, 2-4 Shirakata-shirane, Tokai, Ibaraki 319-1195 (Japan); Kawamoto, Masahide [Kyushu Synchrotron Light Research Center, 8-7 Yayoigaoka, Tosu, Saga 841-0005 (Japan); Tokunaga, Hiroko; Ishibashi, Matsujiro [Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065 (Japan); Blaber, Michael [Japan Atomic Energy Agency, 2-4 Shirakata-shirane, Tokai, Ibaraki 319-1195 (Japan); Florida State University, 1115 West Call Street, Tallahassee, FL 32306-4300 (United States); Tokunaga, Masao [Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065 (Japan); Kuroki, Ryota, E-mail: kuroki.ryota@jaea.go.jp [Japan Atomic Energy Agency, 2-4 Shirakata-shirane, Tokai, Ibaraki 319-1195 (Japan)

    2015-03-01

    The tertiary structure of a β-lactamase derived from the halobacterium Chromohalobacter sp. 560 (HaBLA) was determined by X-ray crystallography. Three unique Sr{sup 2+}-binding sites and one Cs{sup +}-binding site were discovered in the HaBLA molecule. Environmentally friendly absorbents are needed for Sr{sup 2+} and Cs{sup +}, as the removal of the radioactive Sr{sup 2+} and Cs{sup +} that has leaked from the Fukushima Nuclear Power Plant is one of the most important problems in Japan. Halophilic proteins are known to have many acidic residues on their surface that can provide specific binding sites for metal ions such as Cs{sup +} or Sr{sup 2+}. The crystal structure of a halophilic β-lactamase from Chromohalobacter sp. 560 (HaBLA) was determined to resolutions of between 1.8 and 2.9 Å in space group P3{sub 1} using X-ray crystallography. Moreover, the locations of bound Sr{sup 2+} and Cs{sup +} ions were identified by anomalous X-ray diffraction. The location of one Cs{sup +}-specific binding site was identified in HaBLA even in the presence of a ninefold molar excess of Na{sup +} (90 mM Na{sup +}/10 mM Cs{sup +}). From an activity assay using isothermal titration calorimetry, the bound Sr{sup 2+} and Cs{sup +} ions do not significantly affect the enzymatic function of HaBLA. The observation of a selective and high-affinity Cs{sup +}-binding site provides important information that is useful for the design of artificial Cs{sup +}-binding sites that may be useful in the bioremediation of radioactive isotopes.

  12. A first principles comparison of the mechanism and site requirements for the electrocatalytic oxidation of methanol and formic acid over Pt.

    Science.gov (United States)

    Neurock, Matthew; Janik, Michael; Wieckowski, Andrzej

    2008-01-01

    First principles density functional theoretical calculations were carried out to examine and compare the reaction paths and ensembles for the electrocatalytic oxidation of methanol and formic acid in the presence of solution and applied electrochemical potential. Methanol proceeds via both direct and indirect pathways which are governed by the initial C-H and O-H bond activation, respectively. The primary path requires an ensemble size of between 3-4 Pt atoms, whereas the secondary path is much less structure sensitive, requiring only 1-2 metal atoms. The CO that forms inhibits the surface at potentials below 0.66 V NHE. The addition of Ru results in bifunctional as well as electronic effects that lower the onset potential for CO oxidation. In comparison, formic acid proceeds via direct, indirect and formate pathways. The direct path, which involves the activation of the C-H bond followed by the rapid activation of the O-H bond, was calculated to be the predominant path especially at potentials greater than 0.6 V. The activation of the O-H bond of formic acid has a very low barrier and readily proceeds to form surface formate intermediates as the first step of the indirect formate path. Adsorbed formate, however, was calculated to be very stable, and thus acts as a spectator species. At potentials below 0.6 V NHE, CO, which forms via the non-Faradaic hydrolytic splitting of the C-O bond over stepped or defect sites in the indirect path, can build up and poison the surface. The results indicate that the direct path only requires a single Pt atom whereas the indirect path requires a larger surface ensemble and stepped sites. This suggests that alloys will not have the same influence on formic acid oxidation as they do for methanol oxidation.

  13. Hydroxamic acid interactions with solvated cerium hydroxides in the flotation of monazite and bastnäsite-Experiments and DFT study

    Science.gov (United States)

    Sarvaramini, A.; Azizi, D.; Larachi, F.

    2016-11-01

    Density functional theory (DFT) simulations and experiments were performed to clarify the interaction mechanisms between hydroxamic acid collectors and cerium hydroxides during the flotation of bastnäsite and monazite minerals. These minerals showed considerable floatability at moderately alkaline pH which was related to the adsorption of hydroxamic acids on their surfaces as confirmed by vibrational spectroscopic and zeta potential measurements. DFT simulations showed that at moderately alkaline pH, the interactions between solvated Ce(OH)2+ and Ce(OH)2+ and heptyl-hydroxamic acid (HHA) anions resulted in the formation of, respectively, [Ce(OH)(HHA)x(H2O)y]2-x (x[y = ] = 1[6],2[3],3[1]) and [Ce(OH)2(HHA)x(H2O)y]1-x (x[y = ] = 1[5],2[1],3[0]) complexes. The collector anions were found to interact directly through formation of two covalent bonds between their two polar-head oxygen atoms and cerium in the hydroxide complexes. However, formation of such new bonds resulted in breakage of a few covalent/electrostatic bonds between cerium and water molecules initially present in the first hydration shell of the rare-earth metal cation. Building up in the electric double layer of the semi-soluble minerals, these complexes, and by extension, those from other rare-earth elements belonging to monazite and bastnäsite, are speculated to play a role in the interactions between rare-earth minerals and hydroxamic acid collectors.

  14. Mapping Substance P Binding Sites on the Neurokinin-1 Receptor Using Genetic Incorporation of a Photoreactive Amino Acid

    DEFF Research Database (Denmark)

    Valentin-Hansen, Louise; Park, Minyoung; Huber, Thomas;

    2014-01-01

    Substance P (SP) is a neuropeptide that mediates numerous physiological responses, including transmission of pain and inflammation through the neurokinin-1 (NK1) receptor, a G protein-coupled receptor. Previous mutagenesis studies and photoaffinity labeling using ligand analogues suggested that t...... possess multiple determinants for SP binding and demonstrate the utility of genetically encoded photocross-linking to map complex multitopic binding sites on G protein-coupled receptors in a cell-based assay format....... that the binding site for SP includes multiple domains in the N-terminal (Nt) segment and the second extracellular loop (ECLII) of NK1. To map precisely the NK1 residues that interact with SP, we applied a novel receptor-based targeted photocross-linking approach. We used amber codon suppression to introduce...

  15. Amino Acid Hydrolysis and Analysis System for Investigation of Site Directed Nucleation and Growth of Ceramic Films on Metallic Surfaces

    Science.gov (United States)

    2008-09-30

    of biomineralization by hemocytes isolated from a bivalve on a metal substrate outside of the organism. These results indicate that it is possible...to deposit a ceramic material onto a metal substrate at ambient temperature and pressure. Figure I A-B. SEM evidence of cellular biomineralization on...hydrolysis and analysis system for investigation of site directed nucleation and growth of cera1nic films on metallic surfaces Sb. GRANT NUMBER

  16. Evolving Technologies: A View to Tomorrow

    Science.gov (United States)

    Tamarkin, Molly; Rodrigo, Shelley

    2011-01-01

    Technology leaders must participate in strategy creation as well as operational delivery within higher education institutions. The future of higher education--the view to tomorrow--is irrevocably integrated and intertwined with evolving technologies. This article focuses on two specific evolving technologies: (1) alternative IT sourcing; and (2)…

  17. Evolving Technologies: A View to Tomorrow

    Science.gov (United States)

    Tamarkin, Molly; Rodrigo, Shelley

    2011-01-01

    Technology leaders must participate in strategy creation as well as operational delivery within higher education institutions. The future of higher education--the view to tomorrow--is irrevocably integrated and intertwined with evolving technologies. This article focuses on two specific evolving technologies: (1) alternative IT sourcing; and (2)…

  18. The Problem of Evolving a Genetic Code

    Science.gov (United States)

    Woese, Carl R.

    1970-01-01

    Proposes models for the evolution of the genetic code and translation mechanisms. Suggests that the translation process is so complex and precise that it must have evolved in many stages, and that the evolution of the code was influenced by the constraints imposed by the evolving translation mechanism. (EB)

  19. The Computational Complexity of Evolving Systems

    NARCIS (Netherlands)

    Verbaan, P.R.A.

    2006-01-01

    Evolving systems are systems that change over time. Examples of evolving systems are computers with soft-and hardware upgrades and dynamic networks of computers that communicate with each other, but also colonies of cooperating organisms or cells within a single organism. In this research, several m

  20. Inheritance of evolved resistance to a novel herbicide (pyroxasulfone).

    Science.gov (United States)

    Busi, Roberto; Gaines, Todd A; Vila-Aiub, Martin M; Powles, Stephen B

    2014-03-01

    Agricultural weeds have rapidly adapted to intensive herbicide selection and resistance to herbicides has evolved within ecological timescales. Yet, the genetic basis of broad-spectrum generalist herbicide resistance is largely unknown. This study aims to determine the genetic control of non-target-site herbicide resistance trait(s) that rapidly evolved under recurrent selection of the novel lipid biosynthesis inhibitor pyroxasulfone in Lolium rigidum. The phenotypic segregation of pyroxasulfone resistance in parental, F1 and back-cross (BC) families was assessed in plants exposed to a gradient of pyroxasulfone doses. The inheritance of resistance to chemically dissimilar herbicides (cross-resistance) was also evaluated. Evolved resistance to the novel selective agent (pyroxasulfone) is explained by Mendelian segregation of one semi-dominant allele incrementally herbicide-selected at higher frequency in the progeny. In BC families, cross-resistance is conferred by an incompletely dominant single major locus. This study confirms that herbicide resistance can rapidly evolve to any novel selective herbicide agents by continuous and repeated herbicide use. The results imply that the combination of herbicide options (rotation, mixtures or combinations) to exploit incomplete dominance can provide acceptable control of broad-spectrum generalist resistance-endowing monogenic traits. Herbicide diversity within a set of integrated management tactics can be one important component to reduce the herbicide selection intensity.

  1. Transcriptome sequencing revealed the transcriptional organization at ribosome-mediated attenuation sites in Corynebacterium glutamicum and identified a novel attenuator involved in aromatic amino acid biosynthesis.

    Science.gov (United States)

    Neshat, Armin; Mentz, Almut; Rückert, Christian; Kalinowski, Jörn

    2014-11-20

    The Gram-positive bacterium Corynebacterium glutamicum belongs to the order Corynebacteriales and is used as a producer of amino acids at industrial scales. Due to its economic importance, gene expression and particularly the regulation of amino acid biosynthesis has been investigated extensively. Applying the high-resolution technique of transcriptome sequencing (RNA-seq), recently a vast amount of data has been generated that was used to comprehensively analyze the C. glutamicum transcriptome. By analyzing RNA-seq data from a small RNA cDNA library of C. glutamicum, short transcripts in the known transcriptional attenuators sites of the trp operon, the ilvBNC operon and the leuA gene were verified. Furthermore, whole transcriptome RNA-seq data were used to elucidate the transcriptional organization of these three amino acid biosynthesis operons. In addition, we discovered and analyzed the novel attenuator aroR, located upstream of the aroF gene (cg1129). The DAHP synthase encoded by aroF catalyzes the first step in aromatic amino acid synthesis. The AroR leader peptide contains the amino acid sequence motif F-Y-F, indicating a regulatory effect by phenylalanine and tyrosine. Analysis by real-time RT-PCR suggests that the attenuator regulates the transcription of aroF in dependence of the cellular amount of tRNA loaded with phenylalanine when comparing a phenylalanine-auxotrophic C. glutamicum mutant fed with limiting and excess amounts of a phenylalanine-containing dipeptide. Additionally, the very interesting finding was made that all analyzed attenuators are leaderless transcripts.

  2. Voyages Through Time: Everything Evolves

    Science.gov (United States)

    Fisher, Jane; Tarter, Jill; Devore, Edna; Pendleton, Yvonne; O'Sullivan, Kathleen; Burke, Meg

    2004-06-01

    The SETI Institute, the California Academy of Sciences, NASA Ames Research Center, and San Francisco State University have developed standards-based curriculum materials for a one-year high school integrated science course centered on the unifying theme of evolution. Scientists, teachers, curriculum writers, and media specialists are currently finalizing six modules that integrate astronomical, geological, and biological sciences as well as the history of science and technology. The sequence of lessons in each module is designed to promote students' understanding and skills as defined by the National Science Education Standards and Benchmarks for Science Literacy. The modules cover: Cosmic Evolution, Planetary Evolution, Origin of Life, Evolution of Life, Hominid Evolution, and the Evolution of Technology. The core lessons for all six modules are provided via CD-ROM, including instructional guidelines, science background information, and additional resources (print, audiovisual, software, WWW sites, and databases). These products will be published as a complete set for use as a yearlong science course and will also be available as individual modules for use in discipline-based courses. Evolutionary change is a powerful framework for studying our world and our place therein. It is a story of epic size, capable of inspiring awe and of expanding our sense of time and place. This story is the basis of Voyages Through Time.

  3. Identification of amino acids related to catalytic function of Sulfolobus solfataricus P1 carboxylesterase by site-directed mutagenesis and molecular modeling

    Science.gov (United States)

    Choi, Yun-Ho; Lee, Ye-Na; Park, Young-Jun; Yoon, Sung-Jin; Lee, Hee-Bong

    2016-01-01

    The archaeon Sulfolobus solfataricus P1 carboxylesterase is a thermostable enzyme with a molecular mass of 33.5 kDa belonging to the mammalian hormone-sensitive lipase (HSL) family. In our previous study, we purified the enzyme and suggested the expected amino acids related to its catalysis by chemical modification and a sequence homology search. For further validating these amino acids in this study, we modified them using site-directed mutagenesis and examined the activity of the mutant enzymes using spectrophotometric analysis and then estimated by homology modeling and fluorescence analysis. As a result, it was identified that Ser151, Asp244, and His274 consist of a catalytic triad, and Gly80, Gly81, and Ala152 compose an oxyanion hole of the enzyme. In addition, it was also determined that the cysteine residues are located near the active site or at the positions inducing any conformational changes of the enzyme by their replacement with serine residues. [BMB Reports 2016; 49(6): 349-354] PMID:27222124

  4. Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response.

    Science.gov (United States)

    Fu, Lingchen; Kilberg, Michael S

    2013-02-15

    Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/CRE site upstream of the CARE that also contributes to AAR-induced ATF3 transcription. ATF4 binds to the ATF/CRE and CARE sequences and both are required for a maximal response to ATF4 induction. ATF3, which antagonizes ATF4 and represses its own gene, also exhibited binding activity to the ATF/CRE and CARE sequences. The AAR resulted in elevated total cJUN and p-cJUN protein levels and both forms exhibited binding activity to the ATF/CRE and CARE ATF3 sequences. Knockdown of AAR-enhanced cJUN expression blocked induction of the ATF3 gene and mutation of either the ATF/CRE or the CARE site prevented the cJUN-dependent increase in ATF3-driven luciferase activity. The results indicate that both increased cJUN and the cis-acting ATF/CRE sequence within the ATF3 promoter contribute to the transcriptional activation of the gene during the AAR.

  5. Isoaspartic acid is present at specific sites in myelin basic protein from multiple sclerosis patients: could this represent a trigger for disease onset?

    Science.gov (United States)

    Friedrich, Michael G; Hancock, Sarah E; Raftery, Mark J; Truscott, Roger J W

    2016-08-12

    Multiple sclerosis (MS) is associated with breakdown of the myelin sheath that coats neurons in the central nervous system. The cause of MS is not known, although the pathogenesis involves destruction of myelin by the immune system. It was the aim of this study to examine the abundant myelin protein, myelin basic protein (MBP), to determine if there are sites of modification that may be characteristic for MS. MBP from the cerebellum was examined from controls and MS patients across the age range using mass spectrometry and amino acid analysis. Amino acid racemization data indicated that myelin basic protein is long-lived and proteomic analysis of MBP showed it to be highly modified. A common modification of MBP was racemization of Asp and this was significantly greater in MS patients. In long-lived proteins, L-Asp and L-Asn can racemize to three other isomers, D-isoAsp, L-isoAsp and D-Asp and this is significant because isoAsp formation in peptides renders them immunogenic.Proteomic analysis revealed widespread modifications of MBP with two surface regions that are altered in MS. In particular, isoAsp was significantly elevated at these sites in MS patients. The generation of isoAsp could be responsible for eliciting an immune response to modified MBP and therefore be implicated in the etiology of MS.

  6. Accurate and easy-to-use assessment of contiguous DNA methylation sites based on proportion competitive quantitative-PCR and lateral flow nucleic acid biosensor.

    Science.gov (United States)

    Xu, Wentao; Cheng, Nan; Huang, Kunlun; Lin, Yuehe; Wang, Chenguang; Xu, Yuancong; Zhu, Longjiao; Du, Dan; Luo, Yunbo

    2016-06-15

    Many types of diagnostic technologies have been reported for DNA methylation, but they require a standard curve for quantification or only show moderate accuracy. Moreover, most technologies have difficulty providing information on the level of methylation at specific contiguous multi-sites, not to mention easy-to-use detection to eliminate labor-intensive procedures. We have addressed these limitations and report here a cascade strategy that combines proportion competitive quantitative PCR (PCQ-PCR) and lateral flow nucleic acid biosensor (LFNAB), resulting in accurate and easy-to-use assessment. The P16 gene with specific multi-methylated sites, a well-studied tumor suppressor gene, was used as the target DNA sequence model. First, PCQ-PCR provided amplification products with an accurate proportion of multi-methylated sites following the principle of proportionality, and double-labeled duplex DNA was synthesized. Then, a LFNAB strategy was further employed for amplified signal detection via immune affinity recognition, and the exact level of site-specific methylation could be determined by the relative intensity of the test line and internal reference line. This combination resulted in all recoveries being greater than 94%, which are pretty satisfactory recoveries in DNA methylation assessment. Moreover, the developed cascades show significantly high usability as a simple, sensitive, and low-cost tool. Therefore, as a universal platform for sensing systems for the detection of contiguous multi-sites of DNA methylation without external standards and expensive instrumentation, this PCQ-PCR-LFNAB cascade method shows great promise for the point-of-care diagnosis of cancer risk and therapeutics.

  7. On-site cellulase production by Trichoderma reesei 3EMS35 mutant and same vessel saccharification and fermentation of acid treated wheat straw for ethanol production

    Science.gov (United States)

    Khokhar, Zia-ullah; Syed, Qurat-ul-Ain; Wu, Jing; Athar, Muhammad Amin

    2014-01-01

    Bioethanol production from lignocellulosic raw materials involves process steps like pre-treatment, enzymatic hydrolysis, fermentation and distillation. In this study, wheat straw was explored as feedstock for on-site cellulase production by T. reesei 3EMS35 mutant, and as a substrate for second generation bioethanol production from baker yeast. Scanning electron microscopy (SEM) and X-ray diffractography (XRD) of untreated wheat straw (UWS) and acid treated wheat straw (TWS) were done to understand the structural organization and changes in the cellulase accessibility and reactivity. The effect of delignification and structural modification for on-site cellulase enzyme production was comparably studied. The efficiency of crude cellulase enzyme for digestion of UWS and TWS and then production of ethanol from TWS was studied using same-vessel saccharification and fermentation (SVSF) technique, both in shaking flasks as well as in fermenters. Two different methods of operation were tested, i.e. the UWSEnz method, where UWS was used for on-site enzyme production, and TWSEnz method where TWS was applied as substrate for cellullase production. Results obtained showed structural modifications in cellulose of TWS due to delignification, removal of wax and change of crystallinity. UWS was better substrate than TWS for cellulase production due to the fact that lignin did not hinder the enzyme production by fungus but acted as a booster. On-site cellulase enzyme produced by T. reesei 3EMS35 mutant hydrolyzed most of cellulose (91 %) in TWS within first 24 hrs. Shake flasks experiments showed that ethanol titers and yields with UWSEnz were 2.9 times higher compared to those obtained with TWSEnz method respectively. Comparatively, titer of ethanol in shake flask experiments was 10 % higher than this obtained in 3 L fermenter with UWSEnz. Outcomes from this investigation clearly demonstrated the potential of on-site cellulase enzyme production and SVSF for ethanol production

  8. A cluster DFT study of NH{sub 3} and NO adsorption on the (MoO{sub 2}){sup 2+}/HZSM-5 surface: Lewis versus Brønsted acid sites

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Zhifeng [College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China); College of Material Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China); Zuo, Zhijun [Key Laboratory of Coal Science and Technology of Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China); Li, Zhe, E-mail: lizhe@tyut.edu.cn [College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China); Zhang, Jinshan [College of Material Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China)

    2014-12-01

    Graphical abstract: - Highlights: • NH{sub 3} adsorption is found to be more favorable energetically than NO adsorption on both Lewis and Brønsted acid sites. • Lewis and Brønsted acid sites are competitive energetically for NH{sub 3} adsorption. • Reduced-state Mo{sup 5+} is suggested to play a key role in adsorption and activation of NO{sub x} together with the adsorbed NH{sub 4}{sup +}. - Abstract: A systematic DFT study was carried out to investigate NH{sub 3} and NO adsorption on both Lewis and Brønsted acid sites of (MoO{sub 2}){sup 2+}/HZSM-5 catalyst by using cluster models. The adsorption energy results indicate that NH{sub 3} could strongly adsorb on both Lewis and Brønsted acid sites in the form of coordinated NH{sub 3} and NH{sub 4}{sup +}, respectively, whereas NO represents poorer adsorption ability. It is also found that Lewis and Brønsted acid sites are competitive energetically for NH{sub 3} adsorption. According to the difference in the proposed mechanisms for NH{sub 3} adsorption on different acid sites, particular attention has been focused on the first dissociation of coordinated NH{sub 3} for Lewis acid site and the effect of Mo site on the introduction of NO for Brønsted acid site. For the coordinated NH{sub 3} on Lewis acid site, the more electron donation from NH{sub 3} is, the greater its adsorption stability is and the higher active its H atoms are. In addition, DOS results show that stability of the H atoms is enhanced by interacting with framework oxygen and especially the H atoms chemical-bonded with framework oxygen. For the NH{sub 4}{sup +} on Brønsted acid site, reduced-state Mo{sup 5+} holds stronger reducibility and oxidizability than terminal oxygen, which is suggested to play a key role in adsorption and activation of NO{sub x} together with the adsorbed NH{sub 4}{sup +}.

  9. The NH4+-NO3--Cl--SO42--H2O aerosol system and its gas phase precursors at a pasture site in the Amazon Basin: How relevant are mineral cations and soluble organic acids?

    NARCIS (Netherlands)

    Trebs, I.; Metzger, S.; Meixner, F.X.; Helas, G.N.; Hoffer, A.; Rudich, Y.; Falkovich, A.H.; Moura, M.A.L.; Silva, da R.S.; Artaxo, P.; Slanina, J.; Andreae, M.O.

    2005-01-01

    Real-time measurements of ammonia, nitric acid, hydrochloric acid, sulfur dioxide and the water-soluble inorganic aerosol species, ammonium, nitrate, chloride, and sulfate were performed at a pasture site in the Amazon Basin (Rondônia, Brazil). The measurements were made during the late dry season (

  10. Exploration of the labeling of [11C]Tubastatin A at the hydroxamic acid site with [11C]carbon monoxide

    Science.gov (United States)

    Lu, Shuiyu; Zhang, Yi; Kalin, Jay; Cai, Lisheng; Kozikowski, Alan P.; Pike, Victor W.

    2015-01-01

    We aimed to label tubastatin A (1) with carbon-11 (t1/2 = 20.4 min) in the hydroxamic acid site to provide a potential radiotracer for imaging histone deacetylase 6 (HDAC6) in vivo with positron emission tomography (PET). Initial attempts at a one-pot Pd-mediated insertion of [11C]carbon monoxide between the aryl iodide (2) and hydroxylamine gave low radiochemical yields (< 5%) of [11C]1. Labeling was achieved in useful radiochemical yields (16.1 ± 5.6%, n = 4) through a two-step process based on Pd-mediated insertion of [11C]carbon monoxide between the aryl iodide (2) and p-nitrophenol to give the [11C]p-nitrophenyl ester ([11C]5), followed by ultrasound-assisted hydroxyaminolysis of the activated ester with excess hydroxylamine in DMSO/THF mixture in the presence of a strong phosphazene base P1-t-Bu. However, the success in labeling the hydroxamic acid group of [11C]tubastatin A was not transferable to the labeling of three other model hydroxamic acids. PMID:26647018

  11. Characterization of Site-Specific N-Glycopeptide Isoforms of α-1-Acid Glycoprotein from an Interlaboratory Study Using LC-MS/MS.

    Science.gov (United States)

    Lee, Ju Yeon; Lee, Hyun Kyoung; Park, Gun Wook; Hwang, Heeyoun; Jeong, Hoi Keun; Yun, Ki Na; Ji, Eun Sun; Kim, Kwang Hoe; Kim, Jun Seok; Kim, Jong Won; Yun, Sung Ho; Choi, Chi-Won; Kim, Seung Il; Lim, Jong-Sun; Jeong, Seul-Ki; Paik, Young-Ki; Lee, Soo-Youn; Park, Jisook; Kim, Su Yeon; Choi, Young-Jin; Kim, Yong-In; Seo, Jawon; Cho, Je-Yoel; Oh, Myoung Jin; Seo, Nari; An, Hyun Joo; Kim, Jin Young; Yoo, Jong Shin

    2016-12-02

    Glycoprotein conformations are complex and heterogeneous. Currently, site-specific characterization of glycopeptides is a challenge. We sought to establish an efficient method of N-glycoprotein characterization using mass spectrometry (MS). Using alpha-1-acid glycoprotein (AGP) as a model N-glycoprotein, we identified its tryptic N-glycopeptides and examined the data reproducibility in seven laboratories running different LC-MS/MS platforms. We used three test samples and one blind sample to evaluate instrument performance with entire sample preparation workflow. 165 site-specific N-glycopeptides representative of all N-glycosylation sites were identified from AGP 1 and AGP 2 isoforms. The glycopeptide fragmentations by collision-induced dissociation or higher-energy collisional dissociation (HCD) varied based on the MS analyzer. Orbitrap Elite identified the greatest number of AGP N-glycopeptides, followed by Triple TOF and Q-Exactive Plus. Reproducible generation of oxonium ions, glycan-cleaved glycopeptide fragment ions, and peptide backbone fragment ions was essential for successful identification. Laboratory proficiency affected the number of identified N-glycopeptides. The relative quantities of the 10 major N-glycopeptide isoforms of AGP detected in four laboratories were compared to assess reproducibility. Quantitative analysis showed that the coefficient of variation was N-glycopeptide isoforms of AGP from control and disease plasma sample.

