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Sample records for exploiting disulfide assisted

  1. Purification of correctly oxidized MHC class I heavy-chain molecules under denaturing conditions: a novel strategy exploiting disulfide assisted protein folding

    DEFF Research Database (Denmark)

    Ferré, Henrik; Ruffet, Emmanuel; Blicher, Thomas

    2003-01-01

    The aim of this study has been to develop a strategy for purifying correctly oxidized denatured major histocompability complex class I (MHC-I) heavy-chain molecules, which on dilution, fold efficiently and become functional. Expression of heavy-chain molecules in bacteria results in the formation...... of insoluble cellular inclusion bodies, which must be solubilized under denaturing conditions. Their subsequent purification and refolding is complicated by the fact that (1). correct folding can only take place in combined presence of beta(2)-microglobulin and a binding peptide; and (2). optimal in vitro...... conditions for disulfide bond formation ( approximately pH 8) and peptide binding ( approximately pH 6.6) are far from complementary. Here we present a two-step strategy, which relies on uncoupling the events of disulfide bond formation and peptide binding. In the first phase, heavy-chain molecules...

  2. Purification of correctly oxidized MHC class I heavy-chain molecules under denaturing conditions: A novel strategy exploiting disulfide assisted protein folding

    DEFF Research Database (Denmark)

    Ferré, Henrik; Ruffet, E.; Blicher, T.

    2003-01-01

    The aim of this study has been to develop a strategy for purifying correctly oxidized denatured major histocompability complex class I (MHC-I) heavy-chain molecules, which on dilution, fold efficiently and become functional. Expression of heavy-chain molecules in bacteria results in the formation...... of insoluble cellular inclusion bodies, which must be solubilized under denaturing conditions. Their subsequent purification and refolding is complicated by the fact that (1) correct folding can only take place in combined presence of beta(2)-microglobulin and a binding peptide; and (2) optimal in vitro...... conditions for disulfide bond formation (similar topH 8) and peptide binding (similar topH 6.6) are far from complementary. Here we present a two-step strategy, which relies on uncoupling the events of disulfide bond formation and peptide binding. In the first phase, heavy-chain molecules with correct...

  3. Hydrogen-assisted post-growth substitution of tellurium into molybdenum disulfide monolayers with tunable compositions

    Science.gov (United States)

    Yin, Guoli; Zhu, Dancheng; Lv, Danhui; Hashemi, Arsalan; Fei, Zhen; Lin, Fang; Krasheninnikov, Arkady V.; Zhang, Ze; Komsa, Hannu-Pekka; Jin, Chuanhong

    2018-04-01

    Herein we report the successful doping of tellurium (Te) into molybdenum disulfide (MoS2) monolayers to form MoS2x Te2(1-x) alloy with variable compositions via a hydrogen-assisted post-growth chemical vapor deposition process. It is confirmed that H2 plays an indispensable role in the Te substitution into as-grown MoS2 monolayers. Atomic-resolution transmission electron microscopy allows us to determine the lattice sites and the concentration of introduced Te atoms. At a relatively low concentration, tellurium is only substituted in the sulfur sublattice to form monolayer MoS2(1-x)Te2x alloy, while with increasing Te concentration (up to ˜27.6% achieved in this study), local regions with enriched tellurium, large structural distortions, and obvious sulfur deficiency are observed. Statistical analysis of the Te distribution indicates the random substitution. Density functional theory calculations are used to investigate the stability of the alloy structures and their electronic properties. Comparison with experimental results indicate that the samples are unstrained and the Te atoms are predominantly substituted in the top S sublattice. Importantly, such ultimately thin Janus structure of MoS2(1-x)Te2x exhibits properties that are distinct from their constituents. We believe our results will inspire further exploration of the versatile properties of asymmetric 2D TMD alloys.

  4. Microwave-assisted acid and base hydrolysis of intact proteins containing disulfide bonds for protein sequence analysis by mass spectrometry.

    Science.gov (United States)

    Reiz, Bela; Li, Liang

    2010-09-01

    Controlled hydrolysis of proteins to generate peptide ladders combined with mass spectrometric analysis of the resultant peptides can be used for protein sequencing. In this paper, two methods of improving the microwave-assisted protein hydrolysis process are described to enable rapid sequencing of proteins containing disulfide bonds and increase sequence coverage, respectively. It was demonstrated that proteins containing disulfide bonds could be sequenced by MS analysis by first performing hydrolysis for less than 2 min, followed by 1 h of reduction to release the peptides originally linked by disulfide bonds. It was shown that a strong base could be used as a catalyst for microwave-assisted protein hydrolysis, producing complementary sequence information to that generated by microwave-assisted acid hydrolysis. However, using either acid or base hydrolysis, amide bond breakages in small regions of the polypeptide chains of the model proteins (e.g., cytochrome c and lysozyme) were not detected. Dynamic light scattering measurement of the proteins solubilized in an acid or base indicated that protein-protein interaction or aggregation was not the cause of the failure to hydrolyze certain amide bonds. It was speculated that there were some unknown local structures that might play a role in preventing an acid or base from reacting with the peptide bonds therein. 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

  5. Electrochemistry-assisted top-down characterization of disulfide-containing proteins.

    Science.gov (United States)

    Zhang, Yun; Cui, Weidong; Zhang, Hao; Dewald, Howard D; Chen, Hao

    2012-04-17

    Covalent disulfide bond linkage in a protein represents an important challenge for mass spectrometry (MS)-based top-down protein structure analysis as it reduces the backbone cleavage efficiency for MS/MS dissociation. This study presents a strategy for solving this critical issue via integrating electrochemistry (EC) online with a top-down MS approach. In this approach, proteins undergo electrolytic reduction in an electrochemical cell to break disulfide bonds and then undergo online ionization into gaseous ions for analysis by electron-capture dissociation (ECD) and collision-induced dissociation (CID). The electrochemical reduction of proteins allows one to remove disulfide bond constraints and also leads to increased charge numbers of the resulting protein ions. As a result, sequence coverage was significantly enhanced, as exemplified by β-lactoglobulin A (24 vs 75 backbone cleavages before and after electrolytic reduction, respectively) and lysozyme (5 vs 66 backbone cleavages before and after electrolytic reduction, respectively). This methodology is fast and does not need chemical reductants, which would have an important impact in high-throughput proteomics research.

  6. Assisting children born of sexual exploitation and abuse

    Directory of Open Access Journals (Sweden)

    Lauren Rumble

    2007-01-01

    Full Text Available The UN Secretary-General has issued a strategy tosupport victims of sexual exploitation and abuse by UNstaff. It includes a controversial proposal to introduceDNA sampling for all UN staff. Unless this suggestionis adopted, an important opportunity to implementa truly survivor-centred approach may be lost.

  7. An Educational Program to Assist Clinicians in Identifying Elder Investment Fraud and Financial Exploitation

    Science.gov (United States)

    Mills, Whitney L.; Roush, Robert E.; Moye, Jennifer; Kunik, Mark E.; Wilson, Nancy L.; Taffet, George E.; Naik, Aanand D.

    2012-01-01

    Due to age-related factors and illnesses, older adults may become vulnerable to elder investment fraud and financial exploitation (EIFFE). The authors describe the development and preliminary evaluation of an educational program to raise awareness and assist clinicians in identifying older adults at risk. Participants (n = 127) gave high ratings…

  8. Human-Assisted Machine Information Exploitation: a crowdsourced investigation of information-based problem solving

    Science.gov (United States)

    Kase, Sue E.; Vanni, Michelle; Caylor, Justine; Hoye, Jeff

    2017-05-01

    The Human-Assisted Machine Information Exploitation (HAMIE) investigation utilizes large-scale online data collection for developing models of information-based problem solving (IBPS) behavior in a simulated time-critical operational environment. These types of environments are characteristic of intelligence workflow processes conducted during human-geo-political unrest situations when the ability to make the best decision at the right time ensures strategic overmatch. The project takes a systems approach to Human Information Interaction (HII) by harnessing the expertise of crowds to model the interaction of the information consumer and the information required to solve a problem at different levels of system restrictiveness and decisional guidance. The design variables derived from Decision Support Systems (DSS) research represent the experimental conditions in this online single-player against-the-clock game where the player, acting in the role of an intelligence analyst, is tasked with a Commander's Critical Information Requirement (CCIR) in an information overload scenario. The player performs a sequence of three information processing tasks (annotation, relation identification, and link diagram formation) with the assistance of `HAMIE the robot' who offers varying levels of information understanding dependent on question complexity. We provide preliminary results from a pilot study conducted with Amazon Mechanical Turk (AMT) participants on the Volunteer Science scientific research platform.

  9. Tungsten disulfide nanosheet and exonuclease III co-assisted amplification strategy for highly sensitive fluorescence polarization detection of DNA glycosylase activity

    International Nuclear Information System (INIS)

    Zhao, Jingjin; Ma, Yefei; Kong, Rongmei; Zhang, Liangliang; Yang, Wen; Zhao, Shulin

    2015-01-01

    Herein, we introduced a tungsten disulfide (WS 2 ) nanosheet and exonuclease III (Exo III) co-assisted signal amplification strategy for highly sensitive fluorescent polarization (FP) assay of DNA glycosylase activity. Two DNA glycosylases, uracil-DNA glycosylase (UDG) and human 8-oxoG DNA glycosylase 1 (hOGG1), were tested. A hairpin-structured probe (HP) which contained damaged bases in the stem was used as the substrate. The removal of damaged bases from substrate by DNA glycosylase would lower the melting temperature of HP. The HP was then opened and hybridized with a FAM dye-labeled single strand DNA (DP), generating a duplex with a recessed 3′-terminal of DP. This design facilitated the Exo III-assisted amplification by repeating the hybridization and digestion of DP, liberating numerous FAM fluorophores which could not be adsorbed on WS 2 nanosheet. Thus, the final system exhibited a small FP signal. However, in the absence of DNA glycosylases, no hybridization between DP and HP was occurred, hampering the hydrolysis of DP by Exo III. The intact DP was then adsorbed on the surface of WS 2 nanosheet that greatly amplified the mass of the labeled-FAM fluorophore, resulting in a large FP value. With the co-assisted amplification strategy, the sensitivity was substantially improved. In addition, this method was applied to detect UDG activity in cell extracts. The study of the inhibition of UDG was also performed. Furthermore, this method is simple in design, easy in implementation, and selective, which holds potential applications in the DNA glycosylase related mechanism research and molecular diagnostics. - Highlights: • A fluorescence polarization strategy for DNA glycosylase activity detection was developed. • The present method was based on WS 2 nanosheet and exonuclease III co-assisted signal amplification. • A high sensitivity and desirable selectivity were achieved. • This method provides a promising universal platform for DNA glycosylase

  10. Manipulation of local optical properties and structures in molybdenum-disulfide monolayers using electric field-assisted near-field techniques.

    Science.gov (United States)

    Nozaki, Junji; Fukumura, Musashi; Aoki, Takaaki; Maniwa, Yutaka; Yomogida, Yohei; Yanagi, Kazuhiro

    2017-04-05

    Remarkable optical properties, such as quantum light emission and large optical nonlinearity, have been observed in peculiar local sites of transition metal dichalcogenide monolayers, and the ability to tune such properties is of great importance for their optoelectronic applications. For that purpose, it is crucial to elucidate and tune their local optical properties simultaneously. Here, we develop an electric field-assisted near-field technique. Using this technique we can clarify and tune the local optical properties simultaneously with a spatial resolution of approximately 100 nm due to the electric field from the cantilever. The photoluminescence at local sites in molybdenum-disulfide (MoS 2 ) monolayers is reversibly modulated, and the inhomogeneity of the charge neutral points and quantum yields is suggested. We successfully etch MoS 2 crystals and fabricate nanoribbons using near-field techniques in combination with an electric field. This study creates a way to tune the local optical properties and to freely design the structural shapes of atomic monolayers using near-field optics.

  11. Tungsten disulfide nanosheet and exonuclease III co-assisted amplification strategy for highly sensitive fluorescence polarization detection of DNA glycosylase activity

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jingjin; Ma, Yefei [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China); Kong, Rongmei [The Key Laboratory of Life-Organic Analysis, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165 (China); Zhang, Liangliang, E-mail: liangzhang319@163.com [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China); Yang, Wen; Zhao, Shulin [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China)

    2015-08-05

    Herein, we introduced a tungsten disulfide (WS{sub 2}) nanosheet and exonuclease III (Exo III) co-assisted signal amplification strategy for highly sensitive fluorescent polarization (FP) assay of DNA glycosylase activity. Two DNA glycosylases, uracil-DNA glycosylase (UDG) and human 8-oxoG DNA glycosylase 1 (hOGG1), were tested. A hairpin-structured probe (HP) which contained damaged bases in the stem was used as the substrate. The removal of damaged bases from substrate by DNA glycosylase would lower the melting temperature of HP. The HP was then opened and hybridized with a FAM dye-labeled single strand DNA (DP), generating a duplex with a recessed 3′-terminal of DP. This design facilitated the Exo III-assisted amplification by repeating the hybridization and digestion of DP, liberating numerous FAM fluorophores which could not be adsorbed on WS{sub 2} nanosheet. Thus, the final system exhibited a small FP signal. However, in the absence of DNA glycosylases, no hybridization between DP and HP was occurred, hampering the hydrolysis of DP by Exo III. The intact DP was then adsorbed on the surface of WS{sub 2} nanosheet that greatly amplified the mass of the labeled-FAM fluorophore, resulting in a large FP value. With the co-assisted amplification strategy, the sensitivity was substantially improved. In addition, this method was applied to detect UDG activity in cell extracts. The study of the inhibition of UDG was also performed. Furthermore, this method is simple in design, easy in implementation, and selective, which holds potential applications in the DNA glycosylase related mechanism research and molecular diagnostics. - Highlights: • A fluorescence polarization strategy for DNA glycosylase activity detection was developed. • The present method was based on WS{sub 2} nanosheet and exonuclease III co-assisted signal amplification. • A high sensitivity and desirable selectivity were achieved. • This method provides a promising universal platform for DNA

  12. Genomics-Assisted Exploitation of Heterosis in Perennial Ryegrass (Lolium perenne L.)

    DEFF Research Database (Denmark)

    Islam, Md. Shofiqul

    ryegrass for the development of improved varieties. During his PhD studies, Mohammad Shofiqul Islam studied the feasibility of developing novel hybrid breeding schemes based on cytoplasmic male sterility (CMS) systems in perennial ryegrass. He successfully completed the assembly and annotation of a male......-fertile perennial ryegrass mitochondrial genome, and identified candidate genes responsible for the CMS phenotype by comparing male-fertile and male-sterile mitochondrial genomes. His findings constitute a good basis for continuing research to produce hybrid grass varieties to address the future needs......, breeding activities have been carried out to improve the population and develop synthetic varieties. This does not fully exploit the potential of heterosis, however. Hybrid breeding is an alternative strategy and provides opportunities to fully exploit the genetically available heterosis in perennial...

  13. Exploiting Sequential Patterns Found in Users' Solutions and Virtual Tutor Behavior to Improve Assistance in ITS

    Science.gov (United States)

    Fournier-Viger, Philippe; Faghihi, Usef; Nkambou, Roger; Nguifo, Engelbert Mephu

    2010-01-01

    We propose to mine temporal patterns in Intelligent Tutoring Systems (ITSs) to uncover useful knowledge that can enhance their ability to provide assistance. To discover patterns, we suggest using a custom, sequential pattern-mining algorithm. Two ways of applying the algorithm to enhance an ITS's capabilities are addressed. The first is to…

  14. Exploitation of humid air latent heat by means of solar assisted heat pumps operating below the dew point

    International Nuclear Information System (INIS)

    Scarpa, Federico; Tagliafico, Luca A.

    2016-01-01

    Highlights: • The opportunity of humid air latent heat exploitation by DX-SAHP is investigated. • A set of experimental tests confirms this opportunity and quantifies it as relevant. • A parametric analysis is performed, via simulation, to deepen the subject. • The energy gain is relevant during both night and daytime. - Abstract: Nowadays, the exploitation of environmental exergy resources for heating purposes (solar energy, convection heat transfer from ambient air, moist air humidity condensation) by means of properly designed heat pump systems is a possible opportunity. In particular, the use of direct expansion solar assisted heat pumps (DX-SAHP) is investigated in this study, when a bare external plate (the solar collector) is kept at temperatures lower than the dew point temperature of ambient air, so that condensation takes place on it. The potential of this technology is settled and an instrumented prototype of a small DX-SAHP system is used to verify the actual performance of the system, in terms of specific thermal energy delivered to the user, efficiency and regulation capabilities. Results clearly show that the contribution of the condensation is significant (20%–30% of the total harvested energy) overnight or in cloudy days with very low or no solar irradiation, and must be taken into account in a system model devoted to describe the DX-SAHP behavior. During daytime, the percentage gain decreases but is still consistent. By investigating along these lines, the heat due to condensation harvested by the collector is found to be a function of the dew-point temperature alone.

  15. Radioiodine-labeled disulfide: a novel radiotracer for evaluation of tumor uptake

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, E. K.; Choi, Y. S.; Byun, S. S.; Baek, J. Y.; Lee, K. H.; Kim, S. E.; Choi, Y.; Kim, B. T. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Diallyl disulfide found in garlic has been known to inhibit the growth of various cancer cells. In this study, iodine-substituted disulfides were synthesized and their growth inhibitory effects on cancer cells (SUN C5 and MCF-7) were investigated. Dibenzyl disulfide was labeled with {sup 123}I/{sup 125}I for evaluation of tumor uptake. Halogen-substituted disulfides were synthesized using 2,2'-dithiobis(benzothiazole) and one equivalent each of the corresponding thiols. Growth inhibition studies were performed on cancer cells that were grown at 37 .deg. C for 48 hr prior to exposure to the disulfides. Radioiodine-labeled disulfide was prepared by halogen exchange reaction on the 4-bromodibenzyl disulfide in the presence of Na{sup 123}I/{sup 125}I and CuCl at 150 .deg. C for 60 min, followed by HPLC purification. Uptake of the radioactivity to SUN C5 cells was measured as a function of time, and inhibition studies were performed in the presence of either S-methyl methanethiosulfonate (MMTS) or diallyl disulfide. Disulfides were synthesized in the high yields (90%). Tumor growth inhibition studies by the 3 iododisulfides showed the inhibition (>95%) comparable to diallyl disulfide (100%). Cu(I)-assisted radioiodination gave 4-{sup 123}I/{sup 125}I-iododibenzyl disulfide in overall 30-40% radiochemical yield and with high specific activity. Cell uptake studies of the radiolabeled disulfide showed a time-dependent increase of the uptake (4-fold increase from 15 min to 2 hr). Both MMTS, a glutathione depleting agent, and diallyl disulfide reduced the uptake of the radioactivity in a dose-dependent manner. Inhibition studies suggest that uptake of disulfide to the tumor cells could be mediated by thiol-disulfide exchange. This study demonstrates that radioiodine-labeled dibenzyl disulfide may be useful for evaluation of tumor uptake.

  16. Quantification of thiols and disulfides

    DEFF Research Database (Denmark)

    Winther, Jakob R.; Thorpe, Colin

    2014-01-01

    lengths to regulate thiol-disulfide bond homeostasis, typically with several, apparently redundant, systems working in parallel. Dissecting the extent of oxidation and reduction of disulfides is an ongoing challenge due, in part, to the facility of thiol/disulfide exchange reactions.......Disulfide bond formation is a key posttranslational modification, with implications for structure, function and stability of numerous proteins. While disulfide bond formation is a necessary and essential process for many proteins, it is deleterious and disruptive for others. Cells go to great...

  17. Additional disulfide bonds in insulin

    DEFF Research Database (Denmark)

    Vinther, Tine N; Pettersson, Ingrid; Huus, Kasper

    2015-01-01

    The structure of insulin, a glucose homeostasis-controlling hormone, is highly conserved in all vertebrates and stabilized by three disulfide bonds. Recently, we designed a novel insulin analogue containing a fourth disulfide bond located between positions A10-B4. The N-terminus of insulin's B......-chain is flexible and can adapt multiple conformations. We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cβ cut-off distance had...... in comparison to analogues with additional disulfide bonds that were more difficult to predict. In contrast, addition of the fourth disulfide bond rendered all analogues resistant to fibrillation under stress conditions and all stable analogues bound to the insulin receptor with picomolar affinities. Thus...

  18. Disulfide-functional poly(amido amine)s with tunable degradability for gene delivery

    NARCIS (Netherlands)

    Elzes, M. Rachel; Akeroyd, Niels; Engbersen, Johan F. J.; Paulusse, Jos M. J.

    2016-01-01

    Controlled degradability in response to the local environment is one of the most effective strategies to achieve spatiotemporal release of genes from a polymeric carrier. Exploiting the differences in reduction potential between the extracellular and intracellular environment, disulfides are

  19. Multiple ways to make disulfides

    DEFF Research Database (Denmark)

    Bulleid, Neil J; Ellgaard, Lars

    2011-01-01

    Our concept of how disulfides form in proteins entering the secretory pathway has changed dramatically in recent years. The discovery of endoplasmic reticulum (ER) oxidoreductin 1 (ERO1) was followed by the demonstration that this enzyme couples oxygen reduction to de novo formation of disulfides...

  20. Complete Mapping of Complex Disulfide Patterns with Closely-Spaced Cysteines by In-Source Reduction and Data-Dependent Mass Spectrometry

    DEFF Research Database (Denmark)

    Cramer, Christian N; Kelstrup, Christian D; Olsen, Jesper V

    2017-01-01

    bonds are present in complicated patterns. This includes the presence of disulfide bonds in nested patterns and closely spaced cysteines. Unambiguous mapping of such disulfide bonds typically requires advanced MS approaches. In this study, we exploited in-source reduction (ISR) of disulfide bonds during...... the electrospray ionization process to facilitate disulfide bond assignments. We successfully developed a LC-ISR-MS/MS methodology to use as an online and fully automated partial reduction procedure. Postcolumn partial reduction by ISR provided fast and easy identification of peptides involved in disulfide bonding......Mapping of disulfide bonds is an essential part of protein characterization to ensure correct cysteine pairings. For this, mass spectrometry (MS) is the most widely used technique due to fast and accurate characterization. However, MS-based disulfide mapping is challenged when multiple disulfide...

  1. Analysis of Disulfide Bond Formation

    NARCIS (Netherlands)

    Braakman, Ineke; Lamriben, Lydia; van Zadelhoff, Guus; Hebert, Daniel N.

    2017-01-01

    In this unit, protocols are provided for detection of disulfide bond formation in cultures of intact cells and in an in vitro translation system containing isolated microsomes or semi-permeabilized cells. First, the newly synthesized protein of interest is biosynthetically labeled with radioactive

  2. Exploiting the Complementarity between Dereplication and Computer-Assisted Structure Elucidation for the Chemical Profiling of Natural Cosmetic Ingredients: Tephrosia purpurea as a Case Study.

    Science.gov (United States)

    Hubert, Jane; Chollet, Sébastien; Purson, Sylvain; Reynaud, Romain; Harakat, Dominique; Martinez, Agathe; Nuzillard, Jean-Marc; Renault, Jean-Hugues

    2015-07-24

    The aqueous-ethanolic extract of Tephrosia purpurea seeds is currently exploited in the cosmetic industry as a natural ingredient of skin lotions. The aim of this study was to chemically characterize this ingredient by combining centrifugal partition extraction (CPE) as a fractionation tool with two complementary identification approaches involving dereplication and computer-assisted structure elucidation. Following two rapid fractionations of the crude extract (2 g), seven major compounds namely, caffeic acid, quercetin-3-O-rutinoside, ethyl galactoside, ciceritol, stachyose, saccharose, and citric acid, were unambiguously identified within the CPE-generated simplified mixtures by a recently developed (13)C NMR-based dereplication method. The structures of four additional compounds, patuletin-3-O-rutinoside, kaempferol-3-O-rutinoside, guaiacylglycerol 8-vanillic acid ether, and 2-methyl-2-glucopyranosyloxypropanoic acid, were automatically elucidated by using the Logic for Structure Determination program based on the interpretation of 2D NMR (HSQC, HMBC, and COSY) connectivity data. As more than 80% of the crude extract mass was characterized without need for tedious and labor-intensive multistep purification procedures, the identification tools involved in this work constitute a promising strategy for an efficient and time-saving chemical profiling of natural extracts.

  3. In-Depth Characterization of Protein Disulfide Bonds by Online Liquid Chromatography-Electrochemistry-Mass Spectrometry

    Science.gov (United States)

    Switzar, Linda; Nicolardi, Simone; Rutten, Julie W.; Oberstein, Saskia A. J. Lesnik; Aartsma-Rus, Annemieke; van der Burgt, Yuri E. M.

    2016-01-01

    Disulfide bonds are an important class of protein post-translational modifications, yet this structurally crucial modification type is commonly overlooked in mass spectrometry (MS)-based proteomics approaches. Recently, the benefits of online electrochemistry-assisted reduction of protein S-S bonds prior to MS analysis were exemplified by successful characterization of disulfide bonds in peptides and small proteins. In the current study, we have combined liquid chromatography (LC) with electrochemistry (EC) and mass analysis by Fourier transform ion cyclotron resonance (FTICR) MS in an online LC-EC-MS platform to characterize protein disulfide bonds in a bottom-up proteomics workflow. A key advantage of a LC-based strategy is the use of the retention time in identifying both intra- and interpeptide disulfide bonds. This is demonstrated by performing two sequential analyses of a certain protein digest, once without and once with electrochemical reduction. In this way, the "parent" disulfide-linked peptide detected in the first run has a retention time-based correlation with the EC-reduced peptides detected in the second run, thus simplifying disulfide bond mapping. Using this platform, both inter- and intra-disulfide-linked peptides were characterized in two different proteins, ß-lactoglobulin and ribonuclease B. In order to prevent disulfide reshuffling during the digestion process, proteins were digested at a relatively low pH, using (a combination of) the high specificity proteases trypsin and Glu-C. With this approach, disulfide bonds in ß-lactoglobulin and ribonuclease B were comprehensively identified and localized, showing that online LC-EC-MS is a useful tool for the characterization of protein disulfide bonds.

  4. Intradomain Confinement of Disulfides in the Folding of Two Consecutive Modules of the LDL Receptor.

    Directory of Open Access Journals (Sweden)

    Juan Martínez-Oliván

    Full Text Available The LDL receptor internalizes circulating LDL and VLDL particles for degradation. Its extracellular binding domain contains ten (seven LA and three EGF cysteine-rich modules, each bearing three disulfide bonds. Despite the enormous number of disulfide combinations possible, LDLR oxidative folding leads to a single native species with 30 unique intradomain disulfides. Previous folding studies of the LDLR have shown that non native disulfides are initially formed that lead to compact species. Accordingly, the folding of the LDLR has been described as a "coordinated nonvectorial" reaction, and it has been proposed that early compaction funnels the reaction toward the native structure. Here we analyze the oxidative folding of LA4 and LA5, the modules critical for ApoE binding, isolated and in the LA45 tandem. Compared to LA5, LA4 folding is slow and inefficient, resembling that of LA5 disease-linked mutants. Without Ca++, it leads to a mixture of many two-disulfide scrambled species and, with Ca++, to the native form plus two three-disulfide intermediates. The folding of the LA45 tandem seems to recapitulate that of the individual repeats. Importantly, although the folding of the LA45 tandem takes place through formation of scrambled isomers, no interdomain disulfides are detected, i.e. the two adjacent modules fold independently without the assistance of interdomain covalent interactions. Reduction of incredibly large disulfide combinatorial spaces, such as that in the LDLR, by intradomain confinement of disulfide bond formation might be also essential for the efficient folding of other homologous disulfide-rich receptors.

  5. Redefining Exploitation

    DEFF Research Database (Denmark)

    Agarwala, Rina

    2016-01-01

    This article examines how self-employed workers are organizing in the garments and waste collection industries in India. Although the question of who is profiting from self-employed workers’ labor is complex, the cases outlined in this paper highlight telling instances of how some self......-employed workers are organizing as workers. They are fighting labor exploitation by redefining the concept to include additional exploitation axes (from the state and middle class) and forms (including sexual). In doing so, they are redefining potential solutions, including identities and material benefits, to fit...... their unique needs. By expanding the category of “workers” beyond those defined by a narrow focus on a standard employer-employee relationship, these movements are also fighting exclusion from earlier labor protections by increasing the number of entitled beneficiaries. These struggles provide an important...

  6. Amino Acid Patterns around Disulfide Bonds

    Directory of Open Access Journals (Sweden)

    Brett Drury

    2010-11-01

    Full Text Available Disulfide bonds provide an inexhaustible source of information on molecular evolution and biological specificity. In this work, we described the amino acid composition around disulfide bonds in a set of disulfide-rich proteins using appropriate descriptors, based on ANOVA (for all twenty natural amino acids or classes of amino acids clustered according to their chemical similarities and Scheffé (for the disulfide-rich proteins superfamilies statistics. We found that weakly hydrophilic and aromatic amino acids are quite abundant in the regions around disulfide bonds, contrary to aliphatic and hydrophobic amino acids. The density distributions (as a function of the distance to the center of the disulfide bonds for all defined entities presented an overall unimodal behavior: the densities are null at short distances, have maxima at intermediate distances and decrease for long distances. In the end, the amino acid environment around the disulfide bonds was found to be different for different superfamilies, allowing the clustering of proteins in a biologically relevant way, suggesting that this type of chemical information might be used as a tool to assess the relationship between very divergent sets of disulfide-rich proteins.

  7. Characterization of Disulfide-Linked Peptides Using Tandem Mass Spectrometry Coupled with Automated Data Analysis Software

    Science.gov (United States)

    Liang, Zhidan; McGuinness, Kenneth N.; Crespo, Alejandro; Zhong, Wendy

    2018-05-01

    Disulfide bond formation is critical for maintaining structure stability and function of many peptides and proteins. Mass spectrometry has become an important tool for the elucidation of molecular connectivity. However, the interpretation of the tandem mass spectral data of disulfide-linked peptides has been a major challenge due to the lack of appropriate tools. Developing proper data analysis software is essential to quickly characterize disulfide-linked peptides. A thorough and in-depth understanding of how disulfide-linked peptides fragment in mass spectrometer is a key in developing software to interpret the tandem mass spectra of these peptides. Two model peptides with inter- and intra-chain disulfide linkages were used to study fragmentation behavior in both collisional-activated dissociation (CAD) and electron-based dissociation (ExD) experiments. Fragments generated from CAD and ExD can be categorized into three major types, which result from different S-S and C-S bond cleavage patterns. DiSulFinder is a computer algorithm that was newly developed based on the fragmentation observed in these peptides. The software is vendor neutral and capable of quickly and accurately identifying a variety of fragments generated from disulfide-linked peptides. DiSulFinder identifies peptide backbone fragments with S-S and C-S bond cleavages and, more importantly, can also identify fragments with the S-S bond still intact to aid disulfide linkage determination. With the assistance of this software, more comprehensive disulfide connectivity characterization can be achieved. [Figure not available: see fulltext.

  8. Characterization of Disulfide-Linked Peptides Using Tandem Mass Spectrometry Coupled with Automated Data Analysis Software.

    Science.gov (United States)

    Liang, Zhidan; McGuinness, Kenneth N; Crespo, Alejandro; Zhong, Wendy

    2018-01-25

    Disulfide bond formation is critical for maintaining structure stability and function of many peptides and proteins. Mass spectrometry has become an important tool for the elucidation of molecular connectivity. However, the interpretation of the tandem mass spectral data of disulfide-linked peptides has been a major challenge due to the lack of appropriate tools. Developing proper data analysis software is essential to quickly characterize disulfide-linked peptides. A thorough and in-depth understanding of how disulfide-linked peptides fragment in mass spectrometer is a key in developing software to interpret the tandem mass spectra of these peptides. Two model peptides with inter- and intra-chain disulfide linkages were used to study fragmentation behavior in both collisional-activated dissociation (CAD) and electron-based dissociation (ExD) experiments. Fragments generated from CAD and ExD can be categorized into three major types, which result from different S-S and C-S bond cleavage patterns. DiSulFinder is a computer algorithm that was newly developed based on the fragmentation observed in these peptides. The software is vendor neutral and capable of quickly and accurately identifying a variety of fragments generated from disulfide-linked peptides. DiSulFinder identifies peptide backbone fragments with S-S and C-S bond cleavages and, more importantly, can also identify fragments with the S-S bond still intact to aid disulfide linkage determination. With the assistance of this software, more comprehensive disulfide connectivity characterization can be achieved. Graphical Abstract ᅟ.

  9. Functional Poly(ε-caprolactone)s via Copolymerization of ε-Caprolactone and Pyridyl Disulfide-Containing Cyclic Carbonate: Controlled Synthesis and Facile Access to Reduction-Sensitive Biodegradable Graft Copolymer Micelles

    NARCIS (Netherlands)

    Chen, Wei; Zou, Yan; Jia, Junna; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

    2013-01-01

    Pyridyl disulfide-functionalized cyclic carbonate (PDSC) monomer was obtained in four straightforward steps from 3-methyl-3-oxetanemethanol and exploited for facile preparation of functional poly(ε-caprolactone) (PCL) containing pendant pyridyl disulfide (PDS) groups via ring-opening

  10. Soft Computing Methods for Disulfide Connectivity Prediction.

    Science.gov (United States)

    Márquez-Chamorro, Alfonso E; Aguilar-Ruiz, Jesús S

    2015-01-01

    The problem of protein structure prediction (PSP) is one of the main challenges in structural bioinformatics. To tackle this problem, PSP can be divided into several subproblems. One of these subproblems is the prediction of disulfide bonds. The disulfide connectivity prediction problem consists in identifying which nonadjacent cysteines would be cross-linked from all possible candidates. Determining the disulfide bond connectivity between the cysteines of a protein is desirable as a previous step of the 3D PSP, as the protein conformational search space is highly reduced. The most representative soft computing approaches for the disulfide bonds connectivity prediction problem of the last decade are summarized in this paper. Certain aspects, such as the different methodologies based on soft computing approaches (artificial neural network or support vector machine) or features of the algorithms, are used for the classification of these methods.

  11. Piezoelectricity in two dimensions: Graphene vs. molybdenum disulfide

    Science.gov (United States)

    Song, Xiaoxue; Hui, Fei; Knobloch, Theresia; Wang, Bingru; Fan, Zhongchao; Grasser, Tibor; Jing, Xu; Shi, Yuanyuan; Lanza, Mario

    2017-08-01

    The synthesis of piezoelectric two-dimensional (2D) materials is very attractive for implementing advanced energy harvesters and transducers, as these materials provide enormously large areas for the exploitation of the piezoelectric effect. Among all 2D materials, molybdenum disulfide (MoS2) has shown the largest piezoelectric activity. However, all research papers in this field studied just a single material, and this may raise concerns because different setups could provide different values depending on experimental parameters (e.g., probes used and areas analyzed). By using conductive atomic force microscopy, here we in situ demonstrate that the piezoelectric currents generated in MoS2 are gigantic (65 mA/cm2), while the same experiments in graphene just showed noise currents. These results provide the most reliable comparison yet reported on the piezoelectric effect in graphene and MoS2.

  12. How thioredoxin dissociates its mixed disulfide.

    Directory of Open Access Journals (Sweden)

    Goedele Roos

    2009-08-01

    Full Text Available The dissociation mechanism of the thioredoxin (Trx mixed disulfide complexes is unknown and has been debated for more than twenty years. Specifically, opposing arguments for the activation of the nucleophilic cysteine as a thiolate during the dissociation of the complex have been put forward. As a key model, the complex between Trx and its endogenous substrate, arsenate reductase (ArsC, was used. In this structure, a Cys29(Trx-Cys89(ArsC intermediate disulfide is formed by the nucleophilic attack of Cys29(Trx on the exposed Cys82(ArsC-Cys89(ArsC in oxidized ArsC. With theoretical reactivity analysis, molecular dynamics simulations, and biochemical complex formation experiments with Cys-mutants, Trx mixed disulfide dissociation was studied. We observed that the conformational changes around the intermediate disulfide bring Cys32(Trx in contact with Cys29(Trx. Cys32(Trx is activated for its nucleophilic attack by hydrogen bonds, and Cys32(Trx is found to be more reactive than Cys82(ArsC. Additionally, Cys32(Trx directs its nucleophilic attack on the more susceptible Cys29(Trx and not on Cys89(ArsC. This multidisciplinary approach provides fresh insights into a universal thiol/disulfide exchange reaction mechanism that results in reduced substrate and oxidized Trx.

  13. On the photostability of the disulfide bond

    DEFF Research Database (Denmark)

    Stephansen, Anne Boutrup; Larsen, Martin Alex Bjørn; Klein, Liv Bærenholdt

    2014-01-01

    Photostability is an essential property of molecular building blocks of nature. Disulfides are central in the structure determination of proteins, which is in striking contradiction to the result that the S-S bond is a photochemically labile structural entity that cleaves to form free radicals upon...... on a sub 50 fs timescale without further ado. In a cyclic motif resembling the cysteine-disulfide bond in proteins, light can perturb the S-S bond to generate short-lived diradicaloid species, but the sulfur atoms are conformationally restricted by the ring that prevents the sulfur atoms from flying apart...... the photostability of disulfide-bonds must be ascribed a cyclic structural arrangement....

  14. Measurement of glutathione-protein mixed disulfides

    International Nuclear Information System (INIS)

    Livesey, J.C.; Reed, D.J.

    1984-01-01

    The development of a sensitive and highly specific assay for the presence of mixed disulfides between protein thiol groups and endogenous thiols has been undertaken. Previous investigations on the concentrations of glutathione (GSH), glutathione disulfide (GSSG) and protein glutathione mixed disulfides (ProSSG) have been of limited usefulness because of the poor specificity of the assays used. Our assay for these forms of glutathione is based on high performance liquid chromatography (HPLC) and is an extension of an earlier method. After perchloric acid precipitation, the protein sample is washed with an organic solvent to fully denature the protein. Up to a 10-fold increase in GSH released from fetal bovine serum (FBS) protein has been found when the protein precipitate is washed with ethanol rather than ether, as earlier suggested. Similar effects have been observed with an as yet unidentified thiol which elutes in the chromatography system with a retention volume similar to cysteine

  15. Brain MRI findings of carbon disulfide poisoning

    International Nuclear Information System (INIS)

    Cha, Joo Hee; Kim, Mi Jung; Yim, Sang Hyuk; Kim, Sam Soo; Han, Heon; Kim, Rok Ho

    2002-01-01

    To evaluate the findings of brain MRI in patients with carbon disulfide poisoning. Ninety-one patients who had suffered carbon disulfide poisoning [male:female=87:4; age, 32-74 (mean 53.3) years] were included in this study. To determine the extent of white matter hyperintensity (Grade 0-V) and lacunar infarction, T2-weighted MR imaging of the brain was performed. T2-weighted images depicted white matter hyperintensity in 70 patients (76.9%) and lacunar infarcts in 27 (29.7%). In these patients, the prevalent findings at T2-weighted MR imaging of the brain were white matter hyperintensity and lacunar infarcts. Disturbance of the cardiovascular system by carbon disulfide might account for these results

  16. Dynamic combinatorial chemistry with diselenides and disulfides in water

    DEFF Research Database (Denmark)

    Rasmussen, Brian; Sørensen, Anne; Gotfredsen, Henrik

    2014-01-01

    Diselenide exchange is introduced as a reversible reaction in dynamic combinatorial chemistry in water. At neutral pH, diselenides are found to mix with disulfides and form dynamic combinatorial libraries of diselenides, disulfides, and selenenylsulfides. This journal is......Diselenide exchange is introduced as a reversible reaction in dynamic combinatorial chemistry in water. At neutral pH, diselenides are found to mix with disulfides and form dynamic combinatorial libraries of diselenides, disulfides, and selenenylsulfides. This journal is...

  17. The human protein disulfide isomerase gene family

    Directory of Open Access Journals (Sweden)

    Galligan James J

    2012-07-01

    Full Text Available Abstract Enzyme-mediated disulfide bond formation is a highly conserved process affecting over one-third of all eukaryotic proteins. The enzymes primarily responsible for facilitating thiol-disulfide exchange are members of an expanding family of proteins known as protein disulfide isomerases (PDIs. These proteins are part of a larger superfamily of proteins known as the thioredoxin protein family (TRX. As members of the PDI family of proteins, all proteins contain a TRX-like structural domain and are predominantly expressed in the endoplasmic reticulum. Subcellular localization and the presence of a TRX domain, however, comprise the short list of distinguishing features required for gene family classification. To date, the PDI gene family contains 21 members, varying in domain composition, molecular weight, tissue expression, and cellular processing. Given their vital role in protein-folding, loss of PDI activity has been associated with the pathogenesis of numerous disease states, most commonly related to the unfolded protein response (UPR. Over the past decade, UPR has become a very attractive therapeutic target for multiple pathologies including Alzheimer disease, Parkinson disease, alcoholic and non-alcoholic liver disease, and type-2 diabetes. Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR.

  18. Functional differences in yeast protein disulfide isomerases

    DEFF Research Database (Denmark)

    Nørgaard, P; Westphal, V; Tachibana, C

    2001-01-01

    PDI1 is the essential gene encoding protein disulfide isomerase in yeast. The Saccharomyces cerevisiae genome, however, contains four other nonessential genes with homology to PDI1: MPD1, MPD2, EUG1, and EPS1. We have investigated the effects of simultaneous deletions of these genes. In several...

  19. The Ethics of Exploitation

    Directory of Open Access Journals (Sweden)

    Paul McLaughlin

    2008-11-01

    Full Text Available Philosophical inquiry into exploitation has two major deficiencies to date: it assumes that exploitation is wrong by definition; and it pays too much attention to the Marxian account of exploitation. Two senses of exploitation should be distinguished: the ‘moral’ or pejorative sense and the ‘non-moral’ or ‘non-prejudicial’ sense. By demonstrating the conceptual inadequacy of exploitation as defined in the first sense, and by defining exploitation adequately in the latter sense, we seek to demonstrate the moral complexity of exploitation. We contend, moreover, that moral evaluation of exploitation is only possible once we abandon a strictly Marxian framework and attempt, in the long run, to develop an integral ethic along Godwinian lines.

  20. Characterization of cyclic peptides containing disulfide bonds

    OpenAIRE

    Johnson, Mindy; Liu, Mingtao; Struble, Elaine; Hettiarachchi, Kanthi

    2015-01-01

    Unlike linear peptides, analysis of cyclic peptides containing disulfide bonds is not straightforward and demands indirect methods to achieve a rigorous proof of structure. Three peptides that belong to this category, p-Cl-Phe-DPDPE, DPDPE, and CTOP, were analyzed and the results are presented in this paper. The great potential of two dimensional NMR and ESI tandem mass spectrometry was harnessed during the course of peptide characterizations. A new RP-HPLC method for the analysis of trifluor...

  1. SHuffle, a novel Escherichia coli protein expression strain capable of correctly folding disulfide bonded proteins in its cytoplasm

    Directory of Open Access Journals (Sweden)

    Lobstein Julie

    2012-05-01

    Full Text Available Abstract Background Production of correctly disulfide bonded proteins to high yields remains a challenge. Recombinant protein expression in Escherichia coli is the popular choice, especially within the research community. While there is an ever growing demand for new expression strains, few strains are dedicated to post-translational modifications, such as disulfide bond formation. Thus, new protein expression strains must be engineered and the parameters involved in producing disulfide bonded proteins must be understood. Results We have engineered a new E. coli protein expression strain named SHuffle, dedicated to producing correctly disulfide bonded active proteins to high yields within its cytoplasm. This strain is based on the trxB gor suppressor strain SMG96 where its cytoplasmic reductive pathways have been diminished, allowing for the formation of disulfide bonds in the cytoplasm. We have further engineered a major improvement by integrating into its chromosome a signal sequenceless disulfide bond isomerase, DsbC. We probed the redox state of DsbC in the oxidizing cytoplasm and evaluated its role in assisting the formation of correctly folded multi-disulfide bonded proteins. We optimized protein expression conditions, varying temperature, induction conditions, strain background and the co-expression of various helper proteins. We found that temperature has the biggest impact on improving yields and that the E. coli B strain background of this strain was superior to the K12 version. We also discovered that auto-expression of substrate target proteins using this strain resulted in higher yields of active pure protein. Finally, we found that co-expression of mutant thioredoxins and PDI homologs improved yields of various substrate proteins. Conclusions This work is the first extensive characterization of the trxB gor suppressor strain. The results presented should help researchers design the appropriate protein expression conditions using

  2. Widespread Disulfide Bonding in Proteins from Thermophilic Archaea

    Directory of Open Access Journals (Sweden)

    Julien Jorda

    2011-01-01

    Full Text Available Disulfide bonds are generally not used to stabilize proteins in the cytosolic compartments of bacteria or eukaryotic cells, owing to the chemically reducing nature of those environments. In contrast, certain thermophilic archaea use disulfide bonding as a major mechanism for protein stabilization. Here, we provide a current survey of completely sequenced genomes, applying computational methods to estimate the use of disulfide bonding across the Archaea. Microbes belonging to the Crenarchaeal branch, which are essentially all hyperthermophilic, are universally rich in disulfide bonding while lesser degrees of disulfide bonding are found among the thermophilic Euryarchaea, excluding those that are methanogenic. The results help clarify which parts of the archaeal lineage are likely to yield more examples and additional specific data on protein disulfide bonding, as increasing genomic sequencing efforts are brought to bear.

  3. Widespread disulfide bonding in proteins from thermophilic archaea.

    Science.gov (United States)

    Jorda, Julien; Yeates, Todd O

    2011-01-01

    Disulfide bonds are generally not used to stabilize proteins in the cytosolic compartments of bacteria or eukaryotic cells, owing to the chemically reducing nature of those environments. In contrast, certain thermophilic archaea use disulfide bonding as a major mechanism for protein stabilization. Here, we provide a current survey of completely sequenced genomes, applying computational methods to estimate the use of disulfide bonding across the Archaea. Microbes belonging to the Crenarchaeal branch, which are essentially all hyperthermophilic, are universally rich in disulfide bonding while lesser degrees of disulfide bonding are found among the thermophilic Euryarchaea, excluding those that are methanogenic. The results help clarify which parts of the archaeal lineage are likely to yield more examples and additional specific data on protein disulfide bonding, as increasing genomic sequencing efforts are brought to bear.

  4. Widespread Disulfide Bonding in Proteins from Thermophilic Archaea

    OpenAIRE

    Jorda, Julien; Yeates, Todd O.

    2011-01-01

    Disulfide bonds are generally not used to stabilize proteins in the cytosolic compartments of bacteria or eukaryotic cells, owing to the chemically reducing nature of those environments. In contrast, certain thermophilic archaea use disulfide bonding as a major mechanism for protein stabilization. Here, we provide a current survey of completely sequenced genomes, applying computational methods to estimate the use of disulfide bonding across the Archaea. Microbes belonging to the Crenarchaea...

  5. Thiol-Disulfide Exchange between Glutaredoxin and Glutathione

    DEFF Research Database (Denmark)

    Iversen, Rasmus; Andersen, Peter Anders; Jensen, Kristine Steen

    2010-01-01

    Glutaredoxins are ubiquitous thiol-disulfide oxidoreductases which catalyze the reduction of glutathione-protein mixed disulfides. Belonging to the thioredoxin family, they contain a conserved active site CXXC motif. The N-proximal active site cysteine can form a mixed disulfide with glutathione ...... has been replaced with serine. The exchange reaction between the reduced protein and oxidized glutathione leading to formation of the mixed disulfide could readily be monitored by isothermal titration calorimetry (ITC) due to the enthalpic contributions from the noncovalent interactions...

  6. Disulfide Linkage Characterization of Disulfide Bond-Containing Proteins and Peptides by Reducing Electrochemistry and Mass Spectrometry

    DEFF Research Database (Denmark)

    Cramer, Christian N; Haselmann, Kim F; Olsen, Jesper V

    2016-01-01

    in protein sequencing by tandem MS (MS/MS). Electrochemical (EC) reduction of disulfide bonds has recently been demonstrated to provide efficient reduction efficiencies, significantly enhancing sequence coverages in online coupling with MS characterization. In this study, the potential use of EC disulfide...... link between parent disulfide-linked fragments and free reduced peptides in an LC-EC-MS platform of nonreduced proteolytic protein digestions. Here we report the successful use of EC as a partial reduction approach in mapping of disulfide bonds of intact human insulin (HI) and lysozyme. In addition, we...... established a LC-EC-MS platform advantageous in disulfide characterization of complex and highly disulfide-bonded proteins such as human serum albumin (HSA) by online EC reduction of nonreduced proteolytic digestions....

  7. Exploit Kit traffic analysis

    OpenAIRE

    Καπίρης, Σταμάτης; Kapiris, Stamatis

    2017-01-01

    Exploit kits have become one of the most widespread and destructive threat that Internet users face on a daily basis. Since the first actor, which has been categorized as exploit kit, namely MPack, appeared in 2006, we have seen a new era on exploit kit variants compromising popular websites, infecting hosts and delivering destructive malware, following an exponentially evolvement to date. With the growing threat landscape, large enterprises to domestic networks, have starte...

  8. Exploitability Assessment with TEASER

    Science.gov (United States)

    2017-05-01

    for architectural neutral taint analysis on top of LLVM and QEMU. POC Proof of Concept : Demonstration of an exploit on a program . vii RCE Remote Code...bug with a Proof of Concept (POC), or input to a program demonstrating the ability to use a bug to exploit the application, to demonstrate the...often leads to either computationally difficult constraint solving problems or taint explosion. Given the computational difficulty of exploit

  9. Anthropology of sexual exploitation

    Directory of Open Access Journals (Sweden)

    Lalić Velibor

    2009-01-01

    Full Text Available In this paper, the authors observe sexual exploitation from an anthropological perspective. They analyze the rational, ethical, emotional and mythological dimensions of human sexuality. Consequently, after setting the phenomenon in a social and historical context, sexual exploitation is closely observed in the contemporary age. Based on thoughts of relevant thinkers, they make the conclusion that the elimination of sexual exploitation is not an utterly legal issue, but political and economical issues as well. Namely, legal norms are not sufficient to overcome sexual exploitation, but, political and economical relationships in contemporary societies, which will be based on sincere equal opportunities must be established.

  10. Structural Characterization and Disulfide Assignment of Spider Peptide Phα1β by Mass Spectrometry

    Science.gov (United States)

    Wormwood, Kelly L.; Ngounou Wetie, Armand Gatien; Gomez, Marcus Vinicius; Ju, Yue; Kowalski, Paul; Mihasan, Marius; Darie, Costel C.

    2018-05-01

    Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1β is known; however, the exact structure and disulfide arrangement has yet to be determined. Determination of the disulfide linkages and exact structure could greatly assist in pharmacological analysis and determination of why this peptide is such an effective analgesic. Here, we used biochemical and mass spectrometry approaches to determine the disulfide linkages present in the recombinant Phα1β peptide. Using a combination of MALDI-MS, direct infusion ESI-MS, and nanoLC-MS/MS analysis of the undigested recombinant Phα1β peptide and digested with AspN, trypsin, or AspN/trypsin, we were able to identify and confirm all six disulfide linkages present in the peptide as Cys1-2, Cys3-4, Cys5-6, Cys7-8, Cys9-10, and Cys11-12. These results were also partially confirmed in the native Phα1β peptide. These experiments provide essential structural information about Phα1β and may assist in providing insight into the peptide's analgesic effect with very low side effects. [Figure not available: see fulltext.

  11. Structural Characterization and Disulfide Assignment of Spider Peptide Phα1β by Mass Spectrometry

    Science.gov (United States)

    Wormwood, Kelly L.; Ngounou Wetie, Armand Gatien; Gomez, Marcus Vinicius; Ju, Yue; Kowalski, Paul; Mihasan, Marius; Darie, Costel C.

    2018-04-01

    Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1β is known; however, the exact structure and disulfide arrangement has yet to be determined. Determination of the disulfide linkages and exact structure could greatly assist in pharmacological analysis and determination of why this peptide is such an effective analgesic. Here, we used biochemical and mass spectrometry approaches to determine the disulfide linkages present in the recombinant Phα1β peptide. Using a combination of MALDI-MS, direct infusion ESI-MS, and nanoLC-MS/MS analysis of the undigested recombinant Phα1β peptide and digested with AspN, trypsin, or AspN/trypsin, we were able to identify and confirm all six disulfide linkages present in the peptide as Cys1-2, Cys3-4, Cys5-6, Cys7-8, Cys9-10, and Cys11-12. These results were also partially confirmed in the native Phα1β peptide. These experiments provide essential structural information about Phα1β and may assist in providing insight into the peptide's analgesic effect with very low side effects. [Figure not available: see fulltext.

  12. Exploitation and disadvantage

    NARCIS (Netherlands)

    Ferguson, B.

    2016-01-01

    According to some accounts of exploitation, most notably Ruth Sample's (2003) degradation-based account and Robert Goodin's (1987) vulnerability-based account, exploitation occurs when an advantaged party fails to constrain their advantage in light of another's disadvantage, regardless of the cause

  13. EXPLOITATION OF GRANITE BOULDER

    Directory of Open Access Journals (Sweden)

    Ivan Cotman

    1994-12-01

    Full Text Available The processes of forming, petrography, features, properties and exploitation of granite boulders are described. The directional drilling and black powder blasting is the succesful method in exploitation of granite boulders (boulder technology (the paper is published in Croatian.

  14. Compact conformations of human protein disulfide isomerase.

    Directory of Open Access Journals (Sweden)

    Shang Yang

    Full Text Available Protein disulfide isomerase (PDI composed of four thioredoxin-like domains a, b, b', and a', is a key enzyme catalyzing oxidative protein folding in the endoplasmic reticulum. Large scale molecular dynamics simulations starting from the crystal structures of human PDI (hPDI in the oxidized and reduced states were performed. The results indicate that hPDI adopts more compact conformations in solution than in the crystal structures, which are stabilized primarily by inter-domain interactions, including the salt bridges between domains a and b' observed for the first time. A prominent feature of the compact conformations is that the two catalytic domains a and a' can locate close enough for intra-molecular electron transfer, which was confirmed by the characterization of an intermediate with a disulfide between the two domains. Mutations, which disrupt the inter-domain interactions, lead to decreased reductase activity of hPDI. Our molecular dynamics simulations and biochemical experiments reveal the intrinsic conformational dynamics of hPDI and its biological impact.

  15. CuI-Catalyzed: One-Pot Synthesis of Diaryl Disulfides from Aryl Halides and Carbon Disulfide

    Directory of Open Access Journals (Sweden)

    Mohammad Soleiman-Beigi

    2013-01-01

    Full Text Available A new application of carbon disulfide in the presence of KF/Al2O3 is reported for the synthesis of organic symmetrical diaryl disulfides. These products were synthesized by one-pot reaction of aryl halides with the in situ generated trithiocarbonate ion in the presence of copper under air atmosphere.

  16. Poverty-Exploitation-Alienation.

    Science.gov (United States)

    Bronfenbrenner, Martin

    1980-01-01

    Illustrates how knowledge derived from the discipline of economics can be used to help shed light on social problems such as poverty, exploitation, and alienation, and can help decision makers form policy to minimize these and similar problems. (DB)

  17. Protein Disulfide Isomerase and Host-Pathogen Interaction

    Directory of Open Access Journals (Sweden)

    Beatriz S. Stolf

    2011-01-01

    Full Text Available Reactive oxygen species (ROS production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation and (ii phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections.

  18. Exploiting VM/XA

    International Nuclear Information System (INIS)

    Boeheim, C.

    1990-03-01

    The Stanford Linear Accelerator Center has recently completed a conversion to IBM's VM/XA SP Release 2 operating system. The primary physics application had been constrained by the previous 16 megabyte memory limit. Work is underway to enable this application to exploit the new features of VM/XA. This paper presents a brief tutorial on how to convert an application to exploit VM/XA and discusses some of the SLAC experiences in doing so. 13 figs

  19. Thermal ripples in model molybdenum disulfide monolayers

    Energy Technology Data Exchange (ETDEWEB)

    Remsing, Richard C.; Klein, Michael L. [Institute for Computational Molecular Science, Center for the Computational, Design of Functional Layered Materials, and Department of Chemistry, Temple University, 1925 N. 12th St., 19122, Philadelphia, PA (United States); Waghmare, Umesh V. [Theoretical Sciences Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, 560 064, Jakkur, Bangalore (India)

    2017-01-15

    Molybdenum disulfide (MoS{sub 2}) monolayers have the potential to revolutionize nanotechnology. To reach this potential, it will be necessary to understand the behavior of this two-dimensional (2D) material on large length scales and under thermal conditions. Herein, we use molecular dynamics (MD) simulations to investigate the nature of the rippling induced by thermal fluctuations in monolayers of the 2H and 1T phases of MoS{sub 2}. The 1T phase is found to be more rigid than the 2H phase. Both monolayer phases are predicted to follow long wavelength scaling behavior typical of systems with anharmonic coupling between vibrational modes as predicted by classic theories of membrane-like systems. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. Preparation and Photoluminescence of Tungsten Disulfide Monolayer

    Directory of Open Access Journals (Sweden)

    Yanfei Lv

    2018-05-01

    Full Text Available Tungsten disulfide (WS2 monolayer is a direct band gap semiconductor. The growth of WS2 monolayer hinders the progress of its investigation. In this paper, we prepared the WS2 monolayer through chemical vapor transport deposition. This method makes it easier for the growth of WS2 monolayer through the heterogeneous nucleation-and-growth process. The crystal defects introduced by the heterogeneous nucleation could promote the photoluminescence (PL emission. We observed the strong photoluminescence emission in the WS2 monolayer, as well as thermal quenching, and the PL energy redshift as the temperature increases. We attribute the thermal quenching to the energy or charge transfer of the excitons. The redshift is related to the dipole moment of WS2.

  1. Chemoreactomic analysis of thiamine disulfide, thiamine hydrochloride, and benfotiamine molecules

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2017-01-01

    Full Text Available Objective: to analyze the interactions that could indicate the potential pharmacological properties of the molecules of thiamin, thiamine disulfide, and others.Material and methods. The investigators simulated the properties of thiamine disulfide (bistiamin versus those of the reference molecules of thiamin hydrochloride and benfotiamine. The study was performed using chemoreactomic simulation that is the newest area in post-genome pharmacology.Results and discussion. Chemoreactomic analysis has shown that thiamine disulfide can inhibit the molecular receptors involved in blood pressure regulation: adrenoceptors, vasopressin receptor, and angiotensin receptor. Thiamine disulfide can inhibit the reuptake of serotonin, increase its levels, inhibit benzodiazepine receptor and dopamine reuptake, and enhance neuronal acetylcholine release to a large extent than benfotiamine. These molecular effects are consistent with the sedative and anticonvulsant action profile of thiamine disulfide. Simulation has indicated that thiamine disulfide has neuroprotective, anti-inflammatory, normolipidemic, and antitumor activities.Conclusion. The simulation results are confirmed by the available clinical and experimental findings and indicate the virtually unstudied molecular mechanisms of action of thiamine disulfide, benfotiamine, and thiamin hydrochloride. 

  2. Steric effects in peptide and protein exchange with activated disulfides.

    Science.gov (United States)

    Kerr, Jason; Schlosser, Jessica L; Griffin, Donald R; Wong, Darice Y; Kasko, Andrea M

    2013-08-12

    Disulfide exchange is an important bioconjugation tool, enabling chemical modification of peptides and proteins containing free cysteines. We previously reported the synthesis of a macromer bearing an activated disulfide and its incorporation into hydrogels. Despite their ability to diffuse freely into hydrogels, larger proteins were unable to undergo in-gel disulfide exchange. In order to understand this phenomenon, we synthesized four different activated disulfide-bearing model compounds (Mn = 300 Da to 10 kDa) and quantified their rate of disulfide exchange with a small peptide (glutathione), a moderate-sized protein (β-lactoglobulin), and a large protein (bovine serum albumin) in four different pH solutions (6.0, 7.0, 7.4, and 8.0) to mimic biological systems. Rate constants of exchange depend significantly on the size and accessibility of the thiolate. pH also significantly affects the rate of reaction, with the faster reactions occurring at higher pH. Surprisingly, little difference in exchange rates is seen between macromolecular disulfides of varying size (Mn = 2 kDa - 10 kDa), although all undergo exchange more slowly than their small molecule analogue (MW = 300 g/mol). The maximum exchange efficiencies (% disulfides exchanged after 24 h) are not siginificantly affected by thiol size or pH, but somewhat affected by disulfide size. Therefore, while all three factors investigated (pH, disulfide size, and thiolate size) can influence the exchange kinetics and extent of reaction, the size of the thiolate and its accessibility plays the most significant role.

  3. 25 CFR 20.516 - How are child abuse, neglect or exploitation cases to be handled?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false How are child abuse, neglect or exploitation cases to be... FINANCIAL ASSISTANCE AND SOCIAL SERVICES PROGRAMS Child Assistance Foster Care § 20.516 How are child abuse, neglect or exploitation cases to be handled? Reported child abuse, neglect or exploitation cases and the...

  4. Dissemination and Exploitation Strategy

    DEFF Research Database (Denmark)

    Badger, Merete; Monaco, Lucio; Fransson, Torsten

    of Technology in Sweden, Politecnico di Torino in Italy, and Eindhoven University of Technology in the Netherlands. The project is partially funded by the European Commission under the 7th Framework Programme (project no. RI-283746). This report describes the final dissemination and exploitation strategy...... for project Virtual Campus Hub. A preliminary dissemination and exploitation plan was setup early in the project as described in the deliverable D6.1 Dissemination strategy paper - preliminary version. The plan has been revised on a monthly basis during the project’s lifecycle in connection with the virtual...

  5. Chemoreactomic analysis of thiamine disulfide, thiamine hydrochloride, and benfotiamine molecules

    OpenAIRE

    O. A. Gromova; I. Yu. Torshin; L. V. Stakhovskaya; L. E. Fedotova

    2017-01-01

    Objective: to analyze the interactions that could indicate the potential pharmacological properties of the molecules of thiamin, thiamine disulfide, and others.Material and methods. The investigators simulated the properties of thiamine disulfide (bistiamin) versus those of the reference molecules of thiamin hydrochloride and benfotiamine. The study was performed using chemoreactomic simulation that is the newest area in post-genome pharmacology.Results and discussion. Chemoreactomic analysis...

  6. Lithium/disulfide battery R and D

    Science.gov (United States)

    Kaun, T. D.; Deluca, W.; Lee, J.; Redey, L.; Nelson, P. A.

    The focus of molten-salt cell R and D in the past year at Argonne National Laboratory has been on developing an understanding of the excellent performance and stability of a lithium/disulfide cell using LiCl-LiBr-KBr electrolyte. For further improvement, we have initiated development of a rod-electrode cell design and design of cells which can tolerate overdischarge and overcharge abuse. Earlier Li/FeS2 cells offered performance quite below expectations and had high capacity decline rates: 0.10 to 0.25 percent per cycle. Approaches for reducing the capacity decline rates of the earlier cells also reduced cell performance. However, our improved Li/FeS2 cell tests indicate good prospects for attaining cell development goals of specific energy of 200 Wh/kg at a 4-h discharge rate, a specific power of 200 W/kg at 80 percent depth of discharge, and a cycle life of 1000 cycles.

  7. Raman Signatures of Polytypism in Molybdenum Disulfide.

    Science.gov (United States)

    Lee, Jae-Ung; Kim, Kangwon; Han, Songhee; Ryu, Gyeong Hee; Lee, Zonghoon; Cheong, Hyeonsik

    2016-02-23

    Since the stacking order sensitively affects various physical properties of layered materials, accurate determination of the stacking order is important for studying the basic properties of these materials as well as for device applications. Because 2H-molybdenum disulfide (MoS2) is most common in nature, most studies so far have focused on 2H-MoS2. However, we found that the 2H, 3R, and mixed stacking sequences exist in few-layer MoS2 exfoliated from natural molybdenite crystals. The crystal structures are confirmed by HR-TEM measurements. The Raman signatures of different polytypes are investigated by using three different excitation energies that are nonresonant and resonant with A and C excitons, respectively. The low-frequency breathing and shear modes show distinct differences for each polytype, whereas the high-frequency intralayer modes show little difference. For resonant excitations at 1.96 and 2.81 eV, distinct features are observed that enable determination of the stacking order.

  8. A single disulfide bond disruption in the β3 integrin subunit promotes thiol/disulfide exchange, a molecular dynamics study.

    Directory of Open Access Journals (Sweden)

    Lihie Levin

    Full Text Available The integrins are a family of membrane receptors that attach a cell to its surrounding and play a crucial function in cell signaling. The combination of internal and external stimuli alters a folded non-active state of these proteins to an extended active configuration. The β3 subunit of the platelet αIIbβ3 integrin is made of well-structured domains rich in disulfide bonds. During the activation process some of the disulfides are re-shuffled by a mechanism requiring partial reduction of some of these bonds; any disruption in this mechanism can lead to inherent blood clotting diseases. In the present study we employed Molecular Dynamics simulations for tracing the sequence of structural fluctuations initiated by a single cysteine mutation in the β3 subunit of the receptor. These simulations showed that in-silico protein mutants exhibit major conformational deformations leading to possible disulfide exchange reactions. We suggest that any mutation that prevents Cys560 from reacting with one of the Cys(567-Cys(581 bonded pair, thus disrupting its ability to participate in a disulfide exchange reaction, will damage the activation mechanism of the integrin. This suggestion is in full agreement with previously published experiments. Furthermore, we suggest that rearrangement of disulfide bonds could be a part of a natural cascade of thiol/disulfide exchange reactions in the αIIbβ3 integrin, which are essential for the native activation process.

  9. Design, Synthesis and Biological Evaluation of Brain-Targeted Thiamine Disulfide Prodrugs of Ampakine Compound LCX001

    Directory of Open Access Journals (Sweden)

    Dian Xiao

    2016-04-01

    Full Text Available Ampakine compounds have been shown to reverse opiate-induced respiratory depression by activation of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA glutamate receptors. However, their pharmacological exploitations are hindered by low blood-brain barrier (BBB permeability and limited brain distribution. Here, we explored whether thiamine disulfide prodrugs with the ability of “lock-in” can be used to solve these problems. A series of thiamine disulfide prodrugs 7a–7f of ampakine compound LCX001 was synthesized and evaluated. The trials in vitro showed that prodrugs 7e, 7d, 7f possessed a certain stability in plasma and quickly decomposed in brain homogenate by the disulfide reductase. In vivo, prodrug 7e decreased the peripheral distribution of LCX001 and significantly increased brain distribution of LCX001 after i.v. administration. This compound showed 2.23- and 3.29-fold greater increases in the AUC0-t and MRT0-t of LCX001 in brain, respectively, than did LCX001 itself. A preliminary pharmacodynamic study indicated that the required molar dose of prodrug 7e was only one eighth that of LCX001 required to achieve the same effect in mice. These findings provide an important reference to evaluate the clinical outlook of ampakine compounds.

  10. Disulfide Bridges: Bringing Together Frustrated Structure in a Bioactive Peptide.

    Science.gov (United States)

    Zhang, Yi; Schulten, Klaus; Gruebele, Martin; Bansal, Paramjit S; Wilson, David; Daly, Norelle L

    2016-04-26

    Disulfide bridges are commonly found covalent bonds that are usually believed to maintain structural stability of proteins. Here, we investigate the influence of disulfide bridges on protein dynamics through molecular dynamics simulations on the cysteine-rich trypsin inhibitor MCoTI-II with three disulfide bridges. Correlation analysis of the reduced cyclic peptide shows that two of the three disulfide distances (Cys(11)-Cys(23) and Cys(17)-Cys(29)) are anticorrelated within ∼1 μs of bridge formation or dissolution: when the peptide is in nativelike structures and one of the distances shortens to allow bond formation, the other tends to lengthen. Simulations over longer timescales, when the denatured state is less structured, do not show the anticorrelation. We propose that the native state contains structural elements that frustrate one another's folding, and that the two bridges are critical for snapping the frustrated native structure into place. In contrast, the Cys(4)-Cys(21) bridge is predicted to form together with either of the other two bridges. Indeed, experimental chromatography and nuclear magnetic resonance data show that an engineered peptide with the Cys(4)-Cys(21) bridge deleted can still fold into its near-native structure even in its noncyclic form, confirming the lesser role of the Cys(4)-Cys(21) bridge. The results highlight the importance of disulfide bridges in a small bioactive peptide to bring together frustrated structure in addition to maintaining protein structural stability. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Thiol/disulfide redox states in signaling and sensing

    Science.gov (United States)

    Go, Young-Mi; Jones, Dean P.

    2015-01-01

    Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol-disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady-states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling, and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol-disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities. PMID:23356510

  12. Hacking the art of exploitation

    CERN Document Server

    Erickson, Jon

    2003-01-01

    A comprehensive introduction to the techniques of exploitation and creative problem-solving methods commonly referred to as "hacking," Hacking: The Art of Exploitation is for both technical and non-technical people who are interested in computer security. It shows how hackers exploit programs and write exploits, instead of just how to run other people's exploits. Unlike many so-called hacking books, this book explains the technical aspects of hacking, including stack based overflows, heap based overflows, string exploits, return-into-libc, shellcode, and cryptographic attacks on 802.11b.

  13. Nanostructured Basaltfiberconcrete Exploitational Characteristics

    Science.gov (United States)

    Saraykina, K. A.; Shamanov, V. A.

    2017-11-01

    The article demonstrates that the mass use of basalt fiber concrete (BFC) is constrained by insufficient study of their durability and serviceability in a variety of environments. This research is aimed at the study of the basalt fiber corrosion processes in the cement stone of BFC, the control of the new products structure formation in order to protect the reinforcing fiber from alkaline destruction and thereby improve the exploitational characteristics of the composite. The research result revealed that the modification of basaltfiber concrete by the dispersion of MWNTs contributes to the directional formation of new products in the cement matrix. The HAM additive in basaltfiberconcrete provides for the binding of portlandite to low-basic calcium hydroaluminosilicates, thus reducing the aggressive effect of the cement environment on the reinforcing fibers properties. The complex modification of BFC with nanostructured additives provides for an increase in its durability and exploitational properties (strength, frost resistance and water resistance) due to basalt fiber protection from alkali corrosion on account of the compacting of the contact zone “basalt fiber - cement stone” and designing of the new products structure and morphology of cement matrix over the fiber surface.

  14. A molybdenum disulfide/carbon nanotube heterogeneous complementary inverter.

    Science.gov (United States)

    Huang, Jun; Somu, Sivasubramanian; Busnaina, Ahmed

    2012-08-24

    We report a simple, bottom-up/top-down approach for integrating drastically different nanoscale building blocks to form a heterogeneous complementary inverter circuit based on layered molybdenum disulfide and carbon nanotube (CNT) bundles. The fabricated CNT/MoS(2) inverter is composed of n-type molybdenum disulfide (MOS(2)) and p-type CNT transistors, with a high voltage gain of 1.3. The CNT channels are fabricated using directed assembly while the layered molybdenum disulfide channels are fabricated by mechanical exfoliation. This bottom-up fabrication approach for integrating various nanoscale elements with unique characteristics provides an alternative cost-effective methodology to complementary metal-oxide-semiconductors, laying the foundation for the realization of high performance logic circuits.

  15. Quantifying the global cellular thiol-disulfide status

    DEFF Research Database (Denmark)

    Hansen, Rosa E; Roth, Doris; Winther, Jakob R

    2009-01-01

    It is widely accepted that the redox status of protein thiols is of central importance to protein structure and folding and that glutathione is an important low-molecular-mass redox regulator. However, the total cellular pools of thiols and disulfides and their relative abundance have never been...... determined. In this study, we have assembled a global picture of the cellular thiol-disulfide status in cultured mammalian cells. We have quantified the absolute levels of protein thiols, protein disulfides, and glutathionylated protein (PSSG) in all cellular protein, including membrane proteins. These data...... cell types. However, when cells are exposed to a sublethal dose of the thiol-specific oxidant diamide, PSSG levels increase to >15% of all protein cysteine. Glutathione is typically characterized as the "cellular redox buffer"; nevertheless, our data show that protein thiols represent a larger active...

  16. Transnational gestational surrogacy: does it have to be exploitative?

    Science.gov (United States)

    Kirby, Jeffrey

    2014-01-01

    This article explores the controversial practice of transnational gestational surrogacy and poses a provocative question: Does it have to be exploitative? Various existing models of exploitation are considered and a novel exploitation-evaluation heuristic is introduced to assist in the analysis of the potentially exploitative dimensions/elements of complex health-related practices. On the basis of application of the heuristic, I conclude that transnational gestational surrogacy, as currently practiced in low-income country settings (such as rural, western India), is exploitative of surrogate women. Arising out of consideration of the heuristic's exploitation conditions, a set of public education and enabled choice, enhanced protections, and empowerment reforms to transnational gestational surrogacy practice is proposed that, if incorporated into a national regulatory framework and actualized within a low income country, could possibly render such practice nonexploitative.

  17. Electrostatic influence of local cysteine environments on disulfide exchange kinetics.

    Science.gov (United States)

    Snyder, G H; Cennerazzo, M J; Karalis, A J; Field, D

    1981-11-10

    The ionic strength dependence of the bimolecular rate constant for reaction of the negative disulfide 5,5'-dithiobis (2-nitrobenzoic acid) with cysteines in fragments of naturally occurring proteins was determined by stopped-flow spectroscopy. The Debye-Hückel relationship was applied to determine the effective charge at the cysteine and thereby determine the extent to which nearby neighbors in the primary sequence influence the kinetics. Corrections for the secondary salt effect on cysteine pKs were determined by direct spectrometric pH titration of sulfhydryl groups or by observation of the ionic strength dependence of kinetics of cysteine reaction with the neutral disulfide 2,2'-dithiodipyridine. Quantitative expressions was verified by model studies with N-acetyl-cystein. At ionic strengths equal to or greater than 20 mM, the net charge at the polypeptide cysteine site is the sum of the single negative charge of the thiolate anion and the charges of the amino acids immediately preceding and following the cysteine in the primary sequence. At lower ionic strengths, more distant residues influence kinetics. At pH 7.0, 23 degree C, and an ionic strength of 20 mM, rate constants for reaction of the negative disulfide with a cysteine having two positive neighbors, one positive and one neutral neighbor, or two neutral neighbors are 132000, 3350, and 367 s-1 M-1, respectively. This corresponds to a contribution to the activation energy of 0.65- 1.1 kcal/mol per ion pair involved in collision between the cysteine and disulfide regions. The results permit the estimation that cysteine local environments may provide a means of achieving a 10(6)-fold range in rate constants in disulfide exchange reactions in random-coil proteins. This range may prove useful in developing strategies for directing disulfide pairing in synthetic proteins.

  18. Structures and related properties of helical, disulfide-stabilized peptides

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, Mark D. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1993-11-01

    The three dimensional structure of several peptides were determined by NMR spectroscopy and distance geometry calculations. Each peptide formed a predictable, rigid structure, consisting of an α-helix, a "scaffold" region which packed along one face of the helix, and two disulfide bridges which covalently connect the helix and scaffold regions. The peptide Apa-M5 was designed to constrain the M5 peptide from MLCK in a helical geometry using the apamin disulfide scaffold. This scaffold constrains the N- terminal end of the helix with two disulfide bridges and a reverse turn. Like the M5 peptide, Apa-M5 was found to bind calmodulin in a Ca2+-dependent 1:1 stoichiometry. However, the dissociation constant of the (Apa-M5)-calmodulin complex, 107 nM, was 100-fold higher than the dissociation constant of the M5-calmodulin complex. This difference was due to a putative steric overlap between the Apa-M5 scaffold and calmodulin. The peptide Apa-Cro was designed to replace the large structural protein matrix of λ Cro with the apamin disulfide scaffold. However, Apa-Cro did not bind the consensus DNA operator half-site of λ Cro, probably due to a steric overlap between the Apa-Cro disulfide framework and the DNA. The amino acid sequence of the scaffold-disulfide bridge arrangement of the peptide Max was derived from the core sequence of scyllatoxin, which contains an α-helix constrained at the C-terminal end by two disulfide bridges and a two-stranded βsheet scaffold. Max was shown to fold with >84% yield to form a predictable, stable structure that is similar to scyllatoxin. The folding and stability properties of Max make this scaffold and disulfide bridge arrangement an ideal candidate for the development of hybrid sequence peptides. The dynamics of a fraying C-terminal end of the helix of the peptide Apa-AlaN was determined by analysis of 15N NMR relaxation properties.

  19. Exploitation by Economic Necessity

    Directory of Open Access Journals (Sweden)

    Kristian F. Braekkan

    2015-10-01

    Full Text Available This study develops and tests a model that proposes economic necessity moderates the relationship between psychological contract violations (PCVs and organizational commitment and trust in the employing organization among non-unionized manufacturing workers (N = 226. Moderated regression analyses revealed that there was a significant interaction between PCV and economic necessity in predicting both outcomes. Specifically, the findings indicated that individuals experiencing high PCV and high economic necessity did not decrease their organizational commitment like their counterparts who endorsed lower economic necessity. They did, however, experience significantly decreased trust in their employer. The findings suggest that individuals who are forced to sell their labor power and obtain what they need through the market are more likely to continue to be exploited by their employer, as they have no other options than to continue the relationship. The importance of the findings is discussed, and recommendations for future research are provided.

  20. Exploitative Learning by Exporting

    DEFF Research Database (Denmark)

    Golovko, Elena; Lopes Bento, Cindy; Sofka, Wolfgang

    Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies...... and learning about new markets ? R&D investments and marketing investments, in search of novel insights into the content and process underlying learning by exporting. We draw from organizational learning theory for predicting changes in both R&D and marketing investment patterns that accompany firm entry......, it is predominantly the marketing-related investment decisions associated with starting to export that lead to increases in firm productivity. We conclude that learning-by-exporting might be more properly characterized as ?learning about and exploiting new markets? rather than ?learning about new technologies...

  1. Learning Metasploit exploitation and development

    CERN Document Server

    Balapure, Aditya

    2013-01-01

    A practical, hands-on tutorial with step-by-step instructions. The book will follow a smooth and easy-to-follow tutorial approach, covering the essentials and then showing the readers how to write more sophisticated exploits.This book targets exploit developers, vulnerability analysts and researchers, network administrators, and ethical hackers looking to gain advanced knowledge in exploitation development and identifying vulnerabilities. The primary goal is to take readers wishing to get into more advanced exploitation discovery and reaching the next level.Prior experience exploiting basic st

  2. Electrical Transport Properties of Polycrystalline Monolayer Molybdenum Disulfide

    Science.gov (United States)

    2014-07-14

    Lou, Sina Najmaei, Matin Amani, Matthew L. Chin, Zheng Se. TASK NUMBER Liu Sf. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAMES AND ADDRESSES 8...Transport Properties of Polycrystalline Monolayer Molybdenum Disulfide Sina Najmaei,t.§ Matin Ama ni,M Matthew L. Chin,* Zhe ng liu/ ·"·v: A. Gle n

  3. UV Photofragmentation Dynamics of Protonated Cystine: Disulfide Bond Rupture.

    Science.gov (United States)

    Soorkia, Satchin; Dehon, Christophe; Kumar, S Sunil; Pedrazzani, Mélanie; Frantzen, Emilie; Lucas, Bruno; Barat, Michel; Fayeton, Jacqueline A; Jouvet, Christophe

    2014-04-03

    Disulfide bonds (S-S) play a central role in stabilizing the native structure of proteins against denaturation. Experimentally, identification of these linkages in peptide and protein structure characterization remains challenging. UV photodissociation (UVPD) can be a valuable tool in identifying disulfide linkages. Here, the S-S bond acts as a UV chromophore and absorption of one UV photon corresponds to a σ-σ* transition. We have investigated the photodissociation dynamics of protonated cystine, which is a dimer of two cysteines linked by a disulfide bridge, at 263 nm (4.7 eV) using a multicoincidence technique in which fragments coming from the same fragmentation event are detected. Two types of bond cleavages are observed corresponding to the disulfide (S-S) and adjacent C-S bond ruptures. We show that the S-S cleavage leads to three different fragment ions via three different fragmentation mechanisms. The UVPD results are compared to collision-induced dissociation (CID) and electron-induced dissociation (EID) studies.

  4. Alpha-cyclodextrins reversibly capped with disulfide bonds

    Czech Academy of Sciences Publication Activity Database

    Kumprecht, Lukáš; Buděšínský, Miloš; Bouř, Petr; Kraus, Tomáš

    2010-01-01

    Roč. 34, č. 10 (2010), s. 2254-2260 ISSN 1144-0546 R&D Projects: GA AV ČR IAA400550810 Institutional research plan: CEZ:AV0Z40550506 Keywords : cyclodextrins * disulfide bond * dynamic covalent bond Subject RIV: CC - Organic Chemistry Impact factor: 2.631, year: 2010

  5. Impaired Thiol-Disulfide Balance in Acute Brucellosis.

    Science.gov (United States)

    Kolgelier, Servet; Ergin, Merve; Demir, Lutfi Saltuk; Inkaya, Ahmet Cagkan; Aktug Demir, Nazlim; Alisik, Murat; Erel, Ozcan

    2017-05-24

    The objective of this study was to examine a novel profile: thiol-disulfide homeostasis in acute brucellosis. The study included 90 patients with acute brucellosis, and 27 healthy controls. Thiol-disulfide profile tests were analyzed by a recently developed method, and ceruloplasmin levels were determined. Native thiol levels were 256.72 ± 48.20 μmol/L in the acute brucellosis group and 461.13 ± 45.37 μmol/L in the healthy group, and total thiol levels were 298.58 ± 51.78 μmol/L in the acute brucellosis group and 504.83 ± 51.05 μmol/L in the healthy group (p brucellosis than in the healthy controls (p brucellosis. The strong associations between thiol-disulfide parameters and a positive acute-phase reactant reflected the disruption of the balance between the antioxidant and oxidant systems. Since thiol groups act as anti-inflammatory mediators, the alteration in the thiol-disulfide homeostasis may be involved in brucellosis.

  6. Domain architecture of protein-disulfide isomerase facilitates its dual role as an oxidase and an isomerase in Ero1p-mediated disulfide formation

    DEFF Research Database (Denmark)

    Kulp, M. S.; Frickel, E. M.; Ellgaard, Lars

    2006-01-01

    reduction/rearrangement of non-native disulfides is poorly understood. We analyzed the role of individual PDI domains in disulfide bond formation in a reaction driven by their natural oxidant, Ero1p. We found that Ero1p oxidizes the isolated PDI catalytic thioredoxin domains, A and A' at the same rate......Native disulfide bond formation in eukaryotes is dependent on protein-disulfide isomerase (PDI) and its homologs, which contain varying combinations of catalytically active and inactive thioredoxin domains. However, the specific contribution of PDI to the formation of new disulfides versus...... catalytic (A) domain. The specific order of thioredoxin domains in PDI is important in establishing the asymmetry in the rate of oxidation of the two active sites thus allowing A and A', two thioredoxin domains that are similar in sequence and structure, to serve opposing functional roles as a disulfide...

  7. Recent mass spectrometry-based techniques and considerations for disulfide bond characterization in proteins.

    Science.gov (United States)

    Lakbub, Jude C; Shipman, Joshua T; Desaire, Heather

    2018-04-01

    Disulfide bonds are important structural moieties of proteins: they ensure proper folding, provide stability, and ensure proper function. With the increasing use of proteins for biotherapeutics, particularly monoclonal antibodies, which are highly disulfide bonded, it is now important to confirm the correct disulfide bond connectivity and to verify the presence, or absence, of disulfide bond variants in the protein therapeutics. These studies help to ensure safety and efficacy. Hence, disulfide bonds are among the critical quality attributes of proteins that have to be monitored closely during the development of biotherapeutics. However, disulfide bond analysis is challenging because of the complexity of the biomolecules. Mass spectrometry (MS) has been the go-to analytical tool for the characterization of such complex biomolecules, and several methods have been reported to meet the challenging task of mapping disulfide bonds in proteins. In this review, we describe the relevant, recent MS-based techniques and provide important considerations needed for efficient disulfide bond analysis in proteins. The review focuses on methods for proper sample preparation, fragmentation techniques for disulfide bond analysis, recent disulfide bond mapping methods based on the fragmentation techniques, and automated algorithms designed for rapid analysis of disulfide bonds from liquid chromatography-MS/MS data. Researchers involved in method development for protein characterization can use the information herein to facilitate development of new MS-based methods for protein disulfide bond analysis. In addition, individuals characterizing biotherapeutics, especially by disulfide bond mapping in antibodies, can use this review to choose the best strategies for disulfide bond assignment of their biologic products. Graphical Abstract This review, describing characterization methods for disulfide bonds in proteins, focuses on three critical components: sample preparation, mass

  8. The synthesis of unsymmetric disulfides for use as radio-protectives

    International Nuclear Information System (INIS)

    Chang, S.H.H.

    1988-01-01

    Unsymmetric disulfides with radioprotective potential were synthesized by linking biomolecules, and related substances, to known radio-protective aminothiols via a disulfide bond. The biomolecules used in this research include mercaptoalcohols, mercaptopyridines and mercaptophenothiazines. Unsymmetric disulfides were synthesized by reacting two thiols with diethyl azodicarboxylate sequentially at low temperature. The reactions of thiols with thiosulfinate were studied as an alternative for synthesizing disulfides. A cross-linked polystyrene was thiolated by different reagents. The thiolation of polymers is part of a methodological study using solid phase synthesis to synthesize unsymmetric disulfides

  9. Modulation of Thiol-Disulfide Oxidoreductases for Increased Production of Disulfide-Bond-Containing Proteins in Bacillus subtilis

    NARCIS (Netherlands)

    Kouwen, Thijs R. H. M.; Dubois, Jean-Yves F.; Freudl, Roland; Quax, Wim J.; van Dijl, Jan Maarten

    2008-01-01

    Disulfide bonds are important for the correct folding, structural integrity, and activity of many biotechnologically relevant proteins. For synthesis and subsequent secretion of these proteins in bacteria, such as the well-known "cell factory" Bacillus subtilis, it is often the correct formation of

  10. Profits and Exploitation: A Reappraisal

    OpenAIRE

    Yoshihara, Naoki; Veneziani, Roberto

    2011-01-01

    This paper provides a mathematical analysis of the Marxian theory of the exploitation of labour in general equilibrium models. The two main definitions of Marxian exploitation in the literature, proposed by Morishima (1974) and Roemer (1982), respectively, are analysed in the context of general convex economies. It is shown that, contrary to the received view, in general these definitions do not preserve the so-called Fundamental Marxian Theorem (FMT), which states that the exploitation of la...

  11. Consensual exploitation : the moral wrong in exploitation and legal restrictions on consensual exploitative transactions

    OpenAIRE

    van der Neut, Wendy

    2014-01-01

    This thesis is about so-­‐called consensual exploitative transactions: transactions to which all parties agree voluntarily, and which are beneficial for all parties, but which are still widely considered exploitative, and for that reason legally restricted in many countries. The thesis asks two main questions: 1. What is wrong with consensual exploitation? 2.What implications does the answer to this question have for the legal restriction of consensual transactions ...

  12. A structural model of pestivirus E(rns) based on disulfide bond connectivity and homology modeling reveals an extremely rare vicinal disulfide

    NARCIS (Netherlands)

    Langedijk, J.P.M.; Veelen, van P.A.; Schaaper, W.M.M.; Ru, de A.H.; Meloen, R.H.; Hulst, M.M.

    2002-01-01

    Erns is a pestivirus envelope glycoprotein and is the only known viral surface protein with RNase activity. Erns is a disulfide-linked homodimer of 100 kDa; it is found on the surface of pestivirus-infected cells and is secreted into the medium. In this study, the disulfide arrangement of the nine

  13. Photodegradable, Photoadaptable Hydrogels via Radical-Mediated Disulfide Fragmentation Reaction.

    Science.gov (United States)

    Fairbanks, Benjamin D; Singh, Samir P; Bowman, Christopher N; Anseth, Kristi S

    2011-04-26

    Various techniques have been adopted to impart a biological responsiveness to synthetic hydrogels for the delivery of therapeutic agents as well as the study and manipulation of biological processes and tissue development. Such techniques and materials include polyelectrolyte gels that swell and deswell with changes in pH, thermosensitive gels that contract at physiological temperatures, and peptide cross-linked hydrogels that degrade upon peptidolysis by cell-secreted enzymes. Herein we report a unique approach to photochemically deform and degrade disulfide cross-linked hydrogels, mitigating the challenges of light attenuation and low quantum yield, permitting the degradation of hydrogels up to 2 mm thick within 120 s at low light intensities (10 mW/cm(2) at 365 nm). Hydrogels were formed by the oxidation of thiol-functionalized 4-armed poly(ethylene glycol) macromolecules. These disulfide cross-linked hydrogels were then swollen in a lithium acylphosphinate photoinitiator solution. Upon exposure to light, photogenerated radicals initiate multiple fragmentation and disulfide exchange reactions, permitting and promoting photodeformation, photowelding, and photodegradation. This novel, but simple, approach to generate photoadaptable hydrogels portends the study of cellular response to mechanically and topographically dynamic substrates as well as novel encapsulations by the welding of solid substrates. The principles and techniques described herein hold implications for more than hydrogel materials but also for photoadaptable polymers more generally.

  14. The influence of zinc(II) on thioredoxin/glutathione disulfide exchange: QM/MM studies to explore how zinc(II) accelerates exchange in higher dielectric environments.

    Science.gov (United States)

    Kurian, Roby; Bruce, Mitchell R M; Bruce, Alice E; Amar, François G

    2015-08-01

    QM/MM studies were performed to explore the energetics of exchange reactions of glutathione disulfide (GSSG) and the active site of thioredoxin [Cys32-Gly33-Pro34-Cys35] with and without zinc(II), in vacuum and solvated models. The activation energy for exchange, in the absence of zinc, is 29.7 kcal mol(-1) for the solvated model. This is 3.3 kcal mol(-1) higher than the activation energy for exchange in the gas phase, due to ground state stabilization of the active site Cys-32 thiolate in a polar environment. In the presence of zinc, the activation energy for exchange is 4.9 kcal mol(-1) lower than in the absence of zinc (solvated models). The decrease in activation energy is attributed to stabilization of the charge-separated transition state, which has a 4-centered, cyclic arrangement of Zn-S-S-S with an estimated dipole moment of 4.2 D. A difference of 4.9 kcal mol(-1) in activation energy would translate to an increase in rate by a factor of about 4000 for zinc-assisted thiol-disulfide exchange. The calculations are consistent with previously reported experimental results, which indicate that metal-thiolate, disulfide exchange rates increase as a function of solvent dielectric. This trend is opposite to that observed for the influence of the dielectric environment on the rate of thiol-disulfide exchange in the absence of metal. The results suggest a dynamic role for zinc in thiol-disulfide exchange reactions, involving accessible cysteine sites on proteins, which may contribute to redox regulation and mechanistic pathways during oxidative stress.

  15. Kinetic and Thermodynamic Aspects of Cellular Thiol-Disulfide Redox Regulation

    DEFF Research Database (Denmark)

    Jensen, Kristine Steen; Hansen, Rosa Erritzøe; Winther, Jakob R

    2009-01-01

    . In the cytosol regulatory disulfide bonds are typically formed in spite of the prevailing reducing conditions and may thereby function as redox switches. Such disulfide bonds are protected from enzymatic reduction by kinetic barriers and are thus allowed to exist long enough to elicit the signal. Factors......Regulation of intracellular thiol-disulfide redox status is an essential part of cellular homeostasis. This involves the regulation of both oxidative and reductive pathways, production of oxidant scavengers and, importantly, the ability of cells to respond to changes in the redox environment...... that affect the rate of thiol-disulfide exchange and stability of disulfide bonds are discussed within the framework of the underlying chemical foundations. This includes the effect of thiol acidity (pKa), the local electrostatic environment, molecular strain and entropy. Even though a thiol-disulfide...

  16. Modification of molybdenum disulfide in methanol solvent for hydrogen evolution reaction

    Science.gov (United States)

    Niyitanga, Theophile; Jeong, Hae Kyung

    2018-05-01

    Molybdenum disulfide is a promising catalyst to replace the expensive platinum as an electrocatalyst but needs to be modified to present excellent electrocatalytic properties. Herein, we successfully modify molybdenum disulfide in methanol solvent for hydrogen evolution reaction by using a simple hydrothermal method. Overpotential reduced to -0.6 V from -1.5 V, and energy band gap decreased from 1.73 eV to 1.58 eV after the modification. The modified molybdenum disulfide also demonstrated lower resistance (42 Ω) at high frequency (1000 kHz) compared with that (240 Ω) of the precursor, showing that conductivity of the modified molybdenum disulfide has improved.

  17. Thiol-disulfide exchange in peptides derived from human growth hormone.

    Science.gov (United States)

    Chandrasekhar, Saradha; Epling, Daniel E; Sophocleous, Andreas M; Topp, Elizabeth M

    2014-04-01

    Disulfide bonds stabilize proteins by cross-linking distant regions into a compact three-dimensional structure. They can also participate in hydrolytic and oxidative pathways to form nonnative disulfide bonds and other reactive species. Such covalent modifications can contribute to protein aggregation. Here, we present experimental data for the mechanism of thiol-disulfide exchange in tryptic peptides derived from human growth hormone in aqueous solution. Reaction kinetics was monitored to investigate the effect of pH (6.0-10.0), temperature (4-50°C), oxidation suppressants [ethylenediaminetetraacetic acid (EDTA) and N2 sparging], and peptide secondary structure (amide cyclized vs. open form). The concentrations of free thiol containing peptides, scrambled disulfides, and native disulfide-linked peptides generated via thiol-disulfide exchange and oxidation reactions were determined using reverse-phase HPLC and liquid chromatography-mass spectrometry. Concentration versus time data were fitted to a mathematical model using nonlinear least squares regression analysis. At all pH values, the model was able to fit the data with R(2) ≥ 0.95. Excluding oxidation suppressants (EDTA and N2 sparging) resulted in an increase in the formation of scrambled disulfides via oxidative pathways but did not influence the intrinsic rate of thiol-disulfide exchange. In addition, peptide secondary structure was found to influence the rate of thiol-disulfide exchange. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  18. The effect of tensile stress on the conformational free energy landscape of disulfide bonds.

    Directory of Open Access Journals (Sweden)

    Padmesh Anjukandi

    Full Text Available Disulfide bridges are no longer considered to merely stabilize protein structure, but are increasingly recognized to play a functional role in many regulatory biomolecular processes. Recent studies have uncovered that the redox activity of native disulfides depends on their C-C-S-S dihedrals, χ2 and χ'2. Moreover, the interplay of chemical reactivity and mechanical stress of disulfide switches has been recently elucidated using force-clamp spectroscopy and computer simulation. The χ2 and χ'2 angles have been found to change from conformations that are open to nucleophilic attack to sterically hindered, so-called closed states upon exerting tensile stress. In view of the growing evidence of the importance of C-C-S-S dihedrals in tuning the reactivity of disulfides, here we present a systematic study of the conformational diversity of disulfides as a function of tensile stress. With the help of force-clamp metadynamics simulations, we show that tensile stress brings about a large stabilization of the closed conformers, thereby giving rise to drastic changes in the conformational free energy landscape of disulfides. Statistical analysis shows that native TDi, DO and interchain Ig protein disulfides prefer open conformations, whereas the intrachain disulfide bridges in Ig proteins favor closed conformations. Correlating mechanical stress with the distance between the two a-carbons of the disulfide moiety reveals that the strain of intrachain Ig protein disulfides corresponds to a mechanical activation of about 100 pN. Such mechanical activation leads to a severalfold increase of the rate of the elementary redox S(N2 reaction step. All these findings constitute a step forward towards achieving a full understanding of functional disulfides.

  19. Methods of measuring Protein Disulfide Isomerase activity: a critical overview

    Science.gov (United States)

    Watanabe, Monica; Laurindo, Francisco; Fernandes, Denise

    2014-09-01

    Protein disulfide isomerase is an essential redox chaperone from the endoplasmic reticulum (ER) and is responsible for correct disulfide bond formation in nascent proteins. PDI is also found in other cellular locations in the cell, particularly the cell surface. Overall, PDI contributes to ER and global cell redox homeostasis and signaling. The knowledge about PDI structure and function progressed substantially based on in vitro studies using recombinant PDI and chimeric proteins. In these experimental scenarios, PDI reductase and chaperone activities are readily approachable. In contrast, assays to measure PDI isomerase activity, the hallmark of PDI family, are more complex. Assessment of PDI roles in cells and tissues mainly relies on gain- or loss-of-function studies. However, there is limited information regarding correlation of experimental readouts with the distinct types of PDI activities. In this mini-review, we evaluate the main methods described for measuring the different kinds of PDI activity: thiol reductase, thiol oxidase, thiol isomerase and chaperone. We emphasize the need to use appropriate controls and the role of critical interferents (e.g., detergent, presence of reducing agents). We also discuss the translation of results from in vitro studies with purified recombinant PDI to cellular and tissue samples, with critical comments on the interpretation of results.

  20. Folding and activity of hybrid sequence, disulfide-stabilized peptides

    Energy Technology Data Exchange (ETDEWEB)

    Pease, J.H.B.; Storrs, R.W.; Wemmer, D.E. (Univ. of California, Berkeley (USA))

    1990-08-01

    Peptides have been synthesized that have hybrid sequences, partially derived from the bee venom peptide apamin and partially from the S peptide of ribonuclease A. The hybrid peptides were demonstrated by NMR spectroscopy to fold, forming the same disulfides and basic three-dimensional structure as native apamin, containing a {beta}-turn and an {alpha}-helix. These hybrids were active in complementing S protein, reactivating nuclease activity. In addition, the hybrid peptide was effective in inducing antibodies that cross-react with the RNase, without conjugation to a carrier protein. The stability of the folded structure of this peptide suggests that it should be possible to elicit antibodies that will react not only with a specific sequence, but also with a specific secondary structure. Hybrid sequence peptides also provide opportunities to study separately nucleation and propagation steps in formation of secondary structure. The authors show that in S peptide the {alpha}-helix does not end abruptly but rather terminates gradually over four or five residues. In general, these hybrid sequence peptides, which fold predictably because of disulfide bond formation, can provide opportunities for examining structure - function relationships for many biologically active sequences.

  1. Folding and activity of hybrid sequence, disulfide-stabilized peptides

    International Nuclear Information System (INIS)

    Pease, J.H.B.; Storrs, R.W.; Wemmer, D.E.

    1990-01-01

    Peptides have been synthesized that have hybrid sequences, partially derived from the bee venom peptide apamin and partially from the S peptide of ribonuclease A. The hybrid peptides were demonstrated by NMR spectroscopy to fold, forming the same disulfides and basic three-dimensional structure as native apamin, containing a β-turn and an α-helix. These hybrids were active in complementing S protein, reactivating nuclease activity. In addition, the hybrid peptide was effective in inducing antibodies that cross-react with the RNase, without conjugation to a carrier protein. The stability of the folded structure of this peptide suggests that it should be possible to elicit antibodies that will react not only with a specific sequence, but also with a specific secondary structure. Hybrid sequence peptides also provide opportunities to study separately nucleation and propagation steps in formation of secondary structure. The authors show that in S peptide the α-helix does not end abruptly but rather terminates gradually over four or five residues. In general, these hybrid sequence peptides, which fold predictably because of disulfide bond formation, can provide opportunities for examining structure - function relationships for many biologically active sequences

  2. Selenocysteine in thiol/disulfide-like exchange reactions.

    Science.gov (United States)

    Hondal, Robert J; Marino, Stefano M; Gladyshev, Vadim N

    2013-05-01

    Among trace elements used as cofactors in enzymes, selenium is unique in that it is incorporated into proteins co-translationally in the form of an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one atom (selenium versus sulfur), yet this switch dramatically influences important aspects of enzyme reactivity. The main focus of this review is an updated and critical discussion on how Sec might be used to accelerate thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with their Cys-containing homologs. We discuss in detail three major aspects associated with thiol/disulfide exchange reactions: (i) nucleophilicity of the attacking thiolate (or selenolate); (ii) electrophilicity of the center sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or selenium). In all these cases, we analyze the benefits that selenium might provide in these types of reactions. It is the biological thiol oxidoreductase-like function that benefits from the use of Sec, since Sec functions to chemically accelerate the rate of these reactions. We review various hypotheses that could help explain why Sec is used in enzymes, particularly with regard to competitive chemical advantages provided by the presence of the selenium atom in enzymes. Ultimately, these chemical advantages must be connected to biological functions of Sec.

  3. Identification of thioredoxin target disulfides in proteins released from barley aleurone layers

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, J.; Yang, Fen

    2010-01-01

    Thioredoxins are ubiquitous disulfide reductases involved in a wide range of cellular processes including DNA synthesis, oxidative stress response and apoptosis. In cereal seeds thioredoxins are proposed to facilitate the germination process by reducing disulfide bonds in storage proteins and other...

  4. The Chemistry of Alk-1-yn-1-yl DisulfidesA Review

    DEFF Research Database (Denmark)

    Senning, Alexander Erich Eugen

    2009-01-01

    The preparation and the properties of the elusive alk-1-yn-1-yl disulfides are reviewed, including the most recent quantum chemical findings with regard to their reactivity.......The preparation and the properties of the elusive alk-1-yn-1-yl disulfides are reviewed, including the most recent quantum chemical findings with regard to their reactivity....

  5. Regulation of interleukin-4 signaling by extracellular reduction of intramolecular disulfides

    International Nuclear Information System (INIS)

    Curbo, Sophie; Gaudin, Raphael; Carlsten, Mattias; Malmberg, Karl-Johan; Troye-Blomberg, Marita; Ahlborg, Niklas; Karlsson, Anna; Johansson, Magnus; Lundberg, Mathias

    2009-01-01

    Interleukin-4 (IL-4) contains three structurally important intramolecular disulfides that are required for the bioactivity of the cytokine. We show that the cell surface of HeLa cells and endotoxin-activated monocytes can reduce IL-4 intramolecular disulfides in the extracellular space and inhibit binding of IL-4 to the IL-4Rα receptor. IL-4 disulfides were in vitro reduced by thioredoxin 1 (Trx1) and protein disulfide isomerase (PDI). Reduction of IL-4 disulfides by the cell surface of HeLa cells was inhibited by auranofin, an inhibitor of thioredoxin reductase that is an electron donor to both Trx1 and PDI. Both Trx1 and PDI have been shown to be located at the cell surface and our data suggests that these enzymes are involved in catalyzing reduction of IL-4 disulfides. The pro-drug N-acetylcysteine (NAC) that promotes T-helper type 1 responses was also shown to mediate the reduction of IL-4 disulfides. Our data provides evidence for a novel redox dependent pathway for regulation of cytokine activity by extracellular reduction of intramolecular disulfides at the cell surface by members of the thioredoxin enzyme family.

  6. Inhibition of carbon disulfide on bio-desulfurization in the process of ...

    African Journals Online (AJOL)

    Biological desulfurization is a novel technology for the removal of hydrogen sulfide from some biogas or sour gas, in which there are always a certain amounts of carbon disulfide together with much hydrogen sulfide. Nowadays, carbon disulfide is found to have negative effect on the biological desulfurization, but seldom ...

  7. Application des fluides supercritiques à la production d'hydrocarbures. Exploitation des gisements par récupération assistée et applications diverses : pétrole, sables, schistes, charbons Application of Supercritical Fluids to Hydrocarbon Production. Enhanced Oi Recovery and Miscellaneous Applications: Oil, Tar Sands, Shales, Coals

    Directory of Open Access Journals (Sweden)

    Behar E.

    2006-11-01

    Full Text Available Le taux moyen de récupération par drainage naturel des gisements pétroliers atteint à peine 30 %. La récupération assistée désigne l'ensemble des procédés d'exploitation qui permettent d'accroître très sensiblement ce taux. Parmi ces procédés, l'injection de fluides supercritiques joue un rôle prometteur. Les principaux fluides actuellement utilisés sont : le méthane (ou plus généralement les gaz hydrocarbures dits pauvres , l'azote et enfin le gaz carbonique. Les domaines d'application et les mécanismes thermodynamiques mis en jeu sont brièvement exposés, les sources de fluides supercritiques disponibles au voisinage des gisements pétroliers sont rapidement répertoriées et certains problèmes d'exploitation évoqués. Outre leur application en récupération assistée, les fluides supercritiques sont également impliqués dans des procédés de raffinage et d'extraction divers. C'est le procédé de désasphaltage de fractions pétrolières lourdes qui, en 1956, a fait l'objet de la première application industrielle exploitant les fortes variations du pouvoir solvant d'un fluide au voisinage de son point critique. Ce procédé connaît, depuis une dizaine d'années, un regain d'intérêt du fait de l'économie d'énergie qu'il permet de réaliser. D'autre part, les schistes bitumineux, les sables asphaltiques et les charbons, sources d'hydrocarbures considérables pour l'avenir, constituent des domaines d'applications potentielles originales des fluides supercritiques. Les procédés spécifiques, pour la plupart en cours de développement au stade pilote, sont passés en revue. The average recovery by natural drainage from oil fields is barely 30%. Enhanced recovery includes all production processes which appreciably increase this rate. Among such processes, supercritical fluid flooding is quite promising. The main fluids now used are methane (or, more generally, so-called leangaseous hydrocarbons, nitrogen and carbon

  8. Conformational analysis and design of cross-strand disulfides in antiparallel β-sheets.

    Science.gov (United States)

    Indu, S; Kochat, V; Thakurela, S; Ramakrishnan, C; Varadarajan, Raghavan

    2011-01-01

    Cross-strand disulfides bridge two cysteines in a registered pair of antiparallel β-strands. A nonredundant data set comprising 5025 polypeptides containing 2311 disulfides was used to study cross-strand disulfides. Seventy-six cross-strand disulfides were found of which 75 and 1 occurred at non-hydrogen-bonded (NHB) and hydrogen-bonded (HB) registered pairs, respectively. Conformational analysis and modeling studies demonstrated that disulfide formation at HB pairs necessarily requires an extremely rare and positive χ¹ value for at least one of the cysteine residues. Disulfides at HB positions also have more unfavorable steric repulsion with the main chain. Thirteen pairs of disulfides were introduced in NHB and HB pairs in four model proteins: leucine binding protein (LBP), leucine, isoleucine, valine binding protein (LIVBP), maltose binding protein (MBP), and Top7. All mutants LIVBP T247C V331C showed disulfide formation either on purification, or on treatment with oxidants. Protein stability in both oxidized and reduced states of all mutants was measured. Relative to wild type, LBP and MBP mutants were destabilized with respect to chemical denaturation, although the sole exposed NHB LBP mutant showed an increase of 3.1°C in T(m). All Top7 mutants were characterized for stability through guanidinium thiocyanate chemical denaturation. Both exposed and two of the three buried NHB mutants were appreciably stabilized. All four HB Top7 mutants were destabilized (ΔΔG⁰ = -3.3 to -6.7 kcal/mol). The data demonstrate that introduction of cross-strand disulfides at exposed NHB pairs is a robust method of improving protein stability. All four exposed Top7 disulfide mutants showed mild redox activity. © 2010 Wiley-Liss, Inc.

  9. Teotihuacan, tepeapulco, and obsidian exploitation.

    Science.gov (United States)

    Charlton, T H

    1978-06-16

    Current cultural ecological models of the development of civilization in central Mexico emphasize the role of subsistence production techniques and organization. The recent use of established and productive archeological surface survey techniques along natural corridors of communication between favorable niches for cultural development within the Central Mexican symbiotic region resulted in the location of sites that indicate an early development of a decentralized resource exploitation, manufacturing, and exchange network. The association of the development of this system with Teotihuacán indicates the importance such nonsubsistence production and exchange had in the evolution of this first central Mexican civilization. The later expansion of Teotihuacán into more distant areas of Mesoamerica was based on this resource exploitation model. Later civilizations centered at Tula and Tenochtitlán also used such a model in their expansion.

  10. Network exploitation using WAMI tracks

    Science.gov (United States)

    Rimey, Ray; Record, Jim; Keefe, Dan; Kennedy, Levi; Cramer, Chris

    2011-06-01

    Creating and exploiting network models from wide area motion imagery (WAMI) is an important task for intelligence analysis. Tracks of entities observed moving in the WAMI sensor data are extracted, then large numbers of tracks are studied over long time intervals to determine specific locations that are visited (e.g., buildings in an urban environment), what locations are related to other locations, and the function of each location. This paper describes several parts of the network detection/exploitation problem, and summarizes a solution technique for each: (a) Detecting nodes; (b) Detecting links between known nodes; (c) Node attributes to characterize a node; (d) Link attributes to characterize each link; (e) Link structure inferred from node attributes and vice versa; and (f) Decomposing a detected network into smaller networks. Experimental results are presented for each solution technique, and those are used to discuss issues for each problem part and its solution technique.

  11. Raman investigation of molybdenum disulfide with different polytypes

    Science.gov (United States)

    Lee, Jae-Ung; Kim, Kangwon; Han, Songhee; Ryu, Gyeong Hee; Lee, Zonghoon; Cheong, Hyeonsik

    The Raman spectra of molybdenum disulfide (MoS2) with different polytypes are investigated. Although 2H-MoS2 is most common in nature, the 3R phase can exist due to a small difference in the formation energy. However, only a few studies are reported for the 3R phase, and most studies have focused on the 2H phase. We found the 2H, 3R and mixed phases of exfoliated few-layer MoS2 from natural molybdenite crystals. The crystal structures of 2H- and 3R-MoS2 are confirmed by the HR-TEM measurements. By using 3 different excitation energies, we compared the Raman spectra of different polytypes in detail. We show that the Raman spectroscopy can be used to identify not only the number of layers but also the polytypes of MoS2.

  12. Graphite oxide and molybdenum disulfide composite for hydrogen evolution reaction

    Science.gov (United States)

    Niyitanga, Theophile; Jeong, Hae Kyung

    2017-10-01

    Graphite oxide and molybdenum disulfide (GO-MoS2) composite is prepared through a wet process by using hydrolysis of ammonium tetrathiomolybdate, and it exhibits excellent catalytic activity of the hydrogen evolution reaction (HER) with a low overpotential of -0.47 V, which is almost two and three times lower than those of precursor MoS2 and GO. The high performance of HER of the composite attributes to the reduced GO supporting MoS2, providing a conducting network for fast electron transport from MoS2 to electrodes. The composite also shows high stability after 500 cycles, demonstrating a synergistic effect of MoS2 and GO for efficient HER.

  13. Plasmon modes of bilayer molybdenum disulfide: a density functional study

    Science.gov (United States)

    Torbatian, Z.; Asgari, R.

    2017-11-01

    We explore the collective electronic excitations of bilayer molybdenum disulfide (MoS2) using density functional theory together with random phase approximation. The many-body dielectric function and electron energy-loss spectra are calculated using an ab initio based model involving material-realistic physical properties. The electron energy-loss function of the bilayer MoS2 system is found to be sensitive to either electron or hole doping and this is due to the fact that the Kohn-Sham band dispersions are not symmetric for energies above and below the zero Fermi level. Three plasmon modes are predicted, a damped high-energy mode, one optical mode (in-phase mode) for which the plasmon dispersion exhibits \\sqrt q in the long wavelength limit originating from low-energy electron scattering and finally a highly damped acoustic mode (out-of-phase mode).

  14. Tuning thermal conductivity in molybdenum disulfide by electrochemical intercalation

    Science.gov (United States)

    Zhu, Gaohua; Liu, Jun; Zheng, Qiye; Zhang, Ruigang; Li, Dongyao; Banerjee, Debasish; Cahill, David G.

    2016-01-01

    Thermal conductivity of two-dimensional (2D) materials is of interest for energy storage, nanoelectronics and optoelectronics. Here, we report that the thermal conductivity of molybdenum disulfide can be modified by electrochemical intercalation. We observe distinct behaviour for thin films with vertically aligned basal planes and natural bulk crystals with basal planes aligned parallel to the surface. The thermal conductivity is measured as a function of the degree of lithiation, using time-domain thermoreflectance. The change of thermal conductivity correlates with the lithiation-induced structural and compositional disorder. We further show that the ratio of the in-plane to through-plane thermal conductivity of bulk crystal is enhanced by the disorder. These results suggest that stacking disorder and mixture of phases is an effective mechanism to modify the anisotropic thermal conductivity of 2D materials. PMID:27767030

  15. Thermodynamic and mechanical effects of disulfide bonds in CXCLl7 chemokine

    Science.gov (United States)

    Singer, Christopher

    Chemokines are a family of signaling proteins mainly responsible for the chemotaxis of leukocytes, where their biological activity is modulated by their oligomerization state. Here, the dynamics and thermodynamic stability are characterized in monomer and homodimer structures of CXCL7, one of the most abundant platelet chemokines. The effects of dimerization and disulfide bond formation are investigated using computational methods that include molecular dynamics (MD) simulations and the Distance Constraint Model (DCM). A consistent picture emerges for the effect of dimerization and role of the Cys5-Cys31 and Cys7- Cys47 disulfide bonds. Surprisingly, neither disulfide bond is critical for maintaining structural stability in the monomer or dimer, although the monomer is destabilized more than the dimer upon removal of disulfide bonds. Instead, it is found that disulfide bonds influence the native state dynamics as well as modulates the relative stability between monomer and dimer. The combined analysis elucidates how CXCL7 is mechanically stable as a monomer, and how upon dimerization flexibly correlated motions are induced between the 30s and 50s loop within each monomer and across the dimer interface. Interestingly, the greatest gain in flexibility upon dimerization occurs when both disulfide bonds are present in each domain, and the homodimer is least stable relative to its two monomers. These results suggest the highly conserved disulfide bonds in chemokines facilitate a structural mechanism for distinguishing functional characteristics between monomer and dimer.

  16. Determination of disulfide bridges of two spider toxins: hainantoxin-III and hainantoxin-IV

    Directory of Open Access Journals (Sweden)

    W Wang

    2009-01-01

    Full Text Available Peptide toxins are usually highly bridged proteins with multipairs of intrachain disulfide bonds. Analysis of disulfide connectivity is an important facet of protein structure determination. In this paper, we successfully assigned the disulfide linkage of two novel peptide toxins, called HNTX-III and HNTX-IV, isolated from the venom of Ornithoctonus hainana spider. Both peptides are useful inhibitors of TTX-sensitive voltage-gated sodium channels and are composed of six cysteine residues that form three disulfide bonds, respectively. Firstly, the peptides were partially reduced by tris(2-carboxyethyl-phosphine (TCEP in 0.1 M citrate buffer containing 6 M guanidine-HCl at 40° C for ten minutes. Subsequently, the partially reduced intermediates containing free thiols were separated by reversed-phase high-performance liquid chromatography (RP-HPLC and alkylated by rapid carboxamidomethylation. Then, the disulfide bonds of the intermediates were analyzed by Edman degradation. By using the strategy above, disulfide linkages of HNTX-III and HNTX-IV were determined as I-IV, II-V and III-VI pattern. In addition, this study also showed that this method may have a great potential for determining the disulfide bonds of spider peptide toxins.

  17. Large area synthesis, characterization, and anisotropic etching of two dimensional tungsten disulfide films

    International Nuclear Information System (INIS)

    Mutlu, Zafer; Ozkan, Mihrimah; Ozkan, Cengiz S.

    2016-01-01

    Emergent properties of tungsten disulfide at the quantum confinement limit hold promise for electronic and optoelectronic applications. Here we report on the large area synthesis of atomically thin tungsten disulfide films with strong photoluminescence properties via sulfurization of the pre-deposited tungsten films. Detailed characterization of the pre-deposited tungsten films and tungsten disulfide films are performed using microscopy and spectroscopy methods. By directly heating tungsten disulfide films in air, we have shown that the films tend to be etched into a series of triangular shaped pits with the same orientations, revealing the anisotropic etching behavior of tungsten disulfide edges. Moreover, the dimensions of the triangular pits increase with the number of layers, suggesting a thickness dependent behavior of etching in tungsten disulfide films. This method offers a promising new avenue for engineering the edge structures of tungsten disulfide films. - Highlights: • Large-scale synthesis of WS_2 films is achieved via sulfurization of W films. • Annealing of W films leads to a substantial improvement in the quality of WS_2 films. • WS_2 films show laser power dependent photoluminescence characteristics. • WS_2 films are etched with well-oriented triangular pits upon annealing in air. • Anisotropic oxidative etching is greatly affected by the thickness of WS_2 films.

  18. Positions of disulfide bonds in rye (Secale cereale) seed chitinase-a.

    Science.gov (United States)

    Yamagami, T; Funatsu, G; Ishiguro, M

    2000-06-01

    The positions of disulfide bonds of rye seed chitinase-a (RSC-a) were identified by the isolation of disulfide-containing peptides produced with enzymatic and/or chemical cleavages of RSC-a, followed by sequencing them. An unequivocal assignment of disulfide bonds in this enzyme was as follows: Cys3-Cysl8, Cys12-Cys24, Cys15-Cys42, Cys17-Cys31, and Cys35-Cys39 in the chitin-binding domain (CB domain), Cys82-Cys144, Cys156-Cys164, and Cys282-Cys295 in the catalytic domain (Cat domain), and Cys263 was a free form.

  19. Solvent Induced Disulfide Bond Formation in 2,5-dimercapto-1,3,4-thiadiazole

    OpenAIRE

    Palanisamy Kalimuthu; Palraj Kalimuthu; S. Abraham John

    2007-01-01

    Disulfide bond formation is the decisive event in the protein folding to determine the conformation and stability of protein. To achieve this disulfide bond formation in vitro, we took 2,5-dimercapto-1,3,4-thiadiazole (DMcT) as a model compound. We found that disulfide bond formation takes place between two sulfhydryl groups of DMcT molecules in methanol. UV-Vis, FT-IR and mass spectroscopic as well as cyclic voltammetry were used to monitor the course of reaction. We proposed a mechanism for...

  20. The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach

    OpenAIRE

    Hoskins, J.T.; Zhou, Z.; Harding, P.A.

    2008-01-01

    A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide bonds within human HB-EGF by substituting serine for both cysteine residues that contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF-Cys/Ser108/121, HB-EGF-Cys/Ser116/132, and HB-EGF-Cys/Ser134/143) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with Mr of 6.5, 21 and 24kDa were observed from lys...

  1. The ESA Geohazard Exploitation Platform

    Science.gov (United States)

    Bally, Philippe; Laur, Henri; Mathieu, Pierre-Philippe; Pinto, Salvatore

    2015-04-01

    Earthquakes represent one of the world's most significant hazards in terms both of loss of life and damages. In the first decade of the 21st century, earthquakes accounted for 60 percent of fatalities from natural disasters, according to the United Nations International Strategy for Disaster Reduction (UNISDR). To support mitigation activities designed to assess and reduce risks and improve response in emergency situations, satellite EO can be used to provide a broad range of geo-information services. This includes for instance crustal block boundary mapping to better characterize active faults, strain rate mapping to assess how rapidly faults are deforming, soil vulnerability mapping to help estimate how the soil is behaving in reaction to seismic phenomena, geo-information to assess the extent and intensity of the earthquake impact on man-made structures and formulate assumptions on the evolution of the seismic sequence, i.e. where local aftershocks or future main shocks (on nearby faults) are most likely to occur. In May 2012, the European Space Agency and the GEO Secretariat convened the International Forum on Satellite EO for Geohazards now known as the Santorini Conference. The event was the continuation of a series of international workshops such as those organized by the Geohazards Theme of the Integrated Global Observing Strategy Partnership. In Santorini the seismic community has set out a vision of the EO contribution to an operational global seismic risk program, which lead to the Geohazard Supersites and Natural Laboratories (GSNL) initiative. The initial contribution of ESA to suuport the GSNL was the first Supersites Exploitation Platform (SSEP) system in the framework of Grid Processing On Demand (GPOD), now followed by the Geohazard Exploitation Platform (GEP). In this presentation, we will describe the contribution of the GEP for exploiting satellite EO for geohazard risk assessment. It is supporting the GEO Supersites and has been further

  2. Prospects of geothermal resource exploitation

    International Nuclear Information System (INIS)

    Bourrelier, P.H.; Cornet, F.; Fouillac, C.

    1994-01-01

    The use of geothermal energy to generate electricity has only occurred during the past 50 years by drilling wells in aquifers close to magmas and producing either dry steam or hot water. The world's production of electricity from geothermal energy is over 6000 MWe and is still growing. The direct use of geothermal energy for major urban communities has been developed recently by exploitation of aquifers in sedimentary basins under large towns. Scaling up the extraction of heat implies the exploitation of larger and better located fields requiring an appropriate method of extraction; the objective of present attempts in USA, Japan and Europe is to create heat exchangers by the circulation of water between several deep wells. Two field categories are considered: the extension of classical geothermal fields beyond the aquifer areas, and areas favoured by both a high geothermal gradient, fractures inducing a natural permeability at large scale, and good commercial prospects (such as in the Rhenan Graben). Hot dry rocks concept has gained a large interest. 1 fig., 5 tabs., 11 refs

  3. Protein disulfide bond generation in Escherichia coli DsbB–DsbA

    International Nuclear Information System (INIS)

    Inaba, Kenji

    2008-01-01

    The crystal structure of the DsbB–DsbA–ubiquinone ternary complex has revealed a mechanism of protein disulfide bond generation in Escherichia coli. Protein disulfide bond formation is catalyzed by a series of Dsb enzymes present in the periplasm of Escherichia coli. The crystal structure of the DsbB–DsbA–ubiquinone ternary complex provided important insights into mechanisms of the de novo disulfide bond generation cooperated by DsbB and ubiquinone and of the disulfide bond shuttle from DsbB to DsbA. The structural basis for prevention of the crosstalk between the DsbA–DsbB oxidative and the DsbC–DsbD reductive pathways has also been proposed

  4. Edge eigen-stress and eigen-displacement of armchair molybdenum disulfide nanoribbons

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Quan; Li, Xi [Corrosion and Protection Center, Key Laboratory for Environmental Fracture (MOE), University of Science and Technology Beijing, Beijing 100083 (China); Volinsky, Alex A., E-mail: volinsky@usf.edu [Department of Mechanical Engineering, University of South Florida, Tampa, FL 33620 (United States); Su, Yanjing, E-mail: yjsu@ustb.edu.cn [Corrosion and Protection Center, Key Laboratory for Environmental Fracture (MOE), University of Science and Technology Beijing, Beijing 100083 (China)

    2017-05-10

    Edge effects on mechanical properties of armchair molybdenum disulfide nanoribbons were investigated using first principles calculations. The edge eigen-stress model was applied to explain the relaxation process of forming molybdenum disulfide nanoribbon. Edge effects on surface atoms fluctuation degree were obtained from each fully relaxed nanoribbon with different width. Changes of the relaxed armchair molybdenum disulfide nanoribbons structure can be expressed using hexagonal perimeters pattern. Based on the thickness change, relaxed armchair molybdenum disulfide nanoribbons tensile/compression tests were simulated, providing intrinsic edge elastic parameters, such as eigen-stress, Young's modulus and Poisson's ratio. - Highlights: • Edge effects on mechanical properties of armchair MoS{sub 2} nanoribbons were investigated. • Structure changes of different width armchair MoS{sub 2} nanoribbons were obtained. • Tensile/compressive tests were conducted to determine elastic constants. • Mechanical properties are compared for two and three dimensional conditions.

  5. Conformational landscape and pathway of disulfide bond reduction of human alpha defensin

    NARCIS (Netherlands)

    Snijder, Joost; Van De Waterbeemd, Michiel; Glover, Matthew S.; Shi, Liuqing; Clemmer, David E.; Heck, Albert J R

    2015-01-01

    Human alpha defensins are a class of antimicrobial peptides with additional antiviral activity. Such antimicrobial peptides constitute a major part of mammalian innate immunity. Alpha defensins contain six cysteines, which form three well defined disulfide bridges under oxidizing conditions.

  6. Identification of Thioredoxin Target Disulfides Using Isotope-Coded Affinity Tags

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji

    2014-01-01

    Thioredoxins (Trx) are small redox proteins that reduce disulfide bonds in various target proteins and maintain cellular thiol redox control. Here, a thiol-specific labeling and affinity enrichment approach for identification and relative quantification of Trx target disulfides in complex protein...... reduction is determined by LC-MS/MS-based quantification of tryptic peptides labeled with "light" (12C) and "heavy" (13C) ICAT reagents. The methodology can be adapted to monitor the effect of different reductants or oxidants on the redox status of thiol/disulfide proteomes in biological systems....... extracts is described. The procedure utilizes the isotope-coded affinity tag (ICAT) reagents containing a thiol reactive iodoacetamide group and a biotin affinity tag to target peptides containing reduced cysteine residues. The identification of substrates for Trx and the extent of target disulfide...

  7. Radiation-induced cleavage of disulfide bonds in proteins. Clivage radiolytique des ponts disulfure des proteines

    Energy Technology Data Exchange (ETDEWEB)

    Favaudon, V; Tourbez, H; Lhoste, J M [Paris-11 Univ., 91 - Orsay (FR); Houee-Levin, C [Paris-5 Univ., 75 (FR)

    1991-06-01

    The reduction of the disulfide bonds in apo-Riboflavin-Binding Protein (apoRBP) by the CO{sub 2}{sup -}{center dot} radical occurred under {gamma}-ray irradiation as a chain reaction whose efficiency increased upon acidification of the medium. Pulse-radiolysis analysis showed a rapid one-electron oxidation of the disulfide bonds yielding the anionic or protonated form of the disulfide radical. The main decay path of this radical under acidic conditions consisted of the rapid formation of a thiyl radical intermediate in equilibrium with the closed, cyclic form. At pH 8 the disulfide radical anion decayed via intramolecular and/or intermolecular routes including disproportionation, protein-protein crosslinking, non-dismutative recombination processes, and reaction with sulfhydryl groups in pre-reduced systems.

  8. Electrochemical reduction of disulfide-containing proteins for hydrogen/deuterium exchange monitored by mass spectrometry

    DEFF Research Database (Denmark)

    Mysling, Simon; Salbo, Rune; Ploug, Michael

    2014-01-01

    Characterization of disulfide bond-containing proteins by hydrogen/deuterium exchange monitored by mass spectrometry (HDX-MS) requires reduction of the disulfide bonds under acidic and cold conditions, where the amide hydrogen exchange reaction is quenched (pH 2.5, 0 °C). The reduction typically...... of TCEP. In the present study, we explore the feasibility of using electrochemical reduction as a substitute for TCEP in HDX-MS analyses. Our results demonstrate that efficient disulfide bond reduction is readily achieved by implementing an electrochemical cell into the HDX-MS workflow. We also identify...... some challenges in using electrochemical reduction in HDX-MS analyses and provide possible conditions to attenuate these limitations. For example, high salt concentrations hamper disulfide bond reduction, necessitating additional dilution of the sample with aqueous acidic solution at quench conditions....

  9. Structural basis for target protein recognition by the protein disulfide reductase thioredoxin

    DEFF Research Database (Denmark)

    Maeda, Kenji; Hägglund, Per; Finnie, Christine

    2006-01-01

    Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley alpha-amylase/subtilisin inhibitor (BASI). The crystal structure...... of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays...... a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares...

  10. Generation of a Multicomponent Library of Disulfide Donor-Acceptor Architectures Using Dynamic Combinatorial Chemistry.

    Science.gov (United States)

    Drożdż, Wojciech; Kołodziejski, Michał; Markiewicz, Grzegorz; Jenczak, Anna; Stefankiewicz, Artur R

    2015-07-17

    We describe here the generation of new donor-acceptor disulfide architectures obtained in aqueous solution at physiological pH. The application of a dynamic combinatorial chemistry approach allowed us to generate a large number of new disulfide macrocyclic architectures together with a new type of [2]catenanes consisting of four distinct components. Up to fifteen types of structurally-distinct dynamic architectures have been generated through one-pot disulfide exchange reactions between four thiol-functionalized aqueous components. The distribution of disulfide products formed was found to be strongly dependent on the structural features of the thiol components employed. This work not only constitutes a success in the synthesis of topologically- and morphologically-complex targets, but it may also open new horizons for the use of this methodology in the construction of molecular machines.

  11. Increasing the reactivity of an artificial dithiol-disulfide pair through modification of the electrostatic milieu

    DEFF Research Database (Denmark)

    Hansen, Rosa E; Østergaard, Henrik; Winther, Jakob R

    2005-01-01

    K(a) value of Cys149, as well as favorable electrostatic interactions with the negatively charged reagents. The results presented here show that the electrostatic milieu of cysteine thiols in proteins can have substantial effects on the rates of the thiol-disulfide exchange reactions.......The thiol-disulfide exchange reaction plays a central role in the formation of disulfide bonds in newly synthesized proteins and is involved in many aspects of cellular metabolism. Because the thiolate form of the cysteine residue is the key reactive species, its electrostatic milieu is thought...... surface. We have studied properties of vicinal cysteine residues in proteins using a model system based on redox-sensitive yellow fluorescent protein (rxYFP). In this system, the formation of a disulfide bond between two cysteines Cys149 and Cys202 is accompanied by a 2.2-fold decrease in fluorescence...

  12. Insulin analog with additional disulfide bond has increased stability and preserved activity

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Ribel, Ulla

    2013-01-01

    Insulin is a key hormone controlling glucose homeostasis. All known vertebrate insulin analogs have a classical structure with three 100% conserved disulfide bonds that are essential for structural stability and thus the function of insulin. It might be hypothesized that an additional disulfide...... bond may enhance insulin structural stability which would be highly desirable in a pharmaceutical use. To address this hypothesis, we designed insulin with an additional interchain disulfide bond in positions A10/B4 based on Cα-Cα distances, solvent exposure, and side-chain orientation in human insulin...... (HI) structure. This insulin analog had increased affinity for the insulin receptor and apparently augmented glucodynamic potency in a normal rat model compared with HI. Addition of the disulfide bond also resulted in a 34.6°C increase in melting temperature and prevented insulin fibril formation...

  13. A new measure of interpersonal exploitativeness

    Directory of Open Access Journals (Sweden)

    Amy B. Brunell

    2013-05-01

    Full Text Available Measures of exploitativeness evidence problems with validity and reliability. The present set of studies assessed a new measure (the Interpersonal Exploitativeness Scale that defines exploitativeness in terms of reciprocity. In Studies 1 and 2, 33 items were administered to participants. Exploratory and Confirmatory Factor Analysis demonstrated that a single factor consisting of six items adequately assess interpersonal exploitativeness. Study 3 results revealed that the Interpersonal Exploitativeness Scale was positively associated with normal narcissism, pathological narcissism, psychological entitlement, and negative reciprocity and negatively correlated with positive reciprocity. In Study 4, participants competed in a commons dilemma. Those who scored higher on the Interpersonal Exploitativeness Scale were more likely to harvest a greater share of resources over time, even while controlling for other relevant variables, such as entitlement. Together, these studies show the Interpersonal Exploitativeness Scale to be a valid and reliable measure of interpersonal exploitativeness. The authors discuss the implications of these studies.

  14. Molecular Characterization and Analysis of a Novel Protein Disulfide Isomerase-Like Protein of Eimeria tenella

    OpenAIRE

    Han, Hongyu; Dong, Hui; Zhu, Shunhai; Zhao, Qiping; Jiang, Lianlian; Wang, Yange; Li, Liujia; Wu, Youlin; Huang, Bing

    2014-01-01

    Protein disulfide isomerase (PDI) and PDI-like proteins are members of the thioredoxin superfamily. They contain thioredoxin-like domains and catalyze the physiological oxidation, reduction and isomerization of protein disulfide bonds, which are involved in cell function and development in prokaryotes and eukaryotes. In this study, EtPDIL, a novel PDI-like gene of Eimeria tenella, was cloned using rapid amplification of cDNA ends (RACE) according to the expressed sequence tag (EST). The EtPDI...

  15. Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions.

    Science.gov (United States)

    Netto, Luis Eduardo S; de Oliveira, Marcos Antonio; Tairum, Carlos A; da Silva Neto, José Freire

    2016-01-01

    Thiol-disulfide exchange reactions are highly reversible, displaying nucleophilic substitutions mechanism (S(N)2 type). For aliphatic, low molecular thiols, these reactions are slow, but can attain million times faster rates in enzymatic processes. Thioredoxin (Trx) proteins were the first enzymes described to accelerate thiol-disulfide exchange reactions and their high reactivity is related to the high nucleophilicity of the attacking thiol. Substrate specificity in Trx is achieved by several factors, including polar, hydrophobic, and topological interactions through a groove in the active site. Glutaredoxin (Grx) enzymes also contain the Trx fold, but they do not share amino acid sequence similarity with Trx. A conserved glutathione binding site is a typical feature of Grx that can reduce substrates by two mechanisms (mono and dithiol). The high reactivity of Grx enzymes is related to the very acid pK(a) values of reactive Cys that plays roles as good leaving groups. Therefore, although distinct oxidoreductases catalyze similar thiol–disulfide exchange reactions, their enzymatic mechanisms vary. PDI and DsbA are two other oxidoreductases, but they are involved in disulfide bond formation, instead of disulfide reduction, which is related to the oxidative environment where they are found. PDI enzymes and DsbC are endowed with disulfide isomerase activity, which is related with their tetra-domain architecture. As illustrative description of specificity in thiol-disulfide exchange, redox aspects of transcription activation in bacteria, yeast, and mammals are presented in an evolutionary perspective. Therefore, thiol-disulfide exchange reactions play important roles in conferring specificity to pathways, a required feature for signaling.

  16. N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization

    DEFF Research Database (Denmark)

    Nørskov-Lauritsen, Lenea; Jørgensen, Stine; Bräuner-Osborne, Hans

    2015-01-01

    Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expr...... covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed....

  17. Exploitation in International Paid Surrogacy Arrangements

    OpenAIRE

    Wilkinson, Stephen

    2015-01-01

    Abstract Many critics have suggested that international paid surrogacy is exploitative. Taking such concerns as its starting point, this article asks: (1) how defensible is the claim that international paid surrogacy is exploitative and what could be done to make it less exploitative? (2) In the light of the answer to (1), how strong is the case for prohibiting it? Exploitation could in principle be dealt with by improving surrogates' pay and conditions. However, doing so may exacerbate probl...

  18. The exploitation argument against commercial surrogacy.

    Science.gov (United States)

    Wilkinson, Stephen

    2003-04-01

    This paper discusses the exploitation argument against commercial surrogacy: the claim that commercial surrogacy is morally objectionable because it is exploitative. The following questions are addressed. First, what exactly does the exploitation argument amount to? Second, is commercial surrogacy in fact exploitative? Third, if it were exploitative, would this provide a sufficient reason to prohibit (or otherwise legislatively discourage) it? The focus throughout is on the exploitation of paid surrogates, although it is noted that other parties (e.g. 'commissioning parents') may also be the victims of exploitation. It is argued that there are good reasons for believing that commercial surrogacy is often exploitative. However, even if we accept this, the exploitation argument for prohibiting (or otherwise legislatively discouraging) commercial surrogacy remains quite weak. One reason for this is that prohibition may well 'backfire' and lead to potential surrogates having to do other things that are more exploitative and/or more harmful than paid surrogacy. It is concluded therefore that those who oppose exploitation should (rather than attempting to stop particular practices like commercial surrogacy) concentrate on: (a) improving the conditions under which paid surrogates 'work'; and (b) changing the background conditions (in particular, the unequal distribution of power and wealth) which generate exploitative relationships.

  19. The Exploitation of Evolving Resources

    CERN Document Server

    McGlade, Jacqueline; Law, Richard

    1993-01-01

    The impact of man on the biosphere is profound. Quite apart from our capacity to destroy natural ecosystems and to drive species to extinction, we mould the evolution of the survivors by the selection pressures we apply to them. This has implications for the continued health of our natural biological resources and for the way in which we seek to optimise yield from those resources. Of these biological resources, fish stocks are particularly important to mankind as a source of protein. On a global basis, fish stocks provide the major source of protein for human consumption from natural ecosystems, amounting to some seventy million tonnes in 1970. Although fisheries management has been extensively developed over the last century, it has not hitherto considered the evolutionary consequences of fishing activity. While this omission may not have been serious in the past, the ever increasing intensity of exploitation and the deteriorating health of fish stocks has generated an urgent need for a better understanding...

  20. Swedish mines. Underground exploitation methods

    International Nuclear Information System (INIS)

    Paucard, A.

    1960-01-01

    Between 1949 and 1957, 10 engineers of the Mining research and exploitation department of the CEA visited 17 Swedish mines during 5 field trips. This paper presents a compilation of the information gathered during these field trips concerning the different underground mining techniques used in Swedish iron mines: mining with backfilling (Central Sweden and Boliden mines); mining without backfilling (mines of the polar circle area). The following techniques are described successively: pillar drawing and backfilled slices (Ammeberg, Falun, Garpenberg, Boliden group), sub-level pillar drawing (Grangesberg, Bloettberget, Haeksberg), empty room and sub-level pillar drawing (Bodas, Haksberg, Stripa, Bastkarn), storage chamber pillar drawing (Bodas, Haeksberg, Bastkarn), and pillar drawing by block caving (ldkerberget). Reprint of a paper published in Revue de l'Industrie Minerale, vol. 41, no. 12, 1959 [fr

  1. Exploiting social evolution in biofilms

    DEFF Research Database (Denmark)

    Boyle, Kerry E; Heilmann, Silja; van Ditmarsch, Dave

    2013-01-01

    Bacteria are highly social organisms that communicate via signaling molecules, move collectively over surfaces and make biofilm communities. Nonetheless, our main line of defense against pathogenic bacteria consists of antibiotics-drugs that target individual-level traits of bacterial cells...... and thus, regrettably, select for resistance against their own action. A possible solution lies in targeting the mechanisms by which bacteria interact with each other within biofilms. The emerging field of microbial social evolution combines molecular microbiology with evolutionary theory to dissect...... the molecular mechanisms and the evolutionary pressures underpinning bacterial sociality. This exciting new research can ultimately lead to new therapies against biofilm infections that exploit evolutionary cheating or the trade-off between biofilm formation and dispersal....

  2. Energy for lunar resource exploitation

    Science.gov (United States)

    Glaser, Peter E.

    1992-02-01

    Humanity stands at the threshold of exploiting the known lunar resources that have opened up with the access to space. America's role in the future exploitation of space, and specifically of lunar resources, may well determine the level of achievement in technology development and global economic competition. Space activities during the coming decades will significantly influence the events on Earth. The 'shifting of history's tectonic plates' is a process that will be hastened by the increasingly insistent demands for higher living standards of the exponentially growing global population. Key to the achievement of a peaceful world in the 21st century, will be the development of a mix of energy resources at a societally acceptable and affordable cost within a realistic planning horizon. This must be the theme for the globally applicable energy sources that are compatible with the Earth's ecology. It is in this context that lunar resources development should be a primary goal for science missions to the Moon, and for establishing an expanding human presence. The economic viability and commercial business potential of mining, extracting, manufacturing, and transporting lunar resource based materials to Earth, Earth orbits, and to undertake macroengineering projects on the Moon remains to be demonstrated. These extensive activities will be supportive of the realization of the potential of space energy sources for use on Earth. These may include generating electricity for use on Earth based on beaming power from Earth orbits and from the Moon to the Earth, and for the production of helium 3 as a fuel for advanced fusion reactors.

  3. Graphene oxide – molybdenum disulfide hybrid membranes for hydrogen separation

    KAUST Repository

    Ostwal, Mayur

    2017-12-24

    Graphene oxide – molybdenum disulfide hybrid membranes were prepared using vacuum filtration technique. The thickness and the MoS2 content in the membranes were varied and their H2 permeance and H2/CO2 selectivity are reported. A 60nm hybrid membrane containing ~75% by weight of MoS2 exhibited the highest H2 permeance of 804×10−9mol/m2·s·Pa with corresponding H2/CO2 selectivity of 26.7; while a 150nm hybrid membrane with ~29% MoS2 showed the highest H2/CO2 selectivity of 44.2 with corresponding H2 permeance of 287×10−9mol/m2·s·Pa. The hybrid membranes exhibited much higher H2 permeance compared to graphene oxide membranes and higher selectivity compared to MoS2 membranes, which fully demonstrated the synergistic effect of both nanomaterials. The membranes also displayed excellent operational long-term stability.

  4. DNA origami deposition on native and passivated molybdenum disulfide substrates

    Directory of Open Access Journals (Sweden)

    Xiaoning Zhang

    2014-04-01

    Full Text Available Maintaining the structural fidelity of DNA origami structures on substrates is a prerequisite for the successful fabrication of hybrid DNA origami/semiconductor-based biomedical sensor devices. Molybdenum disulfide (MoS2 is an ideal substrate for such future sensors due to its exceptional electrical, mechanical and structural properties. In this work, we performed the first investigations into the interaction of DNA origami with the MoS2 surface. In contrast to the structure-preserving interaction of DNA origami with mica, another atomically flat surface, it was observed that DNA origami structures rapidly lose their structural integrity upon interaction with MoS2. In a further series of studies, pyrene and 1-pyrenemethylamine, were evaluated as surface modifications which might mitigate this effect. While both species were found to form adsorption layers on MoS2 via physisorption, 1-pyrenemethylamine serves as a better protective agent and preserves the structures for significantly longer times. These findings will be beneficial for the fabrication of future DNA origami/MoS2 hybrid electronic structures.

  5. Graphene oxide – molybdenum disulfide hybrid membranes for hydrogen separation

    KAUST Repository

    Ostwal, Mayur; Shinde, Digambar B.; Wang, Xinbo; Gadwal, Ikhlas; Lai, Zhiping

    2017-01-01

    Graphene oxide – molybdenum disulfide hybrid membranes were prepared using vacuum filtration technique. The thickness and the MoS2 content in the membranes were varied and their H2 permeance and H2/CO2 selectivity are reported. A 60nm hybrid membrane containing ~75% by weight of MoS2 exhibited the highest H2 permeance of 804×10−9mol/m2·s·Pa with corresponding H2/CO2 selectivity of 26.7; while a 150nm hybrid membrane with ~29% MoS2 showed the highest H2/CO2 selectivity of 44.2 with corresponding H2 permeance of 287×10−9mol/m2·s·Pa. The hybrid membranes exhibited much higher H2 permeance compared to graphene oxide membranes and higher selectivity compared to MoS2 membranes, which fully demonstrated the synergistic effect of both nanomaterials. The membranes also displayed excellent operational long-term stability.

  6. Prediction of dimethyl disulfide levels from biosolids using statistical modeling.

    Science.gov (United States)

    Gabriel, Steven A; Vilalai, Sirapong; Arispe, Susanna; Kim, Hyunook; McConnell, Laura L; Torrents, Alba; Peot, Christopher; Ramirez, Mark

    2005-01-01

    Two statistical models were used to predict the concentration of dimethyl disulfide (DMDS) released from biosolids produced by an advanced wastewater treatment plant (WWTP) located in Washington, DC, USA. The plant concentrates sludge from primary sedimentation basins in gravity thickeners (GT) and sludge from secondary sedimentation basins in dissolved air flotation (DAF) thickeners. The thickened sludge is pumped into blending tanks and then fed into centrifuges for dewatering. The dewatered sludge is then conditioned with lime before trucking out from the plant. DMDS, along with other volatile sulfur and nitrogen-containing chemicals, is known to contribute to biosolids odors. These models identified oxidation/reduction potential (ORP) values of a GT and DAF, the amount of sludge dewatered by centrifuges, and the blend ratio between GT thickened sludge and DAF thickened sludge in blending tanks as control variables. The accuracy of the developed regression models was evaluated by checking the adjusted R2 of the regression as well as the signs of coefficients associated with each variable. In general, both models explained observed DMDS levels in sludge headspace samples. The adjusted R2 value of the regression models 1 and 2 were 0.79 and 0.77, respectively. Coefficients for each regression model also had the correct sign. Using the developed models, plant operators can adjust the controllable variables to proactively decrease this odorant. Therefore, these models are a useful tool in biosolids management at WWTPs.

  7. 9-Fluorenylmethyl (Fm) Disulfides: Biomimetic Precursors for Persulfides

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chung-Min; Johnson, Brett A.; Duan, Jicheng; Park, Jeong-Jin; Day, Jacob J.; Gang, David; Qian, Wei-Jun; Xian, Ming

    2016-03-04

    Protein S-sulfhydration has been recognized as an important post-translational modification that regulates H2S signals. However, the reactivity and biological implications of the products of S-sulfhydration, i.e. persulfides, are still unclear. This is mainly due to the instability of persulfides and difficulty to access these molecules. Under physiological conditions persulfides mainly exist in anionic forms because of their low pKa values. However, current methods do not allow for the direct generation of persulfide anions under biomimetic and non-H2S conditions. Herein we report the development of a functional disulfide, FmSSPy-A (Fm =9-fluorenylmethyl; Py = pyridinyl). This reagent can effectively convert both small molecule and protein thiols (-SH) to form –S-SFm adducts under mild conditions. It allows for a H2S-free and biomimetic protocol to generate highly reactive persulfides (in their anionic forms). We also demonstrated the high nucleophilicity of persulfides toward a number of thiol-blocking reagents. This method holds promise for further understanding the chemical biology of persulfides and S-sulfhydration.

  8. Metallic molybdenum disulfide nanosheet-based electrochemical actuators

    Science.gov (United States)

    Acerce, Muharrem; Akdoğan, E. Koray; Chhowalla, Manish

    2017-09-01

    Actuators that convert electrical energy to mechanical energy are useful in a wide variety of electromechanical systems and in robotics, with applications such as steerable catheters, adaptive wings for aircraft and drag-reducing wind turbines. Actuation systems can be based on various stimuli, such as heat, solvent adsorption/desorption, or electrochemical action (in systems such as carbon nanotube electrodes, graphite electrodes, polymer electrodes and metals). Here we demonstrate that the dynamic expansion and contraction of electrode films formed by restacking chemically exfoliated nanosheets of two-dimensional metallic molybdenum disulfide (MoS2) on thin plastic substrates can generate substantial mechanical forces. These films are capable of lifting masses that are more than 150 times that of the electrode over several millimetres and for hundreds of cycles. Specifically, the MoS2 films are able to generate mechanical stresses of about 17 megapascals—higher than mammalian muscle (about 0.3 megapascals) and comparable to ceramic piezoelectric actuators (about 40 megapascals)—and strains of about 0.6 per cent, operating at frequencies up to 1 hertz. The actuation performance is attributed to the high electrical conductivity of the metallic 1T phase of MoS2 nanosheets, the elastic modulus of restacked MoS2 layers (2 to 4 gigapascals) and fast proton diffusion between the nanosheets. These results could lead to new electrochemical actuators for high-strain and high-frequency applications.

  9. Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells.

    Science.gov (United States)

    Wise, Randi; Duhachek-Muggy, Sara; Qi, Yue; Zolkiewski, Michal; Zolkiewska, Anna

    2016-06-01

    Metastatic breast cancer cells are exposed to stress of detachment from the extracellular matrix (ECM). Cultured breast cancer cells that survive this stress and are capable of anchorage-independent proliferation form mammospheres. The purpose of this study was to explore a link between mammosphere growth, ECM gene expression, and the protein quality control system in the endoplasmic reticulum (ER). We compared the mRNA and protein levels of ER folding factors in SUM159PT and MCF10DCIS.com breast cancer cells grown as mammospheres versus adherent conditions. Publicly available gene expression data for mammospheres formed by primary breast cancer cells and for circulating tumor cells (CTCs) were analyzed to assess the status of ECM/ER folding factor genes in clinically relevant samples. Knock-down of selected protein disulfide isomerase (PDI) family members was performed to examine their roles in SUM159PT mammosphere growth. We found that cells grown as mammospheres had elevated expression of ECM genes and ER folding quality control genes. CTC gene expression data for an index patient indicated that upregulation of ECM and ER folding factor genes occurred at the time of acquired therapy resistance and disease progression. Knock-down of PDI, ERp44, or ERp57, three members of the PDI family with elevated protein levels in mammospheres, in SUM159PT cells partially inhibited the mammosphere growth. Thus, breast cancer cell survival and growth under detachment conditions require enhanced assistance of the ER protein folding machinery. Targeting ER folding factors, in particular members of the PDI family, may improve the therapeutic outcomes in metastatic breast cancer.

  10. PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum.

    Science.gov (United States)

    van Lith, Marcel; Hartigan, Nichola; Hatch, Jennifer; Benham, Adam M

    2005-01-14

    Protein disulfide isomerase (PDI) is the archetypal enzyme involved in the formation and reshuffling of disulfide bonds in the endoplasmic reticulum (ER). PDI achieves its redox function through two highly conserved thioredoxin domains, and PDI can also operate as an ER chaperone. The substrate specificities and the exact functions of most other PDI family proteins remain important unsolved questions in biology. Here, we characterize a new and striking member of the PDI family, which we have named protein disulfide isomerase-like protein of the testis (PDILT). PDILT is the first eukaryotic SXXC protein to be characterized in the ER. Our experiments have unveiled a novel, glycosylated PDI-like protein whose tissue-specific expression and unusual motifs have implications for the evolution, catalytic function, and substrate selection of thioredoxin family proteins. We show that PDILT is an ER resident glycoprotein that liaises with partner proteins in disulfide-dependent complexes within the testis. PDILT interacts with the oxidoreductase Ero1alpha, demonstrating that the N-terminal cysteine of the CXXC sequence is not required for binding of PDI family proteins to ER oxidoreductases. The expression of PDILT, in addition to PDI in the testis, suggests that PDILT performs a specialized chaperone function in testicular cells. PDILT is an unusual PDI relative that highlights the adaptability of chaperone and redox function in enzymes of the endoplasmic reticulum.

  11. Enhancing Protein Disulfide Bond Cleavage by UV Excitation and Electron Capture Dissociation for Top-Down Mass Spectrometry

    OpenAIRE

    Wongkongkathep, Piriya; Li, Huilin; Zhang, Xing; Loo, Rachel R. Ogorzalek; Julian, Ryan R.; Loo, Joseph A.

    2015-01-01

    The application of ion pre-activation with 266 nm ultraviolet (UV) laser irradiation combined with electron capture dissociation (ECD) is demonstrated to enhance top-down mass spectrometry sequence coverage of disulfide bond containing proteins. UV-based activation can homolytically cleave a disulfide bond to yield two separated thiol radicals. Activated ECD experiments of insulin and ribonuclease A containing three and four disulfide bonds, respectively, were performed. UV-activation in comb...

  12. A novel engineered interchain disulfide bond in the constant region enhances the thermostability of adalimumab Fab.

    Science.gov (United States)

    Nakamura, Hitomi; Oda-Ueda, Naoko; Ueda, Tadashi; Ohkuri, Takatoshi

    2018-01-01

    We constructed a system for expressing the Fab of the therapeutic human monoclonal antibody adalimumab at a yield of 20 mg/L in the methylotrophic yeast Pichia pastoris. To examine the contribution of interchain disulfide bonds to conformational stability, we prepared adalimumab Fab from which the interchain disulfide bond at the C-terminal region at both the CH 1 and CL domains was deleted by substitution of Cys with Ala (Fab ΔSS ). DSC measurements showed that the Tm values of Fab ΔSS were approximately 5 °C lower than those of wild-type Fab, suggesting that the interchain disulfide bond contributes to conformational thermostability. Using computer simulations, we designed a novel interchain disulfide bond outside the C-terminal region to increase the stability of Fab ΔSS . The resulting Fab (mutSS Fab ΔSS ) had the mutations H:V177C and L:Q160C in Fab ΔSS , confirming the formation of the disulfide bond between CH 1 and CL. The thermostability of mutSS Fab ΔSS was approximately 5 °C higher than that of Fab ΔSS . Therefore, the introduction of the designed interchain disulfide bond enhanced the thermostability of Fab ΔSS and mitigated the destabilization caused by partial reduction of the interchain disulfide bond at the C-terminal region, which occurs in site-specific modification such as PEGylation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Preventing disulfide bond formation weakens non-covalent forces among lysozyme aggregates.

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Ravi

    Full Text Available Nonnative disulfide bonds have been observed among protein aggregates in several diseases like amyotrophic lateral sclerosis, cataract and so on. The molecular mechanism by which formation of such bonds promotes protein aggregation is poorly understood. Here in this work we employ previously well characterized aggregation of hen eggwhite lysozyme (HEWL at alkaline pH to dissect the molecular role of nonnative disulfide bonds on growth of HEWL aggregates. We employed time-resolved fluorescence anisotropy, atomic force microscopy and single-molecule force spectroscopy to quantify the size, morphology and non-covalent interaction forces among the aggregates, respectively. These measurements were performed under conditions when disulfide bond formation was allowed (control and alternatively when it was prevented by alkylation of free thiols using iodoacetamide. Blocking disulfide bond formation affected growth but not growth kinetics of aggregates which were ∼50% reduced in volume, flatter in vertical dimension and non-fibrillar in comparison to control. Interestingly, single-molecule force spectroscopy data revealed that preventing disulfide bond formation weakened the non-covalent interaction forces among monomers in the aggregate by at least ten fold, thereby stalling their growth and yielding smaller aggregates in comparison to control. We conclude that while constrained protein chain dynamics in correctly disulfide bonded amyloidogenic proteins may protect them from venturing into partial folded conformations that can trigger entry into aggregation pathways, aberrant disulfide bonds in non-amyloidogenic proteins (like HEWL on the other hand, may strengthen non-covalent intermolecular forces among monomers and promote their aggregation.

  14. Exploiting Symmetry on Parallel Architectures.

    Science.gov (United States)

    Stiller, Lewis Benjamin

    1995-01-01

    This thesis describes techniques for the design of parallel programs that solve well-structured problems with inherent symmetry. Part I demonstrates the reduction of such problems to generalized matrix multiplication by a group-equivariant matrix. Fast techniques for this multiplication are described, including factorization, orbit decomposition, and Fourier transforms over finite groups. Our algorithms entail interaction between two symmetry groups: one arising at the software level from the problem's symmetry and the other arising at the hardware level from the processors' communication network. Part II illustrates the applicability of our symmetry -exploitation techniques by presenting a series of case studies of the design and implementation of parallel programs. First, a parallel program that solves chess endgames by factorization of an associated dihedral group-equivariant matrix is described. This code runs faster than previous serial programs, and discovered it a number of results. Second, parallel algorithms for Fourier transforms for finite groups are developed, and preliminary parallel implementations for group transforms of dihedral and of symmetric groups are described. Applications in learning, vision, pattern recognition, and statistics are proposed. Third, parallel implementations solving several computational science problems are described, including the direct n-body problem, convolutions arising from molecular biology, and some communication primitives such as broadcast and reduce. Some of our implementations ran orders of magnitude faster than previous techniques, and were used in the investigation of various physical phenomena.

  15. Two questions about surrogacy and exploitation.

    Science.gov (United States)

    Wertheimer, Alan

    1992-01-01

    In this article I will consider two related questions about surrogacy and exploitation: (1) Is surrogacy exploitative? (2) If surrogacy is exploitative, what is the moral force of this exploitation? Briefly stated, I shall argue that whether surrogacy is exploitative depends on whether exploitation must be harmful to the exploited party or whether (as I think) there can be mutually advantageous exploitation. It also depends on some facts about surrogacy about which we have little reliable evidence and on our philosophical view on what counts as a harm to the surrogate. Our answer to the second question will turn in part on the account of exploitation we invoke in answering the first question and in part on the way in which we resolve some other questions about the justification of state interference. I shall suggest, however, that if surrogacy is a form of voluntary and mutually advantageous exploitation, then there is a strong presumption that surrogacy contracts should be permitted and even enforceable, although that presumption may be overridden on other grounds.

  16. Kinetic analysis of the mechanism and specificity of protein-disulfide isomerase using fluorescence-quenched peptides

    DEFF Research Database (Denmark)

    Westphal, V; Spetzler, J C; Meldal, M

    1998-01-01

    Protein-disulfide isomerase (PDI) is an abundant folding catalyst in the endoplasmic reticulum of eukaryotic cells. PDI introduces disulfide bonds into newly synthesized proteins and catalyzes disulfide bond isomerizations. We have synthesized a library of disulfide-linked fluorescence......-quenched peptides, individually linked to resin beads, for two purposes: 1) to probe PDI specificity, and 2) to identify simple, sensitive peptide substrates of PDI. Using this library, beads that became rapidly fluorescent by reduction by human PDI were selected. Amino acid sequencing of the bead-linked peptides...

  17. Enhancing Protein Disulfide Bond Cleavage by UV Excitation and Electron Capture Dissociation for Top-Down Mass Spectrometry.

    Science.gov (United States)

    Wongkongkathep, Piriya; Li, Huilin; Zhang, Xing; Loo, Rachel R Ogorzalek; Julian, Ryan R; Loo, Joseph A

    2015-11-15

    The application of ion pre-activation with 266 nm ultraviolet (UV) laser irradiation combined with electron capture dissociation (ECD) is demonstrated to enhance top-down mass spectrometry sequence coverage of disulfide bond containing proteins. UV-based activation can homolytically cleave a disulfide bond to yield two separated thiol radicals. Activated ECD experiments of insulin and ribonuclease A containing three and four disulfide bonds, respectively, were performed. UV-activation in combination with ECD allowed the three disulfide bonds of insulin to be cleaved and the overall sequence coverage to be increased. For the larger sized ribonuclease A with four disulfide bonds, irradiation from an infrared laser (10.6 µm) to disrupt non-covalent interactions was combined with UV-activation to facilitate the cleavage of up to three disulfide bonds. Preferences for disulfide bond cleavage are dependent on protein structure and sequence. Disulfide bonds can reform if the generated radicals remain in close proximity. By varying the time delay between the UV-activation and the ECD events, it was determined that disulfide bonds reform within 10-100 msec after their UV-homolytic cleavage.

  18. Radiation environmental impact assessment of copper exploitation

    International Nuclear Information System (INIS)

    Fan Guang; Wen Zhijian

    2010-01-01

    The radiation environmental impact of mineral exploitation on the surrounding environment has become a public concern. This paper presents the radiation environmental impact assessment of copper exploitation. Based on the project description and detailed investigations of surrounding environment, systematic radiation environmental impacts have been identified. The environmental impacts are assessed during both construction and operation phase. The environmental protection measures have also been proposed. The related conclusion and measures can play an active role in copper exploitation and environmental protection. (authors)

  19. Exploitation and exploration dynamics in recessionary times

    OpenAIRE

    Walrave, B.

    2012-01-01

    Firm performance largely depends on the ability to adapt to, and exploit, changes in the business environment. That is, firms should maintain ecological fitness by reconfiguring their resource base to cope with emerging threats and explore new opportunities, while at the same time exploiting existing resources. As such, firms possessing the ability to simultaneously perform exploitative and explorative initiatives are more resilient. In this respect, the performance implications of balancing ...

  20. Disulfide bond within mu-calpain active site inhibits activity and autolysis.

    Science.gov (United States)

    Lametsch, René; Lonergan, Steven; Huff-Lonergan, Elisabeth

    2008-09-01

    Oxidative processes have the ability to influence mu-calpain activity. In the present study the influence of oxidation on activity and autolysis of mu-calpain was examined. Furthermore, LC-MS/MS analysis was employed to identify and characterize protein modifications caused by oxidation. The results revealed that the activity of mu-calpain is diminished by oxidation with H2O2 in a reversible manner involving cysteine and that the rate of autolysis of mu-calpain concomitantly slowed. The LC-MS/MS analysis of the oxidized mu-calpain revealed that the amino acid residues 105-133 contained a disulfide bond between Cys(108) and Cys(115). The finding that the active site cysteine in mu-calpain is able to form a disulfide bond has, to our knowledge, not been reported before. This could be part of a unique oxidation mechanism for mu-calpain. The results also showed that the formation of the disulfide bond is limited in the control (no oxidant added), and further limited in a concentration-dependent manner when beta-mercaptoethanol is added. However, the disulfide bond is still present to some extent in all conditions indicating that the active site cysteine is potentially highly susceptible to the formation of this intramolecular disulfide bond.

  1. Changes in Thiol-Disulfide Homeostasis of the Body to Surgical Trauma in Laparoscopic Cholecystectomy Patients.

    Science.gov (United States)

    Polat, Murat; Ozcan, Onder; Sahan, Leyla; Üstündag-Budak, Yasemin; Alisik, Murat; Yilmaz, Nigar; Erel, Özcan

    2016-12-01

    We aimed to investigate the short-term effect of laparoscopic surgery on serum thiol-disulfide homeostasis levels as a marker of oxidant stress of surgical trauma in elective laparoscopic cholecystectomy patients. Venous blood samples were collected, and levels of native thiols, total thiols, and disulfides were determined with a novel automated assay. Total antioxidant capacity (measured as the ferric-reducing ability of plasma) and serum ischemia modified albumin, expressed as absorbance units assayed by the albumin cobalt binding test, were determined. The major findings of the present study were that native thiol (283 ± 45 versus 241 ± 61 μmol/L), total thiol (313 ± 49 versus 263 ± 67 μmol/L), and disulfide (14.9 ± 4.6 versus 11.0 ± 6.1 μmol/L) levels were decreased significantly during operation and although they increased, they did not return to preoperation levels 24 hours after laparoscopic surgery compared to the levels at baseline. Disulfide/native thiol and disulfide/total thiol levels did not change during laparoscopic surgery. The decrease in plasma level of native and total thiol groups suggests impairment of the antioxidant capacity of plasma; however, the delicate balance between the different redox forms of thiols was maintained during surgery.

  2. The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach

    International Nuclear Information System (INIS)

    Hoskins, J.T.; Zhou, Z.; Harding, P.A.

    2008-01-01

    A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide bonds within human HB-EGF by substituting serine for both cysteine residues that contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF-Cys/Ser 108/121 , HB-EGF-Cys/Ser 116/132 , and HB-EGF-Cys/Ser 134/143 ) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with M r of 6.5, 21 and 24 kDa were observed from lysates of HB-EGF and each HB-EGF disulfide analogue. HB-EGF immunohistochemical analyses of each HB-EGF stable cell line demonstrated ubiquitous protein expression except HB-EGF-Cys/Ser 108/121 and HB-EGF-Cys/Ser 116/132 stable cell lines which exhibited accumulated expression immediately outside the nucleus. rHB-EGF, HB-EGF, and HB-EGF 134/143 proteins competed with 125 I-EGF in an A431 competitive binding assay, whereas HB-EGF-Cys/Ser 108/121 and HB-EGF-Cys/Ser 116/132 failed to compete. Each HB-EGF disulfide analogue lacked the ability to stimulate tyrosine phosphorylation of the 170 kDa EGFR. These results suggest that HB-EGF-Cys/Ser 134/143 antagonizes EGFRs

  3. The moral basis of animal-assisted therapy.

    Science.gov (United States)

    Zamir, Tzachi

    2006-01-01

    Is nonhuman animal-assisted therapy (AAT) a form of exploitation? After exploring possible moral vindications of AAT and after establishing a distinction between "use" and "exploitation," the essay distinguishes between forms of animal-assisted therapy that are morally unobjectionable and those modes of it that ought to be abolished.

  4. Multi-terminal memtransistors from polycrystalline monolayer molybdenum disulfide

    Science.gov (United States)

    Sangwan, Vinod K.; Lee, Hong-Sub; Bergeron, Hadallia; Balla, Itamar; Beck, Megan E.; Chen, Kan-Sheng; Hersam, Mark C.

    2018-02-01

    Memristors are two-terminal passive circuit elements that have been developed for use in non-volatile resistive random-access memory and may also be useful in neuromorphic computing. Memristors have higher endurance and faster read/write times than flash memory and can provide multi-bit data storage. However, although two-terminal memristors have demonstrated capacity for basic neural functions, synapses in the human brain outnumber neurons by more than a thousandfold, which implies that multi-terminal memristors are needed to perform complex functions such as heterosynaptic plasticity. Previous attempts to move beyond two-terminal memristors, such as the three-terminal Widrow-Hoff memristor and field-effect transistors with nanoionic gates or floating gates, did not achieve memristive switching in the transistor. Here we report the experimental realization of a multi-terminal hybrid memristor and transistor (that is, a memtransistor) using polycrystalline monolayer molybdenum disulfide (MoS2) in a scalable fabrication process. The two-dimensional MoS2 memtransistors show gate tunability in individual resistance states by four orders of magnitude, as well as large switching ratios, high cycling endurance and long-term retention of states. In addition to conventional neural learning behaviour of long-term potentiation/depression, six-terminal MoS2 memtransistors have gate-tunable heterosynaptic functionality, which is not achievable using two-terminal memristors. For example, the conductance between a pair of floating electrodes (pre- and post-synaptic neurons) is varied by a factor of about ten by applying voltage pulses to modulatory terminals. In situ scanning probe microscopy, cryogenic charge transport measurements and device modelling reveal that the bias-induced motion of MoS2 defects drives resistive switching by dynamically varying Schottky barrier heights. Overall, the seamless integration of a memristor and transistor into one multi-terminal device could

  5. Shedding light on disulfide bond formation: engineering a redox switch in green fluorescent protein

    DEFF Research Database (Denmark)

    Østergaard, H.; Henriksen, A.; Hansen, Flemming G.

    2001-01-01

    To visualize the formation of disulfide bonds in living cells, a pair of redox-active cysteines was introduced into the yellow fluorescent variant of green fluorescent protein. Formation of a disulfide bond between the two cysteines was fully reversible and resulted in a >2-fold decrease...... in the intrinsic fluorescence. Inter conversion between the two redox states could thus be followed in vitro as well as in vivoby non- invasive fluorimetric measurements. The 1.5 Angstrom crystal structure of the oxidized protein revealed a disulfide bond- induced distortion of the beta -barrel, as well...... the physiological range for redox-active cysteines. In the cytoplasm of Escherichia coli, the protein was a sensitive probe for the redox changes that occur upon disruption of the thioredoxin reductive pathway....

  6. Selective disulfide reduction for labeling and enhancement of Fab antibody fragments

    International Nuclear Information System (INIS)

    Kirley, Terence L.; Greis, Kenneth D.; Norman, Andrew B.

    2016-01-01

    Many methods have been developed for chemical labeling and enhancement of the properties of antibodies and their common fragments, including the Fab and F(ab’) 2 fragments. Somewhat selective reduction of some antibody disulfide bonds has been previously achieved, yielding antibodies and antibody fragments that can be labeled at defined sites, enhancing their utility and properties. Selective reduction of the two hinge disulfide bonds present in F(ab’) 2 fragments using mild reduction has been useful. However, such reduction is often not quantitative and results in the reduction of multiple disulfide bonds, and therefore subsequent multiple labeling or conjugation sites are neither homogenous nor stoichiometric. Here, a simple and efficient selective reduction of the single disulfide bond linking the partial heavy chain and the intact light chain which compose the Fab fragment is accomplished utilizing tris(2-carboxyethyl)phosphine (TCEP) immobilized on agarose beads. The resultant reduced cysteine residues were labeled with several cysteine-selective fluorescent reagents, as well as by cysteine-directed PEGylation. These two cysteine residues can also be re-ligated by means of a bifunctional cysteine cross-linking agent, dibromobimane, thereby both restoring a covalent linkage between the heavy and light chains at this site, far removed from the antigen binding site, and also introducing a fluorescent probe. There are many other research and clinical uses for these selectively partially reduced Fab fragments, including biotinylation, toxin and drug conjugation, and incorporation of radioisotopes, and this technique enables simple generation of very useful Fab fragment derivatives with many potential applications. - Highlights: • TCEP agarose is effective for selective reduction of a single Fab disulfide bond. • This disulfide is solvent accessible and distant from the antigen binding site. • A variety of buffers of varying pHs can be used, simplifying

  7. New analogs of the CART peptide with anorexigenic potency: the importance of individual disulfide bridges.

    Science.gov (United States)

    Blechová, Miroslava; Nagelová, Veronika; Záková, Lenka; Demianová, Zuzana; Zelezná, Blanka; Maletínská, Lenka

    2013-01-01

    The CART (cocaine- and amphetamine-regulated transcript) peptide is an anorexigenic neuropeptide that acts in the hypothalamus. The receptor and the mechanism of action of this peptide are still unknown. In our previous study, we showed that the CART peptide binds specifically to PC12 rat pheochromocytoma cells in both the native and differentiated into neuronal phenotype. Two biologically active forms, CART(55-102) and CART(61-102), with equal biological activity, contain three disulfide bridges. To clarify the importance of each of these disulfide bridges in maintaining the biological activity of CART(61-102), an Ala scan at particular S-S bridges forming cysteines was performed, and analogs with only one or two disulfide bridges were synthesized. In this study, a stabilized CART(61-102) analog with norleucine instead of methionine at position 67 was also prepared and was found to bind to PC12 cells with an anorexigenic potency similar to that of CART(61-102). The binding study revealed that out of all analogs tested, [Ala(68,86)]CART(61-102), which contains two disulfide bridges (positions 74-94 and 88-101), preserved a high affinity to both native PC12 cells and those that had been differentiated into neurons. In food intake and behavioral tests with mice after intracerebroventricular administration, this analog showed strong and long-lasting anorexigenic potency. Therefore, the disulfide bridge between cysteines 68 and 86 in CART(61-102) can be omitted without a loss of biological activity, but the preservation of two other disulfide bridges and the full-length peptide are essential for biological activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. On the relevance of sophisticated structural annotations for disulfide connectivity pattern prediction.

    Directory of Open Access Journals (Sweden)

    Julien Becker

    Full Text Available Disulfide bridges strongly constrain the native structure of many proteins and predicting their formation is therefore a key sub-problem of protein structure and function inference. Most recently proposed approaches for this prediction problem adopt the following pipeline: first they enrich the primary sequence with structural annotations, second they apply a binary classifier to each candidate pair of cysteines to predict disulfide bonding probabilities and finally, they use a maximum weight graph matching algorithm to derive the predicted disulfide connectivity pattern of a protein. In this paper, we adopt this three step pipeline and propose an extensive study of the relevance of various structural annotations and feature encodings. In particular, we consider five kinds of structural annotations, among which three are novel in the context of disulfide bridge prediction. So as to be usable by machine learning algorithms, these annotations must be encoded into features. For this purpose, we propose four different feature encodings based on local windows and on different kinds of histograms. The combination of structural annotations with these possible encodings leads to a large number of possible feature functions. In order to identify a minimal subset of relevant feature functions among those, we propose an efficient and interpretable feature function selection scheme, designed so as to avoid any form of overfitting. We apply this scheme on top of three supervised learning algorithms: k-nearest neighbors, support vector machines and extremely randomized trees. Our results indicate that the use of only the PSSM (position-specific scoring matrix together with the CSP (cysteine separation profile are sufficient to construct a high performance disulfide pattern predictor and that extremely randomized trees reach a disulfide pattern prediction accuracy of [Formula: see text] on the benchmark dataset SPX[Formula: see text], which corresponds to

  9. The economics of exploiting gas hydrates

    International Nuclear Information System (INIS)

    Döpke, Lena-Katharina; Requate, Till

    2014-01-01

    We investigate the optimal exploitation of methane hydrates, a recent discovery of methane resources under the sea floor, mainly located along the continental margins. Combustion of methane (releasing CO2) and leakage through blow-outs (releasing CH4) contribute to the accumulation of greenhouse gases. A second externality arises since removing solid gas hydrates from the sea bottom destabilizes continental margins and thus increases the risk of marine earthquakes. We show that in such a model three regimes can occur: i) resource exploitation will be stopped in finite time, and some of the resource will stay in situ, ii) the resource will be used up completely in finite time, and iii) the resource will be exhausted in infinite time. We also show how to internalize the externalities by policy instruments. - Highlights: • We set up a model of optimal has hydrate exploitation • We incorporate to types of damages: contribution to global warming and geo-hazards • We characterize optimal exploitation paths and study decentralization with an exploitation tax. • Three regimes can occur: • i) exploitation in finite time and some of the stock remaining in situ, • ii) exploitation in finite time and the resource will be exhausted, • iii) exploitation and exhaustion in infinite time

  10. Exploitation and exploration dynamics in recessionary times

    NARCIS (Netherlands)

    Walrave, B.

    2012-01-01

    Firm performance largely depends on the ability to adapt to, and exploit, changes in the business environment. That is, firms should maintain ecological fitness by reconfiguring their resource base to cope with emerging threats and explore new opportunities, while at the same time exploiting

  11. Packaging of Sin Goods - Commitment or Exploitation?

    DEFF Research Database (Denmark)

    Nafziger, Julia

    to such self-control problems, and possibly exploit them, by offering different package sizes. In a competitive market, either one or three (small, medium and large) packages are offered. In contrast to common intuition, the large, and not the small package is a commitment device. The latter serves to exploit...

  12. SEXUAL EXPLOITATION AND ABUSE BY UN PEACEKEEPERS ...

    African Journals Online (AJOL)

    Allaiac

    sexual exploitation of children by peacekeepers is particularly insidious. ... sexual exploitation and abuse should involve an understanding of the social .... The charges of sexual misconduct, and the consequent media exposure, have ..... awareness programmes such as video tapes, lectures and training manuals, designed.

  13. Exploration, Exploitation, and Organizational Coordination Mechanisms

    Directory of Open Access Journals (Sweden)

    Silvio Popadiuk

    2016-03-01

    Full Text Available This paper presents an empirical relationship among exploration, exploitation, and organizational coordination mechanisms, classified as the centralization of decision-making, formalization, and connectedness. In order to analyze the findings of this survey, we used two techniques: Principal Component Analysis (PCA and Partial Least Squares Path Modeling (PLS-PM. Our analysis was supported by 249 answers from managers of companies located in Brazil (convenience sampling. Contrary to expectations, centralization and exploitation were negatively associated. Our data supports the research hypothesis that formalization is positively associated with exploitation. Although the relationship between formalization and exploration were significant, the result is contrary to the research hypothesis that we made. The relationships among connectedness and exploitation, and connectedness and exploration were both positive and significant. This relationship means that the more connectedness increases, the higher the likelihood of exploitation and exploration.

  14. Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides

    DEFF Research Database (Denmark)

    Safavi-Hemami, Helena; Li, Qing; Jackson, Ronneshia L.

    2016-01-01

    Formation of correct disulfide bonds in the endoplasmic reticulum is a crucial step for folding proteins destined for secretion. Protein disulfide isomerases (PDIs) play a central role in this process. We report a previously unidentified, hypervariable family of PDIs that represents the most...... diverse gene family of oxidoreductases described in a single genus to date. These enzymes are highly expressed specifically in the venom glands of predatory cone snails, animals that synthesize a remarkably diverse set of cysteine-rich peptide toxins (conotoxins). Enzymes in this PDI family, termed...

  15. Inactivation of barley limit dextrinase inhibitor by thioredoxin-catalysed disulfide reduction

    DEFF Research Database (Denmark)

    Jensen, Johanne Mørch; Hägglund, Per; Christensen, Hans Erik Mølager

    2012-01-01

    and one glutathionylated cysteine. Here, thioredoxin is shown to progressively reduce disulfide bonds in LDI accompanied by loss of activity. A preferential reduction of the glutathionylated cysteine, as indicated by thiol quantification and molecular mass analysis using electrospray ionisation mass......Barley limit dextrinase (LD) that catalyses hydrolysis of α-1,6 glucosidic linkages in starch-derived dextrins is inhibited by limit dextrinase inhibitor (LDI) found in mature seeds. LDI belongs to the chloroform/methanol soluble protein family (CM-protein family) and has four disulfide bridges...... spectrometry, was not related to LDI inactivation. LDI reduction is proposed to cause conformational destabilisation leading to loss of function....

  16. Enhanced production of a single domain antibody with an engineered stabilizing extra disulfide bond.

    Science.gov (United States)

    Liu, Jinny L; Goldman, Ellen R; Zabetakis, Dan; Walper, Scott A; Turner, Kendrick B; Shriver-Lake, Lisa C; Anderson, George P

    2015-10-09

    Single domain antibodies derived from the variable region of the unique heavy chain antibodies found in camelids yield high affinity and regenerable recognition elements. Adding an additional disulfide bond that bridges framework regions is a proven method to increase their melting temperature, however often at the expense of protein production. To fulfill their full potential it is essential to achieve robust protein production of these stable binding elements. In this work, we tested the hypothesis that decreasing the isoelectric point of single domain antibody extra disulfide bond mutants whose production fell due to the incorporation of the extra disulfide bond would lead to recovery of the protein yield, while maintaining the favorable melting temperature and affinity. Introduction of negative charges into a disulfide bond mutant of a single domain antibody specific for the L1 antigen of the vaccinia virus led to approximately 3.5-fold increase of protein production to 14 mg/L, while affinity and melting temperature was maintained. In addition, refolding following heat denaturation improved from 15 to 70 %. It also maintained nearly 100 % of its binding function after heating to 85 °C for an hour at 1 mg/mL. Disappointingly, the replacement of neutral or positively charged amino acids with negatively charged ones to lower the isoelectric point of two anti-toxin single domain antibodies stabilized with a second disulfide bond yielded only slight increases in protein production. Nonetheless, for one of these binders the charge change itself stabilized the structure equivalent to disulfide bond addition, thus providing an alternative route to stabilization which is not accompanied by loss in production. The ability to produce high affinity, stable single domain antibodies is critical for their utility. While the addition of a second disulfide bond is a proven method for enhancing stability of single domain antibodies, it frequently comes at the cost of reduced

  17. Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4'-dipyridyl disulfide

    DEFF Research Database (Denmark)

    López-Mirabal, H Reynaldo; Thorsen, Michael; Kielland-Brandt, Morten C

    2007-01-01

    Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma-glutamyl-c......Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma...... antioxidant pools of glutathione (GSH) and thioredoxin are required for resistance to DPS. We found that DPS-sensitive mutants display increases in the disulfide form of GSH (GSSG) during DPS exposure that roughly correlate with their more oxidizing GSH redox potential in the cytosol and their degree of DPS...

  18. The road to the first, fully active and more stable human insulin variant with an additional disulfide bond

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Kjeldsen, Thomas B.; Jensen, Knud Jørgen

    2015-01-01

    Insulin, a small peptide hormone, is crucial in maintaining blood glucose homeostasis. The stability and activity of the protein is directed by an intricate system involving disulfide bonds to stabilize the active monomeric species and by their non-covalent oligomerization. All known insulin...... variants in vertebrates consist of two peptide chains and have six cysteine residues, which form three disulfide bonds, two of them link the two chains and a third is an intra-chain bond in the A-chain. This classical insulin fold appears to have been conserved over half a billion years of evolution. We...... addressed the question whether a human insulin variant with four disulfide bonds could exist and be fully functional. In this review, we give an overview of the road to engineering four-disulfide bonded insulin analogs. During our journey, we discovered several active four disulfide bonded insulin analogs...

  19. Herbivory eliminates fitness costs of mutualism exploiters.

    Science.gov (United States)

    Simonsen, Anna K; Stinchcombe, John R

    2014-04-01

    A common empirical observation in mutualistic interactions is the persistence of variation in partner quality and, in particular, the persistence of exploitative phenotypes. For mutualisms between hosts and symbionts, most mutualism theory assumes that exploiters always impose fitness costs on their host. We exposed legume hosts to mutualistic (nitrogen-fixing) and exploitative (non-nitrogen-fixing) symbiotic rhizobia in field conditions, and manipulated the presence or absence of insect herbivory to determine if the costly fitness effects of exploitative rhizobia are context-dependent. Exploitative rhizobia predictably reduced host fitness when herbivores were excluded. However, insects caused greater damage on hosts associating with mutualistic rhizobia, as a consequence of feeding preferences related to leaf nitrogen content, resulting in the elimination of fitness costs imposed on hosts by exploitative rhizobia. Our experiment shows that herbivory is potentially an important factor in influencing the evolutionary dynamic between legumes and rhizobia. Partner choice and host sanctioning are theoretically predicted to stabilize mutualisms by reducing the frequency of exploitative symbionts. We argue that herbivore pressure may actually weaken selection on choice and sanction mechanisms, thus providing one explanation of why host-based discrimination mechanisms may not be completely effective in eliminating nonbeneficial partners. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  20. Increased Functional Half-life of Fibroblast Growth Factor-1 by Recovering a Vestigial Disulfide Bond

    Directory of Open Access Journals (Sweden)

    Jihun Lee

    2010-12-01

    Full Text Available The fibroblast growth factor (FGF family of proteins contains an absolutely conserved Cys residue at position 83 that is present as a buried free cysteine. We have previously shown that mutation of the structurally adjacent residue, Ala66, to cysteine results in the formation of a stabilizing disulfide bond in FGF-1. This result suggests that the conserved free cysteine residue at position 83 in the FGF family of proteins represents a vestigial half-cystine. Here, we characterize the functional half-life and mitogenic activity of the oxidized form of the Ala66Cys mutation to identify the effect of the recovered vestigial disulfide bond between Cys83 and Cys66 upon the cellular function of FGF-1. The results show that the mitogenic activity of this mutant is significantly increased and that its functional half-life is greatly extended. These favorable effects are conferred by the formation of a disulfide bond that simultaneously increases thermodynamic stability of the protein and removes a reactive buried thiol at position 83. Recovering this vestigial disulfide by introducing a cysteine at position 66 is a potentially useful protein engineering strategy to improve the functional half-life of other FGF family members.

  1. Dynamic thiol/disulfide homeostasis and effects of smoking on homeostasis parameters in patients with psoriasis.

    Science.gov (United States)

    Emre, Selma; Demirseren, Duriye Deniz; Alisik, Murat; Aktas, Akin; Neselioglu, Salim; Erel, Ozcan

    2017-12-01

    Recently, increased reactive oxygen species (ROS), reduced antioxidant capacity, and oxidative stress have been suggested in the pathogenesis of psoriasis. The aim of this study to evaluate the thiol/disulfide homeostasis in patients with psoriasis. Ninety patients with psoriasis who did not receive any systemic treatment in the last six  months were included in the study. Seventy-six age and gender-matched healthy volunteers served as control group. Thiol/disulfide homeostasis was measured in venous blood samples obtained from patient and control groups. Native thiol and total thiol levels were significantly higher in patients than in control group. When thiol/disulfide hemostasis parameters and clinical and demographic characteristics were compared, a negative correlation was detected between native thiol and total thiol with age. The levels of total thiols had also negative correlation with PASI and duration of the disease. When we divided the patients into smokers and non-smokers, native thiol and total thiol levels were significantly higher in smokers than in controls, whereas native thiol and total thiol levels were comparable in non-smoker patients and controls. Thiol/disulfide balance shifted towards thiol in psoriasis patients and this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis.

  2. Role of the Disulfide Bond in Prion Protein Amyloid Formation: A Thermodynamic and Kinetic Analysis.

    Science.gov (United States)

    Honda, Ryo

    2018-02-27

    Prion diseases are associated with the structural conversion of prion protein (PrP) to a β-sheet-rich aggregate, PrP Sc . Previous studies have indicated that a reduction of the disulfide bond linking C179 and C214 of PrP yields an amyloidlike β-rich aggregate in vitro. To gain mechanistic insights into the reduction-induced aggregation, here I characterized how disulfide bond reduction modulates the protein folding/misfolding landscape of PrP, by examining 1) the equilibrium stabilities of the native (N) and aggregated states relative to the unfolded (U) state, 2) the transition barrier separating the U and aggregated states, and 3) the final structure of amyloidlike misfolded aggregates. Kinetic and thermodynamic experiments revealed that disulfide bond reduction decreases the equilibrium stabilities of both the N and aggregated states by ∼3 kcal/mol, without changing either the amyloidlike aggregate structure, at least at the secondary structural level, or the transition barrier of aggregation. Therefore, disulfide bond reduction modulates the protein folding/misfolding landscape by entropically stabilizing disordered states, including the U and transition state of aggregation. This also indicates that the equilibrium stability of the N state, but not the transition barrier of aggregation, is the dominant factor determining the reduction-induced aggregation of PrP. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Differential Labeling of Free and Disulfide-Bound Thiol Functions in Proteins

    NARCIS (Netherlands)

    Seiwert, B.; Hayen, H.; Karst, U.

    2008-01-01

    A method for the simultaneous determination of the number of free cysteine groups and disulfide-bound cysteine groups in proteins has been developed based on the sequential labeling of free and bound thiol functionalities with two ferrocene-based maleimide reagents. Liquid

  4. New thiol-responsive mono-cleavable block copolymer micelles labeled with single disulfides.

    Science.gov (United States)

    Sourkohi, Behnoush Khorsand; Schmidt, Rolf; Oh, Jung Kwon

    2011-10-18

    Thiol-responsive symmetric triblock copolymers having single disulfide linkages in the middle blocks (called mono-cleavable block copolymers, ss-ABP(2)) were synthesized by atom transfer radical polymerization in the presence of a disulfide-labeled difunctional Br-initiator. These brush-like triblock copolymers consist of a hydrophobic polyacrylate block having pendent oligo(propylene oxide) and a hydrophilic polymethacrylate block having pendent oligo(ethylene oxide). Gel permeation chromatography and (1)H NMR results confirmed the synthesis of well-defined mono-cleavable block copolymers and revealed that polymerizations were well controlled. Because of amphiphilic nature, these copolymers self-assembled to form colloidally stable micelles above critical micellar concentration of 0.032 mg · mL(-1). In response to reductive reactions, disulfides in thiol-responsive micelles were cleaved. Atomic force microscopy and dynamic light scattering analysis suggested that the cleavage of disulfides caused dissociation of micelles to smaller-sized assembled structures in water. Moreover, in a biomedical perspective, the mono-cleavable block copolymer micelles are not cytotoxic and thus biocompatible. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Dissecting molecular interactions involved in recognition of target disulfides by the barley thioredoxin system

    DEFF Research Database (Denmark)

    Björnberg, Olof; Maeda, Kenji; Svensson, Birte

    2012-01-01

    Thioredoxin reduces disulfide bonds, thus regulating activities of target proteins in various biological systems, e.g., inactivation of inhibitors of starch hydrolases and proteases in germinating plant seeds. In the three-dimensional structure of a complex with barley α-amylase/subtilisin inhibi......Thioredoxin reduces disulfide bonds, thus regulating activities of target proteins in various biological systems, e.g., inactivation of inhibitors of starch hydrolases and proteases in germinating plant seeds. In the three-dimensional structure of a complex with barley α...... thioredoxin reductase. HvTrxh2 M88G and M88A adjacent to the invariant cis-proline lost efficiency in both BASI disulfide reduction and recycling by thioredoxin reductase. These effects were further pronounced in M88P lacking a backbone NH group. Remarkably, HvTrxh2 E86R in the same loop displayed overall...... retained catalytic properties, with the exception of a 3-fold increased activity toward BASI. From the 104VGA106 loop, a backbone hydrogen bond donated by A106 appears to be important for target disulfide recognition as A106P lost 90% activity toward BASI but was efficiently recycled by thioredoxin...

  6. Disulfide bonds in folding and transport of the mouse hepatitis virus glycoproteins

    NARCIS (Netherlands)

    Horzinek, M.C.; Opstelten, D.-J.E.; Groote, P. de; Vennema, H.; Rottier, P.J.M.

    1993-01-01

    We have analyzed the effects of reducing conditions on the folding of the spike (S) protein and on the intracellular transport of the membrane (M) protein of the mouse hepatitis coronavirus. These proteins differ in their potential to form disulfide bonds in the lumen of the endoplasmic reticulum

  7. Differential expression of disulfide reductase enzymes in a free-living platyhelminth (Dugesia dorotocephala.

    Directory of Open Access Journals (Sweden)

    Alberto Guevara-Flores

    Full Text Available A search of the disulfide reductase activities expressed in the adult stage of the free-living platyhelminth Dugesia dorotocephala was carried out. Using GSSG or DTNB as substrates, it was possible to obtain a purified fraction containing both GSSG and DTNB reductase activities. Through the purification procedure, both disulfide reductase activities were obtained in the same chromatographic peak. By mass spectrometry analysis of peptide fragments obtained after tryptic digestion of the purified fraction, the presence of glutathione reductase (GR, thioredoxin-glutathione reductase (TGR, and a putative thioredoxin reductase (TrxR was detected. Using the gold compound auranofin to selectively inhibit the GSSG reductase activity of TGR, it was found that barely 5% of the total GR activity in the D. dorotocephala extract can be assigned to GR. Such strategy did allow us to determine the kinetic parameters for both GR and TGR. Although It was not possible to discriminate DTNB reductase activity due to TrxR from that of TGR, a chromatofocusing experiment with a D. dorotocephala extract resulted in the obtention of a minor protein fraction enriched in TrxR, strongly suggesting its presence as a functional protein. Thus, unlike its parasitic counterparts, in the free-living platyhelminth lineage the three disulfide reductases are present as functional proteins, albeit TGR is still the major disulfide reductase involved in the reduction of both Trx and GSSG. This fact suggests the development of TGR in parasitic flatworms was not linked to a parasitic mode of life.

  8. Selective removal of heavy metal ions by disulfide linked polymer networks

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Dongah [Department of Environmental Engineering, Technical University of Denmark, Miljøvej 113, 2800 Kgs. Lyngby (Denmark); Lee, Joo Sung [Graduate School of EEWS, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141 (Korea, Republic of); Patel, Hasmukh A. [Department of Chemistry, Northwestern University, Evanston, IL 60208 (United States); Jakobsen, Mogens H. [Department of Micro and Nano technology, Technical University of Denmark, Ørsteds Plads, 345B, 2800 Kgs. Lyngby (Denmark); Hwang, Yuhoon [Department of Environmental Engineering, Seoul National University of Science and Technology, 232 Gongreung-ro, Nowon-gu, Seoul 01811 (Korea, Republic of); Yavuz, Cafer T. [Graduate School of EEWS, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141 (Korea, Republic of); Hansen, Hans Chr. Bruun [Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Andersen, Henrik R., E-mail: henrik@ndersen.net [Department of Environmental Engineering, Technical University of Denmark, Miljøvej 113, 2800 Kgs. Lyngby (Denmark)

    2017-06-15

    Highlights: • Disulfide/thiol polymer networks are promising as sorbent for heavy metals. • Rapid sorption and high Langmuir affinity constant (a{sub L}) for stormwater treatment. • Selective sorption for copper, cadmium, and zinc in the presence of calcium. • Reusability likely due to structure stability of disulfide linked polymer networks. - Abstract: Heavy metal contaminated surface water is one of the oldest pollution problems, which is critical to ecosystems and human health. We devised disulfide linked polymer networks and employed as a sorbent for removing heavy metal ions from contaminated water. Although the polymer network material has a moderate surface area, it demonstrated cadmium removal efficiency equivalent to highly porous activated carbon while it showed 16 times faster sorption kinetics compared to activated carbon, owing to the high affinity of cadmium towards disulfide and thiol functionality in the polymer network. The metal sorption mechanism on polymer network was studied by sorption kinetics, effect of pH, and metal complexation. We observed that the metal ions–copper, cadmium, and zinc showed high binding affinity in polymer network, even in the presence of competing cations like calcium in water.

  9. Research of the technology of obtaining pure and disperse molybdenum disulfide from molybdenum concentrate

    International Nuclear Information System (INIS)

    Hovsepyan, A.H.; Israyelyan, S.M.

    2009-01-01

    The technology of obtaining pure and disperse molybdenum disulfide is worked out. The processes of refinement from the flotation reagents and deslimation by means of decantation, refinement of molybdenite concentrate from impurities by selective leaching methods are studied. The optimal regime of technological process is chosen

  10. Decontamination of Oils Contaminated with Polychlorinated Biphenyls and Dibenzyl Disulfide Using Polar Aprotic Solvents

    Czech Academy of Sciences Publication Activity Database

    Kaštánek, František; Matějková, Martina; Spáčilová, Lucie; Maléterová, Ywetta; Kaštánek, P.; Šolcová, Olga

    2015-01-01

    Roč. 4, č. 2 (2015), s. 41-48 ISSN 2319-5967 R&D Projects: GA TA ČR(CZ) TA04020151 Institutional support: RVO:67985858 Keywords : corrosive sulfur * dibenzyl disulfide * polar aprotic solvents Subject RIV: CI - Industrial Chemistry, Chemical Engineering http://www.ijesit.com/Volume%204/Issue%202/IJESIT201502_06.pdf

  11. Synthesis of tetraalkyl thiuram disulfides using different oxidants in recycling solvent mixture

    Directory of Open Access Journals (Sweden)

    Milosavljević Milutin M.

    2012-01-01

    Full Text Available A new optimized laboratory synthesis of tetraalkyl thiuram disulfides, starting from dialkyl amines and carbon disulfide in presence of three oxidants (hydrogen peroxide, potassium peroxodisulfate and sodium hypochlorite and appropriate reaction medium: two mixtures of isopropyl alcohol - water used in two consecutive syntheses, was presented in this work. First synthesis was performed in a recycled azeotropic mixture of isopropyl alcohol - water 87.7% - 12.3%, and second in a filtrate obtained after first synthesis, which was a mixture of isopropyl alcohol - water 70.4% - 29.6%. After the second synthesis and filtration, recycled azeotropic mixture isopropyl alcohol - water 87.7% - 12.3% was regenerated from the filtrate by rectification. Considering this, the technology for beneficial use of recycling isopropyl alcohol - water mixture as reaction medium for tetraalkyl thiuram disulfides synthesis was developed. Such concept contributes to extraordinary economical benefit of implemented optimal laboratory synthesis at semi-industrial level. High yields of tetraalkyl thiuram disulfides syntheses were obtained at both laboratory and semiindustrial level. Structure and purity of synthesized compounds were confirmed by elemental analysis, as well as FTIR, 1H and 13C NMR, and MS spectral data.

  12. Improvement in the thermostability of chitosanase from Bacillus ehimensis by introducing artificial disulfide bonds.

    Science.gov (United States)

    Sheng, Jun; Ji, Xiaofeng; Zheng, Yuan; Wang, Zhipeng; Sun, Mi

    2016-10-01

    To determine the effects of artificial disulfide bridges on the thermostability and catalytic efficiency of chitosanase EAG1. Five artificial disulfide bridges were designed based on the structural information derived from the three-dimensional (3-D) model of chitosanase EAG1. Two beneficial mutants (G113C/D116C, A207C-L286C) were located in the flexible surface loop region, whereas the similar substitutions introduced in α-helices regions had a negligible effect. Mut5, the most active mutant, had a longer half-life at 50 °C (from 10.5 to 69.3 min) and a 200 % higher catalytic efficiency (K cat/K m) than that of the original EAG1. The contribution of disulfide bridges to enzyme thermostability is mainly dependent on its location within the polypeptide chain. Strategical placement of a disulfide bridge in flexible regions provides a rigid support and creation of a protected microenvironment, which is effective in improving enzyme's thermostability and catalytic efficiency.

  13. Photo-reduction on the rupture of disulfide bonds and the related protein assembling

    Science.gov (United States)

    Wang, Wei

    It has been found that many proteins can self-assemble into nanoscale assemblies when they unfold or partially unfold under harsh conditions, such as low pH, high temperature, or the presence of denaturants, and so on. These nanoscale assemblies can have some applications such as the drug-delivery systems (DDSs). Here we report a study that a very physical way, the UV illumination, can be used to facilitate the formation of protein fibrils and nanoparticles under native conditions by breaking disulfide bonds in some disulfide-containing proteins. By controlling the intensity of UV light and the illumination time, we realized the preparation of self-assembly nanoparticles which encapsulate the anticancer drug doxorubicin (DOX) and can be used as the DDS for inhibiting the growth of tumor. The formation of fibrillary assemblies was also observed. The rupture of disulfide bonds through photo-reduction process due to the effect of tryptophan and tyrosine was studied, and the physical mechanism of the assembling of the related disulfide-containing proteins was also discussed. We thank the financial support from NSF of China and the 973 project.

  14. Per-2,3-O-alkylated beta-cyclodextrin duplexes connected with disulfide bonds

    Czech Academy of Sciences Publication Activity Database

    Tatar, Ameneh; Grishina, Anastasia; Buděšínský, Miloš; Kraus, Tomáš

    2017-01-01

    Roč. 29, č. 1 (2017), s. 40-48 ISSN 1061-0278 R&D Projects: GA MŠk LD12019 Grant - others:COST(XE) CM1005 Institutional support: RVO:61388963 Keywords : cyclodextrins * inclusion complexes * disulfide bonds Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 1.264, year: 2016

  15. Efficacy of HOCl scavenging by sulfur-containing compounds: antioxidant activity of glutathione disulfide?

    NARCIS (Netherlands)

    den Hartog, G.J.M.; Haenen, G.R.M.M.; Vegt, E.; van der Vijgh, W.J.F.; Bast, A.

    2002-01-01

    Efficacy of HOCl scavenging by sulfur-containing compounds: antioxidant activity of glutathione disulfide? den Hartog GJ, Haenen GR, Vegt E, van der Vijgh WJ, Bast A. Department of Pharmacology and Toxicology, Maastricht University, The Netherlands. Hypochlorous acid (HOCl) is a bactericidal

  16. Structural Basis of a Thiol-Disulfide Oxidoreductase in the Hedgehog-Forming Actinobacterium Corynebacterium matruchotii.

    Science.gov (United States)

    Luong, Truc Thanh; Tirgar, Reyhaneh; Reardon-Robinson, Melissa E; Joachimiak, Andrzej; Osipiuk, Jerzy; Ton-That, Hung

    2018-05-01

    The actinobacterium Corynebacterium matruchotii has been implicated in nucleation of oral microbial consortia leading to biofilm formation. Due to the lack of genetic tools, little is known about basic cellular processes, including protein secretion and folding, in this organism. We report here a survey of the C. matruchotii genome, which encodes a large number of exported proteins containing paired cysteine residues, and identified an oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA (MdbA Cd ). Crystallization studies uncovered that the 1.2-Å resolution structure of C. matruchotii MdbA (MdbA Cm ) possesses two conserved features found in actinobacterial MdbA enzymes, a thioredoxin-like fold and an extended α-helical domain. By reconstituting the disulfide bond-forming machine in vitro , we demonstrated that MdbA Cm catalyzes disulfide bond formation within the actinobacterial pilin FimA. A new gene deletion method supported that mdbA is essential in C. matruchotii Remarkably, heterologous expression of MdbA Cm in the C. diphtheriae Δ mdbA mutant rescued its known defects in cell growth and morphology, toxin production, and pilus assembly, and this thiol-disulfide oxidoreductase activity required the catalytic motif CXXC. Altogether, the results suggest that MdbA Cm is a major thiol-disulfide oxidoreductase, which likely mediates posttranslocational protein folding in C. matruchotii by a mechanism that is conserved in Actinobacteria IMPORTANCE The actinobacterium Corynebacterium matruchotii has been implicated in the development of oral biofilms or dental plaque; however, little is known about the basic cellular processes in this organism. We report here a high-resolution structure of a C. matruchotii oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA. By biochemical analysis, we demonstrated that C. matruchotii MdbA catalyzes disulfide

  17. Dissecting the role of disulfide bonds on the amyloid formation of insulin

    International Nuclear Information System (INIS)

    Li, Yang; Gong, Hao; Sun, Yue; Yan, Juan; Cheng, Biao; Zhang, Xin; Huang, Jing; Yu, Mengying; Guo, Yu; Zheng, Ling; Huang, Kun

    2012-01-01

    Highlights: ► We dissect how individual disulfide bond affects the amyloidogenicity of insulin. ► A controlled reduction system for insulin is established in this study. ► Disulfide breakage is associated with unfolding and increased amyloidogenicity. ► Breakage of A6-A11 is associated with significantly increased cytotoxicity. ► Analogs without A6-A11 have a higher potency to form high order toxic oligomers. -- Abstract: Disulfide bonds play a critical role in the stability and folding of proteins. Here, we used insulin as a model system, to investigate the role of its individual disulfide bond during the amyloid formation of insulin. Tris(2-carboxyethyl)phosphine (TCEP) was applied to reduce two of the three disulfide bonds in porcine insulin and the reduced disulfide bonds were then alkylated by iodoacetamide. Three disulfide bond-modified insulin analogs, INS-2 (lack of A6-A11), INS-3 (lack of A7-B7) and INS-6 (lack of both A6-A11 and A7-B7), were obtained. Far-UV circular dichroism (CD) spectroscopy results indicated that the secondary structure of INS-2 was the closest to insulin under neutral conditions, followed by INS-3 and INS-6, whereas in an acidic solution all analogs were essentially unfolded. To test how these modifications affect the amyloidogenicity of insulin, thioflavin-T (ThT) fluorescence and transmission electronic microscopy (TEM) were performed. Our results showed that all analogs were more prone to aggregation than insulin, with the order of aggregation rates being INS-6 > INS-3 > INS-2. Cross-linking of unmodified proteins (PICUP) assay results showed that analogs without A6-A11 (INS-2 and INS-6) have a higher potential for oligomerization than insulin and INS-3, which is accompanied with a higher cytotoxicity as the hemolytic assays of human erythrocytes suggested. The results indicated that breakage of A7-B7 induced more unfolding of the insulin structure and a higher amyloidogenicity than breakage of A6-A11, but breakage of A6

  18. Peat exploitation - Environment. Effects and measures

    International Nuclear Information System (INIS)

    Stenbeck, G.

    1996-01-01

    This report gives a detailed description of the influence of peat exploitation on the land-, water- and atmospheric environments. Proposals for mitigatory measures to minimize damage to the environment are also given

  19. SEXUAL EXPLOITATION AND ABUSE BY UN PEACEKEEPERS ...

    African Journals Online (AJOL)

    Allaiac

    from sexual exploitation and sexual abuse (ST/SGB/2003/13) (UN, Secretary .... In addition, in most situations, UN personnel have enjoyed immunity from local .... 9 Official UN statistics show a higher incidence of allegations reported against.

  20. Exploitation of linkage learning in evolutionary algorithms

    CERN Document Server

    Chen, Ying-ping

    2010-01-01

    The exploitation of linkage learning is enhancing the performance of evolutionary algorithms. This monograph examines recent progress in linkage learning, with a series of focused technical chapters that cover developments and trends in the field.

  1. Exploitative and Deceptive Resource Acquisition Strategies

    Directory of Open Access Journals (Sweden)

    Joshua J. Reynolds

    2015-07-01

    Full Text Available Life history strategy (LHS and life history contingencies (LHCs should theoretically influence the use of exploitative and deceptive resource acquisition strategies. However, little research has been done in this area. The purpose of the present work was to create measures of exploitative strategies and test the predictions of life history theory. Pilot studies developed and validated a behavioral measure of cheating called the Dot Game. The role of individual LHS and LHCs (manipulated via validated story primes on cheating was investigated in Study 1. Studies 2a through 2c were conducted to develop and validate a self-report measure called the Exploitative and Deceptive Resource Acquisition Strategy Scale (EDRASS. Finally, Study 3 investigated life history and EDRASS. Results indicated that while LHS influences exploitative strategies, life history contingences had little effect. Implications of these findings are discussed.

  2. Organ sales: exploitative at any price?

    Science.gov (United States)

    Lawlor, Rob

    2014-05-01

    In many cases, claims that a transaction is exploitative will focus on the details of the transaction, such as the price paid or conditions. For example, in a claim that a worker is exploited, the grounds for the claim are usually that the pay is not sufficient or the working conditions too dangerous. In some cases, however, the claim that a transaction is exploitative is not seen to rely on these finer details. Many, for example, claim that organ sales would be exploitative, in a way that doesn't seem to depend on the details. This article considers, but ultimately rejects, a number of arguments which could be used to defend this sort of claim. © 2012 John Wiley & Sons Ltd.

  3. A Theory of Exploitative Child Labor

    OpenAIRE

    Carol Ann Rogers; Kenneth A. Swinnerton

    2003-01-01

    Child labor laws should aim to protect children who work, instead of trying to remove children from work. In this paper, we identify an instance when the risk of exploitation lowers the expected bene…t of child labor to the child,and therefore suppresses child labor force participation. Targeted legal intervention that lowers or removes the risk of exploitation raises child participation in the labor market, child welfare, and overall societal welfare. Targeting on child labor more broadly ma...

  4. Identification of a disulfide bridge important for transport function of SNAT4 neutral amino acid transporter.

    Directory of Open Access Journals (Sweden)

    Rugmani Padmanabhan Iyer

    Full Text Available SNAT4 is a member of system N/A amino acid transport family that primarily expresses in liver and muscles and mediates the transport of L-alanine. However, little is known about the structure and function of the SNAT family of transporters. In this study, we showed a dose-dependent inhibition in transporter activity of SNAT4 with the treatment of reducing agents, dithiothreitol (DTT and Tris(2-carboxyethylphosphine (TCEP, indicating the possible involvement of disulfide bridge(s. Mutation of residue Cys-232, and the two highly conserved residues Cys-249 and Cys-321, compromised the transport function of SNAT4. However, this reduction was not caused by the decrease of SNAT4 on the cell surface since the cysteine-null mutant generated by replacing all five cysteines with alanine was equally capable of being expressed on the cell surface as wild-type SNAT4. Interestingly, by retaining two cysteine residues, 249 and 321, a significant level of L-alanine uptake was restored, indicating the possible formation of disulfide bond between these two conserved residues. Biotinylation crosslinking of free thiol groups with MTSEA-biotin provided direct evidence for the existence of a disulfide bridge between Cys-249 and Cys-321. Moreover, in the presence of DTT or TCEP, transport activity of the mutant retaining Cys-249 and Cys-321 was reduced in a dose-dependent manner and this reduction is gradually recovered with increased concentration of H2O2. Disruption of the disulfide bridge also decreased the transport of L-arginine, but to a lesser degree than that of L-alanine. Together, these results suggest that cysteine residues 249 and 321 form a disulfide bridge, which plays an important role in substrate transport but has no effect on trafficking of SNAT4 to the cell surface.

  5. Structural characterization of PTX3 disulfide bond network and its multimeric status in cumulus matrix organization.

    Science.gov (United States)

    Inforzato, Antonio; Rivieccio, Vincenzo; Morreale, Antonio P; Bastone, Antonio; Salustri, Antonietta; Scarchilli, Laura; Verdoliva, Antonio; Vincenti, Silvia; Gallo, Grazia; Chiapparino, Caterina; Pacello, Lucrezia; Nucera, Eleonora; Serlupi-Crescenzi, Ottaviano; Day, Anthony J; Bottazzi, Barbara; Mantovani, Alberto; De Santis, Rita; Salvatori, Giovanni

    2008-04-11

    PTX3 is an acute phase glycoprotein that plays key roles in resistance to certain pathogens and in female fertility. PTX3 exerts its functions by interacting with a number of structurally unrelated molecules, a capacity that is likely to rely on its complex multimeric structure stabilized by interchain disulfide bonds. In this study, PAGE analyses performed under both native and denaturing conditions indicated that human recombinant PTX3 is mainly composed of covalently linked octamers. The network of disulfide bonds supporting this octameric assembly was resolved by mass spectrometry and Cys to Ser site-directed mutagenesis. Here we report that cysteine residues at positions 47, 49, and 103 in the N-terminal domain form three symmetric interchain disulfide bonds stabilizing four protein subunits in a tetrameric arrangement. Additional interchain disulfide bonds formed by the C-terminal domain cysteines Cys(317) and Cys(318) are responsible for linking the PTX3 tetramers into octamers. We also identified three intrachain disulfide bonds within the C-terminal domain that we used as structural constraints to build a new three-dimensional model for this domain. Previously it has been shown that PTX3 is a key component of the cumulus oophorus extracellular matrix, which forms around the oocyte prior to ovulation, because cumuli from PTX3(-/-) mice show defective matrix organization. Recombinant PTX3 is able to restore the normal phenotype ex vivo in cumuli from PTX3(-/-) mice. Here we demonstrate that PTX3 Cys to Ser mutants, mainly assembled into tetramers, exhibited wild type rescue activity, whereas a mutant, predominantly composed of dimers, had impaired functionality. These findings indicate that protein oligomerization is essential for PTX3 activity within the cumulus matrix and implicate PTX3 tetramers as the functional molecular units required for cumulus matrix organization and stabilization.

  6. Managing the Innovators for Exploration and Exploitation

    Directory of Open Access Journals (Sweden)

    C. Annique UN

    2007-09-01

    Full Text Available I analyze how to manage employees to achieve a balance between exploration and exploitation in large established firms. Previous studies suggest that, although firms need to undertake both exploration and exploitation simultaneously, this is difficult either because of the scarcity of resources or because of the incompatibility of these two processes. Proposed solutions have been ambidexterity, punctuated equilibrium or specialization. I suggest another method: managing employees. Specifically, I argue that using the so-called “innovative” system of human resource management practices, consisting of team-based incentive system, team-based job design, and job rotation, enables the firm to undertake exploration and exploitation simultaneously because it provides the psychological safety for people to explore new knowledge to make novel products and develops employees to have the perspective-taking capability that enables the integration of knowledge cross-functionally for efficiency. Using the so-called “traditional” system of human resource management practices, consisting of individual-based incentive system, individual-based job design, and no job rotation, has limited impact on either exploration or exploitation because it does not create the psychological safety for people to explore new knowledge and does not develop the perspective-taking capability needed for exploitation. Moreover, mixing practices from both systems is better than only using the traditional system in achieving exploration or exploitation, but less effective than only using the innovative system as the mix of practices can create inconsistent expectations on employees.

  7. 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.

  8. 1,2,3-Triazole Rings as a Disulfide Bond Mimetic in Chimeric AGRP-Melanocortin Peptides: Design, Synthesis, and Functional Characterization.

    Science.gov (United States)

    Tala, Srinivasa R; Singh, Anamika; Lensing, Cody J; Schnell, Sathya M; Freeman, Katie T; Rocca, James R; Haskell-Luevano, Carrie

    2018-05-16

    The melanocortin system is involved in the regulation of complex physiological functions, including energy and weight homeostasis, feeding behavior, inflammation, sexual function, pigmentation, and exocrine gland function. The five melanocortin receptors that belong to the superfamily of G protein-coupled receptors (GPCRs) are regulated by endogenously expressed agonists and antagonists. The aim of this study was to explore the potential of replacing the disulfide bridge in chimeric AGRP-melanocortin peptide Tyr-c[Cys-His-d-Phe-Arg-Trp-Asn-Ala-Phe-Cys]-Tyr-NH 2 (1) with 1,2,3-triazole moieties. A series of 1,2,3-triazole-bridged peptidomimetics were designed, synthesized, and pharmacologically evaluated at the mouse melanocortin receptors. The ligands possessed nanomolar to micromolar agonist cAMP signaling potency. A key finding was that the disulfide bond in peptide 1 can be replaced with the monotriazole ring with minimal effect on the functional activity at the melanocortin receptors. The 1,5-disubstituted triazole-bridged peptide 6 showed equipotent functional activity at the mMC3R and modest 5-fold decreased agonist potency at the mMC4R compared to those of 1. Interestingly, the 1,4- and 1,5-disubstituted isomers of the triazole ring resulted in different selectivities at the receptor subtypes, indicating subtle structural features that may be exploited in the generation of selective melanocortin ligands. Introducing cyclic and acyclic bis-triazole moieties into chimeric AGRP template 1 generally decreased agonist activity. These results will be useful for the further design of neuronal chemical probes for the melanocortin receptors as well as in other receptor systems.

  9. Conformational analysis by quantitative NOE measurements of the β-proton pairs across individual disulfide bonds in proteins

    International Nuclear Information System (INIS)

    Takeda, Mitsuhiro; Terauchi, Tsutomu; Kainosho, Masatsune

    2012-01-01

    NOEs between the β-protons of cysteine residues across disulfide bonds in proteins provide direct information on the connectivities and conformations of these important cross-links, which are otherwise difficult to investigate. With conventional [U- 13 C, 15 N]-proteins, however, fast spin diffusion processes mediated by strong dipolar interactions between geminal β-protons prohibit the quantitative measurements and thus the analyses of long-range NOEs across disulfide bonds. We describe a robust approach for alleviating such difficulties, by using proteins selectively labeled with an equimolar mixture of (2R, 3S)-[β- 13 C; α,β- 2 H 2 ] Cys and (2R, 3R)-[β- 13 C; α,β- 2 H 2 ] Cys, but otherwise fully deuterated. Since either one of the prochiral methylene protons, namely β2 (proS) or β3 (proR), is always replaced with a deuteron and no other protons remain in proteins prepared by this labeling scheme, all four of the expected NOEs for the β-protons across disulfide bonds could be measured without any spin diffusion interference, even with long mixing times. Therefore, the NOEs for the β2 and β3 pairs across each of the disulfide bonds could be observed at high sensitivity, even though they are 25% of the theoretical maximum for each pair. With the NOE information, the disulfide bond connectivities can be unambiguously established for proteins with multiple disulfide bonds. In addition, the conformations around disulfide bonds, namely χ 2 and χ 3 , can be determined based on the precise proton distances of the four β-proton pairs, by quantitative measurements of the NOEs across the disulfide bonds. The feasibility of this method is demonstrated for bovine pancreatic trypsin inhibitor, which has three disulfide bonds.

  10. Exploitation of Labour and Exploitation of Commodities: a “New Interpretation”

    OpenAIRE

    Veneziani, Roberto; Yoshihara, Naoki

    2011-01-01

    In the standard Okishio-Morishima approach, the existence of profits is proved to be equivalent to the exploitation of labour. Yet, it can also be proved that the existence of profits is equivalent to the ‘exploitation’ of any good. Labour and commodity exploitation are just different numerical representations of the productiveness of the economy. This paper presents an alternative approach to exploitation theory which is related to the New Interpretation (Duménil 1980; Foley 1982). In this a...

  11. Exploitation in International Paid Surrogacy Arrangements

    Science.gov (United States)

    Wilkinson, Stephen

    2015-01-01

    Abstract Many critics have suggested that international paid surrogacy is exploitative. Taking such concerns as its starting point, this article asks: (1) how defensible is the claim that international paid surrogacy is exploitative and what could be done to make it less exploitative? (2) In the light of the answer to (1), how strong is the case for prohibiting it? Exploitation could in principle be dealt with by improving surrogates' pay and conditions. However, doing so may exacerbate problems with consent. Foremost amongst these is the argument that surrogates from economically disadvantaged countries cannot validly consent because their background circumstances are coercive. Several versions of this argument are examined and I conclude that at least one has some merit. The article's overall conclusion is that while ethically there is something to be concerned about, paid surrogacy is in no worse a position than many other exploitative commercial transactions which take place against a backdrop of global inequality and constrained options, such as poorly‐paid and dangerous construction work. Hence, there is little reason to single surrogacy out for special condemnation. On a policy level, the case for prohibiting international commercial surrogacy is weak, despite legitimate concerns about consent and background poverty. PMID:27471338

  12. Exploitation in International Paid Surrogacy Arrangements.

    Science.gov (United States)

    Wilkinson, Stephen

    2016-05-01

    Many critics have suggested that international paid surrogacy is exploitative. Taking such concerns as its starting point, this article asks: (1) how defensible is the claim that international paid surrogacy is exploitative and what could be done to make it less exploitative? (2) In the light of the answer to (1), how strong is the case for prohibiting it? Exploitation could in principle be dealt with by improving surrogates' pay and conditions. However, doing so may exacerbate problems with consent. Foremost amongst these is the argument that surrogates from economically disadvantaged countries cannot validly consent because their background circumstances are coercive. Several versions of this argument are examined and I conclude that at least one has some merit. The article's overall conclusion is that while ethically there is something to be concerned about, paid surrogacy is in no worse a position than many other exploitative commercial transactions which take place against a backdrop of global inequality and constrained options, such as poorly-paid and dangerous construction work. Hence, there is little reason to single surrogacy out for special condemnation. On a policy level, the case for prohibiting international commercial surrogacy is weak, despite legitimate concerns about consent and background poverty.

  13. Evaluation of dynamic serum thiol/disulfide homeostasis in locally advanced and metastatic gastric cancer

    Directory of Open Access Journals (Sweden)

    Mutlu Hizal

    2018-04-01

    Full Text Available Background: Gastric cancer is one the most diagnosed cancer and the third leading cause of death from cancer worldwide. As an indicator of antioxidant capacity thiol/disulfide homeostasis regulates detoxification, cell signal mechanisms, apoptosis, transcription and antioxidant defense mechanisms. Disregulation of thiol/disulfide homeostasis identified in other cancer types by recent data. In this study, we aimed to evaluate the thiol/disulfide homeostasis in advanced gastric cancer patients. Methods: The patients who diagnosed with gastric cancer and healthy control subjects were included to study. Serum samples for the thiol-disulphide test were obtained at the time of diagnosis. Thiol-disulphide homeostasis tests were measured by the automated spectrophotometric method. Thiol-disulphide homeostasis was also measured according to clinical and laboratory features. Results: Thirty newly diagnosed advanced gastric adenocarcinoma patients and 28 healthy controls were enrolled in the study. The native thiol (NT and total thiol (TT levels of patients' group were significantly lower compared with controls (p = 0.001 and p < 0.001. In the CEA high (≥5.4 ng/ml group, DS/NT ratio were higher compared with CEA low (<5.4 ng/ml group (p = 0.024. In CA.19-9 high (≥28.3 kU/L group, both DS and DS/NT ratio were significantly higher compared with a CA19-9 low(<28.3 kU/L group (p < 0.05 both. The correlation between CEA and DS levels was also significant (p = 0.02. There was also a positive correlation between CEA levels and DS/NT ratio (p = 0.01. Conclusion: Derangements of thiol/disulfide homeostasis may have a role in gastric cancer pathogenesis and the higher level of oxidative stress may relate to extensive and aggressiveness of the advanced disease. The diagnostic and prognostic values of thiol/disulfide products need to identify with further studies. Keywords: Thiol, Disulfide, Oxidative stress, Gastric cancer, Metastatic

  14. Oil exploitation and the environmental Kuznets curve

    International Nuclear Information System (INIS)

    Esmaeili, Abdoulkarim; Abdollahzadeh, Negar

    2009-01-01

    This study refers to a panel estimation of an environmental Kuznets curve (EKC) for oil to determine the factors most affecting oil exploitation in 38 oil-producing countries during 1990-2000. Control variables such as oil reserves, oil price, population, political rights, and the Gini index were used to determine its contribution to the main EKC model. The empirical results fully support the existence of an EKC for oil exploitation. Furthermore, the result indicates that the proved oil reserves has a significant and positive role in oil production, but oil price and population do not significantly affect crude oil production. Also, increased freedoms and a better income distribution will reduce the rate of oil exploitation. Thus, policies aiming at enhancing democratic society and better income distribution would be more compatible with sustainability. (author)

  15. Oil exploitation and the environmental Kuznets curve

    Energy Technology Data Exchange (ETDEWEB)

    Esmaeili, Abdoulkarim; Abdollahzadeh, Negar [Department of Agricultural Economics, College of Agriculture, Shiraz University, Shiraz, Fars (Iran)

    2009-01-15

    This study refers to a panel estimation of an environmental Kuznets curve (EKC) for oil to determine the factors most affecting oil exploitation in 38 oil-producing countries during 1990-2000. Control variables such as oil reserves, oil price, population, political rights, and the Gini index were used to determine its contribution to the main EKC model. The empirical results fully support the existence of an EKC for oil exploitation. Furthermore, the result indicates that the proved oil reserves has a significant and positive role in oil production, but oil price and population do not significantly affect crude oil production. Also, increased freedoms and a better income distribution will reduce the rate of oil exploitation. Thus, policies aiming at enhancing democratic society and better income distribution would be more compatible with sustainability. (author)

  16. Rethinking exploitation: a process-centered account.

    Science.gov (United States)

    Jansen, Lynn A; Wall, Steven

    2013-12-01

    Exploitation has become an important topic in recent discussions of biomedical and research ethics. This is due in no small measure to the influence of Alan Wertheimer's path-breaking work on the subject. This paper presents some objections to Wertheimer's account of the concept. The objections attempt to show that his account places too much emphasis on outcome-based considerations and too little on process-based considerations. Building on these objections, the paper develops an alternative process-centered account of the concept. This alternative account of exploitation takes as its point of departure the broadly Kantian notion that it is wrong to use another as an instrument for the advancement of one's own ends. It sharpens this slippery notion and adds a number of refinements to it. The paper concludes by arguing that process-centered accounts of exploitation better illuminate the ethical challenges posed by research on human subjects than outcome-centered accounts.

  17. Shale gas exploitation: Status, problems and prospect

    Directory of Open Access Journals (Sweden)

    Shiqian Wang

    2018-02-01

    Full Text Available Over the past five years, great progress has been made in shale gas exploitation, which has become the most driving force for global gas output growth. Hydrocarbon extraction from shale helps drive the USA on the road to energy independence. Besides, shale oil & gas production has been kept in a sustained growth by continuous improvement in drilling efficiency and well productivity in the case of tumbling oil prices and rig counts. Shale gas reserves and production have been in a rapid growth in China owing to the Lower Paleozoic Wufeng and Longmaxi shale gas exploitation in the Sichuan Basin, which has become an important sector for the future increment of gas reserves and output in China. However, substantial progress has been made neither in non-marine shale gas exploitation as previously expected nor in the broad complicated tectonic areas in South China for which a considerable investment was made. Analysis of the basic situation and issues in domestic shale gas development shows that shale gas exploitation prospects are constrained by many problems in terms of resources endowment, horizontal well fracturing technology, etc. especially in non-marine shale deposits and complicated tectonic areas in South China where hot shales are widely distributed but geological structures are found severely deformed and over matured. Discussion on the prospects shows that the sustained and steady growth in shale gas reserves and production capacity in the coming years lies in the discovery and supersession of new shale plays in addition to Wufeng and Longmaxi shale plays, and that a technological breakthrough in ultra-high-pressure and ultra-deep (over 3500 m buried in the Sichuan Basin marine shale gas exploitation is the key and hope. Keywords: Shale gas, Exploitation, Marine facies, Hot shale, Resource endowment, Sichuan Basin, South China, Complicated tectonic area, Gas play

  18. Identification of Thioredoxin Disulfide Targets Using a Quantitative Proteomics Approach Based on Isotope-Coded Affinity Tags

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji

    2008-01-01

    Thioredoxin (Trx) is a ubiquitous protein disulfide reductase involved in a wide range of cellular redox processes. A large number of putative target proteins have been identified using proteomics approaches, but insight into target specificity at the molecular level is lacking since the reactivity...... of Trx toward individual disulfides has not been quantified. Here, a novel proteomics procedure is described for quantification of Trx-mediated target disulfide reduction based on thiol-specific differential labeling with the iodoacetamide-based isotope-coded affinity tag (ICAT) reagents. Briefly......, protein extract of embryos from germinated barley seeds was treated +/- Trx, and thiols released from target protein disulfides were irreversibly blocked with iodoacetamide. The remaining cysteine residues in the Trx-treated and the control (-Trx) samples were then chemically reduced and labeled...

  19. Disulfide bond effects on protein stability: designed variants of Cucurbita maxima trypsin inhibitor-V.

    Science.gov (United States)

    Zavodszky, M; Chen, C W; Huang, J K; Zolkiewski, M; Wen, L; Krishnamoorthi, R

    2001-01-01

    Attempts to increase protein stability by insertion of novel disulfide bonds have not always been successful. According to the two current models, cross-links enhance stability mainly through denatured state effects. We have investigated the effects of removal and addition of disulfide cross-links, protein flexibility in the vicinity of a cross-link, and disulfide loop size on the stability of Cucurbita maxima trypsin inhibitor-V (CMTI-V; 7 kD) by differential scanning calorimetry. CMTI-V offers the advantage of a large, flexible, and solvent-exposed loop not involved in extensive intra-molecular interactions. We have uncovered a negative correlation between retention time in hydrophobic column chromatography, a measure of protein hydrophobicity, and melting temperature (T(m)), an indicator of native state stabilization, for CMTI-V and its variants. In conjunction with the complete set of thermodynamic parameters of denaturation, this has led to the following deductions: (1) In the less stable, disulfide-removed C3S/C48S (Delta Delta G(d)(50 degrees C) = -4 kcal/mole; Delta T(m) = -22 degrees C), the native state is destabilized more than the denatured state; this also applies to the less-stable CMTI-V* (Delta Delta G(d)(50 degrees C) = -3 kcal/mole; Delta T(m) = -11 degrees C), in which the disulfide-containing loop is opened by specific hydrolysis of the Lys(44)-Asp(45) peptide bond; (2) In the less stable, disulfide-inserted E38C/W54C (Delta Delta G(d)(50 degrees C) = -1 kcal/mole; Delta T(m) = +2 degrees C), the denatured state is more stabilized than the native state; and (3) In the more stable, disulfide-engineered V42C/R52C (Delta Delta G(d)(50 degrees C) = +1 kcal/mole; Delta T(m) = +17 degrees C), the native state is more stabilized than the denatured state. These results show that a cross-link stabilizes both native and denatured states, and differential stabilization of the two states causes either loss or gain in protein stability. Removal of hydrogen

  20. Nicotinamidase/pyrazinamidase of Mycobacterium tuberculosis forms homo-dimers stabilized by disulfide bonds.

    Science.gov (United States)

    Rueda, Daniel; Sheen, Patricia; Gilman, Robert H; Bueno, Carlos; Santos, Marco; Pando-Robles, Victoria; Batista, Cesar V; Zimic, Mirko

    2014-12-01

    Recombinant wild-pyrazinamidase from H37Rv Mycobacterium tuberculosis was analyzed by gel electrophoresis under differential reducing conditions to evaluate its quaternary structure. PZAse was fractionated by size exclusion chromatography under non-reducing conditions. PZAse activity was measured and mass spectrometry analysis was performed to determine the identity of proteins by de novo sequencing and to determine the presence of disulfide bonds. This study confirmed that M. tuberculosis wild type PZAse was able to form homo-dimers in vitro. Homo-dimers showed a slightly lower specific PZAse activity compared to monomeric PZAse. PZAse dimers were dissociated into monomers in response to reducing conditions. Mass spectrometry analysis confirmed the existence of disulfide bonds (C72-C138 and C138-C138) stabilizing the quaternary structure of the PZAse homo-dimer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Determination of Disulfide Bond Connectivity of Cysteine-rich Peptide IpTx{sub a}

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chul Won; Kim, Jim Il [Chonnam National Univ., Gwangju (Korea, Republic of); Sato, Kazuki [Fukuoka Women' s Univ., Fukuoka (Japan)

    2013-06-15

    Cysteine-rich peptides stabilized by intramolecular disulfide bonds have often been isolated from venoms of microbes, animals and plants. These peptides typically have much higher stability and improved biopharmaceutical properties compared to their linear counterparts. Therefore the correct disulfide bond formation of small proteins and peptides has been extensively studied for a better understanding of their folding mechanism and achieving efficient generation of the naturally occurring biologically active product. Imperatoxin A (IpTx{sub a}), a peptide toxin containing 6 cysteine residues, was isolated from the venom of scorpion Pandinus imperator, selectively binds the ryanodine receptors and activates Ca{sup 2+} release from sarcoplasmic reticulum (SR). IpTx{sub a} increases the binding of ryanodine to ryanodine receptors (RyRs) and encourages reconstituted single channel to induce subconductance states.

  2. Regional cerebral blood flow after long-term exposure to carbon disulfide

    International Nuclear Information System (INIS)

    Aaserud, O.; Russell, D.; Nyberg-Hansen, R.; Joergensen, E.B.; Gjerstad, L.; Rootwelt, K.; Nakstad, P.; Hommeren, O.J.; Tvedt, B.

    1992-01-01

    Sixteen former rayon viscose workers were investigated four years after the exposure to carbon disulfide was discontinued. Median age was 58 years (range 43-65 years), median exposure time was 17 years (range 10-35 years). Encephalopathy was diagnosed in altogether 14 workers. To further explore pathophysiological mechanisms, cerebrovascular investigations were employed. Doppler ultrasound examination of the precerebral vessels in 15 workers showed a slight stenosis of the left internal carotid artery in one. Regional cerebral blood flow investigation (rCBF) with single photon emission computerized tomography (SPECT) with Xenon-133 gas was performed in 14. There was no significant difference from a control group. Regional side-to-side asymmetries beyond reference limits were demonstrated in eight workers. The abnormalities were modest, but may indicate a tendency toward focal blood flow disturbances in workers with long-term exposure to carbon disulfide. (au)

  3. Reduction-Triggered Transformation of Crosslinking Modules of Disulfide-Containing Micelles with Chemically Tunable Rates.

    Science.gov (United States)

    Deng, Zhengyu; Yuan, Shuai; Xu, Ronald X; Liang, Haojun; Liu, Shiyong

    2018-05-16

    A dilemma exists between the circulation stability and cargo release/mass diffusion at desired sites for designing delivery nanocarriers and in vivo nanoreactors. We herein report disulfide-crosslinked (DCL) micelles exhibiting reduction-triggered switching of crosslinking modules and synchronized hydrophobic-to-hydrophilic transition. Tumor cell-targeted DCL micelles undergo cytoplasmic milieu-triggered disulfide cleavage and cascade self-immolative decaging reactions at chemically adjustable rates, generating primary amine moieties. Extensive amidation reactions with neighboring ester moieties then occur due to high local concentrations and suppression of apparent amine pKa within hydrophobic cores, leading to the transformation of crosslinking modules and formation of tracelessly crosslinked (TCL) micelles with hydrophilic cores inside live cells. We further integrate this design principle with theranostic nanocarriers for selective intracellular drug transport guided by enhanced magnetic resonance (MR) imaging performance. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Rethinking Cysteine Protective Groups: S-Alkylsulfonyl-l-Cysteines for Chemoselective Disulfide Formation.

    Science.gov (United States)

    Schäfer, Olga; Huesmann, David; Muhl, Christian; Barz, Matthias

    2016-12-12

    The ability to reversibly cross-link proteins and peptides grants the amino acid cysteine its unique role in nature as well as in peptide chemistry. We report a novel class of S-alkylsulfonyl-l-cysteines and N-carboxy anhydrides (NCA) thereof for peptide synthesis. The S-alkylsulfonyl group is stable against amines and thus enables its use under Fmoc chemistry conditions and the controlled polymerization of the corresponding NCAs yielding well-defined homo- as well as block co-polymers. Yet, thiols react immediately with the S-alkylsulfonyl group forming asymmetric disulfides. Therefore, we introduce the first reactive cysteine derivative for efficient and chemoselective disulfide formation in synthetic polypeptides, thus bypassing additional protective group cleavage steps. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. A Protein Disulfide Isomerase Gene Fusion Expression System That Increases the Extracellular Productivity of Bacillus brevis

    Science.gov (United States)

    Kajino, Tsutomu; Ohto, Chikara; Muramatsu, Masayoshi; Obata, Shusei; Udaka, Shigezo; Yamada, Yukio; Takahashi, Haruo

    2000-01-01

    We have developed a versatile Bacillus brevis expression and secretion system based on the use of fungal protein disulfide isomerase (PDI) as a gene fusion partner. Fusion with PDI increased the extracellular production of heterologous proteins (light chain of immunoglobulin G, 8-fold; geranylgeranyl pyrophosphate synthase, 12-fold). Linkage to PDI prevented the aggregation of the secreted proteins, resulting in high-level accumulation of fusion proteins in soluble and biologically active forms. We also show that the disulfide isomerase activity of PDI in a fusion protein is responsible for the suppression of the aggregation of the protein with intradisulfide, whereas aggregation of the protein without intradisulfide was prevented even when the protein was fused to a mutant PDI whose two active sites were disrupted, suggesting that another PDI function, such as chaperone-like activity, synergistically prevented the aggregation of heterologous proteins in the PDI fusion expression system. PMID:10653729

  6. Selective removal of heavy metal ions by disulfide linked polymer networks

    DEFF Research Database (Denmark)

    Ko, Dongah; Sung Lee, Joo; Patel, Hasmukh A.

    2017-01-01

    Heavy metal contaminated surface water is one of the oldest pollution problems, which is critical to ecosystems and human health. We devised disulfide linked polymer networks and employed as a sorbent for removing heavy metal ions from contaminated water. Although the polymer network material has...... a moderate surface area, it demonstrated cadmium removal efficiency equivalent to highly porous activated carbon while it showed 16 times faster sorption kinetics compared to activated carbon, owing to the high affinity of cadmium towards disulfide and thiol functionality in the polymer network. The metal...... sorption mechanism on polymer network was studied by sorption kinetics, effect of pH, and metal complexation. We observed that the metal ions―copper, cadmium, and zinc showed high binding affinity in polymer network, even in the presence of competing cations like calcium in water....

  7. Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Hotta, Kinya; Keegan, Ronan M.; Ranganathan, Soumya; Fang, Minyi; Bibby, Jaclyn; Winn, Martyn D.; Sato, Michio; Lian, Mingzhu; Watanabe, Kenji; Rigden, Daniel J.; Kim, Chu-Young (Liverpool); (Daresbury); (NU Singapore); (Shizuoka); (RAL)

    2013-12-02

    Echinomycin is a nonribosomal depsipeptide natural product with a range of interesting bioactivities that make it an important target for drug discovery and development. It contains a thioacetal bridge, a unique chemical motif derived from the disulfide bond of its precursor antibiotic triostin A by the action of an S-adenosyl-L-methionine-dependent methyltransferase, Ecm18. The crystal structure of Ecm18 in complex with its reaction products S-adenosyl-L-homocysteine and echinomycin was determined at 1.50 Å resolution. Phasing was achieved using a new molecular replacement package called AMPLE, which automatically derives search models from structure predictions based on ab initio protein modelling. Structural analysis indicates that a combination of proximity effects, medium effects, and catalysis by strain drives the unique transformation of the disulfide bond into the thioacetal linkage.

  8. MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis.

    Science.gov (United States)

    Liu, Shuzhen; Liu, Hua; Johnston, Andrea; Hanna-Addams, Sarah; Reynoso, Eduardo; Xiang, Yougui; Wang, Zhigao

    2017-09-05

    Mixed-lineage kinase domain-like protein (MLKL) is essential for TNF-α-induced necroptosis. How MLKL promotes cell death is still under debate. Here we report that MLKL forms SDS-resistant, disulfide bond-dependent polymers during necroptosis in both human and mouse cells. MLKL polymers are independent of receptor-interacting protein kinase 1 and 3 (RIPK1/RIPK3) fibers. Large MLKL polymers are more than 2 million Da and are resistant to proteinase K digestion. MLKL polymers are fibers 5 nm in diameter under electron microscopy. Furthermore, the recombinant N-terminal domain of MLKL forms amyloid-like fibers and binds Congo red dye. MLKL mutants that cannot form polymers also fail to induce necroptosis efficiently. Finally, the compound necrosulfonamide conjugates cysteine 86 of human MLKL and blocks MLKL polymer formation and subsequent cell death. These results demonstrate that disulfide bond-dependent, amyloid-like MLKL polymers are necessary and sufficient to induce necroptosis.

  9. Autonomic healable waterborne organic-inorganic polyurethane hybrids based on aromatic disulfide moieties

    Directory of Open Access Journals (Sweden)

    R. H. Aguirresarobe

    2017-04-01

    Full Text Available Aromatic disulfide dynamic structures were incorporated as chain extenders in waterborne organic-inorganic polyurethane hybrids in order to provide autonomic healable characteristics. The synthesis was carried out following the acetone process methodology and the influence of the introduction of the healing agents in the polymer dispersion stability was analyzed. After the crosslinking process at room temperature, organic-inorganic hybrid films, which presented autonomic healing characteristics, were obtained. These features were evaluated by means of stress-strain tests and the films showed repetitive healing abilities. Thus, the optimum healing time at room temperature (25 °C as well as the influence of different parameters in the healing efficiency, such the aromatic disulfide concentration or the physical properties of the polymer matrix were analyzed.

  10. Photo-responsive liquid crystalline epoxy networks with exchangeable disulfide bonds

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuzhan [Washington State Univ., Pullman, WA (United States); Zhang, Yuehong [Washington State Univ., Pullman, WA (United States); Rios, Orlando [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Keum, Jong K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kessler, Michael R. [Washington State Univ., Pullman, WA (United States); North Dakota State Univ., Fargo, ND (United States)

    2017-07-27

    The increasing demand for intelligent materials has driven the development of polymers with a variety of functionalities. However, combining multiple functionalities within one polymer is still challenging because of the difficulties encountered in coordinating different functional building blocks during fabrication. In this work, we demonstrate the fabrication of a multifunctional liquid crystalline epoxy network (LCEN) using the combination of thermotropic liquid crystals, photo-responsive azobenzene molecules, and exchangeable disulfide bonds. In addition to shape memory behavior enabled by the reversible liquid crystalline phase transition and photo-induced bending behavior resulting from the photo-responsive azobenzene molecules, the introduction of dynamic disulfide bonds into the LCEN resulted in a structurally dynamic network, allowing the reshaping, repairing, and recycling of the material.

  11. Enhancing the Thermal Resistance of a Novel Acidobacteria-Derived Phytase by Engineering of Disulfide Bridges.

    Science.gov (United States)

    Tan, Hao; Miao, Renyun; Liu, Tianhai; Cao, Xuelian; Wu, Xiang; Xie, Liyuan; Huang, Zhongqian; Peng, Weihong; Gan, Bingcheng

    2016-10-28

    A novel phytase of Acidobacteria was identified from a soil metagenome, cloned, overexpressed, and purified. It has low sequence similarity (phytases. At the optimum pH (2.5), the phytase shows an activity level of 1,792 μmol/min/mg at physiological temperature (37°C) and could retain 92% residual activity after 30 min, indicating the phytase is acidophilic and acidostable. However the phytase shows poor stability at high temperatures. To improve its thermal resistance, the enzyme was redesigned using Disulfide by Design 2.0, introducing four additional disulfide bridges. The half-life time of the engineered phytase at 60°C and 80°C, respectively, is 3.0× and 2.8× longer than the wild-type, and its activity and acidostability are not significantly affected.

  12. Disruption of reducing pathways is not essential for efficient disulfide bond formation in the cytoplasm of E. coli

    Directory of Open Access Journals (Sweden)

    Hatahet Feras

    2010-09-01

    Full Text Available Abstract Background The formation of native disulfide bonds is a complex and essential post-translational modification for many proteins. The large scale production of these proteins can be difficult and depends on targeting the protein to a compartment in which disulfide bond formation naturally occurs, usually the endoplasmic reticulum of eukaryotes or the periplasm of prokaryotes. It is currently thought to be impossible to produce large amounts of disulfide bond containing protein in the cytoplasm of wild-type bacteria such as E. coli due to the presence of multiple pathways for their reduction. Results Here we show that the introduction of Erv1p, a sulfhydryl oxidase and FAD-dependent catalyst of disulfide bond formation found in the inter membrane space of mitochondria, allows the efficient formation of native disulfide bonds in heterologously expressed proteins in the cytoplasm of E. coli even without the disruption of genes involved in disulfide bond reduction, for example trxB and/or gor. Indeed yields of active disulfide bonded proteins were higher in BL21 (DE3 pLysSRARE, an E. coli strain with the reducing pathways intact, than in the commercial Δgor ΔtrxB strain rosetta-gami upon co-expression of Erv1p. Conclusions Our results refute the current paradigm in the field that disruption of at least one of the reducing pathways is essential for the efficient production of disulfide bond containing proteins in the cytoplasm of E. coli and open up new possibilities for the use of E. coli as a microbial cell factory.

  13. Assistive Technology

    Science.gov (United States)

    ... Page Resize Text Printer Friendly Online Chat Assistive Technology Assistive technology (AT) is any service or tool that helps ... be difficult or impossible. For older adults, such technology may be a walker to improve mobility or ...

  14. Investigation of the deposition and thermal behavior of striped phases of unsymmetric disulfide self-assembled monolayers on Au(111): The case of 11-hydroxyundecyl decyl disulfide

    Energy Technology Data Exchange (ETDEWEB)

    Albayrak, Erol [Department of Materials and Metallurgical Engineering, Ahi Evran University, Kırşehir 40000 (Turkey); Karabuga, Semistan [Department of Chemistry, Kahramanmaraş Sütçü İmam University, Kahramanmaraş 46030 (Turkey); Bracco, Gianangelo [CNR-IMEM and Department of Physics, University of Genoa, via Dodecaneso 33, Genoa 16146 (Italy); Danışman, M. Fatih, E-mail: danisman@metu.edu.tr [Department of Chemistry, Middle East Technical University, Ankara 06800 (Turkey)

    2015-01-07

    Self-assembled monolayers (SAMs) of unsymmetric disulfides on Au(111) are used to form mixed SAMs that can be utilized in many applications. Here, we have studied 11-hydroxyundecyl decyl disulfide (CH{sub 3}–(CH{sub 2}){sub 9}–S–S–(CH{sub 2}){sub 11}–OH, HDD) SAMs produced by supersonic molecular beam deposition and characterized by He diffraction. The film growth was monitored at different temperatures up to a coverage which corresponds to a full lying down phase and the diffraction analysis shows that below 250 K the phase is different from the phase measured above 300 K. During the annealing of the film, two phase transitions were observed, at 250 K and 350 K. The overall data suggest that the former is related to an irreversible phase separation of HDD above 250 K to decanethiolate (–S–(CH{sub 2}){sub 9}–CH{sub 3}, DTT) and hydroxyundecylthiolate (–S–(CH{sub 2}){sub 11}–OH, MUDT), while the latter to a reversible melting of the film. Above 450 K, the specular intensity shows an increase related to film desorption and different chemisorbed states were observed with energies in the same range as observed for decanethiol (H–S–(CH{sub 2}){sub 9}–CH{sub 3}, DT) and mercaptoundecanol (H–S–(CH{sub 2}){sub 11}–OH, MUD) SAMs.

  15. Selective disulfide reduction for labeling and enhancement of Fab antibody fragments.

    Science.gov (United States)

    Kirley, Terence L; Greis, Kenneth D; Norman, Andrew B

    2016-11-25

    Many methods have been developed for chemical labeling and enhancement of the properties of antibodies and their common fragments, including the Fab and F(ab') 2 fragments. Somewhat selective reduction of some antibody disulfide bonds has been previously achieved, yielding antibodies and antibody fragments that can be labeled at defined sites, enhancing their utility and properties. Selective reduction of the two hinge disulfide bonds present in F(ab') 2 fragments using mild reduction has been useful. However, such reduction is often not quantitative and results in the reduction of multiple disulfide bonds, and therefore subsequent multiple labeling or conjugation sites are neither homogenous nor stoichiometric. Here, a simple and efficient selective reduction of the single disulfide bond linking the partial heavy chain and the intact light chain which compose the Fab fragment is accomplished utilizing tris(2-carboxyethyl)phosphine (TCEP) immobilized on agarose beads. The resultant reduced cysteine residues were labeled with several cysteine-selective fluorescent reagents, as well as by cysteine-directed PEGylation. These two cysteine residues can also be re-ligated by means of a bifunctional cysteine cross-linking agent, dibromobimane, thereby both restoring a covalent linkage between the heavy and light chains at this site, far removed from the antigen binding site, and also introducing a fluorescent probe. There are many other research and clinical uses for these selectively partially reduced Fab fragments, including biotinylation, toxin and drug conjugation, and incorporation of radioisotopes, and this technique enables simple generation of very useful Fab fragment derivatives with many potential applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. {sup 13}C-NMR studies on disulfide bond isomerization in bovine pancreatic trypsin inhibitor (BPTI)

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Mitsuhiro [Kumamoto University, Department of Structural BioImaging, Faculty of Life Sciences (Japan); Miyanoiri, Yohei [Nagoya University, Structural Biology Research Center, Graduate School of Science (Japan); Terauchi, Tsutomu [Tokyo Metropolitan University, Graduate School of Science and Engineering (Japan); Kainosho, Masatsune, E-mail: kainosho@tmu.ac.jp [Nagoya University, Structural Biology Research Center, Graduate School of Science (Japan)

    2016-09-15

    Conformational isomerization of disulfide bonds is associated with the dynamics and thus the functional aspects of proteins. However, our understanding of the isomerization is limited by experimental difficulties in probing it. We explored the disulfide conformational isomerization of the Cys14–Cys38 disulfide bond in bovine pancreatic trypsin inhibitor (BPTI), by performing an NMR line-shape analysis of its Cys carbon peaks. In this approach, 1D {sup 13}C spectra were recorded at small temperature intervals for BPTI samples selectively labeled with site-specifically {sup 13}C-enriched Cys, and the recorded peaks were displayed in the order of the temperature after the spectral scales were normalized to a carbon peak. Over the profile of the line-shape, exchange broadening that altered with temperature was manifested for the carbon peaks of Cys14 and Cys38. The Cys14–Cys38 disulfide bond reportedly exists in equilibrium between a high-populated (M) and two low-populated states (m{sub c14} and m{sub c38}). Consistent with the three-site exchange model, biphasic exchange broadening arising from the two processes was observed for the peak of the Cys14 α-carbon. As the exchange broadening is maximized when the exchange rate equals the chemical shift difference in Hz between equilibrating sites, semi-quantitative information that was useful for establishing conditions for {sup 13}C relaxation dispersion experiments was obtained through the carbon line-shape profile. With respect to the m{sub c38} isomerization, the {sup 1}H-{sup 13}C signals at the β-position of the minor state were resolved from the major peaks and detected by exchange experiments at a low temperature.

  17. Modified electrophoretic and digestion conditions allow a simplified mass spectrometric evaluation of disulfide bonds

    Czech Academy of Sciences Publication Activity Database

    Pompach, Petr; Man, Petr; Kavan, Daniel; Hofbauerová, Kateřina; Kumar, Vinay; Bezouška, Karel; Havlíček, Vladimír; Novák, Petr

    2009-01-01

    Roč. 44, č. 11 (2009), s. 1571-1578 ISSN 1076-5174 R&D Projects: GA AV ČR KJB400200501; GA AV ČR IAA5020403; GA AV ČR KJB500200612; GA MŠk LC545; GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50200510 Keywords : disulfide bond * cystamine * gel electrophoresis Subject RIV: CE - Biochemistry Impact factor: 3.411, year: 2009

  18. Photochemical synthesis of ultrafine organosilicon particles from trimethyl(2-propynyloxy)silane and carbon disulfide

    Czech Academy of Sciences Publication Activity Database

    Morita, H.; Nozawa, R.; Bastl, Zdeněk; Šubrt, Jan; Pola, Josef

    2006-01-01

    Roč. 179, 1-2 (2006), s. 142-148 ISSN 1010-6030 Grant - others:MEXT(JP) 767/15085203 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z40320502; CEZ:AV0Z40720504 Keywords : ultrafine particles * photo-polymerization * trimethyl(2-propynyloxy)silane * carbon disulfide Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.098, year: 2006

  19. Role of protein disulfide isomerase and other thiol-reactive proteins in HIV-1 envelope protein-mediated fusion

    International Nuclear Information System (INIS)

    Ou Wu; Silver, Jonathan

    2006-01-01

    Cell-surface protein disulfide isomerase (PDI) has been proposed to promote disulfide bond rearrangements in HIV-1 envelope protein (Env) that accompany Env-mediated fusion. We evaluated the role of PDI in ways that have not been previously tested by downregulating PDI with siRNA and by overexpressing wild-type or variant forms of PDI in transiently and stably transfected cells. These manipulations, as well as treatment with anti-PDI antibodies, had only small effects on infection or cell fusion mediated by NL4-3 or AD8 strains of HIV-1. However, the cell-surface thiol-reactive reagent 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB) had a much stronger inhibitory effect in our system, suggesting that cell-surface thiol-containing molecules other than PDI, acting alone or in concert, have a greater effect than PDI on HIV-1 Env-mediated fusion. We evaluated one such candidate, thioredoxin, a PDI family member reported to reduce a labile disulfide bond in CD4. We found that the ability of thioredoxin to reduce the disulfide bond in CD4 is enhanced in the presence of HIV-1 Env gp120 and that thioredoxin also reduces disulfide bonds in gp120 directly in the absence of CD4. We discuss the implications of these observations for identification of molecules involved in disulfide rearrangements in Env during fusion

  20. Thiol/Disulfide system plays a crucial role in redox protection in the acidophilic iron-oxidizing bacterium Leptospirillum ferriphilum.

    Directory of Open Access Journals (Sweden)

    Javiera Norambuena

    Full Text Available Thiol/disulfide systems are involved in the maintenance of the redox status of proteins and other molecules that contain thiol/disulfide groups. Leptospirillum ferriphilum DSM14647, an acidophilic bacterium that uses Fe(2+ as electron donor, and withstands very high concentrations of iron and other redox active metals, is a good model to study how acidophiles preserve the thiol/disulfide balance. We studied the composition of thiol/disulfide systems and their role in the oxidative stress response in this extremophile bacterium. Bioinformatic analysis using genomic data and enzymatic assays using protein extracts from cells grown under oxidative stress revealed that the major thiol/disulfide system from L. ferriphilum are a cytoplasmic thioredoxin system (composed by thioredoxins Trx and thioredoxin reductase TR, periplasmic thiol oxidation system (DsbA/DsbB and a c-type cytochrome maturation system (DsbD/DsbE. Upon exposure of L. ferriphilum to reactive oxygen species (ROS-generating compounds, transcriptional activation of the genes encoding Trxs and the TR enzyme, which results in an increase of the corresponding activity, was observed. Altogether these data suggest that the thioredoxin-based thiol/disulfide system plays an important role in redox protection of L. ferriphilum favoring the survival of this microorganism under extreme environmental oxidative conditions.

  1. An analytic study of molybdenum disulfide nanofluids using the modern approach of Atangana-Baleanu fractional derivatives

    Science.gov (United States)

    Ali Abro, Kashif; Hussain, Mukkarum; Mahmood Baig, Mirza

    2017-10-01

    The significance of the different shapes of molybdenum disulfide nanoparticles contained in ethylene glycol has recently attracted researchers, because of the numerical or experimental analyses on the shapes of molybdenum disulfide and the lack of fractionalized analytic approaches. This work is dedicated to examining the shape impacts of molybdenum disulfide nanofluids in the mixed convection flow with magnetic field and a porous medium. Ethylene glycol is chosen as the base fluid in which molybdenum disulfide nanoparticles are suspended. Non-spherically shaped molybdenum disulfide nanoparticles, namely, platelet, blade, cylinder and brick, are utilized in this analysis. The modeling of the problem is characterized by employing the modern approach of Atangana-Baleanu fractional derivatives and the governing partial differential equations are solved via Laplace transforms with inversion. Solutions are obtained for temperature distribution and velocity field and expressed in terms of compact form of M-function, Mba(T) . In the end, a figures are drawn to compare the different non-spherically shaped molybdenum disulfide nanoparticles. Furthermore, the Atangana-Baleanu fractional derivatives model has been compared with ordinary derivatives models and discussed graphically by setting various rheological parameters.

  2. Assisted Living

    Science.gov (United States)

    ... it, too. Back to top What is the Cost for Assisted Living? Although assisted living costs less than nursing home ... Primarily, older persons or their families pay the cost of assisted living. Some health and long-term care insurance policies ...

  3. On the dynamics of exploited fish populations

    National Research Council Canada - National Science Library

    Beverton, R. J. H; Holt, Sidney J

    1993-01-01

    ...-brooding cichlids, and viviparity in many sharks and toothcarps. Moreover, fish are of considerable importance to the survival of the human species in the form of nutritious, delicious and diverse food. Rational exploitation and management of our global stocks of fishes must rely upon a detailed and precise insight of their biology. The...

  4. Child Exploitation: Some Pieces of the Puzzle.

    Science.gov (United States)

    Rohlader, Dorothy

    The report addresses the status in North Carolina and in the nation of child exploitation. Legislative and judicial backgrounds of child pornography and child prostitution are reviewed, and difficulties in obtaining statistical data are noted. Law enforcement issues in pornography are cited, and suggestions for further legislation regarding child…

  5. Exploiting a natural auxotrophy for genetic selection.

    Science.gov (United States)

    Ramage, Elizabeth; Gallagher, Larry; Manoil, Colin

    2012-08-01

    We exploited the natural histidine auxotrophy of Francisella species to develop hisD (encodes histidinol dehydrogenase) as a positive selection marker. A shuttle plasmid (pBR103) carrying Escherichia coli hisD and designed for cloning of PCR fragments replicated in both attenuated and highly virulent Francisella strains. During this work, we formulated a simplified defined growth medium for Francisella novicida.

  6. Growth, Mortality and Exploitation Rates of Sarotherodon ...

    African Journals Online (AJOL)

    Evans

    ABSTRACT. Sarotherodon melanotheron population of Dominli Lagoon in the Western Region of Ghana was studied for its growth and mortality parameters as well as exploitation rate. The study generally aimed at providing basic information necessary for the assessment and management of the fish stock in the lagoon.

  7. Economic factors of vulnerability trade and exploitation

    NARCIS (Netherlands)

    Allodi, L.

    2017-01-01

    Cybercrime markets support the development and diffusion of new attack technologies, vulnerability exploits, and malware. Whereas the revenue streams of cyber attackers have been studied multiple times in the literature, no quantitative account currently exists on the economics of attack acquisition

  8. Exploiting indigenous knowledge in the environmental conservation ...

    African Journals Online (AJOL)

    ... of agriculture and reared livestock (especially goats). Over several years, they developed sustainable and effective exploitation mechanisms of the existing biodiversity resources to satisfy their individual needs and those of their societies in general. Journal of Language, Technology and Entrepreneurship in Africa Vol.

  9. Exploiting citation contexts for physics retrieval

    DEFF Research Database (Denmark)

    Dabrowska, Anna; Larsen, Birger

    2015-01-01

    The text surrounding citations within scientific papers may contain terms that usefully describe cited documents and can benefit retrieval. We present a preliminary study that investigates appending ci- tation contexts from citing documents to cited documents in the iSearch test collection. We ex...... in a large collection of physics papers, paving the way for future research that exploits citation contexts for retrieval....

  10. Photoinduced Cross-Linking of Dynamic Poly(disulfide) Films via Thiol Oxidative Coupling.

    Science.gov (United States)

    Feillée, Noémi; Chemtob, Abraham; Ley, Christian; Croutxé-Barghorn, Céline; Allonas, Xavier; Ponche, Arnaud; Le Nouen, Didier; Majjad, Hicham; Jacomine, Léandro

    2016-01-01

    Initially developed as an elastomer with an excellent record of barrier and chemical resistance properties, poly(disulfide) has experienced a revival linked to the dynamic nature of the S-S covalent bond. A novel photobase-catalyzed oxidative polymerization of multifunctional thiols to poly(disulfide) network is reported. Based solely on air oxidation, the single-step process is triggered by the photodecarboxylation of a xanthone acetic acid liberating a strong bicyclic guanidine base. Starting with a 1 μm thick film based on trithiol poly(ethylene oxide) oligomer, the UV-mediated oxidation of thiols to disulfides occurs in a matter of minutes both selectively, i.e., without overoxidation, and quantitatively as assessed by a range of spectroscopic techniques. Thiolate formation and film thickness determine the reaction rates and yield. Spatial control of the photopolymerization serves to generate robust micropatterns, while the reductive cleavage of S-S bridges allows the recycling of 40% of the initial thiol groups. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Abiotic synthesis of organic compounds from carbon disulfide under hydrothermal conditions.

    Science.gov (United States)

    Rushdi, Ahmed I; Simoneit, Bernd R T

    2005-12-01

    Abiotic formation of organic compounds under hydrothermal conditions is of interest to bio, geo-, and cosmochemists. Oceanic sulfur-rich hydrothermal systems have been proposed as settings for the abiotic synthesis of organic compounds. Carbon disulfide is a common component of magmatic and hot spring gases, and is present in marine and terrestrial hydrothermal systems. Thus, its reactivity should be considered as another carbon source in addition to carbon dioxide in reductive aqueous thermosynthesis. We have examined the formation of organic compounds in aqueous solutions of carbon disulfide and oxalic acid at 175 degrees C for 5 and 72 h. The synthesis products from carbon disulfide in acidic aqueous solutions yielded a series of organic sulfur compounds. The major compounds after 5 h of reaction included dimethyl polysulfides (54.5%), methyl perthioacetate (27.6%), dimethyl trithiocarbonate (6.8%), trithianes (2.7%), hexathiepane (1.4%), trithiolanes (0.8%), and trithiacycloheptanes (0.3%). The main compounds after 72 h of reaction consisted of trithiacycloheptanes (39.4%), pentathiepane (11.6%), tetrathiocyclooctanes (11.5%), trithiolanes (10.6%), tetrathianes (4.4%), trithianes (1.2%), dimethyl trisulfide (1.1%), and numerous minor compounds. It is concluded that the abiotic formation of aliphatic straight-chain and cyclic polysulfides is possible under hydrothermal conditions and warrants further studies.

  12. Resolution of Disulfide Heterogeneity in Nogo Receptor 1 Fusion Proteins by Molecular Engineering

    Energy Technology Data Exchange (ETDEWEB)

    P Weinreb; D Wen; F Qian; C Wildes; E Garber; L Walus; M Jung; J Wang; J Relton; et al.

    2011-12-31

    NgRI (Nogo-66 receptor) is part of a signalling complex that inhibits axon regeneration in the central nervous system. Truncated soluble versions of NgRI have been used successfully to promote axon regeneration in animal models of spinal-cord injury, raising interest in this protein as a potential therapeutic target. The LRR (leucine-rich repeat) regions in NgRI are flanked by N- and C-terminal disulfide-containing 'cap' domains (LRRNT and LRRCT respectively). In the present work we show that, although functionally active, the NgRI(310)-Fc fusion protein contains mislinked and heterogeneous disulfide patterns in the LRRCT domain, and we report the generation of a series of variant molecules specifically designed to prevent this heterogeneity. Using these variants we explored the effects of modifying the NgRI truncation site or the spacing between the NgRI and Fc domains, or replacing cysteines within the NgRI or IgG hinge regions. One variant, which incorporates replacements of Cys{sup 266} and Cys{sup 309} with alanine residues, completely eliminated disulfide scrambling while maintaining functional in vitro and in vivo efficacy. This modified NgRI-Fc molecule represents a significantly improved candidate for further pharmaceutical development, and may serve as a useful model for the optimization of other IgG fusion proteins made from LRR proteins.

  13. Metallic and highly conducting two-dimensional atomic arrays of sulfur enabled by molybdenum disulfide nanotemplate

    Science.gov (United States)

    Zhu, Shuze; Geng, Xiumei; Han, Yang; Benamara, Mourad; Chen, Liao; Li, Jingxiao; Bilgin, Ismail; Zhu, Hongli

    2017-10-01

    Element sulfur in nature is an insulating solid. While it has been tested that one-dimensional sulfur chain is metallic and conducting, the investigation on two-dimensional sulfur remains elusive. We report that molybdenum disulfide layers are able to serve as the nanotemplate to facilitate the formation of two-dimensional sulfur. Density functional theory calculations suggest that confined in-between layers of molybdenum disulfide, sulfur atoms are able to form two-dimensional triangular arrays that are highly metallic. As a result, these arrays contribute to the high conductivity and metallic phase of the hybrid structures of molybdenum disulfide layers and two-dimensional sulfur arrays. The experimentally measured conductivity of such hybrid structures reaches up to 223 S/m. Multiple experimental results, including X-ray photoelectron spectroscopy (XPS), transition electron microscope (TEM), selected area electron diffraction (SAED), agree with the computational insights. Due to the excellent conductivity, the current density is linearly proportional to the scan rate until 30,000 mV s-1 without the attendance of conductive additives. Using such hybrid structures as electrode, the two-electrode supercapacitor cells yield a power density of 106 Wh kg-1 and energy density 47.5 Wh kg-1 in ionic liquid electrolytes. Our findings offer new insights into using two-dimensional materials and their Van der Waals heterostructures as nanotemplates to pattern foreign atoms for unprecedented material properties.

  14. Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica.

    Science.gov (United States)

    Nadrah, Peter; Maver, Uroš; Jemec, Anita; Tišler, Tatjana; Bele, Marjan; Dražić, Goran; Benčina, Mojca; Pintar, Albin; Planinšek, Odon; Gaberšček, Miran

    2013-05-01

    With the advancement of drug delivery systems based on mesoporous silica nanoparticles (MSNs), a simple and efficient method regulating the drug release kinetics is needed. We developed redox-responsive release systems with three levels of hindrance around the disulfide bond. A model drug (rhodamine B dye) was loaded into MSNs' mesoporous voids. The pore opening was capped with β-cyclodextrin in order to prevent leakage of drug. Indeed, in absence of a reducing agent the systems exhibited little leakage, while the addition of dithiothreitol cleaved the disulfide bonds and enabled the release of cargo. The release rate and the amount of released dye were tuned by the level of hindrance around disulfide bonds, with the increased hindrance causing a decrease in the release rate as well as in the amount of released drug. Thus, we demonstrated the ability of the present mesoporous systems to intrinsically control the release rate and the amount of the released cargo by only minor structural variations. Furthermore, an in vivo experiment on zebrafish confirmed that the present model delivery system is nonteratogenic.

  15. Dissemination and Exploitation: Project Goals beyond Science

    Science.gov (United States)

    Hamann, Kristin; Reitz, Anja

    2017-04-01

    Dissemination and Exploitation are essential parts of public funded projects. In Horizon 2020 a plan for the exploitation and dissemination of results (PEDR) is a requirement. The plan should contain a clear vision on the objectives of the project in relation to actions for dissemination and potential exploitation of the project results. The actions follow the basic idea to spread the knowledge and results gathered within the project and face the challenge of how to bring the results into potentially relevant policy circle and how they impact the market. The plan follows the purpose to assess the impact of the project and to address various target groups who are interested in the project results. Simply put, dissemination concentrates on the transfer of knowledge and exploitation on the commercialization of the project. Beyond the question of the measurability of project`s impact, strategies within science marketing can serve purposes beyond internal and external communication. Accordingly, project managers are facing the challenge to implement a dissemination and exploitation strategy that ideally supports the identification of all partners with the project and matches the current discourse of the project`s content within the society, politics and economy. A consolidated plan might unite all projects partners under a central idea and supports the identification with the project beyond the individual research questions. Which applications, strategies and methods can be used to bring forward a PEDR that accompanies a project successfully and allows a comprehensive assessment of the project afterwards? Which hurdles might project managers experience in the dissemination process and which tasks should be fulfilled by the project manager?

  16. Trolling may intensify exploitation in crappie fisheries

    Science.gov (United States)

    Meals, K. O.; Dunn, A. W.; Miranda, Leandro E.

    2012-01-01

    In some parts of the USA, anglers targeting crappies Pomoxis spp. are transitioning from mostly stationary angling with a single pole around submerged structures to using multiple poles while drifting with the wind or under power. This shift in fishing methods could result in a change in catch efficiency, possibly increasing exploitation rates to levels that would be of concern to managers. We studied the catch statistics of anglers fishing while trolling with multiple poles (trollers) and those fishing with single poles (polers) in Mississippi reservoirs. Specifically, we tested whether (1) various catch statistics differed between trollers and polers, (2) catch rates of trollers were related to the number of poles fished, and (3) trollers could raise exploitation rates to potentially unsustainable levels. Results showed that participation in the crappie fisheries was about equally split between polers and trollers. In spring, 90% of crappie anglers were polers; in summer, 85% of crappie anglers were trollers. The size of harvested crappies was similar for the two angler groups, but the catch per hour was almost three times higher for trollers than for polers. Catch rates by trollers were directly correlated to the number of poles fished, although the relationship flattened as the number of poles increased. The average harvest rate for one troller fishing with three poles was similar to the harvest rate obtained by one poler. Simulations predicted that at the existing mix of about 50% polers and 50% trollers and with no restrictions on the number of poles used by trollers, exploitation of crappies is about 1.3 times higher than that in a polers-only fishery; under a scenario in which 100% of crappie anglers were trollers, exploitation was forecasted to increase to about 1.7 times the polers-only rate. The efficiency of trolling for crappies should be of concern to fishery managers because crappie fisheries are mostly consumptive and may increase exploitation

  17. Intelligence, mapping, and geospatial exploitation system (IMAGES)

    Science.gov (United States)

    Moellman, Dennis E.; Cain, Joel M.

    1998-08-01

    This paper provides further detail to one facet of the battlespace visualization concept described in last year's paper Battlespace Situation Awareness for Force XXI. It focuses on the National Imagery and Mapping Agency (NIMA) goal to 'provide customers seamless access to tailorable imagery, imagery intelligence, and geospatial information.' This paper describes Intelligence, Mapping, and Geospatial Exploitation System (IMAGES), an exploitation element capable of CONUS baseplant operations or field deployment to provide NIMA geospatial information collaboratively into a reconnaissance, surveillance, and target acquisition (RSTA) environment through the United States Imagery and Geospatial Information System (USIGS). In a baseplant CONUS setting IMAGES could be used to produce foundation data to support mission planning. In the field it could be directly associated with a tactical sensor receiver or ground station (e.g. UAV or UGV) to provide near real-time and mission specific RSTA to support mission execution. This paper provides IMAGES functional level design; describes the technologies, their interactions and interdependencies; and presents a notional operational scenario to illustrate the system flexibility. Using as a system backbone an intelligent software agent technology, called Open Agent ArchitectureTM (OAATM), IMAGES combines multimodal data entry, natural language understanding, and perceptual and evidential reasoning for system management. Configured to be DII COE compliant, it would utilize, to the extent possible, COTS applications software for data management, processing, fusion, exploitation, and reporting. It would also be modular, scaleable, and reconfigurable. This paper describes how the OAATM achieves data synchronization and enables the necessary level of information to be rapidly available to various command echelons for making informed decisions. The reasoning component will provide for the best information to be developed in the timeline

  18. Synthesis of molybdenum disulfide/reduced graphene oxide composites for effective removal of Pb(Ⅱ) from aqueous solutions

    Institute of Scientific and Technical Information of China (English)

    Yi Du; Xiangke Wang; Jian wang; Yidong Zou; Wen Yao; Jing Hou; Liangshu Xia; Anguo Peng; Ahmed Alsaedi; Tasawar Hayat

    2017-01-01

    In this work,a facile method was adopted to synthesize molybdenum disulfide/reduced graphene oxide (MoS2/rGO) composites through an L-cysteine-assisted hydrothermal technique.The as-prepared MoS2/ rGO composites were firstly applied as adsorbents for efficient elimination of Pb(Ⅱ) ions.Batch adsorption experiments showed that the adsorption of Pb(Ⅱ) on MoS2/rGO followed pseudo-second-order kinetic model well.The adsorption of Pb(Ⅱ) was intensely pH-dependent,ionic strength-dependent at pH < 9.0 and ionic strength-independent at pH > 9.0.The presence of humic acid (HA) enhanced Pb(Ⅱ) adsorption obviously.The MoS2/rGO composites exhibited excellent adsorption capacity of 384.16 mg g-1 at pH 5.0 and T =298.15 K,which was superior to MoS2 (279.93 mg g-1) and many other adsorbents.The thermodynamic parameters suggested that the adsorption process of Pb(Ⅱ) on MoS2/rGO composites was spontaneous (△Gθ < 0) and endothermic (△Hθ > 0).The interaction of Pb(Ⅱ) and MoS2/ rGO was mainly dominated by electrostatic attraction and surface complexation between Pb(Ⅱ) and oxygen-containing functional groups of MoS2/rGO.This work highlighted the application of MoS2/rGO as novel and promising materials in the efficient elimination of Pb(Ⅱ) from contaminated water and industrial effluents in environmental pollution management.

  19. Sustainable exploitation and management of aquatic resources

    DEFF Research Database (Denmark)

    Neuenfeldt, Stefan; Köster, Fritz

    2014-01-01

    DTU Aqua conducts research, provides advice,educates at university level and contributes toinnovation in sustainable exploitation andmanagement of aquatic resources. The vision of DTUAqua is to enable ecologically and economicallysustainable exploitation of aquatic resourcesapplying an integrated...... management. Marineecosystems aims at understanding the mechanisms that govern the interaction between individuals,species and populations in an ecosystem enabling us to determine the stability and flexibility of theecosystem.Marine living resources looks at the sustainable utilization of fish and shellfish...... stocks.Ecosystem effects expands from the ecosystem approach to fisheries management to an integratedapproach where other human activities are taken into consideration. Fisheries management developsmethods, models and tools for predicting and evaluating the effects of management measures andregulations...

  20. Exploiting HRM in support of lean manufacturing

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Matthiesen, Rikke

    The purpose of this paper is to investigate the ways in HRM practices are-and could potentially be-exploited to support lean manufacturing in practice. First, a review of the pertinent literature regarding HRM, SHRM, and lean manufacturing is presented to provide an understanding of the mechanisms...... by which HRM practices could, theoretically, be used to support a lean implementation. Data presented in the paper are derived from 1) a longitudinal case study on lean implementation and 2) from managers currently involved with lean manufacturing in a second company. The relevant literature and the data...... depicting the potential role in supporting HRM/lean integrated practices. The analysis of the model with respect to the theoretical background emphasizes a number of areas in which HRM could be more fully exploited in order to more successfully support lean implementation, for example, by stressing HRM...

  1. Exploiting Non-Markovianity for Quantum Control.

    Science.gov (United States)

    Reich, Daniel M; Katz, Nadav; Koch, Christiane P

    2015-07-22

    Quantum technology, exploiting entanglement and the wave nature of matter, relies on the ability to accurately control quantum systems. Quantum control is often compromised by the interaction of the system with its environment since this causes loss of amplitude and phase. However, when the dynamics of the open quantum system is non-Markovian, amplitude and phase flow not only from the system into the environment but also back. Interaction with the environment is then not necessarily detrimental. We show that the back-flow of amplitude and phase can be exploited to carry out quantum control tasks that could not be realized if the system was isolated. The control is facilitated by a few strongly coupled, sufficiently isolated environmental modes. Our paradigmatic example considers a weakly anharmonic ladder with resonant amplitude control only, restricting realizable operations to SO(N). The coupling to the environment, when harnessed with optimization techniques, allows for full SU(N) controllability.

  2. Exploiting Quantum Resonance to Solve Combinatorial Problems

    Science.gov (United States)

    Zak, Michail; Fijany, Amir

    2006-01-01

    Quantum resonance would be exploited in a proposed quantum-computing approach to the solution of combinatorial optimization problems. In quantum computing in general, one takes advantage of the fact that an algorithm cannot be decoupled from the physical effects available to implement it. Prior approaches to quantum computing have involved exploitation of only a subset of known quantum physical effects, notably including parallelism and entanglement, but not including resonance. In the proposed approach, one would utilize the combinatorial properties of tensor-product decomposability of unitary evolution of many-particle quantum systems for physically simulating solutions to NP-complete problems (a class of problems that are intractable with respect to classical methods of computation). In this approach, reinforcement and selection of a desired solution would be executed by means of quantum resonance. Classes of NP-complete problems that are important in practice and could be solved by the proposed approach include planning, scheduling, search, and optimal design.

  3. Exploiting Inhibitory Siglecs to Combat Food Allergies

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0302 TITLE: Exploiting Inhibitory Siglecs to Combat Food Allergies PRINCIPAL INVESTIGATOR: Michael Kulis, Ph.D...CONTRACTING ORGANIZATION: University of North Carolina at Chapel Hill Chapel Hill, NC 27599 REPORT DATES: October 2017 TYPE OF REPORT: Annual PREPARED FOR...Department of Defense, Washington Headquarters Services , Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite

  4. Dandruff: The most commercially exploited skin disease

    Directory of Open Access Journals (Sweden)

    Ranganathan S

    2010-01-01

    Full Text Available The article discuss in detail about the prevalence, pathophysiology, clinical manifestations of dandruff including the etio-pathology. The article also discusses in detail about various treatment methods available for dandruff. The status of dandruff being amphibious - a disease/disorder, and relatively less medical intervention is sought after for the treatment, dandruff is the most commercially exploited skin and scalp disorder/disease by personal care industries.

  5. Exploiting partial knowledge for efficient model analysis

    OpenAIRE

    Macedo, Nuno; Cunha, Alcino; Pessoa, Eduardo José Dias

    2017-01-01

    The advancement of constraint solvers and model checkers has enabled the effective analysis of high-level formal specification languages. However, these typically handle a specification in an opaque manner, amalgamating all its constraints in a single monolithic verification task, which often proves to be a performance bottleneck. This paper addresses this issue by proposing a solving strategy that exploits user-provided partial knowledge, namely by assigning symbolic bounds to the problem’s ...

  6. Amplifiers Exploiting Thermal Noise Canceling: A Review

    OpenAIRE

    Klumperink, Eric A.M.; Bruccoleri, Federico; Stroet, Peter; Nauta, Bram

    2004-01-01

    Wide-band LNAs suffer from a fundamental trade-off between noise figure NF and source impedance matching, which limits NF to values typically above 3dB. Recently, a feed-forward noise canceling technique has been proposed to break this trade-off. This paper reviews the principle of the technique and its key properties. Although the technique has been applied to wideband CMOS LNAs, it can just as well be implemented exploiting transconductance elements realized with oth...

  7. Exploiting thesauri knowledge in medical guideline formalization

    OpenAIRE

    Serban, R.C.; ten Teije, A.C.M.

    2009-01-01

    Objectives: As in software product lifecycle, the effort spent in maintaining medical knowl edge in guidelines can be reduced, if modularization, formalization and tracking of domain knowledge are employed across the guideline development phases. Methods: We propose to exploit and combine knowledge templates with medical background knowledge from existing thesauri in order to produce reusable building blocks used in guideline development. These tem- plates enable easier guideline formalizatio...

  8. Exploitation as the Unequal Exchange of Labour : An Axiomatic Approach

    OpenAIRE

    Yoshihara, Naoki; Veneziani, Roberto

    2009-01-01

    In subsistence economies with general convex technology and rational optimising agents, a new, axiomatic approach is developed, which allows an explicit analysis of the core positive and normative intuitions behind the concept of exploitation. Three main new axioms, called Labour Exploitation in Subsistence Economies , Relational Exploitation , and Feasibility of Non-Exploitation , are presented and it is proved that they uniquely characterise a definition of exploitation conceptually related...

  9. Engineering an improved IgG4 molecule with reduced disulfide bond heterogeneity and increased Fab domain thermal stability.

    Science.gov (United States)

    Peters, Shirley J; Smales, C Mark; Henry, Alistair J; Stephens, Paul E; West, Shauna; Humphreys, David P

    2012-07-13

    The integrity of antibody structure, stability, and biophysical characterization are becoming increasingly important as antibodies receive increasing scrutiny from regulatory authorities. We altered the disulfide bond arrangement of an IgG4 molecule by mutation of the Cys at the N terminus of the heavy chain constant domain 1 (C(H)1) (Kabat position 127) to a Ser and introduction of a Cys at a variety of positions (positions 227-230) at the C terminus of C(H)1. An inter-LC-C(H)1 disulfide bond is thus formed, which mimics the disulfide bond arrangement found in an IgG1 molecule. The antibody species present in the supernatant following transient expression in Chinese hamster ovary cells were analyzed by immunoblot to investigate product homogeneity, and purified product was analyzed by a thermofluor assay to determine thermal stability. We show that the light chain can form an inter-LC-C(H)1 disulfide bond with a Cys when present at several positions on the upper hinge (positions 227-230) and that such engineered disulfide bonds can consequently increase the Fab domain thermal stability between 3 and 6.8 °C. The IgG4 disulfide mutants displaying the greatest increase in Fab thermal stability were also the most homogeneous in terms of disulfide bond arrangement and antibody species present. Importantly, mutations did not affect the affinity for antigen of the resultant molecules. In combination with the previously described S241P mutation, we present an IgG4 molecule with increased Fab thermal stability and reduced product heterogeneity that potentially offers advantages for the production of IgG4 molecules.

  10. Security option file - Exploitation (DOS-Expl)

    International Nuclear Information System (INIS)

    2016-01-01

    This document aims at presenting functions performed by Cigeo during its exploitation phase, its main technical and security options which are envisaged with respect to different types of internal or external risks, and a first assessment of its impact on mankind and on the environment during its exploitation in normal operation as well as in incidental or accidental situations. A first volume addresses security principles, approach and management in relationship with the legal and regulatory framework. The second volume presents input data related to waste parcels and used for the installation sizing and operation, the main site characteristics, the main technical options regarding structures and equipment, and the main options regarding exploitation (parcel management, organisational and human aspects, and effluent management). The third volume describes how parcel are processed from their arrival to their setting in storage compartment, an inventory of internal and external risks, and a first assessment of consequences of scenarios on mankind and on the environment. The fourth volume presents options and operations which are envisaged regarding Cigeo closure, and inventory of associated risks

  11. Novel Roles of the Non-catalytic Elements of Yeast Protein-disulfide Isomerase in Its Interplay with Endoplasmic Reticulum Oxidoreductin 1*

    Science.gov (United States)

    Niu, Yingbo; Zhang, Lihui; Yu, Jiaojiao; Wang, Chih-chen; Wang, Lei

    2016-01-01

    The formation of disulfide bonds in the endoplasmic reticulum (ER) of eukaryotic cells is catalyzed by the sulfhydryl oxidase, ER oxidoreductin 1 (Ero1), and protein-disulfide isomerase (PDI). PDI is oxidized by Ero1 to continuously introduce disulfides into substrates, and feedback regulates Ero1 activity by manipulating the regulatory disulfides of Ero1. In this study we find that yeast Ero1p is enzymatically active even with its regulatory disulfides intact, and further activation of Ero1p by reduction of the regulatory disulfides requires the reduction of non-catalytic Cys90-Cys97 disulfide in Pdi1p. The principal client-binding site in the Pdi1p b′ domain is necessary not only for the functional Ero1p-Pdi1p disulfide relay but also for the activation of Ero1p. We also demonstrate by complementary activation assays that the regulatory disulfides in Ero1p are much more stable than those in human Ero1α. These new findings on yeast Ero1p-Pdi1p interplay reveal significant differences from our previously identified mode of human Ero1α-PDI interplay and provide insights into the evolution of the eukaryotic oxidative protein folding pathway. PMID:26846856

  12. Study of the helium cross-section of unsymmetric disulfide self-assembled monolayers on Au(111)

    Energy Technology Data Exchange (ETDEWEB)

    Albayrak, Erol [Department of Materials and Metallurgical Engineering, Ahi Evran University, Kırşehir 40000 (Turkey); Karabuga, Semistan [Department of Chemistry, Kahramanmaraş Sütçü İmam University, Kahramanmaraş 46030 (Turkey); Bracco, Gianangelo [CNR-IMEM and Department of Physics, University of Genoa, Via Dodecaneso 33, Genoa 16146 (Italy); Danışman, M. Fatih, E-mail: danisman@metu.edu.tr [Department of Chemistry, Middle East Technical University, Ankara 06800 (Turkey)

    2016-12-30

    Highlights: • Unsymmetrtic disulfide (HDD and HOD) self assembled monolayers were grown on Au(111) by supersonic molecular beam deposition. • Helium scattering cross sections for these two different unsymmetric disulfides were determined. • A common low temperature film phase was observed for the studied disulfides. - Abstract: We have investigated the formation of self-assembled monolayers (SAMs) of 11-hydroxyundecyl decyl disulfide (CH{sub 3}-(CH{sub 2}){sub 9}-S-S-(CH{sub 2}){sub 11}-OH, HDD) and 11-hydroxyundecyl octadecyl disulfide (CH{sub 3}-(CH{sub 2}){sub 17}-S-S-(CH{sub 2}){sub 11}-OH, HOD) produced by supersonic molecular beam deposition (SMBD). The study has been carried out by means of helium diffraction at very low film coverage. In this regime helium single molecule cross sections have been estimated in a temperature range between 100 K and 450 K. The results show a different behavior above 300 K that has been interpreted as the starting of mobility with the formation of two thiolate moieties either linked by a gold adatom or distant enough to prevent cross section overlapping. Finally, helium diffraction patterns measured at 80 K for the SAMs grown at 200 K are discussed and the results support the proposed hypothesis of molecular dissociation based on the cross section data.

  13. CD44 Binding to Hyaluronic Acid Is Redox Regulated by a Labile Disulfide Bond in the Hyaluronic Acid Binding Site.

    Directory of Open Access Journals (Sweden)

    Helena Kellett-Clarke

    Full Text Available CD44 is the primary leukocyte cell surface receptor for hyaluronic acid (HA, a component of the extracellular matrix. Enzymatic post translational cleavage of labile disulfide bonds is a mechanism by which proteins are structurally regulated by imparting an allosteric change and altering activity. We have identified one such disulfide bond in CD44 formed by Cys77 and Cys97 that stabilises the HA binding groove. This bond is labile on the surface of leukocytes treated with chemical and enzymatic reducing agents. Analysis of CD44 crystal structures reveal the disulfide bond to be solvent accessible and in the-LH hook configuration characteristic of labile disulfide bonds. Kinetic trapping and binding experiments on CD44-Fc chimeric proteins show the bond is preferentially reduced over the other disulfide bonds in CD44 and reduction inhibits the CD44-HA interaction. Furthermore cells transfected with CD44 no longer adhere to HA coated surfaces after pre-treatment with reducing agents. The implications of CD44 redox regulation are discussed in the context of immune function, disease and therapeutic strategies.

  14. Kinetic study of the interaction of glutathione with four antitumor disulfides: possible mechanism for cellular glutathione depletion.

    Science.gov (United States)

    Kirkpatrick, D L

    1989-01-01

    The reactions between the cellular tripeptide, glutathione (GSH) and four disulfide derivatives of 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) (compounds 1-4) were studied kinetically. The decyl and phenyl derivatives of 6-MP and 6-TG were reacted with GSH in phosphate buffer (pH 7.4 or 6.0) at 25.0 degrees C and were monitored spectrophotometrically by observing the release of 6-MP and 6-TG. Second order kinetics were observed, with rate constants of 142, 564, 4174 and 429 M-1 s-1 being measured for compounds 1-4, respectively. When the reactions were carried out in the presence of GSH-S-transferase the rates were enhanced 1.3-5.4 times those observed in the absence of enzyme. Products of the reactions were isolated by chromatography and tentatively identified by TLC or fast atom bombardment mass spectrometry. It was observed that GSH reacted with each disulfide in a 1:1 manner, forming a mixed disulfide between GSH and decanethiol or thiophenol while releasing 6-MP or 6-TG. It was concluded that the reported depletion of GSH from EMT6 cells after exposure to these disulfides could be due to their reaction with GSH, and the formation of the mixed disulfides.

  15. Antagonistic effect of disulfide-rich peptide aptamers selected by cDNA display on interleukin-6-dependent cell proliferation

    International Nuclear Information System (INIS)

    Nemoto, Naoto; Tsutsui, Chihiro; Yamaguchi, Junichi; Ueno, Shingo; Machida, Masayuki; Kobayashi, Toshikatsu; Sakai, Takafumi

    2012-01-01

    Highlights: ► Disulfide-rich peptide aptamer inhibits IL-6-dependent cell proliferation. ► Disulfide bond of peptide aptamer is essential for its affinity to IL-6R. ► Inhibitory effect of peptide depends on number and pattern of its disulfide bonds. -- Abstract: Several engineered protein scaffolds have been developed recently to circumvent particular disadvantages of antibodies such as their large size and complex composition, low stability, and high production costs. We previously identified peptide aptamers containing one or two disulfide-bonds as an alternative ligand to the interleukin-6 receptor (IL-6R). Peptide aptamers (32 amino acids in length) were screened from a random peptide library by in vitro peptide selection using the evolutionary molecular engineering method “cDNA display”. In this report, the antagonistic activity of the peptide aptamers were examined by an in vitro competition enzyme-linked immunosorbent assay (ELISA) and an IL-6-dependent cell proliferation assay. The results revealed that a disulfide-rich peptide aptamer inhibited IL-6-dependent cell proliferation with similar efficacy to an anti-IL-6R monoclonal antibody.

  16. Kinetics and mechanisms of thiol-disulfide exchange covering direct substitution and thiol oxidation-mediated pathways.

    Science.gov (United States)

    Nagy, Péter

    2013-05-01

    Disulfides are important building blocks in the secondary and tertiary structures of proteins, serving as inter- and intra-subunit cross links. Disulfides are also the major products of thiol oxidation, a process that has primary roles in defense mechanisms against oxidative stress and in redox regulation of cell signaling. Although disulfides are relatively stable, their reduction, isomerisation, and interconversion as well as their production reactions are catalyzed by delicate enzyme machineries, providing a dynamic system in biology. Redox homeostasis, a thermodynamic parameter that determines which reactions can occur in cellular compartments, is also balanced by the thiol-disulfide pool. However, it is the kinetic properties of the reactions that best represent cell dynamics, because the partitioning of the possible reactions depends on kinetic parameters. This review is focused on the kinetics and mechanisms of thiol-disulfide substitution and redox reactions. It summarizes the challenges and advances that are associated with kinetic investigations in small molecular and enzymatic systems from a rigorous chemical perspective using biological examples. The most important parameters that influence reaction rates are discussed in detail. Kinetic studies of proteins are more challenging than small molecules, and quite often investigators are forced to sacrifice the rigor of the experimental approach to obtain the important kinetic and mechanistic information. However, recent technological advances allow a more comprehensive analysis of enzymatic systems via using the systematic kinetics apparatus that was developed for small molecule reactions, which is expected to provide further insight into the cell's machinery.

  17. Differential regulation of tissue thiol-disulfide redox status in a murine model of peritonitis

    Directory of Open Access Journals (Sweden)

    Benton Shana M

    2012-10-01

    Full Text Available Abstract Background Glutathione (GSH/glutathione disulfide (GSSG and cysteine (Cys/cystine (CySS are major redox pools with important roles in cytoprotection. We determined the impact of septic peritonitis on thiol-disulfide redox status in mice. Methods FVB/N mice (6–12 week old; 8/group underwent laparotomy with cecal ligation and puncture (CLP or laparotomy alone (control. Sections of ileum, colon, lung and liver were obtained and GSH, GSSG, Cys and CySS concentrations determined by HPLC 24 h after laparotomy. Redox potential [Eh in millivolts (mV] of the GSH/GSSG and Cys/CySS pools was calculated using the Nernst equation. Data were analyzed by ANOVA (mean ± SE. Results GSH/GSSG Eh in ileum, colon, and liver was significantly oxidized in septic mice versus control mice (ileum: septic −202±4 versus control −228±2 mV; colon: -195±8 versus −214±1 mV; and liver: -194±3 vs. -210±1 mV, all Ph was unchanged with CLP, while liver and lung Cys/CySS Eh became significantly more reducing (liver: septic = −103±3 versus control −90±2 mV; lung: -101±5 versus −81±1 mV, each P Conclusions Septic peritonitis induced by CLP oxidizes ileal and colonic GSH/GSSG redox but Cys/CySS Eh remains unchanged in these intestinal tissues. In liver, CLP oxidizes the GSH/GSSG redox pool and CyS/CySS Eh becomes more reducing; in lung, CLP does not alter GSH/GSSG Eh, and Cys/CySS Eh is less oxidized. CLP-induced infection/inflammation differentially regulates major thiol-disulfide redox pools in this murine model.

  18. Thiol/disulfide homeostasis in pregnant women with obstructive sleep apnea syndrome.

    Science.gov (United States)

    Üstündağ, Yasemin; Demirci, Hakan; Balık, Rifat; Erel, Ozcan; Özaydın, Fahri; Kücük, Bilgen; Ertaş, Dilber; Ustunyurt, Emin

    2017-11-27

    Repetitive episodes of hypoxia and reoxygenation during sleep in patients with obstructive sleep apnea syndrome (OSAS) resemble an ischemia-reperfusion injury. We aimed to test the hypothesis that oxidative stress occurs in pregnant women with OSAS. We also aimed to compare thiol/disulfide homeostasis with ischemia-modified albumin (IMA) and total antioxidant capacity (TAC) as markers of ischemia-reperfusion injury in pregnant women with and without OSAS and healthy control. This study included 29 pregnant women with OSAS, 30 women without OSAS in the third trimester applying for periodic examinations, and 30 healthy women. Serum IMA and TAC (using the ferric reducing power of plasma method) were measured. Serum thiol/disulfide homeostasis was determined by a novel automated method. The mean age of the pregnant women with OSAS was 31.0 ± 4.7 years with a mean gestational age of 36.5 ± 3.0 weeks. The mean age of pregnant women without OSAS was 29.8 ± 4.9 years with a mean gestational age of 36.9 ± 2.7 weeks. The mean age of the nonpregnant control group was 29.7 ± 6.4 years. Both native thiol (291 ± 29 μmol/L versus 314 ± 30 μmol/L; p = .018) and total thiol (325 ± 32 versus 350 ± 32, p = .025) levels were lower in pregnant women with OSAS compared to pregnant women without OSAS, respectively (p total thiol levels were lower in pregnant women with OSAS compared to those without OSAS. However, dynamic thiol/disulfide homeostasis parameters cannot provide valuable information to discriminate OSAS in pregnant women.

  19. Influence of Disulfide Connectivity on Structure and Bioactivity of α-Conotoxin TxIA

    Directory of Open Access Journals (Sweden)

    Yong Wu

    2014-01-01

    Full Text Available Cone snails express a sophisticated arsenal of small bioactive peptides known as conopeptides or conotoxins (CTxs. Through evolutionary selection, these peptides have gained the ability to interact with a range of ion channels and receptors, such as nicotinic acetylcholine receptors (nAChRs. Here, we used reversed-phase high performance liquid chromatography (RP-HPLC and electrospray ionization-mass spectrometry (ESI-MS to explore the venom peptide diversity of Conus textile, a species of cone snail native to Hainan, China. One fraction of C. textile crude venom potently blocked α3β2 nAChRs. Subsequent purification, synthesis, and tandem mass spectrometric analysis demonstrated that the most active compound in this fraction was identical to α-CTx TxIA, an antagonist of α3β2 nAChRs. Then three disulfide isoforms of α-CTx TxIA were synthesized and their activities were investigated systematically for the first time. As we observed, disulfide isomerisation was particularly important for α-CTx TxIA potency. Although both globular and ribbon isomers showed similar retention times in RP-HPLC, globular TxIA potently inhibited α3β2 nAChRs with an IC50 of 5.4 nM, while ribbon TxIA had an IC50 of 430 nM. In contrast, beads isomer had little activity towards α3β2 nAChRs. Two-step oxidation synthesis produced the highest yield of α-CTx TxIA native globular isomer, while a one-step production process based on random oxidation folding was not suitable. In summary, this study demonstrated the relationship between conotoxin activity and disulfide connectivity on α-CTx TxIA.

  20. Intra- and inter-subunit disulfide bond formation is nonessential in adeno-associated viral capsids.

    Directory of Open Access Journals (Sweden)

    Nagesh Pulicherla

    Full Text Available The capsid proteins of adeno-associated viruses (AAV have five conserved cysteine residues. Structural analysis of AAV serotype 2 reveals that Cys289 and Cys361 are located adjacent to each other within each monomer, while Cys230 and Cys394 are located on opposite edges of each subunit and juxtaposed at the pentamer interface. The Cys482 residue is located at the base of a surface loop within the trimer region. Although plausible based on molecular dynamics simulations, intra- or inter-subunit disulfides have not been observed in structural studies. In the current study, we generated a panel of Cys-to-Ser mutants to interrogate the potential for disulfide bond formation in AAV capsids. The C289S, C361S and C482S mutants were similar to wild type AAV with regard to titer and transduction efficiency. However, AAV capsid protein subunits with C230S or C394S mutations were prone to proteasomal degradation within the host cells. Proteasomal inhibition partially blocked degradation of mutant capsid proteins, but failed to rescue infectious virions. While these results suggest that the Cys230/394 pair is critical, a C394V mutant was found viable, but not the corresponding C230V mutant. Although the exact nature of the structural contribution(s of Cys230 and Cys394 residues to AAV capsid formation remains to be determined, these results support the notion that disulfide bond formation within the Cys289/361 or Cys230/394 pair appears to be nonessential. These studies represent an important step towards understanding the role of inter-subunit interactions that drive AAV capsid assembly.

  1. Influence of the degree of crosslinking on the depolymerization of disulfide polymer

    International Nuclear Information System (INIS)

    Rekalicj, J.V.; Radosavljevicj, D.S.; Popovicj, E.M.; Stashicj, L.

    1976-01-01

    The action of nucleophilic reagents (hydrogen sulfide ion, dithionite ion and hydrazine) on disulfide polymers prepd. from bis-2-chloroethyl formal and 1,2,3-trichloropropane, taken in various mol rations is studied. The depolymerization efficiency is higher with hydrazine and dithionite than with a mixt. of sodium hydrogen sulfide and sodium sulfite. An interpretation of the results is given, attempting to correlate the content of SH-groups in the obtained product with the same quantity in some defined compds. which can be present after the depolymerization

  2. Defect-Mediated Lithium Adsorption and Diffusion on Monolayer Molybdenum Disulfide

    OpenAIRE

    Sun, Xiaoli; Wang, Zhiguo; Fu, Yong Qing

    2015-01-01

    Monolayer Molybdenum Disulfide (MoS2) is a promising anode material for lithium ion batteries because of its high capacities. In this work, first principle calculations based on spin density functional theory were performed to investigate adsorption and diffusion of lithium on monolayer MoS2 with defects, such as single- and few-atom vacancies, antisite, and grain boundary. The values of adsorption energies on the monolayer MoS2 with the defects were increased compared to those on the pristin...

  3. Antiradiation compounds XV: condensations of carbon disulfide with amino, chloro, cyanomethyl, and sulfonamido heterocycles

    International Nuclear Information System (INIS)

    Foye, W.O.; Kauffman, J.M.; Lanzillo, J.J.; LaSala, E.F.

    1975-01-01

    Condensations of carbon disulfide were carried out with amino, chloro, and diamino heterocycles to give condensed ring thiazoline-2-thiones and imidazoline-2-thiones, with cyanomethyl heterocycles to give dithio acid derivatives, and with heterocyclic sulfonamides to give sulfonyldithiocarbamates. Of several examples tested, pyrido[3,2-d]thiazoline-2-thione, disodium 2-(5-chloro-2-thienyl)-3,3-dimercaptoacrylonitrile, triethylammonium 4-sulfamoylphenyldithiocarbamate, ammonium β-phenethyldithiocarbamate, and methyl N-(thiophene-2-sulfonyl)dithiocarbamate, only the last-named compound showed any radiation protection for mice. Several compounds gave negative tests for antimalarial activity

  4. Disulfide high mobility group box-1 causes bladder pain through bladder Toll-like receptor 4.

    Science.gov (United States)

    Ma, Fei; Kouzoukas, Dimitrios E; Meyer-Siegler, Katherine L; Westlund, Karin N; Hunt, David E; Vera, Pedro L

    2017-05-25

    Bladder pain is a prominent symptom in several urological conditions (e.g. infection, painful bladder syndrome/interstitial cystitis, cancer). Understanding the mechanism of bladder pain is important, particularly when the pain is not accompanied by bladder pathology. Stimulation of protease activated receptor 4 (PAR4) in the urothelium results in bladder pain through release of urothelial high mobility group box-1 (HMGB1). HGMB1 has two functionally active redox states (disulfide and all-thiol) and it is not known which form elicits bladder pain. Therefore, we investigated whether intravesical administration of specific HMGB1 redox forms caused abdominal mechanical hypersensitivity, micturition changes, and bladder inflammation in female C57BL/6 mice 24 hours post-administration. Moreover, we determined which of the specific HMGB1 receptors, Toll-like receptor 4 (TLR4) or receptor for advanced glycation end products (RAGE), mediate HMGB1-induced changes. Disulfide HMGB1 elicited abdominal mechanical hypersensitivity 24 hours after intravesical (5, 10, 20 μg/150 μl) instillation. In contrast, all-thiol HMGB1 did not produce abdominal mechanical hypersensitivity in any of the doses tested (1, 2, 5, 10, 20 μg/150 μl). Both HMGB1 redox forms caused micturition changes only at the highest dose tested (20 μg/150 μl) while eliciting mild bladder edema and reactive changes at all doses. We subsequently tested whether the effects of intravesical disulfide HMGB1 (10 μg/150 μl; a dose that did not produce inflammation) were prevented by systemic (i.p.) or local (intravesical) administration of either a TLR4 antagonist (TAK-242) or a RAGE antagonist (FPS-ZM1). Systemic administration of either TAK-242 (3 mg/kg) or FPS-ZM1 (10 mg/kg) prevented HMGB1 induced abdominal mechanical hypersensitivity while only intravesical TLR4 antagonist pretreatment (1.5 mg/ml; not RAGE) had this effect. The disulfide form of HMGB1 mediates bladder pain directly (not

  5. Synthesis of tetramethylthiuram disulfide ({sup 35}S); Synthese du disulfure de tetramethylthiurame ({sup 35}S)

    Energy Technology Data Exchange (ETDEWEB)

    Bentov, M [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1958-07-01

    Tetramethylthiuram disulfide ({sup 35}S) has been prepared by exchange between elementary sulfur ({sup 35}S) and sodium N-dithiocarbamate followed by an oxidation with potassium ferricyanide. The method allows to obtain rapidly a pure product with relatively high activity. The radioactive exchange is 82 per cent. (author) [French] Le disurfure de tetramethylthiurame ({sup 35}S) a ete prepare par echange entre le soufre elementaire ({sup 35}S) et le N-dimethyldithiocarbamate de soude suivi d'une oxydation par le ferricyanure de potasse. La methode permet d'obtenir rapidement un produit pur avec une activite relativement haute. L'echange radioactif effectue est de 82 pour cent. (auteur)

  6. Cloud Based Earth Observation Data Exploitation Platforms

    Science.gov (United States)

    Romeo, A.; Pinto, S.; Loekken, S.; Marin, A.

    2017-12-01

    In the last few years data produced daily by several private and public Earth Observation (EO) satellites reached the order of tens of Terabytes, representing for scientists and commercial application developers both a big opportunity for their exploitation and a challenge for their management. New IT technologies, such as Big Data and cloud computing, enable the creation of web-accessible data exploitation platforms, which offer to scientists and application developers the means to access and use EO data in a quick and cost effective way. RHEA Group is particularly active in this sector, supporting the European Space Agency (ESA) in the Exploitation Platforms (EP) initiative, developing technology to build multi cloud platforms for the processing and analysis of Earth Observation data, and collaborating with larger European initiatives such as the European Plate Observing System (EPOS) and the European Open Science Cloud (EOSC). An EP is a virtual workspace, providing a user community with access to (i) large volume of data, (ii) algorithm development and integration environment, (iii) processing software and services (e.g. toolboxes, visualization routines), (iv) computing resources, (v) collaboration tools (e.g. forums, wiki, etc.). When an EP is dedicated to a specific Theme, it becomes a Thematic Exploitation Platform (TEP). Currently, ESA has seven TEPs in a pre-operational phase dedicated to geo-hazards monitoring and prevention, costal zones, forestry areas, hydrology, polar regions, urban areas and food security. On the technology development side, solutions like the multi cloud EO data processing platform provides the technology to integrate ICT resources and EO data from different vendors in a single platform. In particular it offers (i) Multi-cloud data discovery, (ii) Multi-cloud data management and access and (iii) Multi-cloud application deployment. This platform has been demonstrated with the EGI Federated Cloud, Innovation Platform Testbed Poland

  7. Heisenberg's heirs exploit loopholes in his law

    International Nuclear Information System (INIS)

    Taubes, G.

    1994-01-01

    This article describes research into Heisenberg's Uncertainty Principle. Loopholes in the principle have led to a series of experiments using sophisticated optical techniques to extract information from a quantum system without disturbing the variable being measured. The experiments are based on a technique called back-action evasion, which exploits the possibility of channeling all the uncertainty generated by measuring one quantum variable (e.g. laser beam intensity) onto a related variable known as the conjugate observable (beam phase). These experiments and others are described

  8. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...... the reader will gain: The review focuses on strategies that exploit characteristic features of solid tumors, such as abnormal vasculature, overexpression of receptors and enzymes, as well as acidic and thiolytic characteristics of the tumor microenvironment. Take home message: It is concluded that the design...

  9. Pilot plant for exploitation of geothermal waters

    Directory of Open Access Journals (Sweden)

    Stojiljković Dragan T.

    2006-01-01

    Full Text Available In Sijarinska spa, there are some 15 mineral and thermomineral springs, that are already being used for therapeutic purposes. For the exploitation of heat energy boring B-4 is very interesting. It is a boring of a closed type, with the water temperature of about 78°C and a flow rate of about 33 l/s. Waters with the flow rate of about 6 l/s are currently used for heating of the Gejzer hotel, and waters of the flow rate of about 0,121 l/s for the pilot drying plant. The paper presents this pilot plant. .

  10. Exploiting Redundancy in an OFDM SDR Receiver

    Directory of Open Access Journals (Sweden)

    Tomas Palenik

    2009-01-01

    Full Text Available Common OFDM system contains redundancy necessary to mitigate interblock interference and allows computationally effective single-tap frequency domain equalization in receiver. Assuming the system implements an outer error correcting code and channel state information is available in the receiver, we show that it is possible to understand the cyclic prefix insertion as a weak inner ECC encoding and exploit the introduced redundancy to slightly improve error performance of such a system. In this paper, an easy way to implement modification to an existing SDR OFDM receiver is presented. This modification enables the utilization of prefix redundancy, while preserving full compatibility with existing OFDM-based communication standards.

  11. Geothermal resources: exploration and exploitation. A bibliography

    Energy Technology Data Exchange (ETDEWEB)

    1976-07-01

    This comprehensive bibliography contains 5476 citations of foreign and domestic research reports, journal articles, patents, conference proceedings, and books concerned with the exploration and exploitation of geothermal resources. The coverage dates back as far as useful references could be obtained and extends through June 1976. References are arranged in broad subject categories and are made up of complete bibliographic citations. These are followed by a listing of subject descriptors used to describe the subject content of each reference. Four indexes are included: Corporate, Personal Author, Subject, and Report Number. Also included is a list of journals from which articles were selected. (LBS)

  12. Algorithms exploiting ultrasonic sensors for subject classification

    Science.gov (United States)

    Desai, Sachi; Quoraishee, Shafik

    2009-09-01

    Proposed here is a series of techniques exploiting micro-Doppler ultrasonic sensors capable of characterizing various detected mammalian targets based on their physiological movements captured a series of robust features. Employed is a combination of unique and conventional digital signal processing techniques arranged in such a manner they become capable of classifying a series of walkers. These processes for feature extraction develops a robust feature space capable of providing discrimination of various movements generated from bipeds and quadrupeds and further subdivided into large or small. These movements can be exploited to provide specific information of a given signature dividing it in a series of subset signatures exploiting wavelets to generate start/stop times. After viewing a series spectrograms of the signature we are able to see distinct differences and utilizing kurtosis, we generate an envelope detector capable of isolating each of the corresponding step cycles generated during a walk. The walk cycle is defined as one complete sequence of walking/running from the foot pushing off the ground and concluding when returning to the ground. This time information segments the events that are readily seen in the spectrogram but obstructed in the temporal domain into individual walk sequences. This walking sequence is then subsequently translated into a three dimensional waterfall plot defining the expected energy value associated with the motion at particular instance of time and frequency. The value is capable of being repeatable for each particular class and employable to discriminate the events. Highly reliable classification is realized exploiting a classifier trained on a candidate sample space derived from the associated gyrations created by motion from actors of interest. The classifier developed herein provides a capability to classify events as an adult humans, children humans, horses, and dogs at potentially high rates based on the tested sample

  13. Characterization of intramolecular disulfide bonds and secondary modifications of the glycoprotein from viral hemorrhagic septicemia virus, a fish rhabdovirus

    DEFF Research Database (Denmark)

    Einer-Jensen, Katja; Nielsen, Thomas Krogh; Roepstorff, Peter

    1998-01-01

    were analyzed by mass spectrometry before and after chemical reduction, and six disulfide bonds were identified: Cys29-Cys339, Cys44-Cys295, Cys90-Cys132, Cys172-Cys177, Cys195-Cys265, and Cys231-CyS236. Mass spectrometric analysis in combination with glycosidases allowed characterization of the glycan...... of the protein, The present study was initiated to identify the disulfide bonds and other structural aspects relevant to vaccine design. The N-terminal amino acid residue was identified as being a pyroglutamic acid, corresponding to Gln21 of the primary transcript, Peptides from endoproteinase-degraded G protein...... cysteine residues are situated at conserved positions, This finding suggests that there might be some common disulfide bonding pattern among the six rhabdoviruses....

  14. Competing Discourses about Youth Sexual Exploitation in Canadian News Media.

    Science.gov (United States)

    Saewyc, Elizabeth M; Miller, Bonnie B; Rivers, Robert; Matthews, Jennifer; Hilario, Carla; Hirakata, Pam

    2013-10-01

    Media holds the power to create, maintain, or break down stigmatizing attitudes, which affect policies, funding, and services. To understand how Canadian news media depicts the commercial sexual exploitation of children and youth, we examined 835 Canadian newspaper articles from 1989-2008 using a mixed methods critical discourse analysis approach, comparing representations to existing research about sexually exploited youth. Despite research evidence that equal rates of boys and girls experience exploitation, Canadian news media depicted exploited youth predominantly as heterosexual girls, and described them alternately as victims or workers in a trade, often both in the same story. News media mentioned exploiters far less often than victims, and portrayed them almost exclusively as male, most often called 'customers' or 'consumers,' and occasionally 'predators'; in contrast, research has documented the majority of sexually exploited boys report female exploiters. Few news stories over the past two decades portrayed the diversity of victims, perpetrators, and venues of exploitation reported in research. The focus on victims but not exploiters helps perpetuate stereotypes of sexual exploitation as business or a 'victimless crime,' maintains the status quo, and blurs responsibility for protecting youth under the UN Convention on the Rights of the Child. Health care providers and researchers can be advocates for accuracy in media coverage about sexual exploitation; news reporters and editors should focus on exploiters more than victims, draw on existing research evidence to avoid perpetuating stereotypes, and use accurate terms, such as commercial sexual exploitation, rather than terms related to business or trade.

  15. International assistance. Licensing assistance project

    International Nuclear Information System (INIS)

    Aleev, A.

    1999-01-01

    Description of licensing assistance project for VATESI is presented. In licensing of unit No.1 of INPP VATESI is supported by many western countries. Experts from regulatory bodies or scientific organizations of those countries assist VATESI staff in reviewing documentation presented by INPP. Among bilateral cooperation support is provided by European Commission through Phare programme

  16. ROUNDTABLE - SESSION 2 EXPLOITATION, CONSERVATION AND LEGISLATION

    Directory of Open Access Journals (Sweden)

    EDSMAN L.

    2004-01-01

    Full Text Available The link between socioeconomics and conservation and the role of legislation in conservation work was discussed in the group with participants from nine European countries. Interest and knowledge among the general public, stakeholders and managers is the key to successful conservation of native crayfish species. Exploitation and conservation do not necessarily exclude each other. A controlled fishery, where it can be sustained, may be an essential tool for conservation by increasing the general awareness and involving more people in the task of protecting the native crayfish species. This strategy is mainly possible for the noble crayfish in the northern part of its distribution, where strong traditions connected to crayfish also exist. A balance between utilisation and overexploitation has to be found and local guidelines for sustainable exploitation produced. Media, the Internet and educational material aimed at schools and stakeholders are excellent ways of reaching a wide audience with information. Universal objectives, rules and regulations at the European level are desirable and the noble crayfish and the stone crayfish should be included in Annex II of the Habitat Directive. Based on this framework detailed regulations are best worked out at the national level, considering the specific crayfish situation in the country. Information about the legislation, the purpose of the legislation and the consequences when not obeying it should be distributed. Stricter regulation of the trade with live alien crayfish is vital because of the associated risk of introducing new diseases and species.

  17. Uncovering Indicators of Commercial Sexual Exploitation.

    Science.gov (United States)

    Bounds, Dawn; Delaney, Kathleen R; Julion, Wrenetha; Breitenstein, Susan

    2017-07-01

    It is estimated that annually 100,000 to 300,000 youth are at risk for sex trafficking; a commercial sex act induced by force, fraud, or coercion, or any such act where the person induced to perform such an act is younger than 18 years of age. Increasingly, such transactions are occurring online via Internet-based sites that serve the commercial sex industry. Commercial sex transactions involving trafficking are illegal; thus, Internet discussions between those involved must be veiled. Even so, transactions around sex trafficking do occur. Within these transactions are innuendos that provide one avenue for detecting potential activity. The purpose of this study is to identify linguistic indicators of potential commercial sexual exploitation within the online comments of men posted on an Internet site. Six hundred sixty-six posts from five Midwest cities and 363 unique members were analyzed via content analysis. Three main indicators were found: the presence of youth or desire for youthfulness, presence of pimps, and awareness of vulnerability. These findings begin a much-needed dialogue on uncovering online risks of commercial sexual exploitation and support the need for further research on Internet indicators of sex trafficking.

  18. Large size space construction for space exploitation

    Science.gov (United States)

    Kondyurin, Alexey

    2016-07-01

    Space exploitation is impossible without large space structures. We need to make sufficient large volume of pressurized protecting frames for crew, passengers, space processing equipment, & etc. We have to be unlimited in space. Now the size and mass of space constructions are limited by possibility of a launch vehicle. It limits our future in exploitation of space by humans and in development of space industry. Large-size space construction can be made with using of the curing technology of the fibers-filled composites and a reactionable matrix applied directly in free space. For curing the fabric impregnated with a liquid matrix (prepreg) is prepared in terrestrial conditions and shipped in a container to orbit. In due time the prepreg is unfolded by inflating. After polymerization reaction, the durable construction can be fitted out with air, apparatus and life support systems. Our experimental studies of the curing processes in the simulated free space environment showed that the curing of composite in free space is possible. The large-size space construction can be developed. A project of space station, Moon base, Mars base, mining station, interplanet space ship, telecommunication station, space observatory, space factory, antenna dish, radiation shield, solar sail is proposed and overviewed. The study was supported by Humboldt Foundation, ESA (contract 17083/03/NL/SFe), NASA program of the stratospheric balloons and RFBR grants (05-08-18277, 12-08-00970 and 14-08-96011).

  19. PROBA-V Mission Exploitation Platform

    Directory of Open Access Journals (Sweden)

    Erwin Goor

    2016-07-01

    Full Text Available As an extension of the PROBA-Vegetation (PROBA-V user segment, the European Space Agency (ESA, de Vlaamse Instelling voor Technologisch Onderzoek (VITO, and partners TRASYS and Spacebel developed an operational Mission Exploitation Platform (MEP to drastically improve the exploitation of the PROBA-V Earth Observation (EO data archive, the archive from the historical SPOT-VEGETATION mission, and derived products by researchers, service providers, and thematic users. The analysis of the time series of data (petabyte range is addressed, as well as the large scale on-demand processing of the complete archive, including near real-time data. The platform consists of a private cloud environment, a Hadoop-based processing environment and a data manager. Several applications are released to the users, e.g., a full resolution viewing service, a time series viewer, pre-defined on-demand processing chains, and virtual machines with powerful tools and access to the data. After an initial release in January 2016 a research platform was deployed gradually, allowing users to design, debug, and test applications on the platform. From the PROBA-V MEP, access to, e.g., Sentinel-2 and Sentinel-3 data will be addressed as well.

  20. MTH1745, a protein disulfide isomerase-like protein from thermophilic archaea, Methanothermobacter thermoautotrophicum involving in stress response.

    Science.gov (United States)

    Ding, Xia; Lv, Zhen-Mei; Zhao, Yang; Min, Hang; Yang, Wei-Jun

    2008-01-01

    MTH1745 is a putative protein disulfide isomerase characterized with 151 amino acid residues and a CPAC active-site from the anaerobic archaea Methanothermobacter thermoautotrophicum. The potential functions of MTH1745 are not clear. In the present study, we show a crucial role of MTH1745 in protecting cells against stress which may be related to its functions as a disulfide isomerase and its chaperone properties. Using real-time polymerase chain reaction analyses, the level of MTH1745 messenger RNA (mRNA) in the thermophilic archaea M. thermoautotrophicum was found to be stress-induced in that it was significantly higher under low (50 degrees C) and high (70 degrees C) growth temperatures than under the optimal growth temperature for the organism (65 degrees C). Additionally, the expression of MTH1745 mRNA was up-regulated by cold shock (4 degrees C). Furthermore, the survival of MTH1745 expressing Escherichia coli cells was markedly higher than that of control cells in response to heat shock (51.0 degrees C). These results indicated that MTH1745 plays an important role in the resistance of stress. By assay of enzyme activities in vitro, MTH1745 also exhibited a chaperone function by promoting the functional folding of citrate synthase after thermodenaturation. On the other hand, MTH1745 was also shown to function as a disulfide isomerase on the refolding of denatured and reduced ribonuclease A. On the basis of its single thioredoxin domain, function as a disulfide isomerase, and its chaperone activity, we suggest that MTH1745 may be an ancient protein disulfide isomerase. These studies may provide clues to the understanding of the function of protein disulfide isomerase in archaea.

  1. zero day exploits and national readiness for cyber-warfare

    African Journals Online (AJOL)

    HOD

    A zero day vulnerability is an unknown exploit that divulges security flaws in software before such a flaw is publicly ... Keywords: exploits, zero day, vulnerability, cyberspace, cyber-warfare. 1. ..... industries and companies across the globe. The.

  2. Identification and prevention of antibody disulfide bond reduction during cell culture manufacturing.

    Science.gov (United States)

    Trexler-Schmidt, Melody; Sargis, Sandy; Chiu, Jason; Sze-Khoo, Stefanie; Mun, Melissa; Kao, Yung-Hsiang; Laird, Michael W

    2010-06-15

    In the biopharmaceutical industry, therapeutic monoclonal antibodies are primarily produced in mammalian cell culture systems. During the scale-up of a monoclonal antibody production process, we observed excessive mechanical cell shear as well as significant reduction of the antibody's interchain disulfide bonds during harvest operations. This antibody reduction event was catastrophic as the product failed to meet the drug substance specifications and the bulk product was lost. Subsequent laboratory studies have demonstrated that cells subjected to mechanical shear release cellular enzymes that contribute to this antibody reduction phenomenon (manuscript submitted; Kao et al., 2009). Several methods to prevent this antibody reduction event were developed using a lab-scale model to reproduce the lysis and reduction events. These methods included modifications to the cell culture media with chemicals (e.g., cupric sulfate (CuSO(4))), pre- and post-harvest chemical additions to the cell culture fluid (CCF) (e.g., CuSO(4), EDTA, L-cystine), as well as lowering the pH and air sparging of the harvested CCF (HCCF). These methods were evaluated for their effectiveness in preventing disulfide bond reduction and their impact to product quality. Effective prevention methods, which yielded acceptable product quality were evaluated for their potential to be implemented at manufacturing-scale. The work described here identifies numerous effective reduction prevention measures from lab-scale studies; several of these methods were then successfully translated into manufacturing processes. 2010 Wiley Periodicals, Inc.

  3. Intracellular drug delivery nanocarriers of glutathione-responsive degradable block copolymers having pendant disulfide linkages.

    Science.gov (United States)

    Khorsand, Behnoush; Lapointe, Gabriel; Brett, Christopher; Oh, Jung Kwon

    2013-06-10

    Self-assembled micelles of amphiphilic block copolymers (ABPs) with stimuli-responsive degradation (SRD) properties have a great promise as nanotherapeutics exhibiting enhanced release of encapsulated therapeutics into targeted cells. Here, thiol-responsive degradable micelles based on a new ABP consisting of a pendant disulfide-labeled methacrylate polymer block (PHMssEt) and a hydrophilic poly(ethylene oxide) (PEO) block were investigated as effective intracellular nanocarriers of anticancer drugs. In response to glutathione (GSH) as a cellular trigger, the cleavage of pendant disulfide linkages in hydrophobic PHMssEt blocks of micellar cores caused the destabilization of self-assembled micelles due to change in hydrophobic/hydrophilic balance. Such GSH-triggered micellar destabilization changed their size distribution with an appearance of large aggregates and led to enhanced release of encapsulated anticancer drugs. Cell culture results from flow cytometry and confocal laser scanning microscopy for cellular uptake as well as cell viability measurements for high anticancer efficacy suggest that new GSH-responsive degradable PEO-b-PHMssEt micelles offer versatility in multifunctional drug delivery applications.

  4. Structure of α-conotoxin BuIA: influences of disulfide connectivity on structural dynamics

    Directory of Open Access Journals (Sweden)

    Craik David J

    2007-04-01

    Full Text Available Abstract Background α-Conotoxins have exciting therapeutic potential based on their high selectivity and affinity for nicotinic acetylcholine receptors. The spacing between the cysteine residues in α-conotoxins is variable, leading to the classification of sub-families. BuIA is the only α-conotoxin containing a 4/4 cysteine spacing and thus it is of significant interest to examine the structure of this conotoxin. Results In the current study we show the native globular disulfide connectivity of BuIA displays multiple conformations in solution whereas the non-native ribbon isomer has a single well-defined conformation. Despite having multiple conformations in solution the globular form of BuIA displays activity at the nicotinic acetylcholine receptor, contrasting with the lack of activity of the structurally well-defined ribbon isomer. Conclusion These findings are opposite to the general trends observed for α-conotoxins where the native isomers have well-defined structures and the ribbon isomers are generally disordered. This study thus highlights the influence of the disulfide connectivity of BuIA on the dynamics of the three-dimensional structure.

  5. 11-Hydroxyundecyl octadecyl disulfide self-assembled monolayers on Au(1 1 1)

    Energy Technology Data Exchange (ETDEWEB)

    Albayrak, Erol [Department of Materials and Metallurgical Engineering, Ahi Evran University, Kırşehir 40000 (Turkey); Karabuga, Semistan [Department of Chemistry, Kahramanmaraş Sütçü İmam University, Kahramanmaraş 46030 (Turkey); Bracco, Gianangelo [CNR-IMEM and Department of Physics, University of Genoa, via Dodecaneso 33, Genoa 16146 (Italy); Danışman, M. Fatih, E-mail: danisman@metu.edu.tr [Department of Chemistry, Middle East Technical University, Ankara 06800 (Turkey)

    2014-08-30

    Highlights: • 11-Hydroxyundecyl octadecyl disulfide self-assembled monolayers on Au(1 1 1) surface were grown by supersonic molecular beam deposition. • Two different lying down monolayer phases were observed depending on the substrate temperature. • High temperature monolayer phase has a diffraction pattern similar to that of mercaptoundecanol SAMs. • Desorption from several different chemisorbed and physisorbed states were observed. - Abstract: Here, we report a helium atom diffraction study of 11-hydroxyundecyl octadecyl disulfide (CH{sub 3}-(CH{sub 2}){sub 17}-S-S-(CH{sub 2}){sub 11}-OH, HOD) self-assembled monolayers (SAMs) produced by supersonic molecular beam deposition (SMBD). Two different lying down monolayer phases were observed depending on the substrate temperature. At low temperatures a poorly ordered phase was observed, while the diffraction patterns of the film grown at high temperatures were similar to that of mercaptoundecanol (MUD) SAMs reported previously in the literature. The transition from the low temperature phase to the high temperature phase is due to S-S bond cleavage at the surface. Desorption from several different chemisorbed and physisorbed states were observed with energies in the same range as observed for MUD and octadecanelthiol (ODT) SAMs.

  6. Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

    Directory of Open Access Journals (Sweden)

    Christian Dollendorf

    2013-08-01

    Full Text Available A redox-responsive polycationic system was synthesized via copolymerization of N,N-diethylacrylamide (DEAAm and 2-(dimethylaminoethyl methacrylate (DMAEMA. N,N’-bis(4-chlorobutanoylcystamine was used as disulfide-containing cross-linker to form networks by the quaternization of tertiary amine groups. The insoluble cationic hydrogels become soluble by reduction of disulfide to mercaptanes by use of dithiothreitol (DTT, tris(2-carboxyethylphosphine (TCEP or cysteamine, respectively. The soluble polymeric system can be cross-linked again by using oxygen or hydrogen peroxide under basic conditions. The redox-responsive polymer networks can be used for molecular inclusion and controlled release. As an example, phenolphthalein, methylene blue and reactive orange 16 were included into the network. After treatment with DTT a release of the dye could be recognized. Physical properties of the cross-linked materials, e.g., glass transition temperature (Tg, swelling behavior and cloud points (Tc were investigated. Redox-responsive behavior was further analyzed by rheological measurements.

  7. Cysteine-Rich Peptide Family with Unusual Disulfide Connectivity from Jasminum sambac.

    Science.gov (United States)

    Kumari, Geeta; Serra, Aida; Shin, Joon; Nguyen, Phuong Q T; Sze, Siu Kwan; Yoon, Ho Sup; Tam, James P

    2015-11-25

    Cysteine-rich peptides (CRPs) are natural products with privileged peptidyl structures that represent a potentially rich source of bioactive compounds. Here, the discovery and characterization of a novel plant CRP family, jasmintides from Jasminum sambac of the Oleaceae family, are described. Two 27-amino acid jasmintides (jS1 and jS2) were identified at the gene and protein levels. Disulfide bond mapping of jS1 by mass spectrometry and its confirmation by NMR spectroscopy revealed disulfide bond connectivity of C-1-C-5, C-2-C-4, and C-3-C-6, a cystine motif that has not been reported in plant CRPs. Structural determination showed that jS1 displays a well-defined structure framed by three short antiparallel β-sheets. Genomic analysis showed that jasmintides share a three-domain precursor arrangement with a C-terminal mature domain preceded by a long pro-domain of 46 residues and an intron cleavage site between the signal sequence and pro-domain. The compact cysteine-rich structure together with an N-terminal pyroglutamic acid residue confers jasmintides high resistance to heat and enzymatic degradation, including exopeptidase treatment. Collectively, these results reveal a new plant CRP structure with an unusual cystine connectivity, which could be useful as a scaffold for designing peptide drugs.

  8. Functional Role of the Disulfide Isomerase ERp57 in Axonal Regeneration.

    Directory of Open Access Journals (Sweden)

    Valentina Castillo

    Full Text Available ERp57 (also known as grp58 and PDIA3 is a protein disulfide isomerase that catalyzes disulfide bonds formation of glycoproteins as part of the calnexin and calreticulin cycle. ERp57 is markedly upregulated in most common neurodegenerative diseases downstream of the endoplasmic reticulum (ER stress response. Despite accumulating correlative evidence supporting a neuroprotective role of ERp57, the contribution of this foldase to the physiology of the nervous system remains unknown. Here we developed a transgenic mouse model that overexpresses ERp57 in the nervous system under the control of the prion promoter. We analyzed the susceptibility of ERp57 transgenic mice to undergo neurodegeneration. Unexpectedly, ERp57 overexpression did not affect dopaminergic neuron loss and striatal denervation after injection of a Parkinson's disease-inducing neurotoxin. In sharp contrast, ERp57 transgenic animals presented enhanced locomotor recovery after mechanical injury to the sciatic nerve. These protective effects were associated with enhanced myelin removal, macrophage infiltration and axonal regeneration. Our results suggest that ERp57 specifically contributes to peripheral nerve regeneration, whereas its activity is dispensable for the survival of a specific neuronal population of the central nervous system. These results demonstrate for the first time a functional role of a component of the ER proteostasis network in peripheral nerve regeneration.

  9. An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

    International Nuclear Information System (INIS)

    Garcia, C.C.; Topisirovic, I.; Djavani, M.; Borden, K.L.B.; Damonte, E.B.; Salvato, M.S.

    2010-01-01

    The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

  10. Ophthalmological and angiographic findings in workers exposed to carbon disulfide (author's transl)

    Energy Technology Data Exchange (ETDEWEB)

    Savic, S.

    1982-01-01

    Microaneurysms are important in the diagnosis of vascular changes caused by carbon disulfide. They can be diagnosed by ophtholmoscopy, angiography or angioscopy. In our opinion even a careful ophthalmoscopic investigation is sufficient for diagnosis, so that angiography is not absolutely necessary for any mass survey. The incidence of microaneurysms correlates with the duration (both daily and total) as well as with the intensity of exposure to carbon disulfide. The quantity correlates closely with the intensity of exposure. The incidence of microaneurysms is not correlated to age; however it was found to be highest in 40-50-year-old men working with staple fibers, whereas in the spinning department it occurred in 50-55-old men. Microaneurysms are found equally frequently in active workers and invalids. There was no difference between the two groups with regard to degenerative changes of the macula. However, the changes found in the eyes of men from the staple fiber department were more pronounced than in those from the spinning department.

  11. Coupling gold nanoparticles to silica nanoparticles through disulfide bonds for glutathione detection

    International Nuclear Information System (INIS)

    Shi Yupeng; Zhang Heng; Zhang Zhaomin; Yi Changqing; Yue Zhenfeng; Teng, Kar-Seng; Li Meijin; Yang Mengsu

    2013-01-01

    Advances in the controlled assembly of nanoscale building blocks have resulted in functional devices which can find applications in electronics, biomedical imaging, drug delivery etc. In this study, novel covalent nanohybrid materials based upon [Ru(bpy) 3 ] 2+ -doped silica nanoparticles (SiNPs) and gold nanoparticles (AuNPs), which could be conditioned as OFF–ON probes for glutathione (GSH) detection, were designed and assembled in sequence, with the disulfide bonds as the bridging elements. The structural and optical properties of the nanohybrid architectures were characterized using transmission electron microscopy, UV–vis spectroscopy and fluorescence spectroscopy, respectively. Zeta potential measurements, x-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy were employed to monitor the reaction processes of the SiNPs–S–S–COOH and SiNPs–S–S–AuNPs synthesis. It was found that the covalent nanohybrid architectures were fluorescently dark (OFF state), indicating that SiNPs were effectively quenched by AuNPs. The fluorescence of the OFF–ON probe was resumed (ON state) when the bridge of the disulfide bond was cleaved by reducing reagents such as GSH. This work provides a new platform and strategy for GSH detection using covalent nanohybrid materials. (paper)

  12. Degradation of ethyl mercaptan and its major intermediate diethyl disulfide by Pseudomonas sp. strain WL2.

    Science.gov (United States)

    Wang, Xiangqian; Wu, Chao; Liu, Nan; Li, Sujing; Li, Wei; Chen, Jianmeng; Chen, Dongzhi

    2015-04-01

    A Pseudomonas sp. strain WL2 that is able to efficiently metabolize ethyl mercaptan (EM) into diethyl disulfide (DEDS) through enzymatic oxidation was isolated from the activated sludge of a pharmaceutical wastewater plant. One hundred percent removal of 113.5 mg L(-1) EM and 110.3 mg L(-1) DEDS were obtained within 14 and 32 h, respectively. A putative EM degradation pathway that involved the catabolism via DEDS was proposed, which indicated DEDS were further mineralized into carbon dioxide (CO2), bacterial cells, and sulfate (SO4 (2-)) through the transformation of element sulfur and ethyl aldehyde. Degradation kinetics for EM and DEDS with different initial concentrations by strain WL2 were evaluated using Haldane-Andrews model with maximum specific degradation rates of 3.13 and 1.33 g g(-1) h(-1), respectively, and maximum degradation rate constants of 0.522 and 0.175 h(-1) using pseudo-first-order kinetic model were obtained. Results obtained that aerobic degradation of EM by strain WL2 was more efficient than those from previous studies. Substrate range studies of strain WL2 demonstrated its ability to degrade several mercaptans, disulfides, aldehydes, and methanol. All the results obtained highlight the potential of strain WL2 for the use in the biodegradation of volatile organic sulfur compounds (VOSCs).

  13. Rhodium-Catalyzed Insertion Reaction of PhP Group of Pentaphenylcyclopentaphosphine with Acyclic and Cyclic Disulfides.

    Science.gov (United States)

    Arisawa, Mieko; Sawahata, Kyosuke; Yamada, Tomoki; Sarkar, Debayan; Yamaguchi, Masahiko

    2018-02-16

    Organophosphorus compounds with a phosphorus atom attached to a phenyl group and two organothio/organoseleno groups were synthesized using the rhodium-catalyzed insertion reaction of the PhP group of pentaphenylcyclopentaphosphine (PhP) 5 with acyclic disulfides and diselenides. The method was applied to the synthesis of heterocyclic compounds containing the S-P-S group by the reaction of (PhP) 5 and cyclic disulfides such as 1,2-dithietes, 1,2-dithiocane, 1,4,5-dithiopane, and 1,2-dithiolanes.

  14. Mechanism of thioredoxin-catalyzed disulfide reduction. Activation of the buried thiol and role of the variable active-site residues

    NARCIS (Netherlands)

    Carvalho, A.P.; Swart, M.; van Stralen, J.N.P.; Fernandes, P.A.; Ramos, M.E.; Bickelhaupt, F.M.

    2008-01-01

    Thioredoxins (Trx) are enzymes with a characteristic CXYC active-site motif that catalyze the reduction of disulfide bonds in other proteins. We have theoretically explored this reaction mechanism, both in the gas phase and in water, using density functional theory. The mechanism of disulfide

  15. The Theory of Exploitation as the Unequal Exchange of Labour

    OpenAIRE

    Veneziani, Roberto; Yoshihara, Naoki

    2016-01-01

    This paper analyses the normative and positive foundations of the theory of exploitation as the unequal exchange of labour (UEL). The key intuitions behind all of the main approaches to UEL exploitation are explicitly analysed as a series of formal claims in a general economic environment. It is then argued that these intuitions can be captured by one fundamental axiom - called Labour Exploitation - which defines the basic domain of all UEL exploitation forms and identifies the formal and the...

  16. The theory of exploitation as the unequal exchange of labour

    OpenAIRE

    Veneziani, Roberto; Yoshihara, Naoki

    2017-01-01

    This paper analyses the normative and positive foundations of the theory of exploitation as the unequal exchange of labour (UEL). The key intuitions behind all of the main approaches to UEL exploitation are explicitly analysed as a series of formal claims in a general economic environment. It is then argued that these intuitions can be captured by one fundamental axiom - called Labour Exploitation - which defines the basic domain of all UEL exploitation forms and identifies the formal and the...

  17. Total exploitation of an ornamental granite quarry

    Directory of Open Access Journals (Sweden)

    Taboada, J.

    2005-09-01

    Full Text Available In this paper we propose a methodology to estimate the recovery percentage for each of the products which can be obtained from the exploitation of an ornamental granite quarry: block, semiblock, masonry-transverse stone, and the smaller materials that can be used to obtain construction aggregates. This methodology ensures that quarry exploitation is exhaustive, thereby minimising the production of spoils and the consequent negative impact on the environment. The analysis is based on a detailed and exhaustive compilation of discontinuity data from the research fronts, which are then interpreted statistically and projected over the three weakness planes that are a particular feature of ornamental granite deposits. Using this information, and bearing in mind the minimum commercially viable sizes for each kind of granite, the corresponding recovery rates are calculated for each material in each plane. The results are then integrated using spatial techniques, and the result is an evaluation of quarry contents with a view to total exploitation. This methodology was applied to a quarry in the opening phase in order to carry out an a priori assessment of the economic feasibility of the quarry.

    En este trabajo se propone una metodología para estimar el porcentaje de recuperación de cada uno de los productos que se pueden obtener en la explotación de una cantera de granito ornamental: bloque, semibloque, manpostería y per piaños, y material restante destinado a la obtención de áridos. De esta manera se logra un aprovechamiento integral de la cantera, evitándose la generación de estériles y el subsiguiente impacto ambiental producido por éstos. La metodología de análisis se basa en la recopilación detallada y exhaustiva de datos de discontinuidades en los frentes de investigación, que se interpretan estadísticamente y se proyectan sobre los tres planos de debilidad propios del granito ornamental. Con esta información, y las

  18. Conformational analysis of large and highly disulfide-stabilized proteins by integrating online electrochemical reduction into an optimized H/D exchange mass spectrometry workflow

    DEFF Research Database (Denmark)

    Trabjerg, Esben; Jakobsen, Rasmus Uffe; Mysling, Simon

    2015-01-01

    Analysis of disulfide-bonded proteins by HDX-MS requires effective and rapid reduction of disulfide bonds before enzymatic digestion in order to increase sequence coverage. In a conventional HDX-MS workflow, disulfide bonds are reduced chemically by addition of a reducing agent to the quench......-antibody, respectively. The presented results demonstrate the successful electrochemical reduction during HDX-MS analysis of both a small exceptional tightly disulfide-bonded protein (NGF) as well as the largest protein attempted to date (IgG1-antibody). We envision that online electrochemical reduction...... the electrochemical reduction efficiency during HDX-MS analysis of two particularly challenging disulfide stabilized proteins: a therapeutic IgG1-antibody and Nerve Growth Factor-β (NGF). Several different parameters (flow rate, applied square wave potential as well as the type of labeling- and quench buffer) were...

  19. An integrated smart system for ambient-assisted living

    CSIR Research Space (South Africa)

    Foko, Thato E

    2013-08-01

    Full Text Available Ambient-assisted living (AAL) is an initiative to extend the time the elderly can live in their home environment by increasing their autonomy and assisting them carry out their daily activities. AAL systems exploit information and communication...

  20. Environmental effects of geothermal energy exploitation

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, H [Japan Metals and Chemicals Co., Ltd., Japan

    1975-01-01

    The environmental effects of geothermal power generation which cause air and water pollution and destruction of natural areas are reviewed. The production of steam and hot water affect existing hot springs sources and can cause ground subsidence. Harmful gas can be released onto the atmosphere from fumarolic gas and hot springs. Hydrothermal geothermal fields occasionally contain harmful substances such as arsenic in the hot water. Serious environmental effects can result from geothermal exploitation activities such as the felling of trees for road construction, well drilling, and plant construction. Once geothermal power generation has begun, the release of H/sub 2/S into the atmosphere and the reinjection of hot water are conducted continuously and sufficient countermeasures can be taken. One problem is the effects of plant construction and operation on natural parks. It is important to reach a compromise between development and protection of natural senic areas. Two figures, two tables, and 13 references are provided.

  1. CHARACTERISTICS OF HYDROCARBON EXPLOITATION IN ARCTIC CIRCLE

    Directory of Open Access Journals (Sweden)

    Vanja Lež

    2013-12-01

    Full Text Available The existence of large quantities of hydrocarbons is supposed within the Arctic Circle. Assumed quantities are 25% of the total undiscovered hydrocarbon reserves on Earth, mostly natural gas. Over 500 major and minor gas accumulations within the Arctic Circle were discovered so far, but apart from Snøhvit gas field, there is no commercial exploitation of natural gas from these fields. Arctic gas projects are complicated, technically hard to accomplish, and pose a great threat to the return of investment, safety of people and equipment and for the ecosystem. Russia is a country that is closest to the realization of the Arctic gas projects that are based on the giant gas fields. The most extreme weather conditions in the seas around Greenland are the reason why this Arctic region is the least explored and furthest from the realization of any gas project (the paper is published in Croatian .

  2. Protocol to Exploit Waiting Resources for UASNs

    Directory of Open Access Journals (Sweden)

    Li-Ling Hung

    2016-03-01

    Full Text Available The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols.

  3. Exploitation of heterogeneous resources for ATLAS Computing

    CERN Document Server

    Chudoba, Jiri; The ATLAS collaboration

    2018-01-01

    LHC experiments require significant computational resources for Monte Carlo simulations and real data processing and the ATLAS experiment is not an exception. In 2017, ATLAS exploited steadily almost 3M HS06 units, which corresponds to about 300 000 standard CPU cores. The total disk and tape capacity managed by the Rucio data management system exceeded 350 PB. Resources are provided mostly by Grid computing centers distributed in geographically separated locations and connected by the Grid middleware. The ATLAS collaboration developed several systems to manage computational jobs, data files and network transfers. ATLAS solutions for job and data management (PanDA and Rucio) were generalized and now are used also by other collaborations. More components are needed to include new resources such as private and public clouds, volunteers' desktop computers and primarily supercomputers in major HPC centers. Workflows and data flows significantly differ for these less traditional resources and extensive software re...

  4. Geometric saliency to characterize radar exploitation performance

    Science.gov (United States)

    Nolan, Adam; Keserich, Brad; Lingg, Andrew; Goley, Steve

    2014-06-01

    Based on the fundamental scattering mechanisms of facetized computer-aided design (CAD) models, we are able to define expected contributions (EC) to the radar signature. The net result of this analysis is the prediction of the salient aspects and contributing vehicle morphology based on the aspect. Although this approach does not provide the fidelity of an asymptotic electromagnetic (EM) simulation, it does provide very fast estimates of the unique scattering that can be consumed by a signature exploitation algorithm. The speed of this approach is particularly relevant when considering the high dimensionality of target configuration variability due to articulating parts which are computationally burdensome to predict. The key scattering phenomena considered in this work are the specular response from a single bounce interaction with surfaces and dihedral response formed between the ground plane and vehicle. Results of this analysis are demonstrated for a set of civilian target models.

  5. Exploitation and use of coal field gas

    Energy Technology Data Exchange (ETDEWEB)

    Wang, K; Li, Z; Sun, Q

    1982-04-25

    There are slightly more than 440 mine shafts in the world from which gas is pumped at the same time coal is being mined, the volume pumped being 3.125 billion cubic meters. All the countries of the world today widely use gas as a fuel and as a raw material for the chemical industry. In China 40 percent of the total number of mine shafts are high gas mine shafts. In China, gas is used largely as fuel by the people, to fire boilers, to make formaldehyde, and to make carbon ink. Prospects are good for the exploitation of mine shaft gas that is produced in association with coal. Mine shaft gas is a top quality energy source with an extraction life that is longer than coals. (DP)

  6. Summary of radiation protection in exploitation

    International Nuclear Information System (INIS)

    Garcier, Yves; Guers, Rene; Bidard, Francoise; Colson, Philippe; Gonin, Michele; Delabre, Herve; Hemidy, Pierre-Yves; Corgnet, Bruno; Perrin, Marie-Claire; Phan Hoang, Long; Abela, Gonzague; Crepieux, Virginie; Guyot, Pierre; Haranger, Didier; Warembourg, Philippe

    2004-01-01

    This document proposes a large and detailed overview of notions and practices regarding radiation protection in relationship with an NPP exploitation framework. It presents the main notions: matter structure, radioactivity, interactions between matter and radiations, types of ionizing radiation, magnitudes and measurement units, exposure modes, main principles of radiation protection, means of protection against internal and external exposures. The second part proposes an overview of the origin of radiological risks in a nuclear power plant. This origin can be found in fission products, activation products, actinides, designed protections, or circuit contaminations. These radiological risks are more precisely identified and described in terms of detection and prevention (internal exposure risk, contamination risk, iodine-related risk, alpha radiation-related risk, access to the reactor building). The next part addresses the medical and radiological follow-up of exposed workers by a special medical control, by an individual exposure control, by a specific control of female personnel, and by attention to exceptional exposures. Measurement means are presented (detection principles, installation continuous control, workspaces control, personnel contamination control, follow-up of individual dose) as well as collective and individual protection means. The management of radiation protection is addressed through a presentation of decision and management structures for radiation protection, and of EDF objectives and ambitions in this domain. The organization of radiation protection during exploitation is described: responsibilities for radiation protection in a nuclear power station, requirements for workers, preparation of interventions in controlled zone, work execution in controlled zone, zone controls and radiological cleanness of installations. The two last chapters address issues and practices of radiation protection in the case of deconstruction or dismantling, and

  7. Identification, activity and disulfide connectivity of C-di-GMP regulating proteins in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Kajal Gupta

    2010-11-01

    Full Text Available C-di-GMP, a bacterial second messenger plays a key role in survival and adaptation of bacteria under different environmental conditions. The level of c-di-GMP is regulated by two opposing activities, namely diguanylate cyclase (DGC and phosphodiesterase (PDE-A exhibited by GGDEF and EAL domain, respectively in the same protein. Previously, we reported a bifunctional GGDEF-EAL domain protein, MSDGC-1 from Mycobacterium smegmatis showing both these activities (Kumar and Chatterji, 2008. In this current report, we have identified and characterized the homologous protein from Mycobacterium tuberculosis (Rv 1354c named as MtbDGC. MtbDGC is also a bifunctional protein, which can synthesize and degrade c-di-GMP in vitro. Further we expressed Mtbdgc in M. smegmatis and it was able to complement the MSDGC-1 knock out strain by restoring the long term survival of M. smegmatis. Another protein Rv 1357c, named as MtbPDE, is an EAL domain protein and degrades c-di-GMP to pGpG in vitro. Rv1354c and 1357c have seven cysteine amino acids in their sequence, distributed along the full length of the protein. Disulfide bonds play an important role in stabilizing protein structure and regulating protein function. By proteolytic digestion and mass spectrometric analysis of MtbDGC, connectivity between cysteine pairs Cys94-Cys584, Cys2-Cys479 and Cys429-Cys614 was determined, whereas the third cysteine (Cys406 from N terminal was found to be free in MtbDGC protein, which was further confirmed by alkylation with iodoacetamide labeling. Bioinformatics modeling investigations also supported the pattern of disulfide connectivity obtained by Mass spectrometric analysis. Cys406 was mutated to serine by site directed mutagenesis and the mutant MtbC406S was not found to be active and was not able to synthesize or degrade c-di-GMP. The disulfide connectivity established here would help further in understanding the structure - function relationship in MtbDGC.

  8. Interchange reaction of disulfides and denaturation of oxytocin by copper(II)/ascorbic acid/O2 system.

    Science.gov (United States)

    Inoue, H; Hirobe, M

    1987-05-29

    The interchange reaction of disulfides was caused by the copper(II)/ascorbic acid/O2 system. The incubation of two symmetric disulfides, L-cystinyl-bis-L-phenylalanine (PP) and L-cystinyl-bis-L-tyrosine (TT), with L-ascorbic acid and CuSO4 in potassium phosphate buffer (pH 7.2, 50 mM) resulted in the formation of an asymmetric disulfide, L-cystinyl-L-phenylalanine-L-tyrosine (PT), and the final ratio of PP:PT:TT was 1:2:1. As the reaction was inhibited by catalase and DMSO only at the initial time, hydroxyl radical generated by the copper(II)/ascorbic acid/O2 system seemed to be responsible for the initiation of the reaction. Oxytocin and insulin were denatured by this system, and catalase and DMSO similarly inhibited these denaturations. As the composition of amino acids was unchanged after the reaction, hydroxyl radical was thought to cause the cleavage and/or interchange reaction of disulfides to denature the peptides.

  9. S center dot center dot center dot N chalcogen bonded complexes of carbon disulfide with diazines. Theoretical study

    Czech Academy of Sciences Publication Activity Database

    Zierkiewicz, W.; Fanfrlík, Jindřich; Michalczyk, M.; Michalska, D.; Hobza, Pavel

    2018-01-01

    Roč. 500, Jan 26 (2018), s. 37-44 ISSN 0301-0104 Institutional support: RVO:61388963 Keywords : chalcogen bond * carbon disulfide * diazines * DFT Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 1.767, year: 2016

  10. Protein binding of N-2-mercaptoethyl-1,3-diaminopropane via mixed disulfide formation after oral administration of WR 2721

    Energy Technology Data Exchange (ETDEWEB)

    Tabachnik, N.F.; Blackburn, P.; Peterson, C.M.; Cerami, A.

    1982-02-01

    Earlier studies have shown that WR 2721 (H2N-(CH2)3-NH(CH2)2SPO3H2) is converted to its free thiol form, N-2-mercaptoethyl-1,3-diaminopropane (MDP), at the acidic pH of the stomach. MDP is a radioprotective compound and a mucolytic agent capable of decreasing sputum viscosity in the lungs of patients with cystic fibrosis. Conversion of WR 2721 and MDP to the corresponding sulfonic acid (MDP-SO3H) permits quantitative determination of these compounds in physiological fluids by use of an automatic amino acid analyzer. After oral administration of WR 2721 to human patients and rabbits it is converted to MDP and the free thiol form of the drug associates with plasma proteins by mixed disulfide linkage. The plasma proteins serve as a depot and reservoir of MDP for potential exchange at the tissues. When incubated with whole sputum or with purified mucin solutions in vitro, MDP decreased the viscosity of these solutions by reduction of the accessible disulfide bonds of the mucin molecule and was subsequently found in mixed disulfide association with the mucin molecule. The association of MDP with proteins via mixed disulfide linkage has important implications for the development of optimal dose regimens for administration of WR 2721 to patients.

  11. Protein binding of N-2-mercaptoethyl-1,3-diaminopropane via mixed disulfide formation after oral administration of WR 2721

    International Nuclear Information System (INIS)

    Tabachnik, N.F.; Blackburn, P.; Peterson, C.M.; Cerami, A.

    1982-01-01

    Earlier studies have shown that WR 2721 [H2N-(CH2)3-NH(CH2)2SPO3H2] is converted to its free thiol form, N-2-mercaptoethyl-1,3-diaminopropane (MDP), at the acidic pH of the stomach. MDP is a radioprotective compound and a mucolytic agent capable of decreasing sputum viscosity in the lungs of patients with cystic fibrosis. Conversion of WR 2721 and MDP to the corresponding sulfonic acid (MDP-SO3H) permits quantitative determination of these compounds in physiological fluids by use of an automatic amino acid analyzer. After oral administration of WR 2721 to human patients and rabbits it is converted to MDP and the free thiol form of the drug associates with plasma proteins by mixed disulfide linkage. The plasma proteins serve as a depot and reservoir of MDP for potential exchange at the tissues. When incubated with whole sputum or with purified mucin solutions in vitro, MDP decreased the viscosity of these solutions by reduction of the accessible disulfide bonds of the mucin molecule and was subsequently found in mixed disulfide association with the mucin molecule. The association of MDP with proteins via mixed disulfide linkage has important implications for the development of optimal dose regimens for administration of WR 2721 to patients

  12. CO2·- radical induced cleavage of disulfide bonds in proteins. A gamma-ray and pulse radiolysis mechanistic investigation

    International Nuclear Information System (INIS)

    Favaudon, V.; Tourbez, H.; Lhoste, J-M.; Houee-Levin, C.

    1990-01-01

    Disulfide bond reduction by the CO 2 ·- radical was investigated in aponeocarzinostatin, aporiboflavin-binding protein, and bovine immunoglobulin. Protein-bound cysteine free thiols were formed under γ-ray irradiation in the course of a pH-dependent and protein concentration dependent chain reaction. The chain efficiency increased upon acidification of the medium, with an apparent pK a around 5, and decreased abruptly below pH 3.6. It decreased also at neutral pH as cysteine accumulated. From pulse radiolysis analysis, CO 2 ·- proved able to induce rapid one-electron oxidation of thiols and of tyrosine phenolic groups in addition to one-electron donation to exposed disulfide bonds. The bulk rate constant of CO 2 ·- uptake by the native proteins was 5- to 10-fold faster at pH 3 than at pH 8, and the protonated form of the disulfide radical anion, appeared to be the major protein radical species formed under acidic conditions. Formation of the disulfide radical cation, phenoxyl radical Tyr-O · disproportionation, and phenoxyl radical induced oxidation of preformed thiol groups should also be taken into consideration to explain the fate of the oxygen-centered phenoxyl radical

  13. Simultaneous electrochemical determination of L-cysteine and L-cysteine disulfide at carbon ionic liquid electrode.

    Science.gov (United States)

    Safavi, Afsaneh; Ahmadi, Raheleh; Mahyari, Farzaneh Aghakhani

    2014-04-01

    A linear sweep voltammetric method is used for direct simultaneous determination of L-cysteine and L-cysteine disulfide (cystine) based on carbon ionic liquid electrode. With carbon ionic liquid electrode as a high performance electrode, two oxidation peaks for L-cysteine (0.62 V) and L-cysteine disulfide (1.3 V) were observed with a significant separation of about 680 mV (vs. Ag/AgCl) in phosphate buffer solution (pH 6.0). The linear ranges were obtained as 1.0-450 and 5.0-700 μM and detection limits were estimated to be 0.298 and 4.258 μM for L-cysteine and L-cysteine disulfide, respectively. This composite electrode was applied for simultaneous determination of L-cysteine and L-cysteine disulfide in two real samples, artificial urine and nutrient broth. Satisfactory results were obtained which clearly indicate the applicability of the proposed electrode for simultaneous determination of these compounds in complex matrices.

  14. Fast and efficient green synthesis of thiosulfonate S-esters by microwave-supported permanganate oxidation of symmetrical disulfides

    DEFF Research Database (Denmark)

    Thi, Luu Thi Xuan; Thi Nguyen, Thao-Tran; Le, Thach Ngoc

    2015-01-01

    Potassium permanganate absorbed on copper(II) sulfate pentahydrate has been found to be an efficient, inexpensive, and green oxidation agent for the synthesis of “symmetrical” thiosulfonate S-esters by oxidation of the corresponding symmetrical disulfides. The oxidation reactions were carried out...

  15. Single Layer Molybdenum Disulfide under Direct Out-of-Plane Compression: Low-Stress Band-Gap Engineering

    Czech Academy of Sciences Publication Activity Database

    Álvarez, M. P.; del Corro, Elena; Morales-García, A.; Kavan, Ladislav; Kalbáč, Martin; Frank, Otakar

    2015-01-01

    Roč. 15, č. 5 (2015), s. 3139-3146 ISSN 1530-6984 R&D Projects: GA ČR GA14-15357S; GA MŠk LL1301 Institutional support: RVO:61388955 Keywords : Molybdenum disulfide * band gap engineering * out-of-plane compression Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 13.779, year: 2015

  16. The effects of morphology re-arrangements on the pseudocapacitive properties of mesoporous molybdenum disulfide (MoS2) nanoflakes

    CSIR Research Space (South Africa)

    Khawula, TNY

    2016-07-01

    Full Text Available Mesoporous molybdenum disulfide (MoS(sub2)) with different morphologies have been prepared via hydrothermal method using different solvents, water or water/acetone mixture. The MoS(sub2) obtained with water alone gave a graphene-like nanoflakes (g...

  17. Step-wise addition of disulfide bridge in firefly luciferase controls color shift through a flexible loop: a thermodynamic perspective.

    Science.gov (United States)

    Nazari, Mahboobeh; Hosseinkhani, Saman; Hassani, Leila

    2013-02-01

    Multi-color bioluminescence is developed using the introduction of single/double disulfide bridges in firefly luciferase. The bioluminescence reaction, which uses luciferin, Mg(2+)-ATP and molecular oxygen to yield an electronically excited oxyluciferin, is carried out by the luciferase and emits visible light. The bioluminescence color of firefly luciferases is determined by the luciferase sequence and assay conditions. It has been proposed that the stability of a protein may increase through the introduction of a disulfide bridge that decreases the configurational entropy of unfolding. Single and double disulfide bridges are introduced into Photinus pyralis firefly luciferase to make separate mutant enzymes with a single/double bridge (C(81)-A(105)C, L(306)C-L(309)C, P(451)C-V(469)C; C(81)-A(105)C/P(451)C-V(469)C, and A(296)C-A(326)C/P(451)C-V(469)C). By introduction of disulfide bridges using site-directed mutagenesis in Photinus pyralis luciferase the color of emitted light was changed to red or kept in different extents. The bioluminescence color shift occurred with displacement of a critical loop in the luciferase structure without any change in green emitter mutants. Thermodynamic analysis revealed that among mutants, L(306)C-L(309)C shows a remarkable stability against urea denaturation and also a considerable increase in kinetic stability and a clear shift in bioluminescence spectra towards red.

  18. 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.

  19. Chaperonin GroE-facilitated refolding of disulfide-bonded and reduced Taka-amylase A from Aspergillus oryzae.

    Science.gov (United States)

    Kawata, Y; Hongo, K; Mizobata, T; Nagai, J

    1998-12-01

    The refolding characteristics of Taka-amylase A (TAA) from Aspergillus oryzae in the presence of the chaperonin GroE were studied in terms of activity and fluorescence. Disulfide-bonded (intact) TAA and non-disulfide-bonded (reduced) TAA were unfolded in guanidine hydrochloride and refolded by dilution into buffer containing GroE. The intermediates of both intact and reduced enzymes were trapped by GroEL in the absence of nucleotide. Upon addition of nucleotides such as ATP, ADP, CTP or UTP, the intermediates were released from GroEL and recovery of activity was detected. In both cases, the refolding yields in the presence of GroEL and ATP were higher than spontaneous recoveries. Fluorescence studies of intrinsic tryptophan and a hydrophobic probe, 8-anilinonaphthalene-1-sulfonate, suggested that the intermediates trapped by GroEL assumed conformations with different hydrophobic properties. The presence of protein disulfide isomerase or reduced and oxidized forms of glutathione in addition to GroE greatly enhanced the refolding reaction of reduced TAA. These findings suggest that GroE has an ability to recognize folding intermediates of TAA protein and facilitate refolding, regardless of the existence or absence of disulfide bonds in the protein.

  20. 40 CFR 63.500 - Back-end process provisions-carbon disulfide limitations for styrene butadiene rubber by emulsion...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Back-end process provisions-carbon disulfide limitations for styrene butadiene rubber by emulsion processes. 63.500 Section 63.500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR...

  1. Protein disulfide isomerase-like protein 1-1 controls endosperm development through regulation of the amount and composition of seed proteins in rice.

    Directory of Open Access Journals (Sweden)

    Yeon Jeong Kim

    Full Text Available Protein disulfide isomerase (PDI is a chaperone protein involved in oxidative protein folding by acting as a catalyst and assisting folding in the endoplasmic reticulum (ER. A genome database search showed that rice contains 19 PDI-like genes. However, their functions are not clearly identified. This paper shows possible functions of rice PDI-like protein 1-1 (PDIL1-1 during seed development. Seeds of the T-DNA insertion PDIL1-1 mutant, PDIL1-1Δ, identified by genomic DNA PCR and western blot analysis, display a chalky phenotype and a thick aleurone layer. Protein content per seed was significantly lower and free sugar content higher in PDIL1-1Δ mutant seeds than in the wild type. Proteomic analysis of PDIL1-1Δ mutant seeds showed that PDIL1-1 is post-translationally regulated, and its loss causes accumulation of many types of seed proteins including glucose/starch metabolism- and ROS (reactive oxygen species scavenging-related proteins. In addition, PDIL1-1 strongly interacts with the cysteine protease OsCP1. Our data indicate that the opaque phenotype of PDIL1-1Δ mutant seeds results from production of irregular starch granules and protein body through loss of regulatory activity for various proteins involved in the synthesis of seed components.

  2. Piloting the older adult financial exploitation measure in adult safeguarding services.

    Science.gov (United States)

    Phelan, A; Fealy, G; Downes, C

    Financial abuse is arguably the most complex form of elder abuse as it may occur remote to the older person and it is impacted by issues such as cultural values, perpetrator intent and family expectations. Financial abuse may not be recognised by either the older person or the perpetrator, thus, its prevention, early identification and amelioration are important. The (Irish) National Centre for the Protection of Older People undertook a study to determine the appropriateness of the Older Adult Financial Exploitation Measure for use by the national safeguarding older person services. Findings from a small pilot study involving 16 safeguarding staff's use of the Older Adult Financial Exploitation Measure with 52 community dwelling older people referred to their service demonstrate a higher suspicion of financial abuse as well as identifying multiple instances of possible financial exploitation in a single individual. Thus, the Older Adult Financial Exploitation Measure is considered appropriate to assist safeguarding personnel's assessment of older people related to a suspicion of financial abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Proba-V Mission Exploitation Platform

    Science.gov (United States)

    Goor, E.

    2017-12-01

    VITO and partners developed the Proba-V Mission Exploitation Platform (MEP) as an end-to-end solution to drastically improve the exploitation of the Proba-V (an EC Copernicus contributing mission) EO-data archive, the past mission SPOT-VEGETATION and derived vegetation parameters by researchers, service providers (e.g. the EC Copernicus Global Land Service) and end-users. The analysis of time series of data (PB range) is addressed, as well as the large scale on-demand processing of near real-time data on a powerful and scalable processing environment. New features are still developed, but the platform is yet fully operational since November 2016 and offers A time series viewer (browser web client and API), showing the evolution of Proba-V bands and derived vegetation parameters for any country, region, pixel or polygon defined by the user. Full-resolution viewing services for the complete data archive. On-demand processing chains on a powerfull Hadoop/Spark backend. Virtual Machines can be requested by users with access to the complete data archive mentioned above and pre-configured tools to work with this data, e.g. various toolboxes and support for R and Python. This allows users to immediately work with the data without having to install tools or download data, but as well to design, debug and test applications on the platform. Jupyter Notebooks is available with some examples python and R projects worked out to show the potential of the data. Today the platform is already used by several international third party projects to perform R&D activities on the data, and to develop/host data analysis toolboxes. From the Proba-V MEP, access to other data sources such as Sentinel-2 and landsat data is also addressed. Selected components of the MEP are also deployed on public cloud infrastructures in various R&D projects. Users can make use of powerful Web based tools and can self-manage virtual machines to perform their work on the infrastructure at VITO with access to

  4. Mission Exploitation Platform PROBA-V

    Science.gov (United States)

    Goor, Erwin

    2016-04-01

    VITO and partners developed an end-to-end solution to drastically improve the exploitation of the PROBA-V EO-data archive (http://proba-v.vgt.vito.be/), the past mission SPOT-VEGETATION and derived vegetation parameters by researchers, service providers and end-users. The analysis of time series of data (+1PB) is addressed, as well as the large scale on-demand processing of near real-time data. From November 2015 an operational Mission Exploitation Platform (MEP) PROBA-V, as an ESA pathfinder project, will be gradually deployed at the VITO data center with direct access to the complete data archive. Several applications will be released to the users, e.g. - A time series viewer, showing the evolution of PROBA-V bands and derived vegetation parameters for any area of interest. - Full-resolution viewing services for the complete data archive. - On-demand processing chains e.g. for the calculation of N-daily composites. - A Virtual Machine will be provided with access to the data archive and tools to work with this data, e.g. various toolboxes and support for R and Python. After an initial release in January 2016, a research platform will gradually be deployed allowing users to design, debug and test applications on the platform. From the MEP PROBA-V, access to Sentinel-2 and landsat data will be addressed as well, e.g. to support the Cal/Val activities of the users. Users can make use of powerful Web based tools and can self-manage virtual machines to perform their work on the infrastructure at VITO with access to the complete data archive. To realise this, private cloud technology (openStack) is used and a distributed processing environment is built based on Hadoop. The Hadoop ecosystem offers a lot of technologies (Spark, Yarn, Accumulo, etc.) which we integrate with several open-source components. The impact of this MEP on the user community will be high and will completely change the way of working with the data and hence open the large time series to a larger

  5. Efficient assembly of recombinant major histocompatibility complex class I molecules with preformed disulfide bonds

    DEFF Research Database (Denmark)

    Ostergaard Pedersen, L; Nissen, Mogens Holst; Hansen, N J

    2001-01-01

    The expression of major histocompatibility class I (MHC-I) crucially depends upon the binding of appropriate peptides. MHC-I from natural sources are therefore always preoccupied with peptides complicating their purification and analysis. Here, we present an efficient solution to this problem....... Recombinant MHC-I heavy chains were produced in Escherichia coli and subsequently purified under denaturing conditions. In contrast to common practice, the molecules were not reduced during the purification. The oxidized MHC-I heavy chain isoforms were highly active with respect to peptide binding....... This suggests that de novo folding of denatured MHC-I molecules proceed efficiently if directed by preformed disulfide bond(s). Importantly, these molecules express serological epitopes and stain specific T cells; and they bind peptides specifically. Several denatured MHC-I heavy chains were analyzed and shown...

  6. Atomic force microscopy studies on molybdenum disulfide flakes as sodium-ion anodes.

    Science.gov (United States)

    Lacey, Steven D; Wan, Jiayu; von Wald Cresce, Arthur; Russell, Selena M; Dai, Jiaqi; Bao, Wenzhong; Xu, Kang; Hu, Liangbing

    2015-02-11

    A microscale battery comprised of mechanically exfoliated molybdenum disulfide (MoS2) flakes with copper connections and a sodium metal reference was created and investigated as an intercalation model using in situ atomic force microscopy in a dry room environment. While an ethylene carbonate-based electrolyte with a low vapor pressure allowed topographical observations in an open cell configuration, the planar microbattery was used to conduct in situ measurements to understand the structural changes and the concomitant solid electrolyte interphase (SEI) formation at the nanoscale. Topographical observations demonstrated permanent wrinkling behavior of MoS2 electrodes upon sodiation at 0.4 V. SEI formation occurred quickly on both flake edges and planes at voltages before sodium intercalation. Force spectroscopy measurements provided quantitative data on the SEI thickness for MoS2 electrodes in sodium-ion batteries for the first time.

  7. Highly Stretchable Supercapacitors Based on Aligned Carbon Nanotube/Molybdenum Disulfide Composites.

    Science.gov (United States)

    Lv, Tian; Yao, Yao; Li, Ning; Chen, Tao

    2016-08-01

    Stretchable supercapacitors that can sustain their performance under unpredictable tensile force are important elements for practical applications of various portable and wearable electronics. However, the stretchability of most reported supercapacitors was often lower than 100 % because of the limitation of the electrodes used. Herein we developed all-solid-state supercapacitors with a stretchability as high as 240 % by using aligned carbon nanotube composites with compact structure as electrodes. By combined with pseudocapacitive molybdenum disulfide nanosheets, the newly developed supercapacitor showed a specific capacitance of 13.16 F cm(-3) , and also showed excellent cycling retention (98 %) after 10 000 charge-discharge cycles. This work also presents a general and effective approach in developing high-performance electrodes for flexible and stretchable electronics. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Enhanced photoresponse of monolayer molybdenum disulfide (MoS2) based on microcavity structure

    Science.gov (United States)

    Lu, Yanan; Yang, Guofeng; Wang, Fuxue; Lu, Naiyan

    2018-05-01

    There is an increasing interest in using monolayer molybdenum disulfide (MoS2) for optoelectronic devices because of its inherent direct band gap characteristics. However, the weak absorption of monolayer MoS2 restricts its applications, novel concepts need to be developed to address the weakness. In this work, monolayer MoS2 monolithically integrates with plane microcavity structure, which is formed by the top and bottom chirped distributed Bragg reflector (DBR), is demonstrated to improve the absorption of MoS2. The optical absorption is 17-fold enhanced, reaching values over 70% at work wavelength. Moreover, the monolayer MoS2-based photodetector device with microcavity presents a significantly increased photoresponse, demonstrating its promising prospects in MoS2-based optoelectronic devices.

  9. Simultaneous Disulfide and Boronic Acid Ester Exchange in Dynamic Combinatorial Libraries

    Directory of Open Access Journals (Sweden)

    Sanna L. Diemer

    2015-09-01

    Full Text Available Dynamic combinatorial chemistry has emerged as a promising tool for the discovery of complex receptors in supramolecular chemistry. At the heart of dynamic combinatorial chemistry are the reversible reactions that enable the exchange of building blocks between library members in dynamic combinatorial libraries (DCLs ensuring thermodynamic control over the system. If more than one reversible reaction operates in a single dynamic combinatorial library, the complexity of the system increases dramatically, and so does its possible applications. One can imagine two reversible reactions that operate simultaneously or two reversible reactions that operate independently. Both these scenarios have advantages and disadvantages. In this contribution, we show how disulfide exchange and boronic ester transesterification can function simultaneous in dynamic combinatorial libraries under appropriate conditions. We describe the detailed studies necessary to establish suitable reaction conditions and highlight the analytical techniques appropriate to study this type of system.

  10. Simple one-pot synthesis of thioureas from amine, carbon disulfide and oxidants in water

    Directory of Open Access Journals (Sweden)

    Milosavljević Milutin M.

    2016-01-01

    Full Text Available The present study reports the new facile methodology for synthesis of symmetrical and asymmetrical thioureas by an one-pot reaction of amine, carbon disulfide and oxidants: hydrogen peroxide, ethylenediamine tetraacetic acid (EDTA/sodium percarbonate system or air. The structures of the synthesized compounds were confirmed by IR, 1H and 13C NMR and MS methods. Reaction mechanism has been proposed on the basis of reaction intermediate isolation and their structure determination. The synthetic benefits of the presented methods is reflected in the operational simplicity, mild reaction conditions, short reaction times, recycling of solvent, high purity and yield of products, absence of dangerous by-products and technological applicability at industrial scale. Considering commercial importance of the thioureas, it can be emphasized that implementation of the optimal synthesis of thiourea, based on presented methods, at industrial level of production would provide concurrent alternative to existing technologies in use. [Projekat Ministarstva nauke Republike Srbije, br. 172013

  11. In situ aquifer bioremediation of organics including cyanide and carbon disulfide

    International Nuclear Information System (INIS)

    Abou-Rizk, J.A.M.; Leavitt, M.E.; Graves, D.A.

    1995-01-01

    Low levels (< 1 mg/L) of acetone, cyanide, phenol, naphthalene, 2-methylnaphthalene, and carbon disulfide from an inactive industrial landfill were found above background levels in a shallow aquifer at an eastern coastal site. In situ biodegradation was evaluated for treatment of these contaminants. Two soil samples and three groundwater samples were taken from the site for a laboratory bioassessment and a biotreatability test. The positive results of the bioassessment suggested moving forward with biotreatability testing. Biotreatability test results indicated suitable site conditions for bioremediation and that all the contaminants of concern at the site could be biodegraded to nondetect or very low levels (< 50 microg/L) with oxygen only; i.e., addition of nutrients was not required. Pilot-scale testing was undertaken on site to provide information for full-scale design, including oxygen requirements and air injection well spacing. This report describes the approach, the results, and their impact on the full-scale remediation system

  12. Identification of intra- and intermolecular disulfide bridges in the multidrug resistance transporter ABCG2

    DEFF Research Database (Denmark)

    Henriksen, Ulla Birk; Fog, Jacob U; Litman, Thomas

    2005-01-01

    cysteines predicted to be on the extracellular face of ABCG2. Upon mutation of Cys-592 or Cys-608 to alanine (C592A and C608A), ABCG2 migrated as a dimer in SDS-PAGE under non-reducing conditions; however, mutation of Cys-603 to Ala (C603A) caused the transporter to migrate as a single monomeric band....... Despite this change, C603A displayed efficient membrane targeting and preserved transport function. Because the transporter migrated as a dimer in SDS-PAGE, when only Cys-603 was present (C592A-C608A), the data suggest that Cys-603 forms a symmetrical intermolecular disulfide bridge in the ABCG2 homodimer...

  13. Spin-Polarized Tunneling through Chemical Vapor Deposited Multilayer Molybdenum Disulfide.

    Science.gov (United States)

    Dankert, André; Pashaei, Parham; Kamalakar, M Venkata; Gaur, Anand P S; Sahoo, Satyaprakash; Rungger, Ivan; Narayan, Awadhesh; Dolui, Kapildeb; Hoque, Md Anamul; Patel, Ram Shanker; de Jong, Michel P; Katiyar, Ram S; Sanvito, Stefano; Dash, Saroj P

    2017-06-27

    The two-dimensional (2D) semiconductor molybdenum disulfide (MoS 2 ) has attracted widespread attention for its extraordinary electrical-, optical-, spin-, and valley-related properties. Here, we report on spin-polarized tunneling through chemical vapor deposited multilayer MoS 2 (∼7 nm) at room temperature in a vertically fabricated spin-valve device. A tunnel magnetoresistance (TMR) of 0.5-2% has been observed, corresponding to spin polarization of 5-10% in the measured temperature range of 300-75 K. First-principles calculations for ideal junctions result in a TMR up to 8% and a spin polarization of 26%. The detailed measurements at different temperature, bias voltages, and density functional theory calculations provide information about spin transport mechanisms in vertical multilayer MoS 2 spin-valve devices. These findings form a platform for exploring spin functionalities in 2D semiconductors and understanding the basic phenomena that control their performance.

  14. Room temperature humidity sensor based on polyaniline-tungsten disulfide composite

    Science.gov (United States)

    Manjunatha, S.; Chethan, B.; Ravikiran, Y. T.; Machappa, T.

    2018-05-01

    Polyaniline-tungsten disulfide (PANI-WS2) composite was synthesized using in situ polymerization technique by adding finely grinded powder of WS2 during the polymerization of aniline. Field emission scanning electron microscopy (FESEM) images showed the granular morphology with porous nature. Energy dispersive X-ray spectroscopy (EDX) confirmed the presence of carbon, nitrogen, chlorine of PANI, tungsten and sulfur elements of WS2. Humidity sensing property of the composite was investigated by plotting change in its resistance with different relative humidity environments ranging from 10 to 97% RH. Decrease in resistance of the composite was observed with increase in relative humidity. Maximum sensing response of the composite was found to be 88.46%. Response and recovery times of the composite at 97%RH were fair enough to fabricate a sensor based on it. Stability of the composite with respect to the humidity sensing behavior was observed to be unchanged even after two months.

  15. Few-layer molybdenum disulfide transistors and circuits for high-speed flexible electronics

    Science.gov (United States)

    Cheng, Rui; Jiang, Shan; Chen, Yu; Liu, Yuan; Weiss, Nathan; Cheng, Hung-Chieh; Wu, Hao; Huang, Yu; Duan, Xiangfeng

    2014-01-01

    Two-dimensional layered materials, such as molybdenum disulfide, are emerging as an exciting material system for future electronics due to their unique electronic properties and atomically thin geometry. Here we report a systematic investigation of MoS2 transistors with optimized contact and device geometry, to achieve self-aligned devices with performance including an intrinsic gain over 30, an intrinsic cut-off frequency fT up to 42 GHz and a maximum oscillation frequency fMAX up to 50 GHz, exceeding the reported values for MoS2 transistors to date (fT ~ 0.9 GHz, fMAX ~ 1 GHz). Our results show that logic inverters or radio frequency amplifiers can be formed by integrating multiple MoS2 transistors on quartz or flexible substrates with voltage gain in the gigahertz regime. This study demonstrates the potential of two-dimensional layered semiconductors for high-speed flexible electronics. PMID:25295573

  16. Quantum transport model for zigzag molybdenum disulfide nanoribbon structures : A full quantum framework

    International Nuclear Information System (INIS)

    Chen, Chun-Nan; Shyu, Feng-Lin; Chung, Hsien-Ching; Lin, Chiun-Yan; Wu, Jhao-Ying

    2016-01-01

    Mainly based on non-equilibrium Green’s function technique in combination with the three-band model, a full atomistic-scale and full quantum method for solving quantum transport problems of a zigzag-edge molybdenum disulfide nanoribbon (zMoSNR) structure is proposed here. For transport calculations, the relational expressions of a zMoSNR crystalline solid and its whole device structure are derived in detail and in its integrity. By adopting the complex-band structure method, the boundary treatment of this open boundary system within the non-equilibrium Green’s function framework is so straightforward and quite sophisticated. The transmission function, conductance, and density of states of zMoSNR devices are calculated using the proposed method. The important findings in zMoSNR devices such as conductance quantization, van Hove singularities in the density of states, and contact interaction on channel are presented and explored in detail.

  17. Quantum transport model for zigzag molybdenum disulfide nanoribbon structures : A full quantum framework

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chun-Nan, E-mail: quantum@mail.tku.edu.tw, E-mail: ccn1114@kimo.com [Quantum Engineering Laboratory, Department of Physics, Tamkang University, Tamsui, New Taipei 25137, Taiwan (China); Shyu, Feng-Lin [Department of Physics, R.O.C. Military Academy, Kaohsiung 830, Taiwan (China); Chung, Hsien-Ching; Lin, Chiun-Yan [Department of Physics, National Cheng Kung University, Tainan 70101, Taiwan (China); Wu, Jhao-Ying [Center of General Studies, National Kaohsiung Marine University, Kaohsiung 811, Taiwan (China)

    2016-08-15

    Mainly based on non-equilibrium Green’s function technique in combination with the three-band model, a full atomistic-scale and full quantum method for solving quantum transport problems of a zigzag-edge molybdenum disulfide nanoribbon (zMoSNR) structure is proposed here. For transport calculations, the relational expressions of a zMoSNR crystalline solid and its whole device structure are derived in detail and in its integrity. By adopting the complex-band structure method, the boundary treatment of this open boundary system within the non-equilibrium Green’s function framework is so straightforward and quite sophisticated. The transmission function, conductance, and density of states of zMoSNR devices are calculated using the proposed method. The important findings in zMoSNR devices such as conductance quantization, van Hove singularities in the density of states, and contact interaction on channel are presented and explored in detail.

  18. Determination of glutathione and glutathione disulfide in biological samples: an in-depth review.

    Science.gov (United States)

    Monostori, Péter; Wittmann, Gyula; Karg, Eszter; Túri, Sándor

    2009-10-15

    Glutathione (GSH) is a thiol-containing tripeptide, which plays central roles in the defence against oxidative damage and in signaling pathways. Upon oxidation, GSH is transformed to glutathione disulfide (GSSG). The concentrations of GSH and GSSG and their molar ratio are indicators of cell functionality and oxidative stress. Assessment of redox homeostasis in various clinical states and medical applications for restoration of the glutathione status are of growing importance. This review is intended to provide a state-of-the-art overview of issues relating to sample pretreatment and choices for the separation and detection of GSH and GSSG. High-performance liquid chromatography, capillary electrophoresis and gas chromatography (as techniques with a separation step) with photometric, fluorimetric, electrochemical and mass spectrometric detection are discussed, stress being laid on novel approaches.

  19. Alkali metal and alkali metal hydroxide intercalates of the layered transition metal disulfides

    International Nuclear Information System (INIS)

    Kanzaki, Y.; Konuma, M.; Matsumoto, O.

    1981-01-01

    The intercalation reaction of some layered transition metal disulfides with alkali metals, alkali metal hydroxides, and tetraalkylammonium hydroxides were investigated. The alkali metal intercalates were prepared in the respective metal-hexamethylphosphoric triamide solutions in vaccuo, and the hydroxide intercalates in aqueous hydroxide solutions. According to the intercalation reaction, the c-lattice parameter was increased, and the increase indicated the expansion of the interlayer distance. In the case of alkali metal intercalates, the expansion of the interlayer distance increased continuously, corresponding to the atomic radius of the alkali metal. On the other hand, the hydroxide intercalates showed discrete expansion corresponding to the effective ionic radius of the intercalated cation. All intercalates of TaS 2 amd NbS 2 were superconductors. The expansion of the interlayer distance tended to increase the superconducting transition temperature in the intercalates of TaS 2 and vice versa in those of NbS 2 . (orig.)

  20. Basal-plane thermal conductivity of few-layer molybdenum disulfide

    International Nuclear Information System (INIS)

    Jo, Insun; Ou, Eric; Shi, Li; Pettes, Michael Thompson; Wu, Wei

    2014-01-01

    We report the in-plane thermal conductivity of suspended exfoliated few-layer molybdenum disulfide (MoS 2 ) samples that were measured by suspended micro-devices with integrated resistance thermometers. The obtained room-temperature thermal conductivity values are (44–50) and (48–52) W m −1 K −1 for two samples that are 4 and 7 layers thick, respectively. For both samples, the peak thermal conductivity occurs at a temperature close to 120 K, above which the thermal conductivity is dominated by intrinsic phonon-phonon scattering although phonon scattering by surface disorders can still play an important role in these samples especially at low temperatures

  1. Kinetics and Mechanisms of Thiol–Disulfide Exchange Covering Direct Substitution and Thiol Oxidation-Mediated Pathways

    Science.gov (United States)

    2013-01-01

    Abstract Significance: Disulfides are important building blocks in the secondary and tertiary structures of proteins, serving as inter- and intra-subunit cross links. Disulfides are also the major products of thiol oxidation, a process that has primary roles in defense mechanisms against oxidative stress and in redox regulation of cell signaling. Although disulfides are relatively stable, their reduction, isomerisation, and interconversion as well as their production reactions are catalyzed by delicate enzyme machineries, providing a dynamic system in biology. Redox homeostasis, a thermodynamic parameter that determines which reactions can occur in cellular compartments, is also balanced by the thiol–disulfide pool. However, it is the kinetic properties of the reactions that best represent cell dynamics, because the partitioning of the possible reactions depends on kinetic parameters. Critical Issues: This review is focused on the kinetics and mechanisms of thiol–disulfide substitution and redox reactions. It summarizes the challenges and advances that are associated with kinetic investigations in small molecular and enzymatic systems from a rigorous chemical perspective using biological examples. The most important parameters that influence reaction rates are discussed in detail. Recent Advances and Future Directions: Kinetic studies of proteins are more challenging than small molecules, and quite often investigators are forced to sacrifice the rigor of the experimental approach to obtain the important kinetic and mechanistic information. However, recent technological advances allow a more comprehensive analysis of enzymatic systems via using the systematic kinetics apparatus that was developed for small molecule reactions, which is expected to provide further insight into the cell's machinery. Antioxid. Redox Signal. 18, 1623–1641. PMID:23075118

  2. Disulfide scrambling in superoxide dismutase 1 reduces its cytotoxic effect in cultured cells and promotes protein aggregation.

    Directory of Open Access Journals (Sweden)

    Lina Leinartaitė

    Full Text Available Mutations in the gene coding for superoxide dismutase 1 (SOD1 are associated with familiar forms of the neurodegenerative disease amyotrophic lateral sclerosis (ALS. These mutations are believed to result in a "gain of toxic function", leading to neuronal degeneration. The exact mechanism is still unknown, but misfolding/aggregation events are generally acknowledged as important pathological events in this process. Recently, we observed that demetallated apoSOD1, with cysteine 6 and 111 substituted for alanine, is toxic to cultured neuroblastoma cells. This toxicity depended on an intact, high affinity Zn(2+ site. It was therefor contradictory to discover that wild-type apoSOD1 was not toxic, despite of its high affinity for Zn(2+. This inconsistency was hypothesized to originate from erroneous disulfide formation involving C6 and C111. Using high resolution non-reducing SDS-PAGE, we have in this study demonstrated that the inability of wild-type apoSOD1 to cause cell death stems from formation of non-native intra-molecular disulfides. Moreover, monomeric apoSOD1 variants capable of such disulfide scrambling aggregated into ThT positive oligomers under physiological conditions without agitation. The oligomers were stabilized by inter-molecular disulfides and morphologically resembled what has in other neurodegenerative diseases been termed protofibrils. Disulfide scrambling thus appears to be an important event for misfolding and aggregation of SOD1, but may also be significant for protein function involving cysteines, e.g. mitochondrial import and copper loading.

  3. Thiolato-bridged RuIIAgIRuII trinuclear complex composed of bis(bipyridine)ruthenium(II) units with chelating 2-aminoethanethiolate: conversion to a disulfide-bridged RuIIRuII dinuclear complex.

    Science.gov (United States)

    Tamura, Motoshi; Matsuura, Noriyuki; Kawamoto, Tatsuya; Konno, Takumi

    2007-08-20

    The reaction of [Ru(solvent)2(bpy)2]2+ (bpy = 2,2'-bipyridine) with Haet (2-aminoethanethiol) in ethanol/water in the presence of Ag+ gave a thiolato-bridged RuIIAgIRuII trinuclear complex, [Ag{Ru(aet)(bpy)2}2]3+, in which two [RuII(aet)(bpy)2]+ units are linked by an AgI atom. When this complex was treated with HCl in acetonitrile/water, a disulfide-bridged RuIIRuII dinuclear complex, [Ru2(cysta)(bpy)4]4+ (cysta = cystamine), was produced as a result of the removal of an AgI atom and the autoxidation of thiolato groups. It was found that the dinuclear structure in [Ru2(cysta)(bpy)4]4+ is reverted back to [Ag{Ru(aet)(bpy)2}2]3+ by treatment with Ag+ assisted by Zn reduction.

  4. Relationship between exploitation, oscillation, MSY and extinction.

    Science.gov (United States)

    Ghosh, Bapan; Kar, T K; Legovic, T

    2014-10-01

    We give answers to two important problems arising in current fisheries: (i) how maximum sustainable yield (MSY) policy is influenced by the initial population level, and (ii) how harvesting, oscillation and MSY are related to each other in prey-predator systems. To examine the impact of initial population on exploitation, we analyze a single species model with strong Allee effect. It is found that even when the MSY exists, the dynamic solution may not converge to the equilibrium stock if the initial population level is higher but near the critical threshold level. In a prey-predator system with Allee effect in the prey species, the initial population does not have such important impact neither on MSY nor on maximum sustainable total yield (MSTY). However, harvesting the top predator may cause extinction of all species if odd number of trophic levels exist in the ecosystem. With regard to the second problem, we study two prey-predator models and establish that increasing harvesting effort either on prey, predator or both prey and predator destroys previously existing oscillation. Moreover, equilibrium stock both at MSY and MSTY level is stable. We also discuss the validity of found results to other prey-predator systems. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Exploiting Virtualization and Cloud Computing in ATLAS

    International Nuclear Information System (INIS)

    Harald Barreiro Megino, Fernando; Van der Ster, Daniel; Benjamin, Doug; De, Kaushik; Gable, Ian; Paterson, Michael; Taylor, Ryan; Hendrix, Val; Vitillo, Roberto A; Panitkin, Sergey; De Silva, Asoka; Walker, Rod

    2012-01-01

    The ATLAS Computing Model was designed around the concept of grid computing; since the start of data-taking, this model has proven very successful in the federated operation of more than one hundred Worldwide LHC Computing Grid (WLCG) sites for offline data distribution, storage, processing and analysis. However, new paradigms in computing, namely virtualization and cloud computing, present improved strategies for managing and provisioning IT resources that could allow ATLAS to more flexibly adapt and scale its storage and processing workloads on varied underlying resources. In particular, ATLAS is developing a “grid-of-clouds” infrastructure in order to utilize WLCG sites that make resources available via a cloud API. This work will present the current status of the Virtualization and Cloud Computing R and D project in ATLAS Distributed Computing. First, strategies for deploying PanDA queues on cloud sites will be discussed, including the introduction of a “cloud factory” for managing cloud VM instances. Next, performance results when running on virtualized/cloud resources at CERN LxCloud, StratusLab, and elsewhere will be presented. Finally, we will present the ATLAS strategies for exploiting cloud-based storage, including remote XROOTD access to input data, management of EC2-based files, and the deployment of cloud-resident LCG storage elements.

  6. Exploiting intrinsic fluctuations to identify model parameters.

    Science.gov (United States)

    Zimmer, Christoph; Sahle, Sven; Pahle, Jürgen

    2015-04-01

    Parameterisation of kinetic models plays a central role in computational systems biology. Besides the lack of experimental data of high enough quality, some of the biggest challenges here are identification issues. Model parameters can be structurally non-identifiable because of functional relationships. Noise in measured data is usually considered to be a nuisance for parameter estimation. However, it turns out that intrinsic fluctuations in particle numbers can make parameters identifiable that were previously non-identifiable. The authors present a method to identify model parameters that are structurally non-identifiable in a deterministic framework. The method takes time course recordings of biochemical systems in steady state or transient state as input. Often a functional relationship between parameters presents itself by a one-dimensional manifold in parameter space containing parameter sets of optimal goodness. Although the system's behaviour cannot be distinguished on this manifold in a deterministic framework it might be distinguishable in a stochastic modelling framework. Their method exploits this by using an objective function that includes a measure for fluctuations in particle numbers. They show on three example models, immigration-death, gene expression and Epo-EpoReceptor interaction, that this resolves the non-identifiability even in the case of measurement noise with known amplitude. The method is applied to partially observed recordings of biochemical systems with measurement noise. It is simple to implement and it is usually very fast to compute. This optimisation can be realised in a classical or Bayesian fashion.

  7. Fostering the Exploitation of Open Educational Resources

    Directory of Open Access Journals (Sweden)

    Thomas Richter

    2014-07-01

    Full Text Available The central concept behind Open Educational Resources (OER is opening up the access to educational resources for stakeholders who are not the usual target user group. This concept must be perceived as innovative because it describes a general economic and social paradigm shift: Education, which formerly was limited to a specific group of learners, now, is promoted as a public good. However, despite very good intentions, internationally agreed quality standards, and the availability of the required technological infrastructure, the critical threshold is not yet met. Due to several reasons, the usefulness of OER is often limited to the originally targeted context. Questions arise if the existing quality standards for Technology Enhanced Learning (TEL actually meet the specific requirements within the OER value chain, if the existing quality standards are applicable to OER in a meaningful way, and under which conditions related standards generally could support the exploitation of OER.We analyze quality standards for TEL and contrast the life cycle model of commercial learning resources against the life cycle model of OER. We investigate special demands on quality from the context of OER and, taking the former results into account, derive emergent quality criteria for OER. The paper concludes with recommendations for the design of OER and a future standard development.

  8. Exploiting Genetic Interference for Antiviral Therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Tanner

    2016-05-01

    Full Text Available Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings.

  9. Radiation protection in exploitation of uranium ores

    International Nuclear Information System (INIS)

    Pavlov, I.V.; Shalaev, I.L.

    1976-01-01

    The results are analyzed of the study of the radiation conditions in uranium mines, design and testing of protection means, improvement of methods and equipment for the dosimetric control in different countries since 1968 to 1975. There are outlined radiation hazards and their role in the formation of the radiation situation in mines, dispersive composition of aerosols of short-living daughter products of Rn(DPR) in the mine atmosphere. Among means of the radiation protection the following are dealt with: ventilation including the calculation of air requirements, design of ventilation systems, ventilation practices in working mines; lowering of the release of radon into the mine atmosphere by isolating non-exploited pits, application of gas-proof covers to cofferdams in faces of jointing zones, intensification of mining works in dangerous zones. Methods of air cleaning to remove Rn are suggested in brief. Apparatus are described for the individual control of the level of latent energy in the zone of miners' respiration: track dosimeters, thermoluminescent crystalls (TLC), photographic films, semiconductor systems and biophysical methods of the control for uranium mines. The efficient use of existing protection means provides the normal radiation situation in mines without significant additional investments

  10. Accelerating Large Data Analysis By Exploiting Regularities

    Science.gov (United States)

    Moran, Patrick J.; Ellsworth, David

    2003-01-01

    We present techniques for discovering and exploiting regularity in large curvilinear data sets. The data can be based on a single mesh or a mesh composed of multiple submeshes (also known as zones). Multi-zone data are typical to Computational Fluid Dynamics (CFD) simulations. Regularities include axis-aligned rectilinear and cylindrical meshes as well as cases where one zone is equivalent to a rigid-body transformation of another. Our algorithms can also discover rigid-body motion of meshes in time-series data. Next, we describe a data model where we can utilize the results from the discovery process in order to accelerate large data visualizations. Where possible, we replace general curvilinear zones with rectilinear or cylindrical zones. In rigid-body motion cases we replace a time-series of meshes with a transformed mesh object where a reference mesh is dynamically transformed based on a given time value in order to satisfy geometry requests, on demand. The data model enables us to make these substitutions and dynamic transformations transparently with respect to the visualization algorithms. We present results with large data sets where we combine our mesh replacement and transformation techniques with out-of-core paging in order to achieve significant speed-ups in analysis.

  11. β-Boomerang Antimicrobial and Antiendotoxic Peptides: Lipidation and Disulfide Bond Effects on Activity and Structure.

    Science.gov (United States)

    Mohanram, Harini; Bhattacharjya, Surajit

    2014-04-21

    Drug-resistant Gram-negative bacterial pathogens and endotoxin- or lipopolysaccharide (LPS)-mediated inflammations are among some of the most  prominent health issues globally. Antimicrobial peptides (AMPs) are eminent molecules that can kill drug-resistant strains and neutralize LPS toxicity. LPS, the outer layer of the outer membrane of Gram-negative bacteria safeguards cell integrity against hydrophobic compounds, including antibiotics and AMPs. Apart from maintaining structural integrity, LPS, when released into the blood stream, also induces inflammatory pathways leading to septic shock. In previous works, we have reported the de novo design of a set of 12-amino acid long cationic/hydrophobic peptides for LPS binding and activity. These peptides adopt β-boomerang like conformations in complex with LPS. Structure-activity studies demonstrated some critical features of the β-boomerang scaffold that may be utilized for the further development of potent analogs. In this work, β-boomerang lipopeptides were designed and structure-activity correlation studies were carried out. These lipopeptides were homo-dimerized through a disulfide bridge to stabilize conformations and for improved activity. The designed peptides exhibited potent antibacterial activity and efficiently neutralized LPS toxicity under in vitro assays. NMR structure of C4YI13C in aqueous solution demonstrated the conserved folding of the lipopeptide with a boomerang aromatic lock stabilized with disulfide bond at the C-terminus and acylation at the N-terminus. These lipo-peptides displaying bacterial sterilization and low hemolytic activity may be useful for future applications as antimicrobial and antiendotoxin molecules.

  12. β-Boomerang Antimicrobial and Antiendotoxic Peptides: Lipidation and Disulfide Bond Effects on Activity and Structure

    Directory of Open Access Journals (Sweden)

    Harini Mohanram

    2014-04-01

    Full Text Available Drug-resistant Gram-negative bacterial pathogens and endotoxin- or lipopolysaccharide (LPS-mediated inflammations are among some of the most  prominent health issues globally. Antimicrobial peptides (AMPs are eminent molecules that can kill drug-resistant strains and neutralize LPS toxicity. LPS, the outer layer of the outer membrane of Gram-negative bacteria safeguards cell integrity against hydrophobic compounds, including antibiotics and AMPs. Apart from maintaining structural integrity, LPS, when released into the blood stream, also induces inflammatory pathways leading to septic shock. In previous works, we have reported the de novo design of a set of 12-amino acid long cationic/hydrophobic peptides for LPS binding and activity. These peptides adopt β-boomerang like conformations in complex with LPS. Structure-activity studies demonstrated some critical features of the β-boomerang scaffold that may be utilized for the further development of potent analogs. In this work, β-boomerang lipopeptides were designed and structure-activity correlation studies were carried out. These lipopeptides were homo-dimerized through a disulfide bridge to stabilize conformations and for improved activity. The designed peptides exhibited potent antibacterial activity and efficiently neutralized LPS toxicity under in vitro assays. NMR structure of C4YI13C in aqueous solution demonstrated the conserved folding of the lipopeptide with a boomerang aromatic lock stabilized with disulfide bond at the C-terminus and acylation at the N-terminus. These lipo-peptides displaying bacterial sterilization and low hemolytic activity may be useful for future applications as antimicrobial and antiendotoxin molecules.

  13. Insights into the coal extractive solvent N-methyl-2-pyrrolidone + carbon disulfide

    Energy Technology Data Exchange (ETDEWEB)

    Santiago Aparicio; Mara J. Davila; Rafael Alcalde [University of Burgos, Burgos (Spain). Department of Chemistry

    2009-03-15

    A wide set of experimental and computational tools were used to characterize the N-methyl-2-pyrrolidone (NMP) + carbon disulfide mixed solvent in the full composition range. The interest in this solvent rose from its very efficient use for coal extraction through a mechanism still not fully understood. Thermophysical properties at ambient pressure together with pressure-volume-temperature (PVT) behavior were measured with the objective of providing the required data for the industrial use of the mixed fluid and to get insight into the fluid structure at the molecular level. NMR, FTIR, and solvatochromic studies were performed together with microwave dielectric relaxation spectroscopy (DRS) measurements, thus providing more information on the fluid's structure and allowing one to relate the molecular level behavior with the measured macroscopic properties. Moreover, density functional theory (DFT) and classical molecular dynamics simulations (MD) were used to obtain a detailed picture of the intermolecular interactions within the fluid, at short and long ranges, and of other relevant features leading to the structure of the studied system. The whole study leads to a fluid's picture in which carbon disulfide hinders the development of NMP/NMP intermolecular dipolar interactions, thus increasing the monomer population. We should remark that some properties reported in this work are in remarkable disagreement with previously reported studies, the most important one being the positive excess molar volume in the whole pressure-temperature range studied, which contrasts with the negative values reported in the literature. Previously reported properties are hardly justified with a coherent molecular level picture, whereas the whole collection of properties reported in this work leads to a more reasonable fluid's structure. 56 refs., 17 figs., 2 tabs.

  14. Imbalance of heterologous protein folding and disulfide bond formation rates yields runaway oxidative stress

    Directory of Open Access Journals (Sweden)

    Tyo Keith EJ

    2012-03-01

    Full Text Available Abstract Background The protein secretory pathway must process a wide assortment of native proteins for eukaryotic cells to function. As well, recombinant protein secretion is used extensively to produce many biologics and industrial enzymes. Therefore, secretory pathway dysfunction can be highly detrimental to the cell and can drastically inhibit product titers in biochemical production. Because the secretory pathway is a highly-integrated, multi-organelle system, dysfunction can happen at many levels and dissecting the root cause can be challenging. In this study, we apply a systems biology approach to analyze secretory pathway dysfunctions resulting from heterologous production of a small protein (insulin precursor or a larger protein (α-amylase. Results HAC1-dependent and independent dysfunctions and cellular responses were apparent across multiple datasets. In particular, processes involving (a degradation of protein/recycling amino acids, (b overall transcription/translation repression, and (c oxidative stress were broadly associated with secretory stress. Conclusions Apparent runaway oxidative stress due to radical production observed here and elsewhere can be explained by a futile cycle of disulfide formation and breaking that consumes reduced glutathione and produces reactive oxygen species. The futile cycle is dominating when protein folding rates are low relative to disulfide bond formation rates. While not strictly conclusive with the present data, this insight does provide a molecular interpretation to an, until now, largely empirical understanding of optimizing heterologous protein secretion. This molecular insight has direct implications on engineering a broad range of recombinant proteins for secretion and provides potential hypotheses for the root causes of several secretory-associated diseases.

  15. Reversible end-to-end assembly of gold nanorods using a disulfide-modified polypeptide

    International Nuclear Information System (INIS)

    Walker, David A; Gupta, Vinay K

    2008-01-01

    Directing the self-assembly of colloidal particles into nanostructures is of great interest in nanotechnology. Here, reversible end-to-end assembly of gold nanorods (GNR) is induced by pH-dependent changes in the secondary conformation of a disulfide-modified poly(L-glutamic acid) (SSPLGA). The disulfide anchoring group drives chemisorption of the polyacid onto the end of the gold nanorods in an ethanolic solution. A layer of poly(vinyl pyrrolidone) is adsorbed on the positively charged, surfactant-stabilized GNR to screen the surfactant bilayer charge and provide stability for dispersion of the GNR in ethanol. For comparison, irreversible end-to-end assembly using a bidentate ligand, namely 1,6-hexanedithiol, is also performed. Characterization of the modified GNR and its end-to-end linking behavior using SSPLGA and hexanedithiol is performed using dynamic light scattering (DLS), UV-vis absorption spectroscopy and transmission electron microscopy (TEM). Experimental results show that, in a colloidal solution of GNR-SSPLGA at a pH∼3.5, where the PLGA is in an α-helical conformation, the modified GNR self-assemble into one-dimensional nanostructures. The linking behavior can be reversed by increasing the pH (>8.5) to drive the conformation of the polypeptide to a random coil and this reversal with pH occurs rapidly within minutes. Cycling the pH multiple times between low and high pH values can be used to drive the formation of the nanostructures of the GNR and disperse them in solution.

  16. Mutational analysis of Kex2 recognition sites and a disulfide bond in tannase from Aspergillus oryzae.

    Science.gov (United States)

    Koseki, Takuya; Otsuka, Motohiro; Mizuno, Toshiyuki; Shiono, Yoshihito

    2017-01-22

    Aspergillus oryzae tannase (AoTanA), which contains two Kex2 recognition sites at positions Arg311 and Arg316, consists of two subunits that are generated by the cleavage of tannase gene product by the Kex2 protease. Based on the crystal structure of feruloyl esterase from Aspergillus oryzae (AoFaeB), which has been classified as a member of the fungal tannase family, the catalytic triad residues of AoTanA are predicted to be Ser195, Asp455, and His501, with the serine and histidine residues brought together by a disulfide bond of the neighboring cysteines, Cys194 and Cys502. In this study, we investigated the functional role of the Kex2 recognition sites and disulfide bond between the neighboring cysteines in AoTanA. We constructed a double variant (R311A/R316A), a seven amino-acid deletion variant of region Lys310-Arg316 (ΔKR), and two single variants (C194A and C502A). While the R311A/R316A variant exhibited the two bands similar to wild type by SDS-PAGE after treatment with endoglycosidase H, the ΔKR variant exhibited only one band. R311A/R316A variation had no effect on tannase activity and stability. Meanwhile, the ΔKR variant exhibited higher activity compared to the wild-type. The activities of the C194A and C502A variants decreased considerably (<0.24% of the wild-type) toward methyl gallate. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Crystallographic studies evidencing the high energy tolerance to disrupting the interface disulfide bond of thioredoxin 1 from white leg shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Campos-Acevedo, Adam A; Rudiño-Piñera, Enrique

    2014-12-15

    Thioredoxin (Trx) is a small 12-kDa redox protein that catalyzes the reduction of disulfide bonds in proteins from different biological systems. A recent study of the crystal structure of white leg shrimp thioredoxin 1 from Litopenaeus vannamei (LvTrx) revealed a dimeric form of the protein mediated by a covalent link through a disulfide bond between Cys73 from each monomer. In the present study, X-ray-induced damage in the catalytic and the interface disulfide bond of LvTrx was studied at atomic resolution at different transmission energies of 8% and 27%, 12.8 keV at 100 K in the beamline I-24 at Diamond Light Source. We found that at an absorbed dose of 32 MGy, the X-ray induces the cleavage of the disulfide bond of each catalytic site; however, the interface disulfide bond was cleaved at an X-ray adsorbed dose of 85 MGy; despite being the most solvent-exposed disulfide bond in LvTrx (~50 Å2). This result clearly established that the interface disulfide bond is very stable and, therefore, less susceptible to being reduced by X-rays. In fact, these studies open the possibility of the existence in solution of a dimeric LvTrx.

  18. Crystallographic Studies Evidencing the High Energy Tolerance to Disrupting the Interface Disulfide Bond of Thioredoxin 1 from White Leg Shrimp Litopenaeus vannamei

    Directory of Open Access Journals (Sweden)

    Adam A. Campos-Acevedo

    2014-12-01

    Full Text Available Thioredoxin (Trx is a small 12-kDa redox protein that catalyzes the reduction of disulfide bonds in proteins from different biological systems. A recent study of the crystal structure of white leg shrimp thioredoxin 1 from Litopenaeus vannamei (LvTrx revealed a dimeric form of the protein mediated by a covalent link through a disulfide bond between Cys73 from each monomer. In the present study, X-ray-induced damage in the catalytic and the interface disulfide bond of LvTrx was studied at atomic resolution at different transmission energies of 8% and 27%, 12.8 keV at 100 K in the beamline I-24 at Diamond Light Source. We found that at an absorbed dose of 32 MGy, the X-ray induces the cleavage of the disulfide bond of each catalytic site; however, the interface disulfide bond was cleaved at an X-ray adsorbed dose of 85 MGy; despite being the most solvent-exposed disulfide bond in LvTrx (~50 Å2. This result clearly established that the interface disulfide bond is very stable and, therefore, less susceptible to being reduced by X-rays. In fact, these studies open the possibility of the existence in solution of a dimeric LvTrx.

  19. Production of recombinant disulfide-rich venom peptides for structural and functional analysis via expression in the periplasm of E. coli.

    Directory of Open Access Journals (Sweden)

    Julie K Klint

    Full Text Available Disulfide-rich peptides are the dominant component of most animal venoms. These peptides have received much attention as leads for the development of novel therapeutic agents and bioinsecticides because they target a wide range of neuronal receptors and ion channels with a high degree of potency and selectivity. In addition, their rigid disulfide framework makes them particularly well suited for addressing the crucial issue of in vivo stability. Structural and functional characterization of these peptides necessitates the development of a robust, reliable expression system that maintains their native disulfide framework. The bacterium Escherichia coli has long been used for economical production of recombinant proteins. However, the expression of functional disulfide-rich proteins in the reducing environment of the E. coli cytoplasm presents a significant challenge. Thus, we present here an optimised protocol for the expression of disulfide-rich venom peptides in the periplasm of E. coli, which is where the endogenous machinery for production of disulfide-bonds is located. The parameters that have been investigated include choice of media, induction conditions, lysis methods, methods of fusion protein and peptide purification, and sample preparation for NMR studies. After each section a recommendation is made for conditions to use. We demonstrate the use of this method for the production of venom peptides ranging in size from 2 to 8 kDa and containing 2-6 disulfide bonds.

  20. Assisted Living

    Science.gov (United States)

    ... a resident's needs depends as much on the philosophy and services of the assisted living facility as it does on the quality of care. The Administration on Aging, a part of the U.S. Department of Health and Human Services (HHS), offers these suggestions to help you ...

  1. Assistive Devices

    Science.gov (United States)

    If you have a disability or injury, you may use a number of assistive devices. These are tools, products or types of equipment that help you perform tasks and activities. They may help you move around, see, communicate, eat, or get ...

  2. Microwave assisted chemical vapor infiltration

    International Nuclear Information System (INIS)

    Devlin, D.J.; Currier, R.P.; Barbero, R.S.; Espinoza, B.F.; Elliott, N.

    1991-01-01

    A microwave assisted process for production of continuous fiber reinforced ceramic matrix composites is described. A simple apparatus combining a chemical vapor infiltration reactor with a conventional 700 W multimode oven is described. Microwave induced inverted thermal gradients are exploited with the ultimate goal of reducing processing times on complex shapes. Thermal gradients in stacks of SiC (Nicalon) cloths have been measured using optical thermometry. Initial results on the ''inside out'' deposition of SiC via decomposition of methyltrichlorosilane in hydrogen are presented. Several key processing issues are identified and discussed. 5 refs

  3. Main principles of developing exploitation models of semiconductor devices

    Science.gov (United States)

    Gradoboev, A. V.; Simonova, A. V.

    2018-05-01

    The paper represents primary tasks, solutions of which allow to develop the exploitation modes of semiconductor devices taking into account complex and combined influence of ionizing irradiation and operation factors. The structure of the exploitation model of the semiconductor device is presented, which is based on radiation and reliability models. Furthermore, it was shown that the exploitation model should take into account complex and combine influence of various ionizing irradiation types and operation factors. The algorithm of developing the exploitation model of the semiconductor devices is proposed. The possibility of creating the radiation model of Schottky barrier diode, Schottky field-effect transistor and Gunn diode is shown based on the available experimental data. The basic exploitation model of IR-LEDs based upon double AlGaAs heterostructures is represented. The practical application of the exploitation models will allow to output the electronic products with guaranteed operational properties.

  4. Proba-V Mission Exploitation Platform

    Science.gov (United States)

    Goor, Erwin; Dries, Jeroen

    2017-04-01

    VITO and partners developed the Proba-V Mission Exploitation Platform (MEP) as an end-to-end solution to drastically improve the exploitation of the Proba-V (a Copernicus contributing mission) EO-data archive (http://proba-v.vgt.vito.be/), the past mission SPOT-VEGETATION and derived vegetation parameters by researchers, service providers and end-users. The analysis of time series of data (+1PB) is addressed, as well as the large scale on-demand processing of near real-time data on a powerful and scalable processing environment. Furthermore data from the Copernicus Global Land Service is in scope of the platform. From November 2015 an operational Proba-V MEP environment, as an ESA operation service, is gradually deployed at the VITO data center with direct access to the complete data archive. Since autumn 2016 the platform is operational and yet several applications are released to the users, e.g. - A time series viewer, showing the evolution of Proba-V bands and derived vegetation parameters from the Copernicus Global Land Service for any area of interest. - Full-resolution viewing services for the complete data archive. - On-demand processing chains on a powerfull Hadoop/Spark backend e.g. for the calculation of N-daily composites. - Virtual Machines can be provided with access to the data archive and tools to work with this data, e.g. various toolboxes (GDAL, QGIS, GrassGIS, SNAP toolbox, …) and support for R and Python. This allows users to immediately work with the data without having to install tools or download data, but as well to design, debug and test applications on the platform. - A prototype of jupyter Notebooks is available with some examples worked out to show the potential of the data. Today the platform is used by several third party projects to perform R&D activities on the data, and to develop/host data analysis toolboxes. In parallel the platform is further improved and extended. From the MEP PROBA-V, access to Sentinel-2 and landsat data will

  5. The role of short-range Cys171-Cys178 disulfide bond in maintaining cutinase active site integrity: A molecular dynamics simulation

    International Nuclear Information System (INIS)

    Matak, Mehdi Youssefi; Moghaddam, Majid Erfani

    2009-01-01

    Understanding structural determinants in enzyme active site integrity can provide a good knowledge to design efficient novel catalytic machineries. Fusarium solani pisi cutinase with classic triad Ser-His-Asp is a promising enzyme to scrutinize these structural determinants. We performed two MD simulations: one, with the native structure, and the other with the broken Cys171-Cys178 disulfide bond. This disulfide bond stabilizes a turn in active site on which catalytic Asp175 is located. Functionally important H-bonds and atomic fluctuations in catalytic pocket have been changed. We proposed that this disulfide bond within active site can be considered as an important determinant of cutinase active site structural integrity.

  6. Exploiting Untapped Information Resources in Earth Science

    Science.gov (United States)

    Ramachandran, R.; Fox, P. A.; Kempler, S.; Maskey, M.

    2015-12-01

    One of the continuing challenges in any Earth science investigation is the amount of time and effort required for data preparation before analysis can begin. Current Earth science data and information systems have their own shortcomings. For example, the current data search systems are designed with the assumption that researchers find data primarily by metadata searches on instrument or geophysical keywords, assuming that users have sufficient knowledge of the domain vocabulary to be able to effectively utilize the search catalogs. These systems lack support for new or interdisciplinary researchers who may be unfamiliar with the domain vocabulary or the breadth of relevant data available. There is clearly a need to innovate and evolve current data and information systems in order to improve data discovery and exploration capabilities to substantially reduce the data preparation time and effort. We assert that Earth science metadata assets are dark resources, information resources that organizations collect, process, and store for regular business or operational activities but fail to utilize for other purposes. The challenge for any organization is to recognize, identify and effectively utilize the dark data stores in their institutional repositories to better serve their stakeholders. NASA Earth science metadata catalogs contain dark resources consisting of structured information, free form descriptions of data and pre-generated images. With the addition of emerging semantic technologies, such catalogs can be fully utilized beyond their original design intent of supporting current search functionality. In this presentation, we will describe our approach of exploiting these information resources to provide novel data discovery and exploration pathways to science and education communities

  7. Postural Hand Synergies during Environmental Constraint Exploitation

    Directory of Open Access Journals (Sweden)

    Cosimo Della Santina

    2017-08-01

    Full Text Available Humans are able to intuitively exploit the shape of an object and environmental constraints to achieve stable grasps and perform dexterous manipulations. In doing that, a vast range of kinematic strategies can be observed. However, in this work we formulate the hypothesis that such ability can be described in terms of a synergistic behavior in the generation of hand postures, i.e., using a reduced set of commonly used kinematic patterns. This is in analogy with previous studies showing the presence of such behavior in different tasks, such as grasping. We investigated this hypothesis in experiments performed by six subjects, who were asked to grasp objects from a flat surface. We quantitatively characterized hand posture behavior from a kinematic perspective, i.e., the hand joint angles, in both pre-shaping and during the interaction with the environment. To determine the role of tactile feedback, we repeated the same experiments but with subjects wearing a rigid shell on the fingertips to reduce cutaneous afferent inputs. Results show the persistence of at least two postural synergies in all the considered experimental conditions and phases. Tactile impairment does not alter significantly the first two synergies, and contact with the environment generates a change only for higher order Principal Components. A good match also arises between the first synergy found in our analysis and the first synergy of grasping as quantified by previous work. The present study is motivated by the interest of learning from the human example, extracting lessons that can be applied in robot design and control. Thus, we conclude with a discussion on implications for robotics of our findings.

  8. Exploiting core knowledge for visual object recognition.

    Science.gov (United States)

    Schurgin, Mark W; Flombaum, Jonathan I

    2017-03-01

    Humans recognize thousands of objects, and with relative tolerance to variable retinal inputs. The acquisition of this ability is not fully understood, and it remains an area in which artificial systems have yet to surpass people. We sought to investigate the memory process that supports object recognition. Specifically, we investigated the association of inputs that co-occur over short periods of time. We tested the hypothesis that human perception exploits expectations about object kinematics to limit the scope of association to inputs that are likely to have the same token as a source. In several experiments we exposed participants to images of objects, and we then tested recognition sensitivity. Using motion, we manipulated whether successive encounters with an image took place through kinematics that implied the same or a different token as the source of those encounters. Images were injected with noise, or shown at varying orientations, and we included 2 manipulations of motion kinematics. Across all experiments, memory performance was better for images that had been previously encountered with kinematics that implied a single token. A model-based analysis similarly showed greater memory strength when images were shown via kinematics that implied a single token. These results suggest that constraints from physics are built into the mechanisms that support memory about objects. Such constraints-often characterized as 'Core Knowledge'-are known to support perception and cognition broadly, even in young infants. But they have never been considered as a mechanism for memory with respect to recognition. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. Thermal Property Engineering: Exploiting the Properties of Ceramic Nanocomposites

    Science.gov (United States)

    2018-03-01

    ARL-TR-8308 ● MAR 2018 US Army Research Laboratory Thermal Property Engineering : Exploiting the Properties of Ceramic...return it to the originator. ARL-TR-8308 ● MAR 2018 US Army Research Laboratory Thermal Property Engineering : Exploiting the...2015 – Dec 31 2017 4. TITLE AND SUBTITLE Thermal Property Engineering : Exploiting the Properties of Ceramic Nanocomposites 5a. CONTRACT NUMBER 5b

  10. Foreign assistance

    International Nuclear Information System (INIS)

    1991-07-01

    This paper reports that providing energy assistance to developing countries remains a relatively low priority of the Agency for International Development. AID is helping some developing countries meet their energy needs, but this assistance varies substantially because of the agency's decentralized structure. Most AID energy funding has gone to a handful of countries-primarily Egypt and Pakistan. With limited funding in most other countries, AID concentrates on providing technical expertise and promoting energy policy reforms that will encourage both energy efficiency and leverage investment by the private sector and other donors. Although a 1989 congressional directive to pursue a global warming initiative has had a marginal impact on the agency's energy programming, many AID energy programs, including those directed at energy conservation, help address global warming concerns

  11. Structure of conkunitzin-S1, a neurotoxin and Kunitz-fold disulfide variant from cone snail

    International Nuclear Information System (INIS)

    Dy, Catherine Y.; Buczek, Pawel; Imperial, Julita S.; Bulaj, Grzegorz; Horvath, Martin P.

    2006-01-01

    Most Kunitz proteins like BPTI and α-dendrotoxin are stabilized by three disulfide bonds. The crystal structure shows how subtle repacking of non-covalent interactions may compensate for disulfide bond loss in a naturally occurring two-disulfide variant, conkunitzin-S1, the first discovered member of a new conotoxin family. Cone snails (Conus) are predatory marine mollusks that immobilize prey with venom containing 50–200 neurotoxic polypeptides. Most of these polypeptides are small disulfide-rich conotoxins that can be classified into families according to their respective ion-channel targets and patterns of cysteine–cysteine disulfides. Conkunitzin-S1, a potassium-channel pore-blocking toxin isolated from C. striatus venom, is a member of a newly defined conotoxin family with sequence homology to Kunitz-fold proteins such as α-dendrotoxin and bovine pancreatic trypsin inhibitor (BPTI). While conkunitzin-S1 and α-dendrotoxin are 42% identical in amino-acid sequence, conkunitzin-S1 has only four of the six cysteines normally found in Kunitz proteins. Here, the crystal structure of conkunitzin-S1 is reported. Conkunitzin-S1 adopts the canonical 3 10 –β–β–α Kunitz fold complete with additional distinguishing structural features including two completely buried water molecules. The crystal structure, although completely consistent with previously reported NMR distance restraints, provides a greater degree of precision for atomic coordinates, especially for S atoms and buried solvent molecules. The region normally cross-linked by cysteines II and IV in other Kunitz proteins retains a network of hydrogen bonds and van der Waals interactions comparable to those found in α-dendrotoxin and BPTI. In conkunitzin-S1, glycine occupies the sequence position normally reserved for cysteine II and the special steric properties of glycine allow additional van der Waals contacts with the glutamine residue substituting for cysteine IV. Evolution has thus defrayed the

  12. Exploiting Laboratory and Heliophysics Plasma Synergies

    Directory of Open Access Journals (Sweden)

    Jill Dahlburg

    2010-05-01

    Full Text Available Recent advances in space-based heliospheric observations, laboratory experimentation, and plasma simulation codes are creating an exciting new cross-disciplinary opportunity for understanding fast energy release and transport mechanisms in heliophysics and laboratory plasma dynamics, which had not been previously accessible. This article provides an overview of some new observational, experimental, and computational assets, and discusses current and near-term activities towards exploitation of synergies involving those assets. This overview does not claim to be comprehensive, but instead covers mainly activities closely associated with the authors’ interests and reearch. Heliospheric observations reviewed include the Sun Earth Connection Coronal and Heliospheric Investigation (SECCHI on the National Aeronautics and Space Administration (NASA Solar Terrestrial Relations Observatory (STEREO mission, the first instrument to provide remote sensing imagery observations with spatial continuity extending from the Sun to the Earth, and the Extreme-ultraviolet Imaging Spectrometer (EIS on the Japanese Hinode spacecraft that is measuring spectroscopically physical parameters of the solar atmosphere towards obtaining plasma temperatures, densities, and mass motions. The Solar Dynamics Observatory (SDO and the upcoming Solar Orbiter with the Heliospheric Imager (SoloHI on-board will also be discussed. Laboratory plasma experiments surveyed include the line-tied magnetic reconnection experiments at University of Wisconsin (relevant to coronal heating magnetic flux tube observations and simulations, and a dynamo facility under construction there; the Space Plasma Simulation Chamber at the Naval Research Laboratory that currently produces plasmas scalable to ionospheric and magnetospheric conditions and in the future also will be suited to study the physics of the solar corona; the Versatile Toroidal Facility at the Massachusetts Institute of Technology that

  13. Simulated population responses of common carp to commercial exploitation

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Michael J.; Hennen, Matthew J.; Brown, Michael L.

    2011-12-01

    Common carp Cyprinus carpio is a widespread invasive species that can become highly abundant and impose deleterious ecosystem effects. Thus, aquatic resource managers are interested in controlling common carp populations. Control of invasive common carp populations is difficult, due in part to the inherent uncertainty of how populations respond to exploitation. To understand how common carp populations respond to exploitation, we evaluated common carp population dynamics (recruitment, growth, and mortality) in three natural lakes in eastern South Dakota. Common carp exhibited similar population dynamics across these three systems that were characterized by consistent recruitment (ages 3 to 15 years present), fast growth (K = 0.37 to 0.59), and low mortality (A = 1 to 7%). We then modeled the effects of commercial exploitation on size structure, abundance, and egg production to determine its utility as a management tool to control populations. All three populations responded similarly to exploitation simulations with a 575-mm length restriction, representing commercial gear selectivity. Simulated common carp size structure modestly declined (9 to 37%) in all simulations. Abundance of common carp declined dramatically (28 to 56%) at low levels of exploitation (0 to 20%) but exploitation >40% had little additive effect and populations were only reduced by 49 to 79% despite high exploitation (>90%). Maximum lifetime egg production was reduced from 77 to 89% at a moderate level of exploitation (40%), indicating the potential for recruitment overfishing. Exploitation further reduced common carp size structure, abundance, and egg production when simulations were not size selective. Our results provide insights to how common carp populations may respond to exploitation. Although commercial exploitation may be able to partially control populations, an integrated removal approach that removes all sizes of common carp has a greater chance of controlling population abundance

  14. Rapid Exploitation and Analysis of Documents

    Energy Technology Data Exchange (ETDEWEB)

    Buttler, D J; Andrzejewski, D; Stevens, K D; Anastasiu, D; Gao, B

    2011-11-28

    Analysts are overwhelmed with information. They have large archives of historical data, both structured and unstructured, and continuous streams of relevant messages and documents that they need to match to current tasks, digest, and incorporate into their analysis. The purpose of the READ project is to develop technologies to make it easier to catalog, classify, and locate relevant information. We approached this task from multiple angles. First, we tackle the issue of processing large quantities of information in reasonable time. Second, we provide mechanisms that allow users to customize their queries based on latent topics exposed from corpus statistics. Third, we assist users in organizing query results, adding localized expert structure over results. Forth, we use word sense disambiguation techniques to increase the precision of matching user generated keyword lists with terms and concepts in the corpus. Fifth, we enhance co-occurrence statistics with latent topic attribution, to aid entity relationship discovery. Finally we quantitatively analyze the quality of three popular latent modeling techniques to examine under which circumstances each is useful.

  15. Exploiting for medical and biological applications

    Science.gov (United States)

    Giano, Michael C.

    Biotherapeutics are an emerging class of drug composed of molecules ranging in sizes from peptides to large proteins. Due to their poor stability and mucosal membrane permeability, biotherapeutics are administered by a parenteral method (i.e., syringe, intravenous or intramuscular). Therapeutics delivered systemically often experience short half-lives. While, local administration may involve invasive surgical procedures and suffer from poor retention at the site of application. To compensate, the patient receives frequent doses of highly concentrated therapeutic. Unfortunately, the off-target side effects and discomfort associated with multiple injections results in poor patient compliance. Therefore, new delivery methods which can improve therapeutic retention, reduce the frequency of administration and may aid in decreasing the off-target side effects is a necessity. Hydrogels are a class of biomaterials that are gaining interests for tissue engineering and drug delivery applications. Hydrogel materials are defined as porous, 3-dimensional networks that are primarily composed of water. Generally, they are mechanically rigid, cytocompatible and easily chemically functionalized. Collectively, these properties make hydrogels fantastic candidates to perform as drug delivery depots. Current hydrogel delivery systems physically entrap the target therapeutic which is then subsequently released over time at the site of administration. The swelling and degradation of the material effect the diffusion of the therapy from the hydrogel, and therefore should be controlled. Although these strategies provide some regulation over therapeutic release, full control of the delivery is not achieved. Newer approaches are focused on designing hydrogels that exploit known interactions, covalently attach the therapy or respond to an external stimulus in an effort to gain improved control over the therapy's release. Unfortunately, the biotherapeutic is typically required to be chemically

  16. Quantitation of a PEGylated protein in monkey serum by UHPLC-HRMS using a surrogate disulfide-containing peptide: A new approach to bioanalysis and in vivo stability evaluation of disulfide-rich protein therapeutics.

    Science.gov (United States)

    Zheng, Naiyu; Zeng, Jianing; Manney, Amy; Williams, Lakenya; Aubry, Anne-Françoise; Voronin, Kimberly; Buzescu, Adela; Zhang, Yan J; Allentoff, Alban; Xu, Carrie; Shen, Hongwu; Warner, William; Arnold, Mark E

    2016-04-15

    To quantify a therapeutic PEGylated protein in monkey serum as well as to monitor its potential in vivo instability and methionine oxidation, a novel ultra high performance liquid chromatography-high resolution mass spectrometric (UHPLC-HRMS) assay was developed using a surrogate disulfide-containing peptide, DCP(SS), and a confirmatory peptide, CP, a disulfide-free peptide. DCP(SS) was obtained by eliminating the step of reduction/alkylation before trypsin digestion. It contains an intact disulfide linkage between two peptide sequences that are essential for drug function but susceptible to potential in vivo cleavages. HRMS-based single ion monitoring (SIM) on a Q Exactive™ mass spectrometer was employed to improve assay specificity and sensitivity for DCP(SS) due to its poor fragmentation and low sensitivity with SRM detection. The assay has been validated for the protein drug in monkey serum using both surrogate peptides with excellent accuracy (within ±4.4%Dev) and precision (within 7.5%CV) with a lower limit of quantitation (LLOQ) at 10 ng mL(-1). The protein concentrations in monkey serum obtained from the DCP(SS)-based assay not only provided important pharmacokinetic parameters, but also confirmed in vivo stability of the peptide regions of interest by comparing drug concentrations with those obtained from the CP-based assay or from a ligand-binding assay (LBA). Furthermore, UHPLC-HRMS allowed simultaneous monitoring of the oxidized forms of both surrogate peptides to evaluate potential ex vivo/in vivo oxidation of one methionine present in each of both surrogate peptides. To the best of our knowledge, this is the first report of using a surrogate disulfide-containing peptide for LC-MS bioanalysis of a therapeutic protein. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Human exploitation assisting a threatened species? The case of muttonbirders and Buller's albatross.

    Directory of Open Access Journals (Sweden)

    Susan M Waugh

    Full Text Available Albatrosses are flexible and adaptable predators, relying on live prey as well as carrion. Use of predictable food sources and reliance on human-produced resources are well-known trait in long-range feeders like albatrosses and petrels. Breeding Buller's albatrosses studied at Solander I. (Hautere, New Zealand fed their chicks the remains of sooty shearwater juveniles (tītī in Māori, which are harvested from nearby muttonbirding sites. Evidence of this food type was found at over 10% of nests examined, and 17-40% birds that were fitted with GPS loggers visited muttonbirding sites in this and previous studies. Muttonbirding is a traditional practice that has continued for centuries, with up to 120 tonnes of offal discharged to the sea annually during the present day harvest. It coincides with the energetically-demanding early chick period for the albatrosses. Our finding suggests that the offal may be an important, but overlooked element in the albatross diet. As an important supplementary food for the albatrosses it is likely to have contributed to the 3% per annum growth of their populations since the first comprehensive population surveys in 1969.

  18. Symmetric pseudocapacitors based on molybdenum disulfide (MoS2)-modified carbon nanospheres: correlating physicochemistry and synergistic interaction on energy storage

    CSIR Research Space (South Africa)

    Khawula, TNY

    2016-03-01

    Full Text Available Molybdenum disulfide-modified carbon nanospheres (MoS(sub2)/CNS) with two different morphologies (spherical and flower-like) have been synthesized using hydrothermal techniques and investigated as symmetric pseudocapacitors in an aqueous electrolyte...

  19. Early Sexual Exploitation as an Influence in Prostitution.

    Science.gov (United States)

    Silbert, Mimi H.; Pines, Ayala M.

    1983-01-01

    Surveyed 200 female street prostitutes to determine whether they were sexually exploited during childhood. Results showed 60 percent of the subjects were sexually exploited. The few girls who discussed their abuse with others were met with shame and most often inaction. Only 10 percent were abused by strangers. (JAC)

  20. A Descriptive Study on Sexually Exploited Children in Residential Treatment

    Science.gov (United States)

    Twill, Sarah E.; Green, Denise M.; Traylor, Amy

    2010-01-01

    Sexual exploitation and prostitution of children and adolescents is a multibillion dollar industry in the United States (Estes and Weiner in "Medical, legal & social science aspects of child sexual exploitation: A comprehensive review of pornography, prostitution, and internet crimes, vol I," G.W. Medical Publishing, Inc, St Louis,…

  1. Exploiting opportunities at all cost? Entrepreneurial intent and externalities

    NARCIS (Netherlands)

    Urbig, D.; Weitzel, G.U.; Rosenkranz, S.; van Witteloostuijn, A.

    2011-01-01

    they exploit welfare-enhancing opportunities as it is assumed in several normative models? Do we need to prevent potential entrepreneurs from being destructive or are there intrinsic limits to harm others? We experimentally investigate how people with different entrepreneurial intent exploit risky

  2. Exploitation program of ''Adamow'' quarry up to 2015

    International Nuclear Information System (INIS)

    Hadlaw, A.

    1994-01-01

    The brown coal deposits exploited by the quarry ''Adamow'' located in Central Poland are shortly described and the prognosis of their exploitation up to 2015 is given. The basis data on the perspective deposits in the quarry's area are also presented. All deposits are shown on the map. 3 ills, 2 tabs

  3. Panel discussion on exploitation of geothermal resources in thermal zones

    Energy Technology Data Exchange (ETDEWEB)

    Viramonte, J G; Mange, J; Stefani, G

    1978-03-01

    The topics discussed include the major known geothermal resources, varying ways of exploiting geothermal resources, technical and economic difficulties in the exploitation, the place of geothermal energy in the total energy policy of a given country, advanced exploration techniques, and indications of needed areas of study. The panelists represented most of the South American countries, Mexico, and Italy. (JSR)

  4. Continuous exposure to low-frequency noise and carbon disulfide: Combined effects on hearing.

    Science.gov (United States)

    Venet, Thomas; Carreres-Pons, Maria; Chalansonnet, Monique; Thomas, Aurélie; Merlen, Lise; Nunge, Hervé; Bonfanti, Elodie; Cosnier, Frédéric; Llorens, Jordi; Campo, Pierre

    2017-09-01

    Carbon disulfide (CS 2 ) is used in industry; it has been shown to have neurotoxic effects, causing central and distal axonopathies.However, it is not considered cochleotoxic as it does not affect hair cells in the organ of Corti, and the only auditory effects reported in the literature were confined to the low-frequency region. No reports on the effects of combined exposure to low-frequency noise and CS 2 have been published to date. This article focuses on the effects on rat hearing of combined exposure to noise with increasing concentrations of CS 2 (0, 63,250, and 500ppm, 6h per day, 5 days per week, for 4 weeks). The noise used was a low-frequency noise ranging from 0.5 to 2kHz at an intensity of 106dB SPL. Auditory function was tested using distortion product oto-acoustic emissions, which mainly reflects the cochlear performances. Exposure to noise alone caused an auditory deficit in a frequency area ranging from 3.6 to 6 kHz. The damaged area was approximately one octave (6kHz) above the highest frequency of the exposure noise (2.8kHz); it was a little wider than expected based on the noise spectrum.Consequently, since maximum hearing sensitivity is located around 8kHz in rats, low-frequency noise exposure can affect the cochlear regions detecting mid-range frequencies. Co-exposure to CS 2 (250-ppm and over) and noise increased the extent of the damaged frequency window since a significant auditory deficit was measured at 9.6kHz in these conditions.Moreover, the significance at 9.6kHz increased with the solvent concentrations. Histological data showed that neither hair cells nor ganglion cells were damaged by CS 2 . This discrepancy between functional and histological data is discussed. Like most aromatic solvents, carbon disulfide should be considered as a key parameter in hearing conservation régulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Molecular characterization and analysis of a novel protein disulfide isomerase-like protein of Eimeria tenella.

    Science.gov (United States)

    Han, Hongyu; Dong, Hui; Zhu, Shunhai; Zhao, Qiping; Jiang, Lianlian; Wang, Yange; Li, Liujia; Wu, Youlin; Huang, Bing

    2014-01-01

    Protein disulfide isomerase (PDI) and PDI-like proteins are members of the thioredoxin superfamily. They contain thioredoxin-like domains and catalyze the physiological oxidation, reduction and isomerization of protein disulfide bonds, which are involved in cell function and development in prokaryotes and eukaryotes. In this study, EtPDIL, a novel PDI-like gene of Eimeria tenella, was cloned using rapid amplification of cDNA ends (RACE) according to the expressed sequence tag (EST). The EtPDIL cDNA contained 1129 nucleotides encoding 216 amino acids. The deduced EtPDIL protein belonged to thioredoxin-like superfamily and had a single predicted thioredoxin domain with a non-classical thioredoxin-like motif (SXXC). BLAST analysis showed that the EtPDIL protein was 55-59% identical to PDI-like proteins of other apicomplexan parasites. The transcript and protein levels of EtPDIL at different development stages were investigated by real-time quantitative PCR and western blot. The messenger RNA and protein levels of EtPDIL were higher in sporulated oocysts than in unsporulated oocysts, sporozoites or merozoites. Protein expression was barely detectable in unsporulated oocysts. Western blots showed that rabbit antiserum against recombinant EtPDIL recognized only a native 24 kDa protein from parasites. Immunolocalization with EtPDIL antibody showed that EtPDIL had a disperse distribution in the cytoplasm of whole sporozoites and merozoites. After sporozoites were incubated in complete medium, EtPDIL protein concentrated at the anterior of the sporozoites and appeared on the surface of parasites. Specific staining was more intense and mainly located on the parasite surface after merozoites released from mature schizonts invaded DF-1 cells. After development of parasites in DF-1 cells, staining intensified in trophozoites, immature schizonts and mature schizonts. Antibody inhibition of EtPDIL function reduced the ability of E. tenella to invade DF-1 cells. These results

  6. Hydrothermal Synthesis of Disulfide-Containing Uranyl Compounds. In Situ Ligand Synthesis versus Direct Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Rowland, Clare E. [George Washington Univ., Washington, DC (United States); Belai, Nebebech [George Washington Univ., Washington, DC (United States); Knope, Karah E. [George Washington Univ., Washington, DC (United States); Cahill, Christopher L. [George Washington Univ., Washington, DC (United States)

    2010-01-29

    Three disulfide-containing uranyl compounds, [UO2(C7H4O2S)3]·H2O (1), [UO2(C7H4O2S)2(C7H5O2S)] (2), and [UO2(C7H4O2S)4] (3) have been hydrothermally synthesized. Both in situ disulfide bond formation from 3- and 4-mercaptobenzoic acid (C7H5O2S, MBA) to yield 3,3'- and 4,4'-dithiobisbenzoic acid (C14H8O4S2, DTBA) and direct assembly with the presynthesized dimeric ligands have been explored. While the starting materials 4-MBA and 4,4'-DTBA both yield 2 via in situ ligand synthesis and direct assembly, respectively, we observe the formation of 1 from the starting material 3-MBA via in situ ligand synthesis and of 3 from the direct assembly of the uranyl cation with 3,3'-DTBA. Concurrently with the synthesis of 1 and 2, we have observed the in situ formation of the crystalline dimeric organic species, 3,3'-DTBA, [(C7H5O2S)2] (4) and 4,4'-DTBA, [(C7H5O2S)2] (5). Herein we report the synthesis and crystallographic characterization of 1-5, as well as observations regarding the utility of product formation via direct assembly and in situ ligand synthesis.

  7. Molecular characterization and analysis of a novel protein disulfide isomerase-like protein of Eimeria tenella.

    Directory of Open Access Journals (Sweden)

    Hongyu Han

    Full Text Available Protein disulfide isomerase (PDI and PDI-like proteins are members of the thioredoxin superfamily. They contain thioredoxin-like domains and catalyze the physiological oxidation, reduction and isomerization of protein disulfide bonds, which are involved in cell function and development in prokaryotes and eukaryotes. In this study, EtPDIL, a novel PDI-like gene of Eimeria tenella, was cloned using rapid amplification of cDNA ends (RACE according to the expressed sequence tag (EST. The EtPDIL cDNA contained 1129 nucleotides encoding 216 amino acids. The deduced EtPDIL protein belonged to thioredoxin-like superfamily and had a single predicted thioredoxin domain with a non-classical thioredoxin-like motif (SXXC. BLAST analysis showed that the EtPDIL protein was 55-59% identical to PDI-like proteins of other apicomplexan parasites. The transcript and protein levels of EtPDIL at different development stages were investigated by real-time quantitative PCR and western blot. The messenger RNA and protein levels of EtPDIL were higher in sporulated oocysts than in unsporulated oocysts, sporozoites or merozoites. Protein expression was barely detectable in unsporulated oocysts. Western blots showed that rabbit antiserum against recombinant EtPDIL recognized only a native 24 kDa protein from parasites. Immunolocalization with EtPDIL antibody showed that EtPDIL had a disperse distribution in the cytoplasm of whole sporozoites and merozoites. After sporozoites were incubated in complete medium, EtPDIL protein concentrated at the anterior of the sporozoites and appeared on the surface of parasites. Specific staining was more intense and mainly located on the parasite surface after merozoites released from mature schizonts invaded DF-1 cells. After development of parasites in DF-1 cells, staining intensified in trophozoites, immature schizonts and mature schizonts. Antibody inhibition of EtPDIL function reduced the ability of E. tenella to invade DF-1 cells

  8. A novel disulfide-rich protein motif from avian eggshell membranes.

    Directory of Open Access Journals (Sweden)

    Vamsi K Kodali

    2011-03-01

    Full Text Available Under the shell of a chicken egg are two opposed proteinaceous disulfide-rich membranes. They are fabricated in the avian oviduct using fibers formed from proteins that are extensively coupled by irreversible lysine-derived crosslinks. The intractability of these eggshell membranes (ESM has slowed their characterization and their protein composition remains uncertain. In this work, reductive alkylation of ESM followed by proteolytic digestion led to the identification of a cysteine rich ESM protein (abbreviated CREMP that was similar to spore coat protein SP75 from cellular slime molds. Analysis of the cysteine repeats in partial sequences of CREMP reveals runs of remarkably repetitive patterns. Module a contains a C-X(4-C-X(5-C-X(8-C-X(6 pattern (where X represents intervening non-cysteine residues. These inter-cysteine amino acid residues are also strikingly conserved. The evolutionarily-related module b has the same cysteine spacing as a, but has 11 amino acid residues at its C-terminus. Different stretches of CREMP sequences in chicken genomic DNA fragments show diverse repeat patterns: e.g. all a modules; an alternation of a-b modules; or an a-b-b arrangement. Comparable CREMP proteins are found in contigs of the zebra finch (Taeniopygia guttata and in the oviparous green anole lizard (Anolis carolinensis. In all these cases the long runs of highly conserved modular repeats have evidently led to difficulties in the assembly of full length DNA sequences. Hence the number, and the amino acid lengths, of CREMP proteins are currently unknown. A 118 amino acid fragment (representing an a-b-a-b pattern from a chicken oviduct EST library expressed in Escherichia coli is a well folded, highly anisotropic, protein with a large chemical shift dispersion in 2D solution NMR spectra. Structure is completely lost on reduction of the 8 disulfide bonds of this protein fragment. Finally, solid state NMR spectra suggest a surprising degree of order in intact

  9. Species-Specific Thiol-Disulfide Equilibrium Constant: A Tool To Characterize Redox Transitions of Biological Importance.

    Science.gov (United States)

    Mirzahosseini, Arash; Somlyay, Máté; Noszál, Béla

    2015-08-13

    Microscopic redox equilibrium constants, a new species-specific type of physicochemical parameters, were introduced and determined to quantify thiol-disulfide equilibria of biological significance. The thiol-disulfide redox equilibria of glutathione with cysteamine, cysteine, and homocysteine were approached from both sides, and the equilibrium mixtures were analyzed by quantitative NMR methods to characterize the highly composite, co-dependent acid-base and redox equilibria. The directly obtained, pH-dependent, conditional constants were then decomposed by a new evaluation method, resulting in pH-independent, microscopic redox equilibrium constants for the first time. The 80 different, microscopic redox equilibrium constant values show close correlation with the respective thiolate basicities and provide sound means for the development of potent agents against oxidative stress.

  10. Self-homodimerization of an actinoporin by disulfide bridging reveals implications for their structure and pore formation.

    Science.gov (United States)

    Valle, Aisel; Pérez-Socas, Luis Benito; Canet, Liem; Hervis, Yadira de la Patria; de Armas-Guitart, German; Martins-de-Sa, Diogo; Lima, Jônatas Cunha Barbosa; Souza, Adolfo Carlos Barros; Barbosa, João Alexandre Ribeiro Gonçalves; de Freitas, Sonia Maria; Pazos, Isabel Fabiola

    2018-04-26

    The Trp111 to Cys mutant of sticholysin I, an actinoporin from Stichodactyla helianthus sea anemone, forms a homodimer via a disulfide bridge. The purified dimer is 193 times less hemolytic than the monomer. Ultracentrifugation, dynamic light scattering and size-exclusion chromatography demonstrate that monomers and dimers are the only independent oligomeric states encountered. Indeed, circular dichroism and fluorescence spectroscopies showed that Trp/Tyr residues participate in homodimerization and that the dimer is less thermostable than the monomer. A homodimer three-dimensional model was constructed and indicates that Trp147/Tyr137 are at the homodimer interface. Spectroscopy results validated the 3D-model and assigned 85° to the disulfide bridge dihedral angle responsible for dimerization. The homodimer model suggests that alterations in the membrane/carbohydrate-binding sites in one of the monomers, as result of dimerization, could explain the decrease in the homodimer ability to form pores.

  11. Reduction of disulfide bonds in peptides and proteins. Reduction des groupes disulfure dans les peptides et proteines

    Energy Technology Data Exchange (ETDEWEB)

    Conte, D [Institut Curie, 75 - Paris (France); Houee-Levin, C [Paris-5 Univ., 75 (France)

    1993-04-01

    We have re-examined the mechanism of disulfide bond reduction in oxidized glutathione by C0[sub 2][sup .-] free radicals. The process appears to be a chain reaction whose initial yield depends on pH and on both peptide and formate ion concentrations, but remains independent on the radiation dose rate. Kinetic schemes drawn from studies on dithiothreitol are unable to account for the results obtained with glutathione and proteins, although the disulfide radical anion is the primary intermediate found with all compounds. The rate constant for its formation from C0[sub 2][sup .-] and glutathione is in the same range as those found using proteins, while decay pathways are somewhat different. Hypotheses are proposed to account for these differences. 6 figs., 2 tabs.

  12. Protein redox regulation in the thylakoid lumen: the importance of disulfide bonds for violaxanthin de-epoxidase.

    Science.gov (United States)

    Simionato, Diana; Basso, Stefania; Zaffagnini, Mirko; Lana, Tobia; Marzotto, Francesco; Trost, Paolo; Morosinotto, Tomas

    2015-04-02

    When exposed to saturating light conditions photosynthetic eukaryotes activate the xanthophyll cycle where the carotenoid violaxanthin is converted into zeaxanthin by the enzyme violaxanthin de-epoxidase (VDE). VDE protein sequence includes 13 cysteine residues, 12 of which are strongly conserved in both land plants and algae. Site directed mutagenesis of Arabidopsis thaliana VDE showed that all these 12 conserved cysteines have a major role in protein function and their mutation leads to a strong reduction of activity. VDE is also shown to be active in its completely oxidized form presenting six disulfide bonds. Redox titration showed that VDE activity is sensitive to variation in redox potential, suggesting the possibility that dithiol/disulfide exchange reactions may represent a mechanism for VDE regulation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. Dissulfeto de molibdênio, um material multifuncional e surpreendente Molybdenum disulfide, a multifunctional and remarkable material

    Directory of Open Access Journals (Sweden)

    Fernando Wypych

    2002-02-01

    Full Text Available The aim of this work is to review the chemical and physical properties of layered molybdenum disulfide. The three polymorphic/polytypic modifications of the compound were found, the polytypes 2H (molybdenite and 3R are semiconductors while the polymorph 1T is an electronic conductor. 2H-MoS2 has several important industrial applications as hydrotreatment catalysts, energy storage devices, solar cells, solid lubricants, among others. When intercalated, the 2H phase changes to a distorted 1T phase, producing unstable intercalation compounds that can be exfoliated in solution, producing single layers and consequently nanocomposites. The direct synthesis of the 1T phase produces stable intercalation compounds. Recently molybdenum disulfide was prepared as nanotubes and fulerene-like structures that bring new insights in the investigation of this important material.

  14. Engineering a disulfide bond in the lid hinge region of Rhizopus chinensis lipase: increased thermostability and altered acyl chain length specificity.

    Directory of Open Access Journals (Sweden)

    Xiao-Wei Yu

    Full Text Available The key to enzyme function is the maintenance of an appropriate balance between molecular stability and structural flexibility. The lid domain which is very important for "interfacial activation" is the most flexible part in the lipase structure. In this work, rational design was applied to explore the relationship between lid rigidity and lipase activity by introducing a disulfide bond in the hinge region of the lid, in the hope of improving the thermostability of R. chinensis lipase through stabilization of the lid domain without interfering with its catalytic performance. A disulfide bridge between F95C and F214C was introduced into the lipase from R. chinensis in the hinge region of the lid according to the prediction of the "Disulfide by Design" algorithm. The disulfide variant showed substantially improved thermostability with an eleven-fold increase in the t(1/2 value at 60°C and a 7°C increase of T(m compared with the parent enzyme, probably contributed by the stabilization of the geometric structure of the lid region. The additional disulfide bond did not interfere with the catalytic rate (k(cat and the catalytic efficiency towards the short-chain fatty acid substrate, however, the catalytic efficiency of the disulfide variant towards pNPP decreased by 1.5-fold probably due to the block of the hydrophobic substrate channel by the disulfide bond. Furthermore, in the synthesis of fatty acid methyl esters, the maximum conversion rate by RCLCYS reached 95% which was 9% higher than that by RCL. This is the first report on improving the thermostability of the lipase from R. chinensis by introduction of a disulfide bond in the lid hinge region without compromising the catalytic rate.

  15. Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: possible new targets of pharmacologic agents.

    Science.gov (United States)

    Nagy, Lajos; Nagata, Miki; Szabo, Sandor

    2007-04-14

    To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions (HML) and the mechanism of gastroprotective effect of sucralfate. Rats were given 1 mL of 75% ethanol, 25% NaCl, 0.6 mol/L HCl, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically (i.g.) and sacrificed 1, 3, 6 or 12 min later. Total (reduced and oxidized) glutathione (GSH + GSSG), glutathione disulfide (GSSG), protein free sulfhydryls (PSH), protein-glutathione mixed disulfides (PSSG) and protein cystine disulfides (PSSP) were measured in gastric mucosa and liver. Reduced glutathione (GSH) was depleted in the gastric mucosa after ethanol, HCl or NaCl exposure, while oxidized glutathione (GSSG) concentrations increased, except by HCl and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed, NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals. No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations. Our modified methods are now suitable for direct measurements of major protein and non-protein thiols/disulfides in the gastric mucosa or liver. A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.

  16. Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: Possible new targets of pharmacologic agents

    Institute of Scientific and Technical Information of China (English)

    Lajos Nagy; Miki Nagata; Sandor Szabo

    2007-01-01

    AIM: To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions (HML) and the mechanism of gastroprotective effect of sucralfate.METHODS: Rats were given 1 mL of 75% ethanol, 25%NaCl, 0.6 mol/L HCI, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically (i.g.) and sacrificed 1, 3, 6 or 12 min later. Total (reduced and oxidized) glutathione (GSH + GSSG), glutathione disulfide (GSSG), protein free sulfhydryls (PSH), protein-glutathione mixed disulfides (PSSG) and protein cystine disulfides (PSSP) were measured in gastric mucosa and liver.RESULTS: Reduced glutathione (GSH) was depleted in the gastric mucosa after ethanol, HCI or NaCl exposure,while oxidized glutathione (GSSG) concentrations increased, except by HCI and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed,NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals.No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations.CONCLUSION: Our modified methods are now suitable for direct measurements of major protein and nonprotein thiols/disulfides in the gastric mucosa or liver.A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.

  17. [Ecotourism exploitation model in Bita Lake Natural Reserve of Yunnan].

    Science.gov (United States)

    Yang, G; Wang, Y; Zhong, L

    2000-12-01

    Bita lake provincial natural reserve is located in Shangri-La region of North-western Yunnan, and was set as a demonstrating area for ecotourism exploitation in 1998. After a year's exploitation construction and half a year's operation as a branch of the 99' Kunming International Horticulture Exposition to accept tourists, it was proved that the ecotourism demonstrating area attained four integrated functions of ecotourism, i.e., tourism, protection, poverty clearing and environment education. Five exploitation and management models including function zoned exploitation model, featured tourism communication model signs system designing model, local Tibetan family reception model and environmental monitoring model, were also successful, which were demonstrated and spreaded to the whole province. Bita lake provincial natural reserve could be a good sample for the ecotourism exploitation natural reserves of the whole country.

  18. Detection and function of an intramolecular disulfide bond in the pH-responsive CadC of Escherichia coli

    Directory of Open Access Journals (Sweden)

    Dönhöfer Alexandra

    2011-04-01

    Full Text Available Abstract Background In an acidic and lysine-rich environment Escherichia coli induces expression of the cadBA operon which encodes CadA, the lysine decarboxylase, and CadB, the lysine/cadaverine antiporter. cadBA expression is dependent on CadC, a membrane-integrated transcriptional activator which belongs to the ToxR-like protein family. Activation of CadC requires two stimuli, lysine and low pH. Whereas lysine is detected by an interplay between CadC and the lysine-specific transporter LysP, pH alterations are sensed by CadC directly. Crystal structural analyses revealed a close proximity between two periplasmic cysteines, Cys208 and Cys272. Results Substitution of Cys208 and/or Cys272 by alanine resulted in CadC derivatives that were active in response to only one stimulus, either lysine or pH 5.8. Differential in vivo thiol trapping revealed a disulfide bond between these two residues at pH 7.6, but not at pH 5.8. When Cys208 and Cys272 were replaced by aspartate and lysine, respectively, virtually wild-type behavior was restored indicating that the disulfide bond could be mimicked by a salt bridge. Conclusion A disulfide bond was found in the periplasmic domain of CadC that supports an inactive state of CadC at pH 7.6. At pH 5.8 disulfide bond formation is prevented which transforms CadC into a semi-active state. These results provide new insights into the function of a pH sensor.

  19. Oxidative protein folding: from thiol-disulfide exchange reactions to the redox poise of the endoplasmic reticulum.

    Science.gov (United States)

    Hudson, Devin A; Gannon, Shawn A; Thorpe, Colin

    2015-03-01

    This review examines oxidative protein folding within the mammalian endoplasmic reticulum (ER) from an enzymological perspective. In protein disulfide isomerase-first (PDI-first) pathways of oxidative protein folding, PDI is the immediate oxidant of reduced client proteins and then addresses disulfide mispairings in a second isomerization phase. In PDI-second pathways the initial oxidation is PDI-independent. Evidence for the rapid reduction of PDI by reduced glutathione is presented in the context of PDI-first pathways. Strategies and challenges are discussed for determination of the concentrations of reduced and oxidized glutathione and of the ratios of PDI(red):PDI(ox). The preponderance of evidence suggests that the mammalian ER is more reducing than first envisaged. The average redox state of major PDI-family members is largely to almost totally reduced. These observations are consistent with model studies showing that oxidative protein folding proceeds most efficiently at a reducing redox poise consistent with a stoichiometric insertion of disulfides into client proteins. After a discussion of the use of natively encoded fluorescent probes to report the glutathione redox poise of the ER, this review concludes with an elaboration of a complementary strategy to discontinuously survey the redox state of as many redox-active disulfides as can be identified by ratiometric LC-MS-MS methods. Consortia of oxidoreductases that are in redox equilibrium can then be identified and compared to the glutathione redox poise of the ER to gain a more detailed understanding of the factors that influence oxidative protein folding within the secretory compartment. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Studies of the activity of cytosol on the mixed disulfide bond formed by proteins and radioprotector mercaptoethylguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Horvath, M [National Inst. of Oncology, Budapest (Hungary); Holland, J [Orszagos Onkologiai Intezet, Budapest (Hungary)

    1979-01-01

    The cytoplasm of normal and tumorous rat liver cells contains a heat-resistant compound with reducing ability to break the mixed disulfide bond of albumin-/sup 14/C-mercaptoethylguanidine. The reducing activity of cytosol is destoryed by 1000 krd /sup 60/Co-gamma-ray doses in diluted solution. In vivo supralethal of rats does not affect the activity of cytosol prepared from liver cells.

  1. Mutagenesis of the redox-active disulfide in mercuric ion reductase: Catalysis by mutant enzymes restricted to flavin redox chemistry

    International Nuclear Information System (INIS)

    Distefano, M.D.; Au, K.G.; Walsh, C.T.

    1989-01-01

    Mercuric reductase, a flavoenzyme that possesses a redox-active cystine, Cys 135 Cys 140 , catalyzes the reduction of Hg(II) to Hg(0) by NADPH. As a probe of mechanism, the authors have constructed mutants lacking a redox-active disulfide by eliminating Cys 135 (Ala 135 Cys 140 ), Cys 14 (Cys 135 Ala 140 ), or both (Ala 135 Ala 140 ). Additionally, they have made double mutants that lack Cys 135 (Ala 135 Cys 139 Cys 140 ) or Cys 140 (Cys 135 Cys 139 Ala 140 ) but introduce a new Cys in place of Gly 139 with the aim of constructing dithiol pairs in the active site that do not form a redox-active disulfide. The resulting mutant enzymes all lack redox-active disulfides and are hence restricted to FAD/FADH 2 redox chemistry. Each mutant enzyme possesses unique physical and spectroscopic properties that reflect subtle differences in the FAD microenvironment. Preliminary evidence for the Ala 135 Cys 139 Cys 14 mutant enzyme suggests that this protein forms a disulfide between the two adjacent Cys residues. Hg(II) titration experiments that correlate the extent of charge-transfer quenching with Hg(II) binding indicate that the Ala 135 Cys 140 protein binds Hg(II) with substantially less avidity than does the wild-type enzyme. All mutant mercuric reductases catalyze transhydrogenation and oxygen reduction reactions through obligatory reduced flavin intermediates at rates comparable to or greater than that of the wild-type enzyme. In multiple-turnover assays which monitored the production of Hg(0), two of the mutant enzymes were observed to proceed through at least 30 turnovers at rates ca. 1000-fold slower than that of wild-type mercuric reductase. They conclude that the Cys 135 and Cys 140 thiols serve as Hg(II) ligands that orient the Hg(II) for subsequent reduction by a reduced flavin intermediate

  2. The influence of the Cys46/Cys55 disulfide bond on the redox and spectroscopic properties of human neuroglobin.

    Science.gov (United States)

    Bellei, Marzia; Bortolotti, Carlo Augusto; Di Rocco, Giulia; Borsari, Marco; Lancellotti, Lidia; Ranieri, Antonio; Sola, Marco; Battistuzzi, Gianantonio

    2018-01-01

    Neuroglobin is a monomeric globin containing a six-coordinate heme b, expressed in the nervous system, which exerts an important neuroprotective role. In the human protein (hNgb), Cys46 and Cys55 form an intramolecular disulfide bond under oxidizing conditions, whose cleavage induces a helix-to-strand rearrangement of the CD loop that strengthens the bond between the heme iron and the distal histidine. Hence, it is conceivable that the intramolecular disulfide bridge modulates the functionality of human neuroglobin by controlling exogenous ligand binding. In this work, we investigated the influence of the Cys46/Cys55 disulfide bond on the redox properties and on the pH-dependent conformational equilibria of hNgb, using UV-vis spectroelectrochemistry, cyclic voltammetry, electronic absorption spectroscopy and magnetic circular dichroism (MCD). We found that the SS bridge significantly affects the heme Fe(III) to Fe(II) reduction enthalpy (ΔH°' rc ) and entropy (ΔS°' rc ), mostly as a consequence of changes in the reduction-induced solvent reorganization effects, without affecting the axial ligand-binding interactions and the polarity and electrostatics of the heme environment. Between pH3 and 12, the electronic properties of the heme of ferric hNgb are sensitive to five acid-base equilibria, which are scarcely affected by the Cys46/Cys55 disulfide bridge. The equilibria occurring at extreme pH values induce heme release, while those occurring between pH5 and 10 alter the electronic properties of the heme without modifying its axial coordination and low spin state. They involve the sidechains of non-coordinating aminoacids close to the heme and at least one heme propionate. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Effect of trastuzumab interchain disulfide bond cleavage on Fcγ receptor binding and antibody-dependent tumour cell phagocytosis.

    Science.gov (United States)

    Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Ootsubo, Michiko; Izawa, Ken-ichi; Kohroki, Junya; Masuho, Yasuhiko

    2016-01-01

    The Fc domain of human IgG1 binds to Fcγ receptors (FcγRs) to induce effector functions such as phagocytosis. There are four interchain disulfide bonds between the H and L chains. In this study, the disulfide bonds within the IgG1 trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation or by mild reduction followed by S-alkylation with three different reagents. The cleavage did not change the binding activities of TRA to HER2-bearing SK-BR-3 cells. The binding activities of TRA to FcγRIIA and FcγRIIB were greatly enhanced by modification with mild reduction and S-alkylation with ICH2CONH2 or N-(4-aminophenyl) maleimide, while the binding activities of TRA to FcγRI and FcγRIIIA were decreased by any of the four modifications. However, the interchain disulfide bond cleavage by the different modifications did not change the antibody-dependent cell-mediated phagocytosis (ADCP) of SK-BR-3 cells by activated THP-1 cells. The order of FcγR expression levels on the THP-1 cells was FcγRII > FcγRI > FcγRIII and ADCP was inhibited by blocking antibodies against FcγRI and FcγRII. These results imply that the effect of the interchain disulfide bond cleavage on FcγRs binding and ADCP is dependent on modifications of the cysteine residues and the FcγR isotypes. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  4. Scan-rate dependence in protein calorimetry: the reversible transitions of Bacillus circulans xylanase and a disulfide-bridge mutant.

    OpenAIRE

    Davoodi, J.; Wakarchuk, W. W.; Surewicz, W. K.; Carey, P. R.

    1998-01-01

    The stabilities of Bacillus circulans xylanase and a disulfide-bridge-containing mutant (S100C/N148C) were investigated by differential scanning calorimetry (DSC) and thermal inactivation kinetics. The thermal denaturation of both proteins was found to be irreversible, and the apparent transition temperatures showed a considerable dependence upon scanning rate. In the presence of low (nondenaturing) concentrations of urea, calorimetric transitions were observed for both proteins in the second...

  5. Solubilization and folding of a fully active recombinant Gaussia luciferase with native disulfide bonds by using a SEP-Tag.

    Science.gov (United States)

    Rathnayaka, Tharangani; Tawa, Minako; Nakamura, Takashi; Sohya, Shihori; Kuwajima, Kunihiro; Yohda, Masafumi; Kuroda, Yutaka

    2011-12-01

    Gaussia luciferase (GLuc) is the smallest known bioluminescent protein and is attracting much attention as a potential reporter protein. However, its 10 disulfide bond forming cysteines have hampered the efficient production of recombinant GLuc and thus limited its use in bio-imaging application. Here, we demonstrate that the addition of a short solubility enhancement peptide tag (SEP-Tag) to the C-terminus of GLuc (GLuc-C9D) significantly increased the fraction of soluble protein at a standard expression temperature. The expression time was much shorter, and the final yield of GLuc-C9D was significantly higher than with our previous pCold expression system. Reversed phase HPLC indicated that the GLuc-C9D variant folded with a single disulfide bond pattern after proper oxidization. Further, the thermal denaturation of GLuc-C9D was completely reversible, and its secondary structure content remained unchanged until 40°C as assessed by CD spectroscopy. The (1)H-NMR spectrum of GLuc indicated sharp well dispersed peaks typical for natively folded proteins. GLuc-C9D bioluminescence activity was strong and fully retained even after incubation at high temperatures. These results suggest that solubilization using SEP-Tags can be useful for producing large quantities of proteins containing multiple disulfide bonds. Copyright © 2011. Published by Elsevier B.V.

  6. Multimolecular Salivary Mucin Complex Is Altered in Saliva of Cigarette Smokers: Detection of Disulfide Bridges by Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Motoe Taniguchi

    2013-01-01

    Full Text Available Saliva contains mucins, which protect epithelial cells. We showed a smaller amount of salivary mucin, both MG1 and MG2, in the premenopausal female smokers than in their nonsmoking counterparts. Smokers' MG1, which contains almost 2% cysteine/half cystine in its amino acid residues, turned out to be chemically altered in the nonsmoker’s saliva. The smaller acidic glycoprotein bands were detectable only in smoker’s saliva in the range of 20–25 kDa and at 45 kDa, suggesting that degradation, at least in part, caused the reduction of MG1 mucin. This is in agreement with the previous finding that free radicals in cigarette smoke modify mucins in both sugar and protein moieties. Moreover, proteins such as amylase and albumin are bound to other proteins through disulfide bonds and are identifiable only after reduction with DTT. Confocal laser Raman microspectroscopy identified a disulfide stretch band of significantly stronger intensity per protein in the stimulated saliva of smokers alone. We conclude that the saliva of smokers, especially stimulated saliva, contains significantly more oxidized form of proteins with increased disulfide bridges, that reduces protection for oral epithelium. Raman microspectroscopy can be used for an easy detection of the damaged salivary proteins.

  7. Engineered disulfide bonds increase active-site local stability and reduce catalytic activity of a cold-adapted alkaline phosphatase.

    Science.gov (United States)

    Asgeirsson, Bjarni; Adalbjörnsson, Björn Vidar; Gylfason, Gudjón Andri

    2007-06-01

    Alkaline phosphatase is an extracellular enzyme that is membrane-bound in eukaryotes but resides in the periplasmic space of bacteria. It normally carries four cysteine residues that form two disulfide bonds, for instance in the APs of Escherichia coli and vertebrates. An AP variant from a Vibrio sp. has only one cysteine residue. This cysteine is second next to the nucleophilic serine in the active site. We have individually modified seven residues to cysteine that are on two loops predicted to be within a 5 A radius. Four of them formed a disulfide bond to the endogenous cysteine. Thermal stability was monitored by circular dichroism and activity measurements. Global stability was similar to the wild-type enzyme. However, a significant increase in heat-stability was observed for the disulfide-containing variants using activity as a measure, together with a large reduction in catalytic rates (k(cat)) and a general decrease in Km values. The results suggest that a high degree of mobility near the active site and in the helix carrying the endogenous cysteine is essential for full catalytic efficiency in the cold-adapted AP.

  8. Redox Reactivity of Cerium Oxide Nanoparticles Induces the Formation of Disulfide Bridges in Thiol-Containing Biomolecules.

    Science.gov (United States)

    Rollin-Genetet, Françoise; Seidel, Caroline; Artells, Ester; Auffan, Mélanie; Thiéry, Alain; Vidaud, Claude

    2015-12-21

    The redox state of disulfide bonds is implicated in many redox control systems, such as the cysteine-cystine couple. Among proteins, ubiquitous cysteine-rich metallothioneins possess thiolate metal binding groups susceptible to metal exchange in detoxification processes. CeO2 NPs are commonly used in various industrial applications due to their redox properties. These redox properties that enable dual oxidation states (Ce(IV)/Ce(III)) to exist at their surface may act as oxidants for biomolecules. The interaction among metallothioneins, cysteine, and CeO2 NPs was investigated through various biophysical approaches to shed light on the potential effects of the Ce(4+)/Ce(3+) redox system on the thiol groups of these biomolecules. The possible reaction mechanisms include the formation of a disulfide bridge/Ce(III) complex resulting from the interaction between Ce(IV) and the thiol groups, leading to metal unloading from the MTs, depending on their metal content and cluster type. The formation of stable Ce(3+) disulfide complexes has been demonstrated via their fluorescence properties. This work provides the first evidence of thiol concentration-dependent catalytic oxidation mechanisms between pristine CeO2 NPs and thiol-containing biomolecules.

  9. Engineering nutritious proteins: improvement of stability in the designer protein MB-1 via introduction of disulfide bridges.

    Science.gov (United States)

    Doucet, Alain; Williams, Martin; Gagnon, Mylene C; Sasseville, Maxime; Beauregard, Marc

    2002-01-02

    Protein design is currently used for the creation of new proteins with desirable traits. In this laboratory the focus has been on the synthesis of proteins with high essential amino acid content having potential applications in animal nutrition. One of the limitations faced in this endeavor is achieving stable proteins despite a highly biased amino acid content. Reported here are the synthesis and characterization of two disulfide-bridged mutants derived from the MB-1 designer protein. Both mutants outperformed their parent protein MB-1 with their bridge formed, as shown by circular dichroism, size exclusion chromatography, thermal denaturation, and proteolytic degradation experiments. When the disulfide bridges were cleaved, the mutants' behavior changed: the mutants significantly unfolded, suggesting that the introduction of Cys residues was deleterious to MB-1-folding. In an attempt to compensate for the mutations used, a Tyr62-Trp mutation was performed, leading to an increase in bulk and hydrophobicity in the core. The Trp-containing disulfide-bridged mutants did not behave as well as the original MB-1Trp, suggesting that position 62 might not be adequate for a compensatory mutation.

  10. Design and introduction of a disulfide bridge in firefly luciferase: increase of thermostability and decrease of pH sensitivity.

    Science.gov (United States)

    Imani, Mehdi; Hosseinkhani, Saman; Ahmadian, Shahin; Nazari, Mahboobeh

    2010-08-01

    The thermal sensitivity and pH-sensitive spectral properties of firefly luciferase have hampered its application in a variety of fields. It is proposed that the stability of a protein can be increased by introduction of disulfide bridge that decreases the configurational entropy of unfolding. A disulfide bridge is introduced into Photinus pyralis firefly luciferase to make two separate mutant enzymes with a single bridge. Even though the A103C/S121C mutant showed remarkable thermal stability, its specific activity decreased, whereas the A296C/A326C mutant showed tremendous thermal stability, relative pH insensitivity and 7.3-fold increase of specific activity. Moreover, the bioluminescence emission spectrum of A296C/A326C was resistant against higher temperatures (37 degrees C). Far-UV CD analysis showed slight secondary structure changes for both mutants. Thermal denaturation analysis showed that conformational stabilities of A103C/S121C and A296C/A326C are more than native firefly luciferase. It is proposed that since A296 and A326 are situated in the vicinity of the enzyme active site microenvironment in comparison with A103 and S121, the formation of a disulfide bridge in this region has more impact on enzyme kinetic characteristics.

  11. Ceramic matrix composites by microwave assisted CVI

    International Nuclear Information System (INIS)

    Currier, R.P.; Devlin, D.J.

    1993-01-01

    Chemical vapor infiltration (CVI) processes for producing continuously reinforced ceramic composites are reviewed. Potential advantages of microwave assisted CVI are noted and numerical studies of microwave assisted CVI are reviewed. The models predict inverted thermal gradients in fibrous ceramic preforms subjected to microwave radiation and suggest processing strategies for achieving uniformly dense composites. Comparisons are made to experimental results on silicon-based composite systems. The role played by the relative ability of fiber and matrix to dissipate microwave energy is noted. Results suggest that microwave induced inverted gradients can be exploited to promote inside-out densification. 10 refs., 2 figs

  12. Cleavage of the interchain disulfide bonds in rituximab increases its affinity for FcγRIIIA.

    Science.gov (United States)

    Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Kobayashi, Eiji; Fukuchi, Kaori; Tsukimoto, Mitsutoshi; Kojima, Shuji; Kohroki, Junya; Akimoto, Kazunori; Masuho, Yasuhiko

    2013-07-05

    The Fc region of human IgG1 mediates effector function via binding to Fcγ receptors and complement activation. The H and L chains of IgG1 antibodies are joined by four interchain disulfide bonds. In this study, these bonds within the therapeutic IgG1 rituximab (RTX) were cleaved either by mild reduction followed by alkylation or by mild S-sulfonation; consequently, two modified RTXs - A-RTX (alkylated) and S-RTX (S-sulfonated) - were formed, and both were almost as potent as unmodified RTX when binding CD20 antigen. Unexpectedly, each modified RTX had a higher binding affinity for FcγRIIIA (CD16A) than did unmodified RTX. However, S-RTX and A-RTX were each less potent than RTX in an assay of antibody-dependent cellular cytotoxicity (ADCC). In this ADCC assay, each modified RTX showed decreased secretion of granzyme B, but no change in perforin secretion, from effector cells. These results provide significant information on the structures within IgG1 that are involved in binding FcγRIIIA, and they may be useful in the development of therapeutic antagonists for FcγRIIIA. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Health effect of chronic exposure to carbon disulfide (CS 2 on women employed in viscose industry

    Directory of Open Access Journals (Sweden)

    Krzysztof Sieja

    2018-05-01

    Full Text Available Many women are exposed to carbon disulfide (CS 2 hazards at work every day. Working with CS 2 may cause some women to experience abnormalities in their reproductive health. Until now obtained data is generally concentrated on the health effects of CS 2 observed in the viscose industry. To date, CS 2 has not been studied precisely for its potential to have damaging effects on female reproductive system, especially the frequency of menstrual disturbances and the course of menopause. The aim of the study was to sum up female reproductive health hazards amongst women chronically exposed to CS 2 in their workplace in the viscose industry. In order to study the effect of CS 2 in the contemporary viscose industry, exposure measurements should be collected in prospective or cross-sectional studies. In conclusion, reproductive health hazards for women chronically exposed to CS 2 in the workplace in the viscose industry are the following: 1 menstrual disorders essentially are more frequent than in the case of the healthy women, 2 for women chronically exposed to CS 2 the average menopausal age is statistically earlier, as compared to healthy women, 3 complex disturbances in neurohormonal system for women exposed to CS 2 , resulting from toxic influences of CS 2 , which cause the secretion of estrogens and progesterone in ovaries and dehydroepiandrosterone sulfate in the adrenal gland to diminish. Med Pr 2018;69(3:329–335

  14. Gold nanoparticles physicochemically bonded onto tungsten disulfide nanosheet edges exhibit augmented plasmon damping

    Directory of Open Access Journals (Sweden)

    Gregory T. Forcherio

    2017-07-01

    Full Text Available Augmented plasmonic damping of dipole-resonant gold (Au nanoparticles (NP physicochemically bonded onto edges of tungsten disulfide (WS2 nanosheets, ostensibly due to hot electron injection, is quantified using electron energy loss spectroscopy (EELS. EELS allows single-particle spatial resolution. A measured 0.23 eV bandwidth expansion of the localized surface plasmon resonance upon covalent bonding of 20 nm AuNP to WS2 edges was deemed significant by Welch’s t-test. Approximately 0.19 eV of the measured 0.23 eV expansion went beyond conventional radiative and nonradiative damping mechanisms according to discrete dipole models, ostensibly indicating emergence of hot electron transport from AuNP into the WS2. A quantum efficiency of up to 11±5% spanning a 7 fs transfer process across the optimized AuNP-TMD ohmic junction is conservatively calculated. Putative hot electron transport for AuNP physicochemically bonded to TMD edges exceeded that for AuNP physically deposited onto the TMD basal plane. This arose from contributions due to (i direct physicochemical bond between AuNP and WS2; (ii AuNP deposition at TMD edge sites; and (iii lower intrinsic Schottky barrier. This improves understanding of photo-induced doping of TMD by metal NP which could benefit emerging catalytic and optoelectronic applications.

  15. Tuning the Schottky rectification in graphene-hexagonal boron nitride-molybdenum disulfide heterostructure.

    Science.gov (United States)

    Liu, Biao; Zhao, Yu-Qing; Yu, Zhuo-Liang; Wang, Lin-Zhi; Cai, Meng-Qiu

    2018-03-01

    It was still a great challenge to design high performance of rectification characteristic for the rectifier diode. Lately, a new approach was proposed experimentally to tune the Schottky barrier height (SBH) by inserting an ultrathin insulated tunneling layer to form metal-insulator-semiconductor (MIS) heterostructures. However, the electronic properties touching off the high performance of these heterostructures and the possibility of designing more efficient applications for the rectifier diode were not presently clear. In this paper, the structural, electronic and interfacial properties of the novel MIS diode with the graphene/hexagonal boron nitride/monolayer molybdenum disulfide (GBM) heterostructure had been investigated by first-principle calculations. The calculated results showed that the intrinsic properties of graphene and MoS 2 were preserved due to the weak van der Waals contact. The height of interfacial Schottky barrier can be tuned by the different thickness of hBN layers. In addition, the GBM Schottky diode showed more excellent rectification characteristic than that of GM Schottky diode due to the interfacial band bending caused by the epitaxial electric field. Based on the electronic band structure, we analyzed the relationship between the electronic structure and the nature of the Schottky rectifier, and revealed the potential of utilizing GBM Schottky diode for the higher rectification characteristic devices. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Phosphorene/rhenium disulfide heterojunction-based negative differential resistance device for multi-valued logic

    Science.gov (United States)

    Shim, Jaewoo; Oh, Seyong; Kang, Dong-Ho; Jo, Seo-Hyeon; Ali, Muhammad Hasnain; Choi, Woo-Young; Heo, Keun; Jeon, Jaeho; Lee, Sungjoo; Kim, Minwoo; Song, Young Jae; Park, Jin-Hong

    2016-11-01

    Recently, negative differential resistance devices have attracted considerable attention due to their folded current-voltage characteristic, which presents multiple threshold voltage values. Because of this remarkable property, studies associated with the negative differential resistance devices have been explored for realizing multi-valued logic applications. Here we demonstrate a negative differential resistance device based on a phosphorene/rhenium disulfide (BP/ReS2) heterojunction that is formed by type-III broken-gap band alignment, showing high peak-to-valley current ratio values of 4.2 and 6.9 at room temperature and 180 K, respectively. Also, the carrier transport mechanism of the BP/ReS2 negative differential resistance device is investigated in detail by analysing the tunnelling and diffusion currents at various temperatures with the proposed analytic negative differential resistance device model. Finally, we demonstrate a ternary inverter as a multi-valued logic application. This study of a two-dimensional material heterojunction is a step forward toward future multi-valued logic device research.

  17. Self-healing polyurethane/attapulgite nanocomposites based on disulfide bonds and shape memory effect

    International Nuclear Information System (INIS)

    Xu, Yurun; Chen, Dajun

    2017-01-01

    Nanocomposites with remarkable enhanced mechanical properties have attracted great research efforts recently. In this work, a series of self-healing polyurethane/attapulgite nanocomposites were prepared by solution blending. Introducing self-healing ability and attapulgite (AT) reinforcement simultaneously led to prolonged material lifetime and enhanced mechanical properties. Scanning electron microscope (SEM) observation indicated that AT could achieve a uniform dispersion in polyurethane matrix when AT content was relatively low. The influences on mechanical properties were evaluated by tensile test. Results showed that incorporating an appropriate content of AT would lead to an enhanced tensile properties. The interactions between AT and polyurethane matrix were studied by effective cross-linking density calculation and Fourier transform infrared (FTIR) analysis. Results indicated that rich hydrogen bonds were formed between AT and polyurethane matrix. Displacement data was utilized to evaluate the influence on shape memory effect. With the incorporation of AT, deformation of the sample under external force was restrained. Meanwhile, closure of the scratches still can be accomplished during healing process. Results of healing test suggested that incorporating 1% of AT would also promote self-healing property. - Highlights: • Composites with both self-healing and enhanced mechanical property are prepared. • Healing mechanism relies on disulfide exchange reaction and shape memory effect. • Mechanical enhancement is caused by rich hydrogen bonds introduced by attapulgite.

  18. Phosphorene/rhenium disulfide heterojunction-based negative differential resistance device for multi-valued logic

    Science.gov (United States)

    Shim, Jaewoo; Oh, Seyong; Kang, Dong-Ho; Jo, Seo-Hyeon; Ali, Muhammad Hasnain; Choi, Woo-Young; Heo, Keun; Jeon, Jaeho; Lee, Sungjoo; Kim, Minwoo; Song, Young Jae; Park, Jin-Hong

    2016-01-01

    Recently, negative differential resistance devices have attracted considerable attention due to their folded current–voltage characteristic, which presents multiple threshold voltage values. Because of this remarkable property, studies associated with the negative differential resistance devices have been explored for realizing multi-valued logic applications. Here we demonstrate a negative differential resistance device based on a phosphorene/rhenium disulfide (BP/ReS2) heterojunction that is formed by type-III broken-gap band alignment, showing high peak-to-valley current ratio values of 4.2 and 6.9 at room temperature and 180 K, respectively. Also, the carrier transport mechanism of the BP/ReS2 negative differential resistance device is investigated in detail by analysing the tunnelling and diffusion currents at various temperatures with the proposed analytic negative differential resistance device model. Finally, we demonstrate a ternary inverter as a multi-valued logic application. This study of a two-dimensional material heterojunction is a step forward toward future multi-valued logic device research. PMID:27819264

  19. Defect-Mediated Lithium Adsorption and Diffusion on Monolayer Molybdenum Disulfide.

    Science.gov (United States)

    Sun, Xiaoli; Wang, Zhiguo; Fu, Y Q

    2015-12-22

    Monolayer Molybdenum Disulfide (MoS2) is a promising anode material for lithium ion batteries because of its high capacities. In this work, first principle calculations based on spin density functional theory were performed to investigate adsorption and diffusion of lithium on monolayer MoS2 with defects, such as single- and few-atom vacancies, antisite, and grain boundary. The values of adsorption energies on the monolayer MoS2 with the defects were increased compared to those on the pristine MoS2. The presence of defects causes that the Li is strongly bound to the monolayer MoS2 with adsorption energies in the range between 2.81 and 3.80 eV. The donation of Li 2s electron to the defects causes an enhancement of adsorption of Li on the monolayer MoS2. At the same time, the presence of defects does not apparently affect the diffusion of Li, and the energy barriers are in the range of 0.25-0.42 eV. The presence of the defects can enhance the energy storage capacity, suggesting that the monolayer MoS2 with defects is a suitable anode material for the Li-ion batteries.

  20. Optical spectroscopic elucidation of beta-turns in disulfide bridged cyclic tetrapeptides.

    Science.gov (United States)

    Borics, Attila; Murphy, Richard F; Lovas, Sándor

    2007-01-01

    Vibrational circular dichroism (VCD) spectroscopic features of type II beta-turns were characterized previously, but, criteria for differentiation between beta-turn types had not been established yet. Model tetrapeptides, cyclized through a disulfide bridge, were designed on the basis of previous experimental results and the observed incidence of amino acid residues in the i + 1 and i + 2 positions in beta-turns, to determine the features of VCD spectra of type I and II beta-turns. The results were correlated with electronic circular dichroism (ECD) spectra and VCD spectra calculated from conformational data obtained by molecular dynamics (MD) simulations. All cyclic tetrapeptides yielded VCD signals with a higher frequency negative and a lower frequency positive couplet with negative lobes overlapping. MD simulations confirmed the conformational homogeneity of these peptides in solution. Comparison with ECD spectroscopy, MD, and quantum chemical calculation results suggested that the low frequency component of VCD spectra originating from the tertiary amide vibrations could be used to distinguish between types of beta-turn structures. On the basis of this observation, VCD spectroscopic features of type II and VIII beta-turns and ECD spectroscopic properties of a type VIII beta-turn were suggested. The need for independent experimental as well as theoretical investigations to obtain decisive conformational information was recognized. Copyright 2006 Wiley Periodicals, Inc.

  1. Gold nanoparticles physicochemically bonded onto tungsten disulfide nanosheet edges exhibit augmented plasmon damping

    Science.gov (United States)

    Forcherio, Gregory T.; Dunklin, Jeremy R.; Backes, Claudia; Vaynzof, Yana; Benamara, Mourad; Roper, D. Keith

    2017-07-01

    Augmented plasmonic damping of dipole-resonant gold (Au) nanoparticles (NP) physicochemically bonded onto edges of tungsten disulfide (WS2) nanosheets, ostensibly due to hot electron injection, is quantified using electron energy loss spectroscopy (EELS). EELS allows single-particle spatial resolution. A measured 0.23 eV bandwidth expansion of the localized surface plasmon resonance upon covalent bonding of 20 nm AuNP to WS2 edges was deemed significant by Welch's t-test. Approximately 0.19 eV of the measured 0.23 eV expansion went beyond conventional radiative and nonradiative damping mechanisms according to discrete dipole models, ostensibly indicating emergence of hot electron transport from AuNP into the WS2. A quantum efficiency of up to 11±5% spanning a 7 fs transfer process across the optimized AuNP-TMD ohmic junction is conservatively calculated. Putative hot electron transport for AuNP physicochemically bonded to TMD edges exceeded that for AuNP physically deposited onto the TMD basal plane. This arose from contributions due to (i) direct physicochemical bond between AuNP and WS2; (ii) AuNP deposition at TMD edge sites; and (iii) lower intrinsic Schottky barrier. This improves understanding of photo-induced doping of TMD by metal NP which could benefit emerging catalytic and optoelectronic applications.

  2. ReaxFF Reactive Force-Field Study of Molybdenum Disulfide (MoS2).

    Science.gov (United States)

    Ostadhossein, Alireza; Rahnamoun, Ali; Wang, Yuanxi; Zhao, Peng; Zhang, Sulin; Crespi, Vincent H; van Duin, Adri C T

    2017-02-02

    Two-dimensional layers of molybdenum disulfide, MoS 2 , have been recognized as promising materials for nanoelectronics due to their exceptional electronic and optical properties. Here we develop a new ReaxFF reactive potential that can accurately describe the thermodynamic and structural properties of MoS 2 sheets, guided by extensive density functional theory simulations. This potential is then applied to the formation energies of five different types of vacancies, various vacancy migration barriers, and the transition barrier between the semiconducting 2H and metallic 1T phases. The energetics of ripplocations, a recently observed defect in van der Waals layers, is examined, and the interplay between these defects and sulfur vacancies is studied. As strain engineering of MoS 2 sheets is an effective way to manipulate the sheets' electronic and optical properties, the new ReaxFF description can provide valuable insights into morphological changes that occur under various loading conditions and defect distributions, thus allowing one to tailor the electronic properties of these 2D crystals.

  3. Structure-activity studies of vasoactive intestinal peptide (VIP): cyclic disulfide analogs.

    Science.gov (United States)

    Bolin, D R; Cottrell, J; Garippa, R; O'Neill, N; Simko, B; O'Donnell, M

    1993-02-01

    Analogs of vasoactive intestinal peptide with cysteine residues incorporated at selected sites within the sequence were prepared by solid phase methods, oxidized to the corresponding cyclic disulfides and purified to homogeneity by preparative HPLC. The cyclic compounds were assayed as smooth muscle relaxants on isolated guinea pig trachea, as bronchodilators in vivo in guinea pigs, and for binding to VIP receptors in guinea pig lung membranes. Of the analogs prepared at the N-terminus, one compound, Ac-[D-Cys6,D-Cys11,Lys12,Nle17,Val26,Th r28]-VIP, was found to be a full agonist with slightly more than one tenth the potency of native VIP. Most other cyclic analogs in the N-terminal region were found to be inactive. A second analog, Ac-[Lys12,Cys17,Val26,Cys28]-VIP, was also found to be a full agonist with potency about one third that of native VIP. Furthermore, this compound was active as a bronchodilator in vivo in guinea pig, but with somewhat diminished potency as compared to native VIP. Strikingly, this cyclic compound was found to have significantly longer duration of action (> 40 min) when compared to an analogous acyclic compound (5 min). The conformational restrictions imposed by formation of the cyclic ring structures may have stabilized the molecule to degradation, thus enhancing the effective duration of action. Analysis of this series of cyclic analogs has also yielded information about the requirements for the receptor-active conformation of VIP.

  4. First-principles studies of chromium line-ordered alloys in a molybdenum disulfide monolayer

    Science.gov (United States)

    Andriambelaza, N. F.; Mapasha, R. E.; Chetty, N.

    2017-08-01

    Density functional theory calculations have been performed to study the thermodynamic stability, structural and electronic properties of various chromium (Cr) line-ordered alloy configurations in a molybdenum disulfide (MoS2) hexagonal monolayer for band gap engineering. Only the molybdenum (Mo) sites were substituted at each concentration in this study. For comparison purposes, different Cr line-ordered alloy and random alloy configurations were studied and the most thermodynamically stable ones at each concentration were identified. The configurations formed by the nearest neighbor pair of Cr atoms are energetically most favorable. The line-ordered alloys are constantly lower in formation energy than the random alloys at each concentration. An increase in Cr concentration reduces the lattice constant of the MoS2 system following the Vegard’s law. From density of states analysis, we found that the MoS2 band gap is tunable by both the Cr line-ordered alloys and random alloys with the same magnitudes. The reduction of the band gap is mainly due to the hybridization of the Cr 3d and Mo 4d orbitals at the vicinity of the band edges. The band gap engineering and magnitudes (1.65 eV to 0.86 eV) suggest that the Cr alloys in a MoS2 monolayer are good candidates for nanotechnology devices.

  5. Molybdenum disulfide for ultra-low detection of free radicals: electrochemical response and molecular modeling

    Science.gov (United States)

    Gupta, Ankur; Rawal, Takat B.; Neal, Craig J.; Das, Soumen; Rahman, Talat S.; Seal, Sudipta

    2017-06-01

    Two-dimensional (2D) molybdenum disulfide (MoS2) offers attractive properties due to its band gap modulation and has led to significant research-oriented applications (i.e. DNA and protein detection, cell imaging (fluorescent label) etc.). In biology, detection of free radicals (i.e. reactive oxygen species and reactive nitrogen (NO*) species are very important for early discovery and treatment of diseases. Herein, for the first time, we demonstrate the ultra-low (pico-molar) detection of pharmaceutically relevant free radicals using MoS2 for electrochemical sensing. We present pico- to nano- molar level sensitivity in smaller MoS2 with S-deficiency as revealed by x-ray photoelectron spectroscopy. Furthermore, the detection mechanism and size-dependent sensitivity have been investigated by density functional theory (DFT) showing the change in electronic density of states of Mo atoms at edges which lead to the preferred adsorption of H2O2 on Mo edges. The DFT analysis signifies the role of size and S-deficiency in the higher catalytic activity of smaller MoS2 particles and, thus, ultra-low detection.

  6. Self-healing polyurethane/attapulgite nanocomposites based on disulfide bonds and shape memory effect

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yurun; Chen, Dajun, E-mail: cdj@dhu.edu.cn

    2017-07-01

    Nanocomposites with remarkable enhanced mechanical properties have attracted great research efforts recently. In this work, a series of self-healing polyurethane/attapulgite nanocomposites were prepared by solution blending. Introducing self-healing ability and attapulgite (AT) reinforcement simultaneously led to prolonged material lifetime and enhanced mechanical properties. Scanning electron microscope (SEM) observation indicated that AT could achieve a uniform dispersion in polyurethane matrix when AT content was relatively low. The influences on mechanical properties were evaluated by tensile test. Results showed that incorporating an appropriate content of AT would lead to an enhanced tensile properties. The interactions between AT and polyurethane matrix were studied by effective cross-linking density calculation and Fourier transform infrared (FTIR) analysis. Results indicated that rich hydrogen bonds were formed between AT and polyurethane matrix. Displacement data was utilized to evaluate the influence on shape memory effect. With the incorporation of AT, deformation of the sample under external force was restrained. Meanwhile, closure of the scratches still can be accomplished during healing process. Results of healing test suggested that incorporating 1% of AT would also promote self-healing property. - Highlights: • Composites with both self-healing and enhanced mechanical property are prepared. • Healing mechanism relies on disulfide exchange reaction and shape memory effect. • Mechanical enhancement is caused by rich hydrogen bonds introduced by attapulgite.

  7. Metalorganic chemical vapor deposition of iron disulfide and its use for solar energy conversion

    Science.gov (United States)

    Ennaoui, Ahmed; Fiechter, Sebastian; Vogel, Ralf; Giersig, M.; Weller, Horst; Tributsch, Helmut

    1992-12-01

    Thin polycrystalline films of iron disulfide have been grown on different substrates by chemical vapour deposition. The films were characterized using optical absorption and TEM. RBS and EDAX analysis has been used to explore the chemical stoichiometry. XRD and FTIR allowed the identification of both FeS2 phases pyrite and marcasite. A novel method for sensitization of highly porous Ti02 elecrodes with ultra thin (10-20 nm) polycrystalline films of FeS2 (pyrite) is presented. Photoelectrochemical solar cell using the above electrode generated high photovoltage of up to 600mV compared with single crystalline electrode (200 mV). In this device the semiconductor with a small band gap and high absorption coefficient (FeS2 pyrite; EG = 0.9 eV; a = 6 x 105 cm-1) absorbs the light and injects electrons into the conduction band the wide band gap semiconductor (Ti02 anatase; EG = 3.2 eV). Regeneration of holes is taking place by electron transfer from redox system in the electrolyte.

  8. Few-layer molybdenum disulfide transistors and circuits for high-speed flexible electronics.

    Science.gov (United States)

    Cheng, Rui; Jiang, Shan; Chen, Yu; Liu, Yuan; Weiss, Nathan; Cheng, Hung-Chieh; Wu, Hao; Huang, Yu; Duan, Xiangfeng

    2014-10-08

    Two-dimensional layered materials, such as molybdenum disulfide, are emerging as an exciting material system for future electronics due to their unique electronic properties and atomically thin geometry. Here we report a systematic investigation of MoS2 transistors with optimized contact and device geometry, to achieve self-aligned devices with performance including an intrinsic gain over 30, an intrinsic cut-off frequency fT up to 42 GHz and a maximum oscillation frequency fMAX up to 50 GHz, exceeding the reported values for MoS2 transistors to date (fT~0.9 GHz, fMAX~1 GHz). Our results show that logic inverters or radio frequency amplifiers can be formed by integrating multiple MoS2 transistors on quartz or flexible substrates with voltage gain in the gigahertz regime. This study demonstrates the potential of two-dimensional layered semiconductors for high-speed flexible electronics.

  9. Disulfide mapping the voltage-sensing mechanism of a voltage-dependent potassium channel.

    Science.gov (United States)

    Nozaki, Tomohiro; Ozawa, Shin-Ichiro; Harada, Hitomi; Kimura, Tomomi; Osawa, Masanori; Shimada, Ichio

    2016-11-17

    Voltage-dependent potassium (Kv) channels allow for the selective permeability of potassium ions in a membrane potential dependent manner, playing crucial roles in neurotransmission and muscle contraction. Kv channel is a tetramer, in which each subunit possesses a voltage-sensing domain (VSD) and a pore domain (PD). Although several lines of evidence indicated that membrane depolarization is sensed as the movement of helix S4 of the VSD, the detailed voltage-sensing mechanism remained elusive, due to the difficulty of structural analyses at resting potential. In this study, we conducted a comprehensive disulfide locking analysis of the VSD using 36 double Cys mutants, in order to identify the proximal residue pairs of the VSD in the presence or absence of a membrane potential. An intramolecular SS-bond was formed between 6 Cys pairs under both polarized and depolarized environment, and one pair only under depolarized environment. The multiple conformations captured by the SS-bond can be divided by two states, up and down, where S4 lies on the extracellular and intracellular sides of the membrane, respectively, with axial rotation of 180°. The transition between these two states is caused by the S4 translocation of 12 Å, enabling allosteric regulation of the gating at the PD.

  10. Thermal stability and electrical conductivity in polyethers-molybdenum disulfide nanocomposites

    International Nuclear Information System (INIS)

    Mirabal, N.; Aguirre, P.; Santa Ana, M.A.; Benavente, E.; Gonzalez, Guillermo

    2003-01-01

    The intercalation of poly(ethylene oxide) (PEO), into molybdenum disulfide, like that of other electron pair donors, leads to mixed ionic-electronic conductors. At room temperature, intercalates show electrical and lithium-ion conductivities better than MoS 2 and bulk PEO composites, respectively. However, these products are known to be sensitive to temperature; indeed, in the range 80-100 deg. C an irreversible decrease of the electrical conductivity is observed. In order to investigate these features, the thermal behavior of a series of polyethers of different molecular weights (poly(ethylene glycol) (Mw 3400) and PEO with Mw in the range 10 4 -4x10 6 , pure and intercalated in MoS 2 , (Li x (MoS 2 )(polyether) y with x∼0.1 and y=1.1-1.5), was comparatively analyzed. Furthermore, the effect of thermal treatment of the sample on the electrical conductivity was studied for one of the intercalated products. Results indicate that irreversible changes, detected by both loss of weight and a significant conductivity lowering, are occurring in the range from about 100 deg. C to a temperature near to the decomposition point of the organic phase at about 350 deg. C

  11. Rational design of multifunctional devices based on molybdenum disulfide and graphene hybrid nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yi Rang; Lee, Young Bum; Kim, Seong Ku; Kim, Seong Jun [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Kim, Yooseok; Jeon, Cheolho [Nano-Surface Research Group, Korea Basic Science Institute, Daejeon, 302-333 (Korea, Republic of); Song, Wooseok, E-mail: wssong@krict.re.kr [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Myung, Sung; Lee, Sun Sook; An, Ki-Seok [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of); Lim, Jongsun, E-mail: jslim@krict.re.kr [Thin Film Materials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Post Office Box 107, Daejeon 305-600 (Korea, Republic of)

    2017-01-15

    Highlights: • We fabricated MoS{sub 2}-graphene hybrid thin films for multifunctional applications. • Large-area, uniform multilayer MoS{sub 2} was synthesized on TCVD-grown graphene. • The mobility and photocurrent of the hybrid devices were improved significantly. - Abstract: We rationally designed a new type of hybrid materials, molybdenum disulfide (MoS{sub 2}) synthesized by Mo pre-deposition followed by subsequent sulfurization process directly on thermal chemical vapor deposition (TCVD)-grown graphene, for applications in a multifunctional device. The synthesis of stoichiometric and uniform multilayer MoS{sub 2} and high-crystalline monolayer graphene was evaluated by X-ray photoelectron spectroscopy and Raman spectroscopy. To examine the electrical transport and photoelectrical properties of MoS{sub 2}-graphene hybrid films, field effect transistors (FETs) and visible-light photodetectors based on MoS{sub 2}-graphene were both fabricated. As a result, the extracted mobility for MoS{sub 2}-graphene hybrid FETs was two times higher than that of MoS{sub 2} FETs. In addition, the MoS{sub 2}-graphene photodetectors revealed a significant photocurrent with abrupt switching behavior under periodic illumination.

  12. A rigid disulfide-linked nitroxide side chain simplifies the quantitative analysis of PRE data

    Energy Technology Data Exchange (ETDEWEB)

    Fawzi, Nicolas L. [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Fleissner, Mark R. [University of California, Jules Stein Eye Institute and Department of Chemistry and Biochemistry (United States); Anthis, Nicholas J. [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Kalai, Tamas; Hideg, Kalman [University of Pecs, Institute of Organic and Medicinal Chemistry (Hungary); Hubbell, Wayne L., E-mail: hubbellw@jsei.ucla.edu [University of California, Jules Stein Eye Institute and Department of Chemistry and Biochemistry (United States); Clore, G. Marius, E-mail: mariusc@mail.nih.gov [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)

    2011-09-15

    The measurement of {sup 1}H transverse paramagnetic relaxation enhancement (PRE) has been used in biomolecular systems to determine long-range distance restraints and to visualize sparsely-populated transient states. The intrinsic flexibility of most nitroxide and metal-chelating paramagnetic spin-labels, however, complicates the quantitative interpretation of PREs due to delocalization of the paramagnetic center. Here, we present a novel, disulfide-linked nitroxide spin label, R1p, as an alternative to these flexible labels for PRE studies. When introduced at solvent-exposed {alpha}-helical positions in two model proteins, calmodulin (CaM) and T4 lysozyme (T4L), EPR measurements show that the R1p side chain exhibits dramatically reduced internal motion compared to the commonly used R1 spin label (generated by reacting cysteine with the spin labeling compound often referred to as MTSL). Further, only a single nitroxide position is necessary to account for the PREs arising from CaM S17R1p, while an ensemble comprising multiple conformations is necessary for those observed for CaM S17R1. Together, these observations suggest that the nitroxide adopts a single, fixed position when R1p is placed at solvent-exposed {alpha}-helical positions, greatly simplifying the interpretation of PRE data by removing the need to account for the intrinsic flexibility of the spin label.

  13. A rigid disulfide-linked nitroxide side chain simplifies the quantitative analysis of PRE data

    International Nuclear Information System (INIS)

    Fawzi, Nicolas L.; Fleissner, Mark R.; Anthis, Nicholas J.; Kálai, Tamás; Hideg, Kálmán; Hubbell, Wayne L.; Clore, G. Marius

    2011-01-01

    The measurement of 1 H transverse paramagnetic relaxation enhancement (PRE) has been used in biomolecular systems to determine long-range distance restraints and to visualize sparsely-populated transient states. The intrinsic flexibility of most nitroxide and metal-chelating paramagnetic spin-labels, however, complicates the quantitative interpretation of PREs due to delocalization of the paramagnetic center. Here, we present a novel, disulfide-linked nitroxide spin label, R1p, as an alternative to these flexible labels for PRE studies. When introduced at solvent-exposed α-helical positions in two model proteins, calmodulin (CaM) and T4 lysozyme (T4L), EPR measurements show that the R1p side chain exhibits dramatically reduced internal motion compared to the commonly used R1 spin label (generated by reacting cysteine with the spin labeling compound often referred to as MTSL). Further, only a single nitroxide position is necessary to account for the PREs arising from CaM S17R1p, while an ensemble comprising multiple conformations is necessary for those observed for CaM S17R1. Together, these observations suggest that the nitroxide adopts a single, fixed position when R1p is placed at solvent-exposed α-helical positions, greatly simplifying the interpretation of PRE data by removing the need to account for the intrinsic flexibility of the spin label.

  14. Influence of initial sulfur content in precursor solution for the growth of molybdenum disulfide

    Science.gov (United States)

    Tan, A. L.; Ng, S. S.; Abu Hassan, H.

    2018-04-01

    This work investigated the influence of initial sulfur content in the precursor solution for the growth of molybdenum disulfide (MoS2) films by thermal vapour sulfurization (TVS) with sol-gel spin coating as pre-deposition technique. The early introduction of sulfur shows the presence of grains are uniformly distributed and homogeneous on the surface of the film. MoS2 (002) planes are detected for both films with and without initial sulfur conditions, however, the presence of initial sulfur contents gives slightly higher intensity of diffraction peak. Two phonon modes for MoS2, namely the E2g 1 (in-plane) and the A1g (out-of plane), are well detected from which the frequency difference of Raman peaks between E2g 1 and A1g suggest the grown MoS2 consisted of multi-layers. There is a slight shift of E2g 1 which is caused by the carbon impurities but no shift for A1g. Besides, MoS2 film with the presence of initial sulfur content shows better crystal as indicated by its narrower Raman peaks linewidth. Two broad absorption peaks of MoS2 are detected at 614nm and 665nm. Hence, the early introduction of sulfur content in prepared precursor solution is one way of optimizing the growth of MoS2 films.

  15. Mapping Soluble Guanylyl Cyclase and Protein Disulfide Isomerase Regions of Interaction.

    Directory of Open Access Journals (Sweden)

    Erin J Heckler

    Full Text Available Soluble guanylyl cyclase (sGC is a heterodimeric nitric oxide (NO receptor that produces cyclic GMP. This signaling mechanism is a key component in the cardiovascular system. NO binds to heme in the β subunit and stimulates the catalytic conversion of GTP to cGMP several hundred fold. Several endogenous factors have been identified that modulate sGC function in vitro and in vivo. In previous work, we determined that protein disulfide isomerase (PDI interacts with sGC in a redox-dependent manner in vitro and that PDI inhibited NO-stimulated activity in cells. To our knowledge, this was the first report of a physical interaction between sGC and a thiol-redox protein. To characterize this interaction between sGC and PDI, we first identified peptide linkages between sGC and PDI, using a lysine cross-linking reagent and recently developed mass spectrometry analysis. Together with Flag-immunoprecipitation using sGC domain deletions, wild-type (WT and mutated PDI, regions of sGC involved in this interaction were identified. The observed data were further explored with computational modeling to gain insight into the interaction mechanism between sGC and oxidized PDI. Our results indicate that PDI interacts preferentially with the catalytic domain of sGC, thus providing a mechanism for PDI inhibition of sGC. A model in which PDI interacts with either the α or the β catalytic domain is proposed.

  16. Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer.

    Science.gov (United States)

    Xiong, Ting; Liu, Xiao-Wang; Huang, Xue-Long; Xu, Xiong-Feng; Xie, Wei-Quan; Zhang, Su-Jun; Tu, Jian

    2018-05-01

    Diallyl disulfide (DADS), a volatile component of garlic oil, has various biological properties, including antioxidant, antiangiogenic and anticancer effects. The present study aimed to explore novel targets of DADS that may slow or stop the progression of breast cancer. First, xenograft tumor models were created by subcutaneously injecting