WorldWideScience

Sample records for sop-2 sam domain

  1. Supplementary Material for: A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein

    KAUST Repository

    Smirnova, Ekaterina; Kwan, Jamie; Siu, Ryan; Gao, Xin; Zoidl, Georg; Demeler, Borries; Saridakis, Vivian; Donaldson, Logan

    2016-01-01

    Abstract Background CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions. Results We demonstrate that the crystal structure of the Sterile Alpha Motif (SAM) domain tandem (SAM1-SAM2) oligomer from CASKIN2 is different than CASKIN1, with the minimal repeating unit being a dimer, rather than a monomer. Analytical ultracentrifugation sedimentation velocity methods revealed differences in monomer/dimer equilibria across a range of concentrations and ionic strengths for the wild type CASKIN2 SAM tandem and a structure-directed double mutant that could not oligomerize. Further distinguishing CASKIN2 from CASKIN1, EGFP-tagged SAM tandem proteins expressed in Neuro2a cells produced punctae that were distinct both in shape and size. Conclusions This study illustrates a new way in which neuronal SAM domains can assemble into large macromolecular assemblies that might concentrate and amplify synaptic responses.

  2. The Sam-Sam interaction between Ship2 and the EphA2 receptor: design and analysis of peptide inhibitors.

    Science.gov (United States)

    Mercurio, Flavia Anna; Di Natale, Concetta; Pirone, Luciano; Iannitti, Roberta; Marasco, Daniela; Pedone, Emilia Maria; Palumbo, Rosanna; Leone, Marilisa

    2017-12-12

    The lipid phosphatase Ship2 represents a drug discovery target for the treatment of different diseases, including cancer. Its C-terminal sterile alpha motif domain (Ship2-Sam) associates with the Sam domain from the EphA2 receptor (EphA2-Sam). This interaction is expected to mainly induce pro-oncogenic effects in cells therefore, inhibition of the Ship2-Sam/EphA2-Sam complex may represent an innovative route to discover anti-cancer therapeutics. In the present work, we designed and analyzed several peptide sequences encompassing the interaction interface of EphA2-Sam for Ship2-Sam. Peptide conformational analyses and interaction assays with Ship2-Sam conducted through diverse techniques (CD, NMR, SPR and MST), identified a positively charged penta-amino acid native motif in EphA2-Sam, that once repeated three times in tandem, binds Ship2-Sam. NMR experiments show that the peptide targets the negatively charged binding site of Ship2-Sam for EphA2-Sam. Preliminary in vitro cell-based assays indicate that -at 50 µM concentration- it induces necrosis of PC-3 prostate cancer cells with more cytotoxic effect on cancer cells than on normal dermal fibroblasts. This work represents a pioneering study that opens further opportunities for the development of inhibitors of the Ship2-Sam/EphA2-Sam complex for therapeutic applications.

  3. Structural investigation of a C-terminal EphA2 receptor mutant: Does mutation affect the structure and interaction properties of the Sam domain?

    Science.gov (United States)

    Mercurio, Flavia A; Costantini, Susan; Di Natale, Concetta; Pirone, Luciano; Guariniello, Stefano; Scognamiglio, Pasqualina L; Marasco, Daniela; Pedone, Emilia M; Leone, Marilisa

    2017-09-01

    Ephrin A2 receptor (EphA2) plays a key role in cancer, it is up-regulated in several types of tumors and the process of ligand-induced receptor endocytosis, followed by degradation, is considered as a potential path to diminish tumor malignancy. Protein modulators of this mechanism are recruited at the cytosolic Sterile alpha motif (Sam) domain of EphA2 (EphA2-Sam) through heterotypic Sam-Sam associations. These interactions engage the C-terminal helix of EphA2 and close loop regions (the so called End Helix side). In addition, several studies report on destabilizing mutations in EphA2 related to cataract formation and located in/or close to the Sam domain. Herein, we analyzed from a structural point of view, one of these mutants characterized by the insertion of a novel 39 residue long polypeptide at the C-terminus of EphA2-Sam. A 3D structural model was built by computational methods and revealed partial disorder in the acquired C-terminal tail and a few residues participating in an α-helix and two short β-strands. We investigated by CD and NMR studies the conformational properties in solution of two peptides encompassing the whole C-terminal tail and its predicted helical region, respectively. NMR binding experiments demonstrated that these peptides do not interact relevantly with either EphA2-Sam or its interactor Ship2-Sam. Molecular dynamics (MD) simulations further indicated that the EphA2 mutant could be represented only through a conformational ensemble and that the C-terminal tail should not largely wrap the EphA2-Sam End-Helix interface and affect binding to other Sam domains. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites.

    OpenAIRE

    Smalla, M.; Schmieder, P.; Kelly, M.; Ter Laak, A.; Krause, G.; Ball, L.; Wahl, M.; Bork, P.; Oschkinat, H.

    1999-01-01

    The sterile alpha motif (SAM) is a protein interaction domain of around 70 amino acids present predominantly in the N- and C-termini of more than 60 diverse proteins that participate in signal transduction and transcriptional repression. SAM domains have been shown to homo- and hetero-oligomerize and to mediate specific protein-protein interactions. A highly conserved subclass of SAM domains is present at the intracellular C-terminus of more than 40 Eph receptor tyrosine kinases that are invo...

  5. Targeting EphA2-Sam and Its Interactome: Design and Evaluation of Helical Peptides Enriched in Charged Residues.

    Science.gov (United States)

    Mercurio, Flavia A; Marasco, Daniela; Di Natale, Concetta; Pirone, Luciano; Costantini, Susan; Pedone, Emilia M; Leone, Marilisa

    2016-11-17

    The EphA2 receptor controls diverse physiological and pathological conditions and its levels are often upregulated in cancer. Targeting receptor overexpression, through modulation of endocytosis and consequent degradation, appears to be an appealing strategy for attacking tumor malignancy. In this scenario, the Sam domain of EphA2 plays a pivotal role because it is the site where protein regulators of endocytosis and stability are recruited by means of heterotypic Sam-Sam interactions. Because EphA2-Sam heterotypic complexes are largely based on electrostatic contacts, we have investigated the possibility of attacking these interactions with helical peptides enriched in charged residues. Several peptide sequences with high predicted helical propensities were designed, and detailed conformational analyses were conducted by diverse techniques including NMR, CD, and molecular dynamics (MD) simulations. Interaction studies were also performed by NMR, surface plasmon resonance (SPR), and microscale thermophoresis (MST) and led to the identification of two peptides capable of binding to the first Sam domain of Odin. These molecules represent early candidates for the generation of efficient Sam domain binders and antagonists of Sam-Sam interactions involving EphA2. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Cirtical role for Salmonella effector SopB in regulating inflammasome activation.

    Science.gov (United States)

    Hu, Gui-Qiu; Song, Pei-Xuan; Chen, Wei; Qi, Shuai; Yu, Shui-Xing; Du, Chong-Tao; Deng, Xu-Ming; Ouyang, Hong-Sheng; Yang, Yong-Jun

    2017-10-01

    Salmonella is known to evolve many mechanisms to avoid or delay inflammasome activation which remain largely unknown. In this study, we investigated whether the SopB protein critical to bacteria virulence capacity was an effector that involved in the regulation of inflammasome activation. BMDMs from NLRC4-, NLRP3-, caspase-1/-11-, IFI16- and AIM2-deficient mice were pretreated with LPS, and subsequently stimulated with a series of SopB-related strains of Salmonella, inflammasome induced cell death, IL-1β secretion, cleaved caspase-1 production and ASC speckle formation were detected. We found that SopB could inhibit host IL-1β secretion, caspase-1 activation and inflammasome induced cell death using a series of SopB-related strains of Salmonella; however the reduction of IL-1β secretion was not dependent on sensor that contain PYD domain, such as NLRP3, AIM2 or IFI16, but dependent on NLRC4. Notably, SopB specifically prevented ASC oligomerization and the enzymatic activity of SopB was responsible for the inflammasome inhibition. Furthermore, inhibition of Akt signaling induced enhanced inflammasome activation. These results revealed a novel role in inhibition of NLRC4 inflammasome for Salmonella effector SopB. Copyright © 2017. Published by Elsevier Ltd.

  7. 9 CFR 416.12 - Development of Sanitation SOP's.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Development of Sanitation SOP's. 416... ACT SANITATION § 416.12 Development of Sanitation SOP's. (a) The Sanitation SOP's shall describe all... direct contamination or adulteration of product(s). (b) The Sanitation SOP's shall be signed and dated by...

  8. Sam37 is crucial for formation of the mitochondrial TOM-SAM supercomplex, thereby promoting β-barrel biogenesis.

    Science.gov (United States)

    Wenz, Lena-Sophie; Ellenrieder, Lars; Qiu, Jian; Bohnert, Maria; Zufall, Nicole; van der Laan, Martin; Pfanner, Nikolaus; Wiedemann, Nils; Becker, Thomas

    2015-09-28

    Biogenesis of mitochondrial β-barrel proteins requires two preprotein translocases, the general translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). TOM and SAM form a supercomplex that promotes transfer of β-barrel precursors. The SAM core complex contains the channel protein Sam50, which cooperates with Sam35 in precursor recognition, and the peripheral membrane protein Sam37. The molecular function of Sam37 has been unknown. We report that Sam37 is crucial for formation of the TOM-SAM supercomplex. Sam37 interacts with the receptor domain of Tom22 on the cytosolic side of the mitochondrial outer membrane and links TOM and SAM complexes. Sam37 thus promotes efficient transfer of β-barrel precursors to the SAM complex. We conclude that Sam37 functions as a coupling factor of the translocase supercomplex of the mitochondrial outer membrane. © 2015 Wenz et al.

  9. 9 CFR 416.14 - Maintenance of Sanitation SOP's.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Maintenance of Sanitation SOP's. 416... ACT SANITATION § 416.14 Maintenance of Sanitation SOP's. Each official establishment shall routinely evaluate the effectiveness of the Sanitation SOP's and the procedures therein in preventing direct...

  10. Fabricating an S&OP Process

    DEFF Research Database (Denmark)

    Lichen, Alex Yu

    , constituents of the S&OP process are dispersed in diverse local times and spaces rather than being coordinated in a single time and space by the group demand chain. Accounting is a set of matters of concern. The S&OP process and its purpose of integration come from an “absolute nothingness” – its minimal......Inspired by Latour’s (2005a) notion of matters of concern and M.C. Escher’s Circle Limit III as a representation of the Poincaré Disk, this study follows how an S&OP process was fabricated in a large Swedish manufacturing company. The study claims that when actors are fabricating the S&OP process......, local actors create emergent, ongoing and multiple matters of concern around it. The group demand chain, the actor who is responsible for guiding the implementation of the process, delegates the attempts to close these matters of concern to local actors located in separate times and spaces. As a result...

  11. Context-based Sales and Operations Planning (S&OP) research

    DEFF Research Database (Denmark)

    Kristensen, Jesper; Jonsson, Patrik

    2018-01-01

    must be considered when designing and implementing S&OP. Originality/values – This study focused on identifying relevant research on S&OP design by analysing the contribution of literature to a research framework inspired by contingency based research of operations and supply chain management.......Purpose – This paper’s purpose was to describe and categorize how current literature contributes to S&OP research on how contextual variables affect S&OP design and to frame future areas for context-based S&OP research. Design/methodology/approach – The method used was a systematic literature...... – The review found that S&OP design depends on industry, dynamic complexity, detail complexity and organisational characteristics. The findings of the literature review suggest that future research should study the roles of industry, complexity, system and process and organisational characteristics in S&OP...

  12. Effect of contouring on bending structural stiffness and bending strength of the 3.5 titanium SOP implant.

    Science.gov (United States)

    Rutherford, Scott; Ness, Malcolm G

    2012-11-01

    To compare the bending structural stiffness (BSS) and bending strength (BS) of the 3.5 titanium (Ti) string of pearls (SOP) plate and the 3.5 316LVM stainless steel SOP plate; and the effect of contouring on the BSS and BS of the 3.5 Ti SOP plate. In vitro experimental static 4-point bending materials testing. Twenty-five 3.5 mm Ti and five 3.5 mm 316LVM stainless steel SOP locking bone plates. Each plate was tested in 4-point bending until 10 mm of displacement was achieved. BSS and BS were then calculated for each plate. A 2-sample t-test was used to compare the mean BSS and BS of the different groups. The 3.5 Ti SOP plate had lower mean BSS (0.00263 Nm(2) ) but similar mean BS (12.8 Nm) when compared to the 3.5 316LVM SOP (0.00402 Nm(2) , 13.0 Nm). Prebending the 3.5 Ti SOP diminished its mean BSS (0.00224 Nm(2) ) and mean BS (9.4 Nm) when compared to the Ti control. Pretwisting the 3.5 Ti SOP increased its mean BSS (0.00273 Nm(2) ) but decreased its mean BS (12.4 Nm) when compared to the Ti control. The 3.5 Ti SOP is less stiff but of similar strength to the 3.5 316LVM stainless steel SOP. Prebending the Ti SOP significantly lowers its stiffness and strength. Pretwisting the SOP actually increases its stiffness but slightly lowers its strength. © Copyright 2012 by The American College of Veterinary Surgeons.

  13. PROFIL PERTUMBUHAN, ENZIMATIS, DAN NUTRISI IKAN BANDENG (Chanos chanos GENERASI KEDUA (G-2 TERSELEKSI DENGAN MENERAPKAN STANDAR OPERASIONAL PROSEDUR (SOP PEMELIHARAAN LARVA

    Directory of Open Access Journals (Sweden)

    Daniar Kusumawati

    2017-12-01

    Full Text Available Isu nasional menurunnya produksi budidaya ikan bandeng di tambak pantai utara Pulau Jawa didugasebagai akibat rendahnya kualitas benih produk Hatchery Skala Rumah Tangga (HSRT di Bali, yang secara kontinu merupakan sumber utama pasok benih. Banyak faktor yang mempengaruhi kualitas benih, antara lain kualitas telur dan induk, serta manajemen pemeliharaan induk dan larva. Tujuan penelitian ini adalah untuk mengevaluasi performa pertumbuhan,aktivitas enzim pencernaan dan nutrisi benih ikan bandeng dari HSRT dan generasi kedua (G2 terseleksi yang dipelihara berdasarkan standar operasional prosedur. Penelitian dilakukan di tambak Pejarakan, dengan hewan uji benih produk HSRT dan benih generasi ke-2 (G-2 terseleksi dengan panjang total rata-rata 11,79 ± 1,64 mm, masing-masing dengan padat tebar 5.000 ekor/petak dengan luasan 0,5 Ha/petak, diberi pakan jenis pelet kering berkadar protein 25 % dan dipelihara selama 6 bulan. Hasil penelitian menunjukkan performa benih ikan bandeng dipengaruhi oleh sumber induk dan manajemen pemeliharaan saat larva. Pertumbuhan benih ikan bandeng asal HSRT dengan SOP pemeliharaan larva menunjukkan peningkatan laju pertumbuhan panjang dan bobot sebesar 10,11% dan 47,18% lebih tinggi dibandingkan benih G2-terseleksi, dan 13,82% dan 50,55% lebih tinggi dibandingkan benih HSRT tanpa SOP. Aktivitas enzimatis pada benih HSRT dengan SOP lebih efisien dibandingkan benih G2-terseleksi. Aktivitas enzimatis pada benih HSRT tanpa SOP adalah yang paling rendah dimana hal ini terlihat dari laju pertumbuhannya yang juga paling rendah. Benih HSRT yang dipelihara dengan SOP mampu menekan rasio konversi pakan sebesar 28,29% lebih rendah dibandingkan benih G2-terseleksi, dan 22,64% dibandingkan benih HSRT yang dipelihara tanpa SOP. Currently, there is a national concern regarding the decreasing of milkfish production from ponds in North Java allegedly due to a low quality of milkfish seed produced by small-scale hatcheries in Bali, which

  14. Elp3 and RlmN: A tale of two mitochondrial tail-anchored radical SAM enzymes in Toxoplasma gondii.

    Science.gov (United States)

    Padgett, Leah R; Lentini, Jenna M; Holmes, Michael J; Stilger, Krista L; Fu, Dragony; Sullivan, William J

    2018-01-01

    Radical S-adenosylmethionine (rSAM) enzymes use a 5'-deoxyadensyl 5'-radical to methylate a wide array of diverse substrates including proteins, lipids and nucleic acids. One such enzyme, Elongator protein-3 (TgElp3), is an essential protein in Toxoplasma gondii, a protozoan parasite that can cause life-threatening opportunistic disease. Unlike Elp3 homologues which are present in all domains of life, TgElp3 localizes to the outer mitochondrial membrane (OMM) via a tail-anchored trafficking mechanism in Toxoplasma. Intriguingly, we identified a second tail-anchored rSAM domain containing protein (TgRlmN) that also localizes to the OMM. The transmembrane domain (TMD) on Toxoplasma Elp3 and RlmN homologues is required for OMM localization and has not been seen beyond the chromalveolates. Both TgElp3 and TgRlmN contain the canonical rSAM amino acid sequence motif (CxxxCxxC) necessary to form the 4Fe-4S cluster required for tRNA modifications. In E. coli, RlmN is responsible for the 2-methlyadenosine (m2A) synthesis at purine 37 in tRNA while in S. cerevisiae, Elp3 is necessary for the formation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) at the wobble tRNA position. To investigate why these two rSAM enzymes localize to the mitochondrion in Toxoplasma, and whether or not TgRlmN and TgElp3 possess tRNA methyltransferase activity, a series of mutational and biochemical studies were performed. Overexpression of either TgElp3 or TgRlmN resulted in a significant parasite replication defect, but overexpression was tolerated if either the TMD or rSAM domain was mutated. Furthermore, we show the first evidence that Toxoplasma tRNAGlu contains the mcm5s2U modification, which is the putative downstream product generated by TgElp3 activity.

  15. Abrasion Testing of Products Containing Nanomaterials, SOP-R-2: Scientific Operating Procedure Series: Release (R)

    Science.gov (United States)

    2016-04-01

    Nanotechnologies -- Terminology and definitions for nano-objects -- Nanoparticle, nanofibre and nanoplate Definitions Abrasion - wearing away...ER D C SR -1 6- 2 Environmental Consequences of Nanotechnologies Abrasion Testing of Products Containing Nanomaterials, SOP-R-2...ERDC online library at http://acwc.sdp.sirsi.net/client/default. Environmental Consequences of Nanotechnologies ERDC SR-16-2 April 2016

  16. Proposal of a model for sales and operations planning (S&OP maturity evaluation

    Directory of Open Access Journals (Sweden)

    Carolina Belotti Pedroso

    2017-11-01

    Full Text Available Abstract A successful S&OP implementation can bring many benefits to organizations, and after its implementation, the S&OP process can evolve and reach higher levels of maturity. Considering that, only through a measurement system, goals and benefits can be achieved, thus, it is essential to assess S&OP maturity level. Many papers on literature adopt a quantitative perspective on S&OP, but just few of them deal with uncertainty present in S&OP decision-making, such as maturity model assessment process that carries subjectivity and uncertainty. Thus, this study proposes a decision making model based on fuzzy theory to evaluate and to categorize S&OP maturity levels and to suggest strategies to increase S&OP maturity. A pilot application was conducted in two manufacturing organizations that have implemented the S&OP process. The results, according to the performance presented, suggest different actions must be taken in terms of ensuring enablers to S&OP implementation.

  17. Crystal Structure of Bicc1 SAM Polymer and Mapping of Interactions between the Ciliopathy-Associated Proteins Bicc1, ANKS3, and ANKS6.

    Science.gov (United States)

    Rothé, Benjamin; Leettola, Catherine N; Leal-Esteban, Lucia; Cascio, Duilio; Fortier, Simon; Isenschmid, Manuela; Bowie, James U; Constam, Daniel B

    2018-02-06

    Head-to-tail polymers of sterile alpha motifs (SAM) can scaffold large macromolecular complexes. Several SAM-domain proteins that bind each other are mutated in patients with cystic kidneys or laterality defects, including the Ankyrin (ANK) and SAM domain-containing proteins ANKS6 and ANKS3, and the RNA-binding protein Bicc1. To address how their interactions are regulated, we first determined a high-resolution crystal structure of a Bicc1-SAM polymer, revealing a canonical SAM polymer with a high degree of flexibility in the subunit interface orientations. We further mapped interactions between full-length and distinct domains of Bicc1, ANKS3, and ANKS6. Neither ANKS3 nor ANKS6 alone formed macroscopic homopolymers in vivo. However, ANKS3 recruited ANKS6 to Bicc1, and the three proteins together cooperatively generated giant macromolecular complexes. Thus, the giant assemblies are shaped by SAM domains, their flanking sequences, and SAM-independent protein-protein and protein-mRNA interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. CTEPP STANDARD OPERATING PROCEDURE FOR COLLECTION OF SOIL SAMPLES FOR PERSISTENT ORGANIC POLLUTANTS (SOP-2.20)

    Science.gov (United States)

    This SOP describes the method for collecting soil samples from the child's outdoor play area to measure for persistent organic pollutants. Soil samples are collected by scraping up the top 0.5 cm of soil in a 0.095 m2 (1 ft2) area in the middle of the child's play area.

  19. ASAMPSA-E guidance for level 2 PSA Volume 3. Verification and improvement of SAM strategies with L2 PSA

    International Nuclear Information System (INIS)

    Rahni, N.; Raimond, E.; Jan, P.; Lopez, J.; Loeffler, H.; Mildenberger, O.; Kubicek, J.; Vitazkova, J.; Ivanov, I.; Groudev, P.; Lajtha, G.; Serrano, C.; Zhabin, O.; Prosek, Andrej; Dirksen, G.; Yu, S.; Oury, L.; Hultqvist, G.

    2016-01-01

    For each NPP, severe accident management (SAM) strategies shall make use of components or systems and human resources to limit as far as possible the consequences of any severe accident on-site and off-site. L2 PSA is one of the tools that can be used to verify and improve these strategies. The present report (deliverable D40.5 of the project ASAMPSA-E) provides an opportunity for a comparison of objectives in the different countries in terms of SAM strategies verification and improvement. The report summarizes also experience of each partner (including potential deficiencies) involved in this activity, in order to derive some good practices and required progress, addressing: - SAM modeling in L2 PSA, - Positive and negative aspects in current SAM practices, - Discussion on possible criteria related to L2 PSA for verification and improvement: risk reduction (in relation with WP30 activities on risk metrics), reduction of uncertainties on the severe accident progression paths until NPP stabilization, reduction of human failure conditional probabilities (depending on the SAM strategy, the environmental conditions...), - Review with a perspective of verification and improvement of the main SAM strategies (corium cooling, RCS depressurization, control of flammable gases, reactivity control, containment function, containment pressure control, limitation of radioactive releases,...), - SAM strategies to be considered in the context of an extended L2 PSA (as far possible, depending on existing experience), taking into account all operating modes, accidents also occurring in the SFPs and long term and multi-unit accidents. The deliverable D40.5 is developed from the partners' experience. Many of the topics described here are beyond the common practices of L2 PSA applications: in some countries, L2 PSA application is limited to the calculations of frequencies of release categories with no formal requirement for SAM verification and improvement. (authors)

  20. Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane.

    LENUS (Irish Health Repository)

    Knodler, Leigh A

    2009-11-01

    The Salmonella type III effector, SopB, is an inositol polyphosphate phosphatase that modulates host cell phospholipids at the plasma membrane and the nascent Salmonella-containing vacuole (SCV). Translocated SopB persists for many hours after infection and is ubiquitinated but the significance of this covalent modification has not been investigated. Here we identify by mass spectrometry six lysine residues of SopB that are mono-ubiquitinated. Substitution of these six lysine residues with arginine, SopB-K(6)R, almost completely eliminated SopB ubiquitination. We found that ubiquitination does not affect SopB stability or membrane association, or SopB-dependent events in SCV biogenesis. However, two spatially and temporally distinct events are dependent on ubiquitination, downregulation of SopB activity at the plasma membrane and prolonged retention of SopB on the SCV. Activation of the mammalian pro-survival kinase Akt\\/PKB, a downstream target of SopB, was intensified and prolonged after infection with the SopB-K(6)R mutant. At later times, fewer SCV were decorated with SopB-K(6)R compared with SopB. Instead SopB-K(6)R was present as discrete vesicles spread diffusely throughout the cell. Altogether, our data show that ubiquitination of SopB is not related to its intracellular stability but rather regulates its enzymatic activity at the plasma membrane and intracellular localization.

  1. Crystal structures of the SAM-III/S[subscript MK] riboswitch reveal the SAM-dependent translation inhibition mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Lu, C.; Smith, A.M.; Fuchs, R.T.; Ding, F.; Rajashankar, K.; Henkin, T.M.; Ke, A. (Cornell); (OSU)

    2010-01-07

    Three distinct classes of S-adenosyl-L-methionine (SAM)-responsive riboswitches have been identified that regulate bacterial gene expression at the levels of transcription attenuation or translation inhibition. The SMK box (SAM-III) translational riboswitch has been identified in the SAM synthetase gene in members of the Lactobacillales. Here we report the 2.2-{angstrom} crystal structure of the Enterococcus faecalis SMK box riboswitch. The Y-shaped riboswitch organizes its conserved nucleotides around a three-way junction for SAM recognition. The Shine-Dalgarno sequence, which is sequestered by base-pairing with the anti-Shine-Dalgarno sequence in response to SAM binding, also directly participates in SAM recognition. The riboswitch makes extensive interactions with the adenosine and sulfonium moieties of SAM but does not appear to recognize the tail of the methionine moiety. We captured a structural snapshot of the SMK box riboswitch sampling the near-cognate ligand S-adenosyl-L-homocysteine (SAH) in which SAH was found to adopt an alternative conformation and fails to make several key interactions.

  2. Fabrication and Surface Properties of Composite Films of SAM/Pt/ZnO/SiO 2

    KAUST Repository

    Yao, Ke Xin

    2008-12-16

    Through synthetic architecture and functionalization with self-assembled monolayers (SAMs), complex nanocomposite films of SAM/Pt/ZnO/SiO2 have been facilely prepared in this work. The nanostructured films are highly uniform and porous, showing a wide range of tunable wettabilities from superhydrophilicity to superhydrophobicity (water contact angles: 0° to 170°). Our approach offers synthetic flexibility in controlling film architecture, surface topography, coating texture, crystallite size, and chemical composition of modifiers (e.g., SAMs derived from alkanethiols). For example, wettability properties of the nanocomposite films can be finely tuned with both inorganic phase (i.e., ZnO/SiO2 and Pt/ZnO/SiO2) and organic phase (i.e., SAMs on Pt/ZnO/SiO2). Due to the presence of catalytic components Pt/ZnO within the nanocomposites, surface reactions of the organic modifiers can further take place at room temperature and elevated temperatures, which provides a means for SAM formation and elimination. Because the Pt/ZnO forms an excellent pair of metal-semiconductors for photocatalysis, the anchored SAMs can also be modified or depleted by UV irradiation (i.e., the films possess self-cleaning ability). Potential applications of these nanocomposite films have been addressed. Our durability tests also confirm that the films are thermally stable and structurally robust in modification- regeneration cycles. © 2008 American Chemical Society.

  3. TRX and UO2 criticality benchmarks with SAM-CE

    International Nuclear Information System (INIS)

    Beer, M.; Troubetzkoy, E.S.; Lichtenstein, H.; Rose, P.F.

    1980-01-01

    A set of thermal reactor benchmark calculations with SAM-CE which have been conducted at both MAGI and at BNL are described. Their purpose was both validation of the SAM-CE reactor eigenvalue capability developed by MAGI and a substantial contribution to the data testing of both ENDF/B-IV and ENDF/B-V libraries. This experience also resulted in increased calculational efficiency of the code and an example is given. The benchmark analysis included the TRX-1 infinite cell using both ENDF/B-IV and ENDF/B-V cross section sets and calculations using ENDF/B-IV of the TRX-1 full core and TRX-2 cell. BAPL-UO2-1 calculations were conducted for the cell using both ENDF/B-IV and ENDF/B-V and for the full core with ENDF/B-V

  4. CTEPP STANDARD OPERATING PROCEDURE FOR CONDUCTING STAFF AND PARTICIPANT TRAINING (SOP-2.27)

    Science.gov (United States)

    This SOP describes the method to train project staff and participants to collect various field samples and questionnaire data for the study. The training plan consists of two separate components: project staff training and participant training. Before project activities begin,...

  5. CTEPP STANDARD OPERATING PROCEDURE FOR COLLECTION OF PERSONAL INTERVIEW DATA (SOP-2.21)

    Science.gov (United States)

    This SOP describes the general method for collecting personal interview data from the child's parent (and the day care center staff, if applicable). Study participants, both parents and day care center teachers, will be interviewed by the project staff at a scheduled appointment ...

  6. Analysis of generalized Schwarz alternating procedure for domain decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Engquist, B.; Zhao, Hongkai [Univ. of California, Los Angeles, CA (United States)

    1996-12-31

    The Schwartz alternating method(SAM) is the theoretical basis for domain decomposition which itself is a powerful tool both for parallel computation and for computing in complicated domains. The convergence rate of the classical SAM is very sensitive to the overlapping size between each subdomain, which is not desirable for most applications. We propose a generalized SAM procedure which is an extension of the modified SAM proposed by P.-L. Lions. Instead of using only Dirichlet data at the artificial boundary between subdomains, we take a convex combination of u and {partial_derivative}u/{partial_derivative}n, i.e. {partial_derivative}u/{partial_derivative}n + {Lambda}u, where {Lambda} is some {open_quotes}positive{close_quotes} operator. Convergence of the modified SAM without overlapping in a quite general setting has been proven by P.-L.Lions using delicate energy estimates. The important questions remain for the generalized SAM. (1) What is the most essential mechanism for convergence without overlapping? (2) Given the partial differential equation, what is the best choice for the positive operator {Lambda}? (3) In the overlapping case, is the generalized SAM superior to the classical SAM? (4) What is the convergence rate and what does it depend on? (5) Numerically can we obtain an easy to implement operator {Lambda} such that the convergence is independent of the mesh size. To analyze the convergence of the generalized SAM we focus, for simplicity, on the Poisson equation for two typical geometry in two subdomain case.

  7. Fabrication and Surface Properties of Composite Films of SAM/Pt/ZnO/SiO 2

    KAUST Repository

    Yao, Ke Xin; Zeng, Hua Chun

    2008-01-01

    Through synthetic architecture and functionalization with self-assembled monolayers (SAMs), complex nanocomposite films of SAM/Pt/ZnO/SiO2 have been facilely prepared in this work. The nanostructured films are highly uniform and porous, showing a

  8. Context-based Sales and Operations Planning (S&OP) research: A literature review and future agenda

    DEFF Research Database (Denmark)

    Kristensen, Jesper; Jonsson, Patrik

    2018-01-01

    must be considered when designing and implementing S&OP. Originality/values – This study focused on identifying relevant research on S&OP design by analysing the contribution of literature to a research framework inspired by contingency based research of operations and supply chain management.......&OP design. Research implications – The findings revealed several gaps in the literature on context-dependent S&OP design. To address these gaps, an agenda for future S&OP contingency research is developed. Practical implications – The findings revealed which contextual areas and specific S&OP design issues...

  9. SAM International Case Studies: DPV Analysis in Mexico

    Energy Technology Data Exchange (ETDEWEB)

    McCall, James D [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-03-28

    Presentation demonstrates the use of the System Advisor Model (SAM) in international analyses, specifically Mexico. Two analyses are discussed with relation to SAM modelling efforts: 1) Customer impacts from changes to net metering and billing agreements and 2) Potential benefits of PV for Mexican solar customers, the Mexican Treasury, and the environment. Along with the SAM analyses, integration of the International Utility Rate Database (I-URDB) with SAM and future international SAM work are discussed. Presentation was created for the International Solar Energy Society's (ISES) webinar titled 'International use of the NREL System Advisor Model (SAM) with case studies'.

  10. The SAM, not the electrodes, dominates charge transport in metal-monolayer//Ga2O3/gallium-indium eutectic junctions.

    Science.gov (United States)

    Reus, William F; Thuo, Martin M; Shapiro, Nathan D; Nijhuis, Christian A; Whitesides, George M

    2012-06-26

    The liquid-metal eutectic of gallium and indium (EGaIn) is a useful electrode for making soft electrical contacts to self-assembled monolayers (SAMs). This electrode has, however, one feature whose effect on charge transport has been incompletely understood: a thin (approximately 0.7 nm) film-consisting primarily of Ga(2)O(3)-that covers its surface when in contact with air. SAMs that rectify current have been measured using this electrode in Ag(TS)-SAM//Ga(2)O(3)/EGaIn (where Ag(TS) = template-stripped Ag surface) junctions. This paper organizes evidence, both published and unpublished, showing that the molecular structure of the SAM (specifically, the presence of an accessible molecular orbital asymmetrically located within the SAM), not the difference between the electrodes or the characteristics of the Ga(2)O(3) film, causes the observed rectification. By examining and ruling out potential mechanisms of rectification that rely either on the Ga(2)O(3) film or on the asymmetry of the electrodes, this paper demonstrates that the structure of the SAM dominates charge transport through Ag(TS)-SAM//Ga(2)O(3)/EGaIn junctions, and that the electrical characteristics of the Ga(2)O(3) film have a negligible effect on these measurements.

  11. SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches.

    Science.gov (United States)

    Mirihana Arachchilage, Gayan; Sherlock, Madeline E; Weinberg, Zasha; Breaker, Ronald R

    2018-03-04

    Five distinct riboswitch classes that regulate gene expression in response to the cofactor S-adenosylmethionine (SAM) or its metabolic breakdown product S-adenosylhomocysteine (SAH) have been reported previously. Collectively, these SAM- or SAH-sensing RNAs constitute the most abundant collection of riboswitches, and are found in nearly every major bacterial lineage. Here, we report a potential sixth member of this pervasive riboswitch family, called SAM-VI, which is predominantly found in Bifidobacterium species. SAM-VI aptamers selectively bind the cofactor SAM and strongly discriminate against SAH. The consensus sequence and structural model for SAM-VI share some features with the consensus model for the SAM-III riboswitch class, whose members are mainly found in lactic acid bacteria. However, there are sufficient differences between the two classes such that current bioinformatics methods separately cluster representatives of the two motifs. These findings highlight the abundance of RNA structures that can form to selectively recognize SAM, and showcase the ability of RNA to utilize diverse strategies to perform similar biological functions.

  12. Surface characterization on binary nano/micro-domain composed of alkyl- and amino-terminated self-assembled monolayer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.H. [Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553 (Japan); Ishizaki, T. [Materials Research Institute for Sustainable Development, National Institute of Advanced Industrial Science and Technology, 2266-98 Anagahora, Shimo-Shidami, Moriyama-ku, Nagoya 463-8560 (Japan); Saito, N. [Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagano 464-8603 (Japan)], E-mail: hiro@eco-t.esi.nagoya-u.ac.jp; Takai, O. [EcoTopia Science Institute, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603 (Japan)

    2008-09-15

    The binary alkyl- and amino-terminated self-assembled monolayers (SAMs) composed of nano/micro-sized domains was prepared though a self-assembly technique. In addition, the wetting and electrostatic property of the binary SAMs was investigated by the analysis of the static and dynamic water contact angle and zeta-potentials measurement. The binary SAMs were also characterized by atomic force microscope (AFM), Kelvin probe force microscope (KPFM) and X-ray photoelectron spectroscopy (XPS). The domains on the binary SAMs were observed in topographic and surface potential images. The height of domain and the surface potential between octadecyltrichlorosilanes (OTS)-domain and n-(6-aminohexl)aminopropyl-trimethoxysilane (AHAPS)-SAM were about 1.1 nm and -30 mV. These differences of height and surface potential correspond to the ones between OTS and AHAPS. In XPS N 1s spectra, we confirmed the formation of binary SAMs by an amino peak observed at 399.15 eV. The dynamic and the static water contact angles indicated that the wetting property of the binary SAMs was depended on the OTS domain size. In addition, static water contact angles were measured under the conditions of different pH water and zeta-potential also indicated that the electrostatic property of the binary SAMs depended on OTS domain size. Thus, these results showed that the wetting and electrostatic property on the binary SAMs could be regulated by controlling the domain size.

  13. SAM Photovoltaic Model Technical Reference

    Energy Technology Data Exchange (ETDEWEB)

    Gilman, P. [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2015-05-27

    This manual describes the photovoltaic performance model in the System Advisor Model (SAM). The U.S. Department of Energy’s National Renewable Energy Laboratory maintains and distributes SAM, which is available as a free download from https://sam.nrel.gov. These descriptions are based on SAM 2015.1.30 (SSC 41).

  14. CTEPP STANDARD OPERATING PROCEDURE FOR CONDUCTING INTERNAL FIELD AUDITS AND QUALITY CONTROL (SOP-2.25)

    Science.gov (United States)

    This SOP describes the method for conducting internal field audits and quality control procedures. Internal field audits will be conducted to ensure the collection of high quality data. Internal field audits will be conducted by Field Auditors (the Field QA Officer and the Field...

  15. Efficient degradation of sulfamethazine in simulated and real wastewater at slightly basic pH values using Co-SAM-SCS /H2O2 Fenton-like system.

    Science.gov (United States)

    Cheng, Min; Zeng, Guangming; Huang, Danlian; Lai, Cui; Liu, Yang; Zhang, Chen; Wan, Jia; Hu, Liang; Zhou, Chengyun; Xiong, Weiping

    2018-07-01

    The presence of antibiotics in aquatic environments has attracted global concern. Fenton process is an attractive yet challenging method for antibiotics degradation, especially when such a reaction can be conducted at neutral pH values. In this study, a novel composite Fe/Co catalyst was synthesized via the modification of steel converter slag (SCS) by salicylic acid-methanol (SAM) and cobalt nitrate (Co(NO 3 ) 2 ). The catalysts were characterized by N 2 -Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The results indicated that the Co-SAM-SCS/H 2 O 2 Fenton-like system was very effective for sulfamethazine (SMZ) degradation at a wide pH range. At initial pH of 7.0, the degradation rate of SMZ in Co-SAM-SCS/H 2 O 2 system was 2.48, 3.20, 6.18, and 16.21 times of that in Fe-SAM-SCS/H 2 O 2 , SAM-SCS/H 2 O 2 , Co(NO 3 ) 2 /H 2 O 2 and SCS/H 2 O 2 system, respectively. The preliminary analysis suggested that high surface area of Co-SAM-SCS sample and synergistic effect between introduced Co and SAM-SCS are responsible for the efficient catalytic activity. During the degradation, three main intermediates were identified by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. Based on this, a possible degradation pathway was proposed. The SEM images, XRD patterns and XPS spectra before and after the reactions demonstrate that the crystal and chemical structure of Co-SAM-SCS after five cycles are almost unchanged. Besides, the Co-SAM-SCS presented low iron and cobalt leaching (0.17 mg/L and 2.36 mg/L, respectively). The studied Fenton-like process also showed high degradation of SMZ in river water and municipal wastewater. The progress will bring valuable insights to develop high-performance heterogeneous Fenton-like catalysts for environmental remediation. Copyright © 2018

  16. Monitoring complex detectors: the uSOP approach in the Belle II experiment

    International Nuclear Information System (INIS)

    Capua, F. Di; Aloisio, A.; Giordano, R.; Ameli, F.; Anastasio, A.; Izzo, V.; Tortone, G.; Branchini, P.

    2017-01-01

    uSOP is a general purpose single board computer designed for deep embedded applications in control and monitoring of detectors, sensors and complex laboratory equipments. It is based on the AM3358 (1 GHz ARM Cortex A8 processor), equipped with USB and Ethernet interfaces. On-board RAM and solid state storage allows hosting a full LINUX distribution. In this paper we discuss the main aspects of the hardware and software design and the expandable peripheral architecture built around field busses. We report on several applications of uSOP system in the Belle II experiment, presently under construction at KEK (Tsukuba, Japan). In particular we will report the deployment of uSOP in the monitoring system framework of the endcap electromagnetic calorimeter.

  17. Monitoring complex detectors: the uSOP approach in the Belle II experiment

    Science.gov (United States)

    Di Capua, F.; Aloisio, A.; Ameli, F.; Anastasio, A.; Branchini, P.; Giordano, R.; Izzo, V.; Tortone, G.

    2017-08-01

    uSOP is a general purpose single board computer designed for deep embedded applications in control and monitoring of detectors, sensors and complex laboratory equipments. It is based on the AM3358 (1 GHz ARM Cortex A8 processor), equipped with USB and Ethernet interfaces. On-board RAM and solid state storage allows hosting a full LINUX distribution. In this paper we discuss the main aspects of the hardware and software design and the expandable peripheral architecture built around field busses. We report on several applications of uSOP system in the Belle II experiment, presently under construction at KEK (Tsukuba, Japan). In particular we will report the deployment of uSOP in the monitoring system framework of the endcap electromagnetic calorimeter.

  18. SAM Theory Manual

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Rui [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-03-01

    The System Analysis Module (SAM) is an advanced and modern system analysis tool being developed at Argonne National Laboratory under the U.S. DOE Office of Nuclear Energy’s Nuclear Energy Advanced Modeling and Simulation (NEAMS) program. SAM development aims for advances in physical modeling, numerical methods, and software engineering to enhance its user experience and usability for reactor transient analyses. To facilitate the code development, SAM utilizes an object-oriented application framework (MOOSE), and its underlying meshing and finite-element library (libMesh) and linear and non-linear solvers (PETSc), to leverage modern advanced software environments and numerical methods. SAM focuses on modeling advanced reactor concepts such as SFRs (sodium fast reactors), LFRs (lead-cooled fast reactors), and FHRs (fluoride-salt-cooled high temperature reactors) or MSRs (molten salt reactors). These advanced concepts are distinguished from light-water reactors in their use of single-phase, low-pressure, high-temperature, and low Prandtl number (sodium and lead) coolants. As a new code development, the initial effort has been focused on modeling and simulation capabilities of heat transfer and single-phase fluid dynamics responses in Sodium-cooled Fast Reactor (SFR) systems. The system-level simulation capabilities of fluid flow and heat transfer in general engineering systems and typical SFRs have been verified and validated. This document provides the theoretical and technical basis of the code to help users understand the underlying physical models (such as governing equations, closure models, and component models), system modeling approaches, numerical discretization and solution methods, and the overall capabilities in SAM. As the code is still under ongoing development, this SAM Theory Manual will be updated periodically to keep it consistent with the state of the development.

  19. SAM Photovoltaic Model Technical Reference 2016 Update

    Energy Technology Data Exchange (ETDEWEB)

    Gilman, Paul [National Renewable Energy Laboratory (NREL), Golden, CO (United States); DiOrio, Nicholas A [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Freeman, Janine M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Janzou, Steven [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Dobos, Aron [No longer NREL employee; Ryberg, David [No longer NREL employee

    2018-03-19

    This manual describes the photovoltaic performance model in the System Advisor Model (SAM) software, Version 2016.3.14 Revision 4 (SSC Version 160). It is an update to the 2015 edition of the manual, which describes the photovoltaic model in SAM 2015.1.30 (SSC 41). This new edition includes corrections of errors in the 2015 edition and descriptions of new features introduced in SAM 2016.3.14, including: 3D shade calculator Battery storage model DC power optimizer loss inputs Snow loss model Plane-of-array irradiance input from weather file option Support for sub-hourly simulations Self-shading works with all four subarrays, and uses same algorithm for fixed arrays and one-axis tracking Linear self-shading algorithm for thin-film modules Loss percentages replace derate factors. The photovoltaic performance model is one of the modules in the SAM Simulation Core (SSC), which is part of both SAM and the SAM SDK. SAM is a user-friedly desktop application for analysis of renewable energy projects. The SAM SDK (Software Development Kit) is for developers writing their own renewable energy analysis software based on SSC. This manual is written for users of both SAM and the SAM SDK wanting to learn more about the details of SAM's photovoltaic model.

  20. Deposition of phospholipid layers on SiO{sub 2} surface modified by alkyl-SAM islands

    Energy Technology Data Exchange (ETDEWEB)

    Tero, R.; Takizawa, M.; Li, Y.J.; Yamazaki, M.; Urisu, T

    2004-11-15

    Formation of the supported planar bilayer of dipalmitoylphosphatidylcholine (DPPC) on SiO{sub 2} surfaces modified with the self-assembled monolayer (SAM) of octadecyltrichlorosilane (OTS) has been investigated by atomic force microscopy (AFM). DPPC was deposited by the fusion of vesicles on SiO{sub 2} surfaces with OTS-SAM islands of different sizes and densities. The DPPC bilayer membrane formed self-organizingly on the SiO{sub 2} surface with small and sparse OTS islands, while did not when the OTS islands were larger and denser. The relative size between the vesicles and the SiO{sub 2} regions is the critical factor for the formation of the DPPC bilayer membrane.

  1. Redox Behavior of the S-Adenosylmethionine (SAM)-Binding Fe-S Cluster in Methylthiotransferase RimO, toward Understanding Dual SAM Activity.

    Science.gov (United States)

    Molle, Thibaut; Moreau, Yohann; Clemancey, Martin; Forouhar, Farhad; Ravanat, Jean-Luc; Duraffourg, Nicolas; Fourmond, Vincent; Latour, Jean-Marc; Gambarelli, Serge; Mulliez, Etienne; Atta, Mohamed

    2016-10-18

    RimO, a radical-S-adenosylmethionine (SAM) enzyme, catalyzes the specific C 3 methylthiolation of the D89 residue in the ribosomal S 12 protein. Two intact iron-sulfur clusters and two SAM cofactors both are required for catalysis. By using electron paramagnetic resonance, Mössbauer spectroscopies, and site-directed mutagenesis, we show how two SAM molecules sequentially bind to the unique iron site of the radical-SAM cluster for two distinct chemical reactions in RimO. Our data establish that the two SAM molecules bind the radical-SAM cluster to the unique iron site, and spectroscopic evidence obtained under strongly reducing conditions supports a mechanism in which the first molecule of SAM causes the reoxidation of the reduced radical-SAM cluster, impeding reductive cleavage of SAM to occur and allowing SAM to methylate a HS - ligand bound to the additional cluster. Furthermore, by using density functional theory-based methods, we provide a description of the reaction mechanism that predicts the attack of the carbon radical substrate on the methylthio group attached to the additional [4Fe-4S] cluster.

  2. SAMS--a systems architecture for developing intelligent health information systems.

    Science.gov (United States)

    Yılmaz, Özgün; Erdur, Rıza Cenk; Türksever, Mustafa

    2013-12-01

    In this paper, SAMS, a novel health information system architecture for developing intelligent health information systems is proposed and also some strategies for developing such systems are discussed. The systems fulfilling this architecture will be able to store electronic health records of the patients using OWL ontologies, share patient records among different hospitals and provide physicians expertise to assist them in making decisions. The system is intelligent because it is rule-based, makes use of rule-based reasoning and has the ability to learn and evolve itself. The learning capability is provided by extracting rules from previously given decisions by the physicians and then adding the extracted rules to the system. The proposed system is novel and original in all of these aspects. As a case study, a system is implemented conforming to SAMS architecture for use by dentists in the dental domain. The use of the developed system is described with a scenario. For evaluation, the developed dental information system will be used and tried by a group of dentists. The development of this system proves the applicability of SAMS architecture. By getting decision support from a system derived from this architecture, the cognitive gap between experienced and inexperienced physicians can be compensated. Thus, patient satisfaction can be achieved, inexperienced physicians are supported in decision making and the personnel can improve their knowledge. A physician can diagnose a case, which he/she has never diagnosed before, using this system. With the help of this system, it will be possible to store general domain knowledge in this system and the personnel's need to medical guideline documents will be reduced.

  3. Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation.

    Science.gov (United States)

    Zhang, Hua; Song, Lei; Cong, Haolong; Tien, Po

    2015-10-01

    Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially

  4. A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein

    KAUST Repository

    Smirnova, Ekaterina; Kwan, Jamie J.; Siu, Ryan; Gao, Xin; Zoidl, Georg; Demeler, Borries; Saridakis, Vivian; Donaldson, Logan W.

    2016-01-01

    Background: CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions.

  5. A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein

    KAUST Repository

    Smirnova, Ekaterina

    2016-08-22

    Background: CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions.

  6. 76 FR 54528 - Standard Operating Procedures (SOP) of the Aircraft Certification Service (AIR) Process for the...

    Science.gov (United States)

    2011-09-01

    ...) of the Aircraft Certification Service (AIR) Process for the Sequencing of Certification and... on the Aircraft Certification Service (AIR) standard operating procedure (SOP) describing the process... comments on the SOP : AIR-100-001; Standard Operating Procedure--Aircraft Certification Service Project...

  7. Evaluasi Penerapan Standard Operating Procedure-Good Agriculture Practice (SOP-GAP pada Usahatani Padi Organik di Kabupaten Bantul

    Directory of Open Access Journals (Sweden)

    Sriyadi Sriyadi

    2016-02-01

    Full Text Available Food security has meaning not only the availability of adequate food, but also providing security for producers and consumers and ensuring environmental sustainability for sustainable production. Organic farming systems are expected to solve the problem for realizing food security and enhancement of people's welfare. The results of research indicated that, (1 The implementation level of Standard Operating Procedure-Good Agriculture Practice (SOP-GAP of Organic Rice Farming in Bantul district was quite high, (2 The implementation level of SOP-GAP of Organic Rice Farming related to the availability of capital, the selling price and the purchase price of inputs (seeds and fertilizers, (3 The level of the farmer's decision related to the implementation level of SOP-GAP of organic rice farming, and (4 development of organic rice farming required availability of sufficient capital. In this regard the government, particularly the agriculture authority and food security agency need to disburse or facilitate capital for farmers in revolving as well as low interest loans.

  8. Integración de un Modelo S&OP con un Modelo ALM

    OpenAIRE

    Insuasty Chamorro, Andrés Felipe

    2015-01-01

    DecisionWare International Corp. (DW) Este trabajo presenta los fundamentos metodológicos y la aplicación de la integración de un modelo financiero ALM (Assets Liabilities Management) con los modelos de planificación de la cadena de oferta de una empresa industrial global como son el SCD (Supply Chain Design) y el S&OP (Sales & Operation Planning). La aplicación en este trabajo se concentra en el modelo S&OP vinculado a un modelo ALM. Como resultado práctico se presenta la implementación d...

  9. International Cooperation to Establish Standard Operating Procedure (SOP) for Quarantine Management of Irradiated Foods in International Trade

    International Nuclear Information System (INIS)

    Lee, J. W.; Byun, M. W.; Kim, J. H.; Choi, J. I.; Song, B. S.; Yoon, Y. H.; Kim, D. H.; Kim, W. G.; Kim, K. P.

    2010-02-01

    · Development of SOPs through various research activities such as building international cooperation, and analysing current status of food irradiation in domestic and international markets, export and import, international market size, and of R and D - Analysis of examples for quarantine management in agricultural product exporting countries and use of irradiation technology for agricultural product quarantine, and changes in international quarantine management - Analysis of SOPs for food irradiation quarantine in international organization (CODEX, IPPC, WHO). U.S, EU, China, India, and Australia. - Collaborative researches of India/Korea and China/Korea entered into an agreement for market trials · Publishment of irradiation quarantine management SOPs agreed to CODEX standards - Collaborative researches for quarantine management, avoiding Technical Barrier to Trade (TBT), and Sanitary Phytosanitary Measures were conducted, and advanced SOPs agreed with WTO/FTA system were published

  10. Three-dimensional RF SoP technologies: LTCC versus LCP

    KAUST Repository

    Arabi, Eyad A.; Shamim, Atif

    2014-01-01

    or cover but is a functional part of the system. The leading multilayer packaging technologies for SoP designs: low temperature co-fired ceramic (LTCC) and liquid crystal polymer (LCP) are compared in this work for the first time. Passive components

  11. International Cooperation to Establish Standard Operating Procedure (SOP) for Quarantine Management of Irradiated Foods in International Trade

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. W.; Byun, M. W.; Kim, J. H.; Choi, J. I.; Song, B. S.; Yoon, Y. H.; Kim, D. H.; Kim, W. G.; Kim, K. P.

    2010-02-15

    {center_dot} Development of SOPs through various research activities such as building international cooperation, and analysing current status of food irradiation in domestic and international markets, export and import, international market size, and of R and D - Analysis of examples for quarantine management in agricultural product exporting countries and use of irradiation technology for agricultural product quarantine, and changes in international quarantine management - Analysis of SOPs for food irradiation quarantine in international organization (CODEX, IPPC, WHO). U.S, EU, China, India, and Australia. - Collaborative researches of India/Korea and China/Korea entered into an agreement for market trials {center_dot} Publishment of irradiation quarantine management SOPs agreed to CODEX standards - Collaborative researches for quarantine management, avoiding Technical Barrier to Trade (TBT), and Sanitary Phytosanitary Measures were conducted, and advanced SOPs agreed with WTO/FTA system were published

  12. Samsø Energy Vision 2030

    DEFF Research Database (Denmark)

    Mathiesen, Brian Vad; Hansen, Kenneth; Ridjan, Iva

    The purpose of this report is to investigate potential scenarios for converting Samsø into 100% renewable energy supply in 2030 with focus on local electricity and biomass resources. Firstly, a 2013 reference scenario is established to investigate whether Samsø is 100% renewable today. Next, scen...

  13. Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7

    Directory of Open Access Journals (Sweden)

    Vanessa M. D’Costa

    2015-09-01

    Full Text Available Intracellular bacterial pathogens of a diverse nature share the ability to evade host immunity by impairing trafficking of endocytic cargo to lysosomes for degradation, a process that is poorly understood. Here, we show that the Salmonella enterica type 3 secreted effector SopD2 mediates this process by binding the host regulatory GTPase Rab7 and inhibiting its nucleotide exchange. Consequently, this limits Rab7 interaction with its dynein- and kinesin-binding effectors RILP and FYCO1 and thereby disrupts host-driven regulation of microtubule motors. Our study identifies a bacterial effector capable of directly binding and thereby modulating Rab7 activity and a mechanism of endocytic trafficking disruption that may provide insight into the pathogenesis of other bacteria. Additionally, we provide a powerful tool for the study of Rab7 function, and a potential therapeutic target.

  14. System for Award Management (SAM) API

    Data.gov (United States)

    General Services Administration — The SAM API is a RESTful method of retrieving public information about the businesses, organizations, or individuals (referred to as entities) within the SAM entity...

  15. Replacing -CH2CH2- with -CONH- does not significantly change rates of charge transport through Ag(TS)-SAM//Ga2O3/EGaIn junctions.

    Science.gov (United States)

    Thuo, Martin M; Reus, William F; Simeone, Felice C; Kim, Choongik; Schulz, Michael D; Yoon, Hyo Jae; Whitesides, George M

    2012-07-04

    This paper describes physical-organic studies of charge transport by tunneling through self-assembled monolayers (SAMs), based on systematic variations of the structure of the molecules constituting the SAM. Replacing a -CH(2)CH(2)- group with a -CONH- group changes the dipole moment and polarizability of a portion of the molecule and has, in principle, the potential to change the rate of charge transport through the SAM. In practice, this substitution produces no significant change in the rate of charge transport across junctions of the structure Ag(TS)-S(CH(2))(m)X(CH(2))(n)H//Ga(2)O(3)/EGaIn (TS = template stripped, X = -CH(2)CH(2)- or -CONH-, and EGaIn = eutectic alloy of gallium and indium). Incorporation of the amide group does, however, increase the yields of working (non-shorting) junctions (when compared to n-alkanethiolates of the same length). These results suggest that synthetic schemes that combine a thiol group on one end of a molecule with a group, R, to be tested, on the other (e.g., HS~CONH~R) using an amide-based coupling provide practical routes to molecules useful in studies of molecular electronics.

  16. 78 FR 62627 - Sam Rayburn Dam Rate

    Science.gov (United States)

    2013-10-22

    ..., Wholesale Rates for Hydro Power and Energy Sold to Sam Rayburn Dam Electric Cooperative, Inc. (Contract No... Schedule SRD-08, Wholesale Rates for Hydro Power and Energy Sold to Sam Rayburn Dam Electric Cooperative... ADMINISTRATION RATE SCHEDULE SRD-13 \\1\\ WHOLESALE RATES FOR HYDRO POWER AND ENERGY SOLD TO SAM RAYBURN DAM...

  17. Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weijie, E-mail: 459586768@qq.com; Liu, Yuxi, E-mail: 924013616@qq.com; Wang, Youhua, E-mail: wyouhua1516@163.com

    2016-05-13

    Sam68 (Src-associated in mitosis of 68 kD), a KH domain RNA-binding protein, is not only important in signaling transduction cascades, but crucial in a variety of cellular processes. Sam68 is reported to be involved in the phospoinositide3-kinase (PI3K) and nuclear factor-kappa B (NF-κB) signaling pathways, and it is closely associated with cell proliferation, RNA metabolism, and tumor progression. However, we know little about the role of Sam68 during peripheral nervous system injury and regeneration. In this study, we investigated the expression of Sam68 and its biological significances in sciatic nerve crush. Interestingly, we found Sam68 had a co-localization with S100 (Schwann cell marker). Moreover, after crush, Sam68 had a spatiotemporal protein expression, which was in parallel with proliferation cell nuclear antigen (PCNA). In vitro, we also observed increased expression of Sam68 during the process of TNF-α-induced Schwann cell proliferation model. Besides, flow cytometry analyses, CCK-8, and EDU were all performed with the purpose of investigating the role of Sam68 in the regulation of Schwann cell proliferation. Even more importantly, we discovered that Sam68 could enhance the phosphorylation of Akt while LY294002 (a PI3K inhibitor) obviously reversed Sam68-induced cell proliferation. Finally, we detected the variance during regeneration progress through the rat walk footprint test. In summary, all these evidences demonstrated that Sam68 might participate in Schwann cell proliferation partially via PI3K/Akt pathway and also regulate regeneration after sciatic nerve crush. -- Highlights: •The dynamic changes and location of Sam68 after sciatic nerve crush. •Sam68 promoted Schwann cell proliferation via PI3K/Akt pathway. •Sam68 modulated functional recovery after sciatic nerve crush.

  18. Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush

    International Nuclear Information System (INIS)

    Wu, Weijie; Liu, Yuxi; Wang, Youhua

    2016-01-01

    Sam68 (Src-associated in mitosis of 68 kD), a KH domain RNA-binding protein, is not only important in signaling transduction cascades, but crucial in a variety of cellular processes. Sam68 is reported to be involved in the phospoinositide3-kinase (PI3K) and nuclear factor-kappa B (NF-κB) signaling pathways, and it is closely associated with cell proliferation, RNA metabolism, and tumor progression. However, we know little about the role of Sam68 during peripheral nervous system injury and regeneration. In this study, we investigated the expression of Sam68 and its biological significances in sciatic nerve crush. Interestingly, we found Sam68 had a co-localization with S100 (Schwann cell marker). Moreover, after crush, Sam68 had a spatiotemporal protein expression, which was in parallel with proliferation cell nuclear antigen (PCNA). In vitro, we also observed increased expression of Sam68 during the process of TNF-α-induced Schwann cell proliferation model. Besides, flow cytometry analyses, CCK-8, and EDU were all performed with the purpose of investigating the role of Sam68 in the regulation of Schwann cell proliferation. Even more importantly, we discovered that Sam68 could enhance the phosphorylation of Akt while LY294002 (a PI3K inhibitor) obviously reversed Sam68-induced cell proliferation. Finally, we detected the variance during regeneration progress through the rat walk footprint test. In summary, all these evidences demonstrated that Sam68 might participate in Schwann cell proliferation partially via PI3K/Akt pathway and also regulate regeneration after sciatic nerve crush. -- Highlights: •The dynamic changes and location of Sam68 after sciatic nerve crush. •Sam68 promoted Schwann cell proliferation via PI3K/Akt pathway. •Sam68 modulated functional recovery after sciatic nerve crush.

  19. Standard Operating Procedure (SOP) on Planting and Maintenance of Orchid at Malaysian Nuclear Agency

    International Nuclear Information System (INIS)

    Othman Abu Sari; Suhaimi Musa; Affrida Abu Hassan

    2015-01-01

    Research on orchid mutation breeding has been carried out at Malaysian Nuclear Agency since 1990s. In this study, a large number of irradiated orchid seedlings were planted for screening and the mutants obtained were propagated from time to time. Care should be taken to make sure plants are healthy, hence resulted in reliable and accurate data. For this purpose, SOP for orchid cultivation and maintenance need to be developed. A short attachment on training was carried at Hexagon Green Sdn. Bhd orchid farm, Bukit Changgang, Banting. Besides learning the cultivation, maintenance and management of orchids, consequently the experience obtained from this attachment helped in preparing SOP at Malaysian Nuclear Agency. This paper will discuss the SOP on cultivation and maintenance of orchid from the hardening until maturation stage in the glass house to ensure plants are healthy, produce of high quality flowers and disease free. (author)

  20. [Advantages and disadvantages of different methods for the implementation and the support of standard operating procedures: From PDF files to an app- and webbased SOP management system].

    Science.gov (United States)

    Bauer, M; Riech, S; Brandes, I; Waeschle, R M

    2015-11-01

    The quality assurance of care and patient safety, with increasing cost pressure and performance levels is of major importance in the high-risk and high cost area of the operating room (OR). Standard operating procedures (SOP) are an established tool for structuring and standardization of the clinical treatment pathways and show multiple benefits for quality assurance and process optimization. An internal project was initiated in the department of anesthesiology and a continuous improvement process was carried out to build up a comprehensive SOP library. In the first step the spectrum of procedures in anesthesiology was transferred to PDF-based SOPs. The further development to an app-based SOP library (Aesculapp) was due to the high resource expenditure for the administration and maintenance of the large PDF-based SOP collection and to deficits in the mobile availability. The next developmental stage, the SOP healthcare information assistant (SOPHIA) included a simplified and advanced update feature, an archive feature previously missing and notably the possibility to share the SOP library with other departments including the option to adapt each SOP to the individual situation. A survey of the personnel showed that the app-based allocation of SOPs (Aesculapp, SOPHIA) had a higher acceptance than the PDF-based developmental stage SOP form. The SOP management system SOPHIA combines the benefits of the forerunner version Aesculapp with improved options for intradepartmental maintenance and administration of the SOPs and the possibility of an export and editing function for interinstitutional exchange of SOPs.

  1. System Advisor Model, SAM 2014.1.14: General Description

    Energy Technology Data Exchange (ETDEWEB)

    Blair, Nate [National Renewable Energy Lab. (NREL), Golden, CO (United States); Dobos, Aron P. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Freeman, Janine [National Renewable Energy Lab. (NREL), Golden, CO (United States); Neises, Ty [National Renewable Energy Lab. (NREL), Golden, CO (United States); Wagner, Michael [National Renewable Energy Lab. (NREL), Golden, CO (United States); Ferguson, Tom [Global Resources, Northbrook, IL (United States); Gilman, Paul [National Renewable Energy Lab. (NREL), Golden, CO (United States); Janzou, Steven [Janzou Consulting, Idaho Springs, CO (United States)

    2014-02-01

    This document describes the capabilities of the U.S. Department of Energy and National Renewable Energy Laboratory's System Advisor Model (SAM), Version 2013.9.20, released on September 9, 2013. SAM is a computer model that calculates performance and financial metrics of renewable energy systems. Project developers, policy makers, equipment manufacturers, and researchers use graphs and tables of SAM results in the process of evaluating financial, technology, and incentive options for renewable energy projects. SAM simulates the performance of photovoltaic, concentrating solar power, solar water heating, wind, geothermal, biomass, and conventional power systems. The financial model can represent financial structures for projects that either buy and sell electricity at retail rates (residential and commercial) or sell electricity at a price determined in a power purchase agreement (utility). SAM's advanced simulation options facilitate parametric and sensitivity analyses, and statistical analysis capabilities are available for Monte Carlo simulation and weather variability (P50/P90) studies. SAM can also read input variables from Microsoft Excel worksheets. For software developers, the SAM software development kit (SDK) makes it possible to use SAM simulation modules in their applications written in C/C++, C#, Java, Python, and MATLAB. NREL provides both SAM and the SDK as free downloads at http://sam.nrel.gov. Technical support and more information about the software are available on the website.

  2. Modelo de dinâmica de sistemas para o processo de S&OP ampliado

    Directory of Open Access Journals (Sweden)

    Jean Carlos Domingos

    2015-01-01

    Full Text Available ResumoApesar de o processo de S&OP (Sales and Operations Planning não ser uma prática nova nas empresas, principalmente naquelas de grande porte, ainda é tema de estudos nas suas práticas e ferramentas computacionais de apoio. Modelos e ferramentas computacionais focadas para o auxílio no processo de S&OP são utilizadas e podem contribuir para a melhoria da qualidade da sua execução e dos seus resultados. As ferramentas mais comuns são aquelas baseadas em planilhas eletrônicas, e as mais sofisticadas, em técnicas de pesquisa operacional inseridas em sistemas APS (Advanced Planning Systems. A partir da revisão bibliográfica realizada sobre teoria e técnicas computacionais usadas para o auxílio do processo de S&OP, foi identificada a ausência de estudos relacionados ao uso de Dinâmica de Sistemas (System Dynamics. Adicionalmente, a revisão aponta a necessidade de estudos relacionados à integração de análise econômica e financeira durante a elaboração dos planos agregados e o uso de variáveis probabilísticas no processo que possibilitem a análise estatística no sentido de fornecer planos mais confiáveis. Outra questão relevante observada é que os gestores que participam do processo de S&OP nem sempre têm uma visão global de todas as variáveis e restrições envolvidas neste processo, assim observa-se também que as técnicas e ferramentas utilizadas para execução do processo de S&OP não oferecem uma visão holística das atividades e variáveis envolvidas. Com isso, neste trabalho, é proposto um modelo de Simulação de Dinâmica de Sistemas que proporcione uma visão holística para o processo de S&OP e que permita a integração com os processos da área financeira e o uso de variáveis probabilísticas. A avaliação dos resultados das simulações realizadas com o modelo, apoiada por um projeto de experimentos (DoE, mostra que os planos gerados são compatíveis se comparados com a prática empresarial

  3. Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68

    Science.gov (United States)

    Feracci, Mikael; Foot, Jaelle N.; Grellscheid, Sushma N.; Danilenko, Marina; Stehle, Ralf; Gonchar, Oksana; Kang, Hyun-Seo; Dalgliesh, Caroline; Meyer, N. Helge; Liu, Yilei; Lahat, Albert; Sattler, Michael; Eperon, Ian C.; Elliott, David J.; Dominguez, Cyril

    2016-01-01

    Sam68 and T-STAR are members of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins. T-STAR is a tissue-specific paralogue that regulates the alternative splicing of neuronal pre-mRNAs. STAR proteins differ from most splicing factors, in that they contain a single RNA-binding domain. Their specificity of RNA recognition is thought to arise from their property to homodimerize, but how dimerization influences their function remains unknown. Here, we establish at atomic resolution how T-STAR and Sam68 bind to RNA, revealing an unexpected mode of dimerization different from other members of the STAR family. We further demonstrate that this unique dimerization interface is crucial for their biological activity in splicing regulation, and suggest that the increased RNA affinity through dimer formation is a crucial parameter enabling these proteins to select their functional targets within the transcriptome. PMID:26758068

  4. 核蛋白Sam68的原核表达及鉴定%Prokaryotic Expression and Identification of Nuclear Protein Sam68

    Institute of Scientific and Technical Information of China (English)

    张华; 陈宁; 丁筠; 邹德华; 潘子夜; 李鹏飞; 李丽阳; 肖丽杰; 曹宏伟

    2017-01-01

    为了构建pGEX-4T-1-Sam68原核表达载体,表达并鉴定GST-Sam68融合蛋白,采用PCR扩增Sam68基因,插入pGEX-4T-1的EcoR I和Sal I位点,并转化Rosetta(DE3)大肠杆菌,IPTG诱导表达,SDS-PAGE和Western Blot验证蛋白表达,GST pull-down技术验证Sam68的结合活性.酶切和测序结果证实Sam68基因正确插入pGEX-4T-1载体中,载体能够在Rosetta(DE3)细胞中正确表达,且纯化的GST-Sam68蛋白具有与PI3K p85特异结合的活性,说明成功构建了原核表达载体pGEX-4T-1-Sam68.

  5. Cooperation between Magnesium and Metabolite Controls Collapse of the SAM-I Riboswitch.

    Science.gov (United States)

    Roy, Susmita; Onuchic, José N; Sanbonmatsu, Karissa Y

    2017-07-25

    The S-adenosylmethionine (SAM)-I riboswitch is a noncoding RNA that regulates the transcription termination process in response to metabolite (SAM) binding. The aptamer portion of the riboswitch may adopt an open or closed state depending on the presence of metabolite. Although the transition between the open and closed states is critical for the switching process, its atomistic details are not well understood. Using atomistic simulations, we calculate the effect of SAM and magnesium ions on the folding free energy landscape of the SAM-I riboswitch. These molecular simulation results are consistent with our previous wetlab experiments and aid in interpreting the SHAPE probing measurements. Here, molecular dynamics simulations explicitly identify target RNA motifs sensitive to magnesium ions and SAM. In the simulations, we observe that, whereas the metabolite mostly stabilizes the P1 and P3 helices, magnesium serves an important role in stabilizing a pseudoknot interaction between the P2 and P4 helices, even at high metabolite concentrations. The pseudoknot stabilization by magnesium, in combination with P1 stabilization by SAM, explains the requirement of both SAM and magnesium to form the fully collapsed metabolite-bound closed state of the SAM-I riboswitch. In the absence of SAM, frequent open-to-closed conformational transitions of the pseudoknot occur, akin to breathing. These pseudoknot fluctuations disrupt the binding site by facilitating fluctuations in the 5'-end of helix P1. Magnesium biases the landscape toward a collapsed state (preorganization) by coordinating pseudoknot and 5'-P1 fluctuations. The cooperation between SAM and magnesium in stabilizing important tertiary interactions elucidates their functional significance in transcription regulation. Published by Elsevier Inc.

  6. Surface adhesion and confinement variation of Staphylococcus aurius on SAM surfaces

    Science.gov (United States)

    Amroski, Alicia; Olsen, Morgan; Calabrese, Joseph; Senevirathne, Reshani; Senevirathne, Indrajith

    2012-02-01

    Controlled surface adhesion of non - pathogenic gram positive strain, Staphylococcus aureus is interesting as a model system due to possible development of respective biosensors for prevention and detection of the pathogenic strain methicillin resistant Staphylococcus aureus (MRSA) and further as a study for bio-machine interfacing. Self Assembled Monolayers (SAM) with engineered surfaces of linear thiols on Au(111) were used as the substrate. Sub cultured S. aureus were used for the analysis. The SAM layered surfaces were dipped in 2 -- 4 Log/ml S. aureus solution. Subsequent surface adhesion at different bacterial dilutions on surfaces will be discussed, and correlated with quantitative and qualitative adhesion properties of bacteria on the engineered SAM surfaces. The bacteria adhered SAM surfaces were investigated using intermittent contact, noncontact, lateral force and contact modes of Atomic Force Microscopy (AFM).

  7. Studi Kasus Pada Penerapan Sop Inventori Lobby Bar Shangri-la Hotel and Resort Surabaya : Pengamatan Terhadap Prosedur Pengambilan Bahan, Penyimpanan Serta Perlakuan Selama Penyimpanan Bahan

    OpenAIRE

    Widjojo, Gerald; Kusumawidjaya, Amanda

    2013-01-01

    Penelitian ini dilakukan untuk mengetahui sejauh mana pemahaman staff dari Lobby Lounge Shangri-La Hotel Surabaya terhadap SOP pada inventori bahan yang ada. SOP ini dirasa penting dalam operasional lobby sehari-hari. Penelitian ini merupakan penelitian deskriptif dengan menggunakan wawancara dan checklist dalam menghasilkan data untuk dianalisa. Hasil penelitian menunjukkan bahwa sebagian besar staf sudah memahami SOP yang ada dan sudah mampu menjalankan SOP yang ada dengan baik.

  8. Bringing a Chemical Laboratory Named Sam to Mars on the 2011 Curiosity Rover

    Science.gov (United States)

    Mahaffy, P. R.; Bleacher, L.; Jones, A.; Atreya, S. K.; Manning, H. L.; Cabane, M.; Webster, C. R.; Sam Team

    2010-12-01

    Introduction: An important goal of upcoming missions to Mars is to understand if life could have developed there. The task of the Sample Analysis at Mars (SAM) suite of instruments [1] and the other Curiosity investigations [2] is to move us steadily toward that goal with an assessment of the habitability of our neighboring planet through a series of chemical and geological measurements. SAM is designed to search for organic compounds and inorganic volatiles and measure isotope ratios. Other instruments on Curiosity will provide elemental analysis and identify minerals. SAM will analyze both atmospheric samples and gases evolved from powdered rocks that may have formed billions of years ago with Curiosity providing access to interesting sites scouted by orbiting cameras and spectrometers. SAM Instrument Suite: SAM’s instruments are a Quadrupole Mass Spectrometer (QMS), a 6-column Gas Chromatograph (GC), and a 2-channel Tunable Laser Spectrometer (TLS). SAM can identify organic compounds in Mars rocks to sub-ppb sensitivity and secure precise isotope ratios for C, H, and O in carbon dioxide and water and measure trace levels of methane and its carbon 13 isotope. The SAM gas processing system consists of valves, heaters, pressure sensors, gas scrubbers and getters, traps, and gas tanks used for calibration or combustion experiments [2]. A variety of calibrant compounds interior and exterior to SAM will allow the science and engineering teams to assess SAM’s performance. SAM has been calibrated and tested in a Mars-like environment. Keeping Educators and the Public Informed: The Education and Public Outreach (EPO) goals of the SAM team are to make this complex chemical laboratory and its data widely available to educators, students, and the public. Formal education activities include developing templates for professional development workshops for educators to teach them about SAM and Curiosity, incorporating data into Mars Student Data Teams, and writing articles

  9. GoSam-2.0. A tool for automated one-loop calculations within the Standard Model and beyond

    International Nuclear Information System (INIS)

    Cullen, Gavin; Deurzen, Hans van; Greiner, Nicolas

    2014-05-01

    We present the version 2.0 of the program package GoSam for the automated calculation of one-loop amplitudes. GoSam is devised to compute one-loop QCD and/or electroweak corrections to multi-particle processes within and beyond the Standard Model. The new code contains improvements in the generation and in the reduction of the amplitudes, performs better in computing time and numerical accuracy, and has an extended range of applicability. The extended version of the ''Binoth-Les-Houches-Accord'' interface to Monte Carlo programs is also implemented. We give a detailed description of installation and usage of the code, and illustrate the new features in dedicated examples.

  10. Storifying Samsøs Renewable Energy Transition

    DEFF Research Database (Denmark)

    Papazu, Irina

    2018-01-01

    Through a joint community effort Denmark’s Renewable Energy Island Samsø became self-sufficient with renewable energy over a period of 10 years from 1997 to 2007. Today, the story about Samsø’s successful energy transition has become a global export and a widely known model of community building...... the effects of such well-crafted transition narratives. This tendency toward the ‘storification’ of transition processes is not restricted to Samsø; it is employed as a tactics by environmental organizations operating globally....

  11. [Advanced Trauma Life Support (ATLS) in the emergency room. Is it suitable as an SOP?].

    Science.gov (United States)

    Shafizadeh, S; Tjardes, T; Steinhausen, E; Balke, M; Paffrath, T; Bouillon, B; Bäthis, H

    2010-08-01

    There is clinical evidence that a standardized management of trauma patients in the emergency room improves outcome. ATLS is a training course that teaches a systematic approach to the trauma patient in the emergency room. The aims are a rapid and accurate assessment of the patient's physiologic status, treatment according to priorities, and making decisions on whether the local resources are sufficient for adequate definitive treatment of the patient or if transfer to a trauma center is necessary. Above all it is important to prevent secondary injury, to realize timing as a relevant factor in the initial treatment, and to assure a high standard of care. A standard operating procedure (SOP) exactly regulates the approach to trauma patients and determines the responsibilities of the involved faculties. An SOP moreover incorporates the organizational structure in the treatment of trauma patients as well as the necessary technical equipment and staff requirements. To optimize process and result quality, priorities are in the fields of medical fundamentals of trauma care, education, and fault management. SOPs and training courses increase the process and result quality in the treatment of the trauma patient in the emergency room. These programs should be based on the special demands of the physiology of the trauma as well as the structural specifics of the hospital. ATLS does not equal an SOP but it qualifies as a standardized concept for management of trauma patients in the emergency room.

  12. Unanticipated coordination of tris buffer to the Radical SAM cluster of the RimO methylthiotransferase.

    Science.gov (United States)

    Molle, Thibaut; Clémancey, Martin; Latour, Jean-Marc; Kathirvelu, Velavan; Sicoli, Giuseppe; Forouhar, Farhad; Mulliez, Etienne; Gambarelli, Serge; Atta, Mohamed

    2016-07-01

    Radical SAM enzymes generally contain a [4Fe-4S](2+/1+) (RS cluster) cluster bound to the protein via the three cysteines of a canonical motif CxxxCxxC. The non-cysteinyl iron is used to coordinate SAM via its amino-carboxylate moiety. The coordination-induced proximity between the cluster acting as an electron donor and the adenosyl-sulfonium bond of SAM allows for the homolytic cleavage of the latter leading to the formation of the reactive 5'-deoxyadenosyl radical used for substrate activation. Most of the structures of Radical SAM enzymes have been obtained in the presence of SAM, and therefore, little is known about the situation when SAM is not present. In this report, we show that RimO, a methylthiotransferase belonging to the radical SAM superfamily, binds a Tris molecule in the absence of SAM leading to specific spectroscopic signatures both in Mössbauer and pulsed EPR spectroscopies. These data provide a cautionary note for researchers who work with coordinative unsaturated iron sulfur clusters.

  13. Amine terminated SAMs: Investigating why oxygen is present in these films

    International Nuclear Information System (INIS)

    Baio, J.E.; Weidner, T.; Brison, J.; Graham, D.J.; Gamble, Lara J.; Castner, David G.

    2009-01-01

    Self-assembled monolayers (SAMs) on gold prepared from amine-terminated alkanethiols have long been employed as model positively charged surfaces. Yet in previous studies significant amounts of unexpected oxygen containing species are always detected in amine terminated SAMs. Thus, the goal of this investigation was to determine the source of these oxygen species and minimize their presence in the SAM. The surface composition, structure, and order of amine-terminated SAMs on Au were characterized by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), sum frequency generation (SFG) and near edge X-ray absorption fine structure (NEXAFS) spectroscopy. XPS determined compositions of amine-terminated SAMs in the current study exhibited oxygen concentrations of 2.4 ± 0.4 atomic %, a substantially lower amount of oxygen than reported in previously published studies. High-resolution XPS results from the S 2p , C 1s and N 1s regions did not detect any oxidized species. Angle-resolved XPS indicated that the small amount of oxygen detected was located at or near the amine head group. Small amounts of oxidized nitrogen, carbon and sulfur secondary ions, as well as ions attributed to water, were detected in the ToF-SIMS data due to the higher sensitivity of ToF-SIMS. The lack of N-O, S-O, and C-O stretches in the SFG spectra are consistent with the XPS and ToF-SIMS results and together show that oxidation of the amine-terminated thiols alone can only account for, at most, a small fraction of the oxygen detected by XPS. Both the SFG and angle-dependent NEXAFS indicated the presence of gauche defects in the amine SAMs. However, the SFG spectral features near 2865 cm -1 , assigned to the stretch of the methylene group next to the terminal amine unit, demonstrate the SAM is reasonably ordered. The SFG results also show another broad feature near 3200 cm -1 related to hydrogen-bonded water. From this multi-technique investigation it is

  14. Samâ’ dalam Tradisi Tasawuf

    Directory of Open Access Journals (Sweden)

    Said Aqil Siradj

    2014-01-01

    Full Text Available Samâ‘ in Tasawuf has been a very important element in the dissemination of this spiritual dimension of Islam. Yet, it has received very little both from the practitioners of Tasawuf and its intellectuals. This paper tries to expose this simply in a hope to make it heard in the academic and popular circle. Here, samâ‘ is not only understood as a form of music, as many would do, but also as an art of listening of which music is certainly part. The paper will explore the meaning and definition of this term, putting emphasis on its many-faceted function in the formation and development of one’s soul and spirituality. It is argued that soul is musical and artistic. Using art and music to talk to soul is therefore the proper way and means. The paper will also try to show that samâ‘ is also an indispensable part of spiritual method to reach and know God. Knowledge of God in other words, can be gained through this practice. Hence, samâ‘ is treated not only as a form of entertainment, but also a kind of practical epistemology.

  15. The multi-state energy landscape of the SAM-I riboswitch: A single-molecule Förster resonance energy transfer spectroscopy study

    Science.gov (United States)

    Manz, Christoph; Kobitski, Andrei Yu.; Samanta, Ayan; Jäschke, Andres; Nienhaus, G. Ulrich

    2018-03-01

    RNA (ribonucleic acid) molecules are highly flexible biopolymers fluctuating at physiological temperatures among many different conformations that are represented by minima in a hierarchical conformational free energy landscape. Here we have employed single-molecule FRET (smFRET) to explore the energy landscape of the B. subtilis yitJ SAM-I riboswitch (RS). In this small RNA molecule, specific binding of an S-adenosyl-L-methionine (SAM) ligand in the aptamer domain regulates gene expression by inducing structural changes in another domain, the expression platform, causing transcription termination by the RNA polymerase. We have measured smFRET histograms over wide ranges of Mg2+ concentration for three RS variants that were specifically labeled with fluorescent dyes on different sites. In the analysis, different conformations are associated with discrete Gaussian model distributions, which are typically fairly broad on the FRET efficiency scale and thus can be extremely challenging to unravel due to their mutual overlap. Our earlier work on two SAM-I RS variants revealed four major conformations. By introducing a global fitting procedure which models both the Mg2+ concentration dependencies of the fractional populations and the average FRET efficiencies of the individual FRET distributions according to Mg2+ binding isotherms, we were able to consistently describe the histogram data of both variants at all studied Mg2+ concentrations. With the third FRET-labeled variant, however, we found significant deviations when applying the four-state model to the data. This can arise because the different FRET labeling of the new variant allows two states to be distinguished that were previously not separable due to overlap. Indeed, the resulting five-state model presented here consistently describes the smFRET histograms of all three variants as well as their variations with Mg2+ concentration. We also performed a triangulation of the donor position for two of the constructs

  16. The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells

    International Nuclear Information System (INIS)

    Lawrence, Paul; Schafer, Elizabeth A.; Rieder, Elizabeth

    2012-01-01

    Picornavirus infection can lead to disruption of nuclear pore traffic, shut-off of cell translation machinery, and cleavage of proteins involved in cellular signal transduction and the innate response to infection. Here, we demonstrated that the FMDV 3C pro induced the cleavage of nuclear RNA-binding protein Sam68 C-terminus containing the nuclear localization sequence (NLS). Consequently, it stimulated the redistribution of Sam68 to the cytoplasm. The siRNA knockdown of Sam68 resulted in a 1000-fold reduction in viral titers, which prompted us to study the effect of Sam68 on FMDV post-entry events. Interestingly, Sam68 interacts with the internal ribosomal entry site within the 5′ non-translated region of the FMDV genome, and Sam68 knockdown decreased FMDV IRES-driven activity in vitro suggesting that it could modulate translation of the viral genome. The results uncover a novel role for Sam68 in the context of picornaviruses and the proteolysis of a new cellular target of the FMDV 3C pro .

  17. Experimental and computational investigation of graphene/SAMs/n-Si Schottky diodes

    Science.gov (United States)

    Aydin, H.; Bacaksiz, C.; Yagmurcukardes, N.; Karakaya, C.; Mermer, O.; Can, M.; Senger, R. T.; Sahin, H.; Selamet, Y.

    2018-01-01

    We have investigated the effect of two different self-assembled monolayers (SAMs) on electrical characteristics of bilayer graphene (BLG)/n-Si Schottky diodes. Novel 4″bis(diphenylamino)-1, 1‧:3″-terphenyl-5‧ carboxylic acids (TPA) and 4,4-di-9H-carbazol-9-yl-1,1‧:3‧1‧-terphenyl-5‧ carboxylic acid (CAR) aromatic SAMs have been used to modify n-Si surfaces. Cyclic voltammetry (CV) and Kelvin probe force microscopy (KPFM) results have been evaluated to verify the modification of n-Si surface. The current-voltage (I-V) characteristics of bare and SAMs modified devices show rectification behaviour verifying a Schottky junction at the interface. The ideality factors (n) from ln(I)-V dependences were determined as 2.13, 1.96 and 2.07 for BLG/n-Si, BLG/TPA/n-Si and BLG/CAR/n-Si Schottky diodes, respectively. In addition, Schottky barrier height (SBH) and series resistance (Rs) of SAMs modified diodes were decreased compared to bare diode due to the formation of a compatible interface between graphene and Si as well as π-π interaction between aromatic SAMs and graphene. The CAR-based device exhibits better diode characteristic compared to the TPA-based device. Computational simulations show that the BLG/CAR system exhibits smaller energy-level-differences than the BLG/TPA, which supports the experimental findings of a lower Schottky barrier and series resistance in BLG/CAR diode.

  18. Technical Manual for the SAM Physical Trough Model

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, M. J.; Gilman, P.

    2011-06-01

    NREL, in conjunction with Sandia National Lab and the U.S Department of Energy, developed the System Advisor Model (SAM) analysis tool for renewable energy system performance and economic analysis. This paper documents the technical background and engineering formulation for one of SAM's two parabolic trough system models in SAM. The Physical Trough model calculates performance relationships based on physical first principles where possible, allowing the modeler to predict electricity production for a wider range of component geometries than is possible in the Empirical Trough model. This document describes the major parabolic trough plant subsystems in detail including the solar field, power block, thermal storage, piping, auxiliary heating, and control systems. This model makes use of both existing subsystem performance modeling approaches, and new approaches developed specifically for SAM.

  19. 24-GHz LTCC Fractal Antenna Array SoP With Integrated Fresnel Lens

    KAUST Repository

    Ghaffar, Farhan A.; Khalid, Muhammad Umair; Salama, Khaled N.; Shamim, Atif

    2012-01-01

    A novel 24-GHz mixed low-temperature co-fired ceramic (LTCC) tape based system-on-package (SoP) is presented, which incorporates a fractal antenna array with an integrated grooved Fresnel lens. The four-element fractal array employs a relatively low

  20. Three-dimensional RF SoP technologies: LTCC versus LCP

    KAUST Repository

    Arabi, Eyad A.

    2014-12-18

    The system on package (SoP) is an emerging platform, introduced to provide enhanced functionality, and immense miniaturization through vertically integrated passive components in a multilayer process. This way the package is not a mere holder or cover but is a functional part of the system. The leading multilayer packaging technologies for SoP designs: low temperature co-fired ceramic (LTCC) and liquid crystal polymer (LCP) are compared in this work for the first time. Passive components and filters have been implemented in both technologies to show the advantages of the three-dimensional nature of these technologies. The comparison results show that parallel plate capacitors implemented in the ultra-thin LCP provides the highest capacitance density. For spiral inductors, conversely, LTCC inductors have the highest inductances while LCP inductors offer the highest self-resonant frequencies and the highest quality factors (Q). In a circuit level, simulated and measured results of a bandpass filter at 1.5 GHz show that both LCP and LTCC can provide similar performances with an incredible size reduction for the case of ultra-thin LCP. Also, the thin LCP filter exhibits a large degree of mechanical flexibility which makes this technology suitable for future flexible modules.

  1. Information System through ANIS at CeSAM

    Science.gov (United States)

    Moreau, C.; Agneray, F.; Gimenez, S.

    2015-09-01

    ANIS (AstroNomical Information System) is a web generic tool developed at CeSAM to facilitate and standardize the implementation of astronomical data of various kinds through private and/or public dedicated Information Systems. The architecture of ANIS is composed of a database server which contains the project data, a web user interface template which provides high level services (search, extract and display imaging and spectroscopic data using a combination of criteria, an object list, a sql query module or a cone search interfaces), a framework composed of several packages, and a metadata database managed by a web administration entity. The process to implement a new ANIS instance at CeSAM is easy and fast : the scientific project has to submit data or a data secure access, the CeSAM team installs the new instance (web interface template and the metadata database), and the project administrator can configure the instance with the web ANIS-administration entity. Currently, the CeSAM offers through ANIS a web access to VO compliant Information Systems for different projects (HeDaM, HST-COSMOS, CFHTLS-ZPhots, ExoDAT,...).

  2. 78 FR 47695 - Sam Rayburn Dam Power Rate

    Science.gov (United States)

    2013-08-06

    ... DEPARTMENT OF ENERGY Southwestern Power Administration Sam Rayburn Dam Power Rate AGENCY: Southwestern Power Administration, DOE. ACTION: Notice of public review and comment. SUMMARY: The current Sam..., Southwestern Power Administration (Southwestern), has prepared Current and Revised 2013 Power Repayment Studies...

  3. Estudio del riesgo cardiovascular en pacientes con Síndrome de Ovario Poliquístico (SOP). Creación de grupos de riesgo.

    OpenAIRE

    García Gamón Valero, Marta

    2015-01-01

    El SOP es la endocrinopatía más frecuente en la mujer en edad reproductiva. Muchos son los estudios que se han realizado para poder identificar si la presencia del SOP es per se un factor de riesgo cardiovascular. El hecho de que el SOP presente una serie de patologías asociadas que son factores de riesgo cardiovascular hace que sea complicado esclarecer si la elevación del riesgo cardiovascular en estas pacientes se debe fundamentalmente al síndrome. La presencia de factores de confusión com...

  4. Sop-GPU: accelerating biomolecular simulations in the centisecond timescale using graphics processors.

    Science.gov (United States)

    Zhmurov, A; Dima, R I; Kholodov, Y; Barsegov, V

    2010-11-01

    Theoretical exploration of fundamental biological processes involving the forced unraveling of multimeric proteins, the sliding motion in protein fibers and the mechanical deformation of biomolecular assemblies under physiological force loads is challenging even for distributed computing systems. Using a C(α)-based coarse-grained self organized polymer (SOP) model, we implemented the Langevin simulations of proteins on graphics processing units (SOP-GPU program). We assessed the computational performance of an end-to-end application of the program, where all the steps of the algorithm are running on a GPU, by profiling the simulation time and memory usage for a number of test systems. The ∼90-fold computational speedup on a GPU, compared with an optimized central processing unit program, enabled us to follow the dynamics in the centisecond timescale, and to obtain the force-extension profiles using experimental pulling speeds (v(f) = 1-10 μm/s) employed in atomic force microscopy and in optical tweezers-based dynamic force spectroscopy. We found that the mechanical molecular response critically depends on the conditions of force application and that the kinetics and pathways for unfolding change drastically even upon a modest 10-fold increase in v(f). This implies that, to resolve accurately the free energy landscape and to relate the results of single-molecule experiments in vitro and in silico, molecular simulations should be carried out under the experimentally relevant force loads. This can be accomplished in reasonable wall-clock time for biomolecules of size as large as 10(5) residues using the SOP-GPU package. © 2010 Wiley-Liss, Inc.

  5. The characteristics of the Westinghouse accident procedures and the main differences with SOP

    International Nuclear Information System (INIS)

    Hu Yan; Gan Peijiang; Sun Chen

    2014-01-01

    In this note, the Westinghouse operation file system is summarized. The structures of procedures, design methods, implementation logics of the Westinghouse accident procedures are discussed. And compared with the SOP principles, the main differences are clarified. (authors)

  6. A New Structural Form in the SAM/Metal-Dependent O;#8209;Methyltransferase Family: MycE from the Mycinamicin Biosynthetic Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Akey, David L.; Li, Shengying; Konwerski, Jamie R.; Confer, Laura A.; Bernard, Steffen M.; Anzai, Yojiro; Kato, Fumio; Sherman, David H.; Smith, Janet L. (Michigan); (Toho)

    2012-08-01

    O-linked methylation of sugar substituents is a common modification in the biosynthesis of many natural products and is catalyzed by multiple families of S-adenosyl-l-methionine (SAM or AdoMet)-dependent methyltransferases (MTs). Mycinamicins, potent antibiotics from Micromonospora griseorubida, can be methylated at two positions on a 6-deoxyallose substituent. The first methylation is catalyzed by MycE, a SAM- and metal-dependent MT. Crystal structures were determined for MycE bound to the product S-adenosyl-l-homocysteine (AdoHcy) and magnesium, both with and without the natural substrate mycinamicin VI. This represents the first structure of a natural product sugar MT in complex with its natural substrate. MycE is a tetramer of a two-domain polypeptide, comprising a C-terminal catalytic MT domain and an N-terminal auxiliary domain, which is important for quaternary assembly and for substrate binding. The symmetric MycE tetramer has a novel MT organization in which each of the four active sites is formed at the junction of three monomers within the tetramer. The active-site structure supports a mechanism in which a conserved histidine acts as a general base, and the metal ion helps to position the methyl acceptor and to stabilize a hydroxylate intermediate. A conserved tyrosine is suggested to support activity through interactions with the transferred methyl group from the SAM methyl donor. The structure of the free enzyme reveals a dramatic order-disorder transition in the active site relative to the S-adenosyl-L-homocysteine complexes, suggesting a mechanism for product/substrate exchange through concerted movement of five loops and the polypeptide C-terminus.

  7. The SAMS: Smartphone Addiction Management System and verification.

    Science.gov (United States)

    Lee, Heyoung; Ahn, Heejune; Choi, Samwook; Choi, Wanbok

    2014-01-01

    While the popularity of smartphones has given enormous convenience to our lives, their pathological use has created a new mental health concern among the community. Hence, intensive research is being conducted on the etiology and treatment of the condition. However, the traditional clinical approach based surveys and interviews has serious limitations: health professionals cannot perform continual assessment and intervention for the affected group and the subjectivity of assessment is questionable. To cope with these limitations, a comprehensive ICT (Information and Communications Technology) system called SAMS (Smartphone Addiction Management System) is developed for objective assessment and intervention. The SAMS system consists of an Android smartphone application and a web application server. The SAMS client monitors the user's application usage together with GPS location and Internet access location, and transmits the data to the SAMS server. The SAMS server stores the usage data and performs key statistical data analysis and usage intervention according to the clinicians' decision. To verify the reliability and efficacy of the developed system, a comparison study with survey-based screening with the K-SAS (Korean Smartphone Addiction Scale) as well as self-field trials is performed. The comparison study is done using usage data from 14 users who are 19 to 50 year old adults that left at least 1 week usage logs and completed the survey questionnaires. The field trial fully verified the accuracy of the time, location, and Internet access information in the usage measurement and the reliability of the system operation over more than 2 weeks. The comparison study showed that daily use count has a strong correlation with K-SAS scores, whereas daily use times do not strongly correlate for potentially addicted users. The correlation coefficients of count and times with total K-SAS score are CC = 0.62 and CC =0.07, respectively, and the t-test analysis for the

  8. Recent Updates to the System Advisor Model (SAM)

    Energy Technology Data Exchange (ETDEWEB)

    DiOrio, Nicholas A [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-02-14

    The System Advisor Model (SAM) is a mature suite of techno-economic models for many renewable energy technologies that can be downloaded for free as a desktop application or software development kit. SAM is used for system-level modeling, including generating performance pro the release of the code as an open source project on GitHub. Other additions that will be covered include the ability to download data directly into SAM from the National Solar Radiation Database (NSRDB) and up- dates to a user-interface macro that assists with PV system sizing. A brief update on SAM's battery model and its integration with the detailed photovoltaic model will also be discussed. Finally, an outline of planned work for the next year will be presented, including the addition of a bifacial model, support for multiple MPPT inputs for detailed inverter modeling, and the addition of a model for inverter thermal behavior.

  9. p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K.

    Science.gov (United States)

    Sánchez-Margalet, V; Najib, S

    1999-07-23

    The 68 kDa Src substrate associated during mitosis is an RNA binding protein with Src homology 2 and 3 domain binding sites. A role for Src associated in mitosis 68 as an adaptor protein in signaling transduction has been proposed in different systems such as T-cell receptors. In the present work, we have sought to assess the possible role of Src associated in mitosis 68 in insulin receptor signaling. We performed in vivo studies in HTC-IR cells and in vitro studies using recombinant Src associated in mitosis 68, purified insulin receptor and fusion proteins containing either the N-terminal or the C-terminal Src homology 2 domain of p85 phosphatidylinositol-3-kinase. We have found that Src associated in mitosis 68 is a substrate of the insulin receptor both in vivo and in vitro. Moreover, tyrosine-phosphorylated Src associated in mitosis 68 was found to associate with p85 phosphatidylinositol-3-kinase in response to insulin, as assessed by co-immunoprecipitation studies. Therefore, Src associated in mitosis 68 may be part of the signaling complexes of insulin receptor along with p85. In vitro studies demonstrate that Src associated in mitosis 68 associates with the Src homology 2 domains of p85 after tyrosine phosphorylation by the activated insulin receptor. Moreover, tyr-phosphorylated Src associated in mitosis 68 binds with a higher affinity to the N-terminal Src homology 2 domain of p85 compared to the C-terminal Src homology 2 domain of p85, suggesting a preferential association of Src associated in mitosis 68 with the N-terminal Src homology 2 domain of p85. This association may be important for the link of the signaling with RNA metabolism.

  10. Projeto de implementação do processo Sales and Operations Planning (S&OP) - caso de estudo

    OpenAIRE

    Lima, Daniela Alexandra de Sousa

    2017-01-01

    Apesar de o conceito de Sales and Operations Planning (S&OP) ter sido introduzido há já algumas décadas, este tem ganho um reconhecimento acrescido, uma vez que a incerteza dos mercados e a crescente complexidade das supply chains aumentam a necessidade de determinar ações futuras e criar um plano de vendas e operações comum. S&OP é um processo multifuncional que promove o desenvolvimento e a aceitação de um plano comum, permitindo o alinhamento entre a oferta e a procura, conecta o planeamen...

  11. The Combustion Experiment on the Sample Analysis at Mars (SAM) Instrument Suite on the Curiosity Rover

    Science.gov (United States)

    Stern, J. C.; Malespin, C. A.; Eigenbrode, J. L.; Graham, H. V.; Archer, P. D., Jr.; Brunner, A. E.; Freissinet, C.; Franz, H. B.; Fuentes, J.; Glavin, D. P.; hide

    2014-01-01

    The combustion experiment on the Sample Analysis at Mars (SAM) suite on Curiosity will heat a sample of Mars regolith in the presence of oxygen and measure composition of the evolved gases using quadrupole mass spectrometry (QMS) and tunable laser spectrometry (TLS). QMS will enable detection of combustion products such as CO, CO2, NO, and other oxidized species, while TLS will enable precise measurements of the abundance and carbon isotopic composition (delta(sup 13)C) of the evolved CO2 and hydrogen isotopic composition (deltaD) of H2O. SAM will perform a two-step combustion to isolate combustible materials below approx.550 C and above approx.550 C. The combustion experiment on SAM, if properly designed and executed, has the potential to answer multiple questions regarding the origins of volatiles seen thus far in SAM evolved gas analysis (EGA) on Mars. Constraints imposed by SAM and MSL time and power resources, as well as SAM consumables (oxygen gas), will limit the number of SAM combustion experiments, so it is imperative to design an experiment targeting the most pressing science questions. Low temperature combustion experiments will primarily target the quantification of carbon (and nitrogen) contributed by SAM wet chemistry reagants MTBSTFA (N-Methyl-N-tert-butyldimethylsilyltrifluoroacetamide) and DMF (Dimethylformamide), which have been identified in the background of blank and sample runs and may adsorb to the sample while the cup is in the Sample Manipulation System (SMS). In addition, differences between the sample and "blank" may yield information regarding abundance and delta(sup 13)C of bulk (both organic and inorganic) martian carbon. High temperature combustion experiments primarily aim to detect refractory organic matter, if present in Cumberland fines, as well as address the question of quantification and deltaD value of water evolution associated with hydroxyl hydrogen in clay minerals.

  12. Optimization of pentacene double floating gate memories based on charge injection regulated by SAM functionalization

    Directory of Open Access Journals (Sweden)

    S. Li

    2018-02-01

    Full Text Available Pentacene based double nano-floating gate memories (NFGM by using gold nanoparticles (Au NPs and reduced graphene oxide (rGO sheets as charge trapping layers are prepared and demonstrated. Particularly, the NFGM chemically treated by 2,3,4,5,6-pentafluorobenzenethiol (PFBT self-assembled monolayers (SAM exhibits excellent memory performances, including high mobility of 0.23 cm2V-1s-1, the large memory window of 51 V, and the stable retention property more than 108 s. Comparing the performances of NFGM without treating with PFBT SAM, the improving performances of the memory devices by SAM modification are explained by the increase of charge injection, which could be further investigated by XPS and UPS. In particular, the results highlight the utility of SAM modulations and controlling of charge transport in the development of organic transistor memories.

  13. Optimization of pentacene double floating gate memories based on charge injection regulated by SAM functionalization

    Science.gov (United States)

    Li, S.; Guérin, D.; Lenfant, S.; Lmimouni, K.

    2018-02-01

    Pentacene based double nano-floating gate memories (NFGM) by using gold nanoparticles (Au NPs) and reduced graphene oxide (rGO) sheets as charge trapping layers are prepared and demonstrated. Particularly, the NFGM chemically treated by 2,3,4,5,6-pentafluorobenzenethiol (PFBT) self-assembled monolayers (SAM) exhibits excellent memory performances, including high mobility of 0.23 cm2V-1s-1, the large memory window of 51 V, and the stable retention property more than 108 s. Comparing the performances of NFGM without treating with PFBT SAM, the improving performances of the memory devices by SAM modification are explained by the increase of charge injection, which could be further investigated by XPS and UPS. In particular, the results highlight the utility of SAM modulations and controlling of charge transport in the development of organic transistor memories.

  14. Progress in the development of a reactivity capability in the SAM-CE system for validating fuel management codes. Interim report

    International Nuclear Information System (INIS)

    Lichtenstein, H.; Steinberg, H.; Troubetzkoy, E.; Cohen, M.O.; Chui, C.

    1978-02-01

    The SAM-CE Monte Carlo system (for three dimensional neutron, gamma ray and electron transport) has been expanded to include a reactivity capability. The implemented code modifications have effected the following improvements: (a) Doppler broadening of ENDF/B-IV based nuclear data (including fission); (b) probability table representation for the unresolved resonance range; (c) utilization of thermal scattering law data for the moderator; (d) free gas model in the absence of thermal scattering law data; (e) generalization of the nuclear element data tape structure to facilitate data management; (f) generalization of data management routines; (g) extension of the SAM-CE Complex Combinatorial Geometry capability to facilitate treatment of hexagonal lattices; (h) simultaneous use of 4 different eigenvalue estimators; (i) estimation of the eigenfunction in user prescribed spatial domains; and (j) variance reduction via stratification of source (position, energy, direction) and absorption (based on a quota sampling technique), as well as optional suppression of absorption. The new coding has undergone extensive testing, both specific (via drivers and idealized data) and integral (via comparison with previous computations). Base data have been examined for internal consistency and checked for reasonableness. A documented TRX-1 benchmark calculation has been performed. Agreement with other calculations, as well as with experiment, has served to validate the reactivity mode of SAM-CE. Further refinement of the cross section data processing component of SAM-CE (i.e., SAM-X) is suggested

  15. System on Package (SoP) Millimeter Wave Filters for 5G Applications

    KAUST Repository

    Showail, Jameel

    2018-05-01

    Bandpass filters are an essential component of wireless communication systems that only transmits frequencies corresponding to the communication band and rejects all other frequencies. As the deployment of 5G draws nearer, first deployments are expected in 2020 [1], the need for viable filters at the new frequency bands becomes more imminent. Size and performance are two critical considerations for a filter that will be used in emerging mobile communication applications. The high frequency of 5G communication, 28 GHz as opposed to sub 6 GHz for nearly all previous communication protocols, means that previously utilized lumped component based solutions cannot be implemented since they are ill-suited for mm-wave applications. The focus of this work is the miniaturization of a high-performance filter. The Substrate Integrated Waveguide (SIW) is a high performance and promising structure and Low Temperature Co-Fired Ceramic (LTCC) is a high-performance material that both can operate at higher frequencies than the technologies used for previous telecommunication generations. To miniaturize the structure, a compact folded four-cavity SIW filter is designed, implemented and tested. The feeding structure is integrated into the filter to exploit the System on Package (SoP) attributes of LTCC and further reduce the total area of the filter individually and holistically when looking at the final integrated system. Two unique three dimensional (3D) integrated SoP LTCC two-stage SIW single cavity filters and one unique four-cavity filter all with embedded planar resonators are designed, fabricated and tested. The embedded resonators create a two-stage effect in a single cavity filter. The better single cavity design provides a 15% fractional bandwidth at a center frequency of 28.12 GHz, and with an insertion loss of -0.53 dB. The fabricated four-cavity filter has a 3-dB bandwidth of .98GHz centered at 27.465 GHz, and with an insertion loss of -2.66 dB. The designs presented

  16. Standard Operation Procedure (SOP) on Planting and Curing of Stevia in Malaysian Nuclear Agency

    International Nuclear Information System (INIS)

    Norellia Bahari; Norazlina Noordin; Peng, C.S.

    2015-01-01

    Mutation breeding on stevia study was conducted at the Malaysian Nuclear Agency began in 2012 through the projects under auspices of Science Funs and MOSTI. This research involves the irradiation og gamma rays for acute and chronic tissue culture of stevia. The resulting plant from this tissue cultures process should be planted in a nursery fro the propagation of seedlings for the work of mutant screening potential. For this purpose, the SOP for planting, care and management of stevia has ben developed to ensure that this plant can grow in abundance, disease free and quality. This paper will discuss the SOP including acclimatization techniques of tissue culture plant lets, seedlings and planting in Bio Design Facility, fertilization using fertilizers and planting of trees in the plot for the purpose of potentially screening mutant breeding. (author)

  17. Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM).

    Science.gov (United States)

    Xiong, Kai; Zhou, Yan; Hyttel, Poul; Bolund, Lars; Freude, Kristine Karla; Luo, Yonglun

    2016-11-01

    Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4 and C-MYC. We have validated that the reprogramming cassette is silenced in the SAM iPSC clones. Expression of pluripotency genes (OCT4, SOX2, LIN28A, NANOG, GDF3, SSEA4, and TRA-1-60), differentiation potential to all three germ layers, and normal karyotypes are validated. These SAM-iPSCs provide a novel, useful tool to investigate genetic regulation of stem cell proliferation and differentiation through CRISPR-mediated activation of endogenous genes. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

  18. Spirit Pluralisme dalam Klenteng Sam Po Kong Semarang

    Directory of Open Access Journals (Sweden)

    Edi Nurwahyu Julianto

    2015-07-01

    Full Text Available Klenteng Sam Po Kong has very deep meaning as a symbol of multi cultural; multi ethnic and multi religious. Klenteng Sam Po Kong has a different function, not only used by people with background religious Tri Dharma (Budha, Tao and Konghuchu, but also used by Javanese ethnic with different religious backgrounds. Between ethnic China and Java, mutual respect and tolerance run beliefs and rituals of each. More over, Klenteng Sam Po Kong is a form of pluralism which reflected the fact Sino Javanese Muslim Culture is preserved to date both of sightings physical culture and system cultural in the form of religious rites performed by ethnic China and Java.

  19. Fabrication and tribological properties of self-assembled monolayer of n-alkyltrimethoxysilane on silicon: Effect of SAM alkyl chain length

    International Nuclear Information System (INIS)

    Huo, Lixia; Du, Pengcheng; Zhou, Hui; Zhang, Kaifeng; Liu, Peng

    2017-01-01

    Highlights: • n-Alkyltrimethoxysilanes with various chain lengths were self-assembled on silicon. • Effect of alkyl chain lengths (C6, C12, or C18) on the SAMs was investigated. • Surface roughness of the SAMs decreased with increasing the alkyl chain lengths. • The C 12 -SAM possessed superior friction reduction and wear resistance. - Abstract: It is well known that the self-assembled organic molecules on a solid surface exhibit the friction-reducing performance. However, the effect of the molecular size of the self-assembled organic molecules has not been established. In the present work, self-assembled monolayers (SAMs) of n-alkyltrimethoxysilanes with different alkyl chain lengths (C 6 , C 12 , or C 18 ) were fabricated on silicon substrate. The water contact angles of the SAMs increased from 26.8° of the hydroxylated silicon substrate to near 60° after self-assembly. The atomic force microscopy (AFM) analysis results showed that the mean roughness (R a ) of the SAMs decreased with increasing the alkyl chain length. The tribological properties of the SAMs sliding against Al 2 O 3 ball were evaluated on an UMT-2 tribometer, and the worn surfaces of the samples were analyzed by means of Nano Scratch Tester and surface profilometry. It was found that lowest friction coefficient and smallest width of wear were achieved with the SAMs of C 12 alkyl chain (C 12 -SAM). The superior friction reduction and wear resistance of the SAMs in comparison with the bare silicon substrate are attributed to good adhesion of the self-assembled films to the substrate, especially the C 12 -SAM with desirable alkyl chain length.

  20. Fabrication and tribological properties of self-assembled monolayer of n-alkyltrimethoxysilane on silicon: Effect of SAM alkyl chain length

    Science.gov (United States)

    Huo, Lixia; Du, Pengcheng; Zhou, Hui; Zhang, Kaifeng; Liu, Peng

    2017-02-01

    It is well known that the self-assembled organic molecules on a solid surface exhibit the friction-reducing performance. However, the effect of the molecular size of the self-assembled organic molecules has not been established. In the present work, self-assembled monolayers (SAMs) of n-alkyltrimethoxysilanes with different alkyl chain lengths (C6, C12, or C18) were fabricated on silicon substrate. The water contact angles of the SAMs increased from 26.8° of the hydroxylated silicon substrate to near 60° after self-assembly. The atomic force microscopy (AFM) analysis results showed that the mean roughness (Ra) of the SAMs decreased with increasing the alkyl chain length. The tribological properties of the SAMs sliding against Al2O3 ball were evaluated on an UMT-2 tribometer, and the worn surfaces of the samples were analyzed by means of Nano Scratch Tester and surface profilometry. It was found that lowest friction coefficient and smallest width of wear were achieved with the SAMs of C12 alkyl chain (C12-SAM). The superior friction reduction and wear resistance of the SAMs in comparison with the bare silicon substrate are attributed to good adhesion of the self-assembled films to the substrate, especially the C12-SAM with desirable alkyl chain length.

  1. SAM : an experiment dedicated to the Carbon Quest at Mars

    Science.gov (United States)

    Coll, Patrice; Mahaffy, Paul; Webster, Chris; Cabane, Michel; Tan, F.; Coscia, D.; Nolan, T.; Rahen, E.; Teinturier, S.; Goutail, J. P.; Martin, D.; Montaron, C.; Galic, A.

    SAM is a suite of instruments that will be onboard the Mars Science Laboratory (MSL) rover. The SAM team consist of scientists and engineers at GSFC, U. Paris/CNRS, JPL, and Honeybee Robotics, along with many additional external partners. SAM's five science goals will address three of the most fundamental questions about the ability of Mars to support life -past, present, and future. Question 1: What does the inventory of carbon compounds near the surface of Mars tell us about its potential habitability? 1.Goal 1: Survey carbon compound sources and evaluate their possible mechanism of formation and destruction. 2.Goal 2: Search for organic compounds of biotic and prebiotic importance expecially methane. Question 2: What are the chemical and isotopic states of the lighter elements in the solids and atmosphere of Mars and what do they tell us about its potential habitability? 1.Goal 3: Reveal the chemical and isotopic state of elements (i.e., N, H, O, S and others) that are important for life as we know it. 2.Goal 4: Evaluate the habitability of Mars by studying its atmospheric chemistry and the composition of trace species that are evidence of interactions between the atmosphere and soil. Question 3: Were past habitability conditions different from today's? 1.Goal 5: Understand atmospheric and climatic evolution through measurements of noble gas and light element isotopes.

  2. 24-GHz LTCC Fractal Antenna Array SoP With Integrated Fresnel Lens

    KAUST Repository

    Ghaffar, Farhan A.

    2012-09-30

    A novel 24-GHz mixed low-temperature co-fired ceramic (LTCC) tape based system-on-package (SoP) is presented, which incorporates a fractal antenna array with an integrated grooved Fresnel lens. The four-element fractal array employs a relatively low dielectric constant substrate (CT707, εr = 6.4), whereas the lens has been realized on a high-dielectric-constant superstrate (CT765, εr = 68.7 ). The two (substrate and superstrate) are integrated through four corner posts to realize the required air gap (focal distance). The fractal array alone provides a measured gain of 8.9 dBi. Simulations predict that integration of this array with the lens increases the gain by 6 dB. Measurements reveal that the design is susceptible to LTCC fabrication tolerances. In addition to high gain, the SoP provides a bandwidth of 8%. The high performance and compact size (24 × 24 × 4.8 mm3 ) of the design makes it highly suitable for emerging wireless applications such as automotive radar front end.

  3. Context-based Sales and Operations Planning (S&OP) research

    DEFF Research Database (Denmark)

    Kristensen, Jesper; Jonsson, Patrik

    2018-01-01

    review. Studies for review were obtained through a keyword search of five relevant databases, manual searches of relevant journals and snowballing of citations in relevant papers. In total, 571 papers published between 2000 and 2017 were assessed, and 68 papers were included in the review. Findings...... – The review found that S&OP design depends on industry, dynamic complexity, detail complexity and organisational characteristics. The findings of the literature review suggest that future research should study the roles of industry, complexity, system and process and organisational characteristics in S...

  4. Fabrication and tribological properties of self-assembled monolayer of n-alkyltrimethoxysilane on silicon: Effect of SAM alkyl chain length

    Energy Technology Data Exchange (ETDEWEB)

    Huo, Lixia [National Key Laboratory of Science and Technology on Vacuum Technology and Physics, Lanzhou Institute of Physics, Lanzhou, Gansu 730010 (China); Institute of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Lanzhou University, Gansu 730000 (China); Du, Pengcheng [Institute of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Lanzhou University, Gansu 730000 (China); Zhou, Hui; Zhang, Kaifeng [National Key Laboratory of Science and Technology on Vacuum Technology and Physics, Lanzhou Institute of Physics, Lanzhou, Gansu 730010 (China); Liu, Peng, E-mail: pliu@lzu.edu.cn [Institute of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Lanzhou University, Gansu 730000 (China)

    2017-02-28

    Highlights: • n-Alkyltrimethoxysilanes with various chain lengths were self-assembled on silicon. • Effect of alkyl chain lengths (C6, C12, or C18) on the SAMs was investigated. • Surface roughness of the SAMs decreased with increasing the alkyl chain lengths. • The C{sub 12}-SAM possessed superior friction reduction and wear resistance. - Abstract: It is well known that the self-assembled organic molecules on a solid surface exhibit the friction-reducing performance. However, the effect of the molecular size of the self-assembled organic molecules has not been established. In the present work, self-assembled monolayers (SAMs) of n-alkyltrimethoxysilanes with different alkyl chain lengths (C{sub 6}, C{sub 12}, or C{sub 18}) were fabricated on silicon substrate. The water contact angles of the SAMs increased from 26.8° of the hydroxylated silicon substrate to near 60° after self-assembly. The atomic force microscopy (AFM) analysis results showed that the mean roughness (R{sub a}) of the SAMs decreased with increasing the alkyl chain length. The tribological properties of the SAMs sliding against Al{sub 2}O{sub 3} ball were evaluated on an UMT-2 tribometer, and the worn surfaces of the samples were analyzed by means of Nano Scratch Tester and surface profilometry. It was found that lowest friction coefficient and smallest width of wear were achieved with the SAMs of C{sub 12} alkyl chain (C{sub 12}-SAM). The superior friction reduction and wear resistance of the SAMs in comparison with the bare silicon substrate are attributed to good adhesion of the self-assembled films to the substrate, especially the C{sub 12}-SAM with desirable alkyl chain length.

  5. 3D printed System-on-Package (SoP) for environmental sensing and localization applications

    KAUST Repository

    Zhen, Su; Bilal, Rana Muhammad; Shamim, Atif

    2017-01-01

    This paper presents for the first time an innovative 3D printed SoP sensor node with temperature, pressure and humidity sensing capabilities. It has an integrated wireless readout through a near isotropic (900MHz) GSM antenna-on-package. This sensor

  6. GoSam 2.0. Automated one loop calculations within and beyond the standard model

    International Nuclear Information System (INIS)

    Greiner, Nicolas; Deutsches Elektronen-Synchrotron

    2014-10-01

    We present GoSam 2.0, a fully automated framework for the generation and evaluation of one loop amplitudes in multi leg processes. The new version offers numerous improvements both on generational aspects as well as on the reduction side. This leads to a faster and more stable code for calculations within and beyond the Standard Model. Furthermore it contains the extended version of the standardized interface to Monte Carlo programs which allows for an easy combination with other existing tools. We briefly describe the conceptual innovations and present some phenomenological results.

  7. Evolved Gas Analyses of the Murray Formation in Gale Crater, Mars: Results of the Curiosity Rover's Sample Analysis at Mars (SAM) Instrument

    Science.gov (United States)

    Sutter, B.; McAdam, A. C.; Rampe, E. B.; Thompson, L. M.; Ming, D. W.; Mahaffy, P. R.; Navarro-Gonzalez, R.; Stern, J. C.; Eigenbrode, J. L.; Archer, P. D.

    2017-01-01

    The Sample Analysis at Mars (SAM) instrument aboard the Mars Science Laboratory rover has analyzed 13 samples from Gale Crater. All SAM-evolved gas analyses have yielded a multitude of volatiles (e.g., H2O, SO2, H2S, CO2, CO, NO, O2, HCl) [1- 6]. The objectives of this work are to 1) Characterize recent evolved SO2, CO2, O2, and NO gas traces of the Murray formation mudstone, 2) Constrain sediment mineralogy/composition based on SAM evolved gas analysis (SAM-EGA), and 3) Discuss the implications of these results relative to understanding the geological history of Gale Crater.

  8. Why Nature Uses Radical SAM Enzymes so Widely: Electron Nuclear Double Resonance Studies of Lysine 2,3-Aminomutase Show the 5'-dAdo• "Free Radical" Is Never Free.

    Science.gov (United States)

    Horitani, Masaki; Byer, Amanda S; Shisler, Krista A; Chandra, Tilak; Broderick, Joan B; Hoffman, Brian M

    2015-06-10

    Lysine 2,3-aminomutase (LAM) is a radical S-adenosyl-L-methionine (SAM) enzyme and, like other members of this superfamily, LAM utilizes radical-generating machinery comprising SAM anchored to the unique Fe of a [4Fe-4S] cluster via a classical five-membered N,O chelate ring. Catalysis is initiated by reductive cleavage of the SAM S-C5' bond, which creates the highly reactive 5'-deoxyadenosyl radical (5'-dAdo•), the same radical generated by homolytic Co-C bond cleavage in B12 radical enzymes. The SAM surrogate S-3',4'-anhydroadenosyl-L-methionine (anSAM) can replace SAM as a cofactor in the isomerization of L-α-lysine to L-β-lysine by LAM, via the stable allylic anhydroadenosyl radical (anAdo•). Here electron nuclear double resonance (ENDOR) spectroscopy of the anAdo• radical in the presence of (13)C, (2)H, and (15)N-labeled lysine completes the picture of how the active site of LAM from Clostridium subterminale SB4 "tames" the 5'-dAdo• radical, preventing it from carrying out harmful side reactions: this "free radical" in LAM is never free. The low steric demands of the radical-generating [4Fe-4S]/SAM construct allow the substrate target to bind adjacent to the S-C5' bond, thereby enabling the 5'-dAdo• radical created by cleavage of this bond to react with its partners by undergoing small motions, ∼0.6 Å toward the target and ∼1.5 Å overall, that are controlled by tight van der Waals contact with its partners. We suggest that the accessibility to substrate and ready control of the reactive C5' radical, with "van der Waals control" of small motions throughout the catalytic cycle, is common within the radical SAM enzyme superfamily and is a major reason why these enzymes are the preferred means of initiating radical reactions in nature.

  9. The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members.

    Directory of Open Access Journals (Sweden)

    Jana Kamanova

    2016-04-01

    Full Text Available Salmonella Typhimurium stimulates inflammatory responses in the intestinal epithelium, which are essential for its ability to replicate within the intestinal tract. Stimulation of these responses is strictly dependent on the activity of a type III secretion system encoded within its pathogenicity island 1, which through the delivery of effector proteins, triggers signaling pathways leading to inflammation. One of these effectors is SopA, a HECT-type E3 ligase, which is required for the efficient stimulation of inflammation in an animal model of Salmonella Typhimurium infection. We show here that SopA contributes to the stimulation of innate immune responses by targeting two host E3 ubiquitin ligases, TRIM56 and TRIM65. We also found that TRIM65 interacts with the innate immune receptor MDA5 enhancing its ability to stimulate interferon-β signaling. Therefore, by targeting TRIM56 and TRIM65, SopA can stimulate signaling through two innate immune receptors, RIG-I and MDA5. These findings describe a Salmonella mechanism to modulate inflammatory responses by directly targeting innate immune signaling mechanisms.

  10. Characterization of a SAM-dependent fluorinase from a latent biosynthetic pathway for fluoroacetate and 4-fluorothreonine formation in Nocardia brasiliensis [v1; ref status: indexed, http://f1000r.es/2tz

    Directory of Open Access Journals (Sweden)

    Yaya Wang

    2014-02-01

    Full Text Available Fluorination has been widely used in chemical synthesis, but is rare in nature. The only known biological fluorination scope is represented by the fl pathway from Streptomyces cattleya that produces fluoroacetate (FAc and 4-fluorothreonine (4-FT. Here we report the identification of a novel pathway for FAc and 4-FT biosynthesis from the actinomycetoma-causing pathogen Nocardia brasiliensis ATCC 700358. The new pathway shares overall conservation with the fl pathway in S. cattleya. Biochemical characterization of the conserved domains revealed a novel fluorinase NobA that can biosynthesize 5’-fluoro-5’-deoxyadenosine (5’-FDA from inorganic fluoride and S-adenosyl-l-methionine (SAM. The NobA shows similar halide specificity and characteristics to the fluorination enzyme FlA of the fl pathway. Kinetic parameters for fluoride (Km 4153 μM, kcat 0.073 min-1 and SAM (Km 416 μM, kcat 0.139 min-1 have been determined, revealing that NobA is slightly (2.3 fold slower than FlA. Upon sequence comparison, we finally identified a distinct loop region in the fluorinases that probably accounts for the disparity of fluorination activity.

  11. Parabolic Trough Collector Cost Update for the System Advisor Model (SAM)

    Energy Technology Data Exchange (ETDEWEB)

    Kurup, Parthiv [National Renewable Energy Lab. (NREL), Golden, CO (United States); Turchi, Craig S. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-11-01

    This report updates the baseline cost for parabolic trough solar fields in the United States within NREL's System Advisor Model (SAM). SAM, available at no cost at https://sam.nrel.gov/, is a performance and financial model designed to facilitate decision making for people involved in the renewable energy industry. SAM is the primary tool used by NREL and the U.S. Department of Energy (DOE) for estimating the performance and cost of concentrating solar power (CSP) technologies and projects. The study performed a bottom-up build and cost estimate for two state-of-the-art parabolic trough designs -- the SkyTrough and the Ultimate Trough. The SkyTrough analysis estimated the potential installed cost for a solar field of 1500 SCAs as $170/m2 +/- $6/m2. The investigation found that SkyTrough installed costs were sensitive to factors such as raw aluminum alloy cost and production volume. For example, in the case of the SkyTrough, the installed cost would rise to nearly $210/m2 if the aluminum alloy cost was $1.70/lb instead of $1.03/lb. Accordingly, one must be aware of fluctuations in the relevant commodities markets to track system cost over time. The estimated installed cost for the Ultimate Trough was only slightly higher at $178/m2, which includes an assembly facility of $11.6 million amortized over the required production volume. Considering the size and overall cost of a 700 SCA Ultimate Trough solar field, two parallel production lines in a fully covered assembly facility, each with the specific torque box, module and mirror jigs, would be justified for a full CSP plant.

  12. Modelo quantitativo para avaliação e melhoria de desempenho do processo de S&OP baseado no diagnóstico e redução de falhas A quantitative model for the assessment and performance improvement of S&OP process based on the diagnosis and reduction of failures

    Directory of Open Access Journals (Sweden)

    Fabio José Pandim

    2012-01-01

    Full Text Available O processo de Sales and Operations Planning - Planejamento de Vendas e Operações (S&OP, assim como qualquer processo de nível estratégico ou tático, necessita ter o seu desempenho monitorado para que seja possível realizar ações de melhoria nos aspectos que estejam gerando impactos negativos em seu desempenho. Os modelos para análise de desempenho encontrados na literatura não trazem meios para localizar as causas de ineficiência mais relevantes, quando da utilização de processos S&OP, bem como não fornecem uma maneira de se quantificar o desempenho do processo. Com o objetivo de contribuir com esta necessidade, o presente trabalho apresenta um modelo quantitativo para análise e melhoria de desempenho do processo de S&OP baseado no diagnóstico e na redução de suas ineficiências mais importantes.The S&OP process, like any business process of strategic or tactical level, requires having its performance measured so that, through the monitoring of these measurements, improvement actions for the factors affecting their performance can be created. The models for performance analysis in the literature failed to identify the most relevant causes of inefficiency to the process and do provide a way of measuring the process performance. Therefore, this paper presents a proposal for a quantitative model for the analysis and performance improvement of the S&OP process based on the diagnosis and reduction of its most important inefficiencies.

  13. Bringing a Chemical Laboratory Named Sam to Mars on the 2011 Curiosity Rover

    Science.gov (United States)

    Mahaffy, P. R.; Bleacher, L.; Jones, A.; Conrad, P. G.; Cabane, M.; Webster, C. R.; Atreya, S. A.; Manning, H.

    2010-01-01

    An important goal of upcoming missions to Mars is to understand if life could have developed there. The task of the Sample Analysis at Mars (SAM) suite of instruments [1] and the other Curiosity investigations [2] is to move us steadily toward that goal with an assessment of the habitability of our neighboring planet through a series of chemical and geological measurements. SAM is designed to search for organic compounds and inorganic volatiles and measure isotope ratios. Other instruments on Curiosity will provide elemental analysis and identify minerals. SAM will analyze both atmospheric samples and gases evolved from powdered rocks that may have formed billions of years ago with Curiosity providing access to interesting sites scouted by orbiting cameras and spectrometers.

  14. Evidence for Perchlorates and the Origin of Chlorinated Hydrocarbons Detected by SAM at the Rocknest Aeolian Deposit in Gale Crater

    Science.gov (United States)

    Glavin, Daniel P.; Freissinet, Caroline; Miller, Kristen E.; Eigenbrode, Jennifer L.; Brunner, Anna E.; Buch, Arnaud; Sutter, Brad; Archer, P. Douglas, Jr.; Atreya, Sushil K.; Brinckerhoff, William B.; hide

    2013-01-01

    A single scoop of the Rocknest aeolian deposit was sieved (less than 150 micrometers), and four separate sample portions, each with a mass of approximately 50 mg, were delivered to individual cups inside the Sample Analysis at Mars (SAM) instrument by the Mars Science Laboratory rover's sample acquisition system. The samples were analyzed separately by the SAM pyrolysis evolved gas and gas chromatograph mass spectrometer analysis modes. Several chlorinated hydrocarbons including chloromethane, dichloromethane, trichloromethane, a chloromethylpropene, and chlorobenzene were identified by SAM above background levels with abundances of approximately 0.01 to 2.3 nmol. The evolution of the chloromethanes observed during pyrolysis is coincident with the increase in O2 released from the Rocknest sample and the decomposition of a product of N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide (MTBSTFA), a chemical whose vapors were released from a derivatization cup inside SAM. The best candidate for the oxychlorine compounds in Rocknest is a hydrated calcium perchlorate (Ca(ClO4)2·nH2O), based on the temperature release of O2 that correlates with the release of the chlorinated hydrocarbons measured by SAM, although other chlorine-bearing phases are being considered. Laboratory analog experiments suggest that the reaction of Martian chlorine from perchlorate decomposition with terrestrial organic carbon from MTBSTFA during pyrolysis can explain the presence of three chloromethanes and a chloromethylpropene detected by SAM. Chlorobenzene may be attributed to reactions of Martian chlorine released during pyrolysis with terrestrial benzene or toluene derived from 2,6-diphenylphenylene oxide (Tenax) on the SAM hydrocarbon trap. At this time we do not have definitive evidence to support a nonterrestrial carbon source for these chlorinated hydrocarbons, nor do we exclude the possibility that future SAM analyses will reveal the presence of organic compounds native to the

  15. Motor coordination defects in mice deficient for the Sam68 RNA-binding protein.

    Science.gov (United States)

    Lukong, Kiven E; Richard, Stéphane

    2008-06-03

    The role of RNA-binding proteins in the central nervous system and more specifically their role in motor coordination and learning are poorly understood. We previously reported that ablation of RNA-binding protein Sam68 in mice results in male sterility and delayed mammary gland development and protection against osteoporosis in females. Sam68 however is highly expressed in most regions of the brain especially the cerebellum and thus we investigated the cerebellar-related manifestations in Sam68-null mice. We analyzed the mice for motor function, sensory function, and learning and memory abilities. Herein, we report that Sam68-null mice have motor coordination defects as assessed by beam walking and rotorod performance. Forty-week-old Sam68-null mice (n=12) were compared to their wild-type littermates (n=12). The Sam68-null mice exhibited more hindpaw faults in beam walking tests and fell from the rotating drum at lower speeds and prematurely compared to the wild-type controls. The Sam68-null mice were, however, normal for forelimb strength, tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion. Our findings support a role for Sam68 in the central nervous system in the regulation of motor coordination.

  16. Radiation streaming with SAM-CE

    International Nuclear Information System (INIS)

    De Gangi, N.; Cohen, M.O.; Waluschka, E.; Steinberg, H.A.

    1980-01-01

    The SAM-CE Monte Carlo code has been employed to calculate doses, due to neutron streaming, on the operating floor and other locations of the Millstone Unit II Nuclear Power Facility. Calculated results were compared against measured doses

  17. On LAM's and SAM's for Halley's rotation

    Science.gov (United States)

    Peale, Stanton J.

    1992-01-01

    Non principal axis rotation for comet Halley is inferred from dual periodicities evident in the observations. The modes where the spin axis precesses around the axis of minimum moment of inertia (long axis mode or LAM) and where it precesses around the axis of maximum moment of inertia (short axis mode or SAM) are described from an inertial point of view. The currently favored LAM model for Halley's rotation state satisfies observational and dynamical constraints that apparently no SAM can satisfy. But it cannot reproduce the observed post perihelion brightening through seasonal illumination of localized sources on the nucleus, whereas a SAM can easily produce post or pre perihelion brightening by this mechanism. However, the likelihood of a LAM rotation for elongated nuclei of periodic comets such as Halley together with Halley's extreme post perihelion behavior far from the Sun suggest that Halley's post perihelion brightening may be due to effects other than seasonal illumination of localized sources, and therefore such brightening may not constrain its rotation state.

  18. 78 FR 26103 - Proposed Standard Operating Procedure (SOP) of the Aircraft Certification Service (AIR) Project...

    Science.gov (United States)

    2013-05-03

    ... data, views, or arguments to the above listed address. Please identify ``SOP: AIR-100-001 Standard... Certification Offices (ACOs). The certification programs include: Type certificate (TC), Amended Type Certificate (ATC), Supplemental Type Certificated ATC), Amended Supplemental Type Certificate (ASTC), and...

  19. A magnesium-induced triplex pre-organizes the SAM-II riboswitch.

    Directory of Open Access Journals (Sweden)

    Susmita Roy

    2017-03-01

    Full Text Available Our 13C- and 1H-chemical exchange saturation transfer (CEST experiments previously revealed a dynamic exchange between partially closed and open conformations of the SAM-II riboswitch in the absence of ligand. Here, all-atom structure-based molecular simulations, with the electrostatic effects of Manning counter-ion condensation and explicit magnesium ions are employed to calculate the folding free energy landscape of the SAM-II riboswitch. We use this analysis to predict that magnesium ions remodel the landscape, shifting the equilibrium away from the extended, partially unfolded state towards a compact, pre-organized conformation that resembles the ligand-bound state. Our CEST and SAXS experiments, at different magnesium ion concentrations, quantitatively confirm our simulation results, demonstrating that magnesium ions induce collapse and pre-organization. Agreement between theory and experiment bolsters microscopic interpretation of our simulations, which shows that triplex formation between helix P2b and loop L1 is highly sensitive to magnesium and plays a key role in pre-organization. Pre-organization of the SAM-II riboswitch allows rapid detection of ligand with high selectivity, which is important for biological function.

  20. Renewing Samsø

    DEFF Research Database (Denmark)

    Papazu, Irina

    2017-01-01

    and globally, I ask: if indeed such a process of renewal must be understood as a political process and the island’s energy transition as an inherently political event, what can Samsø teach us about the workings of politics and local democracy as enacted in practice? This is politics not as election result...... or ideological struggle over values, ideals and the distribution of goods, but as the down-to-earth but significant activity of creating something new together....

  1. Why Nature Uses Radical SAM Enzymes so Widely: Electron Nuclear Double Resonance Studies of Lysine 2,3-Aminomutase Show the 5′-dAdo• “Free Radical” Is Never Free

    Science.gov (United States)

    Horitani, Masaki; Byer, Amanda S.; Shisler, Krista A.; Chandra, Tilak; Broderick, Joan B.; Hoffman, Brian M.

    2015-01-01

    Lysine 2,3-aminomutase (LAM) is a radical S-adenosyl-L-methionine (SAM) enzyme and, like other members of this superfamily, LAM utilizes radical-generating machinery comprising SAM anchored to the unique Fe of a [4Fe-4S] cluster via a classical five-membered N,O chelate ring. Catalysis is initiated by reductive cleavage of the SAM S–C5′ bond, which creates the highly reactive 5′-deoxyadenosyl radical (5′-dAdo•), the same radical generated by homolytic Co–C bond cleavage in B12 radical enzymes. The SAM surrogate S-3′,4′-anhydroadenosyl-L-methionine (anSAM) can replace SAM as a cofactor in the isomerization of L-α-lysine to L-β-lysine by LAM, via the stable allylic anhydroadenosyl radical (anAdo•). Here electron nuclear double resonance (ENDOR) spectroscopy of the anAdo• radical in the presence of 13C, 2H, and 15N-labeled lysine completes the picture of how the active site of LAM from Clostridium subterminale SB4 “tames” the 5′-dAdo• radical, preventing it from carrying out harmful side reactions: this “free radical” in LAM is never free. The low steric demands of the radical-generating [4Fe-4S]/SAM construct allow the substrate target to bind adjacent to the S–C5′ bond, thereby enabling the 5′-dAdo• radical created by cleavage of this bond to react with its partners by undergoing small motions, ~0.6 Å toward the target and ~1.5 Å overall, that are controlled by tight van der Waals contact with its partners. We suggest that the accessibility to substrate and ready control of the reactive C5′ radical, with “van der Waals control” of small motions throughout the catalytic cycle, is common within the radical SAM enzyme superfamily and is a major reason why these enzymes are the preferred means of initiating radical reactions in nature. PMID:25923449

  2. Development of the criticality capability for the SAM-CE Monte Carlo System

    International Nuclear Information System (INIS)

    Lichtenstein, H.; Troubetzkoy, E.; Steinberg, H.; Cohen, M.O.

    1979-04-01

    A criticality capabilty has been developed and implemented in the SAM-CE Monte Carlo system. The data processing component, SAM-X, preserves, to any required accuracy, the data quality inherent in the ENDF/B library. The generated data is Doppler-broadened and includes (where applicable) probability tables for the unresolved resonance range, and thermal-scattering law data. Curves of several total and partial cross sections are generated and displayed. The Monte Carlo component, SAM-F, includes several eigenvalue estimators and variance reduction schemes. Stratification was found to effect significant improvement in calculational efficiency, but the usefulness of importance sampling is marginal in criticality problems. The entire system has been installed at BNL, for the analysis of TRX benchmarks. The TRX-1 and TRX-2 cell calculations have been performed, with estimated eigenvalues of 1.1751 +- 0.0016 and 1.1605 +- .0015, respectively. These results are shown to be statistically consistent with other sources

  3. Identification of trans-acting factors regulating SamDC expression in Oryza sativa

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Supratim, E-mail: supratim_genetics@yahoo.co.in [Department of Crop Soil and Environmental Sciences, University of Arkansas, Fayetteville, AR 72701 (United States); Division of Plant Biology, Bose Institute, Kolkata (India); Roychoudhury, Aryadeep [Post Graduate Department of Biotechnology, St. Xavier' s College (Autonomous), 30, Mother Teresa Sarani, Kolkata - 700016, West Bengal (India); Sengupta, Dibyendu N. [Division of Plant Biology, Bose Institute, Kolkata (India)

    2014-03-07

    Highlights: • Identification of cis elements responsible for SamDC expression by in silico analysis. • qPCR analysis of SamDC expression to abiotic and biotic stress treatments. • Detection of SamDC regulators using identified cis-elements as probe by EMSA. • Southwestern Blot analysis to predict the size of the trans-acting factors. - Abstract: Abiotic stress affects the growth and productivity of crop plants; to cope with the adverse environmental conditions, plants have developed efficient defense machinery comprising of antioxidants like phenolics and flavonoids, and osmolytes like polyamines. SamDC is a key enzyme in the polyamine biosynthesis pathway in plants. In our present communication we have done in silico analysis of the promoter region of SamDC to look for the presence of different cis-regulatory elements contributing to its expression. Based on the presence of different cis-regulatory elements we completed comparative analysis of SamDC gene expression in rice lamina of IR-29 and Nonabokra by qPCR in response to the abiotic stress treatments of salinity, drought, cold and the biotic stress treatments of ABA and light. Additionally, to explore the role of the cis-regulatory elements in regulating the expression of SamDC gene in plants we comparatively analyzed the binding of rice nuclear proteins prepared from IR-29 and Nonabokra undergoing various stress treatments. The intensity of the complex formed was low and inducible in IR-29 in contrast to Nonabokra. Southwestern blot analysis helped in predicting the size of the trans-acting factors binding to these cis-elements. To our knowledge this is the first report on the comprehensive analysis of SamDC gene expression in rice and identification of the trans-acting factors regulating its expression.

  4. Evolved Gas Analyses of Sedimentary Materials in Gale Crater, Mars: Results of the Curiosity Rover's Sample Analysis at Mars (SAM) Instrument from Yellowknife Bay to the Stimson Formation

    Science.gov (United States)

    Sutter, B.; McAdam, A. C.; Rampe, E. B.; Ming, D. W.; Mahaffy, P. R.; Navarro-Gonzalez, R.; Stern, J. C.; Eigenbrode, J. L.; Archer, P. D.

    2016-01-01

    The Sample Analysis at Mars (SAM) instrument aboard the Mars Science Laboratory rover has analyzed 10 samples from Gale Crater. All SAM evolved gas analyses have yielded a multitude of volatiles (e.g, H2O, SO2, H2S, CO2, CO, NO, O2, HC1). The objectives of this work are to 1) Characterize the evolved H2O, SO2, CO2, and O2 gas traces of sediments analyzed by SAM through sol 1178, 2) Constrain sediment mineralogy/composition based on SAM evolved gas analysis (SAM-EGA), and 3) Discuss the implications of these results releative to understanding the geochemical history of Gale Crater.

  5. Development and evaluation of Standard Operating Procedures (SOPs) for quality control tests and radiological protection activities in a Nuclear Medicine Service

    Energy Technology Data Exchange (ETDEWEB)

    Krempser, Alexandre R., E-mail: krempser@peb.ufrj.br [Universidade Federal do Rio de Janeiro (PEB/COPPE/UFRJ), RJ (Brazil). Programa de Engenharia Biomedica; Soares, Alexandre B. [Universidade Federal do Rio de Janeiro (IF/UFRJ), Rio de Janeiro, RJ (Brazil). Inst. de Fisica; Corbo, Rossana [Universidade Federal do Rio de Janeiro (FM/UFRJ), Rio de Janeiro, RJ (Brazil). Dept. de Radiologia

    2011-07-01

    The quality management in Nuclear Medicine Services is a requirement of national and international standards. The Brazilian regulatory agency in health surveillance, the Agencia Nacional de Vigilancia Sanitaria (ANVISA), in its Resolucao de Diretoria Colegiada (Collegiate Directory Resolution) no. 38, requires the elaboration of documents describing the technical and clinical routine activities. This study aimed to elaborate, implement and evaluate Standard Operating Procedures (SOPs) for quality control tests and radiological protection activities in the Nuclear Medicine Service of a university hospital. Eighteen SOPs were developed, involving tasks related to dose calibrator, gamma camera, Geiger-Muller detectors and radiological protection activities. The performance of its application was evaluated for a period of six months. It was observed a reduction in 75% of reported operational errors and 42% of the number of reported incidents with contamination by radioactive material. The SOPs were adequate and successful in its application. New procedures involving clinical activities will also be developed and evaluated. (author)

  6. SAM-CE, Time-Dependent 3-D Neutron Transport, Gamma Transport in Complex Geometry by Monte-Carlo

    International Nuclear Information System (INIS)

    2003-01-01

    1 - Nature of physical problem solved: The SAM-CE system comprises two Monte Carlo codes, SAM-F and SAM-A. SAM-F supersedes the forward Monte Carlo code, SAM-C. SAM-A is an adjoint Monte Carlo code designed to calculate the response due to fields of primary and secondary gamma radiation. The SAM-CE system is a FORTRAN Monte Carlo computer code designed to solve the time-dependent neutron and gamma-ray transport equations in complex three-dimensional geometries. SAM-CE is applicable for forward neutron calculations and for forward as well as adjoint primary gamma-ray calculations. In addition, SAM-CE is applicable for the gamma-ray stage of the coupled neutron-secondary gamma ray problem, which may be solved in either the forward or the adjoint mode. Time-dependent fluxes, and flux functionals such as dose, heating, count rates, etc., are calculated as functions of energy, time and position. Multiple scoring regions are permitted and these may be either finite volume regions or point detectors or both. Other scores of interest, e.g., collision and absorption densities, etc., are also made. 2 - Method of solution: A special feature of SAM-CE is its use of the 'combinatorial geometry' technique which affords the user geometric capabilities exceeding those available with other commonly used geometric packages. All nuclear interaction cross section data (derived from the ENDF for neutrons and from the UNC-format library for gamma-rays) are tabulated in point energy meshes. The energy meshes for neutrons are internally derived, based on built-in convergence criteria and user- supplied tolerances. Tabulated neutron data for each distinct nuclide are in unique and appropriate energy meshes. Both resolved and unresolved resonance parameters from ENDF data files are treated automatically, and extremely precise and detailed descriptions of cross section behaviour is permitted. Such treatment avoids the ambiguities usually associated with multi-group codes, which use flux

  7. Study of radiation effects on the senescence accelerated mouse (SAM), 1

    International Nuclear Information System (INIS)

    Kishikawa, Masao; Iseki, Masachika; Kondo, Hisayoshi

    1989-01-01

    The study of age-related changes in the central nervous system due to irradiation is being carried out in our laboratory. The senescence accelerated mouse (SAM P/1, male) was used for this investigation concerning the one-trial passive avoidance reaction. The experimental group of SAM P/1 was irradiated with 4 Gy at 8 weeks old, and passive avoidance reaction (PAR) was measured for 180 seconds as a learning task. At the age of 7 months, statistical analysis of PAR was conducted using the life time analysis method. The passive avoidance reaction of the irradiated group was more impaired than that of the control group. The results of this investigation suggested that the learning and/or memory disturbance of irradiated SAM P/1 is similar to the changes of more aged SAM P/1. (author)

  8. Characterization of a SAM-dependent fluorinase from a latent biosynthetic pathway for fluoroacetate and 4-fluorothreonine formation in Nocardia brasiliensis.

    Science.gov (United States)

    Wang, Yaya; Deng, Zixin; Qu, Xudong

    2014-01-01

    Fluorination has been widely used in chemical synthesis, but is rare in nature. The only known biological fluorination scope is represented by the fl pathway from Streptomyces cattleya that produces fluoroacetate (FAc) and 4-fluorothreonine (4-FT). Here we report the identification of a novel pathway for FAc and 4-FT biosynthesis from the actinomycetoma-causing pathogen Nocardia brasiliensis ATCC 700358. The new pathway shares overall conservation with the fl pathway in S. cattleya. Biochemical characterization of the conserved domains revealed a novel fluorinase NobA that can biosynthesize 5'-fluoro-5'-deoxyadenosine (5'-FDA) from inorganic fluoride and S-adenosyl-l-methionine (SAM). The NobA shows similar halide specificity and characteristics to the fluorination enzyme FlA of the fl pathway. Kinetic parameters for fluoride ( K m 4153 μM, k cat 0.073 min (-1)) and SAM ( K m 416 μM, k cat 0.139 min (-1)) have been determined, revealing that NobA is slightly (2.3 fold) slower than FlA. Upon sequence comparison, we finally identified a distinct loop region in the fluorinases that probably accounts for the disparity of fluorination activity.

  9. Evidence for Smectite Clays from MSL SAM Analyses of Mudstone at Yellowknife Bay, Gale Crater, Mars

    Science.gov (United States)

    McAdam, Amy; Franz, Heather; Mahaffy, Paul R.; Eigenbrode, Jennifer L.; Stern, Jennifer C.; Brunner, Anna; Archer, Paul Douglas; Ming, Douglas W.; Morris, Richard V.; Atreya, Sushil K.

    2013-01-01

    Drilled samples of mudstone from the Sheepbed unit at Yellowknife Bay were analyzed by MSL instruments including the Sample Analysis at Mars (SAM) and Chemistry and Mineralogy (CheMin) instruments in MSL's Analytical Laboratory. CheMin analyses revealed the first in situ X-ray diffraction based evidence of clay minerals on Mars, which are likely trioctahedral smectites (e.g., saponite) and comprise approx 20% of the mudstone sample (e.g., Bristow et al., this meeting). SAM analyses, which heated the mudstone samples to 1000 C and monitored volatiles evolved to perform in situ evolved gas analysis mass spectrometry (EGA-MS), resulted in a H2O trace exhibiting a wide evolution at temperatures smectite interlayer H2O, and structural H2O/OH from bassanite and akaganeite (identified by CheMin) and H2O/OH from amorphous phases in the sample. The high temperature H2O is consistent with the evolution of H2O from the dehydroxylation of the smectite clay mineral. Comparison to EGA-MS data collected under SAM-like conditions on a variety of clay mineral reference materials indicate that a trioctahedral smectite, such as saponite, is most consistent with the high temperature H2O evolution observed. There may also be SAM EGA-MS evidence for a small high temperature H2O evolution from scoop samples from the Yellowknife Bay Rocknest sand shadow bedform. As in the mudstone samples, this evolution may indicate the detection of smectite clays, and the idea that minor clays may be present in Rocknest materials that could be expected to be at least partially derived from local sources is reasonable. But, because smectite clays were not definitively observed in CheMin analyses of Rocknest materials, they must be present at much lower abundances than the approx 20% observed in the mudstone samples. This potential detection underscores the complementary nature of the MSL CheMin and SAM instruments for investigations of martian sample mineralogy. Information on the nature of Yellowknife

  10. CareSam

    DEFF Research Database (Denmark)

    Liveng, Anne; Christensen, Jonas

    2016-01-01

    negative cultural perceptions of help-needing elderly and the people who support them in everyday life? In answering these questions and thereby reflecting on our own work process we apply a caring, a learning and a political perspective. Hereby the article wishes to formulate a methodological point...... to maintain immediately conflicting dimensions in this kind of work.......This article presents findings and discussions generated on the basis of the Danish-Swedish development project CareSam. The article will on the one hand focus on how work in groups consisting of representatives from different levels in the elderly care sector at one time served as learning spaces...

  11. Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM)

    DEFF Research Database (Denmark)

    Xiong, Kai; Zhou, Yan; Hyttel, Poul

    2016-01-01

    Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4...... a novel, useful tool to investigate genetic regulation of stem cell proliferation and differentiation through CRISPR-mediated activation of endogenous genes....

  12. Corporate governance structure which is based in the S&OP process: Case study in la Brazilian cosmetic company

    Directory of Open Access Journals (Sweden)

    Ximena Rojas

    2014-03-01

    Full Text Available (Received: 2014/01/31 - Accepted: 2014/03/25This article is about the generation of a corporate governance structure which is based in the process S&OP for a Brazilian cosmetic industry. The increasing emphasis on business development guided by attention to the requirements and demands of customers, cause nowadays, that the organizations of the commercial sectors work in the creation of a competitive differential. The collaborative business management strategy S&OP is looking for the attention of people who are interested in the improvement of their skills; in order to achieve this differential. With the case study methodology, the objectives are to get knowledge, identify, and analyze the characteristics of the company using analysis tools like SWOT, process analysis, value chain. All with the purpose to get a robust management tool that fits with the requirements and demands of the organization. The analyzed results showed that the principles of collaboration and internal communication were the pillars necessary against any attempt of business development. This supports the proposal of a management structure based on the five step S&OP process. As a complement to this study a methodology CPFR was identified as the platform for an integrated work with the rest of the companies of the supply chain.

  13. Reactions Involving Calcium and Magnesium Sulfates as Potential Sources of Sulfur Dioxide During MSL SAM Evolved Gas Analyses

    Science.gov (United States)

    McAdam, A. C.; Knudson, C. A.; Sutter, B.; Franz, H. B.; Archer, P. D., Jr.; Eigenbrode, J. L.; Ming, D. W.; Morris, R. V.; Hurowitz, J. A.; Mahaffy, P. R.; hide

    2016-01-01

    The Sample Analysis at Mars (SAM) and Chemistry and Mineralogy (CheMin) instruments on the Mars Science Laboratory (MSL) have analyzed several subsamples of 860 C). Sulfides or Fe sulfates were detected by CheMin (e.g., CB, MJ, BK) and could contribute to the high temperature SO2 evolution, but in most cases they are not present in enough abundance to account for all of the SO2. This additional SO2 could be largely associated with x-ray amorphous material, which comprises a significant portion of all samples. It can also be attributed to trace S phases present below the CheMin detection limit, or to reactions which lower the temperatures of SO2 evolution from sulfates that are typically expected to thermally decompose at temperatures outside the SAM temperature range (e.g., Ca and Mg sulfates). Here we discuss the results of SAM-like laboratory analyses targeted at understanding this last possibility, focused on understanding if reactions of HCl or an HCl evolving phase (oxychlorine phases, chlorides, etc.) and Ca and Mg sulfates can result in SO2 evolution in the SAM temperature range.

  14. International Collaboration in Packaging Education: Hands-on System-on-Package (SOP) Graduate Level Courses at Indian Institute of Science and Georgia Tech PRC

    OpenAIRE

    Varadarajan, Mahesh; Bhattacharya, Swapan; Doraiswami, Ravi; Rao, Ananda G; Rao, NJ; May, Gary; Conrad, Leyla; Tummala, Rao

    2005-01-01

    System-on-Package (SOP) continues to revolutionize the realization of convergent systems in microelectronics packaging. The SOP concept which began at the Packaging Research Center (PRC) at Georgia Tech has benefited its international collaborative partners in education including the Indian Institute of Science (IISc). The academic program for electronics packaging currently in the Centre for Electronics Design and Technology (CEDT) at IISc is aimed at educating a new breed of globally-compet...

  15. Automated one-loop calculations with GoSam

    International Nuclear Information System (INIS)

    Cullen, Gavin; Greiner, Nicolas; Heinrich, Gudrun; Reiter, Thomas; Luisoni, Gionata; Mastrolia, Pierpaolo; Ossola, Giovanni; Tramontano, Francesco

    2012-01-01

    We present the program package GoSam which is designed for the automated calculation of one-loop amplitudes for multi-particle processes in renormalisable quantum field theories. The amplitudes, which are generated in terms of Feynman diagrams, can be reduced using either D-dimensional integrand-level decomposition or tensor reduction. GoSam can be used to calculate one-loop QCD and/or electroweak corrections to Standard Model processes and offers the flexibility to link model files for theories Beyond the Standard Model. A standard interface to programs calculating real radiation is also implemented. We demonstrate the flexibility of the program by presenting examples of processes with up to six external legs attached to the loop. (orig.)

  16. Automated One-Loop Calculations with GoSam

    CERN Document Server

    Cullen, Gavin; Heinrich, Gudrun; Luisoni, Gionata; Mastrolia, Pierpaolo; Ossola, Giovanni; Reiter, Thomas; Tramontano, Francesco

    2012-01-01

    We present the program package GoSam which is designed for the automated calculation of one-loop amplitudes for multi-particle processes in renormalisable quantum field theories. The amplitudes, which are generated in terms of Feynman diagrams, can be reduced using either D-dimensional integrand-level decomposition or tensor reduction. GoSam can be used to calculate one-loop QCD and/or electroweak corrections to Standard Model processes and offers the flexibility to link model files for theories Beyond the Standard Model. A standard interface to programs calculating real radiation is also implemented. We demonstrate the flexibility of the program by presenting examples of processes with up to six external legs attached to the loop.

  17. THE MYTH OF MATERIAL SUCCESS AS REFLECTED IN SAM WALTON: MADE IN AMERICA-MY STORY

    Directory of Open Access Journals (Sweden)

    Utut Kurniati

    2015-12-01

    Full Text Available American myth of material success had been orchestrated five basic beliefs that were reflected in Sam Walton’s biography, Sam Walton: Made in America-My Story. Those beliefs were: 1 Having a strong will to be successful man in America, Sam Walton was aware that the American democracy allowed its citizens to rise above any limitation in which they may have been born; 2 Then, he rose up from his limitation by hard work. His hard work successfully brought him to the riches and physical comforts; 3 He believed that those rewards came to those who were deserving of them (virtuous; 4 He also believed that those rewards came to those who had the drive and ambition to attain them. Therefore, he was optimistic to attain success in America; 5 Hard work to attain success made Sam Walton a lucky man who received good luck in his life. As a result, his dream of being a successful man in America came true. Keywords: the myth of material success, American dream, hard work

  18. Teleconnection stationarity, variability and trends of the Southern Annular Mode (SAM) during the last millennium

    Science.gov (United States)

    Dätwyler, Christoph; Neukom, Raphael; Abram, Nerilie J.; Gallant, Ailie J. E.; Grosjean, Martin; Jacques-Coper, Martín; Karoly, David J.; Villalba, Ricardo

    2017-11-01

    The Southern Annular Mode (SAM) is the leading mode of atmospheric interannual variability in the Southern Hemisphere (SH) extra-tropics. Here, we assess the stationarity of SAM spatial correlations with instrumental and paleoclimate proxy data for the past millennium. The instrumental period shows that temporal non-stationarities in SAM teleconnections are not consistent across the SH land areas. This suggests that the influence of the SAM index is modulated by regional effects. However, within key-regions with good proxy data coverage (South America, Tasmania, New Zealand), teleconnections are mostly stationary over the instrumental period. Using different stationarity criteria for proxy record selection, we provide new austral summer and annual mean SAM index reconstructions over the last millennium. Our summer SAM reconstructions are very robust to changes in proxy record selection and the selection of the calibration period, particularly on the multi-decadal timescale. In contrast, the weaker performance and lower agreement in the annual mean SAM reconstructions point towards changing teleconnection patterns that may be particularly important outside the summer months. Our results clearly portend that the temporal stationarity of the proxy-climate relationships should be taken into account in the design of comprehensive regional and hemispherical climate reconstructions. The summer SAM reconstructions show no significant relationship to solar, greenhouse gas and volcanic forcing, with the exception of an extremely strong negative anomaly following the AD 1257 Samalas eruption. Furthermore, reconstructed pre-industrial summer SAM trends are very similar to trends obtained by model control simulations. We find that recent trends in the summer SAM lie outside the 5-95% range of pre-industrial natural variability.

  19. SAMS: The synchronization and monitoring system for ATF [Advanced Toroidal Facility] data acquisition

    International Nuclear Information System (INIS)

    Greenwood, D.E.

    1987-01-01

    SAMS performs much of the synchronization of the distributed data acquisition system for the Advanced Toroidal Facility (ATF). SAMS is responsible for propagating shot information and managing te data system directories and logical names. This paper describes how SAMS communicates with other processes, both within the VAX cluster that supports most of the ATF data acquisition and on VAXes that are connected to the cluster via DECnet. 3 refs

  20. Benchmark Simulation of Natural Circulation Cooling System with Salt Working Fluid Using SAM

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, K. K.; Scarlat, R. O.; Hu, R.

    2017-09-03

    Liquid salt-cooled reactors, such as the Fluoride Salt-Cooled High-Temperature Reactor (FHR), offer passive decay heat removal through natural circulation using Direct Reactor Auxiliary Cooling System (DRACS) loops. The behavior of such systems should be well-understood through performance analysis. The advanced system thermal-hydraulics tool System Analysis Module (SAM) from Argonne National Laboratory has been selected for this purpose. The work presented here is part of a larger study in which SAM modeling capabilities are being enhanced for the system analyses of FHR or Molten Salt Reactors (MSR). Liquid salt thermophysical properties have been implemented in SAM, as well as properties of Dowtherm A, which is used as a simulant fluid for scaled experiments, for future code validation studies. Additional physics modules to represent phenomena specific to salt-cooled reactors, such as freezing of coolant, are being implemented in SAM. This study presents a useful first benchmark for the applicability of SAM to liquid salt-cooled reactors: it provides steady-state and transient comparisons for a salt reactor system. A RELAP5-3D model of the Mark-1 Pebble-Bed FHR (Mk1 PB-FHR), and in particular its DRACS loop for emergency heat removal, provides steady state and transient results for flow rates and temperatures in the system that are used here for code-to-code comparison with SAM. The transient studied is a loss of forced circulation with SCRAM event. To the knowledge of the authors, this is the first application of SAM to FHR or any other molten salt reactors. While building these models in SAM, any gaps in the code’s capability to simulate such systems are identified and addressed immediately, or listed as future improvements to the code.

  1. Alternative function for the mitochondrial SAM complex in biogenesis of alpha-helical TOM proteins.

    Science.gov (United States)

    Stojanovski, Diana; Guiard, Bernard; Kozjak-Pavlovic, Vera; Pfanner, Nikolaus; Meisinger, Chris

    2007-12-03

    The mitochondrial outer membrane contains two preprotein translocases: the general translocase of outer membrane (TOM) and the beta-barrel-specific sorting and assembly machinery (SAM). TOM functions as the central entry gate for nuclear-encoded proteins. The channel-forming Tom40 is a beta-barrel protein, whereas all Tom receptors and small Tom proteins are membrane anchored by a transmembrane alpha-helical segment in their N- or C-terminal portion. Synthesis of Tom precursors takes place in the cytosol, and their import occurs via preexisting TOM complexes. The precursor of Tom40 is then transferred to SAM for membrane insertion and assembly. Unexpectedly, we find that the biogenesis of alpha-helical Tom proteins with a membrane anchor in the C-terminal portion is SAM dependent. Each SAM protein is necessary for efficient membrane integration of the receptor Tom22, whereas assembly of the small Tom proteins depends on Sam37. Thus, the substrate specificity of SAM is not restricted to beta-barrel proteins but also includes the majority of alpha-helical Tom proteins.

  2. A classification model of Hyperion image base on SAM combined decision tree

    Science.gov (United States)

    Wang, Zhenghai; Hu, Guangdao; Zhou, YongZhang; Liu, Xin

    2009-10-01

    Monitoring the Earth using imaging spectrometers has necessitated more accurate analyses and new applications to remote sensing. A very high dimensional input space requires an exponentially large amount of data to adequately and reliably represent the classes in that space. On the other hand, with increase in the input dimensionality the hypothesis space grows exponentially, which makes the classification performance highly unreliable. Traditional classification algorithms Classification of hyperspectral images is challenging. New algorithms have to be developed for hyperspectral data classification. The Spectral Angle Mapper (SAM) is a physically-based spectral classification that uses an ndimensional angle to match pixels to reference spectra. The algorithm determines the spectral similarity between two spectra by calculating the angle between the spectra, treating them as vectors in a space with dimensionality equal to the number of bands. The key and difficulty is that we should artificial defining the threshold of SAM. The classification precision depends on the rationality of the threshold of SAM. In order to resolve this problem, this paper proposes a new automatic classification model of remote sensing image using SAM combined with decision tree. It can automatic choose the appropriate threshold of SAM and improve the classify precision of SAM base on the analyze of field spectrum. The test area located in Heqing Yunnan was imaged by EO_1 Hyperion imaging spectrometer using 224 bands in visual and near infrared. The area included limestone areas, rock fields, soil and forests. The area was classified into four different vegetation and soil types. The results show that this method choose the appropriate threshold of SAM and eliminates the disturbance and influence of unwanted objects effectively, so as to improve the classification precision. Compared with the likelihood classification by field survey data, the classification precision of this model

  3. Quality Control Guidelines for SAM Biotoxin Methods

    Science.gov (United States)

    Learn more about quality control guidelines and recommendations for the analysis of samples using the pathogen methods listed in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  4. Quality Control Guidelines for SAM Radiochemical Methods

    Science.gov (United States)

    Learn more about quality control guidelines and recommendations for the analysis of samples using the radiochemistry methods listed in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  5. Quality Control Guidelines for SAM Pathogen Methods

    Science.gov (United States)

    Learn more about quality control guidelines and recommendations for the analysis of samples using the biotoxin methods listed in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  6. Quality Control Guidelines for SAM Chemical Methods

    Science.gov (United States)

    Learn more about quality control guidelines and recommendations for the analysis of samples using the chemistry methods listed in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  7. Non-Photolithographic Manufacturing Processes for Micro-Channels Functioned by Micro-Contact-Printed SAMs

    Science.gov (United States)

    Saigusa, Hiroki; Suga, Yasuo; Miki, Norihisa

    In this paper we propose non-photolithographic fabrication processes of micro-fluid channels with patterned SAMs (Self-Assembled-Monolayers). SAMs with a thiol group are micro-contact printed on a patterned Au/Ti layer, which is vapor-deposited through a shadow mask. Ti is an adhesion layer. Subsequently, the micro-channels are formed by bonding surface-activated PDMS onto the silicon substrate via a silanol group, producing a SAMs-functioned bottom wall of the micro-channel. No photolithographic processes are necessary and thus, the proposed processes are very simple, quick and low cost. The micro-reactors can have various functions associated with the micro-contact-printed SAMs. We demonstrate successful manufacturing of micro-reactors with two types of SAMs. The micro-reactor with patterned AUT (11-amino-1-undecanethiol) successfully trapped nano-particles with a carboxylic acid group, indicating that micro-contact-printed SAMs remain active after the manufacturing processes of the micro-reactor. AUT -functioned micro-channels are applicable to bioassay and to immobilize proteins for DNA arrays. ODT (1-octadecanethiol) makes surfaces hydrophobic with the methyl terminal group. When water was introduced into the micro-reactor with ODT-patterned surfaces, water droplets remained only in the hydrophilic areas where ODT was not patterned. ODT -functioned micro-channels are applicable to fluid handling.

  8. Data handling with SAM and art at the NOνA experiment

    International Nuclear Information System (INIS)

    Aurisano, A; Backhouse, C; Davies, G S; Illingworth, R; Mengel, M; Norman, A; Mayer, N; Rocco, D; Zirnstein, J

    2015-01-01

    During operations, NOvA produces between 5,000 and 7,000 raw files per day with peaks in excess of 12,000. These files must be processed in several stages to produce fully calibrated and reconstructed analysis files. In addition, many simulated neutrino interactions must be produced and processed through the same stages as data. To accommodate the large volume of data and Monte Carlo, production must be possible both on the Fermilab grid and on off-site farms, such as the ones accessible through the Open Science Grid. To handle the challenge of cataloging these files and to facilitate their off-line processing, we have adopted the SAM system developed at Fermilab. SAM indexes files according to metadata, keeps track of each file's physical locations, provides dataset management facilities, and facilitates data transfer to off-site grids. To integrate SAM with Fermilab's art software framework and the NOvA production workflow, we have developed methods to embed metadata into our configuration files, art files, and standalone ROOT files. A module in the art framework propagates the embedded information from configuration files into art files, and from input art files to output art files, allowing us to maintain a complete processing history within our files. Embedding metadata in configuration files also allows configuration files indexed in SAM to be used as inputs to Monte Carlo production jobs. Further, SAM keeps track of the input files used to create each output file. Parentage information enables the construction of self-draining datasets which have become the primary production paradigm used at NOvA. In this paper we will present an overview of SAM at NOvA and how it has transformed the file production framework used by the experiment. (paper)

  9. Winning Attitude & Dedication to Physical Therapy Keep Sam Schmidt on Track

    Science.gov (United States)

    Bosley, Nikki Prevenslik

    2006-01-01

    This article relates how Sam Schmidt returned to living a productive life after an accident left him with spinal cord injury. Schmidt was a former Indy Racing League driver who founded Sam Schmidt Motorsports after his accident in 2000. Schmidt's car hit the wall as he exited turn two during a practice session at Walt Disney World Speedway in…

  10. Technoeconomic Modeling of Battery Energy Storage in SAM

    Energy Technology Data Exchange (ETDEWEB)

    DiOrio, Nicholas [National Renewable Energy Lab. (NREL), Golden, CO (United States); Dobos, Aron [National Renewable Energy Lab. (NREL), Golden, CO (United States); Janzou, Steven [National Renewable Energy Lab. (NREL), Golden, CO (United States); Nelson, Austin [National Renewable Energy Lab. (NREL), Golden, CO (United States); Lundstrom, Blake [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-09-01

    Detailed comprehensive lead-acid and lithium-ion battery models have been integrated with photovoltaic models in an effort to allow System Advisor Model (SAM) to offer the ability to predict the performance and economic benefit of behind the meter storage. In a system with storage, excess PV energy can be saved until later in the day when PV production has fallen, or until times of peak demand when it is more valuable. Complex dispatch strategies can be developed to leverage storage to reduce energy consumption or power demand based on the utility rate structure. This document describes the details of the battery performance and economic models in SAM.

  11. Sam Wagstaffi unustatud kired / Ahto Külvet

    Index Scriptorium Estoniae

    Külvet, Ahto

    2008-01-01

    Dokumentaalfilm "Black, White & Gray: Sam Wagstaff and Robert Mapplethorpe" : autor ja režissöör James Crump : Ameerika Ühendriigid 2007. Filmi näidati filminädala "Art in America" raames Tallinnas

  12. Detection of Organics at Mars: How Wet Chemistry Onboard SAM Helps

    Science.gov (United States)

    Buch, A.; Freissinet, Caroline; Szopa, C.; Glavin, D.; Coll, P.; Cabane, M.; Eigenbrode, J.; Navarro-Gonzalez, R.; Coscia, D.; Teinturier, S.; hide

    2013-01-01

    For the first time in the history of space exploration, a mission of interest to astrobiology could be able to analyze refractory organic compounds in the soil of Mars. Wet chemistry experiment allow organic components to be altered in such a way that improves there detection either by releasing the compounds from sample matricies or by changing the chemical structure to be amenable to analytical conditions. The latter is particular important when polar compounds are present. Sample Analysis at Mars (SAM), on the Curiosity rover of the Mars Science Laboratory mission, has onboard two wet chemistry experiments: derivatization and thermochemolysis. Here we report on the nature of the MTBSTFA derivatization experiment on SAM, the detection of MTBSTFA in initial SAM results, and the implications of this detection.

  13. A QUALITATIVE EVALUATION ON SOP HRD 2007-2013 IN ROMANIA - FOCUS-GROUP STUDY

    Directory of Open Access Journals (Sweden)

    Bud Angelica Mariana

    2015-07-01

    Full Text Available This paper seeks to underline the main problems faced in implementing and using European Union (EU funds in Romania within the Sectoral Operational Programme Human Resources Development (SOP HRD during the first programing period 2007-2013. The problems and barriers revealed were identified during a focus-group for the second interim evaluation of SOPHRD, organized by the Management Authority of this program in Nord-Vest region, in November 2014. The focus-group represents a small part of the entire process of evaluating the programme for the development of human resources during its implementation, with the purpose of finding beneficiaries opinions about the efficiency, effectiveness and relevance of interventions financed through SOP HRD. Beliefs, personal recommendations from the participants are presented in order to improve the use of European funds for development of human resources (in particular and the use of structural instruments (in general. These results and solutions can be efficiently used during the next financial period 2014-2020 to create the framework for every priority axis and key areas of intervention, during the implementation of new projects and within the entire process that these funds require in order to successfully use the structural instruments to catch up with developed countries. Moreover, some of the problems identified can be found in other operational programmes and therefore, this research can be useful for every one that wants to use this kind of financing or has a project of this kind in implementation, without taking into account the European funding source. Besides the qualitative approach given by focus-group research method, this paper is going to present a general approach over SOP HRD in Romania during 2007-2013, from a quantitative perspective (number of projects submitted, approved, contracted, payment rate, absorption rate. Moreover solutions linked to knowledge management practices will be proposed

  14. Electronic patient self-assessment and management (SAM): a novel framework for cancer survivorship.

    Science.gov (United States)

    Vickers, Andrew J; Salz, Talya; Basch, Ethan; Cooperberg, Matthew R; Carroll, Peter R; Tighe, Foss; Eastham, James; Rosen, Raymond C

    2010-06-17

    We propose a novel framework for management of cancer survivorship: electronic patient Self-Assessment and Management (SAM). SAM is a framework for transfer of information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice. Patients who participate in the SAM system are contacted by email at regular intervals and asked to complete validated questionnaires online. Patient responses on these questionnaires are then analyzed in order to provide patients with real-time, online information about their progress and to provide them with tailored and standardized medical advice. Patient-level data from the questionnaires are ported in real time to the patient's health care provider to be uploaded to clinic notes. An initial version of SAM has been developed at Memorial Sloan-Kettering Cancer Center (MSKCC) and the University of California, San Francisco (UCSF) for aiding the clinical management of patients after surgery for prostate cancer. Pilot testing at MSKCC and UCSF suggests that implementation of SAM systems are feasible, with no major problems with compliance (> 70% response rate) or security. SAM is a conceptually simple framework for passing information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice.

  15. Electronic patient self-assessment and management (SAM: a novel framework for cancer survivorship

    Directory of Open Access Journals (Sweden)

    Tighe Foss

    2010-06-01

    Full Text Available Abstract Background We propose a novel framework for management of cancer survivorship: electronic patient Self-Assessment and Management (SAM. SAM is a framework for transfer of information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice. Methods Patients who participate in the SAM system are contacted by email at regular intervals and asked to complete validated questionnaires online. Patient responses on these questionnaires are then analyzed in order to provide patients with real-time, online information about their progress and to provide them with tailored and standardized medical advice. Patient-level data from the questionnaires are ported in real time to the patient's health care provider to be uploaded to clinic notes. An initial version of SAM has been developed at Memorial Sloan-Kettering Cancer Center (MSKCC and the University of California, San Francisco (UCSF for aiding the clinical management of patients after surgery for prostate cancer. Results Pilot testing at MSKCC and UCSF suggests that implementation of SAM systems are feasible, with no major problems with compliance (> 70% response rate or security. Conclusion SAM is a conceptually simple framework for passing information to and from patients in such a way as to increase both the patient's and the health care provider's understanding of the patient's progress, and to help ensure that patient care follows best practice.

  16. The Performance of CSAM SAM when Cycle Length is extended

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Kyung-ho; Moon, Sang-rae [KHNP, Daejeon (Korea, Republic of)

    2016-10-15

    In order to verify validation of that, CPC Axial Power Distribution is compared with Axial Power Distribution based on ICI every week. The difference between CPC Axial Power Distribution and Axial Power Distribution based on ICI increases according as fuels are burned. It is called CPC Axial Power Distribution Root Mean Square Error (CPC RMS Error). SAM and calibration of ex-core detector are important factors influencing the magnitude of the difference. According to vendor, the difference is limited by 8%. Otherwise, CPC penalty increases as many as difference increase. Therefore, KHNP developed Constrained Simulated Annealing Method (CSAM), which has better performance than that of Least Square Method (LSM), to calculate SAM constant. The CSA SAM contributed largely to maintain CPC operating margin. Somewhat, KHNP is developing the technology to be able to operate nuclear power plants for 24 month to optimize their efficiency. This paper shows trends of CPC RMS Error in a case of 24 months operation. Trends are based on data of a few OPR1000s under operation. It is data of OPR1000s that CSA SAM is applied. KHNP is developing the technology to extend operation cycle length in order to optimize the operation efficiency of OPR1000. To verify effect of extended operation cycle length on CPC, CPC Axial Power Distribution RMS Error in a case of 24 months operation was expected using operation data of six cycles in OPR1000. In cases that CPC Axial Power Distribution RMS Error exceeds threshold, operation margin is decreased due to CPC penalty. To prevent CPC operation margin from being decreased, improved method to calculate SAM or to calibrate ex-core detector is required. KHNP will consider the way to maintain CPC operation margin along with 24 month operation technology development, hereafter.

  17. Celiac Disease in Children with Severe Acute Malnutrition (SAM): A Hospital Based Study.

    Science.gov (United States)

    Beniwal, Neetu; Ameta, Gaurav; Chahar, Chandra Kumar

    2017-05-01

    To evaluate the prevalence and clinical features of Celiac disease among children with severe acute malnutrition (SAM). This prospective observational study was conducted in PBM Children Hospital, Bikaner from July 2012 through December 2013. All consecutively admitted children with SAM were recruited. All subjects were screened for Celiac disease by serological test for IgA-anti tissue Transglutaminase (IgA tTG) antibodies. All seropositive children underwent upper gastrointestinal endoscopy for small bowel biopsy for the confirmation. Clinical features of patients with and without celiac disease were compared. The sero-prevalence (IgA tTg positivity) of Celiac disease was found to be 15.38% while prevalence of biopsy confirmed Celiac disease was 14.42% among SAM children. Abdominal distension, diarrhea, anorexia, constipation, pain in abdomen, vitamin deficiencies, edema, clubbing and mouth ulcers were more common in patients of Celiac disease compared to patients without Celiac disease but the difference was statistically significant only for abdominal distension and pain abdomen. There is a high prevalence of Celiac disease in SAM. Screening for Celiac disease (especially in presence of pain abdomen and abdominal distension) should be an essential part of work-up in all children with SAM.

  18. Identification and Analysis of the SET-Domain Family in Silkworm, Bombyx mori

    Directory of Open Access Journals (Sweden)

    Hailong Zhao

    2015-01-01

    Full Text Available As an important economic insect, Bombyx mori is also a useful model organism for lepidopteran insect. SET-domain-containing proteins belong to a group of enzymes named after a common domain that utilizes the cofactor S-adenosyl-L-methionine (SAM to achieve methylation of its substrates. Many SET-domain-containing proteins have been shown to display catalytic activity towards particular lysine residues on histones, but emerging evidence also indicates that various nonhistone proteins are specifically targeted by this clade of enzymes. To explore their diverse functions of SET-domain superfamily in insect, we identified, cloned, and analyzed the SET-domains proteins in silkworm, Bombyx mori. Firstly, 24 genes containing SET domain from silkworm genome were characterized and 17 of them belonged to six subfamilies of SUV39, SET1, SET2, SUV4-20, EZ, and SMYD. Secondly, SET domains of silkworm SET-domain family were intraspecifically and interspecifically conserved, especially for the catalytic core “NHSC” motif, substrate binding site, and catalytic site in the SET domain. Lastly, further analyses indicated that silkworm SET-domain gene BmSu(var3-9 owned different characterization and expression profiles compared to other invertebrates. Overall, our results provide a new insight into the functional and evolutionary features of SET-domain family.

  19. SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis

    Science.gov (United States)

    Ohashi, Masao; Liu, Fang; Hai, Yang; Chen, Mengbin; Tang, Man-Cheng; Yang, Zhongyue; Sato, Michio; Watanabe, Kenji; Houk, K. N.; Tang, Yi

    2017-09-01

    Pericyclic reactions—which proceed in a concerted fashion through a cyclic transition state—are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-L-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme ‘toolboxes’. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.

  20. Multiple endmember spectral-angle-mapper (SAM) analysis improves discrimination of Savanna tree species

    CSIR Research Space (South Africa)

    Cho, Moses A

    2009-08-01

    Full Text Available of this paper was to evaluate the classification performance of a multiple-endmember spectral angle mapper (SAM) classification approach in discriminating seven common African savanna tree species and to compare the results with the traditional SAM classifier...

  1. GoSam. A program for automated one-loop calculations

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, G. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Greiner, N.; Heinrich, G.; Reiter, T. [Max-Planck-Institut fuer Physik, Muenchen (Germany); Luisoni, G. [Durham Univ. (United Kingdom). Inst. for Particle Physics Phenomenology; Mastrolia, P. [Max-Planck-Institut fuer Physik, Muenchen (Germany); Padua Univ. (Italy). Dipt. di Fisica; Ossola, G. [City Univ. of New York, NY (United States). New York City College of Technology; Tramontano, F. [European Organization for Nuclear Research (CERN), Geneva (Switzerland)

    2011-11-15

    The program package GoSam is presented which aims at the automated calculation of one-loop amplitudes for multi-particle processes. The amplitudes are generated in terms of Feynman diagrams and can be reduced using either D-dimensional integrand-level decomposition or tensor reduction, or a combination of both. GoSam can be used to calculate one-loop corrections to both QCD and electroweak theory, and model files for theories Beyond the Standard Model can be linked as well. A standard interface to programs calculating real radiation is also included. The flexibility of the program is demonstrated by various examples. (orig.)

  2. GoSam. A program for automated one-loop calculations

    International Nuclear Information System (INIS)

    Cullen, G.; Greiner, N.; Heinrich, G.; Reiter, T.; Luisoni, G.

    2011-11-01

    The program package GoSam is presented which aims at the automated calculation of one-loop amplitudes for multi-particle processes. The amplitudes are generated in terms of Feynman diagrams and can be reduced using either D-dimensional integrand-level decomposition or tensor reduction, or a combination of both. GoSam can be used to calculate one-loop corrections to both QCD and electroweak theory, and model files for theories Beyond the Standard Model can be linked as well. A standard interface to programs calculating real radiation is also included. The flexibility of the program is demonstrated by various examples. (orig.)

  3. GoSam: A program for automated one-loop calculations

    International Nuclear Information System (INIS)

    Cullen, G; Greiner, N; Heinrich, G; Mastrolia, P; Reiter, T; Luisoni, G; Ossola, G; Tramontano, F

    2012-01-01

    The program package GoSam is presented which aims at the automated calculation of one-loop amplitudes for multi-particle processes. The amplitudes are generated in terms of Feynman diagrams and can be reduced using either D-dimensional integrand-level decomposition or tensor reduction, or a combination of both. GoSam can be used to calculate one-loop corrections to both QCD and electroweak theory, and model files for theories Beyond the Standard Model can be linked as well. A standard interface to programs calculating real radiation is also included. The flexibility of the program is demonstrated by various examples.

  4. Genome sequencing and annotation of Stenotrophomonas sp. SAM8

    Directory of Open Access Journals (Sweden)

    Samy Selim

    2015-12-01

    Full Text Available We report draft genome sequence of Stenotrophomonas sp. strain SAM8, isolated from environmental water. The draft genome size is 3,665,538 bp with a G + C content of 67.2% and contains 6 rRNA sequence (single copies of 5S, 16S & 23S rRNA. The genome sequence can be accessed at DDBJ/EMBL/GenBank under the accession no. LDAV00000000.

  5. General Quality Control (QC) Guidelines for SAM Methods

    Science.gov (United States)

    Learn more about quality control guidelines and recommendations for the analysis of samples using the methods listed in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  6. A viral protein promotes host SAMS1 activity and ethylene production for the benefit of virus infection.

    Science.gov (United States)

    Zhao, Shanshan; Hong, Wei; Wu, Jianguo; Wang, Yu; Ji, Shaoyi; Zhu, Shuyi; Wei, Chunhong; Zhang, Jinsong; Li, Yi

    2017-10-10

    Ethylene plays critical roles in plant development and biotic stress response, but the mechanism of ethylene in host antiviral response remains unclear. Here, we report that Rice dwarf virus (RDV) triggers ethylene production by stimulating the activity of S-adenosyl-L-methionine synthetase (SAMS), a key component of the ethylene synthesis pathway, resulting in elevated susceptibility to RDV. RDV-encoded Pns11 protein specifically interacted with OsSAMS1 to enhance its enzymatic activity, leading to higher ethylene levels in both RDV-infected and Pns11-overexpressing rice. Consistent with a counter-defense role for ethylene, Pns11-overexpressing rice, as well as those overexpressing OsSAMS1 , were substantially more susceptible to RDV infection, and a similar effect was observed in rice plants treated with an ethylene precursor. Conversely, OsSAMS1- knockout mutants, as well as an osein2 mutant defective in ethylene signaling, resisted RDV infection more robustly. Our findings uncover a novel mechanism which RDV manipulates ethylene biosynthesis in the host plants to achieve efficient infection.

  7. The Porter-Whitesides Discrepancy: Revisiting Odd-Even Effects in Wetting Properties of n-Alkanethiolate SAMs

    Directory of Open Access Journals (Sweden)

    Zhengjia Wang

    2015-12-01

    Full Text Available This review discusses the Porter-Whitesides discrepancy in wetting properties of n-alkanethiolate self-assembled monolayers (SAMs. About 25 years ago, Whitesides and coworker failed to observe any odd-even effect in wetting, however, Porter and his coworker did, albeit in select cases. Most previous studies agreed with Whitesides’ results, suggesting the absence of the odd-even effect in hydrophobicity of n-alkanethiolate SAMs. Recent reports have, however, found the odd-even effect in hydrophobicity of n-alkanethiolate SAMs on smooth substrates, indicating that hydrophobicity, and analogous interfacial properties, of n-alkanethiolate SAMs significantly depends on the properties of substrate. Unfortunately, the Whitesides and Porter papers do not report on the quality of the surfaces used. Based on recent work, we inferred that the original discrepancy between Whitesides and Porter can be attributed to the quality of the surface. Odd-even effect of SAMs in charge transport, capacitance, friction, and SAM structure are also discussed in this review to inform the general discussion. The discrepancy between Porter's group and Whitesides’ group could be due to surface roughness, morphology, oxidation, and adventitious contaminants.

  8. Introducing ionic and/or hydrogen bonds into the SAM//Ga2O3 top-interface of Ag(TS)/S(CH2)nT//Ga2O3/EGaIn junctions.

    Science.gov (United States)

    Bowers, Carleen M; Liao, Kung-Ching; Yoon, Hyo Jae; Rappoport, Dmitrij; Baghbanzadeh, Mostafa; Simeone, Felice C; Whitesides, George M

    2014-06-11

    Junctions with the structure Ag(TS)/S(CH2)nT//Ga2O3/EGaIn (where S(CH2)nT is a self-assembled monolayer, SAM, of n-alkanethiolate bearing a terminal functional group T) make it possible to examine the response of rates of charge transport by tunneling to changes in the strength of the interaction between T and Ga2O3. Introducing a series of Lewis acidic/basic functional groups (T = -OH, -SH, -CO2H, -CONH2, and -PO3H) at the terminus of the SAM gave values for the tunneling current density, J(V) in A/cm(2), that were indistinguishable (i.e., differed by less than a factor of 3) from the values observed with n-alkanethiolates of equivalent length. The insensitivity of the rate of tunneling to changes in the terminal functional group implies that replacing weak van der Waals contact interactions with stronger hydrogen- or ionic bonds at the T//Ga2O3 interface does not change the shape (i.e., the height or width) of the tunneling barrier enough to affect rates of charge transport. A comparison of the injection current, J0, for T = -CO2H, and T = -CH2CH3--two groups having similar extended lengths (in Å, or in numbers of non-hydrogen atoms)--suggests that both groups make indistinguishable contributions to the height of the tunneling barrier.

  9. Safety and Waste Management for SAM Pathogen Methods

    Science.gov (United States)

    The General Safety and Waste Management page offers section-specific safety and waste management details for the pathogens included in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  10. Safety and Waste Management for SAM Biotoxin Methods

    Science.gov (United States)

    The General Safety and Waste Management page offers section-specific safety and waste management details for the biotoxins included in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  11. Thermal and Evolved Gas Analysis of Calcite Under Reduced Operating Pressures: Implications for the 2011 MSL Sample Analysis at Mars (SAM) Instrument

    Science.gov (United States)

    Lauer, H. V. Jr.; Ming, D. W.; Sutter, B.; Mahaffy, P. R.

    2010-01-01

    The Mars Science Laboratory (MSL) is scheduled for launch in 2011. The science objectives for MSL are to assess the past or present biological potential, to characterize the geology, and to investigate other planetary processes that influence habitability at the landing site. The Sample Analysis at Mars (SAM) is a key instrument on the MSL payload that will explore the potential habitability at the landing site [1]. In addition to searching for organic compounds, SAM will have the capability to characterized evolved gases as a function of increasing temperature and provide information on the mineralogy of volatile-bearing phases such as carbonates, sulfates, phyllosilicates, and Fe-oxyhydroxides. The operating conditions in SAM ovens will be maintained at 30 mb pressure with a He carrier gas flowing at 1 sccm. We have previously characterized the thermal and evolved gas behaviors of volatile-bearing species under reduced pressure conditions that simulated operating conditions of the Thermal and Evolved Gas Analyzer (TEGA) that was onboard the 2007 Mars Phoenix Scout Mission [e.g., 2-8]. TEGA ovens operated at 12 mb pressure with a N2 carrier gas flowing at 0.04 sccm. Another key difference between SAM and TEGA is that TEGA was able to perform differential scanning calorimetry whereas SAM only has a pyrolysis oven. The operating conditions for TEGA and SAM have several key parameter differences including operating pressure (12 vs 30 mb), carrier gas (N2 vs. He), and carrier gas flow rate (0.04 vs 1 sccm). The objectives of this study are to characterize the thermal and evolved gas analysis of calcite under SAM operating conditions and then compare it to calcite thermal and evolved gas analysis under TEGA operating conditions.

  12. ISO19770-1:2012 SAM process guidance

    CERN Document Server

    Canavan, Rory

    2012-01-01

    The pocket guide offers a concise summary of the principles of software asset management as conveyed by ISO 19770-1: 2012, and provides advice and guidance on how to kick-start your own SAM programme - something the Standard alone doesn't offer.

  13. Safety and Waste Management for SAM Chemistry Methods

    Science.gov (United States)

    The General Safety and Waste Management page offers section-specific safety and waste management details for the chemical analytes included in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  14. Safety and Waste Management for SAM Radiochemical Methods

    Science.gov (United States)

    The General Safety and Waste Management page offers section-specific safety and waste management details for the radiochemical analytes included in EPA's Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

  15. Membrane topology of Golgi-localized probable S-adenosylmethionine-dependent methyltransferase in tobacco (Nicotiana tabacum) BY-2 cells.

    Science.gov (United States)

    Liu, Jianping; Hayashi, Kyoko; Matsuoka, Ken

    2015-01-01

    S-adenosylmethionine (SAM)-dependent methyltransferases (MTases) transfer methyl groups to substrates. In this study, a novel putative tobacco SAM-MTase termed Golgi-localized methyl transferase 1 (GLMT1) has been characterized. GLMT1 is comprised of 611 amino acids with short N-terminal region, putative transmembrane region, and C-terminal SAM-MTase domain. Expression of monomeric red fluorescence protein (mRFP)-tagged protein in tobacco BY-2 cell indicated that GLMT1 is a Golgi-localized protein. Analysis of the membrane topology by protease digestion suggested that both C-terminal catalytic region and N-terminal region seem to be located to the cytosolic side of the Golgi apparatus. Therefore, GLMT1 might have a different function than the previously studied SAM-MTases in plants.

  16. MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

    Science.gov (United States)

    Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

    2013-05-01

    The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

  17. Monovalent Cation Activation of the Radical SAM Enzyme Pyruvate Formate-Lyase Activating Enzyme.

    Science.gov (United States)

    Shisler, Krista A; Hutcheson, Rachel U; Horitani, Masaki; Duschene, Kaitlin S; Crain, Adam V; Byer, Amanda S; Shepard, Eric M; Rasmussen, Ashley; Yang, Jian; Broderick, William E; Vey, Jessica L; Drennan, Catherine L; Hoffman, Brian M; Broderick, Joan B

    2017-08-30

    Pyruvate formate-lyase activating enzyme (PFL-AE) is a radical S-adenosyl-l-methionine (SAM) enzyme that installs a catalytically essential glycyl radical on pyruvate formate-lyase. We show that PFL-AE binds a catalytically essential monovalent cation at its active site, yet another parallel with B 12 enzymes, and we characterize this cation site by a combination of structural, biochemical, and spectroscopic approaches. Refinement of the PFL-AE crystal structure reveals Na + as the most likely ion present in the solved structures, and pulsed electron nuclear double resonance (ENDOR) demonstrates that the same cation site is occupied by 23 Na in the solution state of the as-isolated enzyme. A SAM carboxylate-oxygen is an M + ligand, and EPR and circular dichroism spectroscopies reveal that both the site occupancy and the identity of the cation perturb the electronic properties of the SAM-chelated iron-sulfur cluster. ENDOR studies of the PFL-AE/[ 13 C-methyl]-SAM complex show that the target sulfonium positioning varies with the cation, while the observation of an isotropic hyperfine coupling to the cation by ENDOR measurements establishes its intimate, SAM-mediated interaction with the cluster. This monovalent cation site controls enzyme activity: (i) PFL-AE in the absence of any simple monovalent cations has little-no activity; and (ii) among monocations, going down Group 1 of the periodic table from Li + to Cs + , PFL-AE activity sharply maximizes at K + , with NH 4 + closely matching the efficacy of K + . PFL-AE is thus a type I M + -activated enzyme whose M + controls reactivity by interactions with the cosubstrate, SAM, which is bound to the catalytic iron-sulfur cluster.

  18. The ALICE Glance Shift Accounting Management System (SAMS)

    Science.gov (United States)

    Martins Silva, H.; Abreu Da Silva, I.; Ronchetti, F.; Telesca, A.; Maidantchik, C.

    2015-12-01

    ALICE (A Large Ion Collider Experiment) is an experiment at the CERN LHC (Large Hadron Collider) studying the physics of strongly interacting matter and the quark-gluon plasma. The experiment operation requires a 24 hours a day and 7 days a week shift crew at the experimental site, composed by the ALICE collaboration members. Shift duties are calculated for each institute according to their correlated members. In order to ensure the full coverage of the experiment operation as well as its good quality, the ALICE Shift Accounting Management System (SAMS) is used to manage the shift bookings as well as the needed training. ALICE SAMS is the result of a joint effort between the Federal University of Rio de Janeiro (UFRJ) and the ALICE Collaboration. The Glance technology, developed by the UFRJ and the ATLAS experiment, sits at the basis of the system as an intermediate layer isolating the particularities of the databases. In this paper, we describe the ALICE SAMS development process and functionalities. The database has been modelled according to the collaboration needs and is fully integrated with the ALICE Collaboration repository to access members information and respectively roles and activities. Run, period and training coordinators can manage their subsystem operation and ensure an efficient personnel management. Members of the ALICE collaboration can book shifts and on-call according to pre-defined rights. ALICE SAMS features a user profile containing all the statistics and user contact information as well as the Institutes profile. Both the user and institute profiles are public (within the scope of the collaboration) and show the credit balance in real time. A shift calendar allows the Run Coordinator to plan data taking periods in terms of which subsystems shifts are enabled or disabled and on-call responsible people and slots. An overview display presents the shift crew present in the control room and allows the Run Coordination team to confirm the presence

  19. Molten Salt Power Tower Cost Model for the System Advisor Model (SAM)

    Energy Technology Data Exchange (ETDEWEB)

    Turchi, C. S.; Heath, G. A.

    2013-02-01

    This report describes a component-based cost model developed for molten-salt power tower solar power plants. The cost model was developed by the National Renewable Energy Laboratory (NREL), using data from several prior studies, including a contracted analysis from WorleyParsons Group, which is included herein as an Appendix. The WorleyParsons' analysis also estimated material composition and mass for the plant to facilitate a life cycle analysis of the molten salt power tower technology. Details of the life cycle assessment have been published elsewhere. The cost model provides a reference plant that interfaces with NREL's System Advisor Model or SAM. The reference plant assumes a nominal 100-MWe (net) power tower running with a nitrate salt heat transfer fluid (HTF). Thermal energy storage is provided by direct storage of the HTF in a two-tank system. The design assumes dry-cooling. The model includes a spreadsheet that interfaces with SAM via the Excel Exchange option in SAM. The spreadsheet allows users to estimate the costs of different-size plants and to take into account changes in commodity prices. This report and the accompanying Excel spreadsheet can be downloaded at https://sam.nrel.gov/cost.

  20. iSAM: An iPhone Stealth Airborne Malware

    OpenAIRE

    Damopoulos , Dimitrios; Kambourakis , Georgios; Gritzalis , Stefanos

    2011-01-01

    Part 2: Malware, Information Flow and DoS Attacks; International audience; Modern and powerful mobile devices comprise an attractive target for any potential intruder or malicious code. The usual goal of an attack is to acquire users’ sensitive data or compromise the device so as to use it as a stepping stone (or bot) to unleash a number of attacks to other targets. In this paper, we focus on the popular iPhone device.We create a new stealth and airborne malware namely iSAM able to wirelessly...

  1. Annals of SAM meeting `96. National meeting on precious metals; Anales de las jornadas SAM `96. Encuentro nacional de metales preciosos

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    Works are presented at the SAM meeting `96 of the Argentine Materials Association. The papers can be grouped under the following main topics: physical metallurgy; ceramics; polymers; precious metals; extractive metallurgy; corrosion; powder metallurgy. refs., ills.

  2. Kuula. Kuu artist Sam Sparro. Kuu plaat / Mart Juur

    Index Scriptorium Estoniae

    Juur, Mart, 1964-

    2008-01-01

    Artistist Sam Sparrost. Heliplaatidest: "Sex And The City" Original Motion Picture Soundtrack, "Maestro: Blue Note Trip", Melvin/Soo/Remmel/Julm "Geografix", Alanis Morrisette "Flavors Of Entanglement", Guillemots "Red"

  3. The SH2 Domain Interaction Landscape

    Directory of Open Access Journals (Sweden)

    Michele Tinti

    2013-04-01

    Full Text Available Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a high-density peptide chip technology that allows for probing of the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique, we have experimentally identified thousands of putative SH2-peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2-mediated probabilistic interaction network, which we make available as a community resource in the PepspotDB database. A predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the extracellular signal-regulated kinase activation loop was validated by experiments in living cells.

  4. The Investigation of Perchlorate/Iron Phase Mixtures as A Possible Source of Oxygen Detected by the Sample Analysis at Mars (SAM) Instrument in Gale Crater, Mars

    Science.gov (United States)

    Sutter, B.; Heil, E.; Morris, R. V.; Archer, P. D.; Ming, D. W.; Niles, P. B.; Eigenbrode, J. L.; Franz, H.; Freissinet C.; Glavin, D. P.; hide

    2015-01-01

    The Sample Analysis at Mars (SAM) instrument onboard the Curiosity rover detected O2 and HCl gas releases from the Rocknest (RN) eolian bedform and the John Klein (JK) and Cumberland (CB) drill hole materials in Gale Crater. Chlorinated hydrocarbons have also been detected by the SAM quadrupole mass spectrometer (QMS) and gas chromatography/mass spectrometer (GCMS). These detections along with the detection of perchlorate (ClO4-) by the Mars Phoenix Lander's Wet Chemistry Laboratory (WCL) suggesting perchlorate is a possible candidate for evolved O2 and chlorine species. Laboratory thermal analysis of individual per-chlorates has yet to provide an unequivocal temperature match to the SAM O2 and HCl release data. These detections along with the detection of perchlorate (ClO4-) by the Mars Phoenix Lander's Wet Chemistry Laboratory suggested perchlorate is a possible candidate for evolved O2 and chlorine species. Laboratory thermal analysis of pure perchlorates has yet to provide an unequivocal temperature match to the SAM O2 and HCl release data. Analog laboratory analysis of iron mineralogy detected in Gale materials that was physically mixed with Ca- and Mg-perchlorate has been shown to catalyze lower O2 release temperatures and approach some SAM O2 release data. Instead of physical mixtures used in previous work, the work presented here utilized perchlorate solutions added to Fe phases. This technique allowed for perchlorate to come in closer contact with the Fe-phase and may more closely mimic Mars conditions where humidity can increase enough to cause deliquescence of the highly hygroscopic perchlorate phases. The objective of this work is to: 1) Utilize a laboratory SAM analog instrument to evaluate the O2 release temperatures from Mg- and Ca-perchlorates solutions applied to Fephases detetected in Gale Crate; and 2) Determine if perchlorate solutions can provide improved matches with the SAM O2 temperature release profiles.

  5. SH2 Domain Histochemistry.

    Science.gov (United States)

    Buhs, Sophia; Nollau, Peter

    2017-01-01

    Among posttranslational modifications, the phosphorylation of tyrosine residues is a key modification in cell signaling. Because of its biological importance, characterization of the cellular state of tyrosine phosphorylation is of great interest. Based on the unique properties of endogenously expressed SH2 domains recognizing tyrosine phosphorylated signaling proteins with high specificity we have developed an alternative approach, coined SH2 profiling, enabling us to decipher complex patterns of tyrosine phosphorylation in various normal and cancerous tissues. So far, SH2 profiling has largely been applied for the analysis of protein extracts with the limitation that information on spatial distribution and intensity of tyrosine phosphorylation within a tissue is lost. Here, we describe a novel SH2 domain based strategy for differential characterization of the state of tyrosine phosphorylation in formaldehyde-fixed and paraffin-embedded tissues. This approach demonstrates that SH2 domains may serve as very valuable tools for the analysis of the differential state of tyrosine phosphorylation in primary tissues fixed and processed under conditions frequently applied by routine pathology laboratories.

  6. Impact analysis of side door of a car and bullet proof vest with material ‘SAM2X5-630’ using finite element analysis

    Science.gov (United States)

    Dhode, Trushant; Patil, Girish; Rajkumar, E.

    2017-11-01

    The components which are bound to impact are subjected to deformation even though it may be for a small scale. The efforts are always on for finding the best material to take impact that has no failure or moreover, less plastic deformation. A newly found material which is glass matrix steel named as ‘SAM2X5-630’ has astounding high elastic limit of 12.5GPa. Thus it can take powerful impact & regain its original shape avoiding the deformation of component under impact. The paper is focused on performing the Finite element analysis to assess the behaviour of ‘SAM2X5-630’ steel under impact loading of side door of car as well as impact of bullet on bulletproof jacket on which the material is assigned. The displacement or deformation occurred during impact is found to be lesser than known materials like Kevlar in bulletproof vest and Aluminium alloy in car door.

  7. Magnetic domain structure and domain-wall energy in UFe8Ni2Si2 and UFe6Ni4Si2 intermetallic compounds

    International Nuclear Information System (INIS)

    Wyslocki, J.J.; Suski, W.; Wochowski, K.

    1994-01-01

    Magnetic domain structures in the UFe 8 Ni 2 Si 2 and UFe 6 Ni 4 Si 2 compounds were studied using the powder pattern method. The domain structure observed is typical for uniaxial materials. The domain-wall energy density γ was determined from the average surface domain width D s observed on surfaces perpendicular to the easy axis as equal to 16 erg/cm 2 for UFe 8 Ni 2 Si 2 and 10 erg/cm 2 for UFe 6 Ni 4 Si 2 . Moreover, the critical diameter for single domain particle D c was calculated for the studied compounds

  8. Niedualna uważność a stan samādhi w kontekście badań neurofenomenologicznych

    Directory of Open Access Journals (Sweden)

    Piotr PŁANETA

    2016-12-01

    Full Text Available The aim of this paper is to compare various meditative states, such as Buddhist dhyāna‑s, yogic nirbīja samādhi and nondual awareness (Tib. gñis‑med. The primary source texts I refere to are Yogasūtras of Patañjali, Ānāpānasmṛtisūtra (MN 118, Samādhisūtra (AN 4.41, The Tibetan Yogas of Dream and Sleep. I also discuss some relevant claims of contemporary empirical studies. First, I define the key terms used in Eastern meditation studies as well as in neurophenomenology, a contemporary method applied to examining the meditative states of mind, such as samādhi, dhyāna, and śamatha. Inspired by Shinzen Young, I distinguish three groups of meditative states that might be identified with nondual awareness. These three groups are: (1 the second, the third and fourth Buddhist dhyāna being equivalent to nirvicāra samādhi and nirānanda samādhi in the classical Indian yoga; (2 nirbīja samādhi and (3 nondual awareness, typical to the Mahayāna contemplative traditions. I explain why we can recognize each of the above states as nondual awareness and how they differ from each other. Then, I make a comparison between meditation practice explained in Ānāpānasmṛtisūtra and nondual awareness presented in the Tibetan Buddhism. Besides, I discuss the above kinds of mental states in terms of recent neurophenomenological findings. While doing so, I am trying to demonstrate that our understanding of meditation can benefit from the empirical studies which help us to objectify this kind of subjective experience, to some degree, if they are given an adequate place in our study.

  9. The SH2 domain interaction landscape.

    Science.gov (United States)

    Tinti, Michele; Kiemer, Lars; Costa, Stefano; Miller, Martin L; Sacco, Francesca; Olsen, Jesper V; Carducci, Martina; Paoluzi, Serena; Langone, Francesca; Workman, Christopher T; Blom, Nikolaj; Machida, Kazuya; Thompson, Christopher M; Schutkowski, Mike; Brunak, Søren; Mann, Matthias; Mayer, Bruce J; Castagnoli, Luisa; Cesareni, Gianni

    2013-04-25

    Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a high-density peptide chip technology that allows for probing of the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique, we have experimentally identified thousands of putative SH2-peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2-mediated probabilistic interaction network, which we make available as a community resource in the PepspotDB database. A predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the extracellular signal-regulated kinase activation loop was validated by experiments in living cells. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Simulated SAM A-scans on multilayer MEMS components

    DEFF Research Database (Denmark)

    Janting, Jakob; Petersen, Dirch Hjorth; Greisen, Christoffer

    2002-01-01

    A spreadsheet program for simulation of Scanning Acoustic Microscopy (SAM) A-scans on multilayer structures has been developed. Using this program, structure variations in samples can be analysed better. Further samples can be prepared to get optimal signal for enhanced failure and materials...

  11. Electrochemistry of 2-dimethylaminoethanethiol SAM on gold electrode: Interaction with SWCNT-poly(m-aminobenzene sulphonic acid), electric field-induced protonation-deprotonation, and surface pKa

    CSIR Research Space (South Africa)

    Pillay, J

    2009-06-01

    Full Text Available -called electric field induced protonation-deprotonation process, hitherto observed for the -COOH terminated SAMs, is also observed for the -N(H)+(CH3)2 terminated. The surface pKa of DMAET was estimated as 7.6, smaller than its solution pKa of 10.8. It is also...

  12. Background of SAM atom-fraction profiles

    International Nuclear Information System (INIS)

    Ernst, Frank

    2017-01-01

    Atom-fraction profiles acquired by SAM (scanning Auger microprobe) have important applications, e.g. in the context of alloy surface engineering by infusion of carbon or nitrogen through the alloy surface. However, such profiles often exhibit an artifact in form of a background with a level that anti-correlates with the local atom fraction. This article presents a theory explaining this phenomenon as a consequence of the way in which random noise in the spectrum propagates into the discretized differentiated spectrum that is used for quantification. The resulting model of “energy channel statistics” leads to a useful semi-quantitative background reduction procedure, which is validated by applying it to simulated data. Subsequently, the procedure is applied to an example of experimental SAM data. The analysis leads to conclusions regarding optimum experimental acquisition conditions. The proposed method of background reduction is based on general principles and should be useful for a broad variety of applications. - Highlights: • Atom-fraction–depth profiles of carbon measured by scanning Auger microprobe • Strong background, varies with local carbon concentration. • Needs correction e.g. for quantitative comparison with simulations • Quantitative theory explains background. • Provides background removal strategy and practical advice for acquisition

  13. Background of SAM atom-fraction profiles

    Energy Technology Data Exchange (ETDEWEB)

    Ernst, Frank

    2017-03-15

    Atom-fraction profiles acquired by SAM (scanning Auger microprobe) have important applications, e.g. in the context of alloy surface engineering by infusion of carbon or nitrogen through the alloy surface. However, such profiles often exhibit an artifact in form of a background with a level that anti-correlates with the local atom fraction. This article presents a theory explaining this phenomenon as a consequence of the way in which random noise in the spectrum propagates into the discretized differentiated spectrum that is used for quantification. The resulting model of “energy channel statistics” leads to a useful semi-quantitative background reduction procedure, which is validated by applying it to simulated data. Subsequently, the procedure is applied to an example of experimental SAM data. The analysis leads to conclusions regarding optimum experimental acquisition conditions. The proposed method of background reduction is based on general principles and should be useful for a broad variety of applications. - Highlights: • Atom-fraction–depth profiles of carbon measured by scanning Auger microprobe • Strong background, varies with local carbon concentration. • Needs correction e.g. for quantitative comparison with simulations • Quantitative theory explains background. • Provides background removal strategy and practical advice for acquisition.

  14. General response of Salmonella enterica serovar Typhimurium to desiccation: A new role for the virulence factors sopD and sseD in survival.

    Directory of Open Access Journals (Sweden)

    Alice Maserati

    Full Text Available Salmonella can survive for long periods under extreme desiccation conditions. This stress tolerance poses a risk for food safety, but relatively little is known about the molecular and cellular regulation of this adaptation mechanism. To determine the genetic components involved in Salmonella's cellular response to desiccation, we performed a global transcriptomic analysis comparing S. enterica serovar Typhimurium cells equilibrated to low water activity (aw 0.11 and cells equilibrated to high water activity (aw 1.0. The analysis revealed that 719 genes were differentially regulated between the two conditions, of which 290 genes were up-regulated at aw 0.11. Most of these genes were involved in metabolic pathways, transporter regulation, DNA replication/repair, transcription and translation, and, more importantly, virulence genes. Among these, we decided to focus on the role of sopD and sseD. Deletion mutants were created and their ability to survive desiccation and exposure to aw 0.11 was compared to the wild-type strain and to an E. coli O157:H7 strain. The sopD and sseD mutants exhibited significant cell viability reductions of 2.5 and 1.3 Log (CFU/g, respectively, compared to the wild-type after desiccation for 4 days on glass beads. Additional viability differences of the mutants were observed after exposure to aw 0.11 for 7 days. E. coli O157:H7 lost viability similarly to the mutants. Scanning electron microscopy showed that both mutants displayed a different morphology compared to the wild-type and differences in production of the extracellular matrix under the same conditions. These findings suggested that sopD and sseD are required for Salmonella's survival during desiccation.

  15. Raman mapping and in situ SERS spectroelectrochemical studies of 6-mercaptopurine SAMs on the gold electrode.

    Science.gov (United States)

    Yang, Haifeng; Liu, Yanli; Liu, Zhimin; Yang, Yu; Jiang, Jianhui; Zhang, Zongrang; Shen, Guoli; Yu, Ruqin

    2005-02-24

    The self-assembled monolayers (SAMs) of 6-mercaptopurine (6MP) were formed at the roughened polycrystalline gold surfaces in acid and alkaline media. The time-dependent Raman mapping spectral analysis in conjunction with the quantum calculations for the vibrational modes using ab initio BLYP/6-31G method suggested that both of the resulted 6MP SAMs adopted the same adsorption mode through the S atom of pyrimidine moiety and the N7 atom of the imidazole moiety anchoring the gold surface in a vertical way. The in situ surface-enhanced Raman scattering spectroelectrochemical experiment was conducted to examine the stability of the SAMs at various bias potentials. It was found that the detaching process of the 6MP SAMs from the surface involved one electron reduction as the voltage was applied at ca. 0.7 V vs a standard calomel electrode.

  16. Proposals for enhancing tactical planning in grocery retailing with S&OP

    DEFF Research Database (Denmark)

    Dreyer, Heidi Carin; Kiil, Kasper; Dukovska-Popovska, Iskra

    2018-01-01

    Purpose-The purpose of this paper is to explore tactical planning in grocery retailing and propose how process and integration mechanisms from sales and operations planning (S&OP) can enhance retail tactical planning.Design/methodology/approach-This work follows an explorative design with case...... studies from the grocery retailing industry in Finland, Norway, and the UK.Findings-The tactical planning process focuses on demand management and securing product availability from suppliers in order to reach sales targets. Less attention is directed toward balancing supply and demand or toward providing...... a single plan to guide company operations. Planning appeared to be functionally oriented with limited coordination between functional plans, but it did include external integration that improved forecast accuracy.Research limitations/implications-The study involves grocery retailer cases with variable...

  17. Orientation of 6-mercaptopurine SAMs at the silver electrode as studied by Raman mapping and in situ SERS.

    Science.gov (United States)

    Chu, Hui; Yang, Haifeng; Huan, Shuangyan; Shen, Guoli; Yu, Ruqin

    2006-03-23

    Self-assembled monolayers (SAMs) of 6-mercaptopurine (6MP) on a silver electrode in acid and alkaline media were investigated by a combination protocol of the SERS technique with Raman mapping, and it was found that the adsorption mode of 6MP SAMs changed with the pH value of the environment. Quantum calculations for the vibrational mode were performed by the BLYP/6-31G method. 6MP was adsorbed on the silver electrode with a tilted orientation via S, N1, and N7 atoms in acid medium, while the SAMs adopted head-on adsorption modes with the S atom and the N1 atom anchoring the silver surface in alkaline medium. However, 6MP SAMs turned to the same upright orientation on the electrode through the S and N7 atoms when either acid or basic solution was removed. Stability of 6MP SAMs was observed by in situ SERS spectroelectrochemical measurements. The results reveal that the desorption potentials of 6MP SAMs formed under acid and alkaline conditions from the Ag electrode were at ca. -1.3 V and -1.6 V vs SCE, respectively.

  18. Atmospheric modeling of Mars CH4 subsurface clathrates releases mimicking SAM and 2003 Earth-based detections

    Science.gov (United States)

    Pla-García, J.; Rafkin, S. C.

    2017-12-01

    The aim of this work is to establish the amount of mixing during all martian seasons to test whether CH4 releases inside or outside of Gale crater are consistent with MSL-SAM observations. Several modeling scenarios were configured, including instantaneous and steady releases, both inside and outside the crater. A simulation to mimic the 2003 Earth-based detections (Mumma et al. 2009 or M09) was also performed. In the instantaneous release inside Gale experiments, Ls270 was shown to be the faster mixing season when air within and outside the crater was well mixed: all tracer mass inside the crater is diluted after just 8 hours. The mixing of near surface crater air with the external environment in the rest of the year is potentially rapid but slower than Ls270.In the instantaneous release outside Gale (NW) experiment, in just 12 hours the CH4 that makes it to the MSL landing location is diluted by six orders of magnitude. The timescale of mixing in MRAMS experiments is on the order of 1 sol regardless of season. The duration of the CH4 peak observed by SAM is 100 sols. Therefore there is a steady release inside the crater, or there is a very large magnitude steady release outside the crater. In the steady release Gale experiments, CH4 flux rate from ground is 1.8 kg m-2 s-1 (derived from Gloesener et al. 2017 clathrates fluxes) and it is not predictive. In these experiments, 200 times lower CH4 values detected by SAM are modeled around MSL location. There are CH4 concentration variations of orders of magnitude depending on the hour, so timing of SAM measurements is important. With a larger (but further away) outside crater release area compared to inside, similar CH4 values around MSL are modeled, so distance to source is important. In the steady experiments mimicking M09 detection release area, only 12 times lower CH4 values detected by SAM are modeled around MSL. The highest value in the M09 modeled scenario (0.6 ppbv) is reached in Ls270. This value is the

  19. miCLIP-MaPseq, a Substrate Identification Approach for Radical SAM RNA Methylating Enzymes.

    Science.gov (United States)

    Stojković, Vanja; Chu, Tongyue; Therizols, Gabriel; Weinberg, David E; Fujimori, Danica Galonić

    2018-06-13

    Although present across bacteria, the large family of radical SAM RNA methylating enzymes is largely uncharacterized. Escherichia coli RlmN, the founding member of the family, methylates an adenosine in 23S rRNA and several tRNAs to yield 2-methyladenosine (m 2 A). However, varied RNA substrate specificity among RlmN enzymes, combined with the ability of certain family members to generate 8-methyladenosine (m 8 A), makes functional predictions across this family challenging. Here, we present a method for unbiased substrate identification that exploits highly efficient, mechanism-based cross-linking between the enzyme and its RNA substrates. Additionally, by determining that the thermostable group II intron reverse transcriptase introduces mismatches at the site of the cross-link, we have identified the precise positions of RNA modification using mismatch profiling. These results illustrate the capability of our method to define enzyme-substrate pairs and determine modification sites of the largely uncharacterized radical SAM RNA methylating enzyme family.

  20. CE-SAM: a conversational interface for ISR mission support

    Science.gov (United States)

    Pizzocaro, Diego; Parizas, Christos; Preece, Alun; Braines, Dave; Mott, David; Bakdash, Jonathan Z.

    2013-05-01

    There is considerable interest in natural language conversational interfaces. These allow for complex user interactions with systems, such as fulfilling information requirements in dynamic environments, without requiring extensive training or a technical background (e.g. in formal query languages or schemas). To leverage the advantages of conversational interactions we propose CE-SAM (Controlled English Sensor Assignment to Missions), a system that guides users through refining and satisfying their information needs in the context of Intelligence, Surveillance, and Reconnaissance (ISR) operations. The rapidly-increasing availability of sensing assets and other information sources poses substantial challenges to effective ISR resource management. In a coalition context, the problem is even more complex, because assets may be "owned" by different partners. We show how CE-SAM allows a user to refine and relate their ISR information needs to pre-existing concepts in an ISR knowledge base, via conversational interaction implemented on a tablet device. The knowledge base is represented using Controlled English (CE) - a form of controlled natural language that is both human-readable and machine processable (i.e. can be used to implement automated reasoning). Users interact with the CE-SAM conversational interface using natural language, which the system converts to CE for feeding-back to the user for confirmation (e.g. to reduce misunderstanding). We show that this process not only allows users to access the assets that can support their mission needs, but also assists them in extending the CE knowledge base with new concepts.

  1. The Seismic Aftershock Monitoring System (SAMS) for OSI - Experiences from IFE14

    Science.gov (United States)

    Gestermann, Nicolai; Sick, Benjamin; Häge, Martin; Blake, Thomas; Labak, Peter; Joswig, Manfred

    2016-04-01

    the triggering event are expected in a very low magnitude range. Therefore the detection threshold of the network is one of the key parameters of SAMS and crucial for the success of the monitoring. One of the objectives was to record magnitude values down to -2.0 ML. The threshold values have been compared with historical seismicity in the region and those monitored during IFE14. Results of the threshold detection estimation and experiences of the exercise will be presented.

  2. Influencia del Estado de Oxidación del Ión Cobalto en la Estabilidad de Electrodos Modificados con Monocapas SAM-TOA-ANTA-Con+-HRP-NHis.

    Directory of Open Access Journals (Sweden)

    Pedro R. Matheus*

    Full Text Available Influence of state oxidation of cobalt ion in the stability electrodes modified with monolayers SAM-TOA-ANTA-Con+-HRP-NHis. Quartz Crystal Microbalance (QCM was used to investigate the adsorption of the HRP-NHis enzyme (horseradish peroxidase, which was modified by the addition of a tail of six histidine on its extreme N-terminal. The QCM operating at flow of 0.025 mL min-1 on a crystal whose gold electrode was modified with monolayers of SAM-TOA-ANTA-Co2+ and SAM-TOA-ANTA -Co3+. The oxidize form was obtained from the electrochemical oxidation of a monolayer of SAM-TOA-ANTA-Co2+. The results suggest that the HRP-NHis is attached to both monolayers in a similar way; on the contrary, the desortion of the attached protein is dramatically different. Thus, whereas the ligand-Co2+ bonds are reversible, which allows that the anchored protein is easily replaced by imidazol molecules. The 3+ oxidation state of the metal does not allow the interchange of protein by the imidazol molecules.

  3. Artificially phase-separated binary self-assembled monolayers composed of 11-amino-1-undecanethiolate and 10-carboxy-1-decanethiolate on Au(1 1 1): A comparative study of two preparing methods

    International Nuclear Information System (INIS)

    Phong, Pham Hong; Tomono, Hyroyuki; Nishi, Naoya; Yamamoto, Masahiro; Kakiuchi, Takashi

    2008-01-01

    Two methods have been compared for preparing artificially phase-separated two-component SAMs on Au(1 1 1) composed of 11-amino-1-undecanethiolates (AUTe) and 10-carboxyl-1-decanethiolates (CDTe), which would form, thermodynamically, a homogeneously mixed binary SAMs. The first method starts with the formation of a phase-separated binary SAM of AUTe and 2-hydroxy-1-ethanethiolate (HETe) as a template of the artificially phase-separated SAM, followed by the selective desorption of HETe domains and succeeding filling of the vacancy with CDTe. The second method utilizes fluoren-9-ylmethyl N-(11-mercaptoundecyl) carbamate (FMUCe) instead of 11-amino-1-undecanethiol in preparing the template. After the filling with CDTe, the 9-fluorenylmethyloxycarbonyl (Fmoc) group is removed to obtain AUTe domains. Both methods yield artificially phase-separated binary SAMs having AUTe domains of tens nanometer across. The molecularly flat SAM surface with nanometer-scale domains of different acid-base and electrostatic properties are thus created. For preparing binary SAMs with a higher degree of phase separation, the second method is a better choice; a more clear-cut phase separation is achieved

  4. The Investigation of Chlorates as a Possible Source of Oxygen and Chlorine Detected by the Sample Analysis at Mars (SAM) Instrument in Gale Crater, Mars

    Science.gov (United States)

    Sutter, B.; Archer, D. P.; Ming, D. W.; Niles, P. B.; Eigenbrode, J. L.; Franz, H.; Glavin, D. P.; McAdam, A. C.; Mahaffy, P; Stern, J. C.; hide

    2014-01-01

    The Sample Analysis at Mars (SAM) instrument onboard the Curiosity rover detect-ed O2 and HCl gas releases from the Rocknest (RN) eolian bedform and the John Klein (JK) and Cumberland (CB) drill hole materials in Gale Crater. Chlorinated hydrocarbons have also been detected by the SAM quadrupole mass spectrometer (QMS) and gas chromatography/mass spectrometer (GCMS). These detections along with the detection of perchlorate (ClO4-) by the Mars Phoenix Lander’s Wet Chemistry Laboratory (WCL) suggesting perchlorate is a possible candidate for evolved O2 and chlorine species. Laboratory thermal analysis of perchlorates has yet to provide an unequivocal temperature match to the SAM O2 and HCl release data. Iron mineralogy found in the Rocknest materials when mixed with Ca-perchlorate does cause O2 release temperatures to be closer match to the SAM O2 release data but more work is required in evaluating the catalytic effects of Fe mineralogy on perchlorate decomposition. Chlorates (ClO3-) are relevant Mars materials and potential O2 and Cl sources. The objective of this work is to evaluate the thermal decomposition of select chlorate (ClO3-) salts as possible sources of the O2 and HCl releases in the Gale Crater materials.

  5. Stool frequency recording in severe acute malnutrition ('StoolSAM'); an agreement study comparing maternal recall versus direct observation using diapers.

    Science.gov (United States)

    Voskuijl, Wieger; Potani, Isabel; Bandsma, Robert; Baan, Anne; White, Sarah; Bourdon, Celine; Kerac, Marko

    2017-06-07

    Approximately 50% of the deaths of children under the age of 5 can be attributed to undernutrition, which also encompasses severe acute malnutrition (SAM). Diarrhoea is strongly associated with these deaths and is commonly diagnosed solely based on stool frequency and consistency obtained through maternal recall. This trial aims to determine whether this approach is equivalent to a 'directly observed method' in which a health care worker directly observed stool frequency using diapers in hospitalised children with complicated SAM. This study was conducted at 'Moyo' Nutritional Rehabilitation Unit, Queen Elizabeth Central Hospital, Malawi. Participants were children aged 5-59 months admitted with SAM. We compared 2 days of stool frequency data obtained with next-day maternal-recall versus a 'gold standard' in which a health care worker observed stool frequency every 2 h using diapers. After study completion, guardians were asked their preferred method and their level of education. We found poor agreement between maternal recall and the 'gold standard' of directly observed diapers. The sensitivity to detect diarrhoea based on maternal recall was poor, with only 75 and 56% of diarrhoea cases identified on days 1 and 2, respectively. However, the specificity was higher with more than 80% of children correctly classified as not having diarrhoea. On day 1, the mean stool frequency difference between the two methods was -0.17 (SD; 1.68) with limits of agreement (of stool frequency) of -3.55 and 3.20 and, similarly on day 2, the mean difference was -0.2 (SD; 1.59) with limits of agreement of -3.38 and 2.98. These limits extend beyond the pre-specified 'acceptable' limits of agreement (±1.5 stool per day) and indicate that the 2 methods are non-equivalent. The higher the stool frequency, the more discrepant the two methods were. Most primary care givers strongly preferred using diapers. This study shows lack of agreement between the assessment of stool frequency in SAM

  6. Produksi Bahasa Tertulis Mahasiswa Penderita Disgrafia Di Fakultas Ilmu Budaya Universitas Sam Ratulangi

    OpenAIRE

    TANGKE, RIMA APRILIANA

    2015-01-01

    This research is entitled “Written Language Production of Student with Disgraphia in Faculty of Humanity Sam Ratulangi University”. The objectives of this research are to describe dysgraphia itself and to analyze the influences of dysgraphia on the written language production of the student in Faculty of Humanity, Sam Ratulangi University. This research uses a descriptive method. There are three steps to finish this research, the first step is preparation. In this step, the writer reads the r...

  7. SH2 domains: modulators of nonreceptor tyrosine kinase activity.

    Science.gov (United States)

    Filippakopoulos, Panagis; Müller, Susanne; Knapp, Stefan

    2009-12-01

    The Src homology 2 (SH2) domain is a sequence-specific phosphotyrosine-binding module present in many signaling molecules. In cytoplasmic tyrosine kinases, the SH2 domain is located N-terminally to the catalytic kinase domain (SH1) where it mediates cellular localization, substrate recruitment, and regulation of kinase activity. Initially, structural studies established a role of the SH2 domain stabilizing the inactive state of Src family members. However, biochemical characterization showed that the presence of the SH2 domain is frequently required for catalytic activity, suggesting a crucial function stabilizing the active state of many nonreceptor tyrosine kinases. Recently, the structure of the SH2-kinase domain of Fes revealed that the SH2 domain stabilizes the active kinase conformation by direct interactions with the regulatory helix alphaC. Stabilizing interactions between the SH2 and the kinase domains have also been observed in the structures of active Csk and Abl. Interestingly, mutations in the SH2 domain found in human disease can be explained by SH2 domain destabilization or incorrect positioning of the SH2. Here we summarize our understanding of mechanisms that lead to tyrosine kinase activation by direct interactions mediated by the SH2 domain and discuss how mutations in the SH2 domain trigger kinase inactivation.

  8. The JH2 domain and SH2-JH2 linker regulate JAK2 activity: A detailed kinetic analysis of wild type and V617F mutant kinase domains.

    Science.gov (United States)

    Sanz Sanz, Arturo; Niranjan, Yashavanthi; Hammarén, Henrik; Ungureanu, Daniela; Ruijtenbeek, Rob; Touw, Ivo P; Silvennoinen, Olli; Hilhorst, Riet

    2014-10-01

    JAK2 tyrosine kinase regulates many cellular functions. Its activity is controlled by the pseudokinase (JH2) domain by still poorly understood mechanisms. The V617F mutation in the pseudokinase domain activates JAK2 and causes myeloproliferative neoplasms. We conducted a detailed kinetic analysis of recombinant JAK2 tyrosine kinase domain (JH1) and wild-type and V617F tandem kinase (JH1JH2) domains using peptide microarrays to define the functions of the kinase domains. The results show that i) JAK2 follows a random Bi-Bi reaction mechanism ii) JH2 domain restrains the activity of the JH1 domain by reducing the affinity for ATP and ATP competitive inhibitors iii) V617F decreases affinity for ATP but increases catalytic activity compared to wild-type and iv) the SH2-JH2 linker region participates in controlling activity by reducing the affinity for ATP. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Analysis of the in-vessel phase of SAM strategy for a Korean 1000 MWe PWR

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sung-Min; Oh, Seung-Jong [KEPCO International Nuclear Graduate School (KINGS), Ulsan (Korea, Republic of). Dept. of NPP Engineering; Diab, Aya [KEPCO International Nuclear Graduate School (KINGS), Ulsan (Korea, Republic of). Dept. of NPP Engineering; Ain Shams Univ., Cairo (Egypt). Mechanical Power Engineering Dept.

    2017-12-15

    This paper focuses on the in-vessel phase of Severe Accident Management (SAM) strategy for a Korean 1000 MWe Pressurized Water Reactor (PWR) with reference to ROAAM+ framework approach. To apply ROAAM+, it is needed to identify epistemic and aleatory uncertainties. The selected scenario is a station blackout (SBO) and the corresponding SAM strategy is RCS depressurization followed by water injection into the reactor pressure vessel (RPV). The analysis considers the depressurization timing and the flow rate and timing of in-vessel injection for scenario variations. For the phenomenological uncertainties, the core melting and relocation process is considered to be the most important phenomenon in the in-vessel phase of SAM strategy. Accordingly, a sensitivity analysis is carried out to assess the impact of the cut-off porosity below which the flow area of a core node is zero (EPSCUT), and the critical temperature for cladding rupture (TCLMAX) on the core melting and relocation process. In this paper, the SAM strategy for maintaining the integrity of RPV is derived after quantification of the scenario and phenomenological uncertainties.

  10. Jahn-teller domains and magnetic domains in Mn2FeO4

    NARCIS (Netherlands)

    Kub, J.; Brabers, V.A.M.; Novák, P.; Gemperle, R.; Simsova, J.

    2000-01-01

    Elastic (Jahn–Teller) domains and magnetic domains in the tetragonal spinel Mn2FeO4 were studied using X-ray double-crystal topography, X-ray diffractometry and the colloid-SEM method. The Jahn–Teller domains of the measured samples are tetragonal with the [0 0 1] c-axis alternating perpendicularly

  11. Expression and Production of SH2 Domain Proteins.

    Science.gov (United States)

    Liu, Bernard A; Ogiue-Ikeda, Mari; Machida, Kazuya

    2017-01-01

    The Src Homology 2 (SH2) domain lies at the heart of phosphotyrosine signaling, coordinating signaling events downstream of receptor tyrosine kinases (RTKs), adaptors, and scaffolds. Over a hundred SH2 domains are present in mammals, each having a unique specificity which determines its interactions with multiple binding partners. One of the essential tools necessary for studying and determining the role of SH2 domains in phosphotyrosine signaling is a set of soluble recombinant SH2 proteins. Here we describe methods, based on a broad experience with purification of all SH2 domains, for the production of SH2 domain proteins needed for proteomic and biochemical-based studies such as peptide arrays, mass-spectrometry, protein microarrays, reverse-phase microarrays, and high-throughput fluorescence polarization (HTP-FP). We describe stepwise protocols for expression and purification of SH2 domains using GST or poly His-tags, two widely adopted affinity tags. In addition, we address alternative approaches, challenges, and validation studies for assessing protein quality and provide general characteristics of purified human SH2 domains.

  12. 77 FR 67813 - Sam Rayburn Dam Project Power Rate

    Science.gov (United States)

    2012-11-14

    ... DEPARTMENT OF ENERGY Southwestern Power Administration Sam Rayburn Dam Project Power Rate AGENCY: Southwestern Power Administration, DOE. ACTION: Notice of Rate Order Approving an Extension of Power Rate on an.... James K. McDonald, Assistant Administrator, Southwestern Power Administration, Department of Energy...

  13. The History of the Austin College Building and Old Main at Sam Houston State University

    Science.gov (United States)

    Singer, Erin; Shields, Samantha

    2017-01-01

    Austin Hall and Old Main serve as the heart of what is now Sam Houston State University. The buildings' rich histories help one to understand how Sam Houston State University and its proud teacher education heritage came to be. To begin with Austin Hall's story, the University's original building has a unique and interesting tale that journeys…

  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.; hide

    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. Dosimetric comparison of the specific anthropomorphic mannequin (SAM) to 14 anatomical head models using a novel definition for the mobile phone positioning

    International Nuclear Information System (INIS)

    Kainz, Wolfgang; Christ, Andreas; Kellom, Tocher; Seidman, Seth; Nikoloski, Neviana; Beard, Brian; Kuster, Niels

    2005-01-01

    This paper presents new definitions for obtaining reproducible results in numerical phone dosimetry. Numerous numerical dosimetric studies have been published about the exposure of mobile phone users which concluded with conflicting results. However, many of these studies lack reproducibility due to shortcomings in the description of the phone positioning. The new approach was tested by two groups applying two different numerical program packages to compare the specific anthropomorphic mannequin (SAM) to 14 anatomically correct head models. A novel definition for the positioning of mobile phones next to anatomically correct head models is given along with other essential parameters to be reported. The definition is solely based on anatomical characteristics of the head. A simple up-to-date phone model was used to determine the peak spatial specific absorption rate (SAR) of mobile phones in SAM and in the anatomically correct head models. The results were validated by measurements. The study clearly shows that SAM gives a conservative estimate of the exposure in anatomically correct head models for head only tissue. Depending on frequency, phone position and head size the numerically calculated 10 g averaged SAR in the pinna can be up to 2.1 times greater than the peak spatial SAR in SAM. Measurements in small structures, such as the pinna, will significantly increase the uncertainty; therefore SAM was designed for SAR assessment in the head only. Whether SAM will provide a conservative value for the pinna depends on the pinna SAR limit of the safety standard considered

  16. A pilot study investigating the feasibility of symptom assessment manager (SAM), a Web-based real-time tool for monitoring challenging behaviors.

    Science.gov (United States)

    Loi, Samantha M; Wanasinghage, Sangeeth; Goh, Anita; Lautenschlager, Nicola T; Darby, David G; Velakoulis, Dennis

    2018-04-01

    Improving and minimizing challenging behaviors seen in psychiatric conditions, including behavioral and psychological symptoms of dementia are important in the care of people with these conditions. Yet there is a lack of systematic evaluation of these as a part of routine clinical care. The Neuropsychiatric Inventory is a validated and reliable tool for rating the severity and disruptiveness of challenging behaviors. We report on the evaluation of a Web-based symptom assessment manager (SAM), designed to address the limitation of previous tools using some of the Neuropsychiatric Inventory functions, to monitor behaviors by staff caring for people with dementia and other psychiatric conditions in inpatient and residential care settings. The SAM was piloted in an 8-bed inpatient neuropsychiatry unit over 5 months. Eleven nurses and 4 clinicians were trained in usage of SAM. Primary outcomes were usage of SAM and perceived usability, utility, and acceptance of SAM. Secondary outcomes were the frequencies of documented behavior. Usage data were analyzed using chi-square and logistic regression analyses. The SAM was used for all admitted patients regardless of diagnosis, with a usage rate of 64% for nurses regularly employed in the unit. Staff provided positive feedback regarding the utility of SAM. The SAM appeared to offer individualized behavior assessment by providing a quick, structured, and standardized platform for assessing behavior in a real-world setting. Further research would involve trialing SAM with more staff in alternative settings such as in home or residential care settings. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Curiosity's Sample Analysis at Mars (SAM) Investigation: Overview of Results from the First 120 Sols on Mars

    Science.gov (United States)

    Mahaffy, P. R.; Cabane, M.; Webster, C. R.; Archer, P. D.; Atreya, S. K.; Benna, M.; Brinckerhoff, W. B.; Brunner, A. E.; Buch, A.; Coll, P.; hide

    2013-01-01

    During the first 120 sols of Curiosity s landed mission on Mars (8/6/2012 to 12/7/2012) SAM sampled the atmosphere 9 times and an eolian bedform named Rocknest 4 times. The atmospheric experiments utilized SAM s quadrupole mass spectrometer (QMS) and tunable laser spectrometer (TLS) while the solid sample experiments also utilized the gas chromatograph (GC). Although a number of core experiments were pre-programmed and stored in EEProm, a high level SAM scripting language enabled the team to optimize experiments based on prior runs.

  18. Global diabatic heating during FGGE SOP-1 and SOP-2

    Science.gov (United States)

    Chen, Tsing-Chang; Baker, Wayman E.

    1986-01-01

    With the increase in the observational data provided by FGGE and the use of global circulation models with full physics for the data assimilation, it is now becoming feasible to attempt to estimate globally the atmospheric diabatic heating. The thermodynamic equation in isobaric coordinates and the data generated by the FGGE III-b analysis of the Goddard Laboratory for Atmospheres (GLA) are employed to serve this purpose. The results of the present study generally agree with other previous investigations. However, some important differences are also revealed. (1) The diabatic heating obtained in the tropics in the present study is larger than that obtained elsewhere; (2) the relatively large heating over the mountainous areas shown in other studies does not appear; (3) no significant negative values of diabatic heating are found in the polar regions; and (4) unlike other studies, cooling is noted over parts of Eurasia in the summer.

  19. Domain engineering of the metastable domains in the 4f-uniaxial-ferromagnet CeRu2Ga2B

    Science.gov (United States)

    Wulferding, D.; Kim, H.; Yang, I.; Jeong, J.; Barros, K.; Kato, Y.; Martin, I.; Ayala-Valenzuela, O. E.; Lee, M.; Choi, H. C.; Ronning, F.; Civale, L.; Baumbach, R. E.; Bauer, E. D.; Thompson, J. D.; Movshovich, R.; Kim, Jeehoon

    2017-04-01

    In search of novel, improved materials for magnetic data storage and spintronic devices, compounds that allow a tailoring of magnetic domain shapes and sizes are essential. Good candidates are materials with intrinsic anisotropies or competing interactions, as they are prone to host various domain phases that can be easily and precisely selected by external tuning parameters such as temperature and magnetic field. Here, we utilize vector magnetic fields to visualize directly the magnetic anisotropy in the uniaxial ferromagnet CeRu2Ga2B. We demonstrate a feasible control both globally and locally of domain shapes and sizes by the external field as well as a smooth transition from single stripe to bubble domains, which opens the door to future applications based on magnetic domain tailoring.

  20. Geometry modeling for SAM-CE Monte Carlo calculations

    International Nuclear Information System (INIS)

    Steinberg, H.A.; Troubetzkoy, E.S.

    1980-01-01

    Three geometry packages have been developed and incorporated into SAM-CE, for representing in three dimensions the transport medium. These are combinatorial geometry - a general (non-lattice) system, complex combinatorial geometry - a very general system with lattice capability, and special reactor geometry - a special purpose system for light water reactor geometries. Their different attributes are described

  1. Toposelective electrochemical desorption of thiol SAMs from neighboring polycrystalline gold surfaces.

    Science.gov (United States)

    Tencer, Michal; Berini, Pierre

    2008-11-04

    We describe a method for the selective desorption of thiol self-assembled monolayers from gold surfaces having micrometer-scale separations on a substrate. In an electrolyte solution, the electrical resistance between the adjacent areas can be much lower than the resistance between a surface and the counter electrode. Also, both reductive and oxidative thiol desorption may occur. Therefore, the potentials of the surfaces must be independently controlled with a multichannel potentiostat and operating windows for a given thiol/electrolyte system must be established. In this study operating windows were established for 1-dodecanethiol-based SAMs in phosphate buffer, phosphate-buffered saline, and sodium hydroxide solution, and selective SAM removal was successfully performed in a four-electrode configuration.

  2. Evolution of Src Homology 2 (SH2) Domain to Recognize Sulfotyrosine.

    Science.gov (United States)

    Ju, Tong; Niu, Wei; Guo, Jiantao

    2016-09-16

    Protein tyrosine O-sulfation is considered as the most common type of post-translational tyrosine modification in nature and plays important roles in extracellular biomolecular interactions. To facilitate the mapping, biological study, and medicinal application of this type of post-translational modification, we seek to evolve a small protein scaffold that recognizes sulfotyrosine with high affinity. We focused our efforts on the engineering of the Src Homology 2 (SH2) domain, which represents the largest class of known phosphotyrosine-recognition domain in nature and has a highly evolvable binding pocket. By using phage display, we successfully engineered the SH2 domain to recognize sulfotyrosine with high affinity. The best mutant, SH2-60.1, displayed more than 1700 fold higher sulfotyrosine-binding affinity than that of the wild-type SH2 domain. We also demonstrated that the evolved SH2 domain mutants could be used to detect sulfoprotein levels on the cell surface. These evolved SH2 domain mutants can be potentially applied to the study of protein tyrosine O-sulfation with proper experimental designs.

  3. Influence of Oxychlorine Phases During the Pyrolysis of Organic Molecules: Implications for the Quest of Organics on Mars with the SAM Experiment Onboard the Curiosity Rover

    Science.gov (United States)

    Millan, M.; Szopa, C.; Buch, A.; Belmahdi, I.; Glavin, D. P.; Freissinet, C.; Eigenbrode, J. L.; Archer, P. D., Jr,; Sutter, B.; Mahaffy, P.

    2017-01-01

    One among the main objectives of the Sample Analysis at Mars (SAM) experiment is the in situ molecular analysis of gases evolving from solid samples heated up to approximately 850 degrees Centigrade, and collected by Curiosity on Mars surface/sub-surface in Gale crater. With this aim, SAM uses a gas-chromatograph coupled to a quadrupole mass spectrometer (GC-QMS) devoted to separate, detect and identify both volatile inorganic and organic compounds. SAM detected chlorinated organic molecules produced in evolved gas analysis (EGA) experiments. Several of these were also detected by the Viking experiments in 1976. SAM also detected oxychlorine compounds that were present at the Phoenix landing site. The oxychlorines may be prevelant over much of the martian surface. The C1 to C3 aliphatic chlorohydrocarbons (chloromethane and di- and trichloromethane) detected by SAM were attributed to reaction products occurring between the oxychlorines phases and the organic compounds coming from SAM instrument background. But SAM also showed the presence of a large excess of chlorobenzene and C2 to C4 dichloroalkanes among the volatile species released by the Cumberland sample of the Sheepbed mudstone. For the first time in the history of the Mars exploration, this proved the presence of Mars indigenous organic material at the Mars' surface. However, the identification of the precursor organic compounds of these chlorohydrocarbons is difficult due to the complexity of the reactions occurring during the sample pyrolysis. Laboratory pyrolysis experiments have demonstrated that oxychlorines phases such as perchlorates and chlorates, decomposed into dioxygen and volatile chlorine bearing molecules (HCl and/or Cl2) during the pyrolysis. These chemical species can then react with the organic molecules present in the martian solid samples through oxidation, chlorination and oxychlorination processes.

  4. Annals of SAM meeting '96. National meeting on precious metals

    International Nuclear Information System (INIS)

    1996-01-01

    Works are presented at the SAM meeting '96 of the Argentine Materials Association. The papers can be grouped under the following main topics: physical metallurgy; ceramics; polymers; precious metals; extractive metallurgy; corrosion; powder metallurgy. refs., ills

  5. Pembuatan Dokumen Sop Keamanan Aset Informasi Yang Mengacu Pada Kontrol Kerangka Kerja Iso 27002:2013 (Studi Kasus : Cv Cempaka Tulungagung

    Directory of Open Access Journals (Sweden)

    Dheni Indra Rachmawan

    2017-03-01

    Full Text Available Dalam mendukung proses bisnis utamanya, suatu organisasi membutuhkan adanya dukungan teknologi informasi. Penggunaan Teknologi Informasi di banyak perusahaan telah menjadi satu hal penting dalam meningkatkan efektifitas dan efisiensi operasional bisnis yang mendukung tercapainya tujuan perusahaan, termasuk juga pada CV Cempaka Tulungagung. Dalam memenuhi kebutuhan keamanan aset informasi tersebut maka diperlukan adanya sebuah tata kelola dalam bentuk dokumen SOP (Standard Operating Procedure keamanan aset informasi untuk mengurangi adanya ancaman dan risiko serta untuk mendukung penyelarasan pencapaian tujuan organisasi dalam proses bisnisnya. Metode penelitian yang digunakan yaitu OCTAVE sebagai pengolah hasil informasi yang didapatkan dari wawancara dan FMEA digunakan untuk menghitung seberapa tinggi dampak untuk perusahaan jika risiko itu terjadi dan membuat ranking prioritas untuk masing-masing risiko. Kemudian basis yang digunakan dalam membuat prosedur kendali akses aset informasi sebagai manajemen risiko adalah kerangka kerja ISO/IEC:27002:2013. Dalam penelitian ini, hasil akhir yang didapatkan adalah sebuah dokumen SOP yang sesuai dengan kebutuhan keamanan informasi bagi perusahaan CV Cempaka berdasarkan pada kontrol kerangka kerja ISO27002:2013.

  6. Possible Detection of Perchlorates by the Sample Analysis at Mars (SAM) Instrument: Comparison with Previous Missions

    Science.gov (United States)

    Navarro-Gonzalex, Rafael; Sutter, Brad; Archer, Doug; Ming, Doug; Eigenbrode, Jennifer; Franz, Heather; Glavin, Daniel; McAdam, Amy; Stern, Jennifer; McKay, Christopher; hide

    2013-01-01

    The first chemical analysis of soluble salts in the soil was carried out by the Phoenix Lander in the Martian Arctic [1]. Surprisingly, chlorine was present as magnesium or calcium perchlorate at 0.4 to 0.6 percent. Additional support for the identification of perchlorate came from the evolved gas analysis which detected the release of molecular oxygen at 350-550C [1]. When Mars-like soils from the Atacama Desert were spiked with magnesium perchlorate (1 percent) and heated using the Viking GC-MS protocol, nearly all the organics were combusted but a small amount was chlorinated, forming chloromethane and dichloromethane [2]. These chlorohydrocarbons were detected by the Viking GC-MS experiments when the Martian soil was analyzed but they were considered to be terrestrial contaminants [3]. Reinterpretation of the Viking results suggests Analysis at Mars (SAM) instrument on board the Mars Science Laboratory (MSL) ran four samples from an aeolian bedform named Rocknest. The samples analyzed were portioned from the fifth scoop at this location. The samples were heated to 835C at 35C/min with a He flow. The SAM QMS detected a major oxygen release (300-500C) [5], coupled with the release of chlorinated hydrocarbons (chloromethane, dichloromethane, trichloromethane, and chloromethylpropene) detected both by SAM QMS and GC-MS derived from known Earth organic contaminants in the instrument [6]. Calcium perchlorate appears to be the best candidate for evolved O2 in the Rocknest samples at this time but other Cl species (e.g., chlorates) are possible and must be evaluated. The potential detection of perchlorates in Rocknest material adds weight to the argument that both Viking Landers measured signatures of perchlorates. Even if the source of the organic carbon detected is still unknown, the chlorine source was likely Martian. Two mechanisms have been hypothesized for the formation of soil perchlorate: (1) Atmospheric oxidation of chlorine; and (2) UV photooxidation of

  7. Miniaturized and Ferrite Based Tunable Bandpass Filters in LCP and LTCC Technologies for SoP Applications

    KAUST Repository

    Arabi, Eyad A.

    2015-04-01

    Wireless systems with emerging applications are leaning towards small size, light-weight and low cost. Another trend for these wireless devices is that new applications and functionalities are being added without increasing the size of the device. To accomplish this, individual components must be miniaturized and the system should be designed to maximize the integration of the individual components. The high level of 3D integration feasible in system on package design (SoP) concept can fulfill the latter requirement. Bandpass filters are important components on all wireless systems to reject the unwanted signals and reduce interference. Being mostly implemented with passive and distributed components, bandpass filters take considerable space in a wireless system. Moreover, with emerging bands and multiple applications encompassed in a single device, many bandpass filters are required. The miniaturization related to bandpass filters can be approached by three main ways: (1) at the component level through the miniaturization of individual bandpass filters, (2) at the system level through the use of tunable filters to reduce the overall number of filters, and (3) at the system level through the high level of integration in a 3D SoP platform. In this work we have focused on all three aspects of miniaturization of band pass filters mentioned above. In the first part of this work, a low frequency (1.5 GHz global positioning system (GPS) band) filter implemented through 3D lumped components in two leading SoP technologies, namely low temperature co-fired ceramic (LTCC) and the liquid crystal polymers (LCP) is demonstrated. The miniaturized filter is based on a second order topology, which has been modified to improve the selectivity and out-of-band rejection without increasing the size. Moreover, for the case of LCP, the filter is realized in an ultra-thin stack up comprising four metallization layers with an overall thickness of only 100 _m. Due to its ultra

  8. The Semi-opened Infrastructure Model (SopIM): A Frame to Set Up an Organizational Learning Process

    Science.gov (United States)

    Grundstein, Michel

    In this paper, we introduce the "Semi-opened Infrastructure Model (SopIM)" implemented to deploy Artificial Intelligence and Knowledge-based Systems within a large industrial company. This model illustrates what could be two of the operating elements of the Model for General Knowledge Management within the Enterprise (MGKME) that are essential to set up the organizational learning process that leads people to appropriate and use concepts, methods and tools of an innovative technology: the "Ad hoc Infrastructures" element, and the "Organizational Learning Processes" element.

  9. Severe accident management (SAM), operator training and instrumentation capabilities - Summary and conclusions

    International Nuclear Information System (INIS)

    2002-01-01

    The Workshop on Operator Training for Severe Accident Management (SAM) and Instrumentation Capabilities During Severe Accidents was organised in collaboration with Electricite de France (Service Etudes et Projets Thermiques et Nucleaires). There were 34 participants, representing thirteen OECD Member countries, the Russian Federation and the OECD/NEA. Almost half the participants represented utilities. The second largest group was regulatory authorities and their technical support organisations. Basically, the Workshop was a follow-up to the 1997 Second Specialist Meeting on Operator Aids for Severe Accident Management (SAMOA-2) [Reports NEA/CSNI/R(97)10 and 27] and to the 1992 Specialist Meeting on Instrumentation to Manage Severe Accidents [Reports NEA/CSNI/R(92)11 and (93)3]. It was aimed at sharing and comparing progress made and experience gained from these two meetings, emphasizing practical lessons learnt during training or incidents as well as feedback from instrumentation capability assessment. The objectives of the Workshop were therefore: - to exchange information on recent and current activities in the area of operator training for SAM, and lessons learnt during the management of real incidents ('operator' is defined hear as all personnel involved in SAM); - to compare capabilities and use of instrumentation available during severe accidents; - to monitor progress made; - to identify and discuss differences between approaches relevant to reactor safety; - and to make recommendations to the Working Group on the Analysis and Management of Accidents and the CSNI (GAMA). The Workshop was organised into five sessions: - 1: Introduction; - 2: Tools and Methods; - 3: Training Programmes and Experience; - 4: SAM Organisation Efficiency; - 5: Instrumentation Capabilities. It was concluded by a Panel and General Discussion. This report presents the summary and conclusions: the meeting confirmed that only limited information is needed for making required decisions

  10. Vibrational Stark Effect of the Electric-Field Reporter 4-Mercaptobenzonitrile as a Tool for Investigating Electrostatics at Electrode/SAM/Solution Interfaces

    Directory of Open Access Journals (Sweden)

    Peter Hildebrandt

    2012-06-01

    Full Text Available 4-mercaptobenzonitrile (MBN in self-assembled monolayers (SAMs on Au and Ag electrodes was studied by surface enhanced infrared absorption and Raman spectroscopy, to correlate the nitrile stretching frequency with the local electric field exploiting the vibrational Stark effect (VSE. Using MBN SAMs in different metal/SAM interfaces, we sorted out the main factors controlling the nitrile stretching frequency, which comprise, in addition to external electric fields, the metal-MBN bond, the surface potential, and hydrogen bond interactions. On the basis of the linear relationships between the nitrile stretching and the electrode potential, an electrostatic description of the interfacial potential distribution is presented that allows for determining the electric field strengths on the SAM surface, as well as the effective potential of zero-charge of the SAM-coated metal. Comparing this latter quantity with calculated values derived from literature data, we note a very good agreement for Au/MBN but distinct deviations for Ag/MBN which may reflect either the approximations and simplifications of the model or the uncertainty in reported structural parameters for Ag/MBN. The present electrostatic model consistently explains the electric field strengths for MBN SAMs on Ag and Au as well as for thiophenol and mercaptohexanoic acid SAMs with MBN incorporated as a VSE reporter.

  11. Assessing the suitability of written stroke materials: an evaluation of the interrater reliability of the suitability assessment of materials (SAM) checklist.

    Science.gov (United States)

    Hoffmann, Tammy; Ladner, Yvette

    2012-01-01

    Written materials are frequently used to provide education to stroke patients and their carers. However, poor quality materials are a barrier to effective information provision. A quick and reliable method of evaluating material quality is needed. This study evaluated the interrater reliability of the Suitability Assessment of Materials (SAM) checklist in a sample of written stroke education materials. Two independent raters evaluated the materials (n = 25) using the SAM, and ratings were analyzed to reveal total percentage agreements and weighted kappa values for individual items and overall SAM rating. The majority of the individual SAM items had high interrater reliability, with 17 of the 22 items achieving substantial, almost perfect, or perfect weighted kappa value scores. The overall SAM rating achieved a weighted kappa value of 0.60, with a percentage total agreement of 96%. Health care professionals should evaluate the content and design characteristics of written education materials before using them with patients. A tool such as the SAM checklist can be used; however, raters should exercise caution when interpreting results from items with more subjective scoring criteria. Refinements to the scoring criteria for these items are recommended. The value of the SAM is that it can be used to identify specific elements that should be modified before education materials are provided to patients.

  12. Comprehensive analysis of interactions between the Src-associated protein in mitosis of 68 kDa and the human Src-homology 3 proteome.

    Directory of Open Access Journals (Sweden)

    Benedikt Asbach

    Full Text Available The protein Sam68 is involved in many cellular processes such as cell-cycle regulation, RNA metabolism, or signal transduction. Sam68 comprises a central RNA-binding domain flanked by unstructured tails containing docking sites for signalling proteins including seven proline-rich sequences (denoted P0 to P6 as potential SH3-domain binding motifs. To comprehensively assess Sam68-SH3-interactions, we applied a phage-display screening of a library containing all approx. 300 human SH3 domains. Thereby we identified five new (from intersectin 2, the osteoclast stimulating factor OSF, nephrocystin, sorting nexin 9, and CIN85 and seven already known high-confidence Sam68-ligands (mainly from the Src-kinase family, as well as several lower-affinity binders. Interaction of the high-affinity Sam68-binders was confirmed in independent assays in vitro (phage-ELISA, GST-pull-down and in vivo (FACS-based FRET-analysis with CFP- and YFP-tagged proteins. Fine-mapping analyses with peptides established P0, P3, P4, and P5 as exclusive docking-sites for SH3 domains, which showed varying preferences for these motifs. Mutational analyses identified individual residues within the proline-rich motifs being crucial for the interactions. Based on these data, we generated a Sam68-mutant incapable of interacting with SH3 domains any more, as subsequently demonstrated by FRET-analyses. In conclusion, we present a thorough characterization of Sam68's interplay with the SH3 proteome. The observed interaction between Sam68 and OSF complements the known Sam68-Src and OSF-Src interactions. Thus, we propose, that Sam68 functions as a classical scaffold protein in this context, assembling components of an osteoclast-specific signalling pathway.

  13. Rhodium deposition onto a 4-mercaptopyridine SAM on Au(1 1 1)

    Energy Technology Data Exchange (ETDEWEB)

    Manolova, M. [Institute of Electrochemistry, University of Ulm, 89069 Ulm (Germany); Kayser, M. [Institute of Electrochemistry, University of Ulm, 89069 Ulm (Germany); Kolb, D.M. [Institute of Electrochemistry, University of Ulm, 89069 Ulm (Germany)]. E-mail: dieter.kolb@uni-ulm.de; Boyen, H.-G. [Institute of Solid State Physics, University of Ulm, 89069 Ulm (Germany); Ziemann, P. [Institute of Solid State Physics, University of Ulm, 89069 Ulm (Germany); Mayer, D. [BASF Electronic Materials GmbH, 67056 Ludwigshafen (Germany); Wirth, A. [BASF Electronic Materials GmbH, 67056 Ludwigshafen (Germany)

    2007-02-10

    The application of a recently developed method for the deposition of Pd and Pt on top of a SAM, has been successfully extended to Rh, thus proving the versatility of the new concept. Experimental evidence from cyclic voltammetry, in situ STM and ex situ X-ray photoemission spectroscopy is presented for the deposition of monoatomic high rhodium islands onto a 4-mercaptopyridine self-assembled monolayer on a Au(1 1 1) electrode. By repetitive complexation of the Rh ions to the ring-nitrogen and reduction in a Rh-ion free solution, an almost completely covered SAM is obtained. The consequences of making contacts for molecular electronics are briefly discussed.

  14. Introduction: History of SH2 Domains and Their Applications.

    Science.gov (United States)

    Liu, Bernard A; Machida, Kazuya

    2017-01-01

    The Src Homology 2 (SH2) domain is the prototypical protein interaction module that lies at the heart of phosphotyrosine signaling. Since its serendipitous discovery, there has been a tremendous advancement in technologies and an array of techniques available for studying SH2 domains and phosphotyrosine signaling. In this chapter, we provide a glimpse of the history of SH2 domains and describe many of the tools and techniques that have been developed along the way and discuss future directions for SH2 domain studies. We highlight the gist of each chapter in this volume in the context of: the structural biology and phosphotyrosine binding; characterizing SH2 specificity and generating prediction models; systems biology and proteomics; SH2 domains in signal transduction; and SH2 domains in disease, diagnostics, and therapeutics. Many of the individual chapters provide an in-depth approach that will allow scientists to interrogate the function and role of SH2 domains.

  15. Classification and Lineage Tracing of SH2 Domains Throughout Eukaryotes.

    Science.gov (United States)

    Liu, Bernard A

    2017-01-01

    Today there exists a rapidly expanding number of sequenced genomes. Cataloging protein interaction domains such as the Src Homology 2 (SH2) domain across these various genomes can be accomplished with ease due to existing algorithms and predictions models. An evolutionary analysis of SH2 domains provides a step towards understanding how SH2 proteins integrated with existing signaling networks to position phosphotyrosine signaling as a crucial driver of robust cellular communication networks in metazoans. However organizing and tracing SH2 domain across organisms and understanding their evolutionary trajectory remains a challenge. This chapter describes several methodologies towards analyzing the evolutionary trajectory of SH2 domains including a global SH2 domain classification system, which facilitates annotation of new SH2 sequences essential for tracing the lineage of SH2 domains throughout eukaryote evolution. This classification utilizes a combination of sequence homology, protein domain architecture and the boundary positions between introns and exons within the SH2 domain or genes encoding these domains. Discrete SH2 families can then be traced across various genomes to provide insight into its origins. Furthermore, additional methods for examining potential mechanisms for divergence of SH2 domains from structural changes to alterations in the protein domain content and genome duplication will be discussed. Therefore a better understanding of SH2 domain evolution may enhance our insight into the emergence of phosphotyrosine signaling and the expansion of protein interaction domains.

  16. Progress towards the development of SH2 domain inhibitors.

    Science.gov (United States)

    Kraskouskaya, Dziyana; Duodu, Eugenia; Arpin, Carolynn C; Gunning, Patrick T

    2013-04-21

    Src homology 2 (SH2) domains are 100 amino acid modular units, which recognize and bind to tyrosyl-phosphorylated peptide sequences on their target proteins, and thereby mediate intracellular protein-protein interactions. This review summarizes the progress towards the development of synthetic agents that disrupt the function of the SH2 domains in different proteins as well as the clinical relevance of targeting a specific SH2 domain. Since 1986, SH2 domains have been identified in over 110 human proteins, including kinases, transcription factors, and adaptor proteins. A number of these proteins are over-activated in many diseases, including cancer, and their function is highly dependent on their SH2 domain. Thus, inhibition of a protein's function through disrupting that of its SH2 domain has emerged as a promising approach towards the development of novel therapeutic modalities. Although targeting the SH2 domain is a challenging task in molecular recognition, the progress reported here demonstrates the feasibility of such an approach.

  17. In situ analysis of Mars soil sample with the sam gcms instrumentation onboard Curiosity : interpretation and comparison of measurements done at Rocknest and Yelloknife bay sites

    Science.gov (United States)

    Szopa, Cyril; Coll, Patrice; Cabane, Michel; Coscia, David; Buch, Arnaud; Francois, Pascaline; Millan, Maeva; Teinturier, Sammy; Navarro-Gonzales, Rafael; Glavin, Daniel; Freissinet, Caro; Steele, Andrew; Eigenbrode, Jen; Mahaffy, Paul

    2014-05-01

    The characterisation of the chemical and mineralogical composition of regolith samples collected with the Curiosity rover is a primary objective of the SAM experiment. These data should provide essential clues on the past habitability of Gale crater. Amongst the SAM suite of instruments [1], SAM-GC (Gas Chromatograph) is devoted to identify and quantify volatiles evolved from the thermal (heating up to about 900°C)/chemical (derivatization procedure) treatment of any soil sample collected by the Curiosity rover. With the aim to search for potential organic molecules outgassed from the samples, a SAM-GC analytical channel composed of thermal-desorption injector and a MXT-CLP chromatographic column was chosen to achieve all the measurements done up today, as it was designed for the separation of a wide range of volatile organic molecules. Three solid samples have been analyzed with GCMS, one sand sample collected at the Rocknest site, and two rock samples (John Klein and Cumberland respectively) collected at the Yellowknife Bay site using the Curiosity driller. All the measurements were successful and they produced complex chromatograms with both detectors used for SAM GC, i.e. a thermal conductivity detector and the SAM quandrupole mass spectrometer. Their interpretation already revealed the presence of an oxychlorine phase present in the sample which is at the origin of chlorohydrocarbons clearly identified [2] but this represents only a fraction of the GCMS signal recorded [3,4]. This work presents a systematic comparison of the GCMS measurements done for the different samples collected, supported by reference data obtained in laboratory with different spare models of the gas chromatograph, with the aim to bring new elements of interpretation of the SAM measurements. References: [1] Mahaffy, P. et al. (2012) Space Sci Rev, 170, 401-478. [2] Glavin, D. et al. (2013), JGR. [3] Leshin L. et al. (2013), Science, [4] Ming D. et al. (2013), Science, 32, 64

  18. Potensi Tinggalan Arkeologis di Kawasan Bandar Udara Sam Ratulangi Manado: Upaya Pelestarian, Pemanfaatan, dan Pengembangan bagi Masyarakat

    Directory of Open Access Journals (Sweden)

    Irfanuddin W. Marzuki

    2016-08-01

    Full Text Available The area of Sam Ratulangi airport’s Manado has archaeological heritage which has been know as it is closed for public. This research used descriptive method, using inductive reasoning. Meanwhile, the analysis method used morphologyl, technology, and contextual analysis. This research aimed to find out the potential of archaeological heritage in Sam Ratulangi airport area of Manado. In addition to its strategy of preservation the haritage included veilbox, bungker, and waruga. The preservation can be conducted by doing protection, development, and utilization. The preservation both physical and non physical protection. The effort for its development and utilization was conducted for the purpose of science, education, culture, and tourism. Kawasan Bandar Udara Sam Ratulangi Manado mempunyai potensi tinggalan arkeologis yang selama ini tidak diketahui masyarakat luas, dikarenakan letak tinggalan yang berada dalam kawasan tertutup untuk umum. Penelitian menggunakan metode deskriptif dengan penalaran induktif. Metode analisis menggunakan analisis morfologi, teknologi dan kontekstual. Tujuan penelitian untuk mengetahui potensi tinggalan arkeologis yang terdapat di kawasan Bandar Udara Sam Ratulangi dan strategi pelestariannya. Tinggalan arkeologis yang terdapat di kawasan Bandar Udara Sam Ratulangi meliputi veilbox, bungker, dan waruga. Upaya pelestarian dapat dilakukan dengan cara perlindungan, pengembangan dan pemanfaatan. Upaya perlindungan meliputi perlindungan secara fisik dan non fisik. Upaya pengembangan dan pemanfaatan dilakukan untuk kepentingan ilmu pengetahuan, pendidikan, kebudayaan dan pariwisata.

  19. Carbon tax effects on the poor: a SAM-based approach

    Science.gov (United States)

    Chapa, Joana; Ortega, Araceli

    2017-09-01

    A SAM-based price model for Mexico is developed in order to assess the effects of the carbon tax, which was part of the fiscal reform approved in 2014. The model is formulated based on a social accounting matrix (SAM) that distinguishes households by the official poverty condition and geographical area. The main results are that the sector that includes coke, refined petroleum and nuclear fuel shows the highest price increase due to the direct impact of the carbon tax; in addition, air transport and inland transport are the most affected sectors, in an indirect manner, because both employ inputs from the former sector. Also, it is found that welfare diminishes more in the rural strata than in the urban one. In the urban area, the carbon tax is regressive: the negative impact of carbon tax on family welfare is greater on the poorest families.

  20. FIGURAL FORMS OF KNOWLEDGE: A STUDY OF THE SHORT PROSE OF SAM SHEPARD

    Directory of Open Access Journals (Sweden)

    RICARDO DA SILVA SOBREIRA

    2008-11-01

    Full Text Available ABSTRACTThe paratactical style and the indeterminacies are literary strategies that resistthe conventional impulse of totalizing the elements projected by the text, becauseinstead of selecting the aspects of reality and subordinating the images andperceptions into a hierarchy, the use of these techniques favors the juxtapositionof multiple perspectives and the frustration of narrative closure. Thus, the useof parataxis and indeterminacies in the collection of short stories Great Dreamof Heaven (2002, by the American author Sam Shepard, tends to challenge theprocess of meaning production through the progressive erasure of narrative“certainties”.KEY WORDS: Postmodern, indeterminacy, parataxis, narrative, Sam Shepard.  

  1. 3D printed System-on-Package (SoP) for environmental sensing and localization applications

    KAUST Repository

    Zhen, Su

    2017-12-22

    This paper presents for the first time an innovative 3D printed SoP sensor node with temperature, pressure and humidity sensing capabilities. It has an integrated wireless readout through a near isotropic (900MHz) GSM antenna-on-package. This sensor node is connected to the internet for remote monitoring and has the capability of localization. The paper presents the design of antenna-on-package as well as details of the communication and localization system. Fabrication challenges unique to 3D printing and integration of electronics on 3D printed circuit board are also discussed. Finally, the paper presents measurement results of antenna radiation pattern, return loss, localization accuracy and accuracy of sensing parameters.

  2. An Adaptor Domain-Mediated Auto-Catalytic Interfacial Kinase Reaction

    Science.gov (United States)

    Liao, Xiaoli; Su, Jing; Mrksich, Milan

    2010-01-01

    This paper describes a model system for studying the auto-catalytic phosphorylation of an immobilized substrate by a kinase enzyme. This work uses self-assembled monolayers (SAMs) of alkanethiolates on gold to present the peptide substrate on a planar surface. Treatment of the monolayer with Abl kinase results in phosphorylation of the substrate. The phosphorylated peptide then serves as a ligand for the SH2 adaptor domain of the kinase and thereby directs the kinase activity to nearby peptide substrates. This directed reaction is intramolecular and proceeds with a faster rate than does the initial, intermolecular reaction, making this an auto-catalytic process. The kinetic non-linearity gives rise to properties that have no counterpart in the corresponding homogeneous phase reaction: in one example, the rate for phosphorylation of a mixture of two peptides is faster than the sum of the rates for phosphorylation of each peptide when presented alone. This work highlights the use of an adaptor domain in modulating the activity of a kinase enzyme for an immobilized substrate and offers a new approach for studying biochemical reactions in spatially inhomogeneous settings. PMID:19821459

  3. SH2 domains: modulators of nonreceptor tyrosine kinase activity

    OpenAIRE

    Filippakopoulos, Panagis; Müller, Susanne; Knapp, Stefan

    2009-01-01

    The Src homology 2 (SH2) domain is a sequence-specific phosphotyrosine-binding module present in many signaling molecules. In cytoplasmic tyrosine kinases, the SH2 domain is located N-terminally to the catalytic kinase domain (SH1) where it mediates cellular localization, substrate recruitment, and regulation of kinase activity. Initially, structural studies established a role of the SH2 domain stabilizing the inactive state of Src family members. However, biochemical characterization showed ...

  4. Voltage-sensing phosphatase modulation by a C2 domain.

    Science.gov (United States)

    Castle, Paul M; Zolman, Kevin D; Kohout, Susy C

    2015-01-01

    The voltage-sensing phosphatase (VSP) is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD), the inter-domain linker, the cytosolic catalytic domain, and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate (PIP) lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] (Kalli et al., 2014). Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5)P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry (VCF) were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5)P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in

  5. Domain 2: Sport Safety and Injury Prevention

    Science.gov (United States)

    Gurchiek, Larry; Mokha, Monique Butcher

    2004-01-01

    Most coaches recognize the importance of creating a safe environment and preventing injuries of their athletes. Domain 2 is dedicated to this important aspect of coaching, and outlines specific areas within safety and injury prevention that coaches should address. Domain 2 sets the standards for facility, equipment, and environmental safety…

  6. Coastal Observations of Weather Features in Senegal during the AMMA SOP-3 Period

    Science.gov (United States)

    Jenkins, G.; Kucera, P.; Joseph, E.; Fuentes, J.; Gaye, A.; Gerlach, J.; Roux, F.; Viltard, N.; Papazzoni, M.; Protat, A.; hide

    2009-01-01

    During 15 August through 30 September 2006, ground and aircraft measurements were obtained from a multi-national group of students and scientists in Senegal. Key measurements were aimed at investigating and understanding precipitation processes, thermodynamic and dynamic environmental conditions, cloud, aerosol and microphysical processes and spaceborne sensors (TRMM, CloudSat/Calipso) validation. Ground and aircraft instruments include: ground based polarimetric radar, disdrometer measurements, a course and a high-density rain gauge network, surface chemical measurements, a 10 m flux tower, broadband IR, solar and microwave measurements, rawinsonde and radiosonde measurements, FA-20 dropsonde, in situ microphysics and cloud radar measurements. Highlights during SOP3 include ground and aircraft measurements of squall lines, African Easterly Waves (AEWs), Saharan Air Layer advances into Senegal, and aircraft measurements of AEWs -- including the perturbation that became Hurricane Isaac.

  7. Structure of an isolated unglycosylated antibody CH2 domain

    International Nuclear Information System (INIS)

    Prabakaran, Ponraj; Vu, Bang K.; Gan, Jianhua; Feng, Yang; Dimitrov, Dimiter S.; Ji, Xinhua

    2008-01-01

    The crystal structure of an isolated unglycosylated antibody C H 2 domain has been determined at 1.7 Å resolution. The C H 2 (C H 3 for IgM and IgE) domain of an antibody plays an important role in mediating effector functions and preserving antibody stability. It is the only domain in human immunoglobulins (Igs) which is involved in weak interchain protein–protein interactions with another C H 2 domain solely through sugar moieties. The N-linked glycosylation at Asn297 is conserved in mammalian IgGs as well as in homologous regions of other antibody isotypes. To examine the structural details of the C H 2 domain in the absence of glycosylation and other antibody domains, the crystal structure of an isolated unglycosylated antibody γ1 C H 2 domain was determined at 1.7 Å resolution and compared with corresponding C H 2 structures from intact Fc, IgG and Fc receptor complexes. Furthermore, the oligomeric state of the protein in solution was studied using size-exclusion chromatography. The results suggested that the unglycosylated human antibody C H 2 domain is a monomer and that its structure is similar to that found in the intact Fc, IgG and Fc receptor complex structures. However, certain structural variations were observed in the Fc receptor-binding sites. Owing to its small size, stability and non-immunogenic Ig template, the C H 2-domain structure could be useful for the development by protein design of antibody domains exerting effector functions and/or antigen specificity and as a robust scaffold in protein-engineering applications

  8. Smoking-Attributable Mortality, Morbidity, and Economic Costs (SAMMEC) - Smoking-Attributable Mortality (SAM)

    Data.gov (United States)

    U.S. Department of Health & Human Services — 2005-2009. SAMMEC - Smoking-Attributable Mortality, Morbidity, and Economic Costs. Smoking-attributable mortality (SAM) is the number of deaths caused by cigarette...

  9. Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure

    Directory of Open Access Journals (Sweden)

    Serrano Luis

    2008-10-01

    Full Text Available Abstract Background Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism that directly relates protein structural dynamics to information exchange between functional sites is still lacking. Results Here we introduce a method to analyze protein dynamics within the framework of information theory and show that signal transduction within proteins can be considered as a particular instance of communication over a noisy channel. In particular, we analyze the conformational correlations between protein residues and apply the concept of mutual information to quantify information exchange. Mapping out changes of mutual information on the protein structure then allows visualizing how distal communication is achieved. We illustrate the approach by analyzing information transfer by the SH2 domain of Fyn tyrosine kinase, obtained from Monte Carlo dynamics simulations. Our analysis reveals that the Fyn SH2 domain forms a noisy communication channel that couples residues located in the phosphopeptide and specificity binding sites and a number of residues at the other side of the domain near the linkers that connect the SH2 domain to the SH3 and kinase domains. We find that for this particular domain, communication is affected by a series of contiguous residues that connect distal sites by crossing the core of the SH2 domain. Conclusion As a result, our method provides a means to directly map the exchange of biological information on the structure of protein domains, making it clear how binding triggers conformational changes in the protein structure. As such it provides a structural road, next to the existing attempts at sequence level, to predict long-range interactions within protein structures.

  10. From SOPs to Reports to Evaluations: Learning and Memory ...

    Science.gov (United States)

    In an era of global trade and regulatory cooperation, consistent and scientifically based interpretation of developmental neurotoxicity (DNT) studies is essential. Because there is flexibility in the selection of test method(s), consistency can be especially challenging for learning and memory tests required by EPA and OECD DNT guidelines (chemicals and pesticides) and recommended for ICH prenatal/postnatal guidelines (pharmaceuticals). A well­ reasoned uniform approach is particularly important for variable endpoints and if non-standard tests are used. An understanding of the purpose behind the tests and expected outcomes is critical, and attention to elements of experimental design, conduct, and reporting can improve study design by the investigator as well as accuracy and consistency of interpretation by evaluators. This understanding also directs which information must be clearly described in study reports. While missing information may be available in standardized operating procedures (SOPs), if not clearly reflected in report submissions there may be questions and misunderstandings by evaluators which could impact risk assessments. A practical example will be presented to provide insights into important variables and reporting approaches. Cognitive functions most often tested in guidelines studies include associative, positional, sequential, and spatial learning and memory in weanling and adult animals. These complex behaviors tap different bra

  11. Potential Precursor Compounds for Chlorohydrocarbons Detected in Gale Crater, Mars, by the SAM Instrument Suite on the Curiosity Rover

    Science.gov (United States)

    Miller, Kristen E.; Eigenbrode, Jennifer L.; Freissinet, Caroline; Glavin, Daniel P.; Kotrc, Benjamin; Francois, Pascaline; Summons, Roger E.

    2016-01-01

    The detection of chlorinated organic compounds in near-surface sedimentary rocks by the Sample Analysis at Mars (SAM) instrument suite aboard the Mars Science Laboratory Curiosity rover represents an important step toward characterizing habitable environments on Mars. However, this discovery also raises questions about the identity and source of their precursor compounds and the processes by which they become chlorinated. Here we present the results of analog experiments, conducted under conditions similar to SAM gas chromatography-mass spectrometry analyses, in which we pyrolyzed potential precursor compounds in the presence of various Cl salts and Fe oxides that have been identified in Martian sediments. While chloromethanes could not be unambiguously identified, 1,2-dichloropropane (1,2-DCP), which is one of the chlorinated compounds identified in SAM data, is formed from the chlorination of aliphatic precursors. Additionally, propanol produced more 1,2-DCP than nonfunctionalized aliphatics such as propane or hexanes. Chlorinated benzenes ranging from chlorobenzene to hexachlorobenzene were identified in experiments with benzene carboxylic acids but not with benzene or toluene. Lastly, the distribution of chlorinated benzenes depended on both the substrate species and the nature and concentration of the Cl salt. Ca and Mg perchlorate, both of which release O2 in addition to Cl2 and HCl upon pyrolysis, formed less chlorobenzene relative to the sum of all chlorinated benzenes than in experiments with ferric chloride. FeCl3, a Lewis acid, catalyzes chlorination but does not aid combustion. Accordingly, both the precursor chemistry and sample mineralogy exert important controls on the distribution of chlorinated organics.

  12. Sexual Desire and Hypoactive Sexual Desire Disorder in Women. Introduction and Overview. Standard Operating Procedure (SOP Part 1)

    DEFF Research Database (Denmark)

    Bitzer, Johannes; Giraldi, Annamaria; Pfaus, Jim

    2013-01-01

    Introduction.  Hypoactive sexual desire disorder (HSDD) is defined in Diagnostic and Statistical Manual of Mental Disorders Fourth Edition as persistent or recurrent deficiency (or absence) of sexual fantasies/thoughts, and/or desire for or receptivity to sexual activity, which causes personal...... must be based on a biopsychosocial, multidimensional, and integrative perspective. Bitzer J, Giraldi A, and Pfaus J. Sexual desire and hypoactive sexual desire disorder in women. Introduction and overview. Standard operating procedure (SOP part 1). J Sex Med **;**:**-**....

  13. Voltage-sensing phosphatase modulation by a C2 domain

    Directory of Open Access Journals (Sweden)

    Paul M. Castle

    2015-04-01

    Full Text Available The voltage-sensing phosphatase (VSP is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD, the inter-domain linker, the cytosolic catalytic domain and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate (PI(4,5P2 (Kalli et al., 2014. Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in

  14. Integration, Validation, and Application of a PV Snow Coverage Model in SAM

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, Janine M. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ryberg, David Severin [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-08-01

    Due to the increasing deployment of PV systems in snowy climates, there is significant interest in a method capable of estimating PV losses resulting from snow coverage that has been verified for a variety of system designs and locations. Many independent snow coverage models have been developed over the last 15 years; however, there has been very little effort verifying these models beyond the system designs and locations on which they were based. Moreover, major PV modeling software products have not yet incorporated any of these models into their workflows. In response to this deficiency, we have integrated the methodology of the snow model developed in the paper by Marion et al. (2013) into the National Renewable Energy Laboratory's (NREL) System Advisor Model (SAM). In this work, we describe how the snow model is implemented in SAM and we discuss our demonstration of the model's effectiveness at reducing error in annual estimations for three PV arrays. Next, we use this new functionality in conjunction with a long term historical data set to estimate average snow losses across the United States for two typical PV system designs. The open availability of the snow loss estimation capability in SAM to the PV modeling community, coupled with our results of the nationwide study, will better equip the industry to accurately estimate PV energy production in areas affected by snowfall.

  15. A lipid binding domain in sphingosine kinase 2

    International Nuclear Information System (INIS)

    Don, Anthony S.; Rosen, Hugh

    2009-01-01

    The lipid second messenger sphingosine 1-phosphate (S1P) is a critical mediator of cellular proliferation and survival signals, and is essential for vasculogenesis and neurogenesis. S1P formation is catalysed by sphingosine kinases 1 and 2 (Sphk1 and Sphk2). We have found that the endogenous glycolipid sulfatide (3-O-sulfogalactosylceramide) binds to and inhibits the activity of Sphk2 and the closely related ceramide kinase (Cerk), but not Sphk1. Using sulfatide as a probe, we mapped the lipid binding domain to the N-terminus of Sphk2 (residues 1-175), a region of sequence that is absent in Sphk1, but aligns with a pleckstrin homology domain in Cerk. Accordingly, Sphk2 bound to phosphatidylinositol monophosphates but not to abundant cellular phospholipids. Deleting the N-terminal domain reduced Sphk2 membrane localisation in cells. We have therefore identified a lipid binding domain in Sphk2 that is important for the enzyme's sub-cellular localisation.

  16. Crystallization and preliminary crystallographic analysis of nosiheptide-resistance methyltransferase from Streptomyces actuosus in complex with SAM

    International Nuclear Information System (INIS)

    Yang, Huirong; Wang, Ping; Dong, Zhenghong; Li, Xueyuan; Gong, Rui; Yang, Ying; Li, Ze; Xu, Youwei; Xu, Yanhui

    2010-01-01

    The expression, purification and crystallization of nosiheptide-resistance methyltransferase (NSR) from Streptomyces actuosus is described. Nosiheptide-resistance methyltransferase (NSR) methylates 23S rRNA at the nucleotide adenosine 1067 in Escherichia coli and thus contributes to resistance against nosiheptide, a sulfur-containing peptide antibiotic. Here, the expression, purification and crystallization of NSR from Streptomyces actuosus are reported. Diffracting crystals were grown by the hanging-drop vapour-diffusion method in reservoir solution consisting of 0.35 M ammonium chloride, 24%(w/v) PEG 3350, 0.1 M MES pH 5.7 at 293 K. Native data have been collected from the apo enzyme and a SAM complex, as well as apo SeMet SAD data. The diffraction patterns of the apo form of NSR, of NSR complexed with SAM and of SeMet-labelled NSR crystals extended to 1.90, 1.95 and 2.25 Å resolution, respectively, using synchrotron radiation. All crystals belonged to space group P2 1 , with approximate unit-cell parameters a = 64.6, b = 69.6, c = 64.9 Å, β = 117.8°

  17. SAMMate: a GUI tool for processing short read alignments in SAM/BAM format

    Directory of Open Access Journals (Sweden)

    Flemington Erik

    2011-01-01

    Full Text Available Abstract Background Next Generation Sequencing (NGS technology generates tens of millions of short reads for each DNA/RNA sample. A key step in NGS data analysis is the short read alignment of the generated sequences to a reference genome. Although storing alignment information in the Sequence Alignment/Map (SAM or Binary SAM (BAM format is now standard, biomedical researchers still have difficulty accessing this information. Results We have developed a Graphical User Interface (GUI software tool named SAMMate. SAMMate allows biomedical researchers to quickly process SAM/BAM files and is compatible with both single-end and paired-end sequencing technologies. SAMMate also automates some standard procedures in DNA-seq and RNA-seq data analysis. Using either standard or customized annotation files, SAMMate allows users to accurately calculate the short read coverage of genomic intervals. In particular, for RNA-seq data SAMMate can accurately calculate the gene expression abundance scores for customized genomic intervals using short reads originating from both exons and exon-exon junctions. Furthermore, SAMMate can quickly calculate a whole-genome signal map at base-wise resolution allowing researchers to solve an array of bioinformatics problems. Finally, SAMMate can export both a wiggle file for alignment visualization in the UCSC genome browser and an alignment statistics report. The biological impact of these features is demonstrated via several case studies that predict miRNA targets using short read alignment information files. Conclusions With just a few mouse clicks, SAMMate will provide biomedical researchers easy access to important alignment information stored in SAM/BAM files. Our software is constantly updated and will greatly facilitate the downstream analysis of NGS data. Both the source code and the GUI executable are freely available under the GNU General Public License at http://sammate.sourceforge.net.

  18. Highlight on the indigenous organic molecules detected on Mars by SAM and potential sources of artifacts and backgrounds generated by the sample preparation

    Science.gov (United States)

    Buch, A.; Belmahdi, I.; Szopa, C.; Freissinet, C.; Glavin, D. P.; Coll, P. J.; Cabane, M.; Millan, M.; Eigenbrode, J. L.; Navarro-Gonzalez, R.; Stern, J. C.; Pinnick, V. T.; Coscia, D.; Teinturier, S.; Stambouli, M.; Dequaire, T.; Mahaffy, P. R.

    2015-12-01

    Among the experiments which explore the martian soil aboard the Curiosity Rover, SAM experiment is mainly dedicated to the search for indigenous organic compounds. To reach its goals SAM can operate in different analysis modes: Pyrolysis-GC-MS and Pyrolysis-MS (EGA). In addition SAM includes wet chemistry experiments [1] to supports extraction of polar organic compounds from solid samples that improves their detection either by increasing the release of chemical species from solid sample matrices, or by changing their chemical structure to make compounds more amenable to gas chromatography mass spectrometry (GCMS). The two wet chemistry experimental capabilities of SAM provide alternatives to the nominal inert-thermal desorption/pyrolysis analytical protocol and are more aptly suited for polar components: MTBSTFA derivatization [2-3] and TMAH thermochemolysis [4-5]. Here we focus on the MTBSTFA derivatization experiment. In order to build a support used to help the interpretation of SAM results, we have investigated the artifacts and backgrounds sources generated by the all analysis process: Solid sample were heated up to approximately 840°C at a rate of 35°C/min under He flow. For GC analyses, the majority of the gas released was trapped on a hydrocarbon trap (Tenax®) over a specific temperature range. Adsorbed volatiles on the GC injection trap (IT) were then released into the GC column (CLP-MXT 30m x 0.25mm x 0.25μm) by rapidly heating the IT to 300°C. Then, in order better understand the part of compounds detected coming from internal reaction we have performed several lab experiments to mimic the SAM device: Among the sources of artifact, we test: (1) the thermal stability and the organic material released during the degradation of Tenax® and carbosieve, (2) the impact of MTBSTFA and a mixture of DMF and MTBSTFA on the adsorbent, (3) the reaction between the different adsorbents (Tenax® and Carbosieve) and calcium perchlorate and then (4) the sources

  19. The Au-S bond and SAM-protein contact in long-range electron transfer of pure and biomimetic metalloproteins via functionalized alkanethiol linkers

    DEFF Research Database (Denmark)

    Chi, Qijin; Ford, Michael J.; Halder, Arnab

    disentangled a wealth of data to identify the nature of the crucial Au-S contact, all suggesting prevalence of a Au(0)-thiyl radical unit. Molecular packing is further determined by the SAM molecular structure and involves binding either to Au-atoms mined out of the surface or directly to a flat surface. We...... functionalized alkanethiols have emerged as core linkers. We have studied molecular linking in the long-range ET (LRET) processes in detail using electrochemistry, in situ STM and AFM, and electronic structure computations. A focus is the electronic structure of the Au-S link and the SAM packing. We have...... is exceedingly sensitive to the structure of the thiol-based SAM molecules, testifying to the crucial importance of SAM packing and Au-S binding, and of the SAM link to the protein. Some of the subtleties are illustrated simpler by similar size (5-6 nm) nanoparticles (NPs). Biomimetic NPs must possess a certain...

  20. REPRESENTASI HOMOSEKSUALITAS DI YOUTUBE: (Studi Semiotika pada Video Pernikahan Sam Tsui

    Directory of Open Access Journals (Sweden)

    Lilis Rucirisyanti

    2017-12-01

    Full Text Available Abstract. Social media is instrumental in giving effect to nitizens, good effects or bad effect, then social media can be also represent a person. Diserve social media make it interesting for nitizens. One of social media is Youtube. Many a lot of video at there, strat from tips and trick videos, journey or vacation video, wedding video, and ect. Everyone can publish their video on Youtube. No exception of same sex enthusiast, in this study are homosexual or gay. One of is a wedding video Sam Tsui and Casey Braves. This research is a qualitative research and this research uses semiotcs analysus of Roland Barthes. By doing an analysis of video that have been published by Sam on Youtube, also do document search and literature. The author sees the existence of verbal and non vebal forms of representation from same sex merriage video of men and men.

  1. Application of the SAM Computer Program for Truckee River Stable Channel Analysis

    National Research Council Canada - National Science Library

    Scott, Stephen H

    2006-01-01

    The purpose of this Coastal and Hydraulics Engineering Technical Note (CHETN) is to demonstrate the utility of the SAM computer programs for evaluating the stability of a stream restoration design on the Truckee River...

  2. Parabolic Trough Reference Plant for Cost Modeling with the Solar Advisor Model (SAM)

    Energy Technology Data Exchange (ETDEWEB)

    Turchi, C.

    2010-07-01

    This report describes a component-based cost model developed for parabolic trough solar power plants. The cost model was developed by the National Renewable Energy Laboratory (NREL), assisted by WorleyParsons Group Inc., for use with NREL's Solar Advisor Model (SAM). This report includes an overview and explanation of the model, two summary contract reports from WorleyParsons, and an Excel spreadsheet for use with SAM. The cost study uses a reference plant with a 100-MWe capacity and six hours of thermal energy storage. Wet-cooling and dry-cooling configurations are considered. The spreadsheet includes capital and operating cost by component to allow users to estimate the impact of changes in component costs.

  3. Superbinder SH2 domains act as antagonists of cell signaling.

    Science.gov (United States)

    Kaneko, Tomonori; Huang, Haiming; Cao, Xuan; Li, Xing; Li, Chengjun; Voss, Courtney; Sidhu, Sachdev S; Li, Shawn S C

    2012-09-25

    Protein-ligand interactions mediated by modular domains, which often play important roles in regulating cellular functions, are generally of moderate affinities. We examined the Src homology 2 (SH2) domain, a modular domain that recognizes phosphorylated tyrosine (pTyr) residues, to investigate how the binding affinity of a modular domain for its ligand influences the structure and cellular function of the protein. We used the phage display method to perform directed evolution of the pTyr-binding residues in the SH2 domain of the tyrosine kinase Fyn and identified three amino acid substitutions that critically affected binding. We generated three SH2 domain triple-point mutants that were "superbinders" with much higher affinities for pTyr-containing peptides than the natural domain. Crystallographic analysis of one of these superbinders revealed that the superbinder SH2 domain recognized the pTyr moiety in a bipartite binding mode: A hydrophobic surface encompassed the phenyl ring, and a positively charged site engaged the phosphate. When expressed in mammalian cells, the superbinder SH2 domains blocked epidermal growth factor receptor signaling and inhibited anchorage-independent cell proliferation, suggesting that pTyr superbinders might be explored for therapeutic applications and useful as biological research tools. Although the SH2 domain fold can support much higher affinity for its ligand than is observed in nature, our results suggest that natural SH2 domains are not optimized for ligand binding but for specificity and flexibility, which are likely properties important for their function in signaling and regulatory processes.

  4. Must, valge + hall : Sam Wagstaffi ja Robert Mapplethorpe'i portree / Madis Palm

    Index Scriptorium Estoniae

    Palm, Madis

    2008-01-01

    Dokumentaalfilm "Black, White & Gray: Sam Wagstaff and Robert Mapplethorpe" : autor ja režissöör James Crump : Ameerika Ühendriigid 2007. Filmi näidati filminädala "Art in America" raames Tallinnas

  5. Evolution of SH2 domains and phosphotyrosine signalling networks

    Science.gov (United States)

    Liu, Bernard A.; Nash, Piers D.

    2012-01-01

    Src homology 2 (SH2) domains mediate selective protein–protein interactions with tyrosine phosphorylated proteins, and in doing so define specificity of phosphotyrosine (pTyr) signalling networks. SH2 domains and protein-tyrosine phosphatases expand alongside protein-tyrosine kinases (PTKs) to coordinate cellular and organismal complexity in the evolution of the unikont branch of the eukaryotes. Examination of conserved families of PTKs and SH2 domain proteins provides fiduciary marks that trace the evolutionary landscape for the development of complex cellular systems in the proto-metazoan and metazoan lineages. The evolutionary provenance of conserved SH2 and PTK families reveals the mechanisms by which diversity is achieved through adaptations in tissue-specific gene transcription, altered ligand binding, insertions of linear motifs and the gain or loss of domains following gene duplication. We discuss mechanisms by which pTyr-mediated signalling networks evolve through the development of novel and expanded families of SH2 domain proteins and the elaboration of connections between pTyr-signalling proteins. These changes underlie the variety of general and specific signalling networks that give rise to tissue-specific functions and increasingly complex developmental programmes. Examination of SH2 domains from an evolutionary perspective provides insight into the process by which evolutionary expansion and modification of molecular protein interaction domain proteins permits the development of novel protein-interaction networks and accommodates adaptation of signalling networks. PMID:22889907

  6. A Novel Tyrosine Kinase Expressed in Breast Tumors

    National Research Council Canada - National Science Library

    Tyner, Angela

    1999-01-01

    .... Sik interacts with Sam68 through both its SH3 and SH2 domains. Transfected Sik and Sam68 colocalize to the nucleoplasm of nontransformed NMuMG mammary epithelial cells, while the human homologue of Sik (BRK...

  7. The Sample at Mars Analysis (SAM) Detections of CO2 and CO in Sedimentary Material from Gale Crater, Mars: Implications for the Presence of Organic Carbon and Microbial Habitability on Mars

    Science.gov (United States)

    Sutter, Brad; Eigenbrode, Jennifer L.; Steele, Andrew; Ming, Douglas W.

    2016-01-01

    Sedimentary rock samples heated to 860 degrees Centigrade in the SAM (Sample at Mars) instrument evolved CO2 and CO indicating the presence of organic-carbon(C) in Gale Crater materials. Martian or exogenous (meteoritic, interplanetary dust) CO2 and CO could be derived from combustion of simple organics (less than 300 degrees Centigrade), complex refractory organics/amorphous carbon (300-600 degrees Centigrade), and/or magmatic carbon (greater than 600 degrees Centigrade) as result of thermal decomposition of Gale Crater perchlorates, and sulfates present that produce O2. Oxidized organic compounds could also evolve CO2 and CO over broad temperature range (150 to 800 degrees Centigrade) and such organics are expected on Mars via exogenous sources. Alternatively, organic-C could also have been oxidized to carboxylic acids [e.g, mellitic acid (RCOOH), acetate (CH3CO2-), and oxalates (C2O42-)] by oxidative radiolytic weathering, or other oxidation processes. The presence of oxidized organics is consistent with the limited detection of reduced organic-C phases by the SAM-gas chromatography. Organic-C content as determined by CO2 and CO contents could range between 800 and 2400 parts per million C indicating that substantial organic-C component is present in Gale Crater. There are contributions from SAM background however, even in worst-case scenarios, this would only account for as much as half of the detected CO2 and CO. Nevertheless, if organic-C levels were assumed to have existed in a reduced form on ancient Mars and this was bioavailable C, then less than 1 percent of C in Gale Crater sediments could have supported an exclusively heterotrophic microbial population of 1 by 10 (sup 5) cells per gram sediment (assumes 9 by 10 (sup -7) microgram per cell and 0.5 micrograms C per microgram cell). While other essential nutrients (e.g., S and P) could be limiting, organic-C contents, may have been sufficient to support limited heterotrophic microbial populations on

  8. Hydrophobic interaction between the SH2 domain and the kinase domain is required for the activation of Csk.

    Science.gov (United States)

    Mikkola, Esa T; Gahmberg, Carl G

    2010-06-18

    The protein tyrosine kinase C-terminal Src kinase (Csk) is activated by the engagement of its Src homology (SH) 2 domain. However, the molecular mechanism required for this is not completely understood. The crystal structure of the active Csk indicates that Csk could be activated by contact between the SH2 domain and the beta3-alphaC loop in the N-terminal lobe of the kinase domain. To study the importance of this interaction for the SH2-domain-mediated activation of Csk, we mutated the amino acid residues forming the contacts between the SH2 domain and the beta3-alphaC loop. The mutation of the beta3-alphaC loop Ala228 to glycine and of the SH2 domain Tyr116, Tyr133, Leu138, and Leu149 to alanine resulted in the inability of the SH2 domain ligand to activate Csk. Furthermore, the overexpressed Csk mutants A228G, Y133A/Y116A, L138A, and L149A were unable to efficiently inactivate endogenous Src in human embryonic kidney 293 cells. The results suggest that the SH2-domain-mediated activation of Csk is dependent on the binding of the beta3-alphaC loop Ala228 to the hydrophobic pocket formed by the side chains of Tyr116, Tyr133, Leu138, and Leu149 on the surface of the SH2 domain. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  9. Simultaneous determination of four active components in Alisma orientale (Sam. Juz. by HPLC–DAD using a single reference standard

    Directory of Open Access Journals (Sweden)

    Yao-Wen Zhang

    2015-04-01

    Full Text Available A rapid, simple and practical high-performance liquid chromatography method coupled with diode array detector (HPLC–DAD was developed to evaluate the quality of Alisma orientale (Sam. Juz. through a simultaneous determination of four major active triterpenes using a single standard to determine the multi-components (SSDMCs. Alisol B 23-acetate was selected as the reference compound for calculating the relative response factors. All calibration curves showed good linearity (R2>0.9998 within test ranges. RSDs for intra- and inter-day of four analytes were less than 3.6% and 2.3%; the overall recovery was 92.1–110.2% (SSDMC. The proposed method was successfully applied to quantify the four components in 20 samples from different localities in China. Moreover, significant variations were demonstrated in the content of these compounds. In addition, hierarchical clustering analysis (HCA and principal components analysis (PCA were performed to differentiate and classify the samples based on the contents of Alisol C 23-acetate, Alisol A, Alisol A 24-acetate and Alisol B 23-acetate. This simple, rapid, low-cost and reliable HPLC–DAD method using SSDMC is suitable for routine quantitative analysis and quality control of A. orientale (Sam. Juz. Keywords: SSDMC, Alisma orientale (Sam. Juz, Quality control, HCA, PCA

  10. Congressmember Sam Farr: Five Decades of Public Service

    OpenAIRE

    Reti, Irene H.; Farr, Sam

    2017-01-01

    Congressmember Sam Farr (born July 4, 1941) represented California’s Central Coast in the United States House of Representatives for twenty-three years until his retirement from office in 2016.  Farr also served six years as a member of the Monterey County Board of Supervisors and twelve years in the California State Assembly. This oral history, a transcript of twenty-five hours of interviews conducted by Irene Reti, director of the UCSC Library’s Regional History Project, during the period i...

  11. Crystal structure of the Ig1 domain of the neural cell adhesion molecule NCAM2 displays domain swapping

    DEFF Research Database (Denmark)

    Rasmussen, Kim Krighaar; Kulahin, Nikolaj; Kristensen, Ole

    2008-01-01

    The crystal structure of the first immunoglobulin (Ig1) domain of neural cell adhesion molecule 2 (NCAM2/OCAM/RNCAM) is presented at a resolution of 2.7 A. NCAM2 is a member of the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). In the structure, two Ig domains interact by domain...

  12. Technical Manual for the SAM Biomass Power Generation Model

    Energy Technology Data Exchange (ETDEWEB)

    Jorgenson, J.; Gilman, P.; Dobos, A.

    2011-09-01

    This technical manual provides context for the implementation of the biomass electric power generation performance model in the National Renewable Energy Laboratory's (NREL's) System Advisor Model (SAM). Additionally, the report details the engineering and scientific principles behind the underlying calculations in the model. The framework established in this manual is designed to give users a complete understanding of behind-the-scenes calculations and the results generated.

  13. Molecular tilt-dependent and tyrosine-enhanced electron transfer across ITO/SAM/[DPPC–Au NP–Tyrosine] Janus nanoparticle junction

    Energy Technology Data Exchange (ETDEWEB)

    Sarangi, Nirod Kumar; Patnaik, Archita, E-mail: archita59@yahoo.com [Indian Institute of Technology Madras, Department of Chemistry (India)

    2016-09-15

    Enhanced interfacial electron transfer (ET) across the otherwise insulating indium tin oxide/alkanethiol self-assembled monolayer (SAM)/redox molecule junction was accomplished when a Janus gold nanoparticle (JNP) protected by bioinspired phosphatidylcholine (DPPC) lipid and tyrosine amino acid ligands was anchored on it. In addition to the most theoretical and experimental investigations on the distance-dependent ET across Metal–Organic SAM–Nanoparticle (NP) architectures, the current results succinctly illustrate molecular tilt angle of the SAM and the characteristic of JNP as key factors in expediting the ET rate via electron tunneling. In the absence of JNP, electron tunneling with a tunneling factor β = 1.1 Å{sup −1} across the SAM was the rate-limiting step, evidenced from electrochemical impedance spectroscopy (EIS). The apparent electron transfer rate constant (k{sub app}{sup 0}) for anchored SAM was enhanced by at least one order of magnitude than the DPPC-only protected nanoparticle, suggesting the potential role of tyrosine towards the enhanced ET. The asymmetric and biogenic nature of the construct sheds light on a potential bioelectronic device for novel electronic attributes.Graphical abstractEntry of TOC .

  14. Non-invasive vibrational SFG spectroscopy reveals that bacterial adhesion can alter the conformation of grafted "brush" chains on SAM.

    Science.gov (United States)

    Bulard, Emilie; Guo, Ziang; Zheng, Wanquan; Dubost, Henri; Fontaine-Aupart, Marie-Pierre; Bellon-Fontaine, Marie-Noëlle; Herry, Jean-Marie; Briandet, Romain; Bourguignon, Bernard

    2011-04-19

    Understanding bacterial adhesion on a surface is a crucial step to design new materials with improved properties or to control biofilm formation and eradication. Sum Frequency Generation (SFG) vibrational spectroscopy has been employed to study in situ the conformational response of a self-assembled monolayer (SAM) of octadecanethiol (ODT) on a gold film to the adhesion of hydrophilic and hydrophobic ovococcoid model bacteria. The present work highlights vibrational SFG spectroscopy as a powerful and unique non-invasive biophysical technique to probe and control bacteria interaction with ordered surfaces. Indeed, the SFG vibrational spectral changes reveal different ODT SAM conformations in air and upon exposure to aqueous solution or bacterial adhesion. Furthermore, this effect depends on the bacterial cell surface properties. The SFG spectral modeling demonstrates that hydrophobic bacteria flatten the ODT SAM alkyl chain terminal part, whereas the hydrophilic ones raise this ODT SAM terminal part. Microorganism-induced alteration of grafted chains can thus affect the desired interfacial functionality, a result that should be considered for the design of new reactive materials. © 2011 American Chemical Society

  15. Molecular junctions based on SAMs of cruciform oligo(phenylene ethynylene)s

    DEFF Research Database (Denmark)

    Wei, Zhongming; Li, Tao; Jennum, Karsten Stein

    2012-01-01

    Cruciform oligo(phenylene ethynylene)s (OPEs) with an extended tetrathiafulvalene (TTF) donor moiety (OPE5-TTF and OPE3-TTF) and their simple analogues (OPE5-S and OPE3) without conjugated substituents were used to form high quality self-assembled monolayers (SAMs) on ultra-flat gold substrates...

  16. Selective translational repression of HIV-1 RNA by Sam68DeltaC occurs by altering PABP1 binding to unspliced viral RNA

    Directory of Open Access Journals (Sweden)

    Soros Vanessa

    2008-10-01

    Full Text Available Abstract HIV-1 structural proteins are translated from incompletely spliced 9 kb and 4 kb mRNAs, which are transported to the cytoplasm by Crm1. It has been assumed that once in the cytoplasm, translation of incompletely spliced HIV-1 mRNAs occurs in the same manner as host mRNAs. Previous analyses have demonstrated that Sam68 and a mutant thereof, Sam68ΔC, have dramatic effects on HIV gene expression, strongly enhancing and inhibiting viral structural protein synthesis, respectively. While investigating the inhibition of incompletely spliced HIV-1 mRNAs by Sam68ΔC, we determined that the effect was independent of the perinuclear bundling of the viral RNA. Inhibition was dependent upon the nuclear export pathway used, as translation of viral RNA exported via the Tap/CTE export pathway was not blocked by Sam68ΔC. We demonstrate that inhibition of HIV expression by Sam68ΔC is correlated with a loss of PABP1 binding with no attendant change in polyadenosine tail length of the affected RNAs. The capacity of Sam68ΔC to selectively inhibit translation of HIV-1 RNAs exported by Crm1 suggests that it is able to recognize unique characteristics of these viral RNPs, a property that could lead to new therapeutic approaches to controlling HIV-1 replication.

  17. Solution structure of tensin2 SH2 domain and its phosphotyrosine-independent interaction with DLC-1.

    Directory of Open Access Journals (Sweden)

    Kun Dai

    Full Text Available Src homology 2 (SH2 domain is a conserved module involved in various biological processes. Tensin family member was reported to be involved in tumor suppression by interacting with DLC-1 (deleted-in-liver-cancer-1 via its SH2 domain. We explore here the important questions that what the structure of tensin2 SH2 domain is, and how it binds to DLC-1, which might reveal a novel binding mode.Tensin2 SH2 domain adopts a conserved SH2 fold that mainly consists of five β-strands flanked by two α-helices. Most SH2 domains recognize phosphorylated ligands specifically. However, tensin2 SH2 domain was identified to interact with nonphosphorylated ligand (DLC-1 as well as phosphorylated ligand.We determined the solution structure of tensin2 SH2 domain using NMR spectroscopy, and revealed the interactions between tensin2 SH2 domain and its ligands in a phosphotyrosine-independent manner.

  18. Increasing the fill factor of inverted P3HT:PCBM solar cells through surface modification of Al-doped ZnO via phosphonic acid-anchored C60 SAMs

    Energy Technology Data Exchange (ETDEWEB)

    Stubhan, Tobias [Institute of Materials for Electronics and Energy Technology (I-MEET), Friedrich-Alexander-University, Erlangen-Nuremberg, Erlangen (Germany); Salinas, Michael; Halik, Marcus [Organic Materials and Devices (OMD)-Institute of Polymer Materials, University Erlangen-Nuremberg, Erlangen (Germany); Ebel, Alexander; Hirsch, Andreas [Institute for Organic Chemistry II, Friedrich-Alexander-University, Erlangen-Nuremberg, Erlangen (Germany); Krebs, Frederick C. [Risoe National Laboratory for Sustainable Energy, Technical University of Denmark, Roskilde (Denmark); Brabec, Christoph J. [Institute of Materials for Electronics and Energy Technology (I-MEET), Friedrich-Alexander-University, Erlangen-Nuremberg, Erlangen (Germany); Bavarian Center for Applied Energy Research (ZAE Bayern), Erlangen (Germany)

    2012-05-15

    The influence of aluminum-doped zinc oxide (AZO) electron extraction layers modified with self-assembled monolayers (SAMs) on inverted polymer solar cells is investigated. It is found that AZO modification with phosphonic acid-anchored Fullerene-SAMs leads to a reduction of the series resistance, while increasing the parallel resistance. This results in an increased efficiency from 2.9 to 3.3%. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Fusion protein based on Grb2-SH2 domain for cancer therapy

    International Nuclear Information System (INIS)

    Saito, Yuriko; Furukawa, Takako; Arano, Yasushi; Fujibayashi, Yasuhisa; Saga, Tsuneo

    2010-01-01

    Research highlights: → Grb2 mediates EGFR signaling through binding to phosphorylate EGFR with SH2 domain. → We generated fusion proteins containing 1 or 2 SH2 domains of Grb2 added with TAT. → The one with 2 SH2 domains (TSSF) interfered ERK phosphorylation. → TSSF significantly delayed the growth of EGFR overexpressing tumor in a mouse model. -- Abstract: Epidermal growth factor receptor (EGFR) is one of the very attractive targets for cancer therapy. In this study, we generated fusion proteins containing one or two Src-homology 2 (SH2) domains of growth factor receptor bound protein 2 (Grb2), which bind to phosphorylated EGFR, added with HIV-1 transactivating transcription for cell membrane penetration (termed TSF and TSSF, respectively). We examined if they can interfere Grb2-mediated signaling pathway and suppress tumor growth as expected from the lack of SH3 domain, which is necessary to intermediate EGFR-Grb2 cell signaling, in the fusion proteins. The transduction efficiency of TSSF was similar to that of TSF, but the binding activity of TSSF to EGFR was higher than that of TSF. Treatment of EGFR-overexpressing cells showed that TSSF decreased p42-ERK phosphorylation, while TSF did not. Both the proteins delayed cell growth but did not induce cell death in culture. TSSF also significantly suppressed tumor growth in vivo under consecutive administration. In conclusion, TSSF showed an ability to inhibit EGFR-Grb2 signaling and could have a potential to treat EGFR-activated cancer.

  20. Jo Ann Baumgartner and Sam Earnshaw: Organizers and Farmers

    OpenAIRE

    Rabkin, Sarah

    2010-01-01

    Jo Ann Baumgartner directs the Wild Farm Alliance, based in Watsonville, California. WFA’s mission, as described on the organization’s website, is “to promote agriculture that helps to protect and restore wild Nature.” Through research, publications, presentations, events, policy work, and consulting, the organization works to “connect food systems with ecosystems.” Sam Earnshaw is Central Coast regional coordinator of the Community Alliance with Family Farmers. Working with CAFF’s f...

  1. Pembuatan Standard Operating Procedure (SOP Service Desk Berdasarkan Kerangka Kerja Itil V3 dengan Menggunakan Metode Analisis Gap Layanan (Studi Kasus: PT. XYZ , Tangerang

    Directory of Open Access Journals (Sweden)

    Annisa Rachmi

    2014-09-01

    Full Text Available Penggunaan Teknologi Informasi di banyak perusahaan telah menjadi satu hal penting dalam meningkatkan efektifitas dan efisiensi operasional bisnis yang mendukung tercapainya tujuan perusahaan, termasuk juga PT XYZ. Unit fungsional service desk sangat dibutuhkan oleh PT XYZ dalam mendukung operasional TI dan menangani permasalahan yang muncul serta memonitor terkait penggunaan TI yang ada di dalam perusahaan. Adanya kebutuhan PT XYZ untuk menjadikan service desk menjadi unit yang dapat berjalan dengan baik sesuai dengan fungsinya, menunjukkan bahwa perlunya penerapan tata kelola TI untuk mengatur dan mengelola aktivitas service desk. Salah satu tata kelola TI yang dimaksud adalah berupa prosedur kerja. Kerangka kerja Information Technology Infrastructure Library (ITIL merupakan suatu best practice yang bertujuan secara berkelanjutan meningkatkan efisiensi operasional TI. Perancangan dan implementasi service desk berdasarkan kerangka kerja ITIL V3 di PT XYZ diperlukan dalam upaya meningkatkan layanan TI dan mengatasi masalah yang ada saat ini. Pembuatan SOP ini diinisialisasi dengan menggunakan metode analisis gap, proses-proses yang dimuat ke dalam SOP merupakan hasil analisis kesenjangan antara kondisi kekinian service desk PT XYZ dengan kondisi ideal service desk framework ITIL.

  2. Reflections on Sam Harris' "Free Will"

    Directory of Open Access Journals (Sweden)

    Daniel C. Dennett

    2017-12-01

    Full Text Available In his book Free Will Sam Harris tries to persuade us to abandon the morally pernicious idea of free will. The following contribution articulates and defends a more sophisticated model of free will that is not only consistent with neuroscience and introspection but also grounds a variety of responsibility that justifies both praise and blame, reward and punishment. This begins with the long lasting parting of opinion between compatibilists (who argue that free will can live comfortably with determinism and incompatibilists (who deny this. While Harris dismisses compatibilism as a form of theology, this article aims at showing that Harris has underestimated and misinterpreted compatibilism and at defending a more sophisticated version of compatibilism that is imprevious to Harris’ criticism.

  3. Growth and Functionality of Cells Cultured on Conducting and Semi-Conducting Surfaces Modified with Self-Assembled Monolayers (SAMs

    Directory of Open Access Journals (Sweden)

    Rajendra K. Aithal

    2016-02-01

    Full Text Available Bioengineering of dermal and epidermal cells on surface modified substrates is an active area of research. The cytotoxicity, maintenance of cell phenotype and long-term functionality of human dermal fibroblast (HDF cells on conducting indium tin oxide (ITO and semi-conducting, silicon (Si and gallium arsenide (GaAs, surfaces modified with self-assembled monolayers (SAMs containing amino (–NH2 and methyl (–CH3 end groups have been investigated. Contact angle measurements and infrared spectroscopic studies show that the monolayers are conformal and preserve their functional end groups. Morphological analyses indicate that HDFs grow well on all substrates except GaAs, exhibiting their normal spindle-shaped morphology and exhibit no visible signs of stress or cytoplasmic vacuolation. Cell viability analyses indicate little cell death after one week in culture on all substrates except GaAs, where cells died within 6 h. Cells on all surfaces proliferate except on GaAs and GaAs-ODT. Cell growth is observed to be greater on SAM modified ITO and Si-substrates. Preservation of cellular phenotype assessed through type I collagen immunostaining and positive staining of HDF cells were observed on all modified surfaces except that on GaAs. These results suggest that conducting and semi-conducting SAM-modified surfaces support HDF growth and functionality and represent a promising area of bioengineering research.

  4. Iron-Rich Carbonates as the Potential Source of Evolved CO2 Detected by the Sample Analysis at Mars (SAM) Instrument in Gale Crater

    Science.gov (United States)

    Sutter, B.; Heil, E.; Rampe, E. B.; Morris, R. V.; Ming, D. W.; Archer, P. D.; Eigenbrode, J. L.; Franz, H. B.; Glavin, D. P.; McAdam, A. C.; hide

    2015-01-01

    The Sample Analysis at Mars (SAM) instrument detected at least 4 distinct CO2 release during the pyrolysis of a sample scooped from the Rocknest (RN) eolian deposit. The highest peak CO2 release temperature (478-502 C) has been attributed to either a Fe-rich carbonate or nano-phase Mg-carbonate. The objective of this experimental study was to evaluate the thermal evolved gas analysis (T/EGA) characteristics of a series of terrestrial Fe-rich carbonates under analog SAM operating conditions to compare with the RN CO2 releases. Natural Fe-rich carbonates (<53 microns) with varying Fe amounts (Fe(0.66)X(0.34)- to Fe(0.99)X(0.01)-CO3, where X refers to Mg and/or Mn) were selected for T/EGA. The carbonates were heated from 25 to 715 C (35 C/min) and evolved CO2 was measured as a function of temperature. The highest Fe containing carbonates (e.g., Fe(0.99)X(0.01)-CO3) yielded CO2 peak temperatures between 466-487 C, which is consistent with the high temperature RN CO2 release. The lower Fe-bearing carbonates (e.g., Fe(0.66)X(0.34)CO3) did not have peak CO2 release temperatures that matched the RN peak CO2 temperatures; however, their entire CO2 releases did occur within RN temperature range of the high temperature CO2 release. Results from this laboratory analog analysis demonstrate that the high temperature RN CO2 release is consistent with Fe-rich carbonate (approx.0.7 to 1 wt.% FeCO3). The similar RN geochemistry with other materials in Gale Crater and elsewhere on Mars (e.g., Gusev Crater, Meridiani) suggests that up to 1 wt. % Fe-rich carbonate may occur throughout the Gale Crater region and could be widespread on Mars. The Rocknest Fe-carbonate may have formed from the interaction of reduced Fe phases (e.g., Fe2+ bearing olivine) with atmospheric CO2 and transient water. Alternatively, the Rocknest Fe-carbonate could be derived by eolian processes that have eroded distally exposed deep crustal material that possesses Fe-carbonate that may have formed through

  5. Sulphur-bearing Compounds Detected by MSL SAM Evolved Gas Analysis of Materials from Yellowknife Bay, Gale Crater, Mars

    Science.gov (United States)

    McAdam, A. C.; Franz, H. B.; Archer, P. D. Jr.; Sutter, B.; Eigenbrode, J. L.; Freissinet, C.; Atreya, S. K.; Bish, D. L.; Blake, D. F.; Brunner, A.; hide

    2014-01-01

    The Sample Analysis at Mars (SAM) and Chemistry and Mineralogy (CheMin) instruments on the Mars Science Laboratory (MSL) analysed several subsamples of sample fines (bearing phases present below the CheMin detection limit or difficult to characterize with XRD (e.g., X-ray amorphous phases). Here, we focus on potential constraints on phases that evolved SO2, H2S, OCS, and CS2 during thermal analysis.

  6. In Situ Analysis of Mars Soil and Rocks Sample with the Sam Gcms Instrumentation Onboard Curiosity : Interpretation and Comparison of Measurements Done during the First Martian Year of Curiosity on Mars

    Science.gov (United States)

    Szopa, C.; Coll, P. J.; Cabane, M.; Buch, A.; Coscia, D.; Millan, M.; Francois, P.; Belmahadi, I.; Teinturier, S.; Navarro-Gonzalez, R.; Glavin, D. P.; Freissinet, C.; Steele, A.; Eigenbrode, J. L.; Mahaffy, P. R.

    2014-12-01

    The characterisation of the chemical and mineralogical composition of solid surface samples collected with the Curiosity rover is a primary objective of the SAM experiment. These data should provide essential clues on the past habitability of Gale crater. Amongst the SAM suite of instruments [1], SAM-GC (Gas Chromatograph) is devoted to identify and quantify volatiles evolved from the thermal (heating up to about 900°C)/chemical (derivatization procedure) treatment of any soil sample collected by the Curiosity rover. With the aim to search for potential organic molecules outgassed from the samples, SAM-GC analytical channels composed of thermal-desorption injector, and a MXT-CLP or a MXT-Q chromatographic column was chosen to achieve all the measurements done up today, with the aim to separate of a wide range of volatile inorganic and organic molecules. Four solid samples have been analyzed with GCMS, one sand sample collected at the Rocknest site, two rock samples (John Klein and Cumberland respectively) collected at the Yellowknife Bay site using the Curiosity driller, and one rock sample collected at the Kimberly site. All the measurements were successful and they produced complex chromatograms with both detectors used for SAM GC, i.e. a thermal conductivity detector and the SAM quandrupole mass spectrometer. Their interpretation already revealed the presence of an oxychlorine phase present in the sample which is at the origin of chlorohydrocarbons clearly identified [2] but this represents only a fraction of the GCMS signal recorded [3,4]. This work presents a systematic comparison of the GCMS measurements done for the different samples collected, supported by reference data obtained in laboratory with different spare models of the gas chromatograph, with the aim to bring new elements of interpretation of the SAM measurements. References: [1] Mahaffy, P. et al. (2012) Space Sci Rev, 170, 401-478. [2] Glavin, D. et al. (2013), JGR. [3] Leshin L. et al. (2013

  7. Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

    Science.gov (United States)

    Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

    2012-11-30

    Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Stealing the gold a celebration of the pioneering physics of Sam Edwards

    CERN Document Server

    Goldenfeld, Nigel; Sherrington, D C; Edwards, S F

    2004-01-01

    This title presents a survey of some of the most exciting topics in condensed matter physics today, from the perspective of the pioneering work of Sam Edwards. Original articles from leaders in the field highlight the historical development as well as new and emerging areas.

  9. The role of zonally asymmetric heating in the vertical and temporal structure of the global scale flow fields during FGGE SOP-1

    Science.gov (United States)

    Paegle, J.; Kalnay, E.; Baker, W. E.

    1981-01-01

    The global scale structure of atmospheric flow is best documented on time scales longer than a few days. Theoretical and observational studies of ultralong waves have emphasized forcing due to global scale variations of topography and surface heat flux, possibly interacting with baroclinically unstable or vertically refracting basic flows. Analyses of SOP-1 data in terms of global scale spherical harmonics is documented with emphasis upon weekly transitions.

  10. Radical SAM Enzymes in the Biosynthesis of Ribosomally Synthesized and Post-translationally Modified Peptides (RiPPs

    Directory of Open Access Journals (Sweden)

    Alhosna Benjdia

    2017-11-01

    Full Text Available Ribosomally-synthesized and post-translationally modified peptides (RiPPs are a large and diverse family of natural products. They possess interesting biological properties such as antibiotic or anticancer activities, making them attractive for therapeutic applications. In contrast to polyketides and non-ribosomal peptides, RiPPs derive from ribosomal peptides and are post-translationally modified by diverse enzyme families. Among them, the emerging superfamily of radical SAM enzymes has been shown to play a major role. These enzymes catalyze the formation of a wide range of post-translational modifications some of them having no counterparts in living systems or synthetic chemistry. The investigation of radical SAM enzymes has not only illuminated unprecedented strategies used by living systems to tailor peptides into complex natural products but has also allowed to uncover novel RiPP families. In this review, we summarize the current knowledge on radical SAM enzymes catalyzing RiPP post-translational modifications and discuss their mechanisms and growing importance notably in the context of the human microbiota.

  11. Método de diagnóstico e análise do S&OP: uma ferramenta para mapeamento do nível de integração do processo e identificação de oportunidades de melhoria

    OpenAIRE

    Silva, Rafael Bernardes da

    2015-01-01

    A integração entre os planos estratégico, tático e operacional é um relevante desafio para as organizações. Visando otimizar o alinhamento organizacional, empresas vêm implementando processos de Sales and Operations Planning (S&OP) e desenvolvendo ações para torná-lo robusto. Entende-se o S&OP como um processo de consolidação dos diversos planos organizacionais e direcionamento estratégico do negócio, permitindo o alcance de vantagem competitiva de modo contínuo e integrando os planos de mark...

  12. International ISOE Workshop - Direction Forward for the Finalization of the EG-SAM Report

    International Nuclear Information System (INIS)

    Okyar, H. Burcin

    2014-01-01

    The objective of the ISOE Expert Group on Occupational Radiation Protection in Severe Accident Management and Post-accident Recovery (EG-SAM) is to develop a report on best radiation protection management procedures for proper radiation protection job coverage during severe accident initial response and recovery efforts to identify good radiation protection practices and to organise and communicate radiation protection lessons learned from previous reactor accidents. The outcome of the work will be a new ISOE publication on Occupational Radiation Protection in severe accident management that will find broad use within the NPP radiation protection community. The EG-SAM has finalized an interim report which was presented at the Washington workshop. The interim report covered the following topics: RP Management and Organisation; RP Training and Exercises related to Severe Accident Management; Facility Configuration and Readiness; Overall Approach for Worker Protection; Monitoring and Managing the Radioactive Releases and Contamination; Key Lessons Learned from Past Accidents; Conclusions. Utilities and Regulatory Authorities have identified the factors and aspects which play key roles in achieving good practices on occupational radiation protection in severe accident management and post-accident recovery: knowledge, experience, technology, regulatory requirements and guidance, worker involvement, information exchange, training aspects, etc. They have analysed and quantified their impact on worker doses, and submitted recommendations for further work. The next step will be a final meeting of the EG-SAM for the finalization of the report with workshop inputs before its submission for approval

  13. SAM - Sistema Automatizado del Método MECAP para Especificar Casos de Prueba

    Directory of Open Access Journals (Sweden)

    Kenyer Domínguez

    2010-12-01

    Full Text Available Existen cuatro elementos que son relevantes al momento de definir las pruebas: Confiabilidad, Costo, Tiempo y Calidad. El tiempo de desarrollo y el costo del producto se incrementan cuando se desean pruebas confiables y un software de calidad. Pero ¿qué se puede hacer para que los involucrados comprendan que las pruebas deben ser vistas como una red de seguridad? Si la calidad no se contempla antes de comenzar las pruebas, entonces ella no estará cuando se éstas terminen. El objetivo de este artículo es presentar la herramienta, SAM – Sistema Automatizado del Método MECAP que permite especificar Casos de Prueba a partir de Casos de Uso incorporando elementos que promueven la verificación y validación de la trazabilidad entre la Gestión de Requerimientos, el Análisis y Diseño y las Pruebas. SAM soporta el proceso de pruebas de forma automatizada, mejorando la confiabilidad de las mismas

  14. Detection of Reduced Nitrogen Compounds at Rocknest Using the Sample Analysis At Mars (SAM) Instrument on the Mars Science Laboratory (MSL)

    Science.gov (United States)

    Stern, J. C.; Steele, A.; Brunner, A.; Coll, P.; Eigenbrode, J.; Franz, H. B.; Freissinet, C.; Glavin, D.; Jones, J. H.; Navarro-Gonzalez, R.; hide

    2013-01-01

    The Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) Curiosity Rover detected nitrogen-bearing compounds during the pyrolysis of Rocknest material at Gale Crater. Hydrogen cyanide and acetonitrile were identified by the quadrupole mass spectrometer (QMS) both in direct evolved gas analysis (EGA). SAM carried out four separate analyses from Rocknest Scoop 5. A significant low temperature release was present in Rocknest runs 1-4, while a smaller high temperature release was also seen in Rocknest runs 1-3. Here we evaluate whether these compounds are indigenous to Mars or a pyrolysis product resulting from known terrestrial materials that are part of the SAM derivatization.

  15. Theorizing the place of evil within Sam Ukala's Radical Theatre: A ...

    African Journals Online (AJOL)

    The perspectives of evil in this essay will be drawn mainly from the works of such thinkers as Paul Ricoeur, St Augustine, and Friedrich Nietzsche, yet not excluding occasional insights from thinkers like Immanuel Kant, Richard B. Sewall, and so on. Sam Ukala's Akpakaland, Break a Boil and Odour of Justice are the plays to ...

  16. Src binds cortactin through an SH2 domain cystine-mediated linkage

    Science.gov (United States)

    Evans, Jason V.; Ammer, Amanda G.; Jett, John E.; Bolcato, Chris A.; Breaux, Jason C.; Martin, Karen H.; Culp, Mark V.; Gannett, Peter M.; Weed, Scott A.

    2012-01-01

    Summary Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions. PMID:23097045

  17. Src binds cortactin through an SH2 domain cystine-mediated linkage.

    Science.gov (United States)

    Evans, Jason V; Ammer, Amanda G; Jett, John E; Bolcato, Chris A; Breaux, Jason C; Martin, Karen H; Culp, Mark V; Gannett, Peter M; Weed, Scott A

    2012-12-15

    Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions.

  18. Promoción de alimentación saludable en hogares comunitarios infantiles del municipio de Sopó (Cundinamarca. Colombia) bajo la estrategia de Atención Primaria en Salud

    OpenAIRE

    Erwin Hernández-Rincón; Diego Severiche-Bueno; Diana Romero-Mayorga; María López-Sánchez; Victoria Espitia-Franco; Adriana Rodríguez-Mancera

    2015-01-01

    Objetivo: Fortalecer hábitos saludables alimenticios en los hogares infantiles comunita-rios y sus familias en el municipio de Sopó (Cundinamarca, Colombia) desde la Atención Primaria en Salud.Metodología: Investigación-acción participativa realizada con 67 niños de 5 hogares comu-nitarios, sus madres comunitarias, padres de familia y administración municipal durante el segundo semestre de 2014, mediante el abordaje de 3 ejes: 1. Conociendo sobre alimentación saludable, 2. Motivando sobre ali...

  19. Exploration of the Habitability of Mars with the SAM Suite Investigation on the 2009 Mars Science Laboratory

    Science.gov (United States)

    Mahaffy, P. R.; Cabane, M.; Webster, C. R.

    2008-01-01

    The 2009 Mars Science Laboratory (MSL) with a substantially larger payload capability that any other Mars rover, to date, is designed to quantitatively assess a local region on Mars as a potential habitat for present or past life. Its goals are (1) to assess past or present biological potential of a target environment, (2) to characterize geology and geochemistry at the MSL landing site, and (3) to investigate planetary processes that influence habitability. The Sample Analysis at Mars (SAM) Suite, in its final stages of integration and test, enables a sensitive search for organic molecules and chemical and isotopic analysis of martian volatiles. MSL contact and remote surface and subsurface survey Instruments establish context for these measurements and facilitate sample identification and selection. The SAM instruments are a gas chromatograph (GC), a mass spectrometer (MS), and a tunable laser spectrometer (TLS). These together with supporting sample manipulation and gas processing devices are designed to analyze either the atmospheric composition or gases extracted from solid phase samples such as rocks and fines. For example, one of the core SAM experiment sequences heats a small powdered sample of a Mars rock or soil from ambient to -1300 K in a controlled manner while continuously monitoring evolved gases. This is followed by GCMS analysis of released organics. The general chemical survey is complemented by a specific search for molecular classes that may be relevant to life including atmospheric methane and its carbon isotope with the TLS and biomarkers with the GCMS.

  20. Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

    International Nuclear Information System (INIS)

    Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Burke, Terrence R.; Inagaki, Fuyuhiko

    2008-01-01

    The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity

  1. Blue Light-excited Light-Oxygen-Voltage-sensing Domain 2 (LOV2) Triggers a Rearrangement of the Kinase Domain to Induce Phosphorylation Activity in Arabidopsis Phototropin1.

    Science.gov (United States)

    Oide, Mao; Okajima, Koji; Kashojiya, Sachiko; Takayama, Yuki; Oroguchi, Tomotaka; Hikima, Takaaki; Yamamoto, Masaki; Nakasako, Masayoshi

    2016-09-16

    Phototropin1 is a blue light (BL) receptor in plants and shows BL-dependent kinase activation. The BL-excited light-oxygen-voltage-sensing domain 2 (LOV2) is primarily responsible for the activation of the kinase domain; however, the molecular mechanism by which conformational changes in LOV2 are transmitted to the kinase domain remains unclear. Here, we investigated BL-induced structural changes of a minimum functional fragment of Arabidopsis phototropin1 composed of LOV2, the kinase domain, and a linker connecting the two domains using small-angle x-ray scattering (SAXS). The fragment existed as a dimer and displayed photoreversible SAXS changes reflected in the radii of gyration of 42.9 Å in the dark and 48.8 Å under BL irradiation. In the dark, the molecular shape reconstructed from the SAXS profiles appeared as two bean-shaped lobes in a twisted arrangement that was 170 Å long, 80 Å wide, and 50 Å thick. The molecular shape under BL became slightly elongated from that in the dark. By fitting the crystal structure of the LOV2 dimer and a homology model of the kinase domain to their inferred shapes, the BL-dependent change could be interpreted as the positional shift in the kinase domain relative to that of the LOV2 dimer. In addition, we found that lysine 475, a functionally important residue, in the N-terminal region of LOV2 plays a critical role in transmitting the structural changes in LOV2 to the kinase domain. The interface between the domains is critical for signaling, suitably changing the structure to activate the kinase in response to conformational changes in the adjoining LOV2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Biodistribution of samarium-153-EDTMP in rats treated with docetaxel Biodistribuição de EDTMP-153-samário em ratos tratados com docetaxel

    Directory of Open Access Journals (Sweden)

    Arthur Villarim Neto

    2009-02-01

    Full Text Available PURPOSE: Many patients with metastatic bone disease have to use radiopharmaceuticals associated with chemotherapy to relieve bone pain. The aim of this study was to assess the influence of docetaxel on the biodistribution of samarium-153-EDTMP in bones and other organs of rats. METHODS: Wistar male rats were randomly allocated into 2 groups of 6 rats each. The DS (docetaxel/samarium group received docetaxel (15 mg/kg intraperitoneally in two cycles 11 days apart. The S (samarium/control group rats were not treated with docetaxel. Nine days after chemotherapy, all the rats were injected with 0.1ml of samarium-153-EDTMP via orbital plexus (25µCi. After 2 hours, the animals were killed and samples of the brain, thyroid, lung, heart, stomach, colon, liver, kidney and both femurs were removed. The percentage radioactivity of each sample (% ATI/g was determined in an automatic gamma-counter (Wizard-1470, Perkin-Elmer, Finland. RESULTS: On the 9th day after the administration of the 2nd chemotherapy cycle, the rats had a significant weight loss (314.50±22.09g compared (pOBJETIVO: Muitos pacientes com metástases ósseas são tratados com radiofármacos associados com quimioterapia para alívio da dor óssea. O objetivo do trabalho foi estudar a influência do docetaxel na biodistribuição do EDTMP-153-samário nos ossos e outros órgãos de ratos. MÉTODOS: Ratos Wistar foram aleatoriamente alocados em 2 grupos de 6 animais cada. O grupo DS (docetaxel/samário recebeu docetaxel (15 mg/kg intraperitoneal em dois ciclos com 11 dias de intervalo. Os ratos do grupo S (samário/controle não foram tratados com docetaxel. Nove dias após a quimioterapia, todos os animais receberam 0,1ml de EDTMP-153-samário via plexo orbital (25µCi. Após 2 horas, os animais foram mortos e feitas biópsias de cérebro, tireóide, pulmão, coração, estômago, cólon, fígado, rim e fêmures. O percentual de radioatividade por grama (%ATI/g de tecido de cada bi

  3. Fatty Acid Detection in Mars-Analogous Rock Samples with the TMAH Wet Chemistry Experiment on the Sample Analysis at Mars (SAM) Instrument

    Science.gov (United States)

    Williams, A. J.; Eigenbrode, J. L.; Wilhelm, M. B.; Johnson, S. S.; Craft, K.; O'Reilly, S.; Lewis, J. M. T.; Williams, R.; Summons, R. E.; Benison, K. C.; Mahaffy, P. R.

    2017-12-01

    The Curiosity rover is exploring sedimentary rock sequences in Gale Crater for evidence of habitability and searching for organic compounds using the Sample Analysis at Mars (SAM) instrument suite. SAM includes a gas chromatograph mass spectrometer (GC-MS) and pyrolysis ovens. SAM has the ability to perform wet chemistry experiments, one of which uses tetramethylammonium hydroxide (TMAH) thermochemolysis to liberate bound lipids, making them sufficiently volatile for detection by GC-MS. To determine the effectiveness of the SAM-like TMAH experiment on fatty acid methyl ester (FAME) biomarker identification, rock and sediment samples were collected from a variety of Mars analog environments including iron oxides from a modern mineral precipitate and older surface gossan at Iron Mountain, CA, as well as modern acid salt and neutral lake sediments with mixed iron oxides and clays from Western Australia; siliceous sinter from recently inactive and modern near-vent Icelandic hot springs deposits; modern carbonate ooids from The Bahamas, and organic-rich shale from Germany. Samples underwent pyrolysis with TMAH. Fatty acids were analyzed by pyro-GC-MS using a SAM-like heating ramp (35°C/min) as well as a 500°C flash on a Frontier pyrolyzer and Agilent GC-MS instrument. Results reveal that FAMEs were detectable with the TMAH experiment in nearly all samples. Low molecular weight (MW) C6:0-C10:0 FAMEs were present in all samples, medium MW C11:0-C18:2 FAMEs were present in select samples, and high MW (HMW) C20:0-C30:0 FAMEs were present in the shale sample. Many of these samples exhibited an even-over-odd carbon number preference, indicating biological production. These experiments demonstrate that TMAH thermochemolysis with SAM-like pyro-GC-MS is effective in fatty acid analysis from natural Mars-analog samples that vary in mineralogy, age, and microbial community input. HMW FAMEs are not detected in iron-dominated samples, and may not be detectable at low

  4. In-Solution SH2 Domain Binding Assay Based on Proximity Ligation.

    Science.gov (United States)

    Machida, Kazuya

    2017-01-01

    Protein-protein interactions mediated by SH2 domains confer specificity in tyrosine kinase pathways. Traditional assays for assessing interactions between an SH2 domain and its interacting protein such as far-Western and pull-down are inherently low throughput. We developed SH2-PLA, an in-solution SH2 domain binding assay, that takes advantage of the speed and sensitivity of proximity ligation and real-time PCR. SH2-PLA allows for rapid assessment of SH2 domain binding to a target protein using only a few microliters of cell lysate, thereby making it an attractive new tool to study tyrosine kinase signaling.

  5. Fabrication of an a-IGZO thin film transistor using selective deposition of cobalt by the self-assembly monolayer (SAM) process.

    Science.gov (United States)

    Cho, Young-Je; Kim, HyunHo; Park, Kyoung-Yun; Lee, Jaegab; Bobade, Santosh M; Wu, Fu-Chung; Choi, Duck-Kyun

    2011-01-01

    Interest in transparent oxide thin film transistors utilizing ZnO material has been on the rise for many years. Recently, however, IGZO has begun to draw more attention due to its higher stability and superior electric field mobility when compared to ZnO. In this work, we address an improved method for patterning an a-IGZO film using the SAM process, which employs a cost-efficient micro-contact printing method instead of the conventional lithography process. After a-IGZO film deposition on the surface of a SiO2-layered Si wafer, the wafer was illuminated with UV light; sources and drains were then patterned using n-octadecyltrichlorosilane (OTS) molecules by a printing method. Due to the low surface energy of OTS, cobalt was selectively deposited on the OTS-free a-IGZO surface. The selective deposition of cobalt electrodes was successful, as confirmed by an optical microscope. The a-IZGO TFT fabricated using the SAM process exhibited good transistor performance: electric field mobility (micro(FE)), threshold voltage (V(th)), subthreshold slope (SS) and on/off ratio were 2.1 cm2/Vs, 2.4 V, 0.35 V/dec and 2.9 x 10(6), respectively.

  6. Wide Range Vacuum Pumps for the SAM Instrument on the MSL Curiosity Rover

    Science.gov (United States)

    Sorensen, Paul; Kline-Schoder, Robert; Farley, Rodger

    2014-01-01

    Creare Incorporated and NASA Goddard Space Flight Center developed and space qualified two wide range pumps (WRPs) that were included in the Sample Analysis at Mars (SAM) instrument. This instrument was subsequently integrated into the Mars Science Laboratory (MSL) "Curiosity Rover," launched aboard an Atlas V rocket in 2011, and landed on August 6, 2012, in the Gale Crater on Mars. The pumps have now operated for more than 18 months in the Gale Crater and have been evacuating the key components of the SAM instrument: a quadrupole mass spectrometer, a tunable laser spectrometer, and six gas chromatograph columns. In this paper, we describe the main design challenges and the ways in which they were solved. This includes the custom design of a miniaturized, high-speed motor to drive the turbo drag pump rotor, analysis of rotor dynamics for super critical operation, and bearing/lubricant design/selection.

  7. Structure of the thioredoxin-fold domain of human phosducin-like protein 2

    International Nuclear Information System (INIS)

    Lou, Xiaochu; Bao, Rui; Zhou, Cong-Zhao; Chen, Yuxing

    2009-01-01

    The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70 Å resolution and resembled the Trx-fold domain of rat phosducin. Human phosducin-like protein 2 (hPDCL2) has been identified as belonging to subgroup II of the phosducin (Pdc) family. The members of this family share an N-terminal helix domain and a C-terminal thioredoxin-fold (Trx-fold) domain. The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70 Å resolution and resembled the Trx-fold domain of rat phosducin. Comparative structural analysis revealed the structural basis of their putative functional divergence

  8. Domain-orientation dependence of levitation force in seeded melt grown single-domain YBa2Cu3Ox

    International Nuclear Information System (INIS)

    Shi, D.; Qu, D.; Sagar, S.; Lahiri, K.

    1997-01-01

    Domain-orientation dependence of levitation force has been determined for single-domain YBa 2 Cu 3 O x . The single-domain material is obtained from a seeded melt growth process. The levitation force has been found to reach a maximum as the c axis of the domain is parallel to the direction of the force. The levitation force decreases in a cosine law fashion as the angle θ (the angle between the direction of the force and the c axis) increases from 0 degree to 60 degree. A maximum anisotropy of levitation force of 2.29 has been found. A physical model is proposed to explain the observed orientation dependence. copyright 1997 American Institute of Physics

  9. Franchising as a Potential Growth Strategy for a Small Business : A Case of Sam-Chi Fast Food Restaurant

    OpenAIRE

    Odunsi, Sadiq

    2015-01-01

    The purpose of this study was to find out whether Sam-Chi fast food restaurant can grow through franchising as well as to give the owners recommendations on how to effectively adopt the franchising business model as a means to grow their business. Sam-Chi restaurant is situated in Lagos, Nigeria and the restaurant is owned and operated by Samuel Okore and his wife Chichi Okore. The theoretical framework of this research is separated into two sections. The first section covers the growth of a ...

  10. Analysis of Domain Architecture and Phylogenetics of Family 2 Glycoside Hydrolases (GH2.

    Directory of Open Access Journals (Sweden)

    David Talens-Perales

    Full Text Available In this work we report a detailed analysis of the topology and phylogenetics of family 2 glycoside hydrolases (GH2. We distinguish five topologies or domain architectures based on the presence and distribution of protein domains defined in Pfam and Interpro databases. All of them share a central TIM barrel (catalytic module with two β-sandwich domains (non-catalytic at the N-terminal end, but differ in the occurrence and nature of additional non-catalytic modules at the C-terminal region. Phylogenetic analysis was based on the sequence of the Pfam Glyco_hydro_2_C catalytic module present in most GH2 proteins. Our results led us to propose a model in which evolutionary diversity of GH2 enzymes is driven by the addition of different non-catalytic domains at the C-terminal region. This model accounts for the divergence of β-galactosidases from β-glucuronidases, the diversification of β-galactosidases with different transglycosylation specificities, and the emergence of bicistronic β-galactosidases. This study also allows the identification of groups of functionally uncharacterized protein sequences with potential biotechnological interest.

  11. Probing SH2-domains using Inhibitor Affinity Purification (IAP).

    Science.gov (United States)

    Höfener, Michael; Heinzlmeir, Stephanie; Kuster, Bernhard; Sewald, Norbert

    2014-01-01

    Many human diseases are correlated with the dysregulation of signal transduction processes. One of the most important protein interaction domains in the context of signal transduction is the Src homology 2 (SH2) domain that binds phosphotyrosine residues. Hence, appropriate methods for the investigation of SH2 proteins are indispensable in diagnostics and medicinal chemistry. Therefore, an affinity resin for the enrichment of all SH2 proteins in one experiment would be desirable. However, current methods are unable to address all SH2 proteins simultaneously with a single compound or a small array of compounds. In order to overcome these limitations for the investigation of this particular protein family in future experiments, a dipeptide-derived probe has been designed, synthesized and evaluated. This probe successfully enriched 22 SH2 proteins from mixed cell lysates which contained 50 SH2 proteins. Further characterization of the SH2 binding properties of the probe using depletion and competition experiments indicated its ability to enrich complexes consisting of SH2 domain bearing regulatory PI3K subunits and catalytic phosphoinositide 3-kinase (PI3K) subunits that have no SH2 domain. The results make this probe a promising starting point for the development of a mixed affinity resin with complete SH2 protein coverage. Moreover, the additional findings render it a valuable tool for the evaluation of PI3K complex interrupting inhibitors.

  12. Rosette Assay: Highly Customizable Dot-Blot for SH2 Domain Screening.

    Science.gov (United States)

    Ng, Khong Y; Machida, Kazuya

    2017-01-01

    With a growing number of high-throughput studies, structural analyses, and availability of protein-protein interaction databases, it is now possible to apply web-based prediction tools to SH2 domain-interactions. However, in silico prediction is not always reliable and requires experimental validation. Rosette assay is a dot blot-based reverse-phase assay developed for the assessment of binding between SH2 domains and their ligands. It is conveniently customizable, allowing for low- to high-throughput analysis of interactions between various numbers of SH2 domains and their ligands, e.g., short peptides, purified proteins, and cell lysates. The binding assay is performed in a 96-well plate (MBA or MWA apparatus) in which a sample spotted membrane is incubated with up to 96 labeled SH2 domains. Bound domains are detected and quantified using a chemiluminescence or near-infrared fluorescence (IR) imaging system. In this chapter, we describe a practical protocol for rosette assay to assess interactions between synthesized tyrosine phosphorylated peptides and a library of GST-tagged SH2 domains. Since the methodology is not confined to assessment of SH2-pTyr interactions, rosette assay can be broadly utilized for ligand and drug screening using different protein interaction domains or antibodies.

  13. The C2 domain of PKCalpha is a Ca2+ -dependent PtdIns(4,5)P2 sensing domain: a new insight into an old pathway.

    Science.gov (United States)

    Sánchez-Bautista, Sonia; Marín-Vicente, Consuelo; Gómez-Fernández, Juan C; Corbalán-García, Senena

    2006-10-06

    The C2 domain is a targeting domain that responds to intracellular Ca2+ signals in classical protein kinases (PKCs) and mediates the translocation of its host protein to membranes. Recent studies have revealed a new motif in the C2 domain, named the lysine-rich cluster, that interacts with acidic phospholipids. The purpose of this work was to characterize the molecular mechanism by which PtdIns(4,5)P2 specifically interacts with this motif. Using a combination of isothermal titration calorimetry, fluorescence resonance energy transfer and time-lapse confocal microscopy, we show here that Ca2+ specifically binds to the Ca2+ -binding region, facilitating PtdIns(4,5)P2 access to the lysine-rich cluster. The magnitude of PtdIns(4,5)P2 binding is greater than in the case of other polyphosphate phosphatidylinositols. Very importantly, the residues involved in PtdIns(4,5)P2 binding are essential for the plasma membrane localization of PKCalpha when RBL-2H3 cells are stimulated through their IgE receptors. Additionally, CFP-PH and CFP-C1 domains were used as bioprobes to demonstrate the co-existence of PtdIns(4,5)P2 and diacylglycerol in the plasma membrane, and it was shown that although a fraction of PtdIns(4,5)P2 is hydrolyzed to generate diacylglycerol and IP3, an important amount still remains in the membrane where it is available to activate PKCalpha. These findings entail revision of the currently accepted model of PKCalpha recruitment to the membrane and its activation.

  14. 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.

  15. Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

    Directory of Open Access Journals (Sweden)

    Fumiaki Obata

    2014-05-01

    Full Text Available Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM levels due to glycine N-methyltransferase (Gnmt upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis.

  16. ISOE EG-SAM interim report - Report on behalf of the Sub expert Group

    International Nuclear Information System (INIS)

    Harris, Willie; Miller, David W.; Djeffal, Salah; Anderson, Ellen; Couasnon, Olivier; Hagemeyer, Derek; Sovijarvi, Jukka; Amaral, Marcos A.; Tarzia, J.P.; Schmidt, Claudia; Fritioff, Karin; Kaulard, Joerg; Lance, Benoit; Fritioff, Karin; Schieber, Caroline; Hayashida, Yoshihisa; Doty, Rick

    2014-01-01

    During its November 2012 meeting, the expert group decided to develop an interim (preliminary) report before the end of 2013 (with a general perspective and discussion of specific severe accident management worker dose issues), and to finalize the report by organizing the international workshop of 2014 to address national experiences, which will be incorporated to the report. The work of the EG-SAM focuses on radiation protection management and organization, radiation protection training and exercises related to severe accident management, facility configuration and readiness, worker protection, radioactive materials, contamination controls and logistics and key lessons learned especially from the TMI, Chernobyl and Fukushima Dai-ichi accidents. This interim report was completed through intensive work of all Group members nominated by the ISOE, and was accomplished during EG-SAM meetings through 2012-2013. This document gathers the different presentations given by the sub expert groups in charge of each chapter of the report

  17. Electrochemical characterization of a 1,8-octanedithiol self-assembled monolayer (ODT-SAM) on a Au(111) single crystal electrode

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Raya, Daniel; Madueno, Rafael; Sevilla, Jose Manuel; Blazquez, Manuel; Pineda, Teresa [Departamento de Quimica Fisica y Termodinamica Aplicada, Universidad de Cordoba, Campus de Rabanales, Cordoba (Spain)

    2008-11-15

    Recently, it has becoming increasingly important to control the organization of self-assembled monolayers (SAMs) of {omega}-functionalized thiols for its potential applications in the construction of more complex molecular architectures. In this paper, we report on the spontaneous formation of a SAM of octanedithiol (ODT) as a function of the modification time. Electrochemical techniques such as cyclic voltammetry, double layer capacitance and electrochemical impedance spectroscopy are used for the characterization of this monolayer. The increase in modification time brings about changes in the octanedithiol self-assembled monolayer (ODT-SAM) reductive desorption voltammograms that indicate an evolution toward a more ordered and compact monolayer. This trend has also been found by following the changes in the electron transfer processes of the redox probe K{sub 3}Fe(CN){sub 6}. In fact, the ODT-SAM formed at low-modification time does not significantly perturb the electrochemical response as it is typical of either a low coverage or of the presence of large defects in the layer. Upon increasing the modification time, the voltammograms of the redox probe adopt a sigmoidal shape indicating the existence of pinholes in the monolayer distributed as an array of microelectrodes. The surface coverage as well as the size and distribution of these pinholes have been determined by the impedance technique that gives a more reliable evaluation of these monolayer structural parameters. (author)

  18. The captain class : the hidden force that creates the world's greatest teams / Sam Walker

    Trove (Australia)

    Walker, Sam

    2017-01-01

    ... it is. It's not the coach. It's not the star. It's not chemistry. It's not a strategy. It's something else entirely. Several years ago, Sam Walker set out to answer one of the most hotly debated questions in sports ...

  19. The 2 × 2 model of perfectionism: a comparison across Asian Canadians and European Canadians.

    Science.gov (United States)

    Franche, Véronique; Gaudreau, Patrick; Miranda, Dave

    2012-10-01

    The 2 × 2 model of perfectionism posits that the 4 within-person combinations of self-oriented and socially prescribed perfectionism (i.e., pure SOP, mixed perfectionism, pure SPP, and nonperfectionism) can be distinctively associated with psychological adjustment. This study examined whether the relationship between the 4 subtypes of perfectionism proposed in the 2 × 2 model (Gaudreau & Thompson, 2010) and academic outcomes (i.e., academic satisfaction and grade-point average [GPA]) differed across 2 sociocultural groups: Asian Canadians and European Canadians. A sample of 697 undergraduate students (23% Asian Canadians) completed self-report measures of dispositional perfectionism, academic satisfaction, and GPA. Results replicated most of the 2 × 2 model's hypotheses on ratings of GPA, thus supporting that nonperfectionism was associated with lower GPA than pure SOP (Hypothesis 1a) but with higher GPA than pure SPP (Hypothesis 2). Results also showed that mixed perfectionism was related to higher GPA than pure SPP (Hypothesis 3) but to similar levels as pure SOP, thus disproving Hypothesis 4. Furthermore, results provided evidence for cross-cultural differences in academic satisfaction. While all 4 hypotheses were supported among European Canadians, only Hypotheses 1a and 3 were supported among Asian Canadians. Future lines of research are discussed in light of the importance of acknowledging the role of culture when studying the influence of dispositional perfectionism on academic outcomes. (c) 2012 APA, all rights reserved.

  20. In Situ Analysis of Martian Regolith with the SAM Experiment During the First Mars Year of the MSL Mission: Identification of Organic Molecules by Gas Chromatography from Laboratory Measurements

    Science.gov (United States)

    Millan, M.; Szopa, C.; Buch, A.; Coll, P.; Glavin, D. P.; Freissinet, C.; Navarro-Gonzalez, R.; Francois, P.; Coscia, D.; Bonnet, J. Y.; hide

    2016-01-01

    The Sample Analysis at Mars (SAM) instrument onboard the Curiosity rover, is specifically designed for in situ molecular and isotopic analyses of martian surface materials and atmosphere. It contributes to the Mars Science Laboratory (MSL) missions primary scientific goal to characterize the potential past, present or future habitability of Mars. In all of the analyses of solid samples delivered to SAM so far, chlorinated organic compounds have been detected above instrument background levels and identified by gas chromatography coupled to mass spectrometry (GC-MS) (Freissinet et al., 2015; Glavin et al., 2013). While some of these may originate from reactions between oxychlorines and terrestrial organic carbon present in the instrument background (Glavin et al., 2013), others have been demonstrated to originate from indigenous organic carbon present in samples (Freissinet et al., 2015). We present here laboratory calibrations that focused on the analyses performed with the MXT-CLP GC column (SAM GC-5 channel) used for nearly all of the GC-MS analyses of the martian soil samples carried out with SAM to date. Complementary to the mass spectrometric data, gas chromatography allows us to separate and identify the species analyzable in a nominal SAM-GC run time of about 21 min. To characterize the analytical capabilities of this channel within the SAM Flight Model (FM) operating conditions on Mars, and their implications on the detection of organic matter, it is required to perform laboratory experimental tests and calibrations on spare model components. This work assesses the SAM flight GC-5 column efficiency, confirms the identification of the molecules based on their retention time, and enables a better understanding of the behavior of the SAM injection trap (IT) and its release of organic molecules. This work will enable further optimization of the SAM-GC runs for additional samples to be analyzed during the MSL mission.

  1. Tyrosine Phosphorylation of the Lyn Src Homology 2 (SH2) Domain Modulates Its Binding Affinity and Specificity*

    Science.gov (United States)

    Jin, Lily L.; Wybenga-Groot, Leanne E.; Tong, Jiefei; Taylor, Paul; Minden, Mark D.; Trudel, Suzanne; McGlade, C. Jane; Moran, Michael F.

    2015-01-01

    Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y194 impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y194 on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases. PMID:25587033

  2. A Study to Evaluate the Organization and the Operating Procedures of the Patient Assistance Function at Brooke Army Medical Center, Fort Sam Houston, Texas

    Science.gov (United States)

    1979-08-01

    15 March 1979. 59Interview with Wendy L. Farace , Head Nurse, Obstetrics/Gynecology Clinic, Brooke Army Medical Center, Fort Sam Houston, Texas, 8...6 February 1979. Farace , Wendy L. Head Nurse, Obstetrica/Gynecology Clinic, Brooke Army Medical Center, Fort Sam Houston, Texas. Interview, 8 January

  3. Effect of aromatic SAMs molecules on graphene/silicon schottky diode performance

    OpenAIRE

    Yağmurcukardeş, Nesli; Aydın, Hasan; Can, Mustafa; Yanılmaz, Alper; Mermer, Ömer; Okur, Salih; Selamet, Yusuf

    2016-01-01

    Au/n-Si/Graphene/Au Schottky diodes were fabricated by transferring atmospheric pressure chemical vapor deposited (APCVD) graphene on silicon substrates. Graphene/n-Si interface properties were improved by using 5-[(3-methylphenyl)(phenyl) amino]isophthalic acid (MePIFA) and 5-(diphenyl)amino]isophthalic acid (DPIFA) aromatic self-assembled monolayer (SAM) molecules. The surface morphologies of modified and non-modified films were investigated by atomic force microscopy and scanning electron ...

  4. The Investigation of Chlorate and Perchlorate/Saponite Mixtures as a Possible Source of Oxygen and Chlorine Detected by the Sample Analysis at Mars (SAM) Instrument in Gale Crater

    Science.gov (United States)

    Clark, J.; Sutter, B.; Min, D. W.; Mahaffy, P.

    2016-01-01

    The Sample Analysis at Mars (SAM) instrument on board the Curiosity Rover has detected O2 and HCl gas releases from all analyzed Gale Crater sediments, which are attributed to the presence of perchlorates and/or chlorates in martian sediment. Previous SAM analog laboratory analyses found that most pure perchlorates and chlorates release O2 and HCl at different temperatures than those observed in the SAM data. Subsequent studies examined the effects of perchlorate and chlorate mixtures with Gale Crater analog iron phases, which are known to catalyze oxychlorine decomposition. Several mixtures produced O2 releases at similar temperatures as Gale Crater materials, but most of these mixtures did not produce significant HCl releases comparable to those detected by the SAM instrument. In order to better explain the Gale Crater HCl releases, perchlorates and chlorates were mixed with Gale Crater analog saponite, which is found at abundances from 8 to 20 wt % in the John Klein and Cumberland drill samples. Mixtures of chlorates or perchlorates with calcium-saponite or ferrian-saponite were heated to 1000 deg C in a Labsys EVO differential scanning calorimeter/mass spectrometer configured to operate similarly to the SAM oven/quadrupole mass spectrometer system. Our results demonstrate that all chlorate and perchlorate mixtures produce significant HCl releases below 1000 deg C as well as depressed oxygen peak release temperatures when mixed with saponite. The type of saponite (calcium or ferrian saponite) did not affect the evolved gas results significantly. Saponite/Mg-perchlorate mixtures produced two HCl releases similar to the Cumberland drilled sample. Mg-chlorate mixed with saponite produced HCl releases similar to the Big Sky drilled sample in an eolian sandstone. A mixture of Ca-perchlorate and saponite produced HCl and oxygen releases similar to the Buckskin mudstone drilled sample and the Gobabeb 2 eolian dune material. Ca-chlorate mixed with saponite produced both

  5. Characterization of self-assembled monolayers (SAMs) on silicon substrate comparative with polymer substrate for Escherichia coli O157:H7 detection

    International Nuclear Information System (INIS)

    Moldovan, Carmen; Mihailescu, Carmen; Stan, Dana; Ruta, Lavinia; Iosub, Rodica; Gavrila, Raluca; Purica, Munizer; Vasilica, Schiopu

    2009-01-01

    This article presents the characterization of two substrates, silicon and polymer coated with gold, that are functionalized by mixed self-assembled monolayers (SAMs) in order to efficiently immobilize the anti-Escherichia coli O157:H7 polyclonal purified antibody. A biosurface functionalized by SAMs (self-assembled monolayers) technique has been developed. Immobilization of goat anti-E. coli O157:H7 antibody was performed by covalently bonding of thiolate mixed self-assembled monolayers (SAMs) realized on two substrates: polymer coated with gold and silicon coated with gold. The F(ab') 2 fragments of the antibodies have been used for eliminating nonspecific bindings between the Fc portions of antibodies and the Fc receptor on cells. The properties of the monolayers and the biofilm formatted with attached antibody molecules were analyzed at each step using infrared spectroscopy (FTIR-ATR), atomic force microscopy (AFM), scanning electron microscopy (SEM) and cyclic voltammetry (CV). In our study the gold-coated silicon substrates approach yielded the best results. These experimental results revealed the necessity to investigate each stage of the immobilization process taking into account in the same time the factors that influence the chemistry of the surface and the further interactions as well and also provide a solid basis for further studies aiming at elaborating sensitive and specific immunosensor or a microarray for the detection of E. coli O157:H7.

  6. Characterization of self-assembled monolayers (SAMs) on silicon substrate comparative with polymer substrate for Escherichia coli O157:H7 detection

    Energy Technology Data Exchange (ETDEWEB)

    Moldovan, Carmen, E-mail: carmen.moldovan@imt.ro [National Institute for R and D in Microtechnologies, IMT-Bucharest, 126A Erou Iancu Nicolae, 077190 Bucharest (Romania); Mihailescu, Carmen, E-mail: carmen_mihail28@yahoo.com [University of Bucharest, 90-92 Sos Panduri, Bucharest (Romania); Stan, Dana, E-mail: dana_stan2005@yahoo.com [DDS Diagnostic, 1 Segovia Street, Bucharest (Romania); Ruta, Lavinia, E-mail: laviniacoco@yahoo.com [University of Bucharest, 90-92 Sos Panduri, Bucharest (Romania); Iosub, Rodica, E-mail: rodica.iosub@imt.ro [National Institute for R and D in Microtechnologies, IMT-Bucharest, 126A Erou Iancu Nicolae, 077190 Bucharest (Romania); Gavrila, Raluca, E-mail: raluca.gavrila@imt.ro [National Institute for R and D in Microtechnologies, IMT-Bucharest, 126A Erou Iancu Nicolae, 077190 Bucharest (Romania); Purica, Munizer, E-mail: munizer.purica@imt.ro [National Institute for R and D in Microtechnologies, IMT-Bucharest, 126A Erou Iancu Nicolae, 077190 Bucharest (Romania); Vasilica, Schiopu, E-mail: vasilica.schiopu@imt.ro [National Institute for R and D in Microtechnologies, IMT-Bucharest, 126A Erou Iancu Nicolae, 077190 Bucharest (Romania)

    2009-08-30

    This article presents the characterization of two substrates, silicon and polymer coated with gold, that are functionalized by mixed self-assembled monolayers (SAMs) in order to efficiently immobilize the anti-Escherichia coli O157:H7 polyclonal purified antibody. A biosurface functionalized by SAMs (self-assembled monolayers) technique has been developed. Immobilization of goat anti-E. coli O157:H7 antibody was performed by covalently bonding of thiolate mixed self-assembled monolayers (SAMs) realized on two substrates: polymer coated with gold and silicon coated with gold. The F(ab'){sub 2} fragments of the antibodies have been used for eliminating nonspecific bindings between the Fc portions of antibodies and the Fc receptor on cells. The properties of the monolayers and the biofilm formatted with attached antibody molecules were analyzed at each step using infrared spectroscopy (FTIR-ATR), atomic force microscopy (AFM), scanning electron microscopy (SEM) and cyclic voltammetry (CV). In our study the gold-coated silicon substrates approach yielded the best results. These experimental results revealed the necessity to investigate each stage of the immobilization process taking into account in the same time the factors that influence the chemistry of the surface and the further interactions as well and also provide a solid basis for further studies aiming at elaborating sensitive and specific immunosensor or a microarray for the detection of E. coli O157:H7.

  7. Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

    International Nuclear Information System (INIS)

    Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

    2012-01-01

    The crystallization and preliminary crystallographic studies of the carboxy-terminal domain of D. melanogaster eukaryotic translation initiation factor 5C domain-containing protein are reported. The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2B∊, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a = b = 81.05, c = 57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal

  8. The two umuDC-like operons, samAB and umuDCST, in Salmonella typhimurium: The umuDCST operon may reduce UV-mutagenesis-promoting ability of the samAB operon

    International Nuclear Information System (INIS)

    Nohmi, Takehiko; Hakura, Atsushi; Watanabe, Masahiko; Yamada, Masami; Sofuni, Toshio; Nakai, Yasuharu; Murayama, Somay Y.

    1993-01-01

    Salmonella typhimurium, especially its derivatives containing pKM101 plasmid, has been widely used in the Ames test for the detection of environmental mutagens and carcinogens. It is known, however, that if the pKM101 plasmid is eliminated, S. typhimurium itself shows a much weaker mutagenic response to UV and some chemical mutagens than does Escherichia coli. In fact, certain potent base-change type mutagens, such as furylfuramide and aflatoxin B 1 , are nonmutagenic to S. typhimurium in the absence of pKM101, whereas they are strongly mutagenic to S. typhimurium in the presence of pKM101 plasmid as well as to E. coli. The low mutability can be restored to levels comparable to E. coli by introducing the plasmid carrying the E. coli umuDC operon or the pKM101 plasmid carrying mucAB operon. Salmonella typhimurium has an SOS regulatory system which resembles that of E. coli. Thus, it was suggested that S. typhimurium is deficient in the function of umuDC operon, which plays an essential role in UV and most chemical mutagenesis in E. coli. In order to clarify the implications of umuDC genes in mutagenesis and antimutagenesis in typhimurium, we have independently screened the umuDC-like genes of S. typhimurium TA1538. Consequently, we have cloned another umuDC-like operon which is 40% diverged from the aforementioned umuDC operon of S. typhimurium LT2 at the nucleotide level (16). We have termed the cloned DNA the samAB (Salmonella; mutagenesis) operon, and tentatively referred to the umuDC operon cloned from S. typhimurium LT2 (27,31) as the umuDC ST operon. Based on the results of the Southern hybridization experiment, we concluded that the two sets of umuDC-like operons reside in the same cells of S. typhimurium LT2 and TA1538. Our results also suggested that the umuDC ST operon reduces the UV-mutagenesis promoting ability of the samAB operon when the two operons are present on the same multi-copy number plasmid

  9. Phase transition in Sr8[Al12O24](MoO4)2 aluminate sodalite (SAM)

    International Nuclear Information System (INIS)

    Depmeier, W.; Melzer, R.; Hu, X.

    1993-01-01

    The cubic-tetragonal phase transition at 571 K of the aluminate sodalite Sr 8 [Al 12 O 24 ](MoO 4 ) 2 (SAM) has ben studied by following the position of the (pseudo-)cubic {400} reflections as a function of temperature. The high resolution of the synchrotron powder diffraction experiment allowed the temperature dependencies to be followed with good precision. The tetragonal a lattice parameter appears to be a linear extrapolation of the cubic one, with only a small upward shift at the transition, whereas the c parameter decreases strongly below 571 K. These observations can be explained by a model which assumes the superposition of a ferroelastic strain component, and a volume strain component. The volume strain can be rationalized as being the result of a 'shearing' of the sodalite framework. Causes and consequences of the 'shearing' in relation to the sodalite framework are discussed. The weakly first-order transition is nearly tricritical; power-law exponents seem to be influenced by defects. The thermal expansion of the cubic lattice parameter, as well as of the tetragonal a axis, is nearly linear. The linear thermal-expansion coefficient α is 8.6(4)x10 -6 K -1 . The tetragonal c axis also expands linearly between room temperature and about Tc-100 K with practically the same coefficient, but behaves non-linearly nearer to the transition temperature. (orig.)

  10. Tyrosine phosphorylation of the Lyn Src homology 2 (SH2) domain modulates its binding affinity and specificity.

    Science.gov (United States)

    Jin, Lily L; Wybenga-Groot, Leanne E; Tong, Jiefei; Taylor, Paul; Minden, Mark D; Trudel, Suzanne; McGlade, C Jane; Moran, Michael F

    2015-03-01

    Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y(194) impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y(194) on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. The Structure of the RNA m5C Methyltransferase YebU from Escherichia coli Reveals a C-terminal RNA-recruiting PUA Domain

    DEFF Research Database (Denmark)

    Hallberg, B. Martin; Ericsson, Ulrika B.; Johnson, Kenneth A

    2006-01-01

    potential that differ from other RNA-MTase structures, suggesting that YebU interacts with its RNA target in a different manner. Docking of YebU onto the 30 S subunit indicates that the PUA and MTase domains make several contacts with 16 S rRNA as well as with the ribosomal protein S12. The ribosomal...... protein interactions would explain why the assembled 30 S subunit, and not naked 16 S rRNA, is the preferred substrate for YebU....... by X-ray crystallography, and we present a molecular model for how YebU specifically recognizes, binds and methylates its ribosomal substrate. The YebU protein has an N-terminal SAM-binding catalytic domain with structural similarity to the equivalent domains in several other m(5)C RNA MTases including...

  12. Efecto de la polietilenimina en la actividad catalítica de la peroxidasa de rábano (horseradish peroxidase inmovilizada en electrodos de oro modificados con monocapas autoensambladas de tioles (SAMs.

    Directory of Open Access Journals (Sweden)

    Pedro R. Matheus

    2009-05-01

    Full Text Available Effect of the Polyethyleneimine in the Activity Catalytic of the horseradish peroxidase Immobilized on Gold Electrodes Modified with a Self-assembled Monolayer of Thiols (SAMs. Studies were conducted bycyclic voltammetry (CV to investigate the effect of the polymer polyethyleneimine (PEI in the electrochemical reversibility of the mediator thionine and thus the catalytic activity of the enzyme horseradish peroxidase of recombinant HRP-NHis (horseradish peroxidase to the has been added to a chain of six histidine in the extreme N-terminal protein. This self produced monolayers of thiols (SAMS on gold electrodes, with chemical modifications obtained through successive stages in the solid phase of the electrode. The gold electrodes were modified with monolayer SAM-TOA-[ANTA/DADOO] -Co2+ [SAM: self-assembled monolayers of thiols, TOA: dithioctic acid, ANTA: nitrilotriacetic acid, DADOO: 1,8-diamino-3,6-dioxa octane]. The results showed that the presence of the polymer improves the electrochemical reversibility of the mediator to endure catalyticcurrents as high as those that are obtained with molar ratios ANTA:DADOO 10:1 in the absence of PEI, and improve the response voltammetric obtained.

  13. Effect of the Presence of Chlorates and Perchlorates on the Pyrolysis of Organic Compounds: Implications for Measurements Done with the SAM Experiment Onboard the Curiosity Rover

    Science.gov (United States)

    Millan, M.; Szopa, C.; Buch, A.; Belmahdi, I.; Coll, P.; Glavin, D. P.; Freissinet, C.; Archer, P. D., Jr.; Sutter, B.; Summons, R. E.; hide

    2016-01-01

    The Mars Science Laboratory (MSL) Curiosity Rover carries a suite of instruments, one of which is the Sample Analysis at Mars (SAM) experiment. SAM is devoted to the in situ molecular analysis of gases evolving from solid samples collected by Curiosity on Mars surface/sub-surface. Among its three analytical devices, SAM has a gaschromatograph coupled to a quadrupole mass spectrometer (GC-QMS). The GC-QMS is devoted to the separation and identification of organic and inorganic material. Before proceeding to the GC-QMS analysis, the solid sample collected by Curiosity is subjected to a thermal treatment thanks to the pyrolysis oven to release the volatiles into the gas processing system. Depending on the sample, a derivatization method by wet chemistry: MTBSTFA of TMAH can also be applied to analyze the most refractory compounds. The GC is able to separate the organic molecules which are then detected and identified by the QMS (Figure 1). For the second time after the Viking landers in 1976, SAM detected chlorinated organic compounds with the pyrolysis GC-QMS experiment. The detection of perchlorates salts (ClO4-) in soil at the Phoenix Landing site suggests that the chlorohydrocarbons detected could come from the reaction of organics with oxychlorines. Indeed, laboratory pyrolysis experiments have demonstrated that oxychlorines decomposed into molecular oxygen and volatile chlorine (HCl and/or Cl2) when heated which then react with the organic matter in the solid samples by oxidation and/or chlorination processes.

  14. Design of potentially active ligands for SH2 domains by molecular modeling methods

    Directory of Open Access Journals (Sweden)

    Hurmach V. V.

    2014-07-01

    Full Text Available Search for new chemical structures possessing specific biological activity is a complex problem that needs the use of the latest achievements of molecular modeling technologies. It is well known that SH2 domains play a major role in ontogenesis as intermediaries of specific protein-protein interactions. Aim. Developing an algorithm to investigate the properties of SH2 domain binding, search for new potential active compounds for the whole SH2 domains class. Methods. In this paper, we utilize a complex of computer modeling methods to create a generic set of potentially active compounds targeting universally at the whole class of SH2 domains. A cluster analysis of all available three-dimensional structures of SH2 domains was performed and general pharmacophore models were formulated. The models were used for virtual screening of collection of drug-like compounds provided by Enamine Ltd. Results. The design technique for library of potentially active compounds for SH2 domains class was proposed. Conclusions. The original algorithm of SH2 domains research with molecular docking method was developed. Using our algorithm, the active compounds for SH2 domains were found.

  15. The 1.7 Å X-ray crystal structure of the porcine factor VIII C2 domain and binding analysis to anti-human C2 domain antibodies and phospholipid surfaces.

    Directory of Open Access Journals (Sweden)

    Caileen M Brison

    Full Text Available The factor VIII C2 domain is essential for binding to activated platelet surfaces as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory antibodies against the C2 domain commonly develop following factor VIII replacement therapy for hemophilia A patients, or they may spontaneously arise in cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for hemophilia patients with inhibitor due to its low cross-reactivity; however, the molecular basis for this behavior is poorly understood. In this study, the X-ray crystal structure of the porcine factor VIII C2 domain was determined, and superposition of the human and porcine C2 domains demonstrates that most surface-exposed differences cluster on the face harboring the "non-classical" antibody epitopes. Furthermore, antibody-binding results illustrate that the "classical" 3E6 antibody can bind both the human and porcine C2 domains, although the inhibitory titer to human factor VIII is 41 Bethesda Units (BU/mg IgG versus 0.8 BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Further structural analysis of differences between the electrostatic surface potentials suggest that the C2 domain binds to the negatively charged phospholipid surfaces of activated platelets primarily through the 3E6 epitope region. In contrast, the G99 face, which contains residue 2227, should be distal to the membrane surface. Phospholipid binding assays indicate that both porcine and human factor VIII C2 domains bind with comparable affinities, and the human K2227A and K2227E mutants bind to phospholipid surfaces with similar affinities as well. Lastly, the G99 IgG bound to PS-immobilized factor VIII C2 domain with an apparent dissociation constant of 15.5 nM, whereas 3E6 antibody binding to PS-bound C2 domain was not observed.

  16. Tunable bandpass filter based on partially magnetized ferrite LTCC with embedded windings for SoP applications

    KAUST Repository

    Arabi, Eyad A.

    2015-01-01

    Tunable filters that are based on ferrite materials often require large and bulky electromagnets. In this work, we present a tunable filter in the Ku-band, which is realized in multilayer ferrite LTCC substrate with embedded bias windings, thus negating the need of a large electromagnet. Also, because of the embedded windings, the bias fields are not lost at the air-substrate interface and therefore the field and current requirements are reduced by an order of magnitude as compared to the previously reported filters. A simulation strategy that uses full permeability tensor with arbitrarily directed magnetic fields has been used to model the filter on a partially magnetized ferrite substrate. Special attention has also been paid to approximate the non-uniform magneto-static fields produced by the embedded windings. The complete design is implemented in 10 layers of ferrite LTCC, making it the first magnetically tunable filter with embedded windings and extremely small size [(5 × 5 × 1.1)mm3]. The filter demonstrates a measured tunability of 4% and an insertion loss of 2.3 dB. With the small form factor, embedded windings, and low bias requirements, the design is highly suitable for compact and tunable SoP applications.

  17. Structure of the interleukin-2 tyrosine kinase Src homology 2 domain; comparison between X-ray and NMR-derived structures

    International Nuclear Information System (INIS)

    Joseph, Raji E.; Ginder, Nathaniel D.; Hoy, Julie A.; Nix, Jay C.; Fulton, D. Bruce; Honzatko, Richard B.; Andreotti, Amy H.

    2012-01-01

    The interleukin-2 tyrosine kinase Src homology 2 domain was crystallized and its structure was solved to 2.35 Å resolution. The structure reveals a domain-swapped dimer that is related to other dimeric SH2 domains solved previously. The cis–trans-prolyl isomerization that is evident from solution studies of Itk SH2 cannot be observed in the crystal structure. The crystal structure of the interleukin-2 tyrosine kinase Src homology domain (Itk SH2) is described and it is found that unlike in studies of this domain using NMR spectroscopy, cis–trans-prolyl isomerization is not readily detected in the crystal structure. Based on similarities between the Itk SH2 crystal form and the cis form of the Itk SH2 NMR structure, it is concluded that it is likely that the prolyl imide bond at least in part adopts the cis conformation in the crystal form. However, the lack of high-resolution data and the dynamic nature of the proline-containing loop mean that the precise imide-bond conformation cannot be determined and prolyl cis–trans isomerization in the crystal cannot be ruled out. Given the preponderance of structures that have been solved by X-ray crystallography in the Protein Data Bank, this result supports the notion that prolyl isomerization in folded proteins has been underestimated among known structures. Interestingly, while the precise status of the proline residue is ambiguous, Itk SH2 crystallizes as a domain-swapped dimer. The domain-swapped structure of Itk SH2 is similar to the domain-swapped SH2 domains of Grb2 and Nck, with domain swapping occurring at the β-meander region of all three SH2 domains. Thus, for Itk SH2 structural analysis by NMR spectroscopy and X-ray crystallography revealed very different structural features: proline isomerization versus domain-swapped dimerization, respectively

  18. Critical role of the FERM domain in Pyk2 stimulated glioma cell migration

    International Nuclear Information System (INIS)

    Lipinski, Christopher A.; Tran, Nhan L.; Dooley, Andrea; Pang, Yuan-Ping; Rohl, Carole; Kloss, Jean; Yang, Zhongbo; McDonough, Wendy; Craig, David; Berens, Michael E.; Loftus, Joseph C.

    2006-01-01

    The strong tendency of malignant glioma cells to invade locally into surrounding normal brain precludes effective surgical resection, reduces the efficacy of radiotherapy, and is associated with increased resistance to chemotherapy regimens. We report that the N-terminal FERM domain of Pyk2 regulates its promigratory function. A 3-dimensional model of the Pyk2 FERM domain was generated and mutagenesis studies identified residues essential for Pyk2 promigratory function. Model-based targeted mutations within the FERM domain decreased Pyk2 phosphorylation and reduced the capacity of Pyk2 to stimulate glioma cell migration but did not significantly alter the intracellular distribution of Pyk2. Expression of autonomous Pyk2 FERM domain fragments containing analogous mutations exhibited reduced capacity to inhibit glioma cell migration and Pyk2 phosphorylation relative to expression of an autonomous wild type FERM domain fragment. These results indicate that the FERM domain plays an important role in regulating the functional competency of Pyk2 as a promigratory factor in glioma

  19. The Search for Organic Compounds of Martian Origin in Gale Crater by the Sample Analysis at Mars (SAM) Instrument on Curiosity

    Science.gov (United States)

    Glavin, Daniel; Freissinet, Caroline; Mahaffy, Paul; Miller, Kristen; Eigenbrode, Jennifer; Summons, Roger; Archer, Douglas, Jr.; Brunner, Anna; Martin, Mildred; Buch, Arrnaud; hide

    2014-01-01

    One of the key objectives of the Mars Science Laboratory rover and the Sample Analysis at Mars (SAM) instrument suite is to determine the inventory of organic and inorganic volatiles in the atmosphere and surface regolith and rocks to help assess the habitability potential of Gale Crater. The SAM instrument on the Curiosity rover can detect volatile organic compounds thermally evolved from solid samples using a combination of evolved gas analysis (EGA) and gas chromatography mass spectrometry (GCMS) (Mahaffy et al. 2012). The first solid samples analyzed by SAM, a scoop of windblown dust and sand at Rocknest, revealed several chloromethanes and a C4-chlorinated hydrocarbon derived primarily from reactions between a martian oxychlorine phase (e.g. perchlorate) and terrestrial carbon from N-methyl-N-(tertbutyldimethylsilyl)- trifluoroacetamide (MTBSTFA) vapor present in the SAM instrument background (Glavin et al. 2013). After the analyses at Rocknest, Curiosity traveled to Yellowknife Bay and drilled two separate holes in a fluvio-lacustrine sediment (the Sheepbed unit) designated John Klein and Cumberland. Analyses of the drilled materials by both SAM and the CheMin X-Ray Diffraction instrument revealed a mudstone consisting of 20 wt% smectite clays (Ming et al. 2013; Vaniman et al. 2013), which on Earth are known to aid the concentration and preservation of organic matter. Oxychlorine compounds were also detected in the Sheepbed mudstone during pyrolysis; however, in contrast to Rocknest, much higher levels of chloromethanes were released from the Sheepbed materials, suggesting an additional, possibly martian source of organic carbon (Ming et al. 2013). In addition, elevated abundances of chlorobenzene and a more diverse suite of chlorinated alkanes including dichloropropane and dichlorobutane detected in Cumberland compared to Rocknest suggest that martian or meteoritic organic carbon sources may be preserved in the mudstone (Freissinet et al. 2013

  20. Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure

    DEFF Research Database (Denmark)

    Lenaerts, Tom; Ferkinghoff-Borg, Jesper; Stricher, Francois

    2008-01-01

    instance of communication over a noisy channel. In particular, we analyze the conformational correlations between protein residues and apply the concept of mutual information to quantify information exchange. Mapping out changes of mutual information on the protein structure then allows visualizing how...... distal communication is achieved. We illustrate the approach by analyzing information transfer by the SH2 domain of Fyn tyrosine kinase, obtained from Monte Carlo dynamics simulations. Our analysis reveals that the Fyn SH2 domain forms a noisy communication channel that couples residues located......Background: Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism...

  1. SH2 Domains Serve as Lipid-Binding Modules for pTyr-Signaling Proteins.

    Science.gov (United States)

    Park, Mi-Jeong; Sheng, Ren; Silkov, Antonina; Jung, Da-Jung; Wang, Zhi-Gang; Xin, Yao; Kim, Hyunjin; Thiagarajan-Rosenkranz, Pallavi; Song, Seohyeon; Yoon, Youngdae; Nam, Wonhee; Kim, Ilshin; Kim, Eui; Lee, Dong-Gyu; Chen, Yong; Singaram, Indira; Wang, Li; Jang, Myoung Ho; Hwang, Cheol-Sang; Honig, Barry; Ryu, Sungho; Lorieau, Justin; Kim, You-Me; Cho, Wonhwa

    2016-04-07

    The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY)-signaling pathways. Genome-wide screening of human SH2 domains reveals that ∼90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction are important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY-signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Research on characteristics of communication content of operation crew in digital main control room of nuclear power plant

    International Nuclear Information System (INIS)

    Zhang Li; Ye Haifeng; Qing Tao; Li Pengcheng

    2015-01-01

    Communication content, communication mode and timeliness of communication are the main three factors that influence the effectiveness of the communication between team members. Based on the work domain analysis to execution of state-oriented procedures (SOP), the assumptions for operation crews' characteristics of the communication content in executing SOP were proposed, which supposed that the power plant status and parameters, power plant system functions and equipment, and SOP as well were the main communication contents. On a full-scope simulator of nuclear power plant, three operation crews performed experiments simulating accident scenarios. The results show that the assumptions of characteristics of the communication content are valid. (authors)

  3. Purification of 1-aminocyclopropane-1-carboxylate synthase from apple fruits using s-adenosyl [3,414C]-methionine (SAM) as a probe

    International Nuclear Information System (INIS)

    Yip, Wingkip; Dong, Jianguo; Yang, Shang Fa

    1989-01-01

    Tomato ACC synthase is inactivated by its substrate SAM, with the moiety of aminobutyrate being covalently linked to ACC synthase during the catalytic reactions. A partial purified ACC synthase (the catalytic activity 100 μmol/h·mg protein) from pellets of apple extract was incubated with [3,4 14 C] SAM. Only one radioactive peak was revealed in a C-4 reverse phase HPLC and one radioactive band on SDS-PAGE with an M.W. of 48 kDa. Apple ACC synthase in native form is resistant to V8, α-chromtrypsin and carboxylpeptidase A digestion, but effectively inactivated by trypsin and ficin, as demonstrated by both the activity assay and SAM labeling. The radioactive protein cut from the SDS-PAGE was injected to three mice, two of the mice showed responses to the protein in western blot analysis. The antibodies from mice is currently under characterization

  4. Substrates adoption methodology (SAM) to achieve “Fast, Flexible, Future (F3)” pharmaceutical production processes

    DEFF Research Database (Denmark)

    Singh, Ravendra; Rozada-Sanchez, Raquel; Wrate, Tim

    within the template. In this way the substrates adoption methodology helps to achieve “fast, flexible, future (F3)” pharmaceutical production processes by adapting a recently designed generic modular process-plant. The supporting tools for the substrate adoption are: (1) an ontological knowledge......There is a significant cost associated with process development of a portfolio of pharmaceutical products, few of which will reach the market. Continuous processing will increase the “chemical space” which can increase development efficiency. For example one, particularly attractive option...... is to develop manufacturing processes based on modular continuous systems; a flexible generic continuous modular plant which can be adapted for different substrates. In the work reported here, a substrates adoption methodology (SAM) has been developed. The proposed SAM identifies the necessary changes...

  5. Conformational determinants of phosphotyrosine peptides complexed with the Src SH2 domain.

    Directory of Open Access Journals (Sweden)

    Joseph Nachman

    2010-06-01

    Full Text Available The inhibition of specific SH2 domain mediated protein-protein interactions as an effective chemotherapeutic approach in the treatment of diseases remains a challenge. That different conformations of peptide-ligands are preferred by different SH2 domains is an underappreciated observation from the structural analysis of phosphotyrosine peptide binding to SH2 domains that may aid in future drug design. To explore the nature of ligand binding, we use simulated annealing (SA to sample the conformational space of phosphotyrosine-containing peptides complexed with the Src SH2 domain. While in good agreement with the crystallographic and NMR studies of high-affinity phosphopeptide-SH2 domain complexes, the results suggest that the structural basis for phopsphopeptide- Src SH2 interactions is more complex than the "two-pronged plug two-hole socket" model. A systematic study of peptides of type pYEEX, where pY is phosphotyrosine and X is a hydrophobic residue, indicates that these peptides can assume two conformations, one extended and one helical, representing the balance between the interaction of residue X with the hydrophobic hole on the surface of the Src SH2 domain, and its contribution to the inherent tendency of the two glutamic acids to form an alpha-helix. In contrast, a beta-turn conformation, almost identical to that observed in the crystal structure of pYVNV bound to the Grb2 SH2 domain, predominates for pYXNX peptides, even in the presence of isoleucine at the third position. While peptide binding affinities, as measured by fluorescence polarization, correlate with the relative proportion of extended peptide conformation, these results suggest a model where all three residues C-terminal to the phosphotyrosine determine the conformation of the bound phosphopeptide. The information obtained in this work can be used in the design of specific SH2 domain inhibitors.

  6. Influence of the solution pH in the 6-mercaptopurine self-assembled monolayer (6MP-SAM) on a Au(111) single-crystal electrode.

    Science.gov (United States)

    Madueño, Rafael; García-Raya, Daniel; Viudez, Alfonso J; Sevilla, José M; Pineda, Teresa; Blázquez, Manuel

    2007-10-23

    Self-assembled monolayers (SAMs) of 6-mercaptopurine (6MP) have been prepared on a Au(111) single-crystal electrode by immersion of the metal surface in a 100 microM 6MP and 0.01 M HClO4 solution. The 6MP-SAM Au(111) single-crystal electrodes were transferred to the cell and allowed to equilibrate with the different aqueous working solutions before the electrochemical experiments. The influence of the solution pH was studied by cyclic voltammetry, double layer capacitance curves, and electrochemical impedance spectroscopy. The electrochemical behavior of the 6MP-SAM in acetic acid at pH 4 presents important differences in comparison to that obtained in 0.1 M KOH solutions. Cyclic voltammograms for the reductive desorption process in acid medium are broad and show some features that can be explained by a phase transition between a chemisorbed and a physisorbed state of the 6MP molecules. The low solubility of these molecules in acid medium could explain this phenomenon and the readsorption of the complete monolayer when the potential is scanned in the positive direction. The variation of the double-layer capacitance values in the potential range of monolayer stability with the pH suggests that the acid-base chemistry of the 6MP molecules is playing a role. This fact has been studied by following the variations of the electron-transfer rate constant of the highly charged redox probes as are Fe(CN)(6)-3/-4 and Ru(NH3)(6)+3/+2 as a function of solution pH. The apparent surface pKa value for the 6MP-SAM (pKa approximately 8) is explained by the total conversion of the different 6MP tautomers that exist in solution to the thiol species in the adsorbed state.

  7. Electrochemical characterization of a 1,8-octanedithiol self-assembled monolayer (ODT-SAM) on a Au(1 1 1) single crystal electrode

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Raya, Daniel; Madueno, Rafael; Sevilla, Jose Manuel; Blazquez, Manuel [Departamento de Quimica Fisica y Termodinamica Aplicada, Universidad de Cordoba, Campus de Rabanales, Ed. Marie Curie, E-14071 Cordoba (Spain); Pineda, Teresa [Departamento de Quimica Fisica y Termodinamica Aplicada, Universidad de Cordoba, Campus de Rabanales, Ed. Marie Curie, E-14071 Cordoba (Spain)], E-mail: tpineda@uco.es

    2008-11-15

    Recently, it has becoming increasingly important to control the organization of self-assembled monolayers (SAMs) of {omega}-functionalized thiols for its potential applications in the construction of more complex molecular architectures. In this paper, we report on the spontaneous formation of a SAM of octanedithiol (ODT) as a function of the modification time. Electrochemical techniques such as cyclic voltammetry, double layer capacitance and electrochemical impedance spectroscopy are used for the characterization of this monolayer. The increase in modification time brings about changes in the octanedithiol self-assembled monolayer (ODT-SAM) reductive desorption voltammograms that indicate an evolution toward a more ordered and compact monolayer. This trend has also been found by following the changes in the electron transfer processes of the redox probe K{sub 3}Fe(CN){sub 6}. In fact, the ODT-SAM formed at low-modification time does not significantly perturb the electrochemical response as it is typical of either a low coverage or of the presence of large defects in the layer. Upon increasing the modification time, the voltammograms of the redox probe adopt a sigmoidal shape indicating the existence of pinholes in the monolayer distributed as an array of microelectrodes. The surface coverage as well as the size and distribution of these pinholes have been determined by the impedance technique that gives a more reliable evaluation of these monolayer structural parameters.

  8. SAM II aerosol profile measurements, Poker Flat, Alaska; July 16-19, 1979

    Science.gov (United States)

    Mccormick, M. P.; Chu, W. P.; Mcmaster, L. R.; Grams, G. W.; Herman, B. M.; Pepin, T. J.; Russell, P. B.; Swissler, T. J.

    1981-01-01

    SAM II satellite measurements during the July 1979 Poker Flat mission, yielded an aerosol extinction coefficient of 0.0004/km at 1.0 micron wavelength, in the region of the stratospheric aerosol mixing ratio peak (12-16 km). The stratospheric aerosol optical depth for these data, calculated from the tropopause through 30 km, is approximately 0.001. These results are consistent with the average 1979 summertime values found throughout the Arctic.

  9. SAM Technical Review Committee Final Report: Summary and Key Recommendations from the Onsite TRC Meeting Held April 22-23, 2013

    Energy Technology Data Exchange (ETDEWEB)

    Blair, N.; Dobos, S.; Janzou, S.; Gilman, P.; Freeman, J.; Kaffine, L.

    2013-08-01

    The System Advisor Model (SAM) is a broad and robust set of models and frameworks for analyzing both system performance and system financing. It does this across a range of technologies dominated by solar technologies including photovoltaics (PV) and concentrated solar power (CSP). The U.S. Department of Energy (DOE) Solar Energy Technology Program requested the SAM development team to review the photovoltaic performance modeling with the development community and specifically, with the independent engineering community. The report summarizes the major effort for this technical review committee (TRC).

  10. Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium of patients with COPD

    NARCIS (Netherlands)

    Song, J; Heijink, I H; Kistemaker, L E M; Reinders-Luinge, M; Kooistra, W; Noordhoek, J A; Gosens, R; Brandsma, C A; Timens, W; Hiemstra, P S; Rots, M G; Hylkema, M N

    2017-01-01

    Background: Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients. Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box

  11. Rainfall declines over Queensland from 1951-2007 and links to the Subtropical Ridge and the SAM

    International Nuclear Information System (INIS)

    Cottrill, D A; Ribbe, J

    2010-01-01

    Much of southern and eastern Australia including Queensland have experienced rainfall declines over recent decades affecting agricultural production and accelerating water infrastructure development. Rainfall declines from southern Australia have now been directly related to changes in the Southern Annular Mode (SAM) and the subtropical ridge. In southern and coastal Queensland, the rainfall declines have occurred mostly in the austral summer and autumn. Observations from this region reveal the rainfall decline is correlated to an increase in the mean sea level pressure (MSLP) at many stations. The largest increases in MSLP are over southeast Queensland and coastal regions, where some of the largest rainfall declines occur. This study indicates the subtropical ridge as one of the main factors in the rainfall decline over this region. SAM is also likely to be important, although its seasonal influence, apart from winter, is harder to determine.

  12. Thickness-dependent a_1/a_2 domain evolution in ferroelectric PbTiO_3 films

    International Nuclear Information System (INIS)

    Li, S.; Zhu, Y.L.; Tang, Y.L.; Liu, Y.; Zhang, S.R.; Wang, Y.J.; Ma, X.L.

    2017-01-01

    Ferroelectric a_1/a_2 domain structure has great potentials in high dielectric capacitors and tunable microwave devices. Understanding its structure is crucial to better control the domain configurations for future applications. In this paper, PbTiO_3 thin films with variant thicknesses are deposited on (110)-oriented GdScO_3 substrates by Pulsed Laser Deposition (PLD) and investigated by using conventional transmission electron microscopy (TEM) and Cs-corrected Scanning TEM. Contrast analysis and electron diffractions reveal that PbTiO_3 films are domain oriented consisting of a_1/a_2 and a/c domain structure. The a_1/a_2 domains are found to distribute periodically and its width increases with increasing film thickness following square root rule. Cs-corrected STEM imaging demonstrates that the domain walls of a_1/a_2 domain structure have the rotation characteristic of 90° ferroelastic domain wall. The interchange of a_1/a_2 domains induces the formation of vertex domains composed of two 90° and one 180° domain walls. Strains are mainly concentrated on the domain walls. The formation of this complex domain configuration is discussed in terms of the effect of the misfit strain, film thickness and cooling rate. These results provide novel information about a_1/a_2 domain structures and are expected to shed some light on modulating a_1/a_2 ferroelectric domain patterns in the design of ferroelectric-based devices.

  13. Post-translational modification of ribosomally synthesized peptides by a radical SAM epimerase in Bacillus subtilis

    Science.gov (United States)

    Benjdia, Alhosna; Guillot, Alain; Ruffié, Pauline; Leprince, Jérôme; Berteau, Olivier

    2017-07-01

    Ribosomally synthesized peptides are built out of L-amino acids, whereas D-amino acids are generally the hallmark of non-ribosomal synthetic processes. Here we show that the model bacterium Bacillus subtilis is able to produce a novel type of ribosomally synthesized and post-translationally modified peptide that contains D-amino acids, and which we propose to call epipeptides. We demonstrate that a two [4Fe-4S]-cluster radical S-adenosyl-L-methionine (SAM) enzyme converts L-amino acids into their D-counterparts by catalysing Cα-hydrogen-atom abstraction and using a critical cysteine residue as the hydrogen-atom donor. Unexpectedly, these D-amino acid residues proved to be essential for the activity of a peptide that induces the expression of LiaRS, a major component of the bacterial cell envelope stress-response system. Present in B. subtilis and in several members of the human microbiome, these epipeptides and radical SAM epimerases broaden the landscape of peptidyl structures accessible to living organisms.

  14. Increasing the Fill Factor of Inverted P3HT:PCBM Solar Cells Through Surface Modification of Al-Doped ZnO via Phosphonic Acid-Anchored C60 SAMs

    DEFF Research Database (Denmark)

    Stubhan, Tobias; Salinas, Michael; Ebel, Alexander

    2012-01-01

    The influence of aluminum-doped zinc oxide (AZO) electron extraction layers modified with self-assembled monolayers (SAMs) on inverted polymer solar cells is investigated. It is found that AZO modification with phosphonic acid-anchored Fullerene–SAMs leads to a reduction of the series resistance,...

  15. Characterizing SH2 Domain Specificity and Network Interactions Using SPOT Peptide Arrays.

    Science.gov (United States)

    Liu, Bernard A

    2017-01-01

    Src Homology 2 (SH2) domains are protein interaction modules that recognize and bind tyrosine phosphorylated ligands. Their ability to distinguish binding to over thousands of potential phosphotyrosine (pTyr) ligands within the cell is critical for the fidelity of receptor tyrosine kinase (RTK) signaling. Within humans there are over a hundred SH2 domains with more than several thousand potential ligands across many cell types and cell states. Therefore, defining the specificity of individual SH2 domains is critical for predicting and identifying their physiological ligands. Here, in this chapter, I describe the broad use of SPOT peptide arrays for examining SH2 domain specificity. An orientated peptide array library (OPAL) approach can uncover both favorable and non-favorable residues, thus providing an in-depth analysis to SH2 specificity. Moreover, I discuss the application of SPOT arrays for paneling SH2 ligand binding with physiological peptides.

  16. SAM: Support Vector Machine Based Active Queue Management

    International Nuclear Information System (INIS)

    Shah, M.S.

    2014-01-01

    Recent years have seen an increasing interest in the design of AQM (Active Queue Management) controllers. The purpose of these controllers is to manage the network congestion under varying loads, link delays and bandwidth. In this paper, a new AQM controller is proposed which is trained by using the SVM (Support Vector Machine) with the RBF (Radial Basis Function) kernal. The proposed controller is called the support vector based AQM (SAM) controller. The performance of the proposed controller has been compared with three conventional AQM controllers, namely the Random Early Detection, Blue and Proportional Plus Integral Controller. The preliminary simulation studies show that the performance of the proposed controller is comparable to the conventional controllers. However, the proposed controller is more efficient in controlling the queue size than the conventional controllers. (author)

  17. An Efficient Semi-supervised Learning Approach to Predict SH2 Domain Mediated Interactions.

    Science.gov (United States)

    Kundu, Kousik; Backofen, Rolf

    2017-01-01

    Src homology 2 (SH2) domain is an important subclass of modular protein domains that plays an indispensable role in several biological processes in eukaryotes. SH2 domains specifically bind to the phosphotyrosine residue of their binding peptides to facilitate various molecular functions. For determining the subtle binding specificities of SH2 domains, it is very important to understand the intriguing mechanisms by which these domains recognize their target peptides in a complex cellular environment. There are several attempts have been made to predict SH2-peptide interactions using high-throughput data. However, these high-throughput data are often affected by a low signal to noise ratio. Furthermore, the prediction methods have several additional shortcomings, such as linearity problem, high computational complexity, etc. Thus, computational identification of SH2-peptide interactions using high-throughput data remains challenging. Here, we propose a machine learning approach based on an efficient semi-supervised learning technique for the prediction of 51 SH2 domain mediated interactions in the human proteome. In our study, we have successfully employed several strategies to tackle the major problems in computational identification of SH2-peptide interactions.

  18. MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

    Science.gov (United States)

    Shelby, Shameka J; Colwill, Karen; Dhe-Paganon, Sirano; Pawson, Tony; Thompson, Debra A

    2013-01-01

    The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE). A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999)), purified and phosphorylated. Ni(2+)-NTA pull downs were performed using 6xHis-rMERTK(571-999) in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999) and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α), VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS), siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

  19. MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Shameka J Shelby

    Full Text Available The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE. A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999, purified and phosphorylated. Ni(2+-NTA pull downs were performed using 6xHis-rMERTK(571-999 in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999 and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α, VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS, siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

  20. Growth dynamics of L-cysteine SAMs on single-crystal gold surfaces: a metastable deexcitation spectroscopy study

    Science.gov (United States)

    Canepa, M.; Lavagnino, L.; Pasquali, L.; Moroni, R.; Bisio, F.; DeRenzi, V.; Terreni, S.; Mattera, L.

    2009-07-01

    We report on a metastable deexcitation spectroscopy investigation of the growth of L-cysteine layers deposited under UHV conditions on well-defined Au(110)- (1 × 2) and Au(111) surfaces. The interaction of He* with molecular orbitals gave rise to well-defined UPS-like Penning spectra which provided information on the SAM assembly dynamics and adsorption configurations. Penning spectra have been interpreted through comparison with molecular orbital DFT calculations of the free molecule and have been compared with XPS results of previous works. Regarding adsorption of first-layer molecules at room temperature (RT), two different growth regimes were observed. On Au(110), the absence of spectral features related to orbitals associated with SH groups indicated the formation of a compact SAM of thiolate molecules. On Au(111), the data demonstrated the simultaneous presence, since the early stages of growth, of strongly and weakly bound molecules, the latter showing intact SH groups. The different growth mode was tentatively assigned to the added rows of the reconstructed Au(110) surface which behave as extended defects effectively promoting the formation of the S-Au bond. The growth of the second molecular layer was instead observed to proceed similarly for both substrates. Second-layer molecules preferably adopt an adsorption configuration in which the SH group protrudes into the vacuum side.

  1. Growth dynamics of L-cysteine SAMs on single-crystal gold surfaces: a metastable deexcitation spectroscopy study

    International Nuclear Information System (INIS)

    Canepa, M; Lavagnino, L; Moroni, R; Bisio, F; Terreni, S; Mattera, L; Pasquali, L; De Renzi, V

    2009-01-01

    We report on a metastable deexcitation spectroscopy investigation of the growth of L-cysteine layers deposited under UHV conditions on well-defined Au(110)- (1 x 2) and Au(111) surfaces. The interaction of He* with molecular orbitals gave rise to well-defined UPS-like Penning spectra which provided information on the SAM assembly dynamics and adsorption configurations. Penning spectra have been interpreted through comparison with molecular orbital DFT calculations of the free molecule and have been compared with XPS results of previous works. Regarding adsorption of first-layer molecules at room temperature (RT), two different growth regimes were observed. On Au(110), the absence of spectral features related to orbitals associated with SH groups indicated the formation of a compact SAM of thiolate molecules. On Au(111), the data demonstrated the simultaneous presence, since the early stages of growth, of strongly and weakly bound molecules, the latter showing intact SH groups. The different growth mode was tentatively assigned to the added rows of the reconstructed Au(110) surface which behave as extended defects effectively promoting the formation of the S-Au bond. The growth of the second molecular layer was instead observed to proceed similarly for both substrates. Second-layer molecules preferably adopt an adsorption configuration in which the SH group protrudes into the vacuum side.

  2. Eldecalcitol improves mechanical strength of cortical bones by stimulating the periosteal bone formation in the senescence-accelerated SAM/P6 mice - a comparison with alfacalcidol.

    Science.gov (United States)

    Shiraishi, Ayako; Sakai, Sadaoki; Saito, Hitoshi; Takahashi, Fumiaki

    2014-10-01

    Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, is a potent inhibitor of bone resorption that has demonstrated a greater effect at reducing the risk of fracture in osteoporotic patients than alfacalcidol (ALF). In the present study, we used the senescence-accelerated mouse strain P6 (SAM/P6), which has low bone mass caused by osteoblast dysfunction, to evaluate the effect of ELD on cortical bone in comparison with ALF. Four-month-old SAM/P6 mice were given either ELD (0.025 or 0.05μg/kg) or ALF (0.2 or 0.4μg/kg) by oral gavage 5 times/week for 6 weeks. Both ELD and ALF increased serum calcium (Ca) in a dose-dependent manner. Serum Ca levels in the ELD 0.05μg/kg group were comparable to those of the ALF 0.2μg/kg group. ELD 0.05μg/kg significantly improved the bone biomechanical properties of the femur compared with the vehicle control group (pBone histomorphometry revealed that in the femoral endocortical surface, the suppression of bone resorption parameters (N.Oc/BS) and bone formation parameters (MS/BS) by ELD (0.05μg/kg) was greater than that by ALF (0.2μg/kg). In contrast, in the femoral periosteal surface, ELD 0.05μg/kg significantly increased bone formation parameters (BFR/BS, MS/BS) compared with the vehicle control group (pbone not only by inhibiting endocortical bone resorption but also by stimulating the periosteal bone formation in SAM/P6 mice. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family.

    Science.gov (United States)

    Register, A C; Leonard, Stephen E; Maly, Dustin J

    2014-11-11

    Src-family kinases (SFKs) make up a family of nine homologous multidomain tyrosine kinases whose misregulation is responsible for human disease (cancer, diabetes, inflammation, etc.). Despite overall sequence homology and identical domain architecture, differences in SH3 and SH2 regulatory domain accessibility and ability to allosterically autoinhibit the ATP-binding site have been observed for the prototypical SFKs Src and Hck. Biochemical and structural studies indicate that the SH2-catalytic domain (SH2-CD) linker, the intramolecular binding epitope for SFK SH3 domains, is responsible for allosterically coupling SH3 domain engagement to autoinhibition of the ATP-binding site through the conformation of the αC helix. As a relatively unconserved region between SFK family members, SH2-CD linker sequence variability across the SFK family is likely a source of nonredundant cellular functions between individual SFKs via its effect on the availability of SH3 and SH2 domains for intermolecular interactions and post-translational modification. Using a combination of SFKs engineered with enhanced or weakened regulatory domain intramolecular interactions and conformation-selective inhibitors that report αC helix conformation, this study explores how SH2-CD sequence heterogeneity affects allosteric coupling across the SFK family by examining Lyn, Fyn1, and Fyn2. Analyses of Fyn1 and Fyn2, isoforms that are identical but for a 50-residue sequence spanning the SH2-CD linker, demonstrate that SH2-CD linker sequence differences can have profound effects on allosteric coupling between otherwise identical kinases. Most notably, a dampened allosteric connection between the SH3 domain and αC helix leads to greater autoinhibitory phosphorylation by Csk, illustrating the complex effects of SH2-CD linker sequence on cellular function.

  4. High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.

    Directory of Open Access Journals (Sweden)

    Kunitake Higo

    Full Text Available Src homology 2 (SH2 domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2 specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

  5. High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.

    Science.gov (United States)

    Higo, Kunitake; Ikura, Teikichi; Oda, Masayuki; Morii, Hisayuki; Takahashi, Jun; Abe, Ryo; Ito, Nobutoshi

    2013-01-01

    Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

  6. Systematic characterization of the specificity of the SH2 domains of cytoplasmic tyrosine kinases.

    Science.gov (United States)

    Zhao, Bing; Tan, Pauline H; Li, Shawn S C; Pei, Dehua

    2013-04-09

    Cytoplasmic tyrosine kinases (CTK) generally contain a Src-homology 2 (SH2) domain, whose role in the CTK family is not fully understood. Here we report the determination of the specificity of 25 CTK SH2 domains by screening one-bead-one-compound (OBOC) peptide libraries. Based on the peptide sequences selected by the SH2 domains, we built Support Vector Machine (SVM) models for the prediction of binding ligands for the SH2 domains. These models yielded support for the progressive phosphorylation model for CTKs in which the overlapping specificity of the CTK SH2 and kinase domains has been proposed to facilitate targeting of the CTK substrates with at least two potential phosphotyrosine (pTyr) sites. We curated 93 CTK substrates with at least two pTyr sites catalyzed by the same CTK, and showed that 71% of these substrates had at least two pTyr sites predicted to bind a common CTK SH2 domain. More importantly, we found 34 instances where there was at least one pTyr site predicted to be recognized by the SH2 domain of the same CTK, suggesting that the SH2 and kinase domains of the CTKs may cooperate to achieve progressive phosphorylation of a protein substrate. This article is part of a Special Issue entitled: From protein structures to clinical applications. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. 2D acoustic-elastic coupled waveform inversion in the Laplace domain

    KAUST Repository

    Bae, Hoseuk

    2010-04-01

    Although waveform inversion has been intensively studied in an effort to properly delineate the Earth\\'s structures since the early 1980s, most of the time- and frequency-domain waveform inversion algorithms still have critical limitations in their applications to field data. This may be attributed to the highly non-linear objective function and the unreliable low-frequency components. To overcome the weaknesses of conventional waveform inversion algorithms, the acoustic Laplace-domain waveform inversion has been proposed. The Laplace-domain waveform inversion has been known to provide a long-wavelength velocity model even for field data, which may be because it employs the zero-frequency component of the damped wavefield and a well-behaved logarithmic objective function. However, its applications have been confined to 2D acoustic media.We extend the Laplace-domain waveform inversion algorithm to a 2D acoustic-elastic coupled medium, which is encountered in marine exploration environments. In 2D acoustic-elastic coupled media, the Laplace-domain pressures behave differently from those of 2D acoustic media, although the overall features are similar to each other. The main differences are that the pressure wavefields for acoustic-elastic coupled media show negative values even for simple geological structures unlike in acoustic media, when the Laplace damping constant is small and the water depth is shallow. The negative values may result from more complicated wave propagation in elastic media and at fluid-solid interfaces.Our Laplace-domain waveform inversion algorithm is also based on the finite-element method and logarithmic wavefields. To compute gradient direction, we apply the back-propagation technique. Under the assumption that density is fixed, P- and S-wave velocity models are inverted from the pressure data. We applied our inversion algorithm to the SEG/EAGE salt model and the numerical results showed that the Laplace-domain waveform inversion

  8. In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.

    Science.gov (United States)

    Côté, Jean-François; Vuori, Kristiina

    2006-01-01

    Rho family GTPases regulate a large variety of biological processes, including the reorganization of the actin cytoskeleton. Like other members of the Ras superfamily of small GTP-binding proteins, Rho GTPases cycle between a GDP-bound (inactive) and a GTP-bound (active) state, and, when active, the GTPases relay extracellular signals to a large number of downstream effectors. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP on Rho GTPases, thereby activating them. Most Rho-GEFs mediate their effects through their signature domain known as the Dbl Homology-Pleckstrin Homology (DH-PH) module. Recently, we and others identified a family of evolutionarily conserved, DOCK180-related proteins that also display GEF activity toward Rho GTPases. The DOCK180-family of proteins lacks the canonical DH-PH module. Instead, they rely on a novel domain, termed DHR-2, DOCKER, or CZH2, to exchange GDP for GTP on Rho targets. In this chapter, the experimental approach that we used to uncover the exchange activity of the DHR-2 domain of DOCK180-related proteins will be described.

  9. Distinct mechanisms of a phosphotyrosyl peptide binding to two SH2 domains.

    Science.gov (United States)

    Pang, Xiaodong; Zhou, Huan-Xiang

    2014-05-01

    Protein phosphorylation is very common post-translational modification, catalyzed by kinases, for signaling and regulation. Phosphotyrosines frequently target SH2 domains. The spleen tyrosine kinase (Syk) is critical for tyrosine phosphorylation of multiple proteins and for regulation of important pathways. Phosphorylation of both Y342 and Y346 in Syk linker B is required for optimal signaling. The SH2 domains of Vav1 and PLC-γ both bind this doubly phosphorylated motif. Here we used a recently developed method to calculate the effects of Y342 and Y346 phosphorylation on the rate constants of a peptide from Syk linker B binding to the SH2 domains of Vav1 and PLC-γ. The predicted effects agree well with experimental observations. Moreover, we found that the same doubly phosphorylated peptide binds the two SH2 domains via distinct mechanisms, with apparent rigid docking for Vav1 SH2 and dock-and-coalesce for PLC-γ SH2.

  10. Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Yun, Ji-Hye; Lee, Won Kyung; Kim, Heeyoun; Kim, Eunhee; Cheong, Chaejoon; Cho, Myeon Haeng; Lee, Weontae

    2014-01-01

    Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminal Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2 1–64 ) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2 1–64 and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences

  11. Functional significance of SRJ domain mutations in CITED2.

    Directory of Open Access Journals (Sweden)

    Chiann-mun Chen

    Full Text Available CITED2 is a transcriptional co-activator with 3 conserved domains shared with other CITED family members and a unique Serine-Glycine Rich Junction (SRJ that is highly conserved in placental mammals. Loss of Cited2 in mice results in cardiac and aortic arch malformations, adrenal agenesis, neural tube and placental defects, and partially penetrant defects in left-right patterning. By screening 1126 sporadic congenital heart disease (CHD cases and 1227 controls, we identified 19 variants, including 5 unique non-synonymous sequence variations (N62S, R92G, T166N, G180-A187del and A187T in patients. Many of the CHD-specific variants identified in this and previous studies cluster in the SRJ domain. Transient transfection experiments show that T166N mutation impairs TFAP2 co-activation function and ES cell proliferation. We find that CITED2 is phosphorylated by MAPK1 in vitro at T166, and that MAPK1 activation enhances the coactivation function of CITED2 but not of CITED2-T166N. In order to investigate the functional significance in vivo, we generated a T166N mutation of mouse Cited2. We also used PhiC31 integrase-mediated cassette exchange to generate a Cited2 knock-in allele replacing the mouse Cited2 coding sequence with human CITED2 and with a mutant form deleting the entire SRJ domain. Mouse embryos expressing only CITED2-T166N or CITED2-SRJ-deleted alleles surprisingly show no morphological abnormalities, and mice are viable and fertile. These results indicate that the SRJ domain is dispensable for these functions of CITED2 in mice and that mutations clustering in the SRJ region are unlikely to be the sole cause of the malformations observed in patients with sporadic CHD. Our results also suggest that coding sequence mutations observed in case-control studies need validation using in vivo models and that predictions based on structural conservation and in vitro functional assays, or even in vivo global loss of function models, may be

  12. Coastal lagoon sediments and benthic foraminifera as indicator for Holocene sea-level change: Samsø, southern Kattegat

    DEFF Research Database (Denmark)

    Sander, Lasse; Morigi, Caterina; Pejrup, Morten

    The island of Samsø is located in the southern Kattegat region of Denmark, a relatively sheltered micro-tidal environment. The area experienced a period of rapid transgression during the early Altantic period, reaching its maximum approx. 7,600 yr BP. Since then, isostatic uplift gradually caused....... Over time, an extensive beach ridge system formed, which eventually connected the islands, giving Samsø its characteristic shape. Ephemeral shallow-water lagoons evolved in topographic depressions along the shores of the island, most of which became inactive until today. A semi-enclosed coastal lagoon......-level and to investigate associated geomorphic responses in coastal lagoon and beach ridge systems. Vibracorings will be carried out in these sedimentary environments and will be supplemented with manual auger corings and ground penetrating radar (GPR) surveys to assess vertical variations in the deposited sediments...

  13. Investigation of phosphotyrosine recognition by the SH2 domain of the Src kinase.

    Science.gov (United States)

    Bradshaw, J M; Mitaxov, V; Waksman, G

    1999-11-05

    The binding of tyrosine phosphorylated targets by SH2 domains is required for propagation of many cellular signals in higher eukaryotes; however, the determinants of phosphotyrosine (pTyr) recognition by SH2 domains are not well understood. In order to identify the attributes of pTyr required for high affinity interaction with SH2 domains, the binding of the SH2 domain of the Src kinase (Src SH2 domain) to a dephosphorylated peptide, a phosphoserine-containing peptide, and the amino acid pTyr was studied using titration calorimetry and compared with the binding of a high affinity tyrosyl phosphopeptide. The dephosphorylated peptide and the phosphoserine containing peptide both bind extremely weakly to the Src SH2 domain (DeltaGo (dephosphorylated)=-3.6 kcal/mol, DeltaGo (phosphoserine) >-3.7 kcal/mol); however, the DeltaGo value of pTyr binding is more favorable (-4.7 kcal/mol, or 50 % of the entire binding free energy of a high affinity tyrosyl phosphopeptide). These results indicate that both the phosphate and the tyrosine ring of the pTyr are critical determinants of high affinity binding. Alanine mutagenesis was also used to evaluate the energetic contribution to binding of ten residues located in the pTyr-binding site. Mutation of the strictly conserved Arg betaB5 resulted in a large increase in DeltaGo (DeltaDeltaGo=3.2 kcal/mol) while elimination of the other examined residues each resulted in a significantly smaller (DeltaDeltaGoSH2 domain, surprisingly increased affinity by eightfold (DeltaDeltaGo=-1.1 kcal/mol). Using a double mutant cycle analysis, it was revealed that residues of the pTyr-binding pocket are not coupled to the peptide residues C-terminal to the pTyr. In addition, comparison of each residue's DeltaDeltaGo value upon mutation with that residue's sequence conservation among SH2 domains revealed only a modest correlation between a residue's energetic contribution to pTyr recognition and its conservation throughout evolution. The results of

  14. Structural Characterization of Monomeric/Dimeric State of p59fyn SH2 Domain.

    Science.gov (United States)

    Huculeci, Radu; Kieken, Fabien; Garcia-Pino, Abel; Buts, Lieven; van Nuland, Nico; Lenaerts, Tom

    2017-01-01

    Src homology 2 (SH2) domains are key modulators in various signaling pathways allowing the recognition of phosphotyrosine sites of different proteins. Despite the fact that SH2 domains acquire their biological functions in a monomeric state, a multitude of reports have shown their tendency to dimerize. Here, we provide a technical description on how to isolate and characterize by gel filtration, circular dichroism (CD), and nuclear magnetic resonance (NMR) each conformational state of p59 fyn SH2 domain.

  15. A paradigm shift for radical SAM reactions: The organometallic intermediate Ω is central to catalysis.

    Science.gov (United States)

    Byer, Amanda S; Yang, Hao; McDaniel, Elizabeth C; Kathiresan, Venkatesan; Impano, Stella; Pagnier, Adrien; Watts, Hope; Denler, Carly; Vagstad, Anna; Piel, Jörn; Duschene, Kaitlin S; Shepard, Eric M; Shields, Thomas P; Scott, Lincoln G; Lilla, Edward A; Yokoyama, Kenichi; Broderick, William E; Hoffman, Brian M; Broderick, Joan B

    2018-06-28

    Radical S-adenosyl-L-methionine (SAM) en-zymes comprise a vast superfamily catalyzing diverse reactions essential to all life through ho-molytic SAM cleavage to liberate the highly-reactive 5-deoxyadenosyl radical (5-dAdo•). Our recent observation of a catalytically compe-tent organometallic intermediate Ω that forms dur-ing reaction of the radical SAM (RS) enzyme py-ruvate formate-lyase activating-enzyme (PFL-AE) was therefore quite surprising, and led to the question of its broad relevance in the superfamily. We now show that Ω in PFL-AE forms as an in-termediate under a variety of mixing order condi-tions, suggesting it is central to catalysis in this enzyme. We further demonstrate that Ω forms in a suite of RS enzymes chosen to span the totality of superfamily reaction types, implicating Ω as essential in catalysis across the RS superfamily. Finally, EPR and electron nuclear double reso-nance spectroscopy establish that Ω involves an Fe-C5 bond between 5-dAdo• and the [4Fe-4S] cluster. An analogous organometallic bond is found in the well-known adenosylcobalamin (co-enzyme B12) cofactor used to initiate radical reac-tions via a 5'-dAdo• intermediate. Generation of a 5'-dAdo• intermediate via homolytic metal-carbon bond cleavage thus appears to be similar for Ω and coenzyme B12. However coenzyme B12 is involved in enzymes catalyzing of only a small number (~12) of distinct reactions, while the RS superfamily has more than 100,000 distinct se-quences and over 80 reaction types character-ized to date. The appearance of Ω across the RS superfamily therefore dramatically enlarges the sphere of bio-organometallic chemistry in Nature.

  16. Purification, crystallization and preliminary crystallographic analysis of the SH2 domain of IL-2-inducible T-cell kinase

    International Nuclear Information System (INIS)

    Joseph, Raji E.; Ginder, Nathaniel D.; Hoy, Julie A.; Nix, Jay C.; Honzatko, Richard B.; Andreotti, Amy H.

    2011-01-01

    Crystallization conditions are described for the cis- and trans-imide bond-containing SH2 domain of IL-2-inducible T-cell kinase. Proline is a unique amino acid owing to the relatively small energy difference between the cis and trans conformations of its peptide bond. The X–Pro imide bond readily undergoes cis–trans isomerization in the context of short peptides as well as some proteins. However, the direct detection of cis–trans proline isomerization in folded proteins is technically challenging. NMR spectroscopy is well suited to the direct detection of proline isomerization in folded proteins. It is less clear how well X-ray crystallography can reveal this conformational exchange event in folded proteins. Conformational heterogeneity owing to cis–trans proline isomerization in the Src homology 2 (SH2) domain of the IL-2-inducible T-cell kinase (ITK) has been extensively characterized by NMR. Using the ITK SH2 domain as a test system, an attempt was made to determine whether proline isomerization could be detected in a crystal structure of the ITK SH2 domain. As a first step towards this goal, the purification, crystallization and preliminary characterization of the ITK SH2 domain are described

  17. Konsep Kehidupan Dalam Ruang Pada Kelenteng Sam Kouw Di Surakarta Studi Kasus : Kelenteng T’ien Kok Sie, Kelenteng Poo An Kiong Dan Cetiya Ksiti Garbha

    Directory of Open Access Journals (Sweden)

    Dyah Susilowati Pradnya Paramita

    2008-09-01

    Full Text Available The kelenteng was used by three traditional religions brought by Chinese traders, namely Tao, Khonghucu and Buddhism which then together named Sam Kouw (Tri Darma The kelenteng Sam Kouw had many worshiped sculptures to which their worship ritualwas based. The kelenteng was taken care by a suhu acted as a mediator during the worship. Due to his role in worship, the Suhu and his family also stayed in the kelenteng.Based on that phenomenon, this research is focused on the rooms usage in kelenteng as a place of interaction of both worship and household routines. This research applies naturalistic qualitative methodology. The researcher played as the main instrument in collecting the data by observation, interview. The data gained during the research was formulated to some topics analyzed inductively before the researcher conducted an inter -topic dialog.. Thi s researched was conducted in three objects with cross sectional method to strengthen the data and sharpen the focus of observation. The three objects are: 1 Kelenteng T’ien Kok Sie in Ketandan; 2 Kelenteng Poo An Kiong in Coyudan, and 3 Cetiya Ksiti Garbha in Srambatan  The result of the research shows that kelenteng Sam Kouw has a public worship room in front of kelenteng , has a particular worship room in behind of kelenteng , and always has a meditation room that has always perpendicular a prominent god altar.

  18. Purification of SOCS (Suppressor of Cytokine Signaling) SH2 Domains for Structural and Functional Studies.

    Science.gov (United States)

    Liau, Nicholas P D; Laktyushin, Artem; Babon, Jeffrey J

    2017-01-01

    Src Homology 2 (SH2) domains are protein domains which have a high binding affinity for specific amino acid sequences containing a phosphorylated tyrosine residue. The Suppressors of Cytokine Signaling (SOCS) proteins use an SH2 domain to bind to components of certain cytokine signaling pathways to downregulate the signaling cascade. The recombinantly produced SH2 domains of various SOCS proteins have been used to undertake structural and functional studies elucidating the method of how such targeting occurs. Here, we describe the protocol for the recombinant production and purification of SOCS SH2 domains, with an emphasis on SOCS3.

  19. Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Ji-Hye [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Won Kyung [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Heeyoun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Eunhee; Cheong, Chaejoon [Magnetic Resonance Team, Korea Basic Science Institute (KBSI), Ochang, Chungbuk 363-883 (Korea, Republic of); Cho, Myeon Haeng [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2014-09-26

    Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminal Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2{sub 1–64}) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2{sub 1–64} and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences.

  20. Crystal structure of Src-like adaptor protein 2 reveals close association of SH3 and SH2 domains through β-sheet formation.

    Science.gov (United States)

    Wybenga-Groot, Leanne E; McGlade, C Jane

    2013-12-01

    The Src-like adaptor proteins (SLAP/SLAP2) are key components of Cbl-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling in hematopoietic cells. SLAP and SLAP2 consist of adjacent SH3 and SH2 domains that are most similar in sequence to Src family kinases (SFKs). Notably, the SH3-SH2 connector sequence is significantly shorter in SLAP/SLAP2 than in SFKs. To understand the structural implication of a short SH3-SH2 connector sequence, we solved the crystal structure of a protein encompassing the SH3 domain, SH3-SH2 connector, and SH2 domain of SLAP2 (SLAP2-32). While both domains adopt typical folds, the short SH3-SH2 connector places them in close association. Strand βe of the SH3 domain interacts with strand βA of the SH2 domain, resulting in the formation of a continuous β sheet that spans the length of the protein. Disruption of the SH3/SH2 interface through mutagenesis decreases SLAP-32 stability in vitro, consistent with inter-domain binding being an important component of SLAP2 structure and function. The canonical peptide binding pockets of the SH3 and SH2 domains are fully accessible, in contrast to other protein structures that display direct interaction between SH3 and SH2 domains, in which either peptide binding surface is obstructed by the interaction. Our results reveal potential sites of novel interaction for SH3 and SH2 domains, and illustrate the adaptability of SH2 and SH3 domains in mediating interactions. As well, our results suggest that the SH3 and SH2 domains of SLAP2 function interdependently, with implications on their mode of substrate binding. © 2013.

  1. Investigation of SAM measures during selected MBLOCA sequences along with Station Blackout in a generic Konvoi PWR using ASTECV2.0

    International Nuclear Information System (INIS)

    Gómez-García-Toraño, Ignacio; Sánchez Espinoza, Víctor Hugo; Stieglitz, Robert

    2017-01-01

    Highlights: • Reflooding is investigated for selected MBLOCA sequences in a Konvoi PWR using ASTEC. • After SBO, there is a grace time of 40 min up to the detection of a CET = 650 °C. • Major core damage prevented if reflood is launched at CET = 650 °C with 25-40 kg/s. • Values depend on the time when the plant is struck by Station Blackout. • Vessel failure cannot be prevented if supplied mass flow rates are lower than 10 kg/s. - Abstract: The Fukushima accidents have shown that further improvement of Severe Accident Management Guidelines (SAMGs) is necessary for the current fleet of Light Water Reactors. The elaboration of SAMGs requires a broad database of deterministic analyses performed with state-of-the art simulation tools. Within this work, the ASTECV2.0 integral severe accident code is used to study the efficiency of core reflooding (as a SAM measure) during postulated Medium Break LOCA (MBLOCA) scenarios in a German Konvoi PWR. In a first step, the progression of selected MBLOCA sequences without SAM measures has been analysed. The sequences postulate a break in the cold leg of the pressurizer loop and the total loss of AC power at a given stage of the accident. Results show the existence of a 40 min grace time up to the detection of a Core Exit Temperature (CET) of 650 °C providing that the AC power has been maintained at least 1 h after SCRAM. In a second step, an extensive analysis on core reflooding has been carried out. The sequences assume that the plant remains in Station Blackout (SBO) and that reflooding occurs at different times with different mobile pumps. The simulations yield the following results: • Reflooding mass flow rates above 60 kg/s have to be supplied as soon as the CET exceeds 650 °C in order to prevent core melting. • Reflooding mass flow rates ranging from 25–40 kg/s at CET = 650 °C mitigate the accident without major core damage depending on when the plant enters in SBO. • Reflooding mass flow rates lower

  2. Presence of an SH2 domain in the actin-binding protein tensin.

    Science.gov (United States)

    Davis, S; Lu, M L; Lo, S H; Lin, S; Butler, J A; Druker, B J; Roberts, T M; An, Q; Chen, L B

    1991-05-03

    The molecular cloning of the complementary DNA coding for a 90-kilodalton fragment of tensin, an actin-binding component of focal contacts and other submembraneous cytoskeletal structures, is reported. The derived amino acid sequence revealed the presence of a Src homology 2 (SH2) domain. This domain is shared by a number of signal transduction proteins including nonreceptor tyrosine kinases such as Abl, Fps, Src, and Src family members, the transforming protein Crk, phospholipase C-gamma 1, PI-3 (phosphatidylinositol) kinase, and guanosine triphosphatase-activating protein (GAP). Like the SH2 domain found in Src, Crk, and Abl, the SH2 domain of tensin bound specifically to a number of phosphotyrosine-containing proteins from v-src-transformed cells. Tensin was also found to be phosphorylated on tyrosine residues. These findings suggest that by possessing both actin-binding and phosphotyrosine-binding activities and being itself a target for tyrosine kinases, tensin may link signal transduction pathways with the cytoskeleton.

  3. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.

    Science.gov (United States)

    Koch, C A; Anderson, D; Moran, M F; Ellis, C; Pawson, T

    1991-05-03

    Src homology (SH) regions 2 and 3 are noncatalytic domains that are conserved among a series of cytoplasmic signaling proteins regulated by receptor protein-tyrosine kinases, including phospholipase C-gamma, Ras GTPase (guanosine triphosphatase)-activating protein, and Src-like tyrosine kinases. The SH2 domains of these signaling proteins bind tyrosine phosphorylated polypeptides, implicated in normal signaling and cellular transformation. Tyrosine phosphorylation acts as a switch to induce the binding of SH2 domains, thereby mediating the formation of heteromeric protein complexes at or near the plasma membrane. The formation of these complexes is likely to control the activation of signal transduction pathways by tyrosine kinases. The SH3 domain is a distinct motif that, together with SH2, may modulate interactions with the cytoskeleton and membrane. Some signaling and transforming proteins contain SH2 and SH3 domains unattached to any known catalytic element. These noncatalytic proteins may serve as adaptors to link tyrosine kinases to specific target proteins. These observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.

  4. Quantitation of the calcium and membrane binding properties of the C2 domains of dysferlin.

    Science.gov (United States)

    Abdullah, Nazish; Padmanarayana, Murugesh; Marty, Naomi J; Johnson, Colin P

    2014-01-21

    Dysferlin is a large membrane protein involved in calcium-triggered resealing of the sarcolemma after injury. Although it is generally accepted that dysferlin is Ca(2+) sensitive, the Ca(2+) binding properties of dysferlin have not been characterized. In this study, we report an analysis of the Ca(2+) and membrane binding properties of all seven C2 domains of dysferlin as well as a multi-C2 domain construct. Isothermal titration calorimetry measurements indicate that all seven dysferlin C2 domains interact with Ca(2+) with a wide range of binding affinities. The C2A and C2C domains were determined to be the most sensitive, with Kd values in the tens of micromolar, whereas the C2D domain was least sensitive, with a near millimolar Kd value. Mutagenesis of C2A demonstrates the requirement for negatively charged residues in the loop regions for divalent ion binding. Furthermore, dysferlin displayed significantly lower binding affinity for the divalent cations magnesium and strontium. Measurement of a multidomain construct indicates that the solution binding affinity does not change when C2 domains are linked. Finally, sedimentation assays suggest all seven C2 domains bind lipid membranes, and that Ca(2+) enhances but is not required for interaction. This report reveals for the first time, to our knowledge, that all dysferlin domains bind Ca(2+) albeit with varying affinity and stoichiometry. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. Surveillance and Measurement System (SAMS). Innovative Technology Summary Report

    International Nuclear Information System (INIS)

    2001-01-01

    The United States Department of Energy (DOE) continually seeks safer and more cost-effective technologies for the decontamination and decommissioning (D and D) of nuclear facilities. The Deactivation and Decommissioning Focus Area (DDFA) of the DOE's Office of Science and Technology sponsors large-scale demonstration and deployment projects (LSDDPs) to identify and demonstrate technologies that will be safer and more cost-effective. At these LSDDPs, developers and vendors of improved or innovative technologies showcase products that are potentially beneficial to the DOE's projects as well as others in the D and D community. Benefits sought include decreased health and safety risks to personnel and the environment, increased productivity, and decreased cost of operation. The Idaho National Engineering and Environmental Laboratory (INEEL) LSDDP generated a list of need statements defining specific needs or problems where improved technologies could be incorporated into ongoing D and D tasks. Advances in characterization technologies are continuously being sought to decrease the cost of sampling and increase the speed of obtaining results. Currently it can take as long as 90 days to receive isotopic analysis of radioactive samples from laboratories on soil, liquid, and paint samples. The cost to analyze these types of samples for radionuclides is about $150 per sample. This demonstration investigated the feasibility of using the Surveillance and Measurement System (SAMS) (innovative technology) to make in situ isotopic radiation measurements in paint and soil. Sample collection and on-site laboratory analysis (baseline technology) is currently being used on D and D sampling activities. Benefits expected from using the innovative technology include: Significant decrease in time to receive results on radiological samples; Decrease in cost associated with sample collection, preparation, analysis, and disposal; Equivalent data quality to laboratory analysis; and Fewer

  6. Improving discrimination of savanna tree species through a multiple endmember spectral-angle-mapper (SAM) approach: canopy level analysis

    CSIR Research Space (South Africa)

    Cho, Moses A

    2010-11-01

    Full Text Available sensing. The objectives of this paper were to (i) evaluate the classification performance of a multiple-endmember spectral angle mapper (SAM) classification approach (conventionally known as the nearest neighbour) in discriminating ten common African...

  7. Séries temporais de NDVI do sensor SPOT Vegetation e algoritmo SAM aplicados ao mapeamento de cana‑de‑açúcar

    Directory of Open Access Journals (Sweden)

    Luiz Eduardo Vicente

    2012-09-01

    Full Text Available O objetivo deste trabalho foi avaliar o mapeamento de área de cana‑de‑açúcar por meio de série temporal, de seis anos de dados do índice de vegetação por diferença normalizada (NDVI, oriundos do sensor Vegetation, a bordo do satélite "système pour l'observation de la Terre" (SPOT. Três classes de cobertura do solo (cana‑de‑açúcar, pasto e floresta, do Estado de São Paulo, foram selecionadas como assinaturas espectro‑temporais de referência, que serviram como membros extremos ("endmembers" para classificação com o algoritmo "spectral angle mapper" (SAM. A partir desta classificação, o mapeamento da área de cana‑de‑açúcar foi realizado com uso de limiares na imagem-regra do SAM, gerados a partir dos valores dos espectros de referência. Os resultados mostram que o algoritmo SAM pode ser aplicado a séries de dados multitemporais de resolução moderada, o que permite eficiente mapeamento de alvo agrícola em escala mesorregional. Dados oficiais de áreas de cana‑de‑açúcar, para as microrregiões paulistas, apresentam boa correlação (r² = 0,8 com os dados obtidos pelo método avaliado. A aplicação do algoritmo SAM mostrou ser útil em análises temporais. As séries temporais de NDVI do sensor SPOT Vegetation podem ser utilizadas para mapeamento da área de cana‑de‑açúcar em baixa resolução.

  8. Functional diversity of Csk, Chk, and Src SH2 domains due to a single residue variation.

    Science.gov (United States)

    Ayrapetov, Marina K; Nam, Nguyen Hai; Ye, Guofeng; Kumar, Anil; Parang, Keykavous; Sun, Gongqin

    2005-07-08

    The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk). Both phosphorylate and inactivate Src family kinases. Recent reports suggest that the Src homology (SH) 2 domains of Csk and Chk may bind to different phosphoproteins, which provides a basis for different cellular functions for Csk and Chk. To verify and characterize such a functional divergence, we compared the binding properties of the Csk, Chk, and Src SH2 domains and investigated the structural basis for the functional divergence. First, the study demonstrated striking functional differences between the Csk and Chk SH2 domains and revealed functional similarities between the Chk and Src SH2 domains. Second, structural analysis and mutagenic studies revealed that the functional differences among the three SH2 domains were largely controlled by one residue, Glu127 in Csk, Ile167 in Chk, and Lys200 in Src. Mutating these residues in the Csk or Chk SH2 domain to the Src counterpart resulted in dramatic gain of function similar to Src SH2 domain, whereas mutating Lys200 in Src SH2 domain to Glu (the Csk counterpart) resulted in loss of Src SH2 function. Third, a single point mutation of E127K rendered Csk responsive to activation by a Src SH2 domain ligand. Finally, the optimal phosphopeptide sequence for the Chk SH2 domain was determined. These results provide a compelling explanation for the functional differences between two homologous protein tyrosine kinases and reveal a new structure-function relationship for the SH2 domains.

  9. Structures of BIR domains from human NAIP and cIAP2

    International Nuclear Information System (INIS)

    Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

    2009-01-01

    The crystal structures of the human NAIP BIR2 and cIAP2 BIR3 domains have been determined. Both BIR domains harbors an amino-terminal tetrapeptide in its peptide-binding groove. The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1′–P4′ side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3′ position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2′ and P4′ pockets make similar interactions to those seen in other BIR domain–peptide complexes. The structures also reveal how a serine in the P1′ position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins

  10. Time-resolved multimodal analysis of Src Homology 2 (SH2) domain binding in signaling by receptor tyrosine kinases.

    Science.gov (United States)

    Jadwin, Joshua A; Oh, Dongmyung; Curran, Timothy G; Ogiue-Ikeda, Mari; Jia, Lin; White, Forest M; Machida, Kazuya; Yu, Ji; Mayer, Bruce J

    2016-04-12

    While the affinities and specificities of SH2 domain-phosphotyrosine interactions have been well characterized, spatio-temporal changes in phosphosite availability in response to signals, and their impact on recruitment of SH2-containing proteins in vivo, are not well understood. To address this issue, we used three complementary experimental approaches to monitor phosphorylation and SH2 binding in human A431 cells stimulated with epidermal growth factor (EGF): 1) phospho-specific mass spectrometry; 2) far-Western blotting; and 3) live cell single-molecule imaging of SH2 membrane recruitment. Far-Western and MS analyses identified both well-established and previously undocumented EGF-dependent tyrosine phosphorylation and binding events, as well as dynamic changes in binding patterns over time. In comparing SH2 binding site phosphorylation with SH2 domain membrane recruitment in living cells, we found in vivo binding to be much slower. Delayed SH2 domain recruitment correlated with clustering of SH2 domain binding sites on the membrane, consistent with membrane retention via SH2 rebinding.

  11. Reply [to: Atlantic Tropical Cyclogenetic Processes during SOP-3 NAMMA in the GEOS-5 Global Data Assimilation and Forecast System

    Science.gov (United States)

    Reale, Oreste; Lau, William K.

    2010-01-01

    This article is a Reply to a Comment by Scott Braun on a previously published article by O. Reale, K.-M. Lau, and E. Brin: "Atlantic tropical cyclogenetic processes during SOP-3 NAMMA in the GEOS-5 global data assimilation and forecast system", by Reale, Lau and Brin, hereafter referred to as RA09. RA09 investigated the role of the Saharan Air Layer (SAL) in tropical cyclogenetic processes associated with a non-developing easterly wave observed during the Special Observation Period (SOP-3) phase of the 2006 NASA African Monsoon Multidisciplinary Analyses (MAMMA). The wave was chosen because both interact heavily with Saharan air. Results showed: a) very steep moisture gradients are associated with the SAL in forecasts and analyses even at great distance from the Sahara; b) a thermal dipole (warm above, cool below) in the non-developing case. RA09A suggested that radiative effect of dust may play some role in producing a thermal structure less favorable to cyclogenesis, and also indicated that only global horizontal resolutions on the order of 20-30 kilometers can capture the large-scale transport and the fine thermal structure of the SAL Braun (2010) questions those results attributing the wave dissipation to midlatitude air. The core discussion is on a dry filament preceding the wave, on the presence of dust, and on the origin of the air contained in this dry filament. In the 'Reply', higher resolution analyses than the ones used by Braun, taken at almost coincident times with Aqua and Terra passes, are shown, to emphasize how the channel of dry air associated with W1 is indeed rich in dust. Backtrajectories on a higher resolution grid are also performed, leading to results drastically different from Braun (2010), and in particularly showing that there is a clear contribution of Saharan air. Finally, the 'Reply' presents evidence on that analyses at a horizontal resolution of one degree are inadequate to investigate such feature.

  12. Systematic substrate adoption methodology (SAM) for future flexible, generic pharmaceutical production processes

    DEFF Research Database (Denmark)

    Singh, Ravendra; Godfrey, Andy; Gregertsen, Björn

    2013-01-01

    (APIs) for early delivery campaigns. Of these candidates only a few will be successful such that further development is required to scale-up the process. Systematic computer-aided methods and tools are required for faster manufacturing of these API candidates. In this work, a substrate adoption...... methodology (SAM) for a series of substrates with similar molecular functionality has been developed. The objective is to achieve “flexible, fast and future” pharmaceutical production processes by adapting a generic modular process template. Application of the methodology is illustrated through a case study...

  13. A sum-over-paths algorithm for third-order impulse-response moment extraction within RC IC-interconnect networks

    Science.gov (United States)

    Wojcik, E. A.; Ni, D.; Lam, T. M.; Le Coz, Y. L.

    2015-07-01

    We have created the first stochastic SoP (Sum-over-Paths) algorithm to extract third-order impulse-response (IR) moment within RC IC interconnects. It employs a newly discovered Feynman SoP Postulate. Importantly, our algorithm maintains computational efficiency and full parallelism. Our approach begins with generation of s-domain nodal-voltage equations. We then perform a Taylor-series expansion of the circuit transfer function. These expansions yield transition diagrams involving mathematical coupling constants, or weight factors, in integral powers of complex frequency s. Our SoP Postulate enables stochastic evaluation of path sums within the circuit transition diagram to order s3-corresponding to the order of IR moment (m3) we seek here. We furnish, for the first time, an informal algebraic proof independently validating our SoP Postulate and algorithm. We list, as well, detailed procedural steps, suitable for coding, that define an efficient stochastic algorithm for m3 IR extraction. Origins of the algorithm's statistical "capacitor-number cubed" correction and "double-counting" weight factors are explained, for completeness. Our algorithm was coded and successfully tested against exact analytical solutions for 3-, 5-, and 10-stage RC lines. We achieved better than 0.65% 1-σ error convergence, after only 10K statistical samples, in less than 1 s of 2-GHz Pentium® execution time. These results continue to suggest that stochastic SoP algorithms may find useful application in circuit analysis of massively coupled networks, such as those encountered in high-end digital IC-interconnect CAD.

  14. Detecting Organic Compounds Released from Iron Oxidizing Bacteria using Sample Analysis at Mars (SAM) Like Instrument Protocols

    Science.gov (United States)

    Glavin, D. P.; Popa, R.; Martin, M. G.; Freissinet, C.; Fisk, M. R.; Dworkin, J. P.; Mahaffy, P. R.

    2012-01-01

    Mars is a planet of great interest for Astrobiology since its past environmental conditions are thought to have been favourable for the emergence life. At present, the Red Planet is extremely cold and dry and the surface is exposed to intense UV and ionizing radiation, conditions generally considered to be incompatible with life as we know it on Earth. It was proposed that the shallow subsurface of Mars, where temperatures can be above freezing and liquid water can exist on rock surfaces, could harbor chemolithoautotrophic bacteria such as the iron oxidizing microorganism Pseudomonas sp. HerB. The Mars Science Laboratory (MSL) mission will provide the next opportunity to carry out in situ measurements for organic compounds of possible biological origin on Mars. One instrument onboard MSL, called the Sample Analysis at Mars (SAM) instrument suite, will carry out a broad and sensitive search for organic compounds in surface samples using either high temperature pyrolysis or chemical extraction followed by gas chromatography mass spectrometry. We present gas chromatograph mass spectrometer (GC/MS) data on crushed olivine rock powders that have been inoculated with Pseudomonas sp. HerB at different concentrations ranging from approx 10(exp 2) to 10(exp 7) cells per gram. The inoculated olivine samples were heated under helium carrier gas flow at 500 C and the pyrolysis products concentrated using a SAM-like hydrocarbon trap set at -20 C followed by trap heating and analysis by GC/Ms. In addition, the samples were also extracted using a low temperature "one-pot" chemical extraction technique using N-methyl, N-(tert-butyldimethylsilyl) trifluoroacetamide (MTBSTFA) as the silylating agent prior to GC/MS analysis. We identified several aldehydes, thiols, and alkene nitriles after pyrolysis GC/MS analysis of the bacteria that were not found in the olivine control samples that had not been inoculated with bacteria. The distribution of pyrolysis products extracted from the

  15. Hydrogeological characterisation and modelling of deformation zones and fracture domains, Forsmark modelling stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Follin, Sven (SF GeoLogic AB, Taeby (SE)); Leven, Jakob (Swedish Nuclear Fuel and Waste Management Co., Stockholm (SE)); Hartley, Lee; Jackson, Peter; Joyce, Steve; Roberts, David; Swift, Ben (Serco Assurance, Harwell (GB))

    2007-09-15

    The work reported here collates the structural-hydraulic information gathered in 21 cored boreholes and 32 percussion-drilled boreholes belonging to Forsmark site description, modelling stage 2.2. The analyses carried out provide the hydrogeological input descriptions of the bedrock in Forsmark needed by the end users Repository Engineering, Safety Assessment and Environmental Impact Assessment; that is, hydraulic properties of deformation zones and fracture domains. The same information is also needed for constructing 3D groundwater flow models of the Forsmark site and surrounding area. The analyses carried out render the following conceptual model regarding the observed heterogeneity in deformation zone transmissivity: We find the geological division of the deterministically modelled deformation zones into eight categories (sets) useful from a hydrogeological point of view. Seven of the eight categories are steeply dipping, WNW, NW, NNW, NNE, NE, ENE and EW, and on is gently dipping, G. All deformation zones, regardless of orientation (strike and dip), are subjected to a substantial decrease in transmissivity with depth. The data gathered suggest a contrast of c. 20,000 times for the uppermost one kilometre of bedrock, i.e. more than four orders of magnitude. The hydraulic properties below this depth are not investigated. The lateral heterogeneity is also substantial but more irregular in its appearance. For instance, for a given elevation and deformation zone category (orientation), the spatial variability in transmissivity within a particular deformation zone appears to be as large as the variability between all deformation zones. This suggests that the lateral correlation length is shorter than the shortest distance between two adjacent observation points and shorter than the category spacing. The observation that the mean transmissivity of the gently-dipping deformation zones is c. one to two orders of magnitude greater than the mean transmissivities of all

  16. Shear at Twin Domain Boundaries in YBa2Cu3O7-x

    Science.gov (United States)

    Caldwell, W. A.; Tamura, N.; Celestre, R. S.; MacDowell, A. A.; Padmore, H. A.; Geballe, T. H.; Koster, G.; Batterman, B. W.; Patel, J. R.

    2004-05-01

    The microstructure and strain state of twin domains in YBa2Cu3O7-x are discussed based upon synchrotron white-beam x-ray microdiffraction measurements. Intensity variations of the fourfold twin splitting of Laue diffraction peaks are used to determine the twin domain structure. Strain analysis shows that interfaces between neighboring twin domains are strained in shear, whereas the interior of these domains are regions of low strain. These measurements are consistent with the orientation relationships of twin boundaries within and across domains and show that basal plane shear stresses can exceed 100MPa where twin domains meet. Our results support stress field pinning of magnetic flux vortices by twin domain boundaries.

  17. PDS4 vs PDS3 - A Comparison of PDS Data for Two Mars Rovers - Existing Mars Curiosity Mission Mass Spectrometer (SAM) PDS3 Data vs Future ExoMars Rover Mass Spectrometer (MOMA) PDS4 Data

    Science.gov (United States)

    Lyness, E.; Franz, H. B.; Prats, B.

    2017-12-01

    The Sample Analysis at Mars (SAM) instrument is a suite of instruments on Mars aboard the Mars Science Laboratory rover. Centered on a mass spectrometer, SAM delivers its data to the PDS Atmosphere's node in PDS3 format. Over five years on Mars the process of operating SAM has evolved and extended significantly from the plan in place at the time the PDS3 delivery specification was written. For instance, SAM commonly receives double or even triple sample aliquots from the rover's drill. SAM also stores samples in spare cups for long periods of time for future analysis. These unanticipated operational changes mean that the PDS data deliveries are absent some valuable metadata without which the data can be confusing. The Mars Organic Molecule Analyzer (MOMA) instrument is another suite of instruments centered on a mass spectrometer bound for Mars. MOMA is part of the European ExoMars rover mission schedule to arrive on Mars in 2021. While SAM and MOMA differ in some important scientific ways - MOMA uses an linear ion trap compared to the SAM quadropole mass spectrometer and MOMA has a laser desorption experiment that SAM lacks - the data content from the PDS point of view is comparable. Both instruments produce data containing mass spectra acquired from solid samples collected on the surface of Mars. The MOMA PDS delivery will make use of PDS4 improvements to provide a metadata context to the data. The MOMA PDS4 specification makes few assumptions of the operational processes. Instead it provides a means for the MOMA operators to provide the important contextual metadata that was unanticipated during specification development. Further, the software tools being developed for instrument operators will provide a means for the operators to add this crucial metadata at the time it is best know - during operations.

  18. SH2 Binding Site Protection Assay: A Method for Identification of SH2 Domain Interaction Partners by Exploiting SH2 Mediated Phosphosite Protection.

    Science.gov (United States)

    Jadwin, Joshua A

    2017-01-01

    Over the last two decades there has been a significant effort in the field to characterize the phosphosite binding specificities of SH2 domains with the goal of deciphering the pY signaling code. Although high throughput studies in various formats using most SH2 domains have collectively provided a rich resource of in vitro SH2-pTyr site specificity maps, this data can only be used approximate what is happening in the cell where protein concentrations and localization are not homogenous, as they are for in vitro experiments. Here we describe an in vivo approach, SH2 site protection assay, which can capture the pTyr binding specificity of SH2 domains in the cell. The basis of this approach is SH2-pY site protection, the ability of SH2 domains to prevent the PTP-dependent dephosphorylation of their pY site binding partners. We overexpress a tracer SH2 domain in cells and quantify the change in abundance of tyrosine phosphorylated sites using MS. Since the method is performed in vivo, it has the advantage of identifying SH2-pY interactions as they occur within in the cell.

  19. A novel calmodulin-regulated Ca2+-ATPase (ACA2) from Arabidopsis with an N-terminal autoinhibitory domain

    Science.gov (United States)

    Harper, J. F.; Hong, B.; Hwang, I.; Guo, H. Q.; Stoddard, R.; Huang, J. F.; Palmgren, M. G.; Sze, H.; Evans, M. L. (Principal Investigator)

    1998-01-01

    To study transporters involved in regulating intracellular Ca2+, we isolated a full-length cDNA encoding a Ca2+-ATPase from a model plant, Arabidopsis, and named it ACA2 (Arabidopsis Ca2+-ATPase, isoform 2). ACA2p is most similar to a "plasma membrane-type" Ca2+-ATPase, but is smaller (110 kDa), contains a unique N-terminal domain, and is missing a long C-terminal calmodulin-binding regulatory domain. In addition, ACA2p is localized to an endomembrane system and not the plasma membrane, as shown by aqueous-two phase fractionation of microsomal membranes. ACA2p was expressed in yeast as both a full-length protein (ACA2-1p) and an N-terminal truncation mutant (ACA2-2p; Delta residues 2-80). Only the truncation mutant restored the growth on Ca2+-depleted medium of a yeast mutant defective in both endogenous Ca2+ pumps, PMR1 and PMC1. Although basal Ca2+-ATPase activity of the full-length protein was low, it was stimulated 5-fold by calmodulin (50% activation around 30 nM). In contrast, the truncated pump was fully active and insensitive to calmodulin. A calmodulin-binding sequence was identified within the first 36 residues of the N-terminal domain, as shown by calmodulin gel overlays on fusion proteins. Thus, ACA2 encodes a novel calmodulin-regulated Ca2+-ATPase distinguished by a unique N-terminal regulatory domain and a non-plasma membrane localization.

  20. Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains.

    Science.gov (United States)

    Sha, Fern; Gencer, Emel Basak; Georgeon, Sandrine; Koide, Akiko; Yasui, Norihisa; Koide, Shohei; Hantschel, Oliver

    2013-09-10

    The dysregulated tyrosine kinase BCR-ABL causes chronic myelogenous leukemia in humans and forms a large multiprotein complex that includes the Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2). The expression of SHP2 is necessary for BCR-ABL-dependent oncogenic transformation, but the precise signaling mechanisms of SHP2 are not well understood. We have developed binding proteins, termed monobodies, for the N- and C-terminal SH2 domains of SHP2. Intracellular expression followed by interactome analysis showed that the monobodies are essentially monospecific to SHP2. Two crystal structures revealed that the monobodies occupy the phosphopeptide-binding sites of the SH2 domains and thus can serve as competitors of SH2-phosphotyrosine interactions. Surprisingly, the segments of both monobodies that bind to the peptide-binding grooves run in the opposite direction to that of canonical phosphotyrosine peptides, which may contribute to their exquisite specificity. When expressed in cells, monobodies targeting the N-SH2 domain disrupted the interaction of SHP2 with its upstream activator, the Grb2-associated binder 2 adaptor protein, suggesting decoupling of SHP2 from the BCR-ABL protein complex. Inhibition of either N-SH2 or C-SH2 was sufficient to inhibit two tyrosine phosphorylation events that are critical for SHP2 catalytic activity and to block ERK activation. In contrast, targeting the N-SH2 or C-SH2 revealed distinct roles of the two SH2 domains in downstream signaling, such as the phosphorylation of paxillin and signal transducer and activator of transcription 5. Our results delineate a hierarchy of function for the SH2 domains of SHP2 and validate monobodies as potent and specific antagonists of protein-protein interactions in cancer cells.

  1. Microbial Habitability in Gale Crater: Sample Analysis at Mars (SAM) Instrument Detection of Microbial Essential Carbon and Nitrogen

    Science.gov (United States)

    Sutter, B.; Ming, D. W.; Eigenbrode, J. E.; Steele, A.; Stern, J. C.; Gonzalez, R. N.; McAdam, A. C.; Mahaffy, P. R.

    2016-01-01

    Chemical analyses of Mars soils and sediments from previous landed missions have demonstrated that Mars surface materials possessed major (e.g., P, K, Ca, Mg, S) and minor (e.g., Fe, Mn, Zn, Ni, Cl) elements essential to support microbial life. However, the detection of microbial essential organic-carbon (C) and nitrate have been more elusive until the Mars Science Laboratory (MSL) rover mission. Nitrate and organic-C in Gale Crater, Mars have been detected by the Sample Analysis at Mars (SAM) instrument onboard the MSL Curiosity rover. Eolian fines and drilled sedimentary rock samples were heated in the SAM oven from approximately 30 to 860 degrees Centigrade where evolved gases (e.g., nitrous oxide (NO) and CO2) were released and analyzed by SAM’s quadrupole mass spectrometer (MS). The temperatures of evolved NO was assigned to nitrate while evolved CO2 was assigned to organic-C and carbonate. The CO2 releases in several samples occurred below 450 degrees Centigrade suggesting organic-C dominated in those samples. As much as 7 micromoles NO3-N per gram and 200 micromoles CO2-C per gram have been detected in the Gale Crater materials. These N and C levels coupled with assumed microbial biomass (9 x 10 (sup -7) micrograms per cell) C (0.5 micrograms C per micrograms cell) and N (0.14 micrograms N per micrograms cell) requirements, suggests that less than 1 percent and less than 10 percent of Gale Crater C and N, respectively, would be required if available, to accommodate biomass requirements of 1 by 10 (sup 5) cells per gram sediment. While nitrogen is the limiting nutrient, the potential exists that sufficient N and organic-C were present to support limited heterotrophic microbial populations that may have existed on ancient Mars.

  2. Environmental Sciences Division Toxicology Laboratory standard operating procedures

    International Nuclear Information System (INIS)

    Kszos, L.A.; Stewart, A.J.; Wicker, L.F.; Logsdon, G.M.

    1989-09-01

    This document was developed to provide the personnel working in the Environmental Sciences Division's Toxicology Laboratory with documented methods for conducting toxicity tests. The document consists of two parts. The first part includes the standard operating procedures (SOPs) that are used by the laboratory in conducting toxicity tests. The second part includes reference procedures from the US Environmental Protection Agency document entitled Short-Term Methods for Estimating the Chronic Toxicity of Effluents and Receiving Waters to Freshwater Organisms, upon which the Toxicology Laboratory's SOPs are based. Five of the SOPs include procedures for preparing Ceriodaphnia survival and reproduction test. These SOPs include procedures for preparing Ceriodaphnia food (SOP-3), maintaining Ceriodaphnia cultures (SOP-4), conducting the toxicity test (SOP-13), analyzing the test data (SOP-13), and conducting a Ceriodaphnia reference test (SOP-15). Five additional SOPs relate specifically to the fathead minnow (Pimephales promelas) larval survival and growth test: methods for preparing fathead minnow larvae food (SOP-5), maintaining fathead minnow cultures (SOP-6), conducting the toxicity test (SOP-9), analyzing the test data (SOP-12), and conducting a fathead minnow reference test (DOP-14). The six remaining SOPs describe methods that are used with either or both tests: preparation of control/dilution water (SOP-1), washing of glassware (SOP-2), collection and handling of samples (SOP-7), preparation of samples (SOP-8), performance of chemical analyses (SOP-11), and data logging and care of technical notebooks (SOP-16)

  3. Efecto bioestimulante de Trichoderma harzianum Rifai en posturas de Leucaena, Cedro y Samán

    Directory of Open Access Journals (Sweden)

    Leonides Castellanos González

    2018-01-01

    Full Text Available El presente artículo evaluó el efecto bioestimulante de Trichoderma harzianum Rifai en la producción de postura de Leucaena leucocephala (Lam de Wit., Cedrela odorata L. y Albizia saman (Jacq. Merr. Se desarrollaron tres experimentos en condiciones de vivero, uno para cada especie. Se empleó un diseño completamente aleatorio con cuatro parcelas por tratamiento. En cada experimento los tratamientos fueron: Trichoderma harzianum a razón de 20 g.L-1, 40 g.L-1 y un testigo. Se evaluó el porcentaje de germinación y las variables morfométricas diámetro y altura del tallo, así como biomasa seca en raíz y parte aérea de la planta. Los tratamientos con Trichoderma no incrementaron el porcentaje de germinación en cedro, samán y leucaena. T. harzianum incrementó la altura, el número de hojas y la biomasa seca del área foliar en las plántulas de cedro, mientras que en leucaena y samán solo provocó incrementos del diámetro basal de las plántulas.

  4. Orientational analysis of dodecanethiol and p-nitrothiophenol SAMs on metals with polarisation-dependent SFG spectroscopy.

    Science.gov (United States)

    Cecchet, Francesca; Lis, Dan; Guthmuller, Julien; Champagne, Benoît; Caudano, Yves; Silien, Christophe; Mani, Alaa Addin; Thiry, Paul A; Peremans, André

    2010-02-22

    Polarisation-dependent sum frequency generation (SFG) spectroscopy is used to investigate the orientation of molecules on metallic surfaces. In particular, self-assembled monolayers (SAMs) of dodecanethiol (DDT) and of p-nitrothiophenol (p-NTP), grown on Pt and on Au, have been chosen as models to highlight the ability of combining ppp and ssp polarisations sets (representing the polarisation of the involved beams in the conventional order of SFG, Vis and IR beam) to infer orientational information at metallic interfaces. Indeed, using only the ppp set of data, as it is usually done for metallic surfaces, is not sufficient to determine the full molecular orientation. We show here that simply combining ppp and ssp polarisations enables both the tilt and rotation angles of methyl groups in DDT SAMs to be determined. Moreover, for p-NTP, while the SFG active vibrations detected with the ppp polarisation alone provide no orientational information, however, the combination with ssp spectra enables to retrieve the tilt angle of the p-NTP 1,4 axis. Though orientational information obtained by polarisation-dependent measurements has been extensively used at insulating interfaces, we report here their first application to metallic surfaces.

  5. Orientational Analysis of Dodecanethiol and P-Nitrothiophenol SAMs on Metals with Polarisation - dependent SFG spectroscopy

    International Nuclear Information System (INIS)

    Manea, A.

    2011-01-01

    Polarisation-dependent sum frequency generation (SFG) spectroscopy is used to investigate the orientation of molecules on metallic surfaces. In particular, self-assembled monolayers (SAMs) of dodecanethiol (DDT) and of p-nitro thiophenol (p-NTP), grown on Pt and on Au, have been chosen as models to highlight the ability of combining ppp and ssp polarizations sets (representing the polarisation of the involved beams in the conventional order of SFG, Vis and IR beam) to infer orientational information at metallic interfaces. Indeed, using only the ppp set of data, as it is usually done for metallic surfaces, is not sufficient to determine the full molecular orientation. We show here that simply combining ppp and ssp polarizations enables both the tilt and rotation angles of methyl groups in DDT SAMs to be determined. Moreover, for p-NTP, while the SFG active vibrations detected with the ppp polarisation alone provide no orientational information, however, the combination with ssp spectra enables to retrieve the tilt angle of the p-NTP 1,4 axis. Though orientational information obtained by polarisation-dependent measurements has been extensively used at insulating interfaces, we report here their first application to metallic surfaces. (author)

  6. Data-Aided Frequency-Domain 2×2 MIMO Equalizer for 112 Gbit/s PDM-QPSK Coherent Transmission Systems

    DEFF Research Database (Denmark)

    Pittalà, Fabio; Hauske, Fabian N.; Ye, Yabin

    2012-01-01

    Benefits of a low-complexity adaptive 32-tap 2×2 MIMO frequency-domain filter update by data-aided channel estimation over a time-domain filter with DD-LMS are shown. Superior stability and convergence speed is demonstrated with identical impairment tolerance....

  7. Effectivity System of Management Information in Information Tehcnology Center University of Sam Ratulangi Manado.

    OpenAIRE

    Kalalo, Intani Kirana; Mandey, Jantje; Pombengi, Jericho

    2015-01-01

    In accordance with Regulation of the Minister of Education and Culture of the Republic of Indonesia on the Organization and Work of Sam Ratulangi University of article 105, paragraph 1, which states that the Information and Communication Technology Unit is a unit of the technical implementation in the field of development and management of systems and information and communication technology. And Article 106, namely, Information and Communication Technology Unit has the t...

  8. Kualitas Udara Beberapa Ruang Perpustakaan Di Universitas Sam Ratulangi Manado Berdasarkan Uji Kualitas Fisika

    OpenAIRE

    Sahilatua, Josefine D

    2014-01-01

    : Air pollution not only comes from the outdoors but also indoors. Library is indoors that could potentially by polluted. Level of air quality that not complies the standard will cause symptoms such as sneezing, coughing, skin irritation, shortness of breathing, eye irritation and headache on library users. This research conducted on the five libraries at the Sam Ratulangi University using observational methods. Data collected was content of physical air quality. The variables were air temper...

  9. Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase.

    Science.gov (United States)

    Kulkarni, Shilpa; Das, Sudipto; Funk, Colin D; Murray, Diana; Cho, Wonhwa

    2002-04-12

    The activation of 5-lipoxygenase (5-LO) involves its calcium-dependent translocation to the nuclear envelope, where it catalyzes the two-step transformation of arachidonic acid into leukotriene A(4), leading to the synthesis of various leukotrienes. To understand the mechanism by which 5-LO is specifically targeted to the nuclear envelope, we studied the membrane binding properties of the amino-terminal domain of 5-LO, which has been proposed to have a C2 domain-like structure. The model building, electrostatic potential calculation, and in vitro membrane binding studies of the isolated C2-like domain of 5-LO and selected mutants show that this Ca(2+)-dependent domain selectively binds zwitterionic phosphatidylcholine, which is conferred by tryptophan residues (Trp(13), Trp(75), and Trp(102)) located in the putative Ca(2+)-binding loops. The spatiotemporal dynamics of the enhanced green fluorescence protein-tagged C2-like domain of 5-LO and mutants in living cells also show that the phosphatidylcholine selectivity of the C2-like domain accounts for the specific targeting of 5-LO to the nuclear envelope. Together, these results show that the C2-like domain of 5-LO is a genuine Ca(2+)-dependent membrane-targeting domain and that the subcellular localization of the domain is governed in large part by its membrane binding properties.

  10. Diversity in peptide recognition by the SH2 domain of SH2B1.

    Science.gov (United States)

    McKercher, Marissa A; Guan, Xiaoyang; Tan, Zhongping; Wuttke, Deborah S

    2018-02-01

    SH2B1 is a multidomain protein that serves as a key adaptor to regulate numerous cellular events, such as insulin, leptin, and growth hormone signaling pathways. Many of these protein-protein interactions are mediated by the SH2 domain of SH2B1, which recognizes ligands containing a phosphorylated tyrosine (pY), including peptides derived from janus kinase 2, insulin receptor, and insulin receptor substrate-1 and -2. Specificity for the SH2 domain of SH2B1 is conferred in these ligands either by a hydrophobic or an acidic side chain at the +3 position C-terminal to the pY. This specificity for chemically disparate species suggests that SH2B1 relies on distinct thermodynamic or structural mechanisms to bind to peptides. Using binding and structural strategies, we have identified unique thermodynamic signatures for each peptide binding mode, and several SH2B1 residues, including K575 and R578, that play distinct roles in peptide binding. The high-resolution structure of the SH2 domain of SH2B1 further reveals conformationally plastic protein loops that may contribute to the ability of the protein to recognize dissimilar ligands. Together, numerous hydrophobic and electrostatic interactions, in addition to backbone conformational flexibility, permit the recognition of diverse peptides by SH2B1. An understanding of this expanded peptide recognition will allow for the identification of novel physiologically relevant SH2B1/peptide interactions, which can contribute to the design of obesity and diabetes pharmaceuticals to target the ligand-binding interface of SH2B1 with high specificity. © 2017 Wiley Periodicals, Inc.

  11. Surface barrier analysis of semi-insulating and n{sup +}-type GaAs(0 0 1) following passivation with n-alkanethiol SAMs

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Gregory M. [Laboratory for Quantum Semiconductors and Photon-Based BioNanotechnology, Department of Electrical and Computer Engineering, Universite de Sherbrooke, Sherbrooke, Quebec, J1K 2R1 (Canada); Institute for Chemical Process and Environmental Technology, National Research Council of Canada, Ottawa, Ontario, K1A 0R6 (Canada); Bensebaa, Farid [Institute for Chemical Process and Environmental Technology, National Research Council of Canada, Ottawa, Ontario, K1A 0R6 (Canada); Dubowski, Jan J., E-mail: jan.j.dubowski@usherbrooke.ca [Laboratory for Quantum Semiconductors and Photon-Based BioNanotechnology, Department of Electrical and Computer Engineering, Universite de Sherbrooke, Sherbrooke, Quebec, J1K 2R1 (Canada)

    2011-02-15

    The surface Fermi level of semi-insulating and n{sup +}-type GaAs(0 0 1) was determined before and after passivation with n-alkanethiol self-assembled monolayers (SAMs) by X-ray photoelectron spectroscopy. Fermi level positioning was achieved using Au calibration pads integrated directly onto the GaAs surface, prior to SAM deposition, in order to provide a surface equipotential binding energy reference. Fermi level pinning within 50 meV and surface barrier characteristics according to the Advanced Unified Defect Model were observed. Our results demonstrate the effectiveness of the Au integration technique for the determination of band-edge referenced Fermi level positions and are relevant to an understanding of emerging technologies based on the molecular-semiconductor junction.

  12. Purification, crystallization and preliminary crystallographic analysis of the SH2 domain of IL-2-inducible T-cell kinase.

    Science.gov (United States)

    Joseph, Raji E; Ginder, Nathaniel D; Hoy, Julie A; Nix, Jay C; Honzatko, Richard B; Andreotti, Amy H

    2011-02-01

    Proline is a unique amino acid owing to the relatively small energy difference between the cis and trans conformations of its peptide bond. The X-Pro imide bond readily undergoes cis-trans isomerization in the context of short peptides as well as some proteins. However, the direct detection of cis-trans proline isomerization in folded proteins is technically challenging. NMR spectroscopy is well suited to the direct detection of proline isomerization in folded proteins. It is less clear how well X-ray crystallography can reveal this conformational exchange event in folded proteins. Conformational heterogeneity owing to cis-trans proline isomerization in the Src homology 2 (SH2) domain of the IL-2-inducible T-cell kinase (ITK) has been extensively characterized by NMR. Using the ITK SH2 domain as a test system, an attempt was made to determine whether proline isomerization could be detected in a crystal structure of the ITK SH2 domain. As a first step towards this goal, the purification, crystallization and preliminary characterization of the ITK SH2 domain are described.

  13. Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB.

    Science.gov (United States)

    Zeng, Lei; Kuti, Miklos; Mujtaba, Shiraz; Zhou, Ming-Ming

    2014-07-01

    The fibroblast growth factor receptor (FGFR) substrate 2 (FRS2) family proteins function as scaffolding adapters for receptor tyrosine kinases (RTKs). The FRS2α proteins interact with RTKs through the phosphotyrosine-binding (PTB) domain and transfer signals from the activated receptors to downstream effector proteins. Here, we report the nuclear magnetic resonance structure of the FRS2α PTB domain bound to phosphorylated TrkB. The structure reveals that the FRS2α-PTB domain is comprised of two distinct but adjacent pockets for its mutually exclusive interaction with either nonphosphorylated juxtamembrane region of the FGFR, or tyrosine phosphorylated peptides TrkA and TrkB. The new structural insights suggest rational design of selective small molecules through targeting of the two conjunct pockets in the FRS2α PTB domain. © 2014 Wiley Periodicals, Inc.

  14. Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2

    International Nuclear Information System (INIS)

    Ivancic, Monika; Daly, Roger J.; Lyons, Barbara A.

    2003-01-01

    The solution structure of the hGrb7-SH2 domain in complex with a ten amino acid phosphorylated peptide ligand representative of the erbB2 receptor tyrosine kinase (pY1139) is presented as determined by nuclear magnetic resonance methods. The hGrb7-SH2 domain structure reveals the Src homology 2 domain topology consisting of a central β-sheet capped at each end by an α-helix. The presence of a four residue insertion in the region between β-strand E and the EF loop and resulting influences on the SH2 domain/peptide complex structure are discussed. The binding conformation of the erbB2 peptide is in a β-turn similar to that found in phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our knowledge this is only the second example of an SH2 domain binding its naturally occurring ligands in a turn, instead of extended, conformation. Close contacts between residues responsible for binding specificity in hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect of mutation of these residues on the hGrb7-SH2 domain structure is discussed

  15. Domain matching epitaxy of cubic In{sub 2}O{sub 3} on r-plane sapphire

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, Patrick; Trampert, Achim; Ramsteiner, Manfred; Bierwagen, Oliver [Paul-Drude-Institut fuer Festkoerperelektronik, Hausvogteiplatz 5-7, 10117, Berlin (Germany)

    2015-07-15

    Undoped, Sn-doped, and Mg-doped In{sub 2}O{sub 3} layers were grown on rhombohedral r-plane sapphire (α-Al{sub 2}O{sub 3} (10.2)) by plasma-assisted molecular beam epitaxy. X-ray diffraction and Raman scattering experiments demonstrated the formation of phase-pure, cubic (110)-oriented In{sub 2}O{sub 3} for Sn- and Mg-concentrations up to 2 x 10{sup 20} and 6 x 10{sup 20} cm{sup -3}, respectively. Scanning electron microscopy images showed facetted domains without any surface-parallel (110) facets. High Mg- or Sn-doping influenced surface morphology and the facet formation. X-ray diffraction Φ-scans indicated the formation of two rotational domains separated by an angle Φ = 86.6 due to the substrate mirror-symmetry around the in-plane-projected Al{sub 2}O{sub 3} c-axis. The in-plane epitaxial relationships to the substrate were determined for both domains. For the first domain it is Al{sub 2}O{sub 3}[01.0] parallel In{sub 2}O{sub 3}[3 anti 3 anti 4]. For the second domain the inplane epitaxial relation is Al{sub 2}O{sub 3}[01.0] parallel In{sub 2}O{sub 3}[3 anti 34]. A low-mismatch coincidence lattice of indium atoms from the film and oxygen atoms from the substrate rationalizes this epitaxial relation by domain-matched epitaxy. Cross-sectional transmission-electron microscopy showed a columnar domain-structure, indicating the vertical growth of the rotational domains after their nucleation. Coincidence structure of In{sub 2}O{sub 3} (110) (In atoms in red) grown on Al{sub 2}O{sub 3} (10.2) (O atoms in blue) showing two rotational domians. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. Crystallization and preliminary X-ray analysis of the V domain of human nectin-2

    International Nuclear Information System (INIS)

    Qian, Xiaomin; Qi, Jianxun; Chu, Fuliang; Liu, Jun; Li, Qing; Yan, Jinghua

    2009-01-01

    Crystals of the V domain of human nectin-2 diffracted to 1.85 Å resolution and were monoclinic, belonging to space group P2 1 , with unit-cell parameters a = 52.3, b = 43.9, c = 56.1 Å, β = 118.2°. Nectin-2 belongs to a family of immunoglobulin-like cell adhesion molecules that are characterized by the presence of three immunoglobulin-like domains (V, C2 and C2) in the extracellular region. The V domain plays important roles in cell adhesion, NK cell activation and the entry of some herpesvirus. In this study, the V domain of human nectin-2 was expressed in Escherichia coli in the form of inclusion bodies, which were subsequently denatured and refolded. The soluble protein was crystallized using the hanging-drop vapour-diffusion method. The crystals diffracted to 1.85 Å resolution and belonged to space group P2 1 , with unit-cell parameters a = 52.3, b = 43.9, c = 56.1 Å, β = 118.2°

  17. High-Throughput Quantification of SH2 Domain-Phosphopeptide Interactions with Cellulose-Peptide Conjugate Microarrays.

    Science.gov (United States)

    Engelmann, Brett W

    2017-01-01

    The Src Homology 2 (SH2) domain family primarily recognizes phosphorylated tyrosine (pY) containing peptide motifs. The relative affinity preferences among competing SH2 domains for phosphopeptide ligands define "specificity space," and underpins many functional pY mediated interactions within signaling networks. The degree of promiscuity exhibited and the dynamic range of affinities supported by individual domains or phosphopeptides is best resolved by a carefully executed and controlled quantitative high-throughput experiment. Here, I describe the fabrication and application of a cellulose-peptide conjugate microarray (CPCMA) platform to the quantitative analysis of SH2 domain specificity space. Included herein are instructions for optimal experimental design with special attention paid to common sources of systematic error, phosphopeptide SPOT synthesis, microarray fabrication, analyte titrations, data capture, and analysis.

  18. The identification of FANCD2 DNA binding domains reveals nuclear localization sequences.

    Science.gov (United States)

    Niraj, Joshi; Caron, Marie-Christine; Drapeau, Karine; Bérubé, Stéphanie; Guitton-Sert, Laure; Coulombe, Yan; Couturier, Anthony M; Masson, Jean-Yves

    2017-08-21

    Fanconi anemia (FA) is a recessive genetic disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. The FA pathway consists of at least 21 FANC genes (FANCA-FANCV), and the encoded protein products interact in a common cellular pathway to gain resistance against DNA interstrand crosslinks. After DNA damage, FANCD2 is monoubiquitinated and accumulates on chromatin. FANCD2 plays a central role in the FA pathway, using yet unidentified DNA binding regions. By using synthetic peptide mapping and DNA binding screen by electromobility shift assays, we found that FANCD2 bears two major DNA binding domains predominantly consisting of evolutionary conserved lysine residues. Furthermore, one domain at the N-terminus of FANCD2 bears also nuclear localization sequences for the protein. Mutations in the bifunctional DNA binding/NLS domain lead to a reduction in FANCD2 monoubiquitination and increase in mitomycin C sensitivity. Such phenotypes are not fully rescued by fusion with an heterologous NLS, which enable separation of DNA binding and nuclear import functions within this domain that are necessary for FANCD2 functions. Collectively, our results enlighten the importance of DNA binding and NLS residues in FANCD2 to activate an efficient FA pathway. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Combining biophysical methods to analyze the disulfide bond in SH2 domain of C-terminal Src kinase.

    Science.gov (United States)

    Liu, Dongsheng; Cowburn, David

    2016-01-01

    The Src Homology 2 (SH2) domain is a structurally conserved protein domain that typically binds to a phosphorylated tyrosine in a peptide motif from the target protein. The SH2 domain of C-terminal Src kinase (Csk) contains a single disulfide bond, which is unusual for most SH2 domains. Although the global motion of SH2 domain regulates Csk function, little is known about the relationship between the disulfide bond and binding of the ligand. In this study, we combined X-ray crystallography, solution NMR, and other biophysical methods to reveal the interaction network in Csk. Denaturation studies have shown that disulfide bond contributes significantly to the stability of SH2 domain, and crystal structures of the oxidized and C122S mutant showed minor conformational changes. We further investigated the binding of SH2 domain to a phosphorylated peptide from Csk-binding protein upon reduction and oxidation using both NMR and fluorescence approaches. This work employed NMR, X-ray cryptography, and other biophysical methods to study a disulfide bond in Csk SH2 domain. In addition, this work provides in-depth understanding of the structural dynamics of Csk SH2 domain.

  20. Prevalence and trend in the use of hospital-based standing orders programs for influenza and pneumococcal vaccination.

    Science.gov (United States)

    Pentakota, Sri Ram; Halperin, William

    2007-08-01

    In 2002, federal regulations authorized the use of standing orders programs (SOPs) for promoting influenza and pneumococcal vaccination. In 2003, the New Jersey Hospital Association conducted a demonstration project illustrating the efficacy of SOPs, and the state health department informed healthcare facilities of their benefits. We describe the prevalence of reported use of SOPs in New Jersey hospitals in 2003 and 2005 and identify hospital characteristics associated with the use of SOPs. A survey was mailed to the directors of infection control at 117 New Jersey hospitals during the period from January to May 2005 (response rate, 90.6%). Data on hospital characteristics were obtained from hospital directories and online resources. The prevalence of use of SOPs for influenza vaccination was 50% (95% confidence interval [CI], 40.1%-59.9%) in 2003, and it increased to 78.3% (95% CI, 69.2%-85.7%) in 2005. The prevalence of SOP use for pneumococcal vaccination was similar. In 2005, the reported rate of use of SOPs for inpatients (influenza vaccination, 76.4%; pneumococcal vaccination, 75.5%) was significantly higher than that for outpatients (influenza vaccination, 9.4%; pneumococcal vaccination, 8.5%). Prevalence ratios for SOP use comparing acute care and non-acute care hospitals were 1.71 (95% CI, 1.2-2.5) for influenza vaccination SOPs and 1.8 for (95% CI, 1.2-2.7) pneumococcal vaccination SOPs. Acute care hospitals with a ratio of admissions to total beds greater than 36.7 reported greater use of SOPs for pneumococcal vaccination, compared with those that had a ratio of less than 36.7. The increase in the prevalence of reported use of SOPs among New Jersey hospitals in 2005, compared with 2003, was contemporaneous with SOP-related actions taken by the federal government, the state government, and the New Jersey Hospital Association. Opportunities persist for increased use of SOPs among non-acute care hospitals and for outpatients.

  1. Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3.

    Science.gov (United States)

    Doan, Ninh; Gettins, Peter G W

    2007-10-01

    Human alpha2M (alpha2-macroglobulin) and the complement components C3 and C4 are thiol ester-containing proteins that evolved from the same ancestral gene. The recent structure determination of human C3 has allowed a detailed prediction of the location of domains within human alpha2M to be made. We describe here the expression and characterization of three alpha(2)M domains predicted to be involved in the stabilization of the thiol ester in native alpha2M and in its activation upon bait region proteolysis. The three newly expressed domains are MG2 (macroglobulin domain 2), TED (thiol ester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain. Together with the previously characterized RBD (receptor-binding domain), they represent approx. 42% of the alpha2M polypeptide. Their expression as folded domains strongly supports the predicted domain organization of alpha2M. An X-ray crystal structure of MG2 shows it to have a fibronectin type-3 fold analogous to MG1-MG8 of C3. TED is, as predicted, an alpha-helical domain. CUB is a spliced domain composed of two stretches of polypeptide that flank TED in the primary structure. In intact C3 TED interacts with RBD, where it is in direct contact with the thiol ester, and with MG2 and CUB on opposite, flanking sides. In contrast, these alpha2M domains, as isolated species, show negligible interaction with one another, suggesting that the native conformation of alpha2M, and the consequent thiol ester-stabilizing domain-domain interactions, result from additional restraints imposed by the physical linkage of these domains or by additional domains in the protein.

  2. HPA and SAM axis responses as correlates of self- vs parental ratings of anxiety in boys with an Autistic Disorder.

    Science.gov (United States)

    Bitsika, Vicki; Sharpley, Christopher F; Sweeney, John A; McFarlane, James R

    2014-03-29

    Anxiety and Autistic Disorder (AD) are both neurological conditions and both disorders share some features that make it difficult to precisely allocate specific symptoms to each disorder. HPA and SAM axis activities have been conclusively associated with anxiety, and may provide a method of validating anxiety rating scale assessments given by parents and their children with AD about those children. Data from HPA axis (salivary cortisol) and SAM axis (salivary alpha amylase) responses were collected from a sample of 32 high-functioning boys (M age=11yr) with an Autistic Disorder (AD) and were compared with the boys' and their mothers' ratings of the boys' anxiety. There was a significant difference between the self-ratings given by the boys and ratings given about them by their mothers. Further, only the boys' self-ratings of their anxiety significantly predicted the HPA axis responses and neither were significantly related to SAM axis responses. Some boys showed cortisol responses which were similar to that previously reported in children who had suffered chronic and severe anxiety arising from stressful social interactions. As well as suggesting that some boys with an AD can provide valid self-assessments of their anxiety, these data also point to the presence of very high levels of chronic HPA-axis arousal and consequent chronic anxiety in these boys. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Boron (B) deprivation increases plasma homocysteine and decreases liver S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in rats

    Science.gov (United States)

    The diverse effects of B deprivation suggest that B affects a biomolecule involved in a variety of biochemical reactions. An experiment was conducted to determine whether dietary B affects the liver concentration of SAM, a frequently used enzyme substrate, especially for methylation reactions that y...

  4. Binding Assays Using Recombinant SH2 Domains: Far-Western, Pull-Down, and Fluorescence Polarization.

    Science.gov (United States)

    Machida, Kazuya; Liu, Bernard

    2017-01-01

    Recognition of phosphotyrosine-containing sequences by SH2 domains confers specificity in tyrosine kinase pathways. By assessing interactions between isolated SH2 domains and their binding proteins, it is possible to gain insight into otherwise inaccessible complex cellular systems. Far-Western, pull-down, and fluorescence polarization (FP) have been frequently used for characterization of phosphotyrosine signaling. Here, we outline standard protocols for these established assays using recombinant SH2 domain, emphasizing the importance of appropriate sample preparation and assay controls.

  5. Regularized Laplace-Fourier-Domain Full Waveform Inversion Using a Weighted l 2 Objective Function

    Science.gov (United States)

    Jun, Hyunggu; Kwon, Jungmin; Shin, Changsoo; Zhou, Hongbo; Cogan, Mike

    2017-03-01

    Full waveform inversion (FWI) can be applied to obtain an accurate velocity model that contains important geophysical and geological information. FWI suffers from the local minimum problem when the starting model is not sufficiently close to the true model. Therefore, an accurate macroscale velocity model is essential for successful FWI, and Laplace-Fourier-domain FWI is appropriate for obtaining such a velocity model. However, conventional Laplace-Fourier-domain FWI remains an ill-posed and ill-conditioned problem, meaning that small errors in the data can result in large differences in the inverted model. This approach also suffers from certain limitations related to the logarithmic objective function. To overcome the limitations of conventional Laplace-Fourier-domain FWI, we introduce a weighted l 2 objective function, instead of the logarithmic objective function, as the data-domain objective function, and we also introduce two different model-domain regularizations: first-order Tikhonov regularization and prior model regularization. The weighting matrix for the data-domain objective function is constructed to suitably enhance the far-offset information. Tikhonov regularization smoothes the gradient, and prior model regularization allows reliable prior information to be taken into account. Two hyperparameters are obtained through trial and error and used to control the trade-off and achieve an appropriate balance between the data-domain and model-domain gradients. The application of the proposed regularizations facilitates finding a unique solution via FWI, and the weighted l 2 objective function ensures a more reasonable residual, thereby improving the stability of the gradient calculation. Numerical tests performed using the Marmousi synthetic dataset show that the use of the weighted l 2 objective function and the model-domain regularizations significantly improves the Laplace-Fourier-domain FWI. Because the Laplace-Fourier-domain FWI is improved, the

  6. Human α2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3

    Science.gov (United States)

    Doan, Ninh; Gettins, Peter G. W.

    2007-01-01

    Human α2M (α2-macroglobulin) and the complement components C3 and C4 are thiol ester-containing proteins that evolved from the same ancestral gene. The recent structure determination of human C3 has allowed a detailed prediction of the location of domains within human α2M to be made. We describe here the expression and characterization of three α2M domains predicted to be involved in the stabilization of the thiol ester in native α2M and in its activation upon bait region proteolysis. The three newly expressed domains are MG2 (macroglobulin domain 2), TED (thiol ester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain. Together with the previously characterized RBD (receptor-binding domain), they represent approx. 42% of the α2M polypeptide. Their expression as folded domains strongly supports the predicted domain organization of α2M. An X-ray crystal structure of MG2 shows it to have a fibronectin type-3 fold analogous to MG1–MG8 of C3. TED is, as predicted, an α-helical domain. CUB is a spliced domain composed of two stretches of polypeptide that flank TED in the primary structure. In intact C3 TED interacts with RBD, where it is in direct contact with the thiol ester, and with MG2 and CUB on opposite, flanking sides. In contrast, these α2M domains, as isolated species, show negligible interaction with one another, suggesting that the native conformation of α2M, and the consequent thiol ester-stabilizing domain–domain interactions, result from additional restraints imposed by the physical linkage of these domains or by additional domains in the protein. PMID:17608619

  7. The [4Fe-4S](2+) cluster in reconstituted biotin synthase binds S-adenosyl-L-methionine.

    Science.gov (United States)

    Cosper, Michele Mader; Jameson, Guy N L; Davydov, Roman; Eidsness, Marly K; Hoffman, Brian M; Huynh, Boi Hanh; Johnson, Michael K

    2002-11-27

    The combination of resonance Raman, electron paramagnetic resonance and Mössbauer spectroscopies has been used to investigate the effect of S-adenosyl-l-methionine (SAM) on the spectroscopic properties of the [4Fe-4S]2+ cluster in biotin synthase. The results indicate that SAM interacts directly at a unique iron site of the [4Fe-4S]2+ cluster in BioB and support the hypothesis of a common inner-sphere mechanism for the reductive cleavage of SAM in the radical SAM family of Fe-S enzymes.

  8. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  9. Microstructure within domains of melt-processed YBa2Cu3O7-x superconductors

    International Nuclear Information System (INIS)

    Alexander, K.B.; Goyal, A.; Kroeger, D.M.; Selvamanickam, V.; Salama, K.

    1992-01-01

    The microstructure within single domains of melt-processed YBa 2 Cu 3 O 7-x (1:2:3) material has been examined. Rather than composing a ''brick-wall'' structure, the stacked, parallel platelets within the domains are actually portions of a single crystal. A growth mechanism is proposed that is consistent with the observed microstructural features. The anisotropic nature of the growth of 1:2:3 results in gaps separating the platelets. The gaps, however, terminate within domains, resulting in interconnected single-crystalline material. The absence of weak-link behavior for current flow along the c axis and the high critical-current densities observed within domains of melt-processed 1:2:3 material are readily explained by the fact that current flow is solely through single-crystalline material

  10. Structural and biophysical investigation of the interaction of a mutant Grb2 SH2 domain (W121G) with its cognate phosphopeptide.

    Science.gov (United States)

    Papaioannou, Danai; Geibel, Sebastian; Kunze, Micha B A; Kay, Christopher W M; Waksman, Gabriel

    2016-03-01

    The adaptor protein Grb2 is a key element of mitogenetically important signaling pathways. With its SH2 domain it binds to upstream targets while its SH3 domains bind to downstream proteins thereby relaying signals from the cell membranes to the nucleus. The Grb2 SH2 domain binds to its targets by recognizing a phosphotyrosine (pY) in a pYxNx peptide motif, requiring an Asn at the +2 position C-terminal to the pY with the residue either side of this Asn being hydrophobic. Structural analysis of the Grb2 SH2 domain in complex with its cognate peptide has shown that the peptide adopts a unique β-turn conformation, unlike the extended conformation that phosphopeptides adopt when bound to other SH2 domains. TrpEF1 (W121) is believed to force the peptide into this unusual conformation conferring this unique specificity to the Grb2 SH2 domain. Using X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and isothermal titration calorimetry (ITC), we describe here a series of experiments that explore the role of TrpEF1 in determining the specificity of the Grb2 SH2 domain. Our results demonstrate that the ligand does not adopt a pre-organized structure before binding to the SH2 domain, rather it is the interaction between the two that imposes the hairpin loop to the peptide. Furthermore, we find that the peptide adopts a similar structure when bound to both the wild-type Grb2 SH2 domain and a TrpEF1Gly mutant. This suggests that TrpEF1 is not the determining factor for the conformation of the phosphopeptide. © 2015 The Protein Society.

  11. Shapes of isolated domains and field induced evolution of regular and random 2D domain structures in LiNbO3 and LiTaO3

    International Nuclear Information System (INIS)

    Chernykh, A.; Shur, V.; Nikolaeva, E.; Shishkin, E.; Shur, A.; Terabe, K.; Kurimura, S.; Kitamura, K.; Gallo, K.

    2005-01-01

    The variety of the shapes of isolated domains, revealed in congruent and stoichiometric LiTaO 3 and LiNbO 3 by chemical etching and visualized by optical and scanning probe microscopy, was obtained by computer simulation. The kinetic nature of the domain shape was clearly demonstrated. The kinetics of domain structure with the dominance of the growth of the steps formed at the domain walls as a result of domain merging was investigated experimentally in slightly distorted artificial regular two-dimensional (2D) hexagonal domain structure and random natural one. The artificial structure has been realized in congruent LiNbO 3 by 2D electrode pattern produced by photolithography. The polarization reversal in congruent LiTaO 3 was investigated as an example of natural domain growth limited by merging. The switching process defined by domain merging was studied by computer simulation. The crucial dependence of the switching kinetics on the nuclei concentration has been revealed

  12. Solution structure, dynamics and thermodynamics of the three SH3 domains of CD2AP

    Energy Technology Data Exchange (ETDEWEB)

    Roldan, Jose L. Ortega [Universidad de Granada, Departamento de Quimica Fisica e Instituto de Biotecnologia, Facultad de Ciencias (Spain); Blackledge, Martin [Institut de Biologie Structurale Jean-Pierre Ebel, CEA, CNRS, UJF UMR 5075, Protein Dynamics and Flexibility by NMR (France); Nuland, Nico A. J. van, E-mail: nvnuland@vub.ac.be [Vrije Universiteit Brussel, Structural Biology Brussels (Belgium); Azuaga, Ana I. [Universidad de Granada, Departamento de Quimica Fisica e Instituto de Biotecnologia, Facultad de Ciencias (Spain)

    2011-06-15

    CD2 associated protein (CD2AP) is an adaptor protein that plays an important role in cell to cell union needed for the kidney function. It contains three N-terminal SH3 domains that are able to interact among others with CD2, ALIX, c-Cbl and Ubiquitin. To understand the role of the individual SH3 domains of this adaptor protein we have performed a complete structural, thermodynamic and dynamic characterization of the separate domains using NMR and DSC. The energetic contributions to the stability and the backbone dynamics have been related to the structural features of each domain using the structure-based FoldX algorithm. We have found that the N-terminal SH3 domain of both adaptor proteins CD2AP and CIN85 are the most stable SH3 domains that have been studied until now. This high stability is driven by a more extensive network of intra-molecular interactions. We believe that this increased stabilization of N-terminal SH3 domains in adaptor proteins is crucial to maintain the necessary conformation to establish the proper interactions critical for the recruitment of their natural targets.

  13. Kto samõi bogatõi v Estonii / Sten-Aleks Pihlak, Kärt Blumberg, Lemmi Kann

    Index Scriptorium Estoniae

    Pihlak, Sten-Aleks

    2008-01-01

    Eesti laevatranspordi kolmik - Ain Hanschmidt, Enn Pant ja Kalev Järvelill on Äripäeva rikaste edetabelis esimesed. Viimaste kuude suure aktsiahinnalanguse tõttu on paljud Äripäeva rikaste edetabelis olijad kaotanud igast kolmest kroonist kaks. Artiklis selgitatakse miks on Äripäeva Rikaste TOPis vähe naisi. Lisad: Iz TOP-500 samõhh bogatõhh ljudei v Estonii; Reitingi bogatshei za prezhnije godõ; Metodika

  14. Selective Targeting of SH2 Domain-Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies.

    Science.gov (United States)

    Kükenshöner, Tim; Schmit, Nadine Eliane; Bouda, Emilie; Sha, Fern; Pojer, Florence; Koide, Akiko; Seeliger, Markus; Koide, Shohei; Hantschel, Oliver

    2017-05-05

    The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively perturb the interactions of even the SFK SH2 family against the rest of the SH2 domains. We have developed synthetic binding proteins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity. Most of these monobodies competed with pY ligand binding and showed strong selectivity for either the SrcA (Yes, Src, Fyn, Fgr) or SrcB subgroup (Lck, Lyn, Blk, Hck). Interactome analysis of intracellularly expressed monobodies revealed that they bind SFKs but no other SH2-containing proteins. Three crystal structures of monobody-SH2 complexes unveiled different and only partly overlapping binding modes, which rationalized the observed selectivity and enabled structure-based mutagenesis to modulate inhibition mode and selectivity. In line with the critical roles of SFK SH2 domains in kinase autoinhibition and T-cell receptor signaling, monobodies binding the Src and Hck SH2 domains selectively activated respective recombinant kinases, whereas an Lck SH2-binding monobody inhibited proximal signaling events downstream of the T-cell receptor complex. Our results show that SFK SH2 domains can be targeted with unprecedented potency and selectivity using monobodies. They are excellent tools for dissecting SFK functions in normal development and signaling and to interfere with aberrant SFK signaling networks in cancer cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. Structures of BIR domains from human NAIP and cIAP2.

    Science.gov (United States)

    Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

    2009-11-01

    The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.

  16. Prevalencia de Neospora caninum y DVB en una finca con problemas reproductivos en Sopó (Cundinamarca

    Directory of Open Access Journals (Sweden)

    John Fredy García-Chaparro

    2015-04-01

    Full Text Available La investigación tuvo como objetivo determinar la prevalencia de Neospora caninum y del virus de la diarrea viral bovina (DVB en bovinos de una finca con problemas reproductivos, en el municipio de Sopó (Cundinamarca, y su relación con la presentación de abortos. Se tomaron muestras de suero sanguíneo de 397 animales de alta producción lechera y con antecedentes reproductivos, seleccionados al azar.Se utilizó la inmunofluoresencia indirecta para la N. caninum, y seroneutralización para DVB, y los procedimientos se realizaron en el Laboratorio de Enfermedades Infecciosas de la Universidad de Parma (Italia. Se encontró una prevalencia de 10.37% para DVB con respecto a 21.26% para N. caninum, y estadísticamente no hubo relación directa con respecto a los problemas reproductivos. De acuerdo con los resultados obtenidos, se reportó mayor presencia significativa de N. caninum con relación a la de DVB en el hato lechero objeto de estudio.

  17. Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses.

    Directory of Open Access Journals (Sweden)

    James Weger-Lucarelli

    Full Text Available Chikungunya virus (CHIKV and other alphaviruses are the etiologic agents of numerous diseases in both humans and animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this virus genus. The alphavirus E2, the receptor-binding envelope protein, is considered to be the predominant target of the protective host immune response. Although envelope protein domains have been studied for vaccine and neutralization in flaviviruses, their role in alphaviruses is less characterized. Here, we describe the role of the alphavirus E2 domains in neutralization and protection through the use of chimeric viruses.Four chimeric viruses were constructed in which individual E2 domains of CHIKV were replaced with the corresponding domain from Semliki Forest virus (SFV (ΔDomA/ΔDomB/ΔDomC/ ΔDomA+B. Vaccination studies in mice (both live and inactivated virus revealed that domain B was the primary determinant of neutralization. Neutralization studies with CHIKV immune serum from humans were consistent with mouse studies, as ΔDomB was poorly neutralized.Using chimeric viruses, it was determined that the alphavirus E2 domain B was the critical target of neutralizing antibodies in both mice and humans. Therefore, chimeric viruses may have more relevance for vaccine discovery than peptide-based approaches, which only detect linear epitopes. This study provides new insight into the role of alphavirus E2 domains on neutralization determinants and may be useful for the design of novel therapeutic technologies.

  18. Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85α regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain.

    Science.gov (United States)

    Hofmann, Bianca T; Jücker, Manfred

    2012-10-01

    The phosphoinositide 3-kinase (PI3K) is frequently activated in human cancer cells due to gain of function mutations in the catalytic (p110) and the regulatory (p85) subunits. The regulatory subunit consists of an SH3 domain and two SH2 domains. An oncogenic form of p85α named p65 lacking the c-terminal SH2 domain (cSH2) has been cloned from an irradiation-induced murine thymic lymphoma and transgenic mice expressing p65 in T lymphocytes develop a lymphoproliferative disorder. We have recently detected a c-terminal truncated form of p85α named p76α in a human lymphoma cell line lacking most of the cSH2 domain due to a frame shift mutation. Here, we report that the deletion of the cSH2 domain enhances the activating effects of the n-terminal SH2 domain (nSH2) mutants K379E and R340E on the PI3K/Akt pathway and micro tumor formation in a focus assay. Further analysis revealed that this transforming effect is mediated by activation of the catalytic PI3K isoform p110α and downstream signaling through mTOR. Our data further support a mechanistic model in which mutations of the cSH2 domain of p85α can abrogate its negative regulatory function on PI3K activity via the nSH2 domain of p85α. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Coupled motions in the SH2 and kinase domains of Csk control Src phosphorylation.

    Science.gov (United States)

    Wong, Lilly; Lieser, Scot A; Miyashita, Osamu; Miller, Meghan; Tasken, Kjetil; Onuchic, Josè N; Adams, Joseph A; Woods, Virgil L; Jennings, Patricia A

    2005-08-05

    The C-terminal Src kinase (Csk) phosphorylates and down-regulates Src family tyrosine kinases. The Csk-binding protein (Cbp) localizes Csk close to its substrates at the plasma membrane, and increases the specific activity of the kinase. To investigate this long-range catalytic effect, the phosphorylation of Src and the conformation of Csk were investigated in the presence of a high-affinity phosphopeptide derived from Cbp. This peptide binds tightly to the SH2 domain and enhances Src recognition (lowers K(m)) by increasing the apparent phosphoryl transfer rate in the Csk active site, a phenomenon detected in rapid quench flow experiments. Previous studies demonstrated that the regulation of Csk activity is linked to conformational changes in the enzyme that can be probed with hydrogen-deuterium exchange methods. We show that the Cbp peptide impacts deuterium incorporation into its binding partner (the SH2 domain), and into the SH2-kinase linker and several sequences in the kinase domain, including the glycine-rich loop in the active site. These findings, along with computational data from normal mode analyses, suggest that the SH2 domain moves in a cantilever fashion with respect to the small lobe of the kinase domain, ordering the active site for catalysis. The binding of a small Cbp-derived peptide to the SH2 domain of Csk modifies these motions, enhancing Src recognition.

  20. Chemical shift assignments of the partially deuterated Fyn SH2-SH3 domain.

    Science.gov (United States)

    Kieken, Fabien; Loth, Karine; van Nuland, Nico; Tompa, Peter; Lenaerts, Tom

    2018-04-01

    Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules involved in regulating the activity of many proteins such as tyrosine kinases and phosphatases by respective recognition of phosphotyrosine and proline-rich regions. In the Src family kinases, the inactive state of the protein is the direct result of the interaction of the SH2 and the SH3 domain with intra-molecular regions, leading to a closed structure incompetent with substrate modification. Here, we report the 1 H, 15 N and 13 C backbone- and side-chain chemical shift assignments of the partially deuterated Fyn SH3-SH2 domain and structural differences between tandem and single domains. The BMRB accession number is 27165.

  1. Effects of soya oligosaccharides and soya oligopeptides on lipid metabolism in hyperlipidaemic rats.

    Science.gov (United States)

    Xie, Shali; Zhu, Jundong; Zhang, Yanqi; Shi, Kai; Shi, Yuangang; Ma, Xiao

    2012-08-01

    In the present study, we aimed to examine the effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on blood lipid levels, release of vasoactive substances, antioxidant activity and faecal bile acid (FBA) excretion in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats were evenly divided into five groups according to diets as follows: regular diet (control), HFD, HFD enriched with 2 % of SOS (SOS), HFD enriched with 3 % of SOP (SOP) and HFD enriched with 2 % SOS and 3 % SOP (SOSP). The results showed that SOS and SOP significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, whereas HDL-cholesterol concentration was significantly increased. Furthermore, SOS and SOP reduced plasma apoB, apoE and the apoB:apoAI ratio, whereas apoAI was significantly increased. Moreover, SOS and SOP also reduced plasma thromboxane A₂ (TXA₂) and the TXA₂:prostacyclin (PGI₂) ratio, whereas plasma PGI₂ and nitric oxide were significantly increased. In addition, SOS and SOP significantly reduced serum and liver malondialdehyde concentrations and increased FBA excretion. However, we did not observe obvious influences of SOS and SOP on superoxide dismutase activities in the liver of HFD-fed rats. The combination of 2 % SOS and 3 % SOP showed a more marked effect than SOS or SOP alone in improving the lipid profile, release of vasoactive substances and increasing FBA excretion (P < 0.05). In summary, SOS and SOP might help prevent atherosclerosis through improving abnormal blood lipid levels, regulating vasoactive substances and protecting against oxidative stress.

  2. A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours

    NARCIS (Netherlands)

    Paridaens, R; Uges, DRA; Barbet, N; Choi, L; Seeghers, M; van der Graaf, WTA; Groen, HJM; Dumez, H; Van Buuren, [No Value; Muskiet, F; Capdeville, R; van Oosterom, AT; de Vries, EGE

    Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme

  3. The development and application of a quantitative peptide microarray platform to SH2 domain specificity space

    Science.gov (United States)

    Engelmann, Brett Warren

    The Src homology 2 (SH2) domains evolved alongside protein tyrosine kinases (PTKs) and phosphatases (PTPs) in metazoans to recognize the phosphotyrosine (pY) post-translational modification. The human genome encodes 121 SH2 domains within 111 SH2 domain containing proteins that represent the primary mechanism for cellular signal transduction immediately downstream of PTKs. Despite pY recognition contributing to roughly half of the binding energy, SH2 domains possess substantial binding specificity, or affinity discrimination between phosphopeptide ligands. This specificity is largely imparted by amino acids (AAs) adjacent to the pY, typically from positions +1 to +4 C-terminal to the pY. Much experimental effort has been undertaken to construct preferred binding motifs for many SH2 domains. However, due to limitations in previous experimental methodologies these motifs do not account for the interplay between AAs. It was therefore not known how AAs within the context of individual peptides function to impart SH2 domain specificity. In this work we identified the critical role context plays in defining SH2 domain specificity for physiological ligands. We also constructed a high quality interactome using 50 SH2 domains and 192 physiological ligands. We next developed a quantitative high-throughput (Q-HTP) peptide microarray platform to assess the affinities four SH2 domains have for 124 physiological ligands. We demonstrated the superior characteristics of our platform relative to preceding approaches and validated our results using established biophysical techniques, literature corroboration, and predictive algorithms. The quantitative information provided by the arrays was leveraged to investigate SH2 domain binding distributions and identify points of binding overlap. Our microarray derived affinity estimates were integrated to produce quantitative interaction motifs capable of predicting interactions. Furthermore, our microarrays proved capable of resolving

  4. Active site labeling of the guanine-7-methyltransferase

    International Nuclear Information System (INIS)

    Streaker, E.; Sitz, T.O.

    1992-01-01

    Studies on the guanine-7-methyltransferase have defined three domains in the active site: the S-adenosylmethionine (SAM) region, the cap region (GpppG), and the RNA binding domain (--NpNpNpNpNp---). The authors attempted to label the SAM binding domain by a photoaffinity label using 8-azido-SAM and another method using 3 H-SAM and long exposures to uv-light. Neither method was successful. The next approach was to attempt to label the cap-RNA binding domain (GpppGpNpNpNpNpN) by synthesizing RNA containing 8-azido-Ap using an in vitro transcription system and T7 RNA polymerase. The 8-azido-ATP inhibited the T7 RNA polymerase preventing the synthesis of RNA. As they were unable to synthesize the photoaffinity label, they next tried to synthesize an end labeled RNA and directly label by long exposures to uv-light. When the enzyme was incubated with 32 P-labeled RNA for 15 min at 37 degrees and then exposed to a germicidal lamp for various times at O degrees, optimal labeling occurred after 45 min. Various enzyme preparations were labeled by this method and two polypeptides were found to specifically bind the non-methylated mRNA analog. This labeling method should allow characterization of the subunit structure and generate information about the nature of the RNA binding domain

  5. Critical role of the Src homology 2 (SH2) domain of neuronal SH2B1 in the regulation of body weight and glucose homeostasis in mice.

    Science.gov (United States)

    Morris, David L; Cho, Kae Won; Rui, Liangyou

    2010-08-01

    SH2B1 is an SH2 domain-containing adaptor protein that plays a key role in the regulation of energy and glucose metabolism in both rodents and humans. Genetic deletion of SH2B1 in mice results in obesity and type 2 diabetes. Single-nucleotide polymorphisms in the SH2B1 loci and chromosomal deletions of the SH2B1 loci associate with obesity and insulin resistance in humans. In cultured cells, SH2B1 promotes leptin and insulin signaling by binding via its SH2 domain to phosphorylated tyrosines in Janus kinase 2 and the insulin receptor, respectively. Here we generated three lines of mice to analyze the role of the SH2 domain of SH2B1 in the central nervous system. Transgenic mice expressing wild-type, SH2 domain-defective (R555E), or SH2 domain-alone (DeltaN503) forms of SH2B1 specifically in neurons were crossed with SH2B1 knockout mice to generate KO/SH2B1, KO/R555E, or KO/DeltaN503 compound mutant mice. R555E had a replacement of Arg(555) with Glu within the SH2 domain. DeltaN503 contained an intact SH2 domain but lacked amino acids 1-503. Neuron-specific expression of recombinant SH2B1, but not R555E or DeltaN503, corrected hyperphagia, obesity, glucose intolerance, and insulin resistance in SH2B1 null mice. Neuron-specific expression of R555E in wild-type mice promoted obesity and insulin resistance. These results indicate that in addition to the SH2 domain, N-terminal regions of neuronal SH2B1 are also required for the maintenance of normal body weight and glucose metabolism. Additionally, mutations in the SH2 domain of SH2B1 may increase the susceptibility to obesity and type 2 diabetes in a dominant-negative manner.

  6. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways.

    Science.gov (United States)

    Sancho, Rosa M; Law, Bernard M H; Harvey, Kirsten

    2009-10-15

    Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2-DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2-DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2-DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2-DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease.

  7. An intact Pms2 ATPase domain is not essential for male fertility.

    Science.gov (United States)

    Fischer, Jared M; Dudley, Sandra; Miller, Ashleigh J; Liskay, R Michael

    2016-03-01

    The DNA mismatch repair (MMR) machinery in mammals plays critical roles in both mutation avoidance and spermatogenesis. Meiotic analysis of knockout mice of two different MMR genes, Mlh1 and Mlh3, revealed both male and female infertility associated with a defect in meiotic crossing over. In contrast, another MMR gene knockout, Pms2 (Pms2(ko/ko)), which contained a deletion of a portion of the ATPase domain, produced animals that were male sterile but female fertile. However, the meiotic phenotype of Pms2(ko/ko) males was less clear-cut than for Mlh1- or Mlh3-deficient meiosis. More recently, we generated a different Pms2 mutant allele (Pms2(cre)), which results in deletion of the same portion of the ATPase domain. Surprisingly, Pms2(cre/cre) male mice were completely fertile, suggesting that the ATPase domain of Pms2 is not required for male fertility. To explore the difference in male fertility, we examined the Pms2 RNA and found that alternative splicing of the Pms2(cre) allele results in a predicted Pms2 containing the C-terminus, which contains the Mlh1-interaction domain, a possible candidate for stabilizing Mlh1 levels. To study further the basis of male fertility, we examined Mlh1 levels in testes and found that whereas Pms2 loss in Pms2(ko/ko) mice results in severely reduced levels of Mlh1 expression in the testes, Mlh1 levels in Pms2(cre/cre) testes were reduced to a lesser extent. Thus, we propose that a primary function of Pms2 during spermatogenesis is to stabilize Mlh1 levels prior to its critical crossing over function with Mlh3. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Effect of assembled time on the corrosion behaviors of SAMs film on the AM60B alloy and its assembled mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xianbin, E-mail: xbliu@imr.ac.cn; Shan, Dayong; Song, Yingwei; Han, En-hou

    2015-01-15

    The influence of assembled time on the corrosion behaviors of SAMs film on the AM60B alloy and its assembled mechanism have been investigated by electrochemical measurements, scanning electron microscopy (SEM) observation and X-ray photoelectron spectroscopy (XPS) analysis. The self-assembled experiment on the AM60B magnesium alloy indicates that the corrosion susceptibility decreases with increasing assembled time until 24 h on cast AM60B alloy and then increases with increase of the assembled time proved by EIS measurement and potentiodynamic curves. The self-assembled experiments on pure magnesium and various heat treated cast AM60B magnesium alloy illuminate that the dissolved aluminum in magnesium solid solution is the key factor for assembled efficiency and is hard to self-assemble on the pure magnesium without aluminum. The corrosion resistance of self-assembled film on AM60B magnesium alloy is monotonically increasing with the dissolved aluminum. The results of XPS analysis reveal the assembled mechanism on AM60B and corroborate the function of Al element. - Highlights: • It is hard to self-assemble on the pure magnesium. • 24 h assembled film has the low corrosion susceptibility by EIS and polarization. • The corrosion susceptibility of SAMs film lie on the Al atom state in AM60B. • The corrosion susceptibility of SAMs film is decreasing with the dissolved Al.

  9. Effect of assembled time on the corrosion behaviors of SAMs film on the AM60B alloy and its assembled mechanism

    International Nuclear Information System (INIS)

    Liu, Xianbin; Shan, Dayong; Song, Yingwei; Han, En-hou

    2015-01-01

    The influence of assembled time on the corrosion behaviors of SAMs film on the AM60B alloy and its assembled mechanism have been investigated by electrochemical measurements, scanning electron microscopy (SEM) observation and X-ray photoelectron spectroscopy (XPS) analysis. The self-assembled experiment on the AM60B magnesium alloy indicates that the corrosion susceptibility decreases with increasing assembled time until 24 h on cast AM60B alloy and then increases with increase of the assembled time proved by EIS measurement and potentiodynamic curves. The self-assembled experiments on pure magnesium and various heat treated cast AM60B magnesium alloy illuminate that the dissolved aluminum in magnesium solid solution is the key factor for assembled efficiency and is hard to self-assemble on the pure magnesium without aluminum. The corrosion resistance of self-assembled film on AM60B magnesium alloy is monotonically increasing with the dissolved aluminum. The results of XPS analysis reveal the assembled mechanism on AM60B and corroborate the function of Al element. - Highlights: • It is hard to self-assemble on the pure magnesium. • 24 h assembled film has the low corrosion susceptibility by EIS and polarization. • The corrosion susceptibility of SAMs film lie on the Al atom state in AM60B. • The corrosion susceptibility of SAMs film is decreasing with the dissolved Al

  10. The N-methyl-D-aspartate receptor subunits NR2A and NR2B bind to the SH2 domains of phospholipase C-gamma.

    Science.gov (United States)

    Gurd, J W; Bissoon, N

    1997-08-01

    The NMDA receptor has recently been found to be phosphorylated on tyrosine. To assess the possible connection between tyrosine phosphorylation of the NMDA receptor and signaling pathways in the postsynaptic cell, we have investigated the relationship between tyrosine phosphorylation and the binding of NMDA receptor subunits to the SH2 domains of phospholipase C-gamma (PLC-gamma). A glutathione S-transferase (GST) fusion protein containing both the N- and the C-proximal SH2 domains of PLC-gamma was bound to glutathione-agarose and reacted with synaptic junctional proteins and glycoproteins. Tyrosine-phosphorylated PSD-GP180, which has been identified as the NR2B subunit of the NMDA receptor, bound to the SH2-agarose beads in a phosphorylation-dependent fashion. Immunoblot analysis with antibodies specific for individual NMDA receptor subunits showed that both NR2A and NR2B subunits bound to the SH2-agarose. No binding occurred to GST-agarose lacking an associated SH2 domain, indicating that binding was specific for the SH2 domains. The binding of receptor subunits increased after the incubation of synaptic junctions with ATP and decreased after treatment of synaptic junctions with exogenous protein tyrosine phosphatase. Immunoprecipitation experiments confirmed that NR2A and NR2B were phosphorylated on tyrosine and further that tyrosine phosphorylation of each of the subunits was increased after incubation with ATP. The results demonstrate that NMDA receptor subunits NR2A and NR2B will bind to the SH2 domains of PLC-gamma and that isolated synaptic junctions contain endogenous protein tyrosine kinase(s) that can phosphorylate both NR2A and NR2B receptor subunits, and suggest that interaction of the tyrosine-phosphorylated NMDA receptor with proteins that contain SH2 domains may serve to link it to signaling pathways in the postsynaptic cell.

  11. Domain decomposition method for solving elliptic problems in unbounded domains

    International Nuclear Information System (INIS)

    Khoromskij, B.N.; Mazurkevich, G.E.; Zhidkov, E.P.

    1991-01-01

    Computational aspects of the box domain decomposition (DD) method for solving boundary value problems in an unbounded domain are discussed. A new variant of the DD-method for elliptic problems in unbounded domains is suggested. It is based on the partitioning of an unbounded domain adapted to the given asymptotic decay of an unknown function at infinity. The comparison of computational expenditures is given for boundary integral method and the suggested DD-algorithm. 29 refs.; 2 figs.; 2 tabs

  12. Reflections on the individual–collective relation in change agency formation in the Samsø renewable energy island project

    DEFF Research Database (Denmark)

    Carlsson, Monica Susanne

    2018-01-01

    This paper offers reflections on change agency formation in the Renewable Energy Island (REI) project on Samsø, following a field visit to the island in June 2016. Both individual and collective agency are set out as central for the processes leading to the change in the REI project, spurring ref...

  13. Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.

    Science.gov (United States)

    Filippakopoulos, Panagis; Kofler, Michael; Hantschel, Oliver; Gish, Gerald D; Grebien, Florian; Salah, Eidarus; Neudecker, Philipp; Kay, Lewis E; Turk, Benjamin E; Superti-Furga, Giulio; Pawson, Tony; Knapp, Stefan

    2008-09-05

    The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.

  14. Seismic aftershock monitoring for on-site inspection purposes. Experience from Integrated Field Exercise 2008.

    Science.gov (United States)

    Labak, P.; Arndt, R.; Villagran, M.

    2009-04-01

    One of the sub-goals of the Integrated Field Experiment in 2008 (IFE08) in Kazakhstan was testing the prototype elements of the Seismic aftershock monitoring system (SAMS) for on-site inspection purposes. The task of the SAMS is to collect the facts, which should help to clarify nature of the triggering event. Therefore the SAMS has to be capable to detect and identify events as small as magnitude -2 in the inspection area size up to 1000 km2. Equipment for 30 mini-arrays and 10 3-component stations represented the field equipment of the SAMS. Each mini-array consisted of a central 3-component seismometer and 3 vertical seismometers at the distance about 100 m from the central seismometer. The mini-arrays covered approximately 80% of surrogate inspection area (IA) on the territory of former Semipalatinsk test site. Most of the stations were installed during the first four days of field operations by the seismic sub-team, which consisted of 10 seismologists. SAMS data center comprised 2 IBM Blade centers and 8 working places for data archiving, detection list production and event analysis. A prototype of SAMS software was tested. Average daily amount of collected raw data was 15-30 GB and increased according to the amount of stations entering operation. Routine manual data screening and data analyses were performed by 2-6 subteam members. Automatic screening was used for selected time intervals. Screening was performed using the Sonoview program in frequency domain and using the Geotool and Hypolines programs for screening in time domain. The screening results were merged into the master event list. The master event list served as a basis of detailed analysis of unclear events and events identified to be potentially in the IA. Detailed analysis of events to be potentially in the IA was performed by the Hypoline and Geotool programs. In addition, the Hyposimplex and Hypocenter programs were also used for localization of events. The results of analysis were integrated

  15. In vivo binding properties of SH2 domains from GTPase-activating protein and phosphatidylinositol 3-kinase.

    Science.gov (United States)

    Cooper, J A; Kashishian, A

    1993-01-01

    We have used a transient expression system and mutant platelet-derived growth factor (PDGF) receptors to study the binding specificities of the Src homology 2 (SH2) regions of the Ras GTPase-activator protein (GAP) and the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3 kinase). A number of fusion proteins, each tagged with an epitope allowing recognition by a monoclonal antibody, were expressed at levels comparable to those of endogenous GAP. Fusion proteins containing the central SH2-SH3-SH2 region of GAP or the C-terminal region of p85 alpha, which includes two SH2 domains, bound to PDGF receptors in response to PDGF stimulation. Both fusion proteins showed the same requirements for tyrosine phosphorylation sites in the PDGF receptor as the full-length proteins from which they were derived, i.e., binding of the GAP fusion protein was reduced by mutation of Tyr-771, and binding of the p85 fusion protein was reduced by mutation of Tyr-740, Tyr-751, or both residues. Fusion proteins containing single SH2 domains from either GAP or p85 alpha did not bind detectably to PDGF receptors in this system, suggesting that two SH2 domains in a single polypeptide cooperate to raise the affinity of binding. The sequence specificities of individual SH2 domains were deduced from the binding properties of fusion proteins containing one SH2 domain from GAP and another from p85. The results suggest that the C-terminal GAP SH2 domain specifies binding to Tyr-771, the C-terminal p85 alpha SH2 domain binds to either Tyr-740 or Tyr-751, and each protein's N-terminal SH2 domain binds to unidentified phosphorylation sites.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8382774

  16. The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.

    Science.gov (United States)

    Bae, Jae Hyun; Lew, Erin Denise; Yuzawa, Satoru; Tomé, Francisco; Lax, Irit; Schlessinger, Joseph

    2009-08-07

    SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. However, the modest binding affinity of SH2 domains to pY containing peptides may not account for and likely represents an oversimplified mechanism for regulation of selectivity of signaling pathways in living cells. Here we describe the crystal structure of the activated tyrosine kinase domain of FGFR1 in complex with a phospholipase Cgamma fragment. The structural and biochemical data and experiments with cultured cells show that the selectivity of phospholipase Cgamma binding and signaling via activated FGFR1 are determined by interactions between a secondary binding site on an SH2 domain and a region in FGFR1 kinase domain in a phosphorylation independent manner. These experiments reveal a mechanism for how SH2 domain selectivity is regulated in vivo to mediate a specific cellular process.

  17. MPEG-2 Compressed-Domain Algorithms for Video Analysis

    Directory of Open Access Journals (Sweden)

    Hesseler Wolfgang

    2006-01-01

    Full Text Available This paper presents new algorithms for extracting metadata from video sequences in the MPEG-2 compressed domain. Three algorithms for efficient low-level metadata extraction in preprocessing stages are described. The first algorithm detects camera motion using the motion vector field of an MPEG-2 video. The second method extends the idea of motion detection to a limited region of interest, yielding an efficient algorithm to track objects inside video sequences. The third algorithm performs a cut detection using macroblock types and motion vectors.

  18. Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A

    Energy Technology Data Exchange (ETDEWEB)

    Quinlan, Casey L.; Kaiser, Stephen E.; Bolaños, Ben; Nowlin, Dawn; Grantner, Rita; Karlicek-Bryant, Shannon; Feng, Jun Li; Jenkinson, Stephen; Freeman-Cook, Kevin; Dann, Stephen G.; Wang, Xiaoli; Wells, Peter A.; Fantin, Valeria R.; Stewart, Al E.; Grant, Stephan K. (Pfizer)

    2017-05-29

    S-Adenosyl-L-methionine (SAM) is an enzyme cofactor used in methyl transfer reactions and polyamine biosynthesis. The biosynthesis of SAM from ATP and L-methionine is performed by the methionine adenosyltransferase enzyme family (Mat; EC 2.5.1.6). Human methionine adenosyltransferase 2A (Mat2A), the extrahepatic isoform, is often deregulated in cancer. We identified a Mat2A inhibitor, PF-9366, that binds an allosteric site on Mat2A that overlaps with the binding site for the Mat2A regulator, Mat2B. Studies exploiting PF-9366 suggested a general mode of Mat2A allosteric regulation. Allosteric binding of PF-9366 or Mat2B altered the Mat2A active site, resulting in increased substrate affinity and decreased enzyme turnover. These data support a model whereby Mat2B functions as an inhibitor of Mat2A activity when methionine or SAM levels are high, yet functions as an activator of Mat2A when methionine or SAM levels are low. The ramification of Mat2A activity modulation in cancer cells is also described.

  19. Functional analysis of the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jung Hwan; Choi, Yoo Jin; Choi, Won Suk; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang, E-mail: wonsang@catholic.ac.kr

    2013-11-01

    Highlights: •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited tumor cell growth. •NH{sub 2}-terminal and BRICHOS domain of GKN1 regulated cell cycle. •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited epigenetic regulators. -- Abstract: Gastrokine 1 (GKN1) protects the gastric antral mucosa and promotes healing by facilitating restitution and proliferation after injury. GKN1 is down-regulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is tightly associated with gastric carcinogenesis. However, the underlying mechanisms as a tumor suppressor are largely unknown. Presently, the hydrophobic region and BRICHOS domain of GKN1, pGKN1{sup D13N}, pGKN1{sup Δ68–199}, and pGKN1{sup Δ1–67,165–199} were shown to suppress gastric cancer cell growth and recapitulate GKN1 functions. As well, the hydrophobic region and BRICHOS domain of GKN1 had a synergistic anti-cancer effect with 5-FU on tumor cell growth, implying that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for tumor suppression, thereby suggesting a therapeutic intervention for gastric cancer. Also, its domain inducing endogenous miR-185 directly targeted the epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. Our results suggest that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for its tumor suppressor activities.

  20. Sample Analysis at Mars (SAM) and Mars Organic Molecule Analyzer (MOMA) as Critical In Situ Investigation for Targeting Mars Returned Samples

    Science.gov (United States)

    Freissinet, C.; Glavin, D. P.; Mahaffy, P. R.; Szopa, C.; Buch, A.; Goesmann, F.; Goetz, W.; Raulin, F.; SAM Science Team; MOMA Science Team

    2018-04-01

    SAM (Curiosity) and MOMA (ExoMars) Mars instruments, seeking for organics and biosignatures, are essential to establish taphonomic windows of preservation of molecules, in order to target the most interesting samples to return from Mars.

  1. Roles of the SH2 and SH3 domains in the regulation of neuronal Src kinase functions.

    Science.gov (United States)

    Groveman, Bradley R; Xue, Sheng; Marin, Vedrana; Xu, Jindong; Ali, Mohammad K; Bienkiewicz, Ewa A; Yu, Xian-Min

    2011-02-01

    Previous studies demonstrated that intra-domain interactions between Src family kinases (SFKs), stabilized by binding of the phosphorylated C-terminus to the SH2 domain and/or binding of the SH2 kinase linker to the SH3 domain, lock the molecules in a closed conformation, disrupt the kinase active site, and inactivate SFKs. Here we report that the up-regulation of N-methyl-D-aspartate receptors (NMDARs) induced by expression of constitutively active neuronal Src (n-Src), in which the C-terminus tyrosine is mutated to phenylalanine (n-Src/Y535F), is significantly reduced by dysfunctions of the SH2 and/or SH3 domains of the protein. Furthermore, we found that dysfunctions of SH2 and/or SH3 domains reduce auto-phosphorylation of the kinase activation loop, depress kinase activity, and decrease NMDAR phosphorylation. The SH2 domain plays a greater regulatory role than the SH3 domain. Our data also show that n-Src binds directly to the C-terminus of the NMDAR NR2A subunit in vitro, with a K(D) of 108.2 ± 13.3 nM. This binding is not Src kinase activity-dependent, and dysfunctions of the SH2 and/or SH3 domains do not significantly affect the binding. These data indicate that the SH2 and SH3 domains may function to promote the catalytic activity of active n-Src, which is important in the regulation of NMDAR functions. © 2010 The Authors Journal compilation © 2010 FEBS.

  2. Interaction of the transactivation domain of B-Myb with the TAZ2 domain of the coactivator p300: molecular features and properties of the complex.

    Directory of Open Access Journals (Sweden)

    Ojore Oka

    Full Text Available The transcription factor B-Myb is a key regulator of the cell cycle in vertebrates, with activation of transcription involving the recognition of specific DNA target sites and the recruitment of functional partner proteins, including the coactivators p300 and CBP. Here we report the results of detailed studies of the interaction between the transactivation domain of B-Myb (B-Myb TAD and the TAZ2 domain of p300. The B-Myb TAD was characterized using circular dichroism, fluorescence and NMR spectroscopy, which revealed that the isolated domain exists as a random coil polypeptide. Pull-down and spectroscopic experiments clearly showed that the B-Myb TAD binds to p300 TAZ2 to form a moderately tight (K(d ~1.0-10 µM complex, which results in at least partial folding of the B-Myb TAD. Significant changes in NMR spectra of p300 TAZ2 suggest that the B-Myb TAD binds to a relatively large patch on the surface of the domain (~1200 Å(2. The apparent B-Myb TAD binding site on p300 TAZ2 shows striking similarity to the surface of CBP TAZ2 involved in binding to the transactivation domain of the transcription factor signal transducer and activator of transcription 1 (STAT1, which suggests that the structure of the B-Myb TAD-p300 TAZ2 complex may share many features with that reported for STAT1 TAD-p300 TAZ2.

  3. Chemical imaging of structured SAMs with a novel SFG microscope

    Science.gov (United States)

    Hoffmann, Dominik M. P.; Kuhnke, Klaus; Kern, Klaus

    2002-11-01

    We present a newly developed microscope for sum frequency generation (SFG) imaging of opaque and reflecting interfaces. The sample is viewed at an angle of 60° with respect to the surface normal in order to increase the collected SFG intensity. Our setup is designed to keep the whole field of view (FOV) in focus and to compensate for the distortion usually related to oblique imaging by means of a blazed grating. The separation of the SFG intensity and the reflected visible beam is accomplished by a suitable combination of spectral filters. The sum frequency microscope (SFM) is capable of in-situ chemically selective imaging by tuning the IR-beam to vibrational transitions of the respective molecules. The SFM is applied to imaging of structured self-assembled monolayers (SAM) of thiol molecules on a gold surface.

  4. Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

    Directory of Open Access Journals (Sweden)

    Zomaya Albert Y

    2006-12-01

    Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

  5. A photoaffinity scan maps regions of the p85 SH2 domain involved in phosphoprotein binding.

    Science.gov (United States)

    Williams, K P; Shoelson, S E

    1993-03-15

    Src homology 2 (SH2) domains are modular phosphotyrosine binding pockets found within a wide variety of cytoplasmic signaling molecules. Here we develop a new approach to analyzing protein-protein interfaces termed photoaffinity scanning, and apply the method to map regions of the phosphatidylinositol 3-kinase p85 SH2 domain that participate in phospho-protein binding. Each residue except phosphotyrosine (pY) within a tightly binding, IRS-1-derived phosphopeptide (GNGDpYMPMSPKS) was substituted with the photoactive amino acid, benzoylphenylalanine (Bpa). Whereas most substitutions had little effect on binding affinity, Bpa substitution of either Met (+1 and +3 with respect to pY) reduced affinity 50-100-fold to confirm their importance in the pYMXM recognition motif. In three cases photolysis of SH2 domain/Bpa phosphopeptide complexes led to cross-linking of > 50% of the SH2 domain; cross-link positions were identified by microsequence, amino acid composition, and electrospray mass spectrometric analyses. Bpa-1 cross-links within alpha-helix I, whereas Bpa+1 and Bpa+4 cross-link the SH2 domain within the flexible loop C-terminal to alpha-helix II. Moreover, cross-linking at any position prevents SH2 domain cleavage at a trypsin-sensitive site within the flexible loop between beta-strands 1 and 2. Therefore, at least three distinct SH2 regions in addition to the beta-sheet participate in phosphoprotein binding; the loop cross-linked by phosphopeptide residues C-terminal to pY appears to confer specificity to the phosphoprotein/SH2 domain interaction.

  6. 2.5-D frequency-domain viscoelastic wave modelling using finite-element method

    Science.gov (United States)

    Zhao, Jian-guo; Huang, Xing-xing; Liu, Wei-fang; Zhao, Wei-jun; Song, Jian-yong; Xiong, Bin; Wang, Shang-xu

    2017-10-01

    2-D seismic modelling has notable dynamic information discrepancies with field data because of the implicit line-source assumption, whereas 3-D modelling suffers from a huge computational burden. The 2.5-D approach is able to overcome both of the aforementioned limitations. In general, the earth model is treated as an elastic material, but the real media is viscous. In this study, we develop an accurate and efficient frequency-domain finite-element method (FEM) for modelling 2.5-D viscoelastic wave propagation. To perform the 2.5-D approach, we assume that the 2-D viscoelastic media are based on the Kelvin-Voigt rheological model and a 3-D point source. The viscoelastic wave equation is temporally and spatially Fourier transformed into the frequency-wavenumber domain. Then, we systematically derive the weak form and its spatial discretization of 2.5-D viscoelastic wave equations in the frequency-wavenumber domain through the Galerkin weighted residual method for FEM. Fixing a frequency, the 2-D problem for each wavenumber is solved by FEM. Subsequently, a composite Simpson formula is adopted to estimate the inverse Fourier integration to obtain the 3-D wavefield. We implement the stiffness reduction method (SRM) to suppress artificial boundary reflections. The results show that this absorbing boundary condition is valid and efficient in the frequency-wavenumber domain. Finally, three numerical models, an unbounded homogeneous medium, a half-space layered medium and an undulating topography medium, are established. Numerical results validate the accuracy and stability of 2.5-D solutions and present the adaptability of finite-element method to complicated geographic conditions. The proposed 2.5-D modelling strategy has the potential to address modelling studies on wave propagation in real earth media in an accurate and efficient way.

  7. Study The Effect of 4 weeks of Special Aerobic Training on CBS and SAM Levels in Hippocampus of Rats with Alzheimer-induced Disease with Aβ1-42 Injection

    Directory of Open Access Journals (Sweden)

    Farhad Azimi

    2018-03-01

    Full Text Available Abstract Background: H2S plays a key role in the pathogenesis of the Alzheimer’s disease. The aim of the present study was to investigate the effects of 4 weeks of the special aerobic training after induction of Alzheimer’s disease by Aβ1-42 injection on CBS and SAM levels in hippocampus of Wistar male rats. Materials and Methods: Twenty male Wistar rats (8 weeks old and weight 195 ± 20 g were divided into four groups including: healthy control, Alzheimer’s control, Alzheimer’s + training and sham. To induce Alzheimer’s disease, Aβ1-42 was infused into the hippocampus of rats. Training group trained for 4-week. For data analysis, one-way ANOVA was used and Eta and Omega squared tests were used to determine the effect size (p<0.05. Results: Findings revealed that 4 weeks of special aerobic training increased significantly the CBS and SAM levels in hippocampus of Alzheimer’s rats compared to the control Alzheimer’s rats ( ES=53; p= 0.007, ES= 92.22; p= 0.001. Also, we showed 4 weeks of special aerobic training increased CBS level in hippocampus of Alzheimer’s rats compared to the healthy cotrol group (ES= 44.07; p= 0.014. Conclusion: It seems that the special aerobic training can be used as a useful non-pharmacologically effective therapeutic treatment for Alzheimer's patients through positive regulation of hydrogen sulfide via CBS and SAM enzymes.

  8. Stool frequency recording in severe acute malnutrition ('StoolSAM'); an agreement study comparing maternal recall versus direct observation using diapers

    NARCIS (Netherlands)

    Voskuijl, Wieger; Potani, Isabel; Bandsma, Robert; Baan, Anne; White, Sarah; Bourdon, Celine; Kerac, Marko

    2017-01-01

    Background: Approximately 50% of the deaths of children under the age of 5 can be attributed to undernutrition, which also encompasses severe acute malnutrition (SAM). Diarrhoea is strongly associated with these deaths and is commonly diagnosed solely based on stool frequency and consistency

  9. Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.

    Science.gov (United States)

    Zhang, Di; Wlodawer, Alexander; Lubkowski, Jacek

    2016-11-20

    The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-α receptor and TYK2. Published by Elsevier Ltd.

  10. Superdiffusive motion of membrane-targeting C2 domains

    Science.gov (United States)

    Campagnola, Grace; Nepal, Kanti; Schroder, Bryce W.; Peersen, Olve B.; Krapf, Diego

    2015-12-01

    Membrane-targeting domains play crucial roles in the recruitment of signalling molecules to the plasma membrane. For most peripheral proteins, the protein-to-membrane interaction is transient. After proteins dissociate from the membrane they have been observed to rebind following brief excursions in the bulk solution. Such membrane hops can have broad implications for the efficiency of reactions on membranes. We study the diffusion of membrane-targeting C2 domains using single-molecule tracking in supported lipid bilayers. The ensemble-averaged mean square displacement (MSD) exhibits superdiffusive behaviour. However, traditional time-averaged MSD analysis of individual trajectories remains linear and does not reveal superdiffusion. Our observations are explained in terms of bulk excursions that introduce jumps with a heavy-tail distribution. These hopping events allow proteins to explore large areas in a short time. The experimental results are shown to be consistent with analytical models of bulk-mediated diffusion and numerical simulations.

  11. Nanoscopic studies of domain structure dynamics in ferroelectric La:HfO2 capacitors

    Science.gov (United States)

    Buragohain, P.; Richter, C.; Schenk, T.; Lu, H.; Mikolajick, T.; Schroeder, U.; Gruverman, A.

    2018-05-01

    Visualization of domain structure evolution under an electrical bias has been carried out in ferroelectric La:HfO2 capacitors by a combination of Piezoresponse Force Microscopy (PFM) and pulse switching techniques to study the nanoscopic mechanism of polarization reversal and the wake-up process. It has been directly shown that the main mechanism behind the transformation of the polarization hysteretic behavior and an increase in the remanent polarization value upon the alternating current cycling is electrically induced domain de-pinning. PFM imaging and local spectroscopy revealed asymmetric switching in the La:HfO2 capacitors due to a significant imprint likely caused by the different boundary conditions at the top and bottom interfaces. Domain switching kinetics can be well-described by the nucleation limited switching model characterized by a broad distribution of the local switching times. It has been found that the domain velocity varies significantly throughout the switching process indicating strong interaction with structural defects.

  12. Isolation and Molecular Characterization of Two Lectins from Dwarf Elder (Sambucus ebulus L. Blossoms Related to the Sam n1 Allergen

    Directory of Open Access Journals (Sweden)

    Tomas Girbes

    2013-10-01

    Full Text Available Sambucus species contain a number of lectins with and without antiribosomal activity. Here, we show that dwarf elder (Sambucus ebulus L. blossoms express two D-galactose-binding lectins that were isolated and purified by affinity chromatography and gel filtration. These proteins, which we named ebulin blo (A-B toxin and SELblo (B-B lectin—blo from blossoms—were subjected to molecular characterization and analysis by MALDI-TOF mass spectrometry and tryptic peptide fingerprinting. Both lectins share a high degree of amino acid sequence homology with Sambucus lectins related to the Sam n1 allergen. Ebulin blo, but not SELblo, was highly toxic by nasal instillation to mice. Overall, our results suggested that both lectins would belong to an allergen family exemplified by Sam n1 and could trigger allergy responses. Furthermore, they raise a concern about ebulin blo toxicity.

  13. The Abl SH2-kinase linker naturally adopts a conformation competent for SH3 domain binding.

    Science.gov (United States)

    Chen, Shugui; Brier, Sébastien; Smithgall, Thomas E; Engen, John R

    2007-04-01

    The core of the Abelson tyrosine kinase (c-Abl) is structurally similar to Src-family kinases where SH3 and SH2 domains pack against the backside of the kinase domain in the down-regulated conformation. Both kinase families depend upon intramolecular association of SH3 with the linker joining the SH2 and kinase domains for suppression of kinase activity. Hydrogen deuterium exchange (HX) and mass spectrometry (MS) were used to probe intramolecular interaction of the c-Abl SH3 domain with the linker in recombinant constructs lacking the kinase domain. Under physiological conditions, the c-Abl SH3 domain undergoes partial unfolding, which is stabilized by ligand binding, providing a unique assay for SH3:linker interaction in solution. Using this approach, we observed dynamic association of the SH3 domain with the linker in the absence of the kinase domain. Truncation of the linker before W254 completely prevented cis-interaction with SH3, while constructs containing amino acids past this point showed SH3:linker interactions. The observation that the Abl linker sequence exhibits SH3-binding activity in the absence of the kinase domain is unique to Abl and was not observed with Src-family kinases. These results suggest that SH3:linker interactions may have a more prominent role in Abl regulation than in Src kinases, where the down-regulated conformation is further stabilized by a second intramolecular interaction between the C-terminal tail and the SH2 domain.

  14. WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer.

    Science.gov (United States)

    Chen, Shuai; Wang, Han; Huang, Yu-Fan; Li, Ming-Li; Cheng, Jiang-Hong; Hu, Peng; Lu, Chuan-Hui; Zhang, Ya; Liu, Na; Tzeng, Chi-Meng; Zhang, Zhi-Ming

    2017-07-19

    The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo. Studies have confirmed that phosphorylated form of WBP2 can move into nuclei and activate the transcription of estrogen receptor (ER) and progesterone receptor (PR), whose expression were the indicators of breast cancer development, indicating that WBP2 may participate in the progression of breast cancer. Both overexpression of WBP2 and activation of tyrosine phosphorylation upregulate the signal cascades in the cross-regulation of the Wnt and ER signaling pathways in breast cancer. Following the binding of WBP2 to the WW domain region of TAZ which can accelerate migration, invasion and is required for the transformed phenotypes of breast cancer cells, the transformation of epithelial to mesenchymal of MCF10A is activated, suggesting that WBP2 is a key player in regulating cell migration. When WBP2 binds with WWOX, a tumor suppressor, ER transactivation and tumor growth can be suppressed. Thus, WBP2 may serve as a molecular on/off switch that controls the crosstalk between E2, WWOX, Wnt, TAZ, and other oncogenic signaling pathways. This review interprets the relationship between WBP2 and breast cancer, and provides comprehensive views about the function of WBP2 in the regulation of the pathogenesis of breast cancer and endocrine therapy in breast cancer treatment.

  15. Sequence analysis of DBL2β domain of vargene of Indonesian Plasmodium falciparum

    Science.gov (United States)

    Sulistyaningsih, E.; Romadhon, B. D.; Palupi, I.; Hidayah, F.; Dewi, R.; Prasetyo, A.

    2018-03-01

    Malaria is a major health problem in tropical countries including Indonesia. The most deadly agent is Plasmodium falciparum. In P. falciparum infection, PfEMP1 is supposed to play an important role in the pathogenesis of malaria. PfEMP1 is encoded by var gene family, it is a polymorphic protein where the extra-cellular portion contains of three distinct binding domains: Duffy binding-like (DBL), Cysteine-rich interdomain regions (CIDR) and C2. PfEMP1 varies in domain composition and binding specificity. The study explored the characteristic of Indonesian DBL2β-var genes and investigated its role to the malaria outcome. Twenty blood samples from clinically mild to severe malaria patients in Jember, East Java were collected for DNA extraction. Diagnosis was confirmed by Giemsa-stained thick blood smear. PCR was conducted using specific primer targeting on the full-length of DBL2ß and resulted approximately single band of 1,7 kb in a sample. This band was observed only from severe malaria sample. Sequence analysis directly from PCR product showed 74-99% similarities with previous sequences in Gene Bank. In conclusion, the DBL2β domain of vargene of Indonesian isolates was 1603 nucleotides in length and there was a possible association of the existence of DBL2β domain with the severity of malaria outcome.

  16. A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity.

    Science.gov (United States)

    Mills, Jamie E; Whitford, Paul C; Shaffer, Jennifer; Onuchic, Jose N; Adams, Joseph A; Jennings, Patricia A

    2007-02-02

    The SH2 domain of the C-terminal Src kinase [Csk] contains a unique disulfide bond that is not present in other known SH2 domains. To investigate whether this unusual disulfide bond serves a novel function, the effects of disulfide bond formation on catalytic activity of the full-length protein and on the structure of the SH2 domain were investigated. The kinase activity of full-length Csk decreases by an order of magnitude upon formation of the disulfide bond in the distal SH2 domain. NMR spectra of the fully oxidized and fully reduced SH2 domains exhibit similar chemical shift patterns and are indicative of similar, well-defined tertiary structures. The solvent-accessible disulfide bond in the isolated SH2 domain is highly stable and far from the small lobe of the kinase domain. However, reduction of this bond results in chemical shift changes of resonances that map to a cluster of residues that extend from the disulfide bond across the molecule to a surface that is in direct contact with the small lobe of the kinase domain in the intact molecule. Normal mode analyses and molecular dynamics calculations suggest that disulfide bond formation has large effects on residues within the kinase domain, most notably within the active-site cleft. Overall, the data indicate that reversible cross-linking of two cysteine residues in the SH2 domain greatly impacts catalytic function and interdomain communication in Csk.

  17. Structure of the N-terminal domain of the protein Expansion: an ‘Expansion’ to the Smad MH2 fold

    International Nuclear Information System (INIS)

    Beich-Frandsen, Mads; Aragón, Eric; Llimargas, Marta; Benach, Jordi; Riera, Antoni; Pous, Joan; Macias, Maria J.

    2015-01-01

    Expansion is a modular protein that is conserved in protostomes. The first structure of the N-terminal domain of Expansion has been determined at 1.6 Å resolution and the new Nα-MH2 domain was found to belong to the Smad/FHA superfamily of structures. Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of protein belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily

  18. Structure of the N-terminal domain of the protein Expansion: an ‘Expansion’ to the Smad MH2 fold

    Energy Technology Data Exchange (ETDEWEB)

    Beich-Frandsen, Mads; Aragón, Eric [Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona (Spain); Llimargas, Marta [Institut de Biologia Molecular de Barcelona, IBMB–CSIC, Baldiri Reixac 10, 08028 Barcelona (Spain); Benach, Jordi [ALBA Synchrotron, BP 1413, km 3.3, Cerdanyola del Vallès (Spain); Riera, Antoni [Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona (Spain); Universitat de Barcelona, Martí i Franqués 1-11, 08028 Barcelona (Spain); Pous, Joan [Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona (Spain); Platform of Crystallography IBMB–CSIC, Baldiri Reixac 10, 08028 Barcelona (Spain); Macias, Maria J., E-mail: maria.macias@irbbarcelona.org [Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona (Spain); Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, 08010 Barcelona (Spain)

    2015-04-01

    Expansion is a modular protein that is conserved in protostomes. The first structure of the N-terminal domain of Expansion has been determined at 1.6 Å resolution and the new Nα-MH2 domain was found to belong to the Smad/FHA superfamily of structures. Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of protein belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily.

  19. Fluorocarbon Contamination from the Drill on the Mars Science Laboratory: Potential Science Impact on Detecting Martian Organics by Sample Analysis at Mars (SAM)

    Science.gov (United States)

    Eigenbrode, J. L.; McAdam, A.; Franz, H.; Freissinet, C.; Bower, H.; Floyd, M.; Conrad, P.; Mahaffy, P.; Feldman, J.; Hurowitz, J.; hide

    2013-01-01

    Polytetrafluoroethylene (PTFE or trade name: Teflon by Dupont Co.) has been detected in rocks drilled during terrestrial testing of the Mars Science Laboratory (MSL) drilling hardware. The PTFE in sediments is a wear product of the seals used in the Drill Bit Assemblies (DBAs). It is expected that the drill assembly on the MSL flight model will also shed Teflon particles into drilled samples. One of the primary goals of the Sample Analysis at Mars (SAM) instrument suite on MSL is to test for the presence of martian organics in samples. Complications introduced by the potential presence of PTFE in drilled samples to the SAM evolved gas analysis (EGA or pyrolysisquadrupole mass spectrometry, pyr-QMS) and pyrolysis- gas chromatography mass spectrometry (Pyr- GCMS) experiments was investigated.

  20. Granular statistical mechanics - Building on the legacy of Sir Sam Edwards

    Science.gov (United States)

    Blumenfeld, Raphael

    When Sir Sam Edwards laid down the foundations for the statistical mechanics of jammed granular materials he opened a new field in soft condensed matter and many followed. In this presentation we review briefly the Edwards formalism and some of its less discussed consequences. We point out that the formalism is useful for other classes of systems - cellular and porous materials. A certain shortcoming of the original formalism is then discussed and a modification to overcome it is proposed. Finally, a derivation of an equation of state with the new formalism is presented; the equation of state is analogous to the PVT relation for thermal gases, relating the volume, the boundary stress and measures of the structural and stress fluctuations. NUDT, Changsha, China, Imperial College London, UK, Cambridge University, UK.

  1. Radical SAM, A Novel Protein Superfamily Linking Unresolved Steps in Familiar Biosynthetic Pathways with Radical Mechanisms: Functional Characterization Using New Analysis and Information Visualization Methods

    Energy Technology Data Exchange (ETDEWEB)

    Sofia, Heidi J.; Chen, Guang; Hetzler, Elizabeth G.; Reyes Spindola, Jorge F.; Miller, Nancy E.

    2001-03-01

    A large protein superfamily with over 500 members has been discovered and analyzed using powerful new bioinformatics and information visualization methods. Evidence exists that these proteins generate a 5?-deoxyadenosyl radical by reductive cleavage of S-adenosylmethionine (SAM) through an unusual Fe-S center. Radical SAM superfamily proteins function in DNA precursor, vitamin, cofactor, antibiotic, and herbicide biosynthesis in a collection of basic and familiar pathways. One of the members is interferon-inducible and is considered a candidate drug target for osteoporosis. The identification of this superfamily suggests that radical-based catalysis is important in a number of previously well-studied but unresolved biochemical pathways.

  2. Did life exist on Mars? Search for organic and inorganic signatures, one of the goals for ``SAM'' (sample analysis at Mars)

    Science.gov (United States)

    Cabane, M.; Coll, P.; Szopa, C.; Israël, G.; Raulin, F.; Sternberg, R.; Mahaffy, P.; Person, A.; Rodier, C.; Navarro-Gonzàlez, R.; Niemann, H.; Harpold, D.; Brinckerhoff, W.

    2004-01-01

    Observation of Mars shows signs of a past Earth-like climate, and, in that case, there is no objection to the possible development of life, in the underground or at the surface, as in the terrestrial primitive biosphere. Sample analysis at Mars (SAM) is an experiment which may be proposed for atmospheric, ground and underground in situ measurements. One of its goals is to bring direct or indirect information on the possibility for life to have developed on Mars, and to detect traces of past or present biological activity. With this aim, it focuses on the detection of organic molecules: volatile organics are extracted from the sample by simple heating, whereas refractory molecules are made analyzable (i.e. volatile), using derivatization technique or fragmentation by pyrolysis. Gaseous mixtures thus obtained are analyzed by gas chromatography associated to mass spectrometry. Beyond organics, carbonates and other salts are associated to the dense and moist atmosphere necessary to the development of life, and might have formed and accumulated in some places on Mars. They represent another target for SAM. Heating of the samples allows the analysis of structural gases of these minerals (CO2 from carbonates, etc.), enabling to identify them. We also show, in this paper, that it may be possible to discriminate between abiotic minerals, and minerals (shells, etc.) created by living organisms.

  3. Partial ion yield and NEXAFS of 2-(perfluorooctyl)ethanethiol self-assembled monolayer: Comparison with PTFE results

    CERN Document Server

    Setoyama, H; Murase, T; Imamura, M; Mase, K; Okudaira, K K; Hara, M; Ueno, N

    2003-01-01

    Partial-ion-yield (PIY) spectra using ion time-of-flight (TOF) method and near-edge absorption fine structure (NEXAFS) spectra were measured for 2-(perfluorooctyl)ethanethiol [CF sub 3 (CF sub 2) sub 7 (CH sub 2) sub 2 SH] self-assembled monolayer (F8-SAM) on Au(1 1 1) near carbon K-edge. The PIY spectra of the F8-SAM at the magic angle, where -CF sub 3 groups exist at the surface were compared with those of the rubbed polytetrafluoroethylene (PTFE) thin film. The F sup + intensity from the F8-SAM at the photon energy of the sharp peak of the NEXAFS, which originates from the excitation of C1s electron to sigma sup * (C-F) states at -CF sub 2 - chain, was extremely smaller than that from the rubbed PTFE film. This result clearly indicates that the ions observed by PIY do not originate from the film inside but from the surface. This was confirmed by changes in ion-TOF mass spectra during soft X-ray induced etching of the F8-SAM. The NEXAFS peaks of the F8-SAM were also assigned by considering PIY results.

  4. The BRCT domain is a phospho-protein binding domain.

    Science.gov (United States)

    Yu, Xiaochun; Chini, Claudia Christiano Silva; He, Miao; Mer, Georges; Chen, Junjie

    2003-10-24

    The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.

  5. The first transmembrane domain (TM1) of β2-subunit binds to the transmembrane domain S1 of α-subunit in BK potassium channels

    Science.gov (United States)

    Morera, Francisco J.; Alioua, Abderrahmane; Kundu, Pallob; Salazar, Marcelo; Gonzalez, Carlos; Martinez, Agustin D.; Stefani, Enrico; Toro, Ligia; Latorre, Ramon

    2012-01-01

    The BK channel is one of the most broadly expressed ion channels in mammals. In many tissues, the BK channel pore-forming α-subunit is associated to an auxiliary β-subunit that modulates the voltage- and Ca2+-dependent activation of the channel. Structural components present in β-subunits that are important for the physical association with the α-subunit are yet unknown. Here, we show through co-immunoprecipitation that the intracellular C-terminus, the second transmembrane domain (TM2) and the extracellular loop of the β2-subunit are dispensable for association with the α-subunit pointing transmembrane domain 1 (TM1) as responsible for the interaction. Indeed, the TOXCAT assay for transmembrane protein–protein interactions demonstrated for the first time that TM1 of the β2-subunit physically binds to the transmembrane S1 domain of the α-subunit. PMID:22710124

  6. Cognitive training and selective attention in the aging brain: an electrophysiological study.

    Science.gov (United States)

    O'Brien, Jennifer L; Edwards, Jerri D; Maxfield, Nathan D; Peronto, Carol L; Williams, Victoria A; Lister, Jennifer J

    2013-11-01

    Age-related deficits in selective attention are hypothesized to result from decrements in inhibition of task-irrelevant information. Speed of processing (SOP) training is an adaptive cognitive intervention designed to enhance processing speed for attention tasks. The effectiveness of SOP training to improve cognitive and everyday functional performance is well documented. However, underlying mechanisms of these training benefits are unknown. Participants completed a visual search task evaluated using event-related potentials (ERPs) before and after 10 weeks of SOP training or no contact. N2pc and P3b components were evaluated to determine SOP training effects on attentional resource allocation and capacity. Selective attention to a target was enhanced after SOP training compared to no training. N2pc and P3b amplitudes increased after training, reflecting attentional allocation and capacity enhancement, consistent with previous studies demonstrating behavioral improvements in selective attention following SOP training. Changes in ERPs related to attention allocation and capacity following SOP training support the idea that training leads to cognitive enhancement. Specifically, we provide electrophysiological evidence that SOP training may be successful in counteracting age-related declines in selective attention. This study provides important evidence of the underlying mechanisms by which SOP training improves cognitive function in older adults. Published by Elsevier Ireland Ltd.

  7. Steric Clash in the SET Domain of Histone Methyltransferase NSD1 as a Cause of Sotos Syndrome and Its Genetic Heterogeneity in a Brazilian Cohort

    Directory of Open Access Journals (Sweden)

    Kyungsoo Ha

    2016-11-01

    Full Text Available Most histone methyltransferases (HMTase harbor a predicted Su(var3–9, Enhancer-of-zeste, Trithorax (SET domain, which transfers a methyl group to a lysine residue in their substrates. Mutations of the SET domains were reported to cause intellectual disability syndromes such as Sotos, Weaver, or Kabuki syndromes. Sotos syndrome is an overgrowth syndrome with intellectual disability caused by haploinsufficiency of the nuclear receptor binding SET domain protein 1 (NSD1 gene, an HMTase at 5q35.2–35.3. Here, we analyzed NSD1 in 34 Brazilian Sotos patients and identified three novel and eight known mutations. Using protein modeling and bioinformatic approaches, we evaluated the effects of one novel (I2007F and 21 previously reported missense mutations in the SET domain. For the I2007F mutation, we observed conformational change and loss of structural stability in Molecular Dynamics (MD simulations which may lead to loss-of-function of the SET domain. For six mutations near the ligand-binding site we observed in simulations steric clashes with neighboring side chains near the substrate S-Adenosyl methionine (SAM binding site, which may disrupt the enzymatic activity of NSD1. These results point to a structural mechanism underlying the pathology of the NSD1 missense mutations in the SET domain in Sotos syndrome. NSD1 mutations were identified in only 32% of the Brazilian Sotos patients in our study cohort suggesting other genes (including unknown disease genes underlie the molecular etiology for the majority of these patients. Our studies also found NSD1 expression to be profound in human fetal brain and cerebellum, accounting for prenatal onset and hypoplasia of cerebellar vermis seen in Sotos syndrome.

  8. Preliminary crystallographic characterization of the Grb2 SH2 domain in complex with a FAK-derived phosphotyrosyl peptide

    International Nuclear Information System (INIS)

    Chen, Hsiao-Hsin; Chen, Cuei-Wen; Chang, Yu-Yung; Shen, Tang-Long; Hsu, Chun-Hua

    2010-01-01

    Crystals of the Grb2 SH2 domain in complex with a phosphotyrosyl peptide corresponding to residues 921–930 of focal adhesion kinase (FAK) have been obtained using the sitting-drop vapour-diffusion technique. Data have been collected to 2.49 Å resolution. Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein with a single SH2 domain that specifically binds to focal adhesion kinase (FAK) when residue Tyr925 of FAK is phosphorylated. The Grb2–FAK interaction is associated with cellular integrin-activated signal transduction events leading to the activation of the Ras-MAPK pathway. Crystals of the Grb2 SH2 domain in complex with a phosphopeptide corresponding to residues 921–930 of FAK have been obtained using the sitting-drop vapour-diffusion technique. The crystals belonged to space group P3 1 21, with unit-cell parameters a = b = 102.7, c = 127.6 Å, α = β = 90.0, γ = 120.0°. A diffraction data set was collected from a flash-cooled crystal at 100 K to 2.49 Å resolution using synchrotron radiation. Structure determination by molecular replacement and analysis of the detailed structure of the complex are currently in progress

  9. Localization and chiral symmetry in 2+1 flavor domain wall QCD

    Energy Technology Data Exchange (ETDEWEB)

    David J. Antonio; Kenneth C. Bowler; Peter A. Boyle; Norman H. Christ; Michael A. Clark; Saul D. Cohen; Chris Dawson; Alistair Hart; Balint Joó; Chulwoo Jung; Richard D. Kenway; Shu Li; Meifeng Lin; Robert D. Mawhinney; Christopher M. Maynard; Shigemi Ohta; Robert J. Tweedie; Azusa Yamaguchi

    2008-01-01

    We present results for the dependence of the residual mass of domain wall fermions (DWF) on the size of the fifth dimension and its relation to the density and localization properties of low-lying eigenvectors of the corresponding hermitian Wilson Dirac operator relevant to simulations of 2+1 flavor domain wall QCD. Using the DBW2 and Iwasaki gauge actions, we generate ensembles of configurations with a $16^3\\times 32$ space-time volume and an extent of 8 in the fifth dimension for the sea quarks. We demonstrate the existence of a regime where the degree of locality, the size of chiral symmetry breaking and the rate of topology change can be acceptable for inverse lattice spacings $a^{-1} \\ge 1.6$ GeV.

  10. Functional properties of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli

    International Nuclear Information System (INIS)

    Wilhelm, O.G.; Jaskunas, S.R.; Vlahos, C.J.; Bang, N.U.

    1990-01-01

    The kringle-2 domain (residues 176-262) of tissue-type plasminogen activator (t-PA) was cloned and expressed in Escherichia coli. The recombinant peptide, which concentrated in cytoplasmic inclusion bodies, was isolated, solubilized, chemically refolded, and purified by affinity chromatography on lysine-Sepharose to apparent homogeneity. [35S]Cysteine-methionine-labeled polypeptide was used to study the interactions of kringle-2 with lysine, fibrin, and plasminogen activator inhibitor-1. The kringle-2 domain bound to lysine-Sepharose and to preformed fibrin with a Kd = 104 +/- 6.2 microM (0.86 +/- 0.012 binding site) and a Kd = 4.2 +/- 1.05 microM (0.80 +/- 0.081 binding site), respectively. Competition experiments and direct binding studies showed that the kringle-2 domain is required for the formation of the ternary t-PA-plasminogen-intact fibrin complex and that the association between the t-PA kringle-2 domain and fibrin does not require plasmin degradation of fibrin and exposure of new COOH-terminal lysine residues. We also observed that kringle-2 forms a complex with highly purified guanidine-activated plasminogen activator inhibitor-1, dissociable by 0.2 M epsilon-aminocaproic acid. The kringle-2 polypeptide significantly inhibited tissue plasminogen activator/plasminogen activator inhibitor-1 interaction. The kringle-2 domain bound to plasminogen activator inhibitor-1 in a specific and saturable manner with a Kd = 0.51 +/- 0.055 microM (0.35 +/- 0.026 binding site). Therefore, the t-PA kringle-2 domain is important for the interaction of t-PA not only with fibrin, but also with plasminogen activator inhibitor-1 and thus represents a key structure in the regulation of fibrinolysis

  11. 3D Mapping of the SPRY2 domain of ryanodine receptor 1 by single-particle cryo-EM.

    Directory of Open Access Journals (Sweden)

    Alex Perálvarez-Marín

    Full Text Available The type 1 skeletal muscle ryanodine receptor (RyR1 is principally responsible for Ca(2+ release from the sarcoplasmic reticulum and for the subsequent muscle contraction. The RyR1 contains three SPRY domains. SPRY domains are generally known to mediate protein-protein interactions, however the location of the three SPRY domains in the 3D structure of the RyR1 is not known. Combining immunolabeling and single-particle cryo-electron microscopy we have mapped the SPRY2 domain (S1085-V1208 in the 3D structure of RyR1 using three different antibodies against the SPRY2 domain. Two obstacles for the image processing procedure; limited amount of data and signal dilution introduced by the multiple orientations of the antibody bound in the tetrameric RyR1, were overcome by modifying the 3D reconstruction scheme. This approach enabled us to ascertain that the three antibodies bind to the same region, to obtain a 3D reconstruction of RyR1 with the antibody bound, and to map SPRY2 to the periphery of the cytoplasmic domain of RyR1. We report here the first 3D localization of a SPRY2 domain in any known RyR isoform.

  12. Should total landings be used to correct estimated catch in numbers or mean-weight-at-age?

    DEFF Research Database (Denmark)

    Lewy, Peter; Lassen, H.

    1997-01-01

    Many ICES fish stock assessment working groups have practised Sum Of Products, SOP, correction. This correction stems from a comparison of total weights of the known landings and the SOP over age of catch in number and mean weight-at-age, which ideally should be identical. In case of SOP...... discrepancies some countries correct catch in numbers while others correct mean weight-at-age by a common factor, the ratio between landing and SOP. The paper shows that for three sampling schemes the SOP corrections are statistically incorrect and should not be made since the SOP is an unbiased estimate...... of the total landings. Calculation of the bias of estimated catch in numbers and mean weight-at-age shows that SOP corrections of either of these estimates may increase the bias. Furthermore, for five demersal and one pelagic North Sea species it is shown that SOP discrepancies greater than 2% from...

  13. The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions.

    Science.gov (United States)

    Ferrao, Ryan; Lupardus, Patrick J

    2017-01-01

    The Janus kinases (JAKs) are non-receptor tyrosine kinases essential for signaling in response to cytokines and interferons and thereby control many essential functions in growth, development, and immune regulation. JAKs are unique among tyrosine kinases for their constitutive yet non-covalent association with class I and II cytokine receptors, which upon cytokine binding bring together two JAKs to create an active signaling complex. JAK association with cytokine receptors is facilitated by N-terminal FERM and SH2 domains, both of which are classical mediators of peptide interactions. Together, the JAK FERM and SH2 domains mediate a bipartite interaction with two distinct receptor peptide motifs, the proline-rich "Box1" and hydrophobic "Box2," which are present in the intracellular domain of cytokine receptors. While the general sidechain chemistry of Box1 and Box2 peptides is conserved between receptors, they share very weak primary sequence homology, making it impossible to posit why certain JAKs preferentially interact with and signal through specific subsets of cytokine receptors. Here, we review the structure and function of the JAK FERM and SH2 domains in light of several recent studies that reveal their atomic structure and elucidate interaction mechanisms with both the Box1 and Box2 receptor motifs. These crystal structures demonstrate how evolution has repurposed the JAK FERM and SH2 domains into a receptor-binding module that facilitates interactions with multiple receptors possessing diverse primary sequences.

  14. Coping with Computer Viruses: General Discussion and Review of Symantec Anti-Virus for the Macintosh.

    Science.gov (United States)

    Primich, Tracy

    1992-01-01

    Discusses computer viruses that attack the Macintosh and describes Symantec AntiVirus for Macintosh (SAM), a commercial program designed to detect and eliminate viruses; sample screen displays are included. SAM is recommended for use in library settings as well as two public domain virus protection programs. (four references) (MES)

  15. Remarkable Electromechanical Coupling in the 22 Composite Based on Single-domain PMN–0.33PT Crystal

    Directory of Open Access Journals (Sweden)

    Vitaly Yu. TOPOLOV

    2009-10-01

    Full Text Available A novel parallel-connected 22 single-domain 0.67Pb(Mg1/3Nb2/3O3 – 0.33PbTiO3 crystal / polymer composite with various orientations of polarization vectors of the components is proposed to analyze behavior of electromechanical coupling factors k*3j and k*k where j = 1, 2 and 3. It is shown that the combination of the highly piezo-active relaxor-ferroelectric single-domain component and the piezoelectric polymer provides considerable values of k*k (min k*k » –0.8 and max k*k» 0.7 and |k*33| (about 0.9. The active role of the polarization orientation effect and the composite structure in attaining the high performance is emphasized in this work. A strong correlation between k*k and the hydrostatic piezoelectric coefficient is first revealed near min k*k and max k*k of the 22 composite. Some advantages concerned with the presence of the single-domain component in the 22 composite are discussed in connection with the large values of k*3j and k*k as well as with the considerable anisotropy of k*3j.

  16. Molecular Mechanisms of SH2- and PTB-Domain-Containing Proteins in Receptor Tyrosine Kinase Signaling

    Science.gov (United States)

    Wagner, Melany J.; Stacey, Melissa M.; Liu, Bernard A.; Pawson, Tony

    2013-01-01

    Intracellular signaling is mediated by reversible posttranslational modifications (PTMs) that include phosphorylation, ubiquitination, and acetylation, among others. In response to extracellular stimuli such as growth factors, receptor tyrosine kinases (RTKs) typically dimerize and initiate signaling through phosphorylation of their cytoplasmic tails and downstream scaffolds. Signaling effectors are recruited to these phosphotyrosine (pTyr) sites primarily through Src homology 2 (SH2) domains and pTyr-binding (PTB) domains. This review describes how these conserved domains specifically recognize pTyr residues and play a major role in mediating precise downstream signaling events. PMID:24296166

  17. Molecular mechanisms of SH2- and PTB-domain-containing proteins in receptor tyrosine kinase signaling.

    Science.gov (United States)

    Wagner, Melany J; Stacey, Melissa M; Liu, Bernard A; Pawson, Tony

    2013-12-01

    Intracellular signaling is mediated by reversible posttranslational modifications (PTMs) that include phosphorylation, ubiquitination, and acetylation, among others. In response to extracellular stimuli such as growth factors, receptor tyrosine kinases (RTKs) typically dimerize and initiate signaling through phosphorylation of their cytoplasmic tails and downstream scaffolds. Signaling effectors are recruited to these phosphotyrosine (pTyr) sites primarily through Src homology 2 (SH2) domains and pTyr-binding (PTB) domains. This review describes how these conserved domains specifically recognize pTyr residues and play a major role in mediating precise downstream signaling events.

  18. Academy of Nutrition and Dietetics: Revised 2017 Standards of Practice and Standards of Professional Performance for Registered Dietitian Nutritionists (Competent, Proficient, and Expert) in Diabetes Care.

    Science.gov (United States)

    Davidson, Patricia; Ross, Tamara; Castor, Chimene

    2018-05-01

    There are 30.3 million people with diabetes and 86 million with prediabetes in the United States, underscoring the growing need for comprehensive diabetes care and nutrition for the management of diabetes and diabetes-related conditions. Management of diabetes is also critical for the prevention of diabetes-related complications such as cardiovascular and renal disease. The Diabetes Care and Education Dietetic Practice Group along with the Academy of Nutrition and Dietetics Quality Management Committee have updated the Standards of Practice (SOP) and Standards of Professional Performance (SOPP) for Registered Dietitian Nutritionists (RDNs) in Diabetes Care. The SOP and SOPP for RDNs in Diabetes Care provide indicators that describe three levels of practice: competent, proficient, and expert. The SOP utilizes the Nutrition Care Process and clinical workflow elements for care and management of those with diabetes and prediabetes. The SOPP describes six domains that focus on professionalism: Quality in Practice, Competence and Accountability, Provision of Services, Application of Research, Communication and Application of Knowledge, and Utilization and Management of Resources. Specific indicators outlined in the SOP and SOPP depict how these standards apply to practice. The SOP and SOPP are complementary resources for RDNs caring for individuals with diabetes or specializing in diabetes care or practicing in other diabetes-related areas, including research. The SOP and SOPP are intended to be used for RDN self-evaluation for ensuring competent practice and for determining potential education and training needs for advancement to a higher practice level in a variety of settings. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  19. Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

    International Nuclear Information System (INIS)

    Vognsen, Tina; Kristensen, Ole

    2012-01-01

    Highlights: ► The crystal structure of the NTF2-like domain of Rasputin protein is presented. ► Differences to known ligand binding sites of nuclear transport factor 2 are discussed. ► A new ligand binding site for the Rasputin and G3BP proteins is proposed. -- Abstract: The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7 Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a β-sheet and three α-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.

  20. Desain dan Implementasi Standar Operasional Prosedur (SOP Keamanan Sistem Informasi Fakultas Teknik Universitas Diponegoro Menggunakan Standar ISO 27001

    Directory of Open Access Journals (Sweden)

    Penji Prasetya

    2015-08-01

    Full Text Available Like today's modern era, information technology is needed to support the business processes of the organization. In the use of information technology organization must have policies and standard operating procedures are good that any work carried out in the appropriate direction of the organization. Not only that, the organization must also pay attention to information security of any assets owned. This final project aims to make policies and standard operating procedures (SOP and assessing the information security risk in the assets of the organization. In the process of this skripsi refers to the standard of ISO 27001 as the standard for information security management and use of qualitative methodology, where qualitative methodology is a methodology that produces descriptive data in the form of words written or spoken of people and behaviors that can be observed. This final project resulted in the level of risk that is contained in the value of assets and generate recommendations to improve the security controls in the information security of assets based on the clauses of ISO 27001. In accordance with the initial objective of this final project also produce information security policy document and document information security standard operating procedures.