  12. Scores of amino acid 0D-3D information as applied in cleavage site prediction and better specificity elucidation for human immunodeficiency virus type 1 protease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A new set of descriptors,namely score vectors of the zero dimension,one dimension,two dimensions and three dimensions(SZOTT),was derived from principle component analysis of a matrix of 1369 structural variables including 0D,1D,2D and 3D information for the 20 coded amino acids. SZOTT scales were then used in cleavage site prediction of human immunodeficiency virus type 1 protease. Linear discriminant analysis(LDA) and support vector machines(SVM) were applied to developing models to predict the cleavage sites. The results obtained by linear discriminant analysis(LDA) and support vector machines(SVM) are as follows. The Matthews correlation coefficients(MCC) by the resubstitution test,leave-one-out cross validation(LOOCV) and external validation are 0.879 and 0.911,0.849 and 0.901,0.822 and 0.846,respectively. The receiver operating characteristic(ROC) analysis showed that the SVM model possesses better simulative and predictive ability in comparison with the LDA model. Satisfactory results show that SZOTT descriptors can be further used to predict cleavage sites of human immunodeficiency virus type 1 protease.

  13. Scores of amino acid 0D-3D information as applied in cleavage site prediction and better specificity elucidation for human immunodeficiency virus type 1 protease

    Institute of Scientific and Technical Information of China (English)

    KANG LiFang; LIANG GuiZhao; SHU Mao; YANG ShanBin; LI ZhiLiang

    2008-01-01

    A new set of descriptors, namely score vectors of the zero dimension, one dimension, two dimensions and three dimensions (SZOTT), was derived from principle component analysis of a matrix of 1369 structural variables including 0D, 1D, 2D and 3D information for the 20 coded amino acids. SZOTT scales were then used in cleavage site prediction of human immunodeficiency virus type 1 protease. Linear discriminant analysis (LDA) and support vector machines (SVM) were applied to developing models to predict the cleavage sites. The results obtained by linear discriminant analysis (LDA) and support vector machines (SVM) are as follows. The Matthews correlation coefficients (MCC) by the resubstitution test, leave-one-out cross validation (LOOCV) and external validation are 0.879 and 0.911, 0.649 and 0.901, 0.822 and 0.846, respectively. The receiver operating characteristic (ROC) analysis showed that the SVM model possesses better simulative and predictive ability in comparison with the LDA model. Satisfactory results show that SZOTT descriptors can be further used to predict cleavage sites of human immunodeficiency virus type 1 protease.

  14. Enhancement of bacterial iron and sulfate respiration for in situ bioremediation of acid mine drainage sites: a case study

    Energy Technology Data Exchange (ETDEWEB)

    Bilgin, A.A.; Harrington, J.M.; Silverstein, J. [ARCADIS G& amp; M, Highlands Ranch, CO (United States)

    2007-08-15

    The prevention of acid mine drainage (AMD) in situ is more attractive than down-gradient treatment alternatives that do not involve source control. AMD source control can be achieved by shifting the microbial activity in the sulfidic rock from pyrite oxidation to anaerobic heterotrophic activity. This is achieved by adding biodegradable organic carbon amendments to the sulfidic rock. This technique was applied to an abandoned coal mine pool in Pennsylvania. The pool had a pH of 3.0 to 3.5. Following treatment, near-neutral pH and decreased effluent heavy metal concentrations were achieved. In situ bioremediation by the enhancement of bacterial iron and sulfate reduction is a promising technology for AMD prevention.

  15. Gephyrin-mediated γ-aminobutyric acid type A and glycine receptor clustering relies on a common binding site

    DEFF Research Database (Denmark)

    Maric, Hans-Michael; Mukherjee, Jayanta; Tretter, Verena

    2011-01-01

    Gephyrin is the major protein determinant for the clustering of inhibitory neurotransmitter receptors. Earlier analyses revealed that gephyrin tightly binds to residues 398-410 of the glycine receptor β subunit (GlyR β) and, as demonstrated only recently, also interacts with GABA(A) receptors (GABA......(A)Rs) containing the α1, α2, and α3 subunits. Here, we dissect the molecular basis underlying the interactions between gephyrin and GABA(A)Rs containing these α-subunits and compare them to the crystal structure of the gephyrin-GlyR β complex. Biophysical and biochemical assays revealed that, in contrast to its...... that are central for gephyrin binding. Consistent with the biochemical data, mutations of the corresponding residues within the cytoplasmic domain of α2 subunit-containing GABA(A)Rs attenuated clustering of these receptors at postsynaptic sites in hippocampal neurons. Taken together, our experiments provide key...

  16. Active-Site Models of Bacterial Nitric Oxide Reductase Featuring Tris-Histidyl and Glutamic Acid Mimics: Influence of Carboxylate Ligand on FeB Binding and Heme Fe/FeB Redox Potential

    Science.gov (United States)

    Collman, James P.; Yan, Yi-Long; Lei, Jianping; Dinolfo, Peter H.

    2008-01-01

    Active-site models of bacterial nitric oxide reductase (NOR) featuring a heme iron and a trisimidazole and a glutaric acid-bound non-heme iron (FeB) have been synthesized. These models closely replicate the proposed active site of native NORs. Examination of these models shows that the glutamic acid mimic is required for both FeB retention in the distal binding site and proper modulation of the redox potentials of both the heme and non-heme irons. PMID:16961346

  17. Diverse CRISPRs evolving in human microbiomes.

    Directory of Open Access Journals (Sweden)

    Mina Rho

    Full Text Available CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats loci, together with cas (CRISPR-associated genes, form the CRISPR/Cas adaptive immune system, a primary defense strategy that eubacteria and archaea mobilize against foreign nucleic acids, including phages and conjugative plasmids. Short spacer sequences separated by the repeats are derived from foreign DNA and direct interference to future infections. The availability of hundreds of shotgun metagenomic datasets from the Human Microbiome Project (HMP enables us to explore the distribution and diversity of known CRISPRs in human-associated microbial communities and to discover new CRISPRs. We propose a targeted assembly strategy to reconstruct CRISPR arrays, which whole-metagenome assemblies fail to identify. For each known CRISPR type (identified from reference genomes, we use its direct repeat consensus sequence to recruit reads from each HMP dataset and then assemble the recruited reads into CRISPR loci; the unique spacer sequences can then be extracted for analysis. We also identified novel CRISPRs or new CRISPR variants in contigs from whole-metagenome assemblies and used targeted assembly to more comprehensively identify these CRISPRs across samples. We observed that the distributions of CRISPRs (including 64 known and 86 novel ones are largely body-site specific. We provide detailed analysis of several CRISPR loci, including novel CRISPRs. For example, known streptococcal CRISPRs were identified in most oral microbiomes, totaling ∼8,000 unique spacers: samples resampled from the same individual and oral site shared the most spacers; different oral sites from the same individual shared significantly fewer, while different individuals had almost no common spacers, indicating the impact of subtle niche differences on the evolution of CRISPR defenses. We further demonstrate potential applications of CRISPRs to the tracing of rare species and the virus exposure of individuals

  18. Evolving ATLAS Computing For Today’s Networks

    CERN Document Server

    Campana, S; The ATLAS collaboration; Jezequel, S; Negri, G; Serfon, C; Ueda, I

    2012-01-01

    The ATLAS computing infrastructure was designed many years ago based on the assumption of rather limited network connectivity between computing centres. ATLAS sites have been organized in a hierarchical model, where only a static subset of all possible network links can be exploited and a static subset of well connected sites (CERN and the T1s) can cover important functional roles such as hosting master copies of the data. The pragmatic adoption of such simplified approach, in respect of a more relaxed scenario interconnecting all sites, was very beneficial during the commissioning of the ATLAS distributed computing system and essential in reducing the operational cost during the first two years of LHC data taking. In the mean time, networks evolved far beyond this initial scenario: while a few countries are still poorly connected with the rest of the WLCG infrastructure, most of the ATLAS computing centres are now efficiently interlinked. Our operational experience in running the computing infrastructure in ...

  19. Signatures of Autotrophic and Heterotrophic Metabolic Activity in Enrichment Cultures from a Sulphur Oxidizing Acid Mine Site

    Science.gov (United States)

    Slater, G. F.; Bernier, L.; Cowie, B. R.; Warren, L. A.

    2006-12-01

    Delineating the role of microorganisms in geochemical processes of interest in natural environments requires the development of tools that provide the ability to distinguish amongst microbial activity associated with different metabolic guilds. The gap between phylogenetic characterization and phenotypic understanding remains, underscoring the need to consider alternative methods. Compound specific analysis of cellular components has the potential to differentiate between active metabolic processes supporting microbial communities and may be especially useful in extreme environments. The goal of this study was to determine whether the phospholipids fatty acid (PLFA) distribution and isotopic signatures associated with autotrophs and heterotrophs enriched from an acid mine drainage (AMD) system differed, and further whether natural consortial autotrophic isolates showed similar signatures to autotrophic pure strains of Acidithiobacillus ferrooxidans and A. thiooxidans. Two distinct initial enrichments with tetrathionate and CO2 yielded primarily autotrophic (95%) Acidithiobaccillus spp. sulphur oxidizing communities. The remaining microbial members of theses enrichments (subculture of the consortial isolates in a medium amended with glucose but without tetrathionate selectively resulted in their visible growth. PLFA profiles and δ13C signatures from autotrophic (1) natural enrichments, pure cultures of (2) A. ferrooxidans and (3) A. thiooxidans were similar, but collectively differed from those of the natural heterotrophic enrichment cultures. The PLFA profiles for the heterotrophic communities were made up of primarily (88-99%) C16:0 and two isomers of C18:1. In contrast, the autotrophic communities had high proportions of C16:1 (up to 18%) as well as cyclo C17 and cyclo C19 PLFA that combined comprised 18 to 58% of the observed PLFA. The δ13C signatures of the PLFA also differed strongly between the two trophic levels. The δ13C of the autotrophic PLFA, - 24 to

  20. WSC-07: Evolving the Web Services Challenge

    NARCIS (Netherlands)

    Blake, M. Brian; Cheung, William K.W.; Jaeger, Michael C.; Wombacher, Andreas

    2007-01-01

    Service-oriented architecture (SOA) is an evolving architectural paradigm where businesses can expose their capabilities as modular, network-accessible software services. By decomposing capabilities into modular services, organizations can share their offerings at multiple levels of granularity whil

  1. Robot navigation system using intrinsic evolvable hardware

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Recently there has been great interest in the idea that evolvable system based on the principle of ar tifcial intelligence can be used to continuously and autonomously adapt the behaviour of physically embedded systems such as autonomous mobile robots and intelligent home devices. Meanwhile, we have seen the introduc tion of evolvable hardware(EHW): new integrated electronic circuits that are able to continuously evolve to a dapt the chages in the environment implemented by evolutionary algorithms such as genetic algorithm(GA)and reinforcement learning. This paper concentrates on developing a robotic navigation system whose basic behav iours are obstacle avoidance and light source navigation. The results demonstrate that the intrinsic evolvable hardware system is able to create the stable robotiiuc behaviours as required in the real world instead of the tra ditional hardware systems.

  2. Evolvability Characterization in the Context of SOA

    Science.gov (United States)

    Arciniegas H., Jose L.; Dueñas L., Juan C.

    Service-Oriented Architecture (SOA) is an architectural style which promotes reuse of self-contained services. These self-contained services allow a better consideration of software quality characteristics as they can be independently analyzed. In our work, the evolvability quality characteristic has been considered, due to its impact in the stages of Maintenance and Evolution (M&E) for the software enterprises. Three goals are underlined in this paper: first, the relationship between SOA and quality characteristics focusing on a precise definition of evolvability of a software product from the SOA perspective, second a M&E model for SOA, and finally, some experiences are presented in order to assess evolvability in real software products. Two case studies have been executed: the first one analyzing the evolvability of the OSGi framework. And in the second case, the model is used in local Small and Medium Enterprises (SMEs), where an improvement process has been executed.

  3. Acquiring Evolving Technologies: Web Services Standards

    Science.gov (United States)

    2016-06-30

    2006 Carnegie Mellon University Acquiring Evolving Technologies: Web Services Standards Harry L. Levinson Software Engineering Institute Carnegie...Acquiring Evolving Technologies: Web Services Standards 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...NUMBER OF PAGES 22 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form

  4. Electrochemically active microorganisms from an acid mine drainage-affected site promote cathode oxidation in microbial fuel cells

    KAUST Repository

    Rojas, Claudia

    2017-08-03

    The limited database of acidophilic or acidotolerant electrochemically active microorganisms prevents advancements on microbial fuel cells (MFCs) operated under low pH. In this study, three MFCs were used to enrich cathodic biofilms using acid mine drainage (AMD) sediments as inoculum. Linear sweep voltammetry showed cathodic current plateaus of 5.5 (± 0.7) mA at about − 170 mV vs Ag/AgCl and 8.5 (± 0.9) mA between − 500 mV to − 450 mV vs Ag/AgCl for biofilms developed on small graphite fiber brushes. After gamma irradiation, biocathodes exhibited a decrease in current density approaching that of abiotic controls. Electrochemical impedance spectroscopy showed six-fold lower charge transfer resistance with viable biofilm. Pyrosequencing data showed that Proteobacteria and Firmicutes dominated the biofilms. Acidithiobacillus representatives were enriched in some biocathodes, supporting the potential importance of these known iron and sulfur oxidizers as cathodic biocatalysts. Other acidophilic chemolithoautotrophs identified included Sulfobacillus and Leptospirillum species. The presence of chemoautotrophs was consistent with functional capabilities predicted by PICRUSt related to carbon fixation pathways in prokaryotic microorganisms. Acidophilic or acidotolerant heterotrophs were also abundant; however, their contribution to cathodic performance is unknown. This study directs subsequent research efforts to particular groups of AMD-associated bacteria that are electrochemically active on cathodes.

  5. Sulfur-H{sub z}(CH{sub x}){sub y}(z = 0,1) functionalized metal oxide nanostructure decorated interfaces: Evidence of Lewis base and Brönsted acid sites – Influence on chemical sensing

    Energy Technology Data Exchange (ETDEWEB)

    Laminack, William; Baker, Caitlin [Department of Physics, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Gole, James, E-mail: james.gole@physics.gatech.edu [Department of Physics, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Department of Mechanical Engineering, Georgia Tech, Atlanta, GA 30332 (United States)

    2015-06-15

    Nanostructure metal oxide decorated n-type extrinsic porous silicon (PS) semiconductor interfaces are modified through in-situ interaction with acidic ethane and butane thiols (EtSH, BuSH) and basic diethyl sulfide (Et{sub 2}S). Highly sensitive conductometric sensor evaluations and X-ray Photoelectron Spectroscopy demonstrate the effect of sulfur group functionalization modifying the acidity of the metal oxides and their interaction with NH{sub 3}. SEM micrographs demonstrate that the sulfur treated particles are less than 30 nm in size. EDAX studies confirm the chemical composition of the modified nanoparticles and suggest the surface interaction of the sulfides and thiols. The acidic thiols can form Brönsted acidic sites enhancing the acidity of the metal oxides, thus broadening the initial metal oxide acidity range. The sulfides interact to lower the Lewis acidity of nanostructured metal oxide sites. Conductometric response matrices with NH{sub 3} at room temperature, corresponding to the thiol and sulfide treated nanostructures of the metal oxides TiO{sub 2}, SnO{sub x}, Ni{sub x}O, Cu{sub x}O, and Au{sub x}O (x >> 1) are evaluated for a dominant electron transduction process forming the basis for reversible chemical sensing in the absence of chemical bond formation. Treatment with the acidic thiols enhances the metal center acidity. It is suggested that the thiols can interact to increase the Brönsted acidity of the doped metal oxide surface if they maintain SH bonds. This process may account for the shift in Lewis acidity as the Brönsted acid sites counter the decrease in Lewis acidity resulting from the interaction of S-(CH{sub x}){sub y} groups. In contrast, treatment with basic Et{sub 2}S decreases the Lewis acidity of the metal oxide sites, enhancing the basicity of the decorated interface. XPS measurements indicate a change in binding energy (BE) of the metal and oxygen centers. The observed changes in conductometric response do not represent a

  6. Acid neutralizing capacity and leachate results for igneous rocks, with associated carbon contents of derived soils, Animas River AML site, Silverton, Colorado

    Science.gov (United States)

    Yager, Douglas B.; Stanton, Mark R.; Choate, LaDonna M.; Burchell,

    2009-01-01

    Mine planning efforts have historically overlooked the possible acid neutralizing capacity (ANC) that local igneous rocks can provide to help neutralize acidmine drainage. As a result, limestone has been traditionally hauled to mine sites for use in neutralizing acid drainage. Local igneous rocks, when used as part of mine life-cycle planning and acid mitigation strategy, may reduce the need to transport limestone to mine sites because these rocks can contain acid neutralizing minerals. Igneous hydrothermal events often introduce moderately altered mineral assemblages peripheral to more intensely altered rocks that host metal-bearing veins and ore bodies. These less altered rocks can contain ANC minerals (calcite-chlorite-epidote) and are referred to as a propylitic assemblage. In addition, the carbon contents of soils in areas of new mining or those areas undergoing restoration have been historically unknown. Soil organic carbon is an important constituent to characterize as a soil recovery benchmark that can be referred to during mine cycle planning and restoration. This study addresses the mineralogy, ANC, and leachate chemistry of propylitic volcanic rocks that host polymetallic mineralization in the Animas River watershed near the historical Silverton, Colorado, mining area. Acid titration tests on volcanic rocks containing calcite (2 – 20 wt %) and chlorite (6 – 25 wt %), have ANC ranging from 4 – 146 kg/ton CaCO3 equivalence. Results from a 6-month duration, kinetic reaction vessel test containing layered pyritic mine waste and underlying ANC volcanic rock (saturated with deionized water) indicate that acid generating mine waste (pH 2.4) has not overwhelmed the ANC of propylitic volcanic rocks (pH 5.8). Sequential leachate laboratory experiments evaluated the concentration of metals liberated during leaching. Leachate concentrations of Cu-Zn-As-Pb for ANC volcanic rock are one-to-three orders of magnitude lower when compared to leached solution from

  7. A smart sealed nucleic acid biosensor based on endogenous reference gene detection to screen and identify mammals on site

    Science.gov (United States)

    Xu, Yuancong; Xiang, Wenjin; Wang, Qin; Cheng, Nan; Zhang, Li; Huang, Kunlun; Xu, Wentao

    2017-01-01

    The identification of meat adulteration is a hotspot for food research worldwide. In this paper, a smart and sealed biosensor that combines loop-mediated isothermal amplification (LAMP) with a lateral flow device (LFD) was developed, resulting in the universal mammalian assessment on site. First, the highly specific chromosomal Glucagon gene (Gcg) was chosen as the endogenous reference gene, and the LAMP approach provided double-labeled duplex DNA products using FITC- and BIO- modified primers. Then, an LFD strategy was used for specific signal recognition through an immunoassay. Meanwhile, LFD-LAMP was compared to LAMP and real-time LAMP, the results showed consistent high specificity and sensitivity but in a more convenient and easy-to-use system. In addition, the detection limit was as low as 10 pg, which was equivalent to 3~5 copies in mammals. All of the reactions were performed in a sealed system regardless of the amplification process or products recognized. Therefore, the smart design demonstrated significantly high specificity and the ability to detect trace amounts of DNA in complex and processed foods with mammalian meat. As a universal and specific platform for the detection of mammalian DNA, this smart biosensor is an excellent prospect for species identification and meat adulteration. PMID:28233849

  8. Engineering D-Amino Acid Containing Collagen Like Peptide at the Cleavage Site of Clostridium histolyticum Collagenase for Its Inhibition.

    Directory of Open Access Journals (Sweden)

    Punitha Velmurugan

    Full Text Available Collagenase is an important enzyme which plays an important role in degradation of collagen in wound healing, cancer metastasis and even in embryonic development. However, the mechanism of this degradation has not yet been completely understood. In the field of biomedical and protein engineering, the design and development of new peptide based materials is of main concern. In the present work an attempt has been made to study the effect of DAla in collagen like peptide (imino-poor region of type I collagen on the structure and stability of peptide against enzyme hydrolysis. Effect of replacement of DAla in the collagen like peptide has been studied using circular dichroic spectroscopy (CD. Our findings suggest that, DAla substitution leads to conformational changes in the secondary structure and favours the formation of polyproline II conformation than its L-counterpart in the imino-poor region of collagen like peptides. Change in the chirality of alanine at the cleavage site of collagenase in the imino-poor region inhibits collagenolytic activity. This may find application in design of peptides and peptidomimics for enzyme-substrate interaction, specifically with reference to collagen and other extra cellular matrix proteins.

  9. Observation of nighttime nitrous acid (HONO) formation at a non-urban site during PRIDE-PRD2004 in China

    Science.gov (United States)

    Su, Hang; Cheng, Ya Fang; Cheng, Peng; Zhang, Yuan Hang; Dong, Shuofei; Zeng, Li Min; Wang, Xuesong; Slanina, Jacob; Shao, Min; Wiedensohler, Alfred

    Though the importance of HONO as an OH precursor has been recognized for years, its chemical formation pathway is still not well understood. This inhibited the simulations of HONO and observation-based formation rates provided an alternative for the air quality models. However, HONO formation rate derived from certain period may be significantly influenced by uncertainties in transport and emission processes. In this study the use of large sample and scaling methods were recommended in the calculation of HONO formation rate. During the Program of Regional Integrated Experiments of Air Quality over Pear River Delta (PRIDE-PRD2004), good correlations between HONO and NO2 were found supporting the involvement of NO2 in HONO formation. An average NO2-to-HONO nighttime conversion rate CHONO of 1.6%h-1 was derived at a non-urban site Xinken. This conversion rate was comparable to other field measurements and could not be explained by gas phase reactions only. If assumed that HONO was formed only on the ground surface, the observed conversion rate could be explained by the reactions of NO2 on ground surfaces only if three deposited NO2 lead to one HONO released. The emission factor of HONO and its sampling interferences during the measurements were also evaluated in this article.

  10. Sulfur-Bearing Phases Detected by Evolved Gas Analysis of the Rocknest Aeolian Deposit, Gale Crater, Mars

    Science.gov (United States)

    Mcadam, Amy Catherine; Franz, Heather Bryant

    2014-01-01

    The Sample Analysis at Mars (SAM) instrument suite detected SO2, H2S, OCS, and CS2 from approx.450 to 800 C during evolved gas analysis (EGA) of materials from the Rocknest aeolian deposit in Gale Crater, Mars. This was the first detection of evolved sulfur species from a Martian surface sample during in situ EGA. SO2(approx. 3-22 micro-mol) is consistent with the thermal decomposition of Fe sulfates or Ca sulfites, or evolution/desorption from sulfur-bearing amorphous phases. Reactions between reduced sulfur phases such as sulfides and evolved O2 or H2O in the SAM oven are another candidate SO2 source. H2S (approx.41-109 nmol) is consistent with interactions of H2O, H2 and/or HCl with reduced sulfur phases and/or SO2 in the SAM oven. OCS (approx.1-5 nmol) and CS2(approx.0.2-1 nmol) are likely derived from reactions between carbon-bearing compounds and reduced sulfur. Sulfates and sulfites indicate some aqueous interactions, although not necessarily at the Rocknest site; Fe sulfates imply interaction with acid solutions whereas Ca sulfites can form from acidic to near-neutral solutions. Sulfides in the Rocknest materials suggest input from materials originally deposited in a reducing environment or from detrital sulfides from an igneous source. The presence of sulfides also suggests that the materials have not been extensively altered by oxidative aqueous weathering. The possibility of both reduced and oxidized sulfur compounds in the deposit indicates a nonequilibrium assemblage. Understanding the sulfur mineralogy in Rocknest materials, which exhibit chemical similarities to basaltic fines analyzed elsewhere on Mars, can provide insight in to the origin and alteration history of Martian surface materials.

  11. Sulfur-bearing phases detected by evolved gas analysis of the Rocknest aeolian deposit, Gale Crater, Mars

    Science.gov (United States)

    McAdam, Amy C.; Franz, Heather B.; Sutter, Brad; Archer, Paul D.; Freissinet, Caroline; Eigenbrode, Jennifer L.; Ming, Douglas W.; Atreya, Sushil K.; Bish, David L.; Blake, David F.; Bower, Hannah E.; Brunner, Anna; Buch, Arnaud; Glavin, Daniel P.; Grotzinger, John P.; Mahaffy, Paul R.; McLennan, Scott M.; Morris, Richard V.; Navarro-González, Rafael; Rampe, Elizabeth B.; Squyres, Steven W.; Steele, Andrew; Stern, Jennifer C.; Sumner, Dawn Y.; Wray, James J.

    2014-02-01

    The Sample Analysis at Mars (SAM) instrument suite detected SO2, H2S, OCS, and CS2 from ~450 to 800°C during evolved gas analysis (EGA) of materials from the Rocknest aeolian deposit in Gale Crater, Mars. This was the first detection of evolved sulfur species from a Martian surface sample during in situ EGA. SO2 (~3-22 µmol) is consistent with the thermal decomposition of Fe sulfates or Ca sulfites, or evolution/desorption from sulfur-bearing amorphous phases. Reactions between reduced sulfur phases such as sulfides and evolved O2 or H2O in the SAM oven are another candidate SO2 source. H2S (~41-109 nmol) is consistent with interactions of H2O, H2 and/or HCl with reduced sulfur phases and/or SO2 in the SAM oven. OCS (~1-5 nmol) and CS2 (~0.2-1 nmol) are likely derived from reactions between carbon-bearing compounds and reduced sulfur. Sulfates and sulfites indicate some aqueous interactions, although not necessarily at the Rocknest site; Fe sulfates imply interaction with acid solutions whereas Ca sulfites can form from acidic to near-neutral solutions. Sulfides in the Rocknest materials suggest input from materials originally deposited in a reducing environment or from detrital sulfides from an igneous source. The presence of sulfides also suggests that the materials have not been extensively altered by oxidative aqueous weathering. The possibility of both reduced and oxidized sulfur compounds in the deposit indicates a nonequilibrium assemblage. Understanding the sulfur mineralogy in Rocknest materials, which exhibit chemical similarities to basaltic fines analyzed elsewhere on Mars, can provide insight in to the origin and alteration history of Martian surface materials.

  12. A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells.

    Science.gov (United States)

    Partanen, Sanna; Storch, Stephan; Löffler, Hans-Gerhard; Hasilik, Andrej; Tyynelä, Jaana; Braulke, Thomas

    2003-01-01

    The substitution of an active-site aspartic acid residue by asparagine in the lysosomal protease cathepsin D (CTSD) results in a loss of enzyme activity and severe cerebrocortical atrophy in a novel form of neuronal ceroid lipofuscinosis in sheep [Tyynelä, Sohar, Sleat, Gin, Donnelly, Baumann, Haltia and Lobel (2000) EMBO J. 19, 2786-2792]. In the present study we have introduced the corresponding mutation by replacing aspartic acid residue 293 with asparagine (D293N) into the mouse CTSD cDNA to analyse its effect on synthesis, transport and stability in transfected HEK-293 cells. The complete inactivation of mutant D293N mouse CTSD was confirmed by a newly developed fluorimetric quantification system. Moreover, in the heterologous overexpression systems used, mutant D293N mouse CTSD was apparently unstable and proteolytically modified during early steps of the secretory pathway, resulting in a loss of mass by about 1 kDa. In the affected sheep, the endogenous mutant enzyme was stable but also showed the shift in its molecular mass. In HEK-293 cells, the transport of the mutant D293N mouse CTSD to the lysosome was delayed and associated with a low secretion rate compared with wild-type CTSD. These data suggest that the mutation may result in a conformational change which affects stability, processing and transport of the enzyme. PMID:12350228

  13. Probing the active site of MIO-dependent aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites.

    Science.gov (United States)

    Cooke, Heather A; Bruner, Steven D

    2010-09-01

    The tyrosine aminomutase SgTAM produces (S)-ss-tyrosine from L-tyrosine in the biosynthesis of the enediyne antitumor antibiotic C-1027. This conversion is promoted by the methylideneimidazole-5-one (MIO) prosthetic group. MIO was first identified in the homologous family of ammonia lyases, which deaminate aromatic amino acids to form alpha,ss-unsaturated carboxylates. Studies of substrate specificity have been described for lyases but there have been limited reports in altering the substrate specificity of aminomutases. Furthermore, it remains unclear as to what structural properties are responsible for catalyzing the presumed readdition of the amino group into the alpha,ss-unsaturated intermediates to form ss-amino acids. Attempts to elucidate specificity and mechanistic determinants of SgTAM have also proved to be difficult as it is recalcitrant to perturbations to the active site via mutagenesis. An X-ray cocrystal structure of the SgTAM mutant of the catalytic base with L-tyrosine verified important substrate binding residues as well as the enzymatic base. Further mutagenesis revealed that removal of these crucial interactions renders the enzyme inactive. Proposed structural determinants for mutase activity probed via mutagenesis, time-point assays and X-ray crystallography revealed a complicated role for these residues in maintaining key quaternary structure properties that aid in catalysis. Copyright 2010 Wiley Periodicals, Inc.

  14. Evolution of hydra, a recently evolved testis-expressed gene with nine alternative first exons in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Shou-Tao Chen

    2007-07-01

    Full Text Available We describe here the Drosophila gene hydra that appears to have originated de novo in the melanogaster subgroup and subsequently evolved in both structure and expression level in Drosophila melanogaster and its sibling species. D. melanogaster hydra encodes a predicted protein of approximately 300 amino acids with no apparent similarity to any previously known proteins. The syntenic region flanking hydra on both sides is found in both D. ananassae and D. pseudoobscura, but hydra is found only in melanogaster subgroup species, suggesting that it originated less than approximately 13 million y ago. Exon 1 of hydra has undergone recurrent duplications, leading to the formation of nine tandem alternative exon 1s in D. melanogaster. Seven of these alternative exons are flanked on their 3' side by the transposon DINE-1 (Drosophila interspersed element-1. We demonstrate that at least four of the nine duplicated exon 1s can function as alternative transcription start sites. The entire hydra locus has also duplicated in D. simulans and D. sechellia. D. melanogaster hydra is expressed most intensely in the proximal testis, suggesting a role in late-stage spermatogenesis. The coding region of hydra has a relatively high Ka/Ks ratio between species, but the ratio is less than 1 in all comparisons, suggesting that hydra is subject to functional constraint. Analysis of sequence polymorphism and divergence of hydra shows that it has evolved under positive selection in the lineage leading to D. melanogaster. The dramatic structural changes surrounding the first exons do not affect the tissue specificity of gene expression: hydra is expressed predominantly in the testes in D. melanogaster, D. simulans, and D. yakuba. However, we have found that expression level changed dramatically (approximately >20-fold between D. melanogaster and D. simulans. While hydra initially evolved in the absence of nearby transposable element insertions, we suggest that the subsequent

  15. Sonolytic and Silent Polymerization of Methacrlyic Acid Butyl Ester Catalyzed by a New Onium Salt with bis-Active Sites in a Biphasic System — A Comparative Investigation

    Directory of Open Access Journals (Sweden)

    Perumberkandgai A. Vivekanand

    2013-02-01

    Full Text Available Currently, ingenious new analytical and process experimental techniques which are environmentally benign techniques, viz., ultrasound irradiation, have become immensely popular in promoting various reactions. In this work, a novel soluble multi-site phase transfer catalyst (PTC viz., 1,4-bis-(propylmethyleneammounium chloridebenzene (BPMACB was synthesized and its catalytic efficiency was assessed by observing the kinetics of sonolytic polymerization of methacrylic acid butyl ester (MABE using potassium persulphate (PPS as an initiator. The ultrasound–multi-site phase transfer catalysis (US-MPTC-assisted polymerization reaction was compared with the silent (non-ultrasonic polymerization reaction. The effects of the catalyst and various reaction parameters on the catalytic performance were in detail investigated by following the kinetics of polymerization of MABE in an ethyl acetate-water biphasic system. From the detailed kinetic investigation we propose a plausible mechanism. Further the kinetic results demonstrate clearly that ultrasound-assisted phase-transfer catalysis significantly increased the reaction rate when compared to silent reactions. Notably, this environmentally benign and cost-effective process has great potential to be applied in various polymer industries.

  16. Site-directed mutagenesis of amino acid residues of D1 protein interacting with phosphatidylglycerol affects the function of plastoquinone QB in photosystem II.

    Science.gov (United States)

    Endo, Kaichiro; Mizusawa, Naoki; Shen, Jian-Ren; Yamada, Masato; Tomo, Tatsuya; Komatsu, Hirohisa; Kobayashi, Masami; Kobayashi, Koichi; Wada, Hajime

    2015-12-01

    Recent X-ray crystallographic analysis of photosystem (PS) II at 1.9-Å resolution identified 20 lipid molecules in the complex, five of which are phosphatidylglycerol (PG). In this study, we mutagenized amino acid residues S232 and N234 of D1, which interact with two of the PG molecules (PG664 and PG694), by site-directed mutagenesis in Synechocystis sp. PCC 6803 to investigate the role of the interaction in PSII. The serine and asparagine residues at positions 232 and 234 from the N-terminus were mutagenized to alanine and aspartic acid, respectively, and a mutant carrying both amino acid substitutions was also produced. Although the obtained mutants, S232A, N234D, and S232AN234D, exhibited normal growth, they showed decreased photosynthetic activities and slower electron transport from QA to QB than the control strain. Thermoluminescence analysis suggested that this slower electron transfer in the mutants was caused by more negative redox potential of QB, but not in those of QA and S2. In addition, the levels of extrinsic proteins, PsbV and PsbU, were decreased in PSII monomer purified from the S232AN234D mutant, while that of Psb28 was increased. In the S232AN234D mutant, the content of PG in PSII was slightly decreased, whereas that of monogalactosyldiacylglycerol was increased compared with the control strain. These results suggest that the interactions of S232 and N234 with PG664 and PG694 are important to maintain the function of QB and to stabilize the binding of extrinsic proteins to PSII.

  17. Binding of 3,4,5,6-Tetrahydroxyazepanes to the Acid-[beta]-glucosidase Active Site: Implications for Pharmacological Chaperone Design for Gaucher Disease

    Energy Technology Data Exchange (ETDEWEB)

    Orwig, Susan D.; Tan, Yun Lei; Grimster, Neil P.; Yu, Zhanqian; Powers, Evan T.; Kelly, Jeffery W.; Lieberman, Raquel L. (Scripps); (GIT)

    2013-03-07

    Pharmacologic chaperoning is a therapeutic strategy being developed to improve the cellular folding and trafficking defects associated with Gaucher disease, a lysosomal storage disorder caused by point mutations in the gene encoding acid-{beta}-glucosidase (GCase). In this approach, small molecules bind to and stabilize mutant folded or nearly folded GCase in the endoplasmic reticulum (ER), increasing the concentration of folded, functional GCase trafficked to the lysosome where the mutant enzyme can hydrolyze the accumulated substrate. To date, the pharmacologic chaperone (PC) candidates that have been investigated largely have been active site-directed inhibitors of GCase, usually containing five- or six-membered rings, such as modified azasugars. Here we show that a seven-membered, nitrogen-containing heterocycle (3,4,5,6-tetrahydroxyazepane) scaffold is also promising for generating PCs for GCase. Crystal structures reveal that the core azepane stabilizes GCase in a variation of its proposed active conformation, whereas binding of an analogue with an N-linked hydroxyethyl tail stabilizes GCase in a conformation in which the active site is covered, also utilizing a loop conformation not seen previously. Although both compounds preferentially stabilize GCase to thermal denaturation at pH 7.4, reflective of the pH in the ER, only the core azepane, which is a mid-micromolar competitive inhibitor, elicits a modest increase in enzyme activity for the neuronopathic G202R and the non-neuronopathic N370S mutant GCase in an intact cell assay. Our results emphasize the importance of the conformational variability of the GCase active site in the design of competitive inhibitors as PCs for Gaucher disease.

  18. Identification of N-methyl-D-aspartic acid (NMDA) receptor subtype-specific binding sites that mediate direct interactions with scaffold protein PSD-95.

    Science.gov (United States)

    Cousins, Sarah L; Stephenson, F Anne

    2012-04-13

    N-methyl-D-aspartate (NMDA) neurotransmitter receptors and the postsynaptic density-95 (PSD-95) membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins are integral components of post-synaptic macromolecular signaling complexes that serve to propagate glutamate responses intracellularly. Classically, NMDA receptor NR2 subunits associate with PSD-95 MAGUKs via a conserved ES(E/D)V amino acid sequence located at their C termini. We previously challenged this dogma to demonstrate a second non-ES(E/D)V PSD-95-binding site in both NMDA receptor NR2A and NR2B subunits. Here, using a combination of co-immunoprecipitations from transfected mammalian cells, yeast two-hybrid interaction assays, and glutathione S-transferase (GST) pulldown assays, we show that NR2A subunits interact directly with PSD-95 via the C-terminal ESDV motif and additionally via an Src homology 3 domain-binding motif that associates with the Src homology 3 domain of PSD-95. Peptide inhibition of co-immunoprecipitations of NR2A and PSD-95 demonstrates that both the ESDV and non-ESDV sites are required for association in native brain tissue. Furthermore, we refine the non-ESDV site within NR2B to residues 1149-1157. These findings provide a molecular basis for the differential association of NMDA receptor subtypes with PSD-95 MAGUK scaffold proteins. These selective interactions may contribute to the organization, lateral mobility, and ultimately the function of NMDA receptor subtypes at synapses. Furthermore, they provide a more general molecular mechanism by which the scaffold, PSD-95, may discriminate between potential interacting partner proteins.

  19. Identification of N-Methyl-d-aspartic Acid (NMDA) Receptor Subtype-specific Binding Sites That Mediate Direct Interactions with Scaffold Protein PSD-95*

    Science.gov (United States)

    Cousins, Sarah L.; Stephenson, F. Anne

    2012-01-01

    N-methyl-d-aspartate (NMDA) neurotransmitter receptors and the postsynaptic density-95 (PSD-95) membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins are integral components of post-synaptic macromolecular signaling complexes that serve to propagate glutamate responses intracellularly. Classically, NMDA receptor NR2 subunits associate with PSD-95 MAGUKs via a conserved ES(E/D)V amino acid sequence located at their C termini. We previously challenged this dogma to demonstrate a second non-ES(E/D)V PSD-95-binding site in both NMDA receptor NR2A and NR2B subunits. Here, using a combination of co-immunoprecipitations from transfected mammalian cells, yeast two-hybrid interaction assays, and glutathione S-transferase (GST) pulldown assays, we show that NR2A subunits interact directly with PSD-95 via the C-terminal ESDV motif and additionally via an Src homology 3 domain-binding motif that associates with the Src homology 3 domain of PSD-95. Peptide inhibition of co-immunoprecipitations of NR2A and PSD-95 demonstrates that both the ESDV and non-ESDV sites are required for association in native brain tissue. Furthermore, we refine the non-ESDV site within NR2B to residues 1149–1157. These findings provide a molecular basis for the differential association of NMDA receptor subtypes with PSD-95 MAGUK scaffold proteins. These selective interactions may contribute to the organization, lateral mobility, and ultimately the function of NMDA receptor subtypes at synapses. Furthermore, they provide a more general molecular mechanism by which the scaffold, PSD-95, may discriminate between potential interacting partner proteins. PMID:22375001

  20. Reliability of genetic networks is evolvable

    Science.gov (United States)

    Braunewell, Stefan; Bornholdt, Stefan

    2008-06-01

    Control of the living cell functions with remarkable reliability despite the stochastic nature of the underlying molecular networks—a property presumably optimized by biological evolution. We ask here to what extent the ability of a stochastic dynamical network to produce reliable dynamics is an evolvable trait. Using an evolutionary algorithm based on a deterministic selection criterion for the reliability of dynamical attractors, we evolve networks of noisy discrete threshold nodes. We find that, starting from any random network, reliability of the attractor landscape can often be achieved with only a few small changes to the network structure. Further, the evolvability of networks toward reliable dynamics while retaining their function is investigated and a high success rate is found.

  1. Quantifying evolvability in small biological networks

    Energy Technology Data Exchange (ETDEWEB)

    Nemenman, Ilya [Los Alamos National Laboratory; Mugler, Andrew [COLUMBIA UNIV; Ziv, Etay [COLUMBIA UNIV; Wiggins, Chris H [COLUMBIA UNIV

    2008-01-01

    The authors introduce a quantitative measure of the capacity of a small biological network to evolve. The measure is applied to a stochastic description of the experimental setup of Guet et al. (Science 2002, 296, pp. 1466), treating chemical inducers as functional inputs to biochemical networks and the expression of a reporter gene as the functional output. The authors take an information-theoretic approach, allowing the system to set parameters that optimise signal processing ability, thus enumerating each network's highest-fidelity functions. All networks studied are highly evolvable by the measure, meaning that change in function has little dependence on change in parameters. Moreover, each network's functions are connected by paths in the parameter space along which information is not significantly lowered, meaning a network may continuously change its functionality without completely losing it along the way. This property further underscores the evolvability of the networks.

  2. Mammals evolve faster on smaller islands.

    Science.gov (United States)

    Millien, Virginie

    2011-07-01

    Island mammals often display remarkable evolutionary changes in size and morphology. Both theory and empirical data support the hypothesis that island mammals evolve at faster rates than their mainland congeners. It is also often assumed that the island effect is stronger and that evolution is faster on the smallest islands. I used a dataset assembled from the literature to test these assumptions for the first time. I show that mammals on smaller islands do indeed evolve more rapidly than mammals on larger islands, and also evolve by a greater amount. These results fit well the theory of an evolutionary burst due to the opening of new ecological opportunities on islands. This evolutionary burst is expected to be the strongest on the smallest islands where the contrast between the island and the mainland environments is the most dramatic.

  3. Metanetworks of artificially evolved regulatory networks

    CERN Document Server

    Danacı, Burçin

    2014-01-01

    We study metanetworks arising in genotype and phenotype spaces, in the context of a model population of Boolean graphs evolved under selection for short dynamical attractors. We define the adjacency matrix of a graph as its genotype, which gets mutated in the course of evolution, while its phenotype is its set of dynamical attractors. Metanetworks in the genotype and phenotype spaces are formed, respectively, by genetic proximity and by phenotypic similarity, the latter weighted by the sizes of the basins of attraction of the shared attractors. We find that populations of evolved networks form giant clusters in genotype space, have Poissonian degree distributions but exhibit hierarchically organized $k$-core decompositions, while random populations of Boolean graphs are typically so far removed from each other genetically that they cannot form a metanetwork. In phenotype space, the metanetworks of evolved populations are super robust both under the elimination of weak connections and random removal of nodes. ...

  4. Evolution of evolvability in gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Anton Crombach

    Full Text Available Gene regulatory networks are perhaps the most important organizational level in the cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of genes. For the last decade, the study of such networks has been fueled by large-scale experiments and renewed attention from the theoretical field. Different models have been proposed to, for instance, investigate expression dynamics, explain the network topology we observe in bacteria and yeast, and for the analysis of evolvability and robustness of such networks. Yet how these gene regulatory networks evolve and become evolvable remains an open question. An individual-oriented evolutionary model is used to shed light on this matter. Each individual has a genome from which its gene regulatory network is derived. Mutations, such as gene duplications and deletions, alter the genome, while the resulting network determines the gene expression pattern and hence fitness. With this protocol we let a population of individuals evolve under Darwinian selection in an environment that changes through time. Our work demonstrates that long-term evolution of complex gene regulatory networks in a changing environment can lead to a striking increase in the efficiency of generating beneficial mutations. We show that the population evolves towards genotype-phenotype mappings that allow for an orchestrated network-wide change in the gene expression pattern, requiring only a few specific gene indels. The genes involved are hubs of the networks, or directly influencing the hubs. Moreover, throughout the evolutionary trajectory the networks maintain their mutational robustness. In other words, evolution in an alternating environment leads to a network that is sensitive to a small class of beneficial mutations, while the majority of mutations remain neutral: an example of evolution of evolvability.

  5. Chemical characteristics of dicarboxylic acids and related organic compounds in PM2.5 during biomass-burning and non-biomass-burning seasons at a rural site of Northeast China.

    Science.gov (United States)

    Cao, Fang; Zhang, Shi-Chun; Kawamura, Kimitaka; Liu, Xiaoyan; Yang, Chi; Xu, Zufei; Fan, Meiyi; Zhang, Wenqi; Bao, Mengying; Chang, Yunhua; Song, Wenhuai; Liu, Shoudong; Lee, Xuhui; Li, Jun; Zhang, Gan; Zhang, Yan-Lin

    2017-08-25

    Fine particulate matter (PM2.5) samples were collected using a high-volume air sampler and pre-combusted quartz filters during May 2013 to January 2014 at a background rural site (47(∘)35 N, 133(∘)31 E) in Sanjiang Plain, Northeast China. A homologous series of dicarboxylic acids (C2-C11) and related compounds (oxoacids, α-dicarbonyls and fatty acids) were analyzed by using a gas chromatography (GC) and GC-MS method employing a dibutyl ester derivatization technique. Intensively open biomass-burning (BB) episodes during the harvest season in fall were characterized by high mass concentrations of PM2.5, dicarboxylic acids and levoglucosan. During the BB period, mass concentrations of dicarboxylic acids and related compounds were increased by up to >20 times with different factors for different organic compounds (i.e., succinic (C4) acid > oxalic (C2) acid > malonic (C3) acid). High concentrations were also found for their possible precursors such as glyoxylic acid (ωC2), 4-oxobutanoic acid, pyruvic acid, glyoxal, and methylglyoxal as well as fatty acids. Levoglucosan showed strong correlations with carbonaceous aerosols (OC, EC, WSOC) and dicarboxylic acids although such good correlations were not observed during non-biomass-burning seasons. Our results clearly demonstrate biomass burning emissions are very important contributors to dicarboxylic acids and related compounds. The selected ratios (e.g., C3/C4, maleic acid/fumaric acid, C2/ωC2, and C2/levoglucosan) were used as tracers for secondary formation of organic aerosols and their aging process. Our results indicate that organic aerosols from biomass burning in this study are fresh without substantial aging or secondary production. The present chemical characteristics of organic compounds in biomass-burning emissions are very important for better understanding the impacts of biomass burning on the atmosphere aerosols. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The sound of an evolving floating sculpture

    CERN Document Server

    Seibold, Benjamin

    2012-01-01

    Commissioned by MIT's in-house artist Jane Philbrick, we evolve an abstract 2D surface (resembling Marta Pan's 1961 "Sculpture Flottante I") under mean curvature, all the while calculating the eigenmodes and eigenvalues of the Laplace-Beltrami operator on the resulting shapes. These are then synthesized into a sound-wave embodying the "swan song" of the surfaces as the evolve to points and vanish. The surface is approximated by a triangulation, and we present a robust approach to approximate the normal directions and the mean curvature. The resulting video and sound-track were parts in the Jane Philbrick's exhibition "Everything Trembles" in Lund, Sweden, 2009.

  7. Interactively Evolving Compositional Sound Synthesis Networks

    DEFF Research Database (Denmark)

    Jónsson, Björn Þór; Hoover, Amy K.; Risi, Sebastian

    2015-01-01

    While the success of electronic music often relies on the uniqueness and quality of selected timbres, many musicians struggle with complicated and expensive equipment and techniques to create their desired sounds. Instead, this paper presents a technique for producing novel timbres that are evolved......, CPPNs can theoretically compute any function and can build on those present in traditional synthesizers (e.g. square, sawtooth, triangle, and sine waves functions) to produce completely novel timbres. Evolved with NeuroEvolution of Augmenting Topologies (NEAT), the aim of this paper is to explore...

  8. How the first biopolymers could have evolved.

    Science.gov (United States)

    Abkevich, V I; Gutin, A M; Shakhnovich, E I

    1996-01-01

    In this work, we discuss a possible origin of the first biopolymers with stable unique structures. We suggest that at the prebiotic stage of evolution, long organic polymers had to be compact to avoid hydrolysis and had to be soluble and thus must not be exceedingly hydrophobic. We present an algorithm that generates such sequences for model proteins. The evolved sequences turn out to have a stable unique structure, into which they quickly fold. This result illustrates the idea that the unique three-dimensional native structures of first biopolymers could have evolved as a side effect of nonspecific physicochemical factors acting at the prebiotic stage of evolution. PMID:8570645

  9. Evolving Intelligent Systems Methodology and Applications

    CERN Document Server

    Angelov, Plamen; Kasabov, Nik

    2010-01-01

    From theory to techniques, the first all-in-one resource for EIS. There is a clear demand in advanced process industries, defense, and Internet and communication (VoIP) applications for intelligent yet adaptive/evolving systems. Evolving Intelligent Systems is the first self- contained volume that covers this newly established concept in its entirety, from a systematic methodology to case studies to industrial applications. Featuring chapters written by leading world experts, it addresses the progress, trends, and major achievements in this emerging research field, with a strong emphasis on th

  10. Self-Adaptation in Evolving Systems

    CERN Document Server

    Stephens, C R; Mora, J; Waelbroeck, H

    1997-01-01

    A theoretical and experimental analysis is made of the effects of self-adaptation in a simple evolving system. Specifically, we consider the effects of coding the mutation and crossover probabilities of a genetic algorithm evolving in certain model fitness landscapes. The resultant genotype-phenotype mapping is degenerate, there being no direct selective advantage for one probability versus another. We show that the action of mutation and crossover breaks this degeneracy leading to an induced symmetry breaking among the genotypic synonyms. We demonstrate that this induced symmetry breaking allows the system to self-adapt in a time dependent environment.

  11. Fluorescence quenching of graphene oxide combined with the site-specific cleavage of restriction endonuclease for deoxyribonucleic acid demethylase activity assay

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Lijuan; Qian, Yingdan; Wu, Ping; Zhang, Hui; Cai, Chenxin, E-mail: cxcai@njnu.edu.cn

    2015-04-15

    Highlights: • An approach for sensitive and selective DNA demethylase activity assay is reported. • This assay is based on the fluorescence quenching of GO and site-specific cleavage of endonuclease. • It can determine as low as 0.05 ng mL{sup −1} of MBD2 with a linear range of 0.2–300 ng mL{sup −1}. • It has an ability to recognize MBD2 from other possibly coexisting proteins and cancer cell extracts. • It can avoid false signals, requiring no bisulfite conversion, PCR amplification, radioisotope-labeling. - Abstract: We report on the development of a sensitive and selective deoxyribonucleic acid (DNA) demethylase (using MBD2 as an example) activity assay by coupling the fluorescence quenching of graphene oxide (GO) with the site-specific cleavage of HpaII endonuclease to improve the selectivity. This approach was developed by designing a single-stranded probe (P1) that carries a binding region to facilitate the interaction with GO, which induces fluorescence quenching of the labeled fluorophore (FAM, 6-carboxyfluorescein), and a sensing region, which contains a hemi-methylated site of 5′-CmCGG-3′, to specifically recognize the target (T1, a 32-mer DNA from the promoter region of p53 gene) and hybridize with it to form a P1/T1 duplex. After demethylation with MBD2, the duplex can be specifically cleaved using HpaII, which releases the labeled FAM from the GO surface and results in the recovery of fluorescence. However, this cleavage is blocked by the hemi-methylation of this site. Thus, the magnitude of the recovered fluorescence signal is related to the MBD2 activity, which establishes the basis of the DNA demethylase activity assay. This assay can determine as low as ∼(0.05 ± 0.01) ng mL{sup −1} (at a signal/noise of 3) of MBD2 with a linear range of 0.2–300 ng mL{sup −1} and recognize MBD2 from other possibly coexisting proteins and cancer cell extracts. The advantage of this assay is its ability to avoid false signals and no

  12. Evolvability Search: Directly Selecting for Evolvability in order to Study and Produce It

    DEFF Research Database (Denmark)

    Mengistu, Henok; Lehman, Joel Anthony; Clune, Jeff

    2016-01-01

    One hallmark of natural organisms is their significant evolvability, i.e.,their increased potential for further evolution. However, reproducing such evolvability in artificial evolution remains a challenge, which both reduces the performance of evolutionary algorithms and inhibits the study of ev...

  13. Active site directed irreversible inactivation of brewers' yeast pyruvate decarboxylase by the conjugated substrate analogue (E)-4-(4-chlorophenyl)-2-oxo-3-butenoic acid: development of a suicide substrate.

    Science.gov (United States)

    Kuo, D J; Jordan, F

    1983-08-01

    (E)-4-(4-Chlorophenyl)-2-oxo-3-butenoic acid (CPB) was found to irreversibly inactivate brewers' yeast pyruvate decarboxylase (PDC, EC 4.1.1.1) in a biphasic, sigmoidal manner, as is found for the kinetic behavior of substrate. An expression was derived for two-site irreversible inhibition of allosteric enzymes, and the kinetic behavior of CPB fit the expression for two-site binding. The calculated Ki's of 0.7 mM and 0.3 mM for CPB were assigned to the catalytic site and the regulatory site, respectively. The presence of pyruvic acid at high concentrations protected PDC from inactivation, whereas low concentrations of pyruvic acid accelerated inactivation by CPB. Pyruvamide, a known allosteric activator of PDC, was found to enhance inactivation by CPB. The results can be explained if pyruvamide binds only to a regulatory site, but CPB and pyruvic acid compete for both the regulatory and the catalytic centers. [1-14C]CPB was found to lose 14CO2 concurrently with the inactivation of the enzyme. Therefore, CPB was being turned over by PDC, in addition to inactivating it. CPB can be labeled a suicide-type inactivator for PDC.

  14. Thermal and Evolved Gas Behavior of Calcite Under Mars Phoenix TEGA Operating Conditions

    Science.gov (United States)

    Ming, D.W.; Niles, P.B.; Morris, R.V.; Boynton, W.V.; Golden, D.C.; Lauer, H.V.; Sutter, B.

    2009-01-01

    The Mars Phoenix Scout Mission with its diverse instrument suite successfully examined several soils on the Northern plains of Mars. The Thermal and Evolved Gas Analyzer (TEGA) was employed to detect organic and inorganic materials by coupling a differential scanning calorimeter (DSC) with a magnetic-sector mass spectrometer (MS). Martian soil was heated up to 1000 C in the DSC ovens and evolved gases from mineral decomposition products were examined with the MS. TEGA s DSC has the capability to detect endothermic and exothermic reactions during heating that are characteristic of minerals present in the Martian soil. Initial TEGA results indicated the presence of endothermic peaks with onset temperatures that ranged from 675 C to 750 C with corresponding CO2 release. This result suggests the presence of calcite (CaCO3. CaO + CO2). Organic combustion to CO2 is not likely since this mostly occurs at temperatures below 550 C. Fe-carbonate and Mg-carbonate are not likely because their decomposition temperatures are less than 600 C. TEGA enthalpy determinations suggest that calcite, may occur in the Martian soil in concentrations of approx.1 to 5 wt. %. The detection of calcite could be questioned based on previous results that suggest Mars soils are mostly acidic. However, the Phoenix landing site soil pH was measured at pH 8.3 0.5, which is typical of terrestrial soils where pH is controlled by calcite solubility. The range of onset temperatures and calcite concentration as calculated by TEGA is poorly con-strained in part because of limited thermal data of cal-cite at reduced pressures. TEGA operates at calcite literature thermal data was obtained at 1000 mbar or higher pressures.

  15. Mass Loss and Variability in Evolved Stars

    OpenAIRE

    Marengo, Massimo

    2014-01-01

    Mass loss and variability are two linked, fundamental properties of evolved stars. In this paper I review our current understanding of these processes, with a particular focus on how observations and models are used to constrain reliable mass loss prescriptions for stellar evolution and population synthesis models.

  16. Views on Evolvability of Embedded Systems

    NARCIS (Netherlands)

    Laar, P. van de; Punter, T.

    2011-01-01

    Evolvability, the ability to respond effectively to change, represents a major challenge to today's high-end embedded systems, such as those developed in the medical domain by Philips Healthcare. These systems are typically developed by multi-disciplinary teams, located around the world, and are in

  17. Systems of Accumulation and the Evolving MEC

    NARCIS (Netherlands)

    S. Ashman (Sam); B. Fine (Ben); S.A. Newman (Susan)

    2013-01-01

    textabstractThe limitations of the Developmental State Paradigm were discussed in the introductory chapter to this volume. This chapter offers an alternative approach to the DSP through use of the notion of systems of (capital) accumulation and its specific application to South Africa’s evolving pol

  18. Toward an Evolved Concept of Landrace.

    Science.gov (United States)

    Casañas, Francesc; Simó, Joan; Casals, Joan; Prohens, Jaime

    2017-01-01

    The term "landrace" has generally been defined as a cultivated, genetically heterogeneous variety that has evolved in a certain ecogeographical area and is therefore adapted to the edaphic and climatic conditions and to its traditional management and uses. Despite being considered by many to be inalterable, landraces have been and are in a constant state of evolution as a result of natural and artificial selection. Many landraces have disappeared from cultivation but are preserved in gene banks. Using modern selection and breeding technology tools to shape these preserved landraces together with the ones that are still cultivated is a further step in their evolution in order to preserve their agricultural significance. Adapting historical landraces to present agricultural conditions using cutting-edge breeding technology represents a challenging opportunity to use them in a modern sustainable agriculture, as an immediate return on the investment is highly unlikely. Consequently, we propose a more inclusive definition of landraces, namely that they consist of cultivated varieties that have evolved and may continue evolving, using conventional or modern breeding techniques, in traditional or new agricultural environments within a defined ecogeographical area and under the influence of the local human culture. This includes adaptation of landraces to new management systems and the unconscious or conscious selection made by farmers or breeders using available technology. In this respect, a mixed selection system might be established in which farmers and other social agents develop evolved landraces from the variability generated by public entities.

  19. Evolving Random Forest for Preference Learning

    DEFF Research Database (Denmark)

    Abou-Zleikha, Mohamed; Shaker, Noor

    2015-01-01

    This paper introduces a novel approach for pairwise preference learning through a combination of an evolutionary method and random forest. Grammatical evolution is used to describe the structure of the trees in the Random Forest (RF) and to handle the process of evolution. Evolved random forests...

  20. Satcom access in the Evolved Packet Core

    NARCIS (Netherlands)

    Cano Soveri, M.D.; Norp, A.H.J.; Popova, M.P.

    2011-01-01

    Satellite communications (Satcom) networks are increasingly integrating with terrestrial communications networks, namely Next Generation Networks (NGN). In the area of NGN the Evolved Packet Core (EPC) is a new network architecture that can support multiple access technologies. When Satcom is consid

  1. Satcom access in the evolved packet core

    NARCIS (Netherlands)

    Cano, M.D.; Norp, A.H.J.; Popova, M.P.

    2012-01-01

    Satellite communications (Satcom) networks are increasingly integrating with terrestrial communications networks, namely Next Generation Networks (NGN). In the area of NGN the Evolved Packet Core (EPC) is a new network architecture that can support multiple access technologies. When Satcom is consid

  2. Thermal and Evolved-Gas Analyzer Illustration

    Science.gov (United States)

    2008-01-01

    This is a computer-aided drawing of the Thermal and Evolved-Gas Analyzer, or TEGA, on NASA's Phoenix Mars Lander. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  3. Market theories evolve, and so do markets

    OpenAIRE

    Friedman, Daniel

    2007-01-01

    Responding to Mirowski's target article, this paper discusses some intellectual currents of 1970s-1990s and offers suggestions on measuring market performance, on including automated agents as market participants, on evolving new market formats, and on dealing with highly differentiated goods. (c) 2006 Elsevier B.V. All rights reserved.

  4. Information Spreading in Stationary Markovian Evolving Graphs

    CERN Document Server

    Clementi, Andrea; Pasquale, Francesco; Silvestri, Riccardo

    2011-01-01

    Markovian evolving graphs are dynamic-graph models where the links among a fixed set of nodes change during time according to an arbitrary Markovian rule. They are extremely general and they can well describe important dynamic-network scenarios. We study the speed of information spreading in the "stationary phase" by analyzing the completion time of the "flooding mechanism". We prove a general theorem that establishes an upper bound on flooding time in any stationary Markovian evolving graph in terms of its node-expansion properties. We apply our theorem in two natural and relevant cases of such dynamic graphs. "Geometric Markovian evolving graphs" where the Markovian behaviour is yielded by "n" mobile radio stations, with fixed transmission radius, that perform independent random walks over a square region of the plane. "Edge-Markovian evolving graphs" where the probability of existence of any edge at time "t" depends on the existence (or not) of the same edge at time "t-1". In both cases, the obtained upper...

  5. A Course Evolves-Physical Anthropology.

    Science.gov (United States)

    O'Neil, Dennis

    2001-01-01

    Describes the development of an online physical anthropology course at Palomar College (California) that evolved from online tutorials. Discusses the ability to update materials on the Web more quickly than in traditional textbooks; creating Web pages that are readable by most Web browsers; test security issues; and clarifying ownership of online…

  6. Mass Loss and Variability in Evolved Stars

    OpenAIRE

    Marengo, Massimo

    2014-01-01

    Mass loss and variability are two linked, fundamental properties of evolved stars. In this paper I review our current understanding of these processes, with a particular focus on how observations and models are used to constrain reliable mass loss prescriptions for stellar evolution and population synthesis models.

  7. Did Language Evolve Like the Vertebrate Eye?

    Science.gov (United States)

    Botha, Rudolf P.

    2002-01-01

    Offers a critical appraisal of the way in which the idea that human language or some of its features evolved like the vertebrate eye by natural selection is articulated in Pinker and Bloom's (1990) selectionist account of language evolution. Argues that this account is less than insightful because it fails to draw some of the conceptual…

  8. Research Notes Openness and Evolvability Legal Assessment

    Science.gov (United States)

    2016-08-01

    enforceable? Are interface providers (granule vendors) legally required to disclose (including license) semantic characteristics of their interfaces to...not be possible to adequately maintain and evolve the supporting material. Similarly, if the tool is proprietary to a related entity (such as the

  9. Site-specific protonation kinetics of acidic side chains in proteins determined by pH-dependent carboxyl (13)C NMR relaxation.

    Science.gov (United States)

    Wallerstein, Johan; Weininger, Ulrich; Khan, M Ashhar I; Linse, Sara; Akke, Mikael

    2015-03-04

    Proton-transfer dynamics plays a critical role in many biochemical processes, such as proton pumping across membranes and enzyme catalysis. The large majority of enzymes utilize acid-base catalysis and proton-transfer mechanisms, where the rates of proton transfer can be rate limiting for the overall reaction. However, measurement of proton-exchange kinetics for individual side-chain carboxyl groups in proteins has been achieved in only a handful of cases, which typically have involved comparative analysis of mutant proteins in the context of reaction network modeling. Here we describe an approach to determine site-specific protonation and deprotonation rate constants (kon and koff, respectively) of carboxyl side chains, based on (13)C NMR relaxation measurements as a function of pH. We validated the method using an extensively studied model system, the B1 domain of protein G, for which we measured rate constants koff in the range (0.1-3) × 10(6) s(-1) and kon in the range (0.6-300) × 10(9) M(-1) s(-1), which correspond to acid-base equilibrium dissociation constants (Ka) in excellent agreement with previous results determined by chemical shift titrations. Our results further reveal a linear free-energy relationship between log kon and pKa, which provides information on the free-energy landscape of the protonation reaction, showing that the variability among residues in these parameters arises primarily from the extent of charge stabilization of the deprotonated state by the protein environment. We find that side-chain carboxyls with extreme values of koff or kon are involved in hydrogen bonding, thus providing a mechanistic explanation for the observed stabilization of the protonated or deprotonated state.

  10. Investigation of the Binding Interaction of Fatty Acids with Human G Protein-Coupled Receptor 40 Using a Site-Specific Fluorescence Probe by Flow Cytometry.

    Science.gov (United States)

    Ren, Xiao-Min; Cao, Lin-Ying; Zhang, Jing; Qin, Wei-Ping; Yang, Yu; Wan, Bin; Guo, Liang-Hong

    2016-04-01

    Human G protein-coupled receptor 40 (hGPR40), with medium- and long-chain free fatty acids (FFAs) as its natural ligands, plays an important role in the enhancement of glucose-dependent insulin secretion. To date, information about the direct binding of FFAs to hGPR40 is very limited, and how carbon-chain length affects the activities of FFAs on hGPR40 is not yet understood. In this study, a fluorescein-fasiglifam analogue (F-TAK-875A) conjugate was designed and synthesized as a site-specific fluorescence probe to study the interaction of FFAs with hGPR40. hGPR40 was expressed in human embryonic kidney 293 cells and labeled with F-TAK-875A. By using flow cytometry, competitive binding of FFA and F-TAK-875A to hGPR40-expressed cells was measured. Binding affinities of 18 saturated FFAs, with carbon-chain lengths ranging from C6 to C23, were analyzed. The results showed that the binding potencies of FFAs to hGPR40 were dependent on carbon length. There was a positive correlation between length and binding potency for seven FFAs (C9-C15), with myristic acid (C15) showing the highest potency, 0.2% relative to TAK-875. For FFAs with a length of fewer than C9 or more than C15, they had very weak or no binding. Molecular docking results showed that the binding pocket of TAK-875 in hGPR40 could enclose FFAs with lengths of C15 or fewer. However, for FFAs with lengths longer than C15, part of the alkyl chain extended out of the binding pocket. This study provided insights into the structural dependence of FFAs binding to and activation of hGPR40.

  11. The Fatty Acid Profile Analysis of Cyperus laxus Used for Phytoremediation of Soils from Aged Oil Spill-Impacted Sites Revealed That This Is a C18:3 Plant Species.

    Directory of Open Access Journals (Sweden)

    Noemí Araceli Rivera Casado

    Full Text Available The effect of recalcitrant hydrocarbons on the fatty acid profile from leaf, basal corm, and roots of Cyperus laxus plants cultivated in greenhouse phytoremediation systems of soils from aged oil spill-impacted sites containing from 16 to 340 g/Kg total hydrocarbons (THC was assessed to investigate if this is a C18:3 species and if the hydrocarbon removal during the phytoremediation process has a relationship with the fatty acid profile of this plant. The fatty acid profile was specific to each vegetative organ and was strongly affected by the hydrocarbons level in the impacted sites. Leaf extracts of plants from uncontaminated soil produced palmitic acid (C16, octadecanoic acid (C18:0, unsaturated oleic acids (C18:1-C18:3, and unsaturated eichosanoic (C20:2-C20:3 acids with a noticeable absence of the unsaturated hexadecatrienoic acid (C16:3; this finding demonstrates, for the first time, that C. laxus is a C18:3 plant. In plants from the phytoremediation systems, the total fatty acid contents in the leaf and the corm were negatively affected by the hydrocarbons presence; however, the effect was positive in root. Interestingly, under contaminated conditions, unusual fatty acids such as odd numbered carbons (C15, C17, C21, and C23 and uncommon unsaturated chains (C20:3n6 and C20:4 were produced together with a remarkable quantity of C22:2 and C24:0 chains in the corm and the leaf. These results demonstrate that weathered hydrocarbons may drastically affect the lipidic composition of C. laxus at the fatty acid level, suggesting that this species adjusts the cover lipid composition in its vegetative organs, mainly in roots, in response to the weathered hydrocarbon presence and uptake during the phytoremediation process.

  12. The Fatty Acid Profile Analysis of Cyperus laxus Used for Phytoremediation of Soils from Aged Oil Spill-Impacted Sites Revealed That This Is a C18:3 Plant Species

    Science.gov (United States)

    Montes Horcasitas, María del Carmen; Rodríguez Vázquez, Refugio; Esparza García, Fernando José; Pérez Vargas, Josefina; Ariza Castolo, Armando; Ferrera-Cerrato, Ronald; Gómez Guzmán, Octavio

    2015-01-01

    The effect of recalcitrant hydrocarbons on the fatty acid profile from leaf, basal corm, and roots of Cyperus laxus plants cultivated in greenhouse phytoremediation systems of soils from aged oil spill-impacted sites containing from 16 to 340 g/Kg total hydrocarbons (THC) was assessed to investigate if this is a C18:3 species and if the hydrocarbon removal during the phytoremediation process has a relationship with the fatty acid profile of this plant. The fatty acid profile was specific to each vegetative organ and was strongly affected by the hydrocarbons level in the impacted sites. Leaf extracts of plants from uncontaminated soil produced palmitic acid (C16), octadecanoic acid (C18:0), unsaturated oleic acids (C18:1-C18:3), and unsaturated eichosanoic (C20:2-C20:3) acids with a noticeable absence of the unsaturated hexadecatrienoic acid (C16:3); this finding demonstrates, for the first time, that C. laxus is a C18:3 plant. In plants from the phytoremediation systems, the total fatty acid contents in the leaf and the corm were negatively affected by the hydrocarbons presence; however, the effect was positive in root. Interestingly, under contaminated conditions, unusual fatty acids such as odd numbered carbons (C15, C17, C21, and C23) and uncommon unsaturated chains (C20:3n6 and C20:4) were produced together with a remarkable quantity of C22:2 and C24:0 chains in the corm and the leaf. These results demonstrate that weathered hydrocarbons may drastically affect the lipidic composition of C. laxus at the fatty acid level, suggesting that this species adjusts the cover lipid composition in its vegetative organs, mainly in roots, in response to the weathered hydrocarbon presence and uptake during the phytoremediation process. PMID:26473488

  13. The Fatty Acid Profile Analysis of Cyperus laxus Used for Phytoremediation of Soils from Aged Oil Spill-Impacted Sites Revealed That This Is a C18:3 Plant Species.

    Science.gov (United States)

    Rivera Casado, Noemí Araceli; Montes Horcasitas, María del Carmen; Rodríguez Vázquez, Refugio; Esparza García, Fernando José; Pérez Vargas, Josefina; Ariza Castolo, Armando; Ferrera-Cerrato, Ronald; Gómez Guzmán, Octavio; Calva Calva, Graciano

    2015-01-01

    The effect of recalcitrant hydrocarbons on the fatty acid profile from leaf, basal corm, and roots of Cyperus laxus plants cultivated in greenhouse phytoremediation systems of soils from aged oil spill-impacted sites containing from 16 to 340 g/Kg total hydrocarbons (THC) was assessed to investigate if this is a C18:3 species and if the hydrocarbon removal during the phytoremediation process has a relationship with the fatty acid profile of this plant. The fatty acid profile was specific to each vegetative organ and was strongly affected by the hydrocarbons level in the impacted sites. Leaf extracts of plants from uncontaminated soil produced palmitic acid (C16), octadecanoic acid (C18:0), unsaturated oleic acids (C18:1-C18:3), and unsaturated eichosanoic (C20:2-C20:3) acids with a noticeable absence of the unsaturated hexadecatrienoic acid (C16:3); this finding demonstrates, for the first time, that C. laxus is a C18:3 plant. In plants from the phytoremediation systems, the total fatty acid contents in the leaf and the corm were negatively affected by the hydrocarbons presence; however, the effect was positive in root. Interestingly, under contaminated conditions, unusual fatty acids such as odd numbered carbons (C15, C17, C21, and C23) and uncommon unsaturated chains (C20:3n6 and C20:4) were produced together with a remarkable quantity of C22:2 and C24:0 chains in the corm and the leaf. These results demonstrate that weathered hydrocarbons may drastically affect the lipidic composition of C. laxus at the fatty acid level, suggesting that this species adjusts the cover lipid composition in its vegetative organs, mainly in roots, in response to the weathered hydrocarbon presence and uptake during the phytoremediation process.

  14. Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein

    Directory of Open Access Journals (Sweden)

    Berkhout Ben

    2006-11-01

    Full Text Available Abstract Background We previously described the selection of a T20-dependent human immunodeficiency virus type-1 (HIV-1 variant in a patient on T20 therapy. The fusion inhibitor T20 targets the viral envelope (Env protein by blocking a conformational switch that is critical for viral entry into the host cell. T20-dependent viral entry is the result of 2 mutations in Env (GIA-SKY, creating a protein that undergoes a premature conformational switch, and the presence of T20 prevents this premature switch and rescues viral entry. In the present study, we performed 6 independent evolution experiments with the T20-dependent HIV-1 variant in the absence of T20, with the aim to identify second site compensatory changes, which may provide new mechanistic insights into Env function and the T20-dependence mechanism. Results Escape variants with improved replication capacity appeared within 42 days in 5 evolution cultures. Strikingly, 3 cultures revealed the same single amino acid change in the CD4 binding region of Env (glycine at position 431 substituted for arginine: G431R. This mutation was sufficient to abolish the T20-dependence phenotype and restore viral replication in the absence of T20. The GIA-SKY-G431R escape variant produces an Env protein that exhibits reduced syncytia formation and reduced cell-cell fusion activity. The escape variant was more sensitive to an antibody acting on an early gp41 intermediate, suggesting that the G431R mutation helps preserve a pre-fusion Env conformation, similar to T20 action. The escape variant was also less sensitive to soluble CD4, suggesting a reduced CD4 receptor affinity. Conclusion The forced evolution experiments indicate that the premature conformational switch of the T20-dependent HIV-1 Env variant (GIA-SKY can be corrected by a second site mutation in Env (GIA-SKY-G431R that affects the interaction with the CD4 receptor.

  15. Improved Evolvability in Genetic Programming with Polyandry

    Directory of Open Access Journals (Sweden)

    Anisa Waganda Ragalo

    2013-12-01

    Full Text Available This paper proposes Polyandry, a new nature-inspired modification to canonical Genetic Programming (GP. Polyandry aims to improve evolvability in GP. Evolvability is a critically important GP trait, the maintenance of which determines the arrival of the GP at the global optimum solution. Specifically evolvability is defined as the ability of the genetic operators employed in GP to produce offspring that are fitter than their parents. When GP fails to exhibit evolvability, further adaptation of the GP individuals towards the global optimum solution becomes impossible. Polyandry improves evolvability by improving the typically disruptive standard GP crossover operator. The algorithm employs a dual strategy towards this goal. The chief part of this strategy is an incorporation of genetic material from multiple mating partners into broods of offspring. Given such a brood, the offspring in the brood then compete according to a culling function, which we make equivalent to the main GP fitness function. Polyandry’s incorporation of genetic material from multiple GP individuals into broods of offspring represents a more aggressive search for building block information. This characteristic of the algorithm leads to an advanced explorative capability in both GP structural space and fitness space. The second component of the Polyandry strategy is an attempt at multiple crossover points, in order to find crossover points that minimize building block disruption from parents to offspring. This strategy is employed by a similar algorithm, Brood Recombination. We conduct experiments to compare Polyandry with the canonical GP. Our experiments demonstrate that Polyandry consistently exhibits better evolvability than the canonical GP. As a consequence, Polyandry achieves higher success rates and finds solutions faster than the latter. The result of these observations is that given certain brood size settings, Polyandry requires less computational effort to

  16. Encapsulation of paclitaxel into lauric acid-O-carboxymethyl chitosan-transferrin micelles for hydrophobic drug delivery and site-specific targeted delivery.

    Science.gov (United States)

    Nam, Joung-Pyo; Park, Seong-Cheol; Kim, Tae-Hun; Jang, Jae-Yeang; Choi, Changyong; Jang, Mi-Kyeong; Nah, Jae-Woon

    2013-11-30

    Transferrin/PEG/O-carboxymethyl chitosan/fatty acid/paclitaxel (TPOCFP) micelles were tested for suitability as a drug carrier characterized by low cytotoxicity, sustained release, high cellular uptake, and site-specific targeted delivery of hydrophobic drugs. Characterization, drug content, encapsulation efficiency, and in vitro drug release were investigated. When the feeding amount of paclitaxel (PTX) was increased, the drug content increased, but loading efficiency decreased. TPOCFP micelles had a spherical shape, with a particle size of approximately 140-649 nm. In vitro cell cytotoxicity and hemolysis assays were conducted to confirm the safety of the micelles. Anticancer activity and confocal laser scanning microscopy (CLSM) were used to confirm the targeting efficiency of target ligand-modified TPOCFP micelles. Anticancer activity and CLSM results clearly demonstrated that transferrin-modified TPOCFP micelles were quickly taken up by the cell. The endocytic pathway of TPOCFP micelles was analyzed by flow cytometry, revealing transfection via receptor-mediated endocytosis. These results suggest that PTX-encapsulated TPOCFP micelles may be used as an effective cancer-targeting drug delivery system for chemotherapy.

  17. Optical investigation of the intergrowth structure and accessibility of Brønsted acid sites in etched SSZ-13 zeolite crystals by confocal fluorescence microscopy.

    Science.gov (United States)

    Sommer, Linn; Svelle, Stian; Lillerud, Karl Petter; Stöcker, Michael; Weckhuysen, Bert M; Olsbye, Unni

    2010-11-02

    Template decomposition followed by confocal fluorescence microscopy reveals a tetragonal-pyramidal intergrowth of subunits in micrometer-sized nearly cubic SSZ-13 zeolite crystals. In order to accentuate intergrowth boundaries and defect-rich areas within the individual large zeolite crystals, a treatment with an etching NaOH solution is applied. The defective areas are visualized by monitoring the spatial distribution of fluorescent tracer molecules within the individual SSZ-13 crystals by confocal fluorescence microscopy. These fluorescent tracer molecules are formed at the inner and outer crystal surfaces by utilizing the catalytic activity of the zeolite in the oligomerization reaction of styrene derivatives. This approach reveals various types of etching patterns that are an indication for the defectiveness of the studied crystals. We can show that specially one type of crystals, denoted as core-shell type, is highly accessible to the styrene molecules after etching. Despite the large crystal dimensions, the whole core-shell type SSZ-13 crystal is utilized for catalytic reaction. Furthermore, the confocal fluorescence microscopy measurements indicate a nonuniform distribution of the catalytically important Brønsted acid sites underlining the importance of space-resolved measurements.

  18. Analysis of an invariant cofactor-protein interaction in thiamin diphosphate-dependent enzymes by site-directed mutagenesis. Glutamic acid 418 in transketolase is essential for catalysis.

    Science.gov (United States)

    Wikner, C; Meshalkina, L; Nilsson, U; Nikkola, M; Lindqvist, Y; Sundström, M; Schneider, G

    1994-12-23

    A homologous expression system and a purification protocol for pure, highly active recombinant yeast transketolase have been developed. The invariant transketolase residue Glu418, which forms a hydrogen bond to the N-1' nitrogen atom of the pyrimidine ring of the cofactor thiamin diphosphate has been replaced by glutamine and alanine. Crystallographic analyses of the mutants show that these amino acid substitutions do not induce structural changes beyond the site of mutation. In both cases, the cofactor binds in a manner identical to the wild-type enzyme. Significant differences in the CD spectra of the mutant transketolases compared with the spectrum of wild-type enzyme indicate differences in the electron distribution of the aminopyrimidine ring of the cofactor. The E418Q mutant shows 2% and the E418A mutant shows about 0.1% of the catalytic activity of wild-type enzyme. The affinities of the mutant enzymes for thiamin diphosphate are comparable with wild-type transketolase. The hydrogen bond between the coenzyme and the side chain of Glu418 is thus not required for coenzyme binding but essential for catalytic activity. The results demonstrate the functional importance of this interaction and support the molecular model for cofactor deprotonation, the first step in enzymatic thiamin catalysis.

  19. Cloning of novel rice blast resistance genes from two rapidly evolving NBS-LRR gene families in rice.

    Science.gov (United States)

    Guo, Changjiang; Sun, Xiaoguang; Chen, Xiao; Yang, Sihai; Li, Jing; Wang, Long; Zhang, Xiaohui

    2016-01-01

    Most rice blast resistance genes (R-genes) encode proteins with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains. Our previous study has shown that more rice blast R-genes can be cloned in rapidly evolving NBS-LRR gene families. In the present study, two rapidly evolving R-gene families in rice were selected for cloning a subset of genes from their paralogs in three resistant rice lines. A total of eight functional blast R-genes were identified among nine NBS-LRR genes, and some of these showed resistance to three or more blast strains. Evolutionary analysis indicated that high nucleotide diversity of coding regions served as important parameters in the determination of gene resistance. We also observed that amino-acid variants (nonsynonymous mutations, insertions, or deletions) in essential motifs of the NBS domain contribute to the blast resistance capacity of NBS-LRR genes. These results suggested that the NBS regions might also play an important role in resistance specificity determination. On the other hand, different splicing patterns of introns were commonly observed in R-genes. The results of the present study contribute to improving the effectiveness of R-gene identification by using evolutionary analysis method and acquisition of novel blast resistance genes.

  20. Rapidly Evolving Mitochondrial Genome and Directional Selection in Mitochondrial Genes in the Parasitic Wasp Nasonia (Hymenoptera: Pteromalidae)

    Science.gov (United States)

    Raychoudhury, Rhitoban; Lavrov, Dennis V.; Werren, John H.

    2008-01-01

    We sequenced the nearly complete mtDNA of 3 species of parasitic wasps, Nasonia vitripennis (2 strains), Nasonia giraulti, and Nasonia longicornis, including all 13 protein-coding genes and the 2 rRNAs, and found unusual patterns of mitochondrial evolution. The Nasonia mtDNA has a unique gene order compared with other insect mtDNAs due to multiple rearrangements. The mtDNAs of these wasps also show nucleotide substitution rates over 30 times faster than nuclear protein-coding genes, indicating among the highest substitution rates found in animal mitochondria (normally <10 times faster). A McDonald and Kreitman test shows that the between-species frequency of fixed replacement sites relative to silent sites is significantly higher compared with within-species polymorphisms in 2 mitochondrial genes of Nasonia, atp6 and atp8, indicating directional selection. Consistent with this interpretation, the Ka/Ks (nonsynonymous/synonymous substitution rates) ratios are higher between species than within species. In contrast, cox1 shows a signature of purifying selection for amino acid sequence conservation, although rates of amino acid substitutions are still higher than for comparable insects. The mitochondrial-encoded polypeptides atp6 and atp8 both occur in F0F1ATP synthase of the electron transport chain. Because malfunction in this fundamental protein severely affects fitness, we suggest that the accelerated accumulation of replacements is due to beneficial mutations necessary to compensate mild-deleterious mutations fixed by random genetic drift or Wolbachia sweeps in the fast evolving mitochondria of Nasonia. We further propose that relatively high rates of amino acid substitution in some mitochondrial genes can be driven by a “Compensation-Draft Feedback”; increased fixation of mildly deleterious mutations results in selection for compensatory mutations, which lead to fixation of additional deleterious mutations in nonrecombining mitochondrial genomes, thus

  1. Evolving Quantum Circuits using Genetic Algorithms

    CERN Document Server

    Prashant

    2005-01-01

    This paper describes an application of genetic algorithm for evolving quantum computing circuits. The circuits use reversible one qubit and two qubit gates which are applied on a multi-qubit system having some initial state. The genetic algorithm automatically searches the space and comes out with the appropriate circuit design, which yields desired output state. The fitness function used matches the output with desired output and the search stops when it is found. The fitness value becomes higher if the output is close to the desired output. The paper briefly discusses the operation of a quantum gate over the multi-qubit system. The paper also demonstrates some examples of the evolved circuits using the algorithm.

  2. A novel evolving model for power grids

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In this paper,a novel power grid evolving model,which can well describe the evolving property of power grids,is presented. Based on the BA model,motivated by the fact that in real power grids,connectivity of node not only depends on its degree,but also is influenced by many uncertain factors,so we introduce the subconnection factor K for each node. Using the mean-field theory,we get the analytical expression of power-law degree distribution with the exponent γ∈ (3,∞ ). Finally,simulation results show that the new model can provide a satisfactory description for empirical characteristics of power network,and power network falls somewhere in between scale-free network and uncertain network.

  3. Evolvement Complexity in an Artificial Stock Market

    Institute of Scientific and Technical Information of China (English)

    YANG Chun-Xia; ZHOU Tao; ZHOU Pei-Ling; LIU Jun; TANG Zi-Nan

    2005-01-01

    @@ An artificial stock market is established based on the multi-agent model.Each agent has a limited memory of the history of stock price, and will choose an action according to its memory and trading strategy.The trading strategy of each agent evolves ceaselessly as a result of a self-teaching mechanism.The simulation results exhibit that large events are frequent in the fluctuation of the stock price generated by the present model when compared with a normal process, and the price returns distribution is a L関y distribution in the central part followed by an approximately exponential truncation.In addition, by defining a variable to gauge the evolvement complexity of this system, we have found a phase cross-over from simple-phase to complex-phase along with the increase of the number of individuals, which may be a ubiquitous phenomenon in multifarious real-life systems.

  4. Architecture for Pseudo Acausal Evolvable Embedded Systems

    CERN Document Server

    Abubakr, Mohd

    2007-01-01

    Advances in semiconductor technology are contributing to the increasing complexity in the design of embedded systems. Architectures with novel techniques such as evolvable nature and autonomous behavior have engrossed lot of attention. This paper demonstrates conceptually evolvable embedded systems can be characterized basing on acausal nature. It is noted that in acausal systems, future input needs to be known, here we make a mechanism such that the system predicts the future inputs and exhibits pseudo acausal nature. An embedded system that uses theoretical framework of acausality is proposed. Our method aims at a novel architecture that features the hardware evolability and autonomous behavior alongside pseudo acausality. Various aspects of this architecture are discussed in detail along with the limitations.

  5. Dust obscuration by an evolving galaxy population

    Science.gov (United States)

    Najita, Joan; Silk, Joseph; Wachter, Kenneth W.

    1990-01-01

    The effect of an evolving luminosity function (LF) on the ability of foreground galaxies to obscure background sources is discussed, using the Press-Schechter/CDM standard evolving LF model. Galaxies are modeled as simplified versions of local spirals and Poisson statistics are used to estimate the fraction of sky covered by intervening dusty galaxies and the mean optical depths due to these galaxies. The results are compared to those obtained in the case of nonevolving luminosity function in a low-density universe. It is found that evolution of the galaxy LF does not allow the quasar dust obscuration hypothesis to be sustained for dust disks with plausible sizes. Even in a low-density universe, where evolution at z = less than 10 is unimportant, large disk radii are needed to achieve the desired obscuring effect. The mean fraction of sky covered is presented as a function of the redshift z along with adequate diagram illustrations.

  6. Interactively Evolving Compositional Sound Synthesis Networks

    DEFF Research Database (Denmark)

    Jónsson, Björn Þór; Hoover, Amy K.; Risi, Sebastian

    2015-01-01

    While the success of electronic music often relies on the uniqueness and quality of selected timbres, many musicians struggle with complicated and expensive equipment and techniques to create their desired sounds. Instead, this paper presents a technique for producing novel timbres that are evolved...... by the musician through interactive evolutionary computation. Each timbre is produced by an oscillator, which is represented by a special type of artificial neural network (ANN) called a compositional pattern producing network (CPPN). While traditional ANNs compute only sigmoid functions at their hidden nodes......, CPPNs can theoretically compute any function and can build on those present in traditional synthesizers (e.g. square, sawtooth, triangle, and sine waves functions) to produce completely novel timbres. Evolved with NeuroEvolution of Augmenting Topologies (NEAT), the aim of this paper is to explore...

  7. Quantum games on evolving random networks

    Science.gov (United States)

    Pawela, Łukasz

    2016-09-01

    We study the advantages of quantum strategies in evolutionary social dilemmas on evolving random networks. We focus our study on the two-player games: prisoner's dilemma, snowdrift and stag-hunt games. The obtained result show the benefits of quantum strategies for the prisoner's dilemma game. For the other two games, we obtain regions of parameters where the quantum strategies dominate, as well as regions where the classical strategies coexist.

  8. Quantum games on evolving random networks

    CERN Document Server

    Pawela, Łukasz

    2015-01-01

    We study the advantages of quantum strategies in evolutionary social dilemmas on evolving random networks. We focus our study on the two-player games: prisoner's dilemma, snowdrift and stag-hunt games. The obtained result show the benefits of quantum strategies for the prisoner's dilemma game. For the other two games, we obtain regions of parameters where the quantum strategies dominate, as well as regions where the classical strategies coexist.

  9. The evolving epidemiology of inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Shanahan, Fergus

    2009-07-01

    Epidemiologic studies in inflammatory bowel disease (IBD) include assessments of disease burden and evolving patterns of disease presentation. Although it is hoped that sound epidemiologic studies provide aetiological clues, traditional risk factor-based epidemiology has provided limited insights into either Crohn\\'s disease or ulcerative colitis etiopathogenesis. In this update, we will summarize how the changing epidemiology of IBD associated with modernization can be reconciled with current concepts of disease mechanisms and will discuss studies of clinically significant comorbidity in IBD.

  10. Circumstellar Molecular Spectra towards Evolved Stars

    CERN Document Server

    Bakker, E J

    1997-01-01

    In this paper we discuss the relevance of, and possible scientific gains which can be acquired from studying circumstellar molecular spectra toward evolved stars. Where can we expect circumstellar molecular spectra, why would we want to study these spectra, which molecules might be present, and what can we learn from these studies? We present an overview of reported detections, and discuss some of the results.

  11. Evolving economic architecture in East Asia

    OpenAIRE

    Kawai, Masahiro

    2007-01-01

    This paper examines how East Asia's economic architecture has been evolving over the last ten years and how it will shape itself in the future. With the progress of market-driven economic integration, East Asian economies have developed various cooperative initiatives for trade and finance, including free trade agreements (FTAs), the Chiang Mai Initiative, the Economic Review and Policy Dialogue, and the Asian Bond Markets Initiative. The paper suggests policy directions for greater regional ...

  12. Continual Learning through Evolvable Neural Turing Machines

    DEFF Research Database (Denmark)

    Lüders, Benno; Schläger, Mikkel; Risi, Sebastian

    2016-01-01

    Continual learning, i.e. the ability to sequentially learn tasks without catastrophic forgetting of previously learned ones, is an important open challenge in machine learning. In this paper we take a step in this direction by showing that the recently proposed Evolving Neural Turing Machine (ENTM......) approach is able to perform one-shot learning in a reinforcement learning task without catastrophic forgetting of previously stored associations....

  13. The Evolving Leadership Path of Visual Analytics

    Energy Technology Data Exchange (ETDEWEB)

    Kluse, Michael; Peurrung, Anthony J.; Gracio, Deborah K.

    2012-01-02

    This is a requested book chapter for an internationally authored book on visual analytics and related fields, coordianted by a UK university and to be published by Springer in 2012. This chapter is an overview of the leadship strategies that PNNL's Jim Thomas and other stakeholders used to establish visual analytics as a field, and how those strategies may evolve in the future.

  14. Evolving Information Filtering for Personalized Information Service

    Institute of Scientific and Technical Information of China (English)

    田范江; 李丛蓉; 王鼎兴

    2001-01-01

    Information filtering (IF) systems are important for personalized information service. However, most current IF systems suffer from low quality and long training time. In this paper, a refined evolving information filtering method is presented. This method describes user's information need from multi-aspects and improves filtering quality through a process like natural selection. Experimental result shows this method can shorten training time, improve filtering quality, and reduce the relevance between filtering results and training sequence.

  15. Evolving networks:from topology to dynamics

    Institute of Scientific and Technical Information of China (English)

    Zhengping FAN; Guanrong CHEN; King Tim KO

    2004-01-01

    A multi-local-world model is introduced to describe the evolving networks that have a localization property such as the Intemet. Based on this model, we show that the traffic load defined by "betweenness centrality" on the multi-local-world scale-free networks' model also follows a power law form. In this kind of network, a few vertices have heavier loads and so play more important roles than the others in the network.

  16. Structural Diversities in Heterometallic Mn-Ca Cluster Chemistry from the Use of Salicylhydroxamic Acid: {Mn(III)4Ca2}, {Mn(II/III)6Ca2}, {Mn(III/IV)8Ca}, and {Mn(III)8Ca2} Complexes with Relevance to Both High- and Low-Valent States of the Oxygen-Evolving Complex.

    Science.gov (United States)

    Alaimo, Alysha A; Koumousi, Evangelia S; Cunha-Silva, Luís; McCormick, Laura J; Teat, Simon J; Psycharis, Vassilis; Raptopoulou, Catherine P; Mukherjee, Shreya; Li, Chaoran; Gupta, Sayak Das; Escuer, Albert; Christou, George; Stamatatos, Theocharis C

    2017-09-05

    One-pot reactions between the [Mn3O(O2CPh)6(py)x](+/0) triangular precursors and either CaBr2·xH2O or CaCl2·6H2O, in the presence of salicylhydroxamic acid (shaH2), have afforded the heterometallic complexes [Mn(III)4Ca2(O2CPh)4(shi)4(H2O)3(Me2CO)] (1) and (pyH)[Mn(II)2Mn(III)4Ca2Cl2(O2CPh)7(shi)4(py)4] (2), respectively, in good yields. Further reactions but using a more flexible synthetic scheme comprising the Mn(NO3)2·4H2O/Ca(NO3)2·4H2O and Mn(O2CPh)2·2H2O/Ca(ClO4)2·4H2O "metal blends" and shaH2, in the presence of external base NEt3, led to the new complexes (NHEt3)2[Mn(III)4Mn(IV)4Ca(OEt)2(shi)10(EtOH)2] (3) and (NHEt3)4[Mn(III)8Ca2(CO3)4(shi)8] (4), respectively. In all reported compounds, the anion of the tetradentate (N,O,O,O)-chelating/bridging ligand salicylhydroxime (shi(3-)), resulting from the in situ metal-ion-assisted amide-iminol tautomerism of shaH2, was found to bridge both Mn and Ca atoms. Complexes 1-4 exhibit a variety of different structures, metal stoichiometries, and Mn oxidation-state descriptions; 1 possesses an overall octahedral metal arrangement, 2 can be described as a Mn4Ca2 octahedron bound to an additional Mn2 unit, 3 consists of a Mn8 "ring" surrounding a Ca(II) atom, and 4 adopts a rectangular cuboidal motif of eight Mn atoms accommodating two Ca(II) atoms. Solid-state direct-current magnetic susceptibility studies revealed the presence of predominant antiferromagnetic exchange interactions between the Mn centers, leading to S = 0 spin ground-state values for all complexes. From a bioinorganic chemistry perspective, the reported compounds may demonstrate some relevance to both high-valent scheme (3) and lower-oxidation-level species (1, 2, and 4) of the catalytic cycle of the oxygen-evolving complex.

  17. Ground-water quality, water year 1995, and statistical analysis of ground-water-quality data, water years 1994-95, at the Chromic Acid Pit site, US Army Air Defense Artillery Center and Fort Bliss, El Paso, Texas

    Science.gov (United States)

    Abeyta, Cynthia G.; Roybal, R.G.

    1996-01-01

    The Chromic Acid Pit site is an inactive waste disposal site that is regulated by the Resource Conservation and Recovery Act of 1976. The 2.2-cubic-yard cement-lined pit was operated from 1980 to 1983 by a contractor to the U.S. Army Air Defense Artillery Center and Fort Bliss. The pit, located on the Fort Bliss military reservation in El Paso, Texas, was used for disposal and evaporation of chromic acid waste generated from chrome plating operations. The site was closed in 1989, and the Texas Natural Resources Conservation Commission issued permit number HW-50296 (U.S. Environmental Protection Agency number TX4213720101), which approved and implemented post-closure care for the Chromic Acid Pit site. In accordance with an approved post-closure plan, the U.S. Geological Survey is cooperating with the U.S. Army in monitoring and evaluating ground-water quality at the site. One upgradient ground-water monitoring well (MW1) and two downgradient ground-water monitoring wells (MW2 and MW3), installed adjacent to the chromic acid pit, are monitored on a quarterly basis. Ground-water sampling of these wells by the U.S. Geological Survey began in December 1993. The ground-water level, measured in a production well located approximately 1,700 feet southeast of the Chromic Acid Pit site, has declined about 29.43 feet from 1982 to 1995. Depth to water at the Chromic Acid Pit site in September 1995 was 284.2 to 286.5 feet below land surface; ground-water flow at the water table is assumed to be toward the southeast. Ground-water samples collected from monitoring wells at the Chromic Acid Pit site during water year 1995 contained dissolved- solids concentrations of 481 to 516 milligrams per liter. Total chromium concentrations detected above the laboratory reporting limit ranged from 0.0061 to 0.030 milligram per liter; dissolved chromium concentrations ranged from 0.0040 to 0.010 milligram per liter. Nitrate as nitrogen concentrations ranged from 2.1 to 2.8 milligrams per

  18. Continuous evaluation of evolving behavioral intervention technologies.

    Science.gov (United States)

    Mohr, David C; Cheung, Ken; Schueller, Stephen M; Hendricks Brown, C; Duan, Naihua

    2013-10-01

    Behavioral intervention technologies (BITs) are web-based and mobile interventions intended to support patients and consumers in changing behaviors related to health, mental health, and well-being. BITs are provided to patients and consumers in clinical care settings and commercial marketplaces, frequently with little or no evaluation. Current evaluation methods, including RCTs and implementation studies, can require years to validate an intervention. This timeline is fundamentally incompatible with the BIT environment, where technology advancement and changes in consumer expectations occur quickly, necessitating rapidly evolving interventions. However, BITs can routinely and iteratively collect data in a planned and strategic manner and generate evidence through systematic prospective analyses, thereby creating a system that can "learn." A methodologic framework, Continuous Evaluation of Evolving Behavioral Intervention Technologies (CEEBIT), is proposed that can support the evaluation of multiple BITs or evolving versions, eliminating those that demonstrate poorer outcomes, while allowing new BITs to be entered at any time. CEEBIT could be used to ensure the effectiveness of BITs provided through deployment platforms in clinical care organizations or BIT marketplaces. The features of CEEBIT are described, including criteria for the determination of inferiority, determination of BIT inclusion, methods of assigning consumers to BITs, definition of outcomes, and evaluation of the usefulness of the system. CEEBIT offers the potential to collapse initial evaluation and postmarketing surveillance, providing ongoing assurance of safety and efficacy to patients and consumers, payers, and policymakers.

  19. Breast cancer management: Past, present and evolving

    Directory of Open Access Journals (Sweden)

    M Akram

    2012-01-01

    Full Text Available Breast cancer is known from ancient time,and the treatment strategy evolved as our understanding of the disease changed with time. In 460 BC Hippocrates described breast cancer as a humoral disease and presently after a lot of studies breast cancer is considered as a local disease with systemic roots. For most of the twentieth century Halsted radical mastectomy was the "established and standardized operation for cancer of the breast in all stages, early or late". New information about tumor biology and its behavior suggested that less radical surgery might be just as effective as the more extensive one. Eventually, with the use of adjuvant therapy likeradiation and systemic therapy, the extent of surgical resection in the breast and axilla got reduced further and led to an era of breast conservation. The radiation treatment of breast cancer has evolved from 2D to 3D Conformal and to accelarated partial breast irradiation, aiming to reduce normal tissue toxicity and overall treatment time. Systemic therapy in the form of hormone therapy, chemotherapy and biological agents is now a well-established modality in treatment of breast cancer. The current perspective of breast cancer management is based on the rapidly evolving and increasingly integrated study on the genetic, molecular , biochemical and cellular basis of disease. The challenge for the future is to take advantage of this knowledge for the prediction of therapeutic outcome and develop therapies and rapidly apply more novel biologic therapeutics.

  20. Transistor Level Circuit Experiments using Evolvable Hardware

    Science.gov (United States)

    Stoica, A.; Zebulum, R. S.; Keymeulen, D.; Ferguson, M. I.; Daud, Taher; Thakoor, A.

    2005-01-01

    The Jet Propulsion Laboratory (JPL) performs research in fault tolerant, long life, and space survivable electronics for the National Aeronautics and Space Administration (NASA). With that focus, JPL has been involved in Evolvable Hardware (EHW) technology research for the past several years. We have advanced the technology not only by simulation and evolution experiments, but also by designing, fabricating, and evolving a variety of transistor-based analog and digital circuits at the chip level. EHW refers to self-configuration of electronic hardware by evolutionary/genetic search mechanisms, thereby maintaining existing functionality in the presence of degradations due to aging, temperature, and radiation. In addition, EHW has the capability to reconfigure itself for new functionality when required for mission changes or encountered opportunities. Evolution experiments are performed using a genetic algorithm running on a DSP as the reconfiguration mechanism and controlling the evolvable hardware mounted on a self-contained circuit board. Rapid reconfiguration allows convergence to circuit solutions in the order of seconds. The paper illustrates hardware evolution results of electronic circuits and their ability to perform under 230 C temperature as well as radiations of up to 250 kRad.

  1. Markov Chain-based Degree Distributions of Evolving Networks

    Institute of Scientific and Technical Information of China (English)

    Xiang Xing KONG; Zhen Ting HOU; Ding Hua SHI; Quan Rong CHEN; Qing Gui ZHAO

    2012-01-01

    In this paper,we study a class of stochastic processes,called evolving network Markov chains,in evolving networks. Our approach is to transform the degree distribution problem of an evolving network to a corresponding problem of evolving network Markov chains.We investigate the evolving network Markov chains,thereby obtaining some exact formulas as well as a precise criterion for determining whether the steady degree distribution of the evolving network is a power-law or not.With this new method,we finally obtain a rigorous,exact and unified solution of the steady degree distribution of the evolving network.

  2. Why, when and where did honey bee dance communication evolve?

    Directory of Open Access Journals (Sweden)

    Robbie eI'Anson Price

    2015-11-01

    Full Text Available Honey bees (Apis sp. are the only known bee genus that uses nest-based communication to provide nest-mates with information about the location of resources, the so-called dance language. Successful foragers perform waggle dances for high quality food sources and suitable nest-sites during swarming. However, since many species of social insects do not communicate the location of resources to their nest-mates, the question of why the dance language evolved is of ongoing interest. We review recent theoretical and empirical research into the ecological circumstances that make dance communication beneficial in present day environments. This research suggests that the dance language is most beneficial when food sources differ greatly in quality and are hard to find. The dances of extant honey bee species differ in important ways, and phylogenetic studies suggest an increase in dance complexity over time: species with the least complex dance were the first to appear and species with the most complex dance are the most derived. We review the fossil record of honey bees and speculate about the time and context (foraging vs. swarming in which spatially referential dance communication might have evolved. We conclude that there are few certainties about when the dance language first appeared; dance communication could be older than 40 million years and, thus, predate the genus Apis, or it could be as recent as 20 million years when extant honey bee species diverged during the early Miocene. The most parsimonious scenario assumes it evolved in a sub-tropical to temperate climate, with patchy vegetation somewhere in Eurasia.

  3. Fitness costs associated with evolved herbicide resistance alleles in plants.

    Science.gov (United States)

    Vila-Aiub, Martin M; Neve, Paul; Powles, Stephen B

    2009-12-01

    Predictions based on evolutionary theory suggest that the adaptive value of evolved herbicide resistance alleles may be compromised by the existence of fitness costs. There have been many studies quantifying the fitness costs associated with novel herbicide resistance alleles, reflecting the importance of fitness costs in determining the evolutionary dynamics of resistance. However, many of these studies have incorrectly defined resistance or used inappropriate plant material and methods to measure fitness. This review has two major objectives. First, to propose a methodological framework that establishes experimental criteria to unequivocally evaluate fitness costs. Second, to present a comprehensive analysis of the literature on fitness costs associated with herbicide resistance alleles. This analysis reveals unquestionable evidence that some herbicide resistance alleles are associated with pleiotropic effects that result in plant fitness costs. Observed costs are evident from herbicide resistance-endowing amino acid substitutions in proteins involved in amino acid, fatty acid, auxin and cellulose biosynthesis, as well as enzymes involved in herbicide metabolism. However, these resistance fitness costs are not universal and their expression depends on particular plant alleles and mutations. The findings of this review are discussed within the context of the plant defence trade-off theory and herbicide resistance evolution.

  4. Isotopic Systematics (U, nitrate and Sr) of the F-Area Acidic Contamination Plume at the Savannah River Site: Clues to Contaminant History and Mobility

    Science.gov (United States)

    Christensen, J. N.; Conrad, M. E.; Bill, M.; Denham, M.; Wan, J.; Rakshit, S.; Stringfellow, W. T.; Spycher, N.

    2010-12-01

    Seepage basins in the F-Area of the Savannah River Site were used from 1955 to 1989 for the disposal of low-level radioactive acidic (ave. pH ˜2.9) waste solutions from site operations involving irradiated uranium billets and other materials used in the production of radionuclides. These disposal activities resulted in a persistent acidic groundwater plume (pH as low as 3.2) beneath the F-Area including contaminants such as tritium, nitrate, 90Sr, 129I and uranium and that has impinged on surface water (Four Mile Branch) about 600 m from the basins. After cessation of disposal in 1989, the basins were capped in 1991. Since that time, remediation has consisted of a pump-and-treat system that has recently been replaced with in situ treatment using a funnel-and-gate system with injection of alkaline solutions in the gates to neutralize pH. In order to delineate the history of contamination and the current mobility and fate of contaminants in F-Area groundwater, we have undertaken a study of variations in the isotopic compositions of U (234U/238U, 235U/238U, 236U/238U), Sr (87Sr/86Sr) and nitrate (δ15N, δ18O) within the contaminant plume. This data can be used to trace U transport within the plume, evaluate chemical changes of nitrate, and potentially track plume/sediment chemical interaction and trace the migration of 90Sr. We have analyzed a suite of groundwater samples from monitoring wells, as well as pore-water samples extracted from aquifer sediment cores to map out the isotopic variation within the plume. The isotopic compositions of U from well samples and porewater samples are all consistent with the variable burn-up of depleted U. The variation in U isotopic composition requires at least three different endmembers, without any significant influence of background natural U. The δ15N and δ18O of nitrate from F-Area plume groundwater are distinct both from natural and unaltered synthetic nitrate, and likely represents fractionation due to waste volume

  5. Evolved differences in larval social behavior mediated by novel pheromones.

    Science.gov (United States)

    Mast, Joshua D; De Moraes, Consuelo M; Alborn, Hans T; Lavis, Luke D; Stern, David L

    2014-12-12

    Pheromones, chemical signals that convey social information, mediate many insect social behaviors, including navigation and aggregation. Several studies have suggested that behavior during the immature larval stages of Drosophila development is influenced by pheromones, but none of these compounds or the pheromone-receptor neurons that sense them have been identified. Here we report a larval pheromone-signaling pathway. We found that larvae produce two novel long-chain fatty acids that are attractive to other larvae. We identified a single larval chemosensory neuron that detects these molecules. Two members of the pickpocket family of DEG/ENaC channel subunits (ppk23 and ppk29) are required to respond to these pheromones. This pheromone system is evolving quickly, since the larval exudates of D. simulans, the sister species of D. melanogaster, are not attractive to other larvae. Our results define a new pheromone signaling system in Drosophila that shares characteristics with pheromone systems in a wide diversity of insects.

  6. Insect sex determination: it all evolves around transformer.

    Science.gov (United States)

    Verhulst, Eveline C; van de Zande, Louis; Beukeboom, Leo W

    2010-08-01

    Insects exhibit a variety of sex determining mechanisms including male or female heterogamety and haplodiploidy. The primary signal that starts sex determination is processed by a cascade of genes ending with the conserved switch doublesex that controls sexual differentiation. Transformer is the doublesex splicing regulator and has been found in all examined insects, indicating its ancestral function as a sex-determining gene. Despite this conserved function, the variation in transformer nucleotide sequence, amino acid composition and protein structure can accommodate a multitude of upstream sex determining signals. Transformer regulation of doublesex and its taxonomic distribution indicate that the doublesex-transformer axis is conserved among all insects and that transformer is the key gene around which variation in sex determining mechanisms has evolved.

  7. Activity modulation of the oligopeptidase B from Serratia proteamaculans by site-directed mutagenesis of amino acid residues surrounding catalytic triad histidine.

    Science.gov (United States)

    Mikhailova, Anna G; Rakitina, Tatiana V; Timofeev, Vladimir I; Karlinsky, David M; Korzhenevskiy, Dmitry A; Agapova, Yulia К; Vlaskina, Anna V; Ovchinnikova, Marina V; Gorlenko, Valentina A; Rumsh, Lev D

    2017-08-01

    Oligopeptidase B (OpdB; EC 3.4.21.83) is a trypsin-like peptidase belonging to the family of serine prolyl oligopeptidases; two-domain structure of the enzyme includes C-terminal peptidase catalytic domain and N-terminal seven-bladed β-propeller domain. Importance of the interface between these domains and particularly of the 5 salt bridges for enzyme activity was established for protozoan OpdBs. However, these salt bridges are not conserved in γ -proteobacterial OpdBs including the peptidase from Serratia proteamaculans (PSP). In this work, using comparative modelling and protozoan OpdBs' crystal structures we created 3D models of PSP in open and closed forms to elucidate the mechanism underlying inactivation of the truncated form of PSP1-655 obtained earlier. Analysis of the models shows that in the closed form of PSP charged amino acid residues of histidine loop, surrounding the catalytic triad His652, participate in formation of the inter-domain contact interface between catalytic and β-propeller domains, while in the open form of PSP disconnection of the catalytic triad and distortion of these contacts can be observed. Complete destruction of this interface by site-directed mutagenesis causes inactivation of PSP while elimination of the individual contacts leads to differential effects on the enzyme activity and substrate specificity. Thus, we identified structural factors regulating activity of PSP and supposedly of other γ-proteobacterial OpdBs and discovered the possibility of directed modulation of their enzymatic features. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  8. The metal-leaching and acid-neutralizing capacity of MSW incinerator ash co-disposed with MSW in landfill sites.

    Science.gov (United States)

    Lo, Huang-Mu; Liao, Yuan-Lung

    2007-04-02

    Municipal solid waste (MSW) incinerator (MSWI) bottom ash and fly ash were used as landfill cover or were co-disposed with MSW to measure their potential metal-releasing and acid-neutralizing capacity (ANC) in landfill sites. Five lysimeters (height 1.2m, diameter 0.2m), simulating landfill conditions, were used in the experiment. Four contained either bottom ash (BA) or fly ash (FA) with BA:MSW ratios of 100 and 200 g L(-1) and FA:MSW ratios of 10 and 20 g L(-1), and the fifth was the control, which contained no ash. The lysimeters were arranged so as to contain four layers, with BA or FA placed on top of MSW within each layer. Each lysimeter was recirculated with 100mL leachate using peristaltic pumps, and 100mL of the leachate was collected weekly to measure the soluble metal concentrations. The results showed that the concentrations of soluble alkali metals measured in the leachate were in the order Ca>K>Na>Mg. In addition, the concentrations of soluble alkali metals of Ca and K collected from the lysimeters containing FA were found to be higher than the concentrations from the lysimeters containing BA. The concentrations of heavy metals (Cd, Cr, Cu, Ni, and Zn) were found to be landfill. Furthermore, heavy metals and trace metals were found in concentrations, which were too low to exert inhibitory effects on anaerobic digestion, and thus they could serve as micronutrients to exert beneficial rather than detrimental effects on landfill biostabilization.

  9. Modeling promoter grammars with evolving hidden Markov models

    DEFF Research Database (Denmark)

    Won, Kyoung-Jae; Sandelin, Albin; Marstrand, Troels Torben

    2008-01-01

    MOTIVATION: Describing and modeling biological features of eukaryotic promoters remains an important and challenging problem within computational biology. The promoters of higher eukaryotes in particular display a wide variation in regulatory features, which are difficult to model. Often several...... factors are involved in the regulation of a set of co-regulated genes. If so, promoters can be modeled with connected regulatory features, where the network of connections is characteristic for a particular mode of regulation. RESULTS: With the goal of automatically deciphering such regulatory structures......, we present a method that iteratively evolves an ensemble of regulatory grammars using a hidden Markov Model (HMM) architecture composed of interconnected blocks representing transcription factor binding sites (TFBSs) and background regions of promoter sequences. The ensemble approach reduces the risk...

  10. Bed bugs evolved unique adaptive strategy to resist pyrethroid insecticides.

    Science.gov (United States)

    Zhu, Fang; Gujar, Hemant; Gordon, Jennifer R; Haynes, Kenneth F; Potter, Michael F; Palli, Subba R

    2013-01-01

    Recent advances in genomic and post-genomic technologies have facilitated a genome-wide analysis of the insecticide resistance-associated genes in insects. Through bed bug, Cimex lectularius transcriptome analysis, we identified 14 molecular markers associated with pyrethroid resistance. Our studies revealed that most of the resistance-associated genes functioning in diverse mechanisms are expressed in the epidermal layer of the integument, which could prevent or slow down the toxin from reaching the target sites on nerve cells, where an additional layer of resistance (kdr) is possible. This strategy evolved in bed bugs is based on their unique morphological, physiological and behavioral characteristics and has not been reported in any other insect species. RNA interference-aided knockdown of resistance associated genes showed the relative contribution of each mechanism towards overall resistance development. Understanding the complexity of adaptive strategies employed by bed bugs will help in designing the most effective and sustainable bed bug control methods.

  11. Evolving Networks with Nonlinear Assignment of Weight

    Institute of Scientific and Technical Information of China (English)

    TANG Chao; TANG Yi

    2006-01-01

    We propose a weighted evolving network model in which the underlying topological structure is still driven by the degree according to the preferential attachment rule while the weight assigned to the newly established edges is dependent on the degree in a nonlinear form. By varying the parameter α that controls the function determining the assignment of weight, a wide variety of power-law behaviours of the total weight distributions as well as the diversity of the weight distributions of edges are displayed. Variation of correlation and heterogeneity in the network is illustrated as well.

  12. The tree length of an evolving coalescent

    CERN Document Server

    Pfaffelhuber, Peter; Weisshaupt, Heinz

    2009-01-01

    A well-established model for the genealogy of a large population in equilibrium is Kingman's coalescent. For the population together with its genealogy evolving in time, this gives rise to a time-stationary tree-valued process. We study the sum of the branch lengths, briefly denoted as tree length, and prove that the (suitably compensated) sequence of tree length processes converges, as the population size tends to infinity, to a limit process with cadlag paths, infinite infinitesimal variance, and a Gumbel distribution as its equilibrium.

  13. Logistic Regression for Evolving Data Streams Classification

    Institute of Scientific and Technical Information of China (English)

    YIN Zhi-wu; HUANG Shang-teng; XUE Gui-rong

    2007-01-01

    Logistic regression is a fast classifier and can achieve higher accuracy on small training data. Moreover,it can work on both discrete and continuous attributes with nonlinear patterns. Based on these properties of logistic regression, this paper proposed an algorithm, called evolutionary logistical regression classifier (ELRClass), to solve the classification of evolving data streams. This algorithm applies logistic regression repeatedly to a sliding window of samples in order to update the existing classifier, to keep this classifier if its performance is deteriorated by the reason of bursting noise, or to construct a new classifier if a major concept drift is detected. The intensive experimental results demonstrate the effectiveness of this algorithm.

  14. Strength dynamics of weighted evolving networks

    Institute of Scientific and Technical Information of China (English)

    Wu Jian-Jun; Gao Zi-You; Sun Hui-Jun

    2007-01-01

    In this paper, a simple model for the strength dynamics of weighted evolving networks is proposed to characterize the weighted networks. By considering the congestion effects, this approach can yield power law strength distribution appeared on the many real weighted networks, such as traffic networks, internet networks. Besides, the relationship between strength and degree is given. Numerical simulations indicate that the strength distribution is strongly related to the strength dynamics decline. The model also provides us with a better description of the real weighted networks.

  15. SALT Spectroscopy of Evolved Massive Stars

    Science.gov (United States)

    Kniazev, A. Y.; Gvaramadze, V. V.; Berdnikov, L. N.

    2017-06-01

    Long-slit spectroscopy with the Southern African Large Telescope (SALT) of central stars of mid-infrared nebulae detected with the Spitzer Space Telescope and Wide-Field Infrared Survey Explorer (WISE) led to the discovery of numerous candidate luminous blue variables (cLBVs) and other rare evolved massive stars. With the recent advent of the SALT fiber-fed high-resolution echelle spectrograph (HRS), a new perspective for the study of these interesting objects is appeared. Using the HRS we obtained spectra of a dozen newly identified massive stars. Some results on the recently identified cLBV Hen 3-729 are presented.

  16. Mobile computing acceptance grows as applications evolve.

    Science.gov (United States)

    Porn, Louis M; Patrick, Kelly

    2002-01-01

    Handheld devices are becoming more cost-effective to own, and their use in healthcare environments is increasing. Handheld devices currently are being used for e-prescribing, charge capture, and accessing daily schedules and reference tools. Future applications may include education on medications, dictation, order entry, and test-results reporting. Selecting the right handheld device requires careful analysis of current and future applications, as well as vendor expertise. It is important to recognize the technology will continue to evolve over the next three years.

  17. SALT spectroscopy of evolved massive stars

    CERN Document Server

    Kniazev, A Y; Berdnikov, L N

    2016-01-01

    Long-slit spectroscopy with the Southern African Large Telescope (SALT) of central stars of mid-infrared nebulae detected with the Spitzer Space Telescope and Wide-field Infrared Survey Explorer (WISE) led to the discovery of numerous candidate luminous blue variables (cLBVs) and other rare evolved massive stars. With the recent advent of the SALT fibre-fed high-resolution echelle spectrograph (HRS), a new perspective for the study of these interesting objects is appeared. Using the HRS we obtained spectra of a dozen newly identified massive stars. Some results on the recently identified cLBV Hen 3-729 are presented.

  18. Evolving NoSQL Databases Without Downtime

    OpenAIRE

    Saur, Karla; Dumitraş, Tudor; Hicks, Michael

    2015-01-01

    NoSQL databases like Redis, Cassandra, and MongoDB are increasingly popular because they are flexible, lightweight, and easy to work with. Applications that use these databases will evolve over time, sometimes necessitating (or preferring) a change to the format or organization of the data. The problem we address in this paper is: How can we support the evolution of high-availability applications and their NoSQL data online, without excessive delays or interruptions, even in the presence of b...

  19. Will the Amaranthus tuberculatus Resistance Mechanism to PPO-Inhibiting Herbicides Evolve in Other Amaranthus Species?

    Directory of Open Access Journals (Sweden)

    Chance W. Riggins

    2012-01-01

    Full Text Available Resistance to herbicides that inhibit protoporphyrinogen oxidase (PPO has been slow to evolve and, to date, is confirmed for only four weed species. Two of these species are members of the genus Amaranthus L. Previous research has demonstrated that PPO-inhibitor resistance in A. tuberculatus (Moq. Sauer, the first weed to have evolved this type of resistance, involves a unique codon deletion in the PPX2 gene. Our hypothesis is that A. tuberculatus may have been predisposed to evolving this resistance mechanism due to the presence of a repetitive motif at the mutation site and that lack of this motif in other amaranth species is why PPO-inhibitor resistance has not become more common despite strong herbicide selection pressure. Here we investigate inter- and intraspecific variability of the PPX2 gene—specifically exon 9, which includes the mutation site—in ten amaranth species via sequencing and a PCR-RFLP assay. Few polymorphisms were observed in this region of the gene, and intraspecific variation was observed only in A. quitensis. However, sequencing revealed two distinct repeat patterns encompassing the mutation site. Most notably, A. palmeri S. Watson possesses the same repetitive motif found in A. tuberculatus. We thus predict that A. palmeri will evolve resistance to PPO inhibitors via the same PPX2 codon deletion that evolved in A. tuberculatus.

  20. Minodronic acid induces morphological changes in osteoclasts at bone resorption sites and reaches a level required for antagonism of purinergic P2X2/3 receptors.

    Science.gov (United States)

    Tanaka, Makoto; Hosoya, Akihiro; Mori, Hiroshi; Kayasuga, Ryoji; Nakamura, Hiroaki; Ozawa, Hidehiro

    2017-02-27

    Minodronic acid is an aminobisphosphonate that is an antagonist of purinergic P2X2/3 receptors involved in pain. The aim of this study was to investigate the action and distribution of minodronic acid and the potential for P2X2/3 receptor antagonism based on the estimated concentration of minodronic acid. Microlocalization of radiolabeled minodronic acid was examined in the femur of neonatal rats. The bone-binding characteristics of minodronic acid and morphological changes in osteoclasts were analyzed in vitro. The minodronic acid concentration around bone resorption lacunae was predicted based on bone binding and the shape of lacunae. In microautoradiography, radioactive silver grains were abundant in bone-attached osteoclasts and were detected in calcified and ossification zones and in the cytoplasm of osteoclasts but not in the hypertrophic cartilage zone. In an osteoclast culture with 1 µM minodronic acid, 65% of minodronic acid was bound to bone, and C-terminal cross-linking telopeptide release was inhibited by 96%. Cultured osteoclasts without minodronic acid treatment formed ruffled borders and bone resorption lacunae and had rich cytoplasm, whereas those treated with 1 µM minodronic acid were not multinucleated, stained densely with toluidine blue, and were detached from the bone surface. In the 1 µM culture, the estimated minodronic acid concentration in resorption lacunae was 880 µM, which is higher than the IC50 for minodronic acid antagonism of P2X2/3 receptors. Thus, inhibition of P2X2/3 receptors around osteoclasts may contribute to the analgesic effect of minodronic acid.

  1. The evolving role of the transfusion practitioner.

    Science.gov (United States)

    Miller, Kristy; Akers, Christine; Davis, Amanda K; Wood, Erica; Hennessy, Clare; Bielby, Linley

    2015-04-01

    Much of the recent work in transfusion practice has shifted to focus on the patient, after efforts over previous decades to ensure the quality and safety of blood products. After the commencement of hemovigilance and transfusion practice improvement programs, the introduction of transfusion practitioners (TP) into health care services and blood centers has continued to increase worldwide. Since this relatively new role was introduced, much work of the TP has focused on patient and staff education, adverse events, transfusion governance, and monitoring of transfusion practices within organizations. The complex nature of the transfusion process makes the TP an integral link in the transfusion chain. Together with hospital transfusion teams and committees, the TP works collaboratively to facilitate the transfusion change management programs and initiatives. Recently, the TP role has evolved to include an emphasis on patient blood management and, to some extent, is shaped by national standards and regulations. These established roles of the TP, together with the ever-changing field of transfusion medicine, provide new opportunities and challenges for a role that is continuing to evolve worldwide. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Netgram: Visualizing Communities in Evolving Networks.

    Directory of Open Access Journals (Sweden)

    Raghvendra Mall

    Full Text Available Real-world complex networks are dynamic in nature and change over time. The change is usually observed in the interactions within the network over time. Complex networks exhibit community like structures. A key feature of the dynamics of complex networks is the evolution of communities over time. Several methods have been proposed to detect and track the evolution of these groups over time. However, there is no generic tool which visualizes all the aspects of group evolution in dynamic networks including birth, death, splitting, merging, expansion, shrinkage and continuation of groups. In this paper, we propose Netgram: a tool for visualizing evolution of communities in time-evolving graphs. Netgram maintains evolution of communities over 2 consecutive time-stamps in tables which are used to create a query database using the sql outer-join operation. It uses a line-based visualization technique which adheres to certain design principles and aesthetic guidelines. Netgram uses a greedy solution to order the initial community information provided by the evolutionary clustering technique such that we have fewer line cross-overs in the visualization. This makes it easier to track the progress of individual communities in time evolving graphs. Netgram is a generic toolkit which can be used with any evolutionary community detection algorithm as illustrated in our experiments. We use Netgram for visualization of topic evolution in the NIPS conference over a period of 11 years and observe the emergence and merging of several disciplines in the field of information processing systems.

  3. BOOK REVIEW: OPENING SCIENCE, THE EVOLVING GUIDE ...

    Science.gov (United States)

    The way we get our funding, collaborate, do our research, and get the word out has evolved over hundreds of years but we can imagine a more open science world, largely facilitated by the internet. The movement towards this more open way of doing and presenting science is coming, and it is not taking hundreds of years. If you are interested in these trends, and would like to find out more about where this is all headed and what it means to you, consider downloding Opening Science, edited by Sönke Bartling and Sascha Friesike, subtitled The Evolving Guide on How the Internet is Changing Research, Collaboration, and Scholarly Publishing. In 26 chapters by various authors from a range of disciplines the book explores the developing world of open science, starting from the first scientific revolution and bringing us to the next scientific revolution, sometimes referred to as “Science 2.0”. Some of the articles deal with the impact of the changing landscape of how science is done, looking at the impact of open science on Academia, or journal publishing, or medical research. Many of the articles look at the uses, pitfalls, and impact of specific tools, like microblogging (think Twitter), social networking, and reference management. There is lots of discussion and definition of terms you might use or misuse like “altmetrics” and “impact factor”. Science will probably never be completely open, and Twitter will probably never replace the journal article,

  4. Collapse of cooperation in evolving games.

    Science.gov (United States)

    Stewart, Alexander J; Plotkin, Joshua B

    2014-12-09

    Game theory provides a quantitative framework for analyzing the behavior of rational agents. The Iterated Prisoner's Dilemma in particular has become a standard model for studying cooperation and cheating, with cooperation often emerging as a robust outcome in evolving populations. Here we extend evolutionary game theory by allowing players' payoffs as well as their strategies to evolve in response to selection on heritable mutations. In nature, many organisms engage in mutually beneficial interactions and individuals may seek to change the ratio of risk to reward for cooperation by altering the resources they commit to cooperative interactions. To study this, we construct a general framework for the coevolution of strategies and payoffs in arbitrary iterated games. We show that, when there is a tradeoff between the benefits and costs of cooperation, coevolution often leads to a dramatic loss of cooperation in the Iterated Prisoner's Dilemma. The collapse of cooperation is so extreme that the average payoff in a population can decline even as the potential reward for mutual cooperation increases. Depending upon the form of tradeoffs, evolution may even move away from the Iterated Prisoner's Dilemma game altogether. Our work offers a new perspective on the Prisoner's Dilemma and its predictions for cooperation in natural populations; and it provides a general framework to understand the coevolution of strategies and payoffs in iterated interactions.

  5. BOOK REVIEW: OPENING SCIENCE, THE EVOLVING GUIDE ...

    Science.gov (United States)

    The way we get our funding, collaborate, do our research, and get the word out has evolved over hundreds of years but we can imagine a more open science world, largely facilitated by the internet. The movement towards this more open way of doing and presenting science is coming, and it is not taking hundreds of years. If you are interested in these trends, and would like to find out more about where this is all headed and what it means to you, consider downloding Opening Science, edited by Sönke Bartling and Sascha Friesike, subtitled The Evolving Guide on How the Internet is Changing Research, Collaboration, and Scholarly Publishing. In 26 chapters by various authors from a range of disciplines the book explores the developing world of open science, starting from the first scientific revolution and bringing us to the next scientific revolution, sometimes referred to as “Science 2.0”. Some of the articles deal with the impact of the changing landscape of how science is done, looking at the impact of open science on Academia, or journal publishing, or medical research. Many of the articles look at the uses, pitfalls, and impact of specific tools, like microblogging (think Twitter), social networking, and reference management. There is lots of discussion and definition of terms you might use or misuse like “altmetrics” and “impact factor”. Science will probably never be completely open, and Twitter will probably never replace the journal article,

  6. Early formation of evolved asteroidal crust.

    Science.gov (United States)

    Day, James M D; Ash, Richard D; Liu, Yang; Bellucci, Jeremy J; Rumble, Douglas; McDonough, William F; Walker, Richard J; Taylor, Lawrence A

    2009-01-08

    Mechanisms for the formation of crust on planetary bodies remain poorly understood. It is generally accepted that Earth's andesitic continental crust is the product of plate tectonics, whereas the Moon acquired its feldspar-rich crust by way of plagioclase flotation in a magma ocean. Basaltic meteorites provide evidence that, like the terrestrial planets, some asteroids generated crust and underwent large-scale differentiation processes. Until now, however, no evolved felsic asteroidal crust has been sampled or observed. Here we report age and compositional data for the newly discovered, paired and differentiated meteorites Graves Nunatak (GRA) 06128 and GRA 06129. These meteorites are feldspar-rich, with andesite bulk compositions. Their age of 4.52 +/- 0.06 Gyr demonstrates formation early in Solar System history. The isotopic and elemental compositions, degree of metamorphic re-equilibration and sulphide-rich nature of the meteorites are most consistent with an origin as partial melts from a volatile-rich, oxidized asteroid. GRA 06128 and 06129 are the result of a newly recognized style of evolved crust formation, bearing witness to incomplete differentiation of their parent asteroid and to previously unrecognized diversity of early-formed materials in the Solar System.

  7. Effects of Zeolite Structure and Si/Al Ratio on Adsorption Thermodynamics and Intrinsic Kinetics of Monomolecular Cracking and Dehydrogenation of Alkanes over Bronsted Acid Sites

    Science.gov (United States)

    Janda, Amber Leigh

    It is well known that the efficacy of acidic zeolite catalysts for the cracking of hydrocarbons originates from the shape and size of the zeolite pores. However, the mechanisms by which changes in pore structure influence cracking kinetics are not well understood or exploited. The aim of this dissertation is to use experiments and simulations to shed light on the ways by which zeolite structure and acid site location affect the apparent and intrinsic kinetics of n-alkane monomolecular cracking and dehydrogenation. In the rate-determining step of these processes, C-C or C-H bonds are cleaved catalytically by Bronsted protons. Thus, the kinetics of monomolecular activation reactions are useful for characterizing the influence of active site structural environment on catalysis. In Chapter 2, the effects of active site distribution on n-butane monomolecular activation kinetics are investigated for commercial samples of MFI having a range of the Si/Al ratio. Based on UV-visible spectroscopic analyses of (Co,Na)-MFI, it is inferred that, with increasing Al concentration, the fraction of Co---and, by extension, Bronsted protons in H-MFI---located at channel intersections increases relative to the fraction located at channels. Concurrently, the first-order rate coefficients (kapp) for cracking and dehydrogenation, the selectivity to terminal cracking versus central cracking, and the selectivity to dehydrogenation versus cracking increase. The stronger dependence of the selectivity to dehydrogenation on Al content is attributed to a product-like transition state, the stability of which is more sensitive to confinement than the stabilities of cracking transition states, which occur earlier along the reaction coordinate. For terminal cracking and dehydrogenation, the intrinsic activation entropy (DeltaS‡int ) increases with Al content, consistent with the larger dimensions of intersections relative to channels. Surprisingly, the rate of dehydrogenation is inhibited by

  8. A possible molecular metric for biological evolvability

    Indian Academy of Sciences (India)

    Aditya Mittal; B Jayaram

    2012-07-01

    Proteins manifest themselves as phenotypic traits, retained or lost in living systems via evolutionary pressures. Simply put, survival is essentially the ability of a living system to synthesize a functional protein that allows for a response to environmental perturbations (adaptation). Loss of functional proteins leads to extinction. Currently there are no universally applicable quantitative metrics at the molecular level for either measuring ‘evolvability’ of life or for assessing the conditions under which a living system would go extinct and why. In this work, we show emergence of the first such metric by utilizing the recently discovered stoichiometric margin of life for all known naturally occurring (and functional) proteins. The constraint of having well-defined stoichiometries of the 20 amino acids in naturally occurring protein sequences requires utilization of the full scope of degeneracy in the genetic code, i.e. usage of all codons coding for an amino acid, by only 11 of the 20 amino acids. This shows that the non-availability of individual codons for these 11 amino acids would disturb the fine stoichiometric balance resulting in non-functional proteins and hence extinction. Remarkably, these amino acids are found in close proximity of any given amino acid in the backbones of thousands of known crystal structures of folded proteins. On the other hand, stoichiometry of the remaining 9 amino acids, found to be farther/distal from any given amino acid in backbones of folded proteins, is maintained independent of the number of codons available to synthesize them, thereby providing some robustness and hence survivability.

  9. Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses

    Directory of Open Access Journals (Sweden)

    Guan Yi

    2007-10-01

    Full Text Available Abstract Background Influenza virus binds to cell receptors via sialic acid (SA linked glycoproteins. They recognize SA on host cells through their haemagglutinins (H. The distribution of SA on cell surfaces is one determinant of host tropism and understanding its expression on human cells and tissues is important for understanding influenza pathogenesis. The objective of this study therefore was to optimize the detection of α2,3-linked and α2,6-linked SA by lectin histochemistry by investigating the binding of Sambucus nigra agglutinin (SNA for SAα2,6Gal and Maackia amurensis agglutinin (MAA for SAα2,3Gal in the respiratory tract of normal adults and children. Methods We used fluorescent and biotinylated SNA and MAA from different suppliers on archived and prospectively collected biopsy and autopsy specimens from the nasopharynx, trachea, bronchus and lungs of fetuses, infants and adults. We compared different methods of unmasking for tissue sections to determine if these would affect lectin binding. Using serial sections we then compared the lectin binding of MAA from different suppliers. Results We found that unmasking using microwave treatment in citrate buffer produced increased lectin binding to the ciliated and glandular epithelium of the respiratory tract. In addition we found that there were differences in tissue distribution of the α2,3 linked SA when 2 different isoforms of MAA (MAA1 and MAA2 lectin were used. MAA1 had widespread binding throughout the upper and lower respiratory tract and showed more binding to the respiratory epithelium of children than in adults. By comparison, MAA2 binding was mainly restricted to the alveolar epithelial cells of the lung with weak binding to goblet cells. SNA binding was detected in bronchial and alveolar epithelial cells and binding of this lectin was stronger to the paediatric epithelium compared to adult epithelium. Furthermore, the MAA lectins from 2 suppliers (Roche and EY Labs tended

  10. Experimental determination of the evolvability of a transcription factor.

    Science.gov (United States)

    Maerkl, Sebastian J; Quake, Stephen R

    2009-11-03

    Sequence-specific binding of a transcription factor to DNA is the central event in any transcriptional regulatory network. However, relatively little is known about the evolutionary plasticity of transcription factors. For example, the exact functional consequence of an amino acid substitution on the DNA-binding specificity of most transcription factors is currently not predictable. Furthermore, although the major structural families of transcription factors have been identified, the detailed DNA-binding repertoires within most families have not been characterized. We studied the sequence recognition code and evolvability of the basic helix-loop-helix transcription factor family by creating all possible 95 single-point mutations of five DNA-contacting residues of Max, a human helix-loop-helix transcription factor and measured the detailed DNA-binding repertoire of each mutant. Our results show that the sequence-specific repertoire of Max accessible through single-point mutations is extremely limited, and we are able to predict 92% of the naturally occurring diversity at these positions. All naturally occurring basic regions were also found to be accessible through functional intermediates. Finally, we observed a set of amino acids that are functional in vitro but are not found to be used naturally, indicating that functionality alone is not sufficient for selection.

  11. The evolution of risk communication at the Weldon Spring site

    Energy Technology Data Exchange (ETDEWEB)

    McCracken, S. [USDOE Weldon Spring Site, St. Charles, MO (United States); Sizemore, M.; Meyer, L. [MK-Ferguson Co., Weldon Spring, MO (United States)]|[Jacobs Engineering Group, Inc., Weldon Spring, MO (United States); MacDonell, M.; Haroun, L. [Argonne National Lab., IL (United States)

    1993-11-01

    Clear risk communication is one of the keys to establishing a positive relationship with the public at an environmental restoration site. This effort has been evolving at the Weldon Spring site over the past few years, with considerable input from the local community. The recent signing of the major cleanup decision for this site, which identifies on-site disposal as the remedy reflects the strength of the communication program that has evolved for the project.

  12. Evolved Mechanisms Versus Underlying Conditional Relations

    Directory of Open Access Journals (Sweden)

    Astorga Miguel López

    2015-03-01

    Full Text Available The social contracts theory claims that, in social exchange circumstances, human reasoning is not necessarily led by logic, but by certain evolved mental mechanisms that are useful for catching offenders. An emblematic experiment carried out with the intention to prove this thesis is the first experiment described by Fiddick, Cosmides, and Tooby in their paper of 2000. Lopez Astorga has questioned that experiment claiming that its results depend on an underlying conditional logical form not taken into account by Fiddick, Cosmides, and Tooby. In this paper, I propose an explanation alternative to that of Lopez Astorga, which does not depend on logical forms and is based on the mental models theory. Thus, I conclude that this other alternative explanation is one more proof that the experiment in question does not demonstrate the fundamental thesis of the social contracts theory.

  13. Evolving Classifiers: Methods for Incremental Learning

    CERN Document Server

    Hulley, Greg

    2007-01-01

    The ability of a classifier to take on new information and classes by evolving the classifier without it having to be fully retrained is known as incremental learning. Incremental learning has been successfully applied to many classification problems, where the data is changing and is not all available at once. In this paper there is a comparison between Learn++, which is one of the most recent incremental learning algorithms, and the new proposed method of Incremental Learning Using Genetic Algorithm (ILUGA). Learn++ has shown good incremental learning capabilities on benchmark datasets on which the new ILUGA method has been tested. ILUGA has also shown good incremental learning ability using only a few classifiers and does not suffer from catastrophic forgetting. The results obtained for ILUGA on the Optical Character Recognition (OCR) and Wine datasets are good, with an overall accuracy of 93% and 94% respectively showing a 4% improvement over Learn++.MT for the difficult multi-class OCR dataset.

  14. Quantum mechanics in an evolving Hilbert space

    CERN Document Server

    Artacho, Emilio

    2016-01-01

    Many basis sets for electronic structure calculations evolve with varying external parameters, such as moving atoms in dynamic simulations, giving rise to extra derivative terms in the dynamical equations. Here we revisit these derivatives in the context of differential geometry, thereby obtaining a more transparent formalisation, and a geometrical perspective for better understanding the resulting equations. The effect of the evolution of the basis set within the spanned Hilbert space separates explicitly from the effect of the turning of the space itself when moving in parameter space, as the tangent space turns when moving in a curved space. New insights are obtained using familiar concepts in that context such as the Riemann curvature. The differential geometry is not strictly that for curved spaces as in general relativity, a more adequate mathematical framework being provided by fibre bundles. The language used here, however, will be restricted to tensors and basic quantum mechanics. The local gauge imp...

  15. THE J STRUCTURE IN ECONOMIC EVOLVING PROCESS

    Institute of Scientific and Technical Information of China (English)

    FANG Fukang; CHEN Qinghua

    2003-01-01

    The economic evolution exhibits complexity. Behind the variable and fiuctuant economic data there exists basic characters and rules. One basic structure in economic evolving process called as "J" structure is studied by us. This kind of structure exists in a wide area, such as economic growth, technology innovation, international trade, education, human capital, ecology and environment etc. From the view of economic evolution, J structure has the character that system should suffer the pressure of initial investment with profit decreasing but get larger return afterwards. It is a kind of adaptation in complex economic systems; it reflects the adaptive and reformative ability of the system under the surrounding change. We illustrate the J structure by discussing economic growth. Based on a two-dimension dynamic system the geometric character and mechanism of J structure are studied, also the phase graphs with its condition are given. Also some further works are discussed.

  16. Design of Evolvable Hardware for Robotic Navigation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper presents an integrated on-line learning system toevolve programmabl e logic array (PLA) controllers for navigating an autonomous robot in a two-dime n sional environment. The integrated on-line learning system consists of two lear n ing modules: one is the module of reinforcement learning based on temporal-diff e rence learning based on genetic algorithms, and the other is the module of evolu tionary learning based on genetic algorithms. The control rules extracted from t he module of reinforcement learning can be used as input to the module of evolut ionary learning, and quickly implemented by the PLA through on-line evolution. T he on-line evolution has shown promise as a method of learning systems in compl e x environment. The evolved PLA controllers can successfully navigate the robot t o a target in the two-dimensional environment while avoiding collisions with ra ndomly positioned obstacles.

  17. Production and decay of evolving horizons

    CERN Document Server

    Visser, M; Nielsen, Alex; Visser, Matt

    2006-01-01

    We consider a simple physical model for an evolving horizon that is strongly interacting with its environment, exchanging arbitrarily large quantities of matter with its environment in the form of both infalling material and outgoing Hawking radiation. We permit fluxes of both lightlike and timelike particles to cross the horizon, and ask how the horizon grows and shrinks in response to such flows. We place a premium on providing a clear and straightforward exposition with simple formulae. To be able to handle such a highly dynamical situation in a simple manner we make one significant physical restriction, that of spherical symmetry, and two technical mathematical restrictions: (1) We choose to slice the spacetime in such a way that the space-time foliations (and hence the horizons) are always spherically symmetric. (2) Furthermore we adopt Painleve-Gullstrand coordinates (which are well suited to the problem because they are nonsingular at the horizon) in order to simplify the relevant calculations. We find...

  18. Epidemic spreading on evolving signed networks

    CERN Document Server

    Saeedian, M; Jafari, G R; Kertesz, J

    2016-01-01

    Most studies of disease spreading consider the underlying social network as obtained without the contagion, though epidemic influences peoples willingness to contact others: A friendly contact may be turned to unfriendly to avoid infection. We study the susceptible-infected (SI) disease spreading model on signed networks, in which each edge is associated with a positive or negative sign representing the friendly or unfriendly relation between its end nodes. In a signed network, according to Heiders theory, edge signs evolve such that finally a state of structural balance is achieved, corresponding to no frustration in physics terms. However, the danger of infection affects the evolution of its edge signs. To describe the coupled problem of the sign evolution and disease spreading, we generalize the notion of structural balance by taking into account the state of the nodes. We introduce an energy function and carry out Monte-Carlo simulations on complete networks to test the energy landscape, where we find loc...

  19. Resiliently evolving supply-demand networks

    CERN Document Server

    Rubido, Nicolás; Baptista, Murilo S

    2013-01-01

    The ability to design a transport network such that commodities are brought from suppliers to consumers in a steady, optimal, and stable way is of great importance for nowadays distribution systems. In this Letter, by using the circuit laws of Kirchhoff and Ohm, we provide the exact capacities of the edges that an optimal supply-demand network should have to operate stably under perturbations. The perturbations we consider are the evolution of the connecting topology, the decentralisation of hub sources or sinks, and the intermittence of suppliers/consumers characteristics. We analyse these conditions and the impact of our results, both on the current UK power-grid structure and on numerically generated evolving archetypal network topologies.

  20. Resiliently evolving supply-demand networks.

    Science.gov (United States)

    Rubido, Nicolás; Grebogi, Celso; Baptista, Murilo S

    2014-01-01

    The ability to design a transport network such that commodities are brought from suppliers to consumers in a steady, optimal, and stable way is of great importance for distribution systems nowadays. In this work, by using the circuit laws of Kirchhoff and Ohm, we provide the exact capacities of the edges that an optimal supply-demand network should have to operate stably under perturbations, i.e., without overloading. The perturbations we consider are the evolution of the connecting topology, the decentralization of hub sources or sinks, and the intermittence of supplier and consumer characteristics. We analyze these conditions and the impact of our results, both on the current United Kingdom power-grid structure and on numerically generated evolving archetypal network topologies.

  1. The Evolving Structure of Galactic Disks

    CERN Document Server

    Martel, H; McGee, S; Gibson, B; Kawata, D; Martel, Hugo; Brook, Chris; Gee, Sean Mc; Gibson, Brad

    2005-01-01

    Observations suggest that the structural parameters of disk galaxies have not changed greatly since redshift 1. We examine whether these observations are consistent with a cosmology in which structures form hierarchically. We use SPH/N-body galaxy-scale simulations to simulate the formation and evolution of Milky-Way-like disk galaxies by fragmentation, followed by hierarchical merging. The simulated galaxies have a thick disk, that forms in a period of chaotic merging at high redshift, during which a large amount of alpha-elements are produced, and a thin disk, that forms later and has a higher metallicity. Our simulated disks settle down quickly and do not evolve much since redshift z~1, mostly because no major mergers take place between z=1 and z=0. During this period, the disk radius increases (inside-out growth) while its thickness remains constant. These results are consistent with observations of disk galaxies at low and high redshift.

  2. Ensuring Query Compatibility with Evolving XML Schemas

    CERN Document Server

    Genevès, Pierre; Quint, Vincent

    2008-01-01

    During the life cycle of an XML application, both schemas and queries may change from one version to another. Schema evolutions may affect query results and potentially the validity of produced data. Nowadays, a challenge is to assess and accommodate the impact of theses changes in rapidly evolving XML applications. This article proposes a logical framework and tool for verifying forward/backward compatibility issues involving schemas and queries. First, it allows analyzing relations between schemas. Second, it allows XML designers to identify queries that must be reformulated in order to produce the expected results across successive schema versions. Third, it allows examining more precisely the impact of schema changes over queries, therefore facilitating their reformulation.

  3. Properties of evolving e-mail networks

    Science.gov (United States)

    Wang, Juan; de Wilde, Philippe

    2004-12-01

    Computer viruses spread by attaching to an e-mail message and sending themselves to users whose addresses are in the e-mail address book of the recipients. Here we investigate a simple model of an evolving e-mail network, with nodes as e-mail address books of users and links as the records of e-mail addresses in the address books. Within specific periods, some new links are generated and some old links are deleted. We study the statistical properties of this e-mail network and observe the effect of the evolution on the structure of the network. We also find that the balance between the generation procedure and deletion procedure is dependent on different parameters of the model.

  4. Regulatory mechanisms link phenotypic plasticity to evolvability.

    Science.gov (United States)

    van Gestel, Jordi; Weissing, Franz J

    2016-04-18

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticity tend to adopt a phenomenological reaction norm (RN) approach, which neglects the mechanisms underlying plasticity. Focusing on a concrete question - the optimal timing of bacterial sporulation - we here also consider a mechanistic approach, the evolution of a gene regulatory network (GRN) underlying plasticity. Using individual-based simulations, we compare the RN and GRN approach and find a number of striking differences. Most importantly, the GRN model results in a much higher diversity of responsive strategies than the RN model. We show that each of the evolved strategies is pre-adapted to a unique set of unseen environmental conditions. The regulatory mechanisms that control plasticity therefore critically link phenotypic plasticity to the adaptive potential of biological populations.

  5. Language as a coordination tool evolves slowly

    Science.gov (United States)

    2016-01-01

    Social living ultimately depends on coordination between group members, and communication is necessary to make this possible. We suggest that this might have been the key selection pressure acting on the evolution of language in humans and use a behavioural coordination model to explore the impact of communication efficiency on social group coordination. We show that when language production is expensive but there is an individual benefit to the efficiency with which individuals coordinate their behaviour, the evolution of efficient communication is selected for. Contrary to some views of language evolution, the speed of evolution is necessarily slow because there is no advantage in some individuals evolving communication abilities that much exceed those of the community at large. However, once a threshold competence has been achieved, evolution of higher order language skills may indeed be precipitate. PMID:28083091

  6. A local-world evolving hypernetwork model

    Science.gov (United States)

    Yang, Guang-Yong; Liu, Jian-Guo

    2014-01-01

    Complex hypernetworks are ubiquitous in the real system. It is very important to investigate the evolution mechanisms. In this paper, we present a local-world evolving hypernetwork model by taking into account the hyperedge growth and local-world hyperedge preferential attachment mechanisms. At each time step, a newly added hyperedge encircles a new coming node and a number of nodes from a randomly selected local world. The number of the selected nodes from the local world obeys the uniform distribution and its mean value is m. The analytical and simulation results show that the hyperdegree approximately obeys the power-law form and the exponent of hyperdegree distribution is γ = 2 + 1/m. Furthermore, we numerically investigate the node degree, hyperedge degree, clustering coefficient, as well as the average distance, and find that the hypernetwork model shares the scale-free and small-world properties, which shed some light for deeply understanding the evolution mechanism of the real systems.

  7. Evolving roles of highly successful mentors.

    Science.gov (United States)

    Melanson, Mark A

    2007-01-01

    This article was written groom mentors, old and new, by identifying the evolving roles that highly successful mentors in order to share wisdom with their protégés. First aspiring mentors need to become subject matter experts in their profession by achieving the relevant benchmarks of mastery in their career fields. Next, they must win the coveted role of respected leader by being trustworthy and putting the development of others first. The mastery of knowledge and earning of respect must also be balanced by genuine humility if the mentor is to be effective in sharing what he or she knows. Highly successful mentors are teachers, plain and simple, and they are most effective in this role when they have a deep passion for teaching. By properly using reflection, adroit mentors look back upon their many adventures and carefully select critical stories to share with their protégés. While outstanding mentors have a lot to say, they need to spend most of their time listening to those they mentor to ensure that they understand their protégés' individualized needs and goals. To help protégés through the setbacks and disappointments that can accompany an Army career, high-speed mentors need to don the role of optimistic cheerleaders, encouraging those they mentor and restoring hope. Once a striving mentor has finally reached the summit of mentoring and is a trusted counselor, he or she must continue to nurture and protect this fragile, but most influential role. Lastly, great mentors need to be consummate students of both their profession and mentoring so that they remain vital and responsive to those they mentor. In closing, it is hoped that by considering and embracing these evolving roles, dedicated students of mentoring will derive a deeper satisfaction and have greater success in this critically important leadership responsibility.

  8. Acquisition of a novel eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site confers intracellular cleavage of an H7N7 influenza virus hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States); Whittaker, Gary R., E-mail: grw7@cornell.edu [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States)

    2012-12-05

    A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.

  9. Evolving circuits in seconds: experiments with a stand-alone board-level evolvable system

    Science.gov (United States)

    Stoica, A.; Zebulum, R. S.; Ferguson, M. I.; Keymeulen, D.; Duong, V.; Guo, X.

    2002-01-01

    The purpose of this paper is twofold: first, to illustrate a stand-alone board-level evolvable system (SABLES) and its performance, and second to illustrate some problems that occur during evolution with real hardware in the loop, or when the intention of the user is not completely reflected in the fitness function.

  10. Identification and characterization of the soybean IPK1 ortholog of a low phytic acid mutant reveals an exon-excluding splice-site mutation.

    Science.gov (United States)

    Yuan, Feng-Jie; Zhu, Dan-Hua; Tan, Yuan-Yuan; Dong, De-Kun; Fu, Xu-Jun; Zhu, Shen-Long; Li, Bai-Quan; Shu, Qing-Yao

    2012-11-01

    Phytic acid (myo-inositol 1, 2, 3, 4, 5, 6 hexakisphosphate) is an important constituent of soybean meal. Since phytic acid and its mineral salts (phytates) are almost indigestible for monogastrics, their abundance in grain food/feed causes nutritional and environmental problems; interest in breeding low phytic acid has therefore increased considerably. Based on gene mapping and the characteristics of inositol polyphosphates profile in the seeds of a soybean mutant line Gm-lpa-ZC-2, the soybean ortholog of inositol 1,3,4,5,6 pentakisphosphate (InsP(5)) 2-kinase (IPK1), which transforms InsP(5) into phytic acid, was first hypothesized as the candidate gene responsible for the low phytic acid alteration in Gm-lpa-ZC-2. One IPK1 ortholog (Glyma14g07880, GmIPK1) was then identified in the mapped region on chromosome 14. Sequencing revealed a G → A point mutation in the genomic DNA sequence and the exclusion of the entire fifth exon in the cDNA sequence of GmIPK1 in Gm-lpa-ZC-2 compared with its wild-type progenitor Zhechun No. 3. The excluded exon encodes 37 amino acids that spread across two conserved IPK1 motifs. Furthermore, complete co-segregation of low phytic acid phenotype with the G → A mutation was observed in the F(2) population of ZC-lpa x Zhexiandou No. 4 (a wild-type cultivar). Put together, the G → A point mutation affected the pre-mRNA splicing and resulted in the exclusion of the fifth exon of GmIPK1 which is expected to disrupt the GmIPK1 functionality, leading to low phytic acid level in Gm-lpa-ZC-2. Gm-lpa-ZC-2, would be a good germplasm source in low phytic acid soybean breeding.

  11. How did viviparity originate and evolve? Of conflict, co-option, and cryptic choice.

    Science.gov (United States)

    Kalinka, Alex T

    2015-07-01

    I propose that the underlying adaptation enabling the reproductive strategy of birthing live young (viviparity) is retraction of the site of fertilization within the female reproductive tract, and that this evolved as a means of postcopulatory sexual selection. There are three conspicuous aspects associated with viviparity: (i) internal development is a complex trait often accompanied by a suite of secondary adaptations, yet it is unclear how the intermediate state of this trait - egg retention - could have evolved; (ii) viviparity often results in a reduction in fecundity; (iii) viviparity has evolved independently many times across a diverse array of animal groups. Focusing on the Diptera (true flies), I provide explanations for these observations. I further propose that fecundity is not traded-off to enable potential benefits of viviparity, but rather that loss of fecundity is directly selected and egg retention is an indirect consequence - a model that provides a unifying common basis for the ubiquity of viviparity.

  12. Tetranectin-binding site on plasminogen kringle 4 involves the lysine-binding pocket and at least one additional amino acid residue

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Sigurskjold, B W; Thøgersen, H C

    2000-01-01

    that all amino acid residues of plasminogen kringle 4 found to be involved in t-AMCHA binding are also involved in binding tetranectin. Notably, one amino acid residue of plasminogen kringle 4, Arg 32, not involved in binding t-AMCHA, is critical for binding tetranectin. We also find that Asp 57 and Asp 55......, we analyze the interaction of wild-type and six single-residue mutants of recombinant plasminogen kringle 4 expressed in Escherichia coli with the recombinant C-type lectin domain of tetranectin and trans-aminomethyl-cyclohexanoic acid (t-AMCHA) using isothermal titration calorimetry. We find...

  13. Identification of S-glutathionylation sites in species-specific proteins by incorporating five sequence-derived features into the general pseudo-amino acid composition.

    Science.gov (United States)

    Zhao, Xiaowei; Ning, Qiao; Ai, Meiyue; Chai, Haiting; Yang, Guifu

    2016-06-07

    As a selective and reversible protein post-translational modification, S-glutathionylation generates mixed disulfides between glutathione (GSH) and cysteine residues, and plays an important role in regulating protein activity, stability, and redox regulation. To fully understand S-glutathionylation mechanisms, identification of substrates and specific S-Glutathionylated sites is crucial. Experimental identification of S-glutathionylated sites is labor-intensive and time consuming, so establishing an effective computational method is much desirable due to their convenient and fast speed. Therefore, in this study, a new bioinformatics tool named SSGlu (Species-Specific identification of Protein S-glutathionylation Sites) was developed to identify species-specific protein S-glutathionylated sites, utilizing support vector machines that combine multiple sequence-derived features with a two-step feature selection. By 5-fold cross validation, the performance of SSGlu was measured with an AUC of 0.8105 and 0.8041 for Homo sapiens and Mus musculus, respectively. Additionally, SSGlu was compared with the existing methods, and the higher MCC and AUC of SSGlu demonstrated that SSGlu was very promising to predict S-glutathionylated sites. Furthermore, a site-specific analysis showed that S-glutathionylation intimately correlated with the features derived from its surrounding sites. The conclusions derived from this study might help to understand more of the S-glutathionylation mechanism and guide the related experimental validation. For public access, SSGlu is freely accessible at http://59.73.198.144:8080/SSGlu/.

  14. PM2.5 acidity at a background site in the Pearl River Delta region in fall-winter of 2007-2012.

    Science.gov (United States)

    Fu, Xiaoxin; Guo, Hai; Wang, Xinming; Ding, Xiang; He, Quanfu; Liu, Tengyu; Zhang, Zhou

    2015-04-09

    Based on field observations and thermodynamic model simulation, the annual trend of PM2.5 acidity and its characteristics on non-hazy and hazy days in fall-winter of 2007-2012 in the Pearl River Delta region were investigated. Total acidity ([H(+)](total)) and in-situ acidity ([H(+)](in-situ)) of PM2.5 significantly decreased (F-test, p 0.6), NH4NO3 was most likely formed via homogenous reaction. When the acidity was high (R ≤ 0.6), the gas-phase formation of NH4NO3 was inhibited, and the proportion of NO3(-) produced via heterogeneous reaction of N2O5 became significant.

  15. Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response

    OpenAIRE

    Fu, Lingchen; Kilberg, Michael S.

    2012-01-01

    Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/C...

  16. The evolving energy budget of accretionary wedges

    Science.gov (United States)

    McBeck, Jessica; Cooke, Michele; Maillot, Bertrand; Souloumiac, Pauline

    2017-04-01

    The energy budget of evolving accretionary systems reveals how deformational processes partition energy as faults slip, topography uplifts, and layer-parallel shortening produces distributed off-fault deformation. The energy budget provides a quantitative framework for evaluating the energetic contribution or consumption of diverse deformation mechanisms. We investigate energy partitioning in evolving accretionary prisms by synthesizing data from physical sand accretion experiments and numerical accretion simulations. We incorporate incremental strain fields and cumulative force measurements from two suites of experiments to design numerical simulations that represent accretionary wedges with stronger and weaker detachment faults. One suite of the physical experiments includes a basal glass bead layer and the other does not. Two physical experiments within each suite implement different boundary conditions (stable base versus moving base configuration). Synthesizing observations from the differing base configurations reduces the influence of sidewall friction because the force vector produced by sidewall friction points in opposite directions depending on whether the base is fixed or moving. With the numerical simulations, we calculate the energy budget at two stages of accretion: at the maximum force preceding the development of the first thrust pair, and at the minimum force following the development of the pair. To identify the appropriate combination of material and fault properties to apply in the simulations, we systematically vary the Young's modulus and the fault static and dynamic friction coefficients in numerical accretion simulations, and identify the set of parameters that minimizes the misfit between the normal force measured on the physical backwall and the numerically simulated force. Following this derivation of the appropriate material and fault properties, we calculate the components of the work budget in the numerical simulations and in the

  17. Using in situ GC-MS for analysis of C2-C7 volatile organic acids in ambient air of a boreal forest site

    Science.gov (United States)

    Hellén, Heidi; Schallhart, Simon; Praplan, Arnaud P.; Petäjä, Tuukka; Hakola, Hannele

    2017-01-01

    An in situ method for studying gas-phase C2-C7 monocarboxylic volatile organic acids (VOAs) in ambient air was developed and evaluated. Samples were collected directly into the cold trap of the thermal desorption unit (TD) and analysed in situ using a gas chromatograph (GC) coupled to a mass spectrometer (MS). A polyethylene glycol column was used for separating the acids. The method was validated in the laboratory and tested on the ambient air of a boreal forest in June 2015. Recoveries of VOAs from fluorinated ethylene propylene (FEP) and heated stainless steel inlets ranged from 83 to 123 %. Different VOAs were fully desorbed from the cold trap and well separated in the chromatograms. Detection limits varied between 1 and 130 pptv and total uncertainty of the method at mean ambient mixing ratios was between 16 and 76 %. All straight chain VOAs except heptanoic acid in the ambient air measurements were found with mixing ratios above the detection limits. The highest mixing ratios were found for acetic acid and the highest relative variations for hexanoic acid. In addition, mixing ratios of acetic and propanoic acids measured by the novel GC-MS method were compared with proton-mass-transfer time-of-flight mass spectrometer (PTR-TOFMS) data. Both instruments showed similar variations, but differences in the mixing ratio levels were significant.

  18. On the Critical Role of Divergent Selection in Evolvability

    Directory of Open Access Journals (Sweden)

    Joel Lehman

    2016-08-01

    Full Text Available An ambitious goal in evolutionary robotics is to evolve increasingly complex robotic behaviors with minimal human design effort. Reaching this goal requires evolutionary algorithms that can unlock from genetic encodings their latent potential for evolvability. One issue clouding this goal is conceptual confusion about evolvability, which often obscures the aspects of evolvability that are important or desirable. The danger from such confusion is that it may establish unrealistic goals for evolvability that prove unproductive in practice. An important issue separate from conceptual confusion is the common misalignment between selection and evolvability in evolutionary robotics. While more expressive encodings can represent higher-level adaptations (e.g. sexual reproduction or developmental systems that increase long-term evolutionary potential (i.e. evolvability, realizing such potential requires gradients of fitness and evolvability to align. In other words, selection is often a critical factor limiting increasing evolvability. Thus, drawing from a series of recent papers, this article seeks to both (1 clarify and focus the ways in which the term evolvability is used within artificial evolution, and (2 argue for the importance of one type of selection, i.e. divergent selection, for enabling evolvability. The main argument is that there is a fundamental connection between divergent selection and evolvability (on both the individual and population level that does not hold for typical goal-oriented selection. The conclusion is that selection pressure plays a critical role in realizing the potential for evolvability, and that divergent selection in particular provides a principled mechanism for encouraging evolvability in artificial evolution.

  19. Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

    Science.gov (United States)

    Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

    2016-02-23

    In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL.

  20. Evolving concepts in primary sclerosing cholangitis.

    Science.gov (United States)

    Krones, Elisabeth; Graziadei, Ivo; Trauner, Michael; Fickert, Peter

    2012-03-01

    Patients suffering from primary sclerosing cholangitis (PSC) show considerable differences regarding clinical manifestations (i.e. large duct versus small-duct PSC, presence or absence of concomitant inflammatory bowel disease), disease progression, risk for malignancy and response to therapy, raising the question whether PSC may represent a mixed bag of diseases of different aetiologies. The growing list of secondary causes and diseases 'mimicking' or even overlapping with PSC (e.g. IgG4-associated sclerosing cholangitis), which frequently causes problems in clear-cut discrimination from classic PSC and the emerging knowledge about potential disease modifier genes (e.g. variants of CFTR, TGR5 and MDR3) support such a conceptual view. In addition, PSC in children differs significantly from PSC in adults in several aspects resulting in distinct therapeutic concepts. From a clinical perspective, appropriate categorization and careful differential diagnosis are essential for the management of concerned patients. Therefore, the aim of the current review is to summarize current and evolving pathophysiological concepts and to provide up-to-date perspectives including future treatment strategies for PSC.

  1. Evolving role of MRI in Crohn's disease.

    Science.gov (United States)

    Yacoub, Joseph H; Obara, Piotr; Oto, Aytekin

    2013-06-01

    MR enterography is playing an evolving role in the evaluation of small bowel Crohn's disease (CD). Standard MR enterography includes a combination of rapidly acquired T2 sequence, balanced steady-state acquisition, and contrast enhanced T1-weighted gradient echo sequence. The diagnostic performance of these sequences has been shown to be comparable, and in some respects superior, to other small bowel imaging modalities. The findings of CD on MR enterography have been well described in the literature. New and emerging techniques such as diffusion-weighted imaging (DWI), dynamic contrast enhanced MRI (DCE-MRI), cinematography, and magnetization transfer, may lead to improved accuracy in characterizing the disease. These advanced techniques can provide quantitative parameters that may prove to be useful in assessing disease activity, severity, and response to treatment. In the future, MR enterography may play an increasing role in management decisions for patients with small bowel CD; however, larger studies are needed to validate these emerging MRI parameters as imaging biomarkers.

  2. UKAEA'S evolving contract philosophy

    Energy Technology Data Exchange (ETDEWEB)

    Nicol, R. D. [UK Atomic Energy Authority, UKAEA, Harwell, Oxfordshire (United Kingdom)

    2003-07-01

    The United Kingdom Atomic Energy Authority (UKAEA) has gone through fundamental change over the last ten years. At the heart of this change has been UKAEA's relationship with the contracting and supply market. This paper describes the way in which UKAEA actively developed the market to support the decommissioning programme, and how the approach to contracting has evolved as external pressures and demands have changed. UKAEA's pro-active approach to industry has greatly assisted the development of a healthy, competitive market for services supporting decommissioning in the UK. There have been difficult changes and many challenges along the way, and some retrenchment was necessary to meet regulatory requirements. Nevertheless, UKAEA has sustained a high level of competition - now measured in terms of competed spend as a proportion of competable spend - with annual out-turns consistently over 80%. The prime responsibility for market development will pass to the new Nuclear Decommissioning Authority (NDA) in 2005, as the owner, on behalf of the Government, of the UK's civil nuclear liabilities. The preparatory work for the NDA indicates that the principles established by UKAEA will be carried forward. (author)

  3. On the Discovery of Evolving Truth.

    Science.gov (United States)

    Li, Yaliang; Li, Qi; Gao, Jing; Su, Lu; Zhao, Bo; Fan, Wei; Han, Jiawei

    2015-08-01

    In the era of big data, information regarding the same objects can be collected from increasingly more sources. Unfortunately, there usually exist conflicts among the information coming from different sources. To tackle this challenge, truth discovery, i.e., to integrate multi-source noisy information by estimating the reliability of each source, has emerged as a hot topic. In many real world applications, however, the information may come sequentially, and as a consequence, the truth of objects as well as the reliability of sources may be dynamically evolving. Existing truth discovery methods, unfortunately, cannot handle such scenarios. To address this problem, we investigate the temporal relations among both object truths and source reliability, and propose an incremental truth discovery framework that can dynamically update object truths and source weights upon the arrival of new data. Theoretical analysis is provided to show that the proposed method is guaranteed to converge at a fast rate. The experiments on three real world applications and a set of synthetic data demonstrate the advantages of the proposed method over state-of-the-art truth discovery methods.

  4. THE EVOLVING CONCEPT OF SUSTAINABLE AGRICULTURE

    Directory of Open Access Journals (Sweden)

    PETRONELA-SONIA NEDEA

    2012-11-01

    Full Text Available Over the years, the definition of sustainability in development literature has varied widely and broadened in scope. The concept arose in response to economic growth models that characterized development approaches over the last half century. It was eventually recognized that such models did not adequately address social inequalities and led to environmental degradation. The concept gained wider use after the World Commission on Environment and Development published "Our common future" (Brundtland 1987. The economic, social, political and ecological dimensions of the rural environment are complex and have multiple implications, starting with theoretical and practical reasons. The process of urbanization that takes place at world-wide level has become one of the global problems of mankind, because of the disparities created between the countryside and the city, which arematerialized in the cultural, economical and social aspects that are synthesized in the terms of urban and rural civilizations, which define the different realities of the geographical space. Because the concept of sustainable agriculture is still evolving, this paper reviews the ideas, practices and policies that make the basis ofsustainable agriculture concept, in order to suggest to others practical steps that may be appropriate for them in moving toward sustainable agriculture.

  5. Epidemic spreading on evolving signed networks

    Science.gov (United States)

    Saeedian, M.; Azimi-Tafreshi, N.; Jafari, G. R.; Kertesz, J.

    2017-02-01

    Most studies of disease spreading consider the underlying social network as obtained without the contagion, though epidemic influences people's willingness to contact others: A "friendly" contact may be turned to "unfriendly" to avoid infection. We study the susceptible-infected disease-spreading model on signed networks, in which each edge is associated with a positive or negative sign representing the friendly or unfriendly relation between its end nodes. In a signed network, according to Heider's theory, edge signs evolve such that finally a state of structural balance is achieved, corresponding to no frustration in physics terms. However, the danger of infection affects the evolution of its edge signs. To describe the coupled problem of the sign evolution and disease spreading, we generalize the notion of structural balance by taking into account the state of the nodes. We introduce an energy function and carry out Monte Carlo simulations on complete networks to test the energy landscape, where we find local minima corresponding to the so-called jammed states. We study the effect of the ratio of initial friendly to unfriendly connections on the propagation of disease. The steady state can be balanced or a jammed state such that a coexistence occurs between susceptible and infected nodes in the system.

  6. Consensus in evolving networks of mobile agents

    Science.gov (United States)

    Baronchelli, Andrea; Díaz-Guilera, Albert

    2012-02-01

    Populations of mobile and communicating agents describe a vast array of technological and natural systems, ranging from sensor networks to animal groups. Here, we investigate how a group-level agreement may emerge in the continuously evolving networks defined by the local interactions of the moving individuals. We adopt a general scheme of motion in two dimensions and we let the individuals interact through the minimal naming game, a prototypical scheme to investigate social consensus. We distinguish different regimes of convergence determined by the emission range of the agents and by their mobility, and we identify the corresponding scaling behaviors of the consensus time. In the same way, we rationalize also the behavior of the maximum memory used during the convergence process, which determines the minimum cognitive/storage capacity needed by the individuals. Overall, we believe that the simple and general model presented in this talk can represent a helpful reference for a better understanding of the behavior of populations of mobile agents.

  7. Stability of Evolving Multi-Agent Systems

    CERN Document Server

    De Wilde, Philippe; 10.1109/TSMCB.2011.2110642

    2011-01-01

    A Multi-Agent System is a distributed system where the agents or nodes perform complex functions that cannot be written down in analytic form. Multi-Agent Systems are highly connected, and the information they contain is mostly stored in the connections. When agents update their state, they take into account the state of the other agents, and they have access to those states via the connections. There is also external, user-generated input into the Multi-Agent System. As so much information is stored in the connections, agents are often memory-less. This memory-less property, together with the randomness of the external input, has allowed us to model Multi-Agent Systems using Markov chains. In this paper, we look at Multi-Agent Systems that evolve, i.e. the number of agents varies according to the fitness of the individual agents. We extend our Markov chain model, and define stability. This is the start of a methodology to control Multi-Agent Systems. We then build upon this to construct an entropy-based defi...

  8. Evolving Galaxies in a Hierachical Universe

    Science.gov (United States)

    Hahn, Changhoon

    2017-01-01

    Observations of galaxies using large surveys (SDSS, COSMOS, PRIMUS, etc.) have firmly established a global view of galaxy properties out to z~1. Galaxies are broadly divided into two classes: blue, typically disk-like star forming galaxies and red, typically elliptical quiescent ones with little star formation. The star formation rates (SFR) and stellar masses of star forming galaxies form an empirical relationship referred to as the "star formation main sequence". Over cosmic time, this sequence undergoes significant decline in SFR and causes the overall cosmic star formation decline. Simultaneously, physical processes cause significant fractions of star forming galaxies to "quench" their star formation. Hierarchical structure formation and cosmological models provide precise predictions of the evolution of the underying dark matter, which serve as the foundation for these detailed trends and their evolution. Whatever trends we observe in galaxy properties can be interpreted within the narrative of the underlying dark matter and halo occupation framework. More importantly, through careful statistical treatment and precise measurements, this connection can be utilized to better constrain and understand key elements of galaxy evolution. In this spirit, for my dissertation I connect observations of evolving galaxy properties to the framework of the hierarchical Universe and use it to better understand physical processes responsible for the cessation of star formation in galaxies. For instance, through this approach, I constrain the quenching timescale of central galaxies and find that they are significantly longer than the quenching timescale of satellite galaxies.

  9. Evolving Decision Rules to Predict Investment Opportunities

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This paper is motivated by the interest in finding significant movements in financial stock prices. However, when the number of profitable opportunities is scarce, the prediction of these cases is difficult. In a previous work, we have introduced evolving decision rules (EDR) to detect financial opportunities. The objective of EDR is to classify the minority class (positive cases) in imbalanced environments. EDR provides a range of classifications to find the best balance between not making mistakes and not missing opportunities. The goals of this paper are: 1) to show that EDR produces a range of solutions to suit the investor's preferences and 2) to analyze the factors that benefit the performance of EDR. A series of experiments was performed. EDR was tested using a data set from the London Financial Market. To analyze the EDR behaviour, another experiment was carried out using three artificial data sets, whose solutions have different levels of complexity. Finally, an illustrative example was provided to show how a bigger collection of rules is able to classify more positive cases in imbalanced data sets. Experimental results show that: 1) EDR offers a range of solutions to fit the risk guidelines of different types of investors, and 2) a bigger collection of rules is able to classify more positive cases in imbalanced environments.

  10. Evolving application of biomimetic nanostructured hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Norberto Roveri

    2010-11-01

    Full Text Available Norberto Roveri, Michele IafiscoLaboratory of Environmental and Biological Structural Chemistry (LEBSC, Dipartimento di Chimica ‘G. Ciamician’, Alma Mater Studiorum, Università di Bologna, Bologna, ItalyAbstract: By mimicking Nature, we can design and synthesize inorganic smart materials that are reactive to biological tissues. These smart materials can be utilized to design innovative third-generation biomaterials, which are able to not only optimize their interaction with biological tissues and environment, but also mimic biogenic materials in their functionalities. The biomedical applications involve increasing the biomimetic levels from chemical composition, structural organization, morphology, mechanical behavior, nanostructure, and bulk and surface chemical–physical properties until the surface becomes bioreactive and stimulates cellular materials. The chemical–physical characteristics of biogenic hydroxyapatites from bone and tooth have been described, in order to point out the elective sides, which are important to reproduce the design of a new biomimetic synthetic hydroxyapatite. This review outlines the evolving applications of biomimetic synthetic calcium phosphates, details the main characteristics of bone and tooth, where the calcium phosphates are present, and discusses the chemical–physical characteristics of biomimetic calcium phosphates, methods of synthesizing them, and some of their biomedical applications.Keywords: hydroxyapatite, nanocrystals, biomimetism, biomaterials, drug delivery, remineralization

  11. Evolving application of biomimetic nanostructured hydroxyapatite.

    Science.gov (United States)

    Roveri, Norberto; Iafisco, Michele

    2010-11-09

    By mimicking Nature, we can design and synthesize inorganic smart materials that are reactive to biological tissues. These smart materials can be utilized to design innovative third-generation biomaterials, which are able to not only optimize their interaction with biological tissues and environment, but also mimic biogenic materials in their functionalities. The biomedical applications involve increasing the biomimetic levels from chemical composition, structural organization, morphology, mechanical behavior, nanostructure, and bulk and surface chemical-physical properties until the surface becomes bioreactive and stimulates cellular materials. The chemical-physical characteristics of biogenic hydroxyapatites from bone and tooth have been described, in order to point out the elective sides, which are important to reproduce the design of a new biomimetic synthetic hydroxyapatite. This review outlines the evolving applications of biomimetic synthetic calcium phosphates, details the main characteristics of bone and tooth, where the calcium phosphates are present, and discusses the chemical-physical characteristics of biomimetic calcium phosphates, methods of synthesizing them, and some of their biomedical applications.

  12. How does cognition evolve? Phylogenetic comparative psychology

    Science.gov (United States)

    Matthews, Luke J.; Hare, Brian A.; Nunn, Charles L.; Anderson, Rindy C.; Aureli, Filippo; Brannon, Elizabeth M.; Call, Josep; Drea, Christine M.; Emery, Nathan J.; Haun, Daniel B. M.; Herrmann, Esther; Jacobs, Lucia F.; Platt, Michael L.; Rosati, Alexandra G.; Sandel, Aaron A.; Schroepfer, Kara K.; Seed, Amanda M.; Tan, Jingzhi; van Schaik, Carel P.; Wobber, Victoria

    2014-01-01

    Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution. PMID:21927850

  13. How does cognition evolve? Phylogenetic comparative psychology.

    Science.gov (United States)

    MacLean, Evan L; Matthews, Luke J; Hare, Brian A; Nunn, Charles L; Anderson, Rindy C; Aureli, Filippo; Brannon, Elizabeth M; Call, Josep; Drea, Christine M; Emery, Nathan J; Haun, Daniel B M; Herrmann, Esther; Jacobs, Lucia F; Platt, Michael L; Rosati, Alexandra G; Sandel, Aaron A; Schroepfer, Kara K; Seed, Amanda M; Tan, Jingzhi; van Schaik, Carel P; Wobber, Victoria

    2012-03-01

    Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution.

  14. The Evolving Luminosity Function of Red Galaxies

    CERN Document Server

    Brown, M J I; Jannuzi, B T; Brand, K; Benson, A J; Brodwin, M; Croton, D J; Eisenhardt, P R M; Brown, Michael J. I.; Dey, Arjun; Jannuzi, Buell T.; Brand, Kate; Benson, Andrew J.; Brodwin, Mark; Croton, Darren J.; Eisenhardt, Peter R.

    2006-01-01

    We trace the assembly history of red galaxies since z=1, by measuring their evolving space density with the B-band luminosity function. Our sample of 39599 red galaxies, selected from 6.96 square degrees of imaging from the NOAO Deep Wide-Field and Spitzer IRAC Shallow surveys, is an order of magnitude larger, in size and volume, than comparable samples in the literature. We measure a higher space density of z=0.9 red galaxies than some of the recent literature, in part because we account for the faint yet significant galaxy flux which falls outside of our photometric aperture. The B-band luminosity density of red galaxies, which effectively measures the evolution of ~L* galaxies, increases by only 36 percent from z=0 to z=1. If red galaxy stellar populations have faded by 1.24 B-band magnitudes since z=1, the stellar mass contained within the red galaxy population has roughly doubled over the past 8 Gyr. This is consistent with star-forming galaxies being transformed into ~L* red galaxies after a decline in ...

  15. Extreme insular dwarfism evolved in a mammoth.

    Science.gov (United States)

    Herridge, Victoria L; Lister, Adrian M

    2012-08-22

    The insular dwarfism seen in Pleistocene elephants has come to epitomize the island rule; yet our understanding of this phenomenon is hampered by poor taxonomy. For Mediterranean dwarf elephants, where the most extreme cases of insular dwarfism are observed, a key systematic question remains unresolved: are all taxa phyletic dwarfs of a single mainland species Palaeoloxodon antiquus (straight-tusked elephant), or are some referable to Mammuthus (mammoths)? Ancient DNA and geochronological evidence have been used to support a Mammuthus origin for the Cretan 'Palaeoloxodon' creticus, but these studies have been shown to be flawed. On the basis of existing collections and recent field discoveries, we present new, morphological evidence for the taxonomic status of 'P'. creticus, and show that it is indeed a mammoth, most probably derived from Early Pleistocene Mammuthus meridionalis or possibly Late Pliocene Mammuthus rumanus. We also show that Mammuthus creticus is smaller than other known insular dwarf mammoths, and is similar in size to the smallest dwarf Palaeoloxodon species from Sicily and Malta, making it the smallest mammoth species known to have existed. These findings indicate that extreme insular dwarfism has evolved to a similar degree independently in two elephant lineages.

  16. The Role of Trends in Evolving Networks

    CERN Document Server

    Mokryn, Osnat; Shavitt, Yuval

    2013-01-01

    Modeling complex networks has been the focus of much research for over a decade. Preferential attachment (PA) is considered a common explanation to the self organization of evolving networks, suggesting that new nodes prefer to attach to more popular nodes. The PA model results in broad degree distributions, found in many networks, but cannot explain other common properties such as: The growth of nodes arriving late and Clustering (community structure). Here we show that when the tendency of networks to adhere to trends is incorporated into the PA model, it can produce networks with such properties. Namely, in trending networks, newly arriving nodes may become central at random, forming new clusters. In particular, we show that when the network is young it is more susceptible to trends, but even older networks may have trendy new nodes that become central in their structure. Alternatively, networks can be seen as composed of two parts: static, governed by a power law degree distribution, and a dynamic part go...

  17. The evolved pulsating CEMP star HD112869

    CERN Document Server

    Začs, L; Grankina, A; Deveikis, V; Kaminskyi, B; Pavlenko, Y; Musaev, F

    2015-01-01

    Radial velocity measurements, $BVR_C$ photometry, and high-resolution spectroscopy in the wavelength region from blue to near infrared are employed in order to clarify the evolutionary status of the carbon-enhanced metal-poor star HD112869 with unique ratio of carbon isotopes in the atmosphere. An LTE abundance analysis was carried out using the method of spectral synthesis and new self consistent 1D atmospheric models. The radial velocity monitoring confirmed semiregular variations with a peak-to-peak amplitude of about 10 km $s^{-1}$ and a dominating period of about 115 days. The light, color and radial velocity variations are typical of the evolved pulsating stars. The atmosphere of HD112869 appears to be less metal-poor than reported before, [Fe/H] = -2.3 $\\pm$0.2 dex. Carbon to oxygen and carbon isotope ratios are found to be extremely high, C/O $\\simeq$ 12.6 and $^{12}C/^{13}C \\gtrsim$ 1500, respectively. The s-process elements yttrium and barium are not enhanced, but neodymium appears to be overabundan...

  18. Evolving epidemiology of HIV-associated malignancies.

    Science.gov (United States)

    Shiels, Meredith S; Engels, Eric A

    2017-01-01

    The purpose of this review is to describe the epidemiology of cancers that occur at an elevated rate among people with HIV infection in the current treatment era, including discussion of the cause of these cancers, as well as changes in cancer incidence and burden over time. Rates of Kaposi sarcoma, non-Hodgkin lymphoma and cervical cancer have declined sharply in developed countries during the highly active antiretroviral therapy era, but remain elevated 800-fold, 10-fold and four-fold, respectively, compared with the general population. Most studies have reported significant increases in liver cancer rates and decreases in lung cancer over time. Although some studies have reported significant increases in anal cancer rates and declines in Hodgkin lymphoma rates, others have shown stable incidence. Declining mortality among HIV-infected individuals has resulted in the growth and aging of the HIV-infected population, causing an increase in the number of non-AIDS-defining cancers diagnosed each year in HIV-infected people. The epidemiology of cancer among HIV-infected people has evolved since the beginning of the HIV epidemic with particularly marked changes since the introduction of modern treatment. Public health interventions aimed at prevention and early detection of cancer among HIV-infected people are needed.

  19. Properties of asymmetrically evolved community networks

    Institute of Scientific and Technical Information of China (English)

    Cui Di; Gao Zi-You; Zheng Jian-Feng

    2009-01-01

    This paper studies a simple asymmetrically evolved community network with a combination of preferential at-tachment and random properties. An important issue about community networks is to discover the different utility increments of two nodes, where the utility is introduced to investigate the asymmetrical effect of connecting two nodes. On the other hand, the connection of two nodes in community networks can be classified as two nodes belonging to the same or to different communities. The simulation results show that the model can reproduce a power-law utility distribution P(u)~ u-σ,σ=2+ 1/p, which can be obtained by using mean-field approximation methods. Furthermore, the model exhibits exponential behaviour with respect to small values of a parameter denoting the random effect in our model at the low-utility region and a power-law feature with respect to big values of this parameter at the high-utility region, which is in good agreement with theoretical analysis. This kind of community network can reproduce a unique utility distribution by theoretical and numerical analysis.

  20. Evolving paradigms in multifocal breast cancer.

    Science.gov (United States)

    Salgado, Roberto; Aftimos, Philippe; Sotiriou, Christos; Desmedt, Christine

    2015-04-01

    The 7th edition of the TNM defines multifocal breast cancer as multiple simultaneous ipsilateral and synchronous breast cancer lesions, provided they are macroscopically distinct and measurable using current traditional pathological and clinical tools. According to the College of American Pathologists (CAP), the characterization of only the largest lesion is considered sufficient, unless the grade and/or histology are different between the lesions. Here, we review three potentially clinically relevant aspects of multifocal breast cancers: first, the importance of a different intrinsic breast cancer subtype of the various lesions; second, the emerging awareness of inter-lesion heterogeneity; and last but not least, the potential introduction of bias in clinical trials due to the unrecognized biological diversity of these cancers. Although the current strategy to assess the lesion with the largest diameter has clearly its advantages in terms of costs and feasibility, this recommendation may not be sustainable in time and might need to be adapted to be compliant with new evolving paradigms in breast cancer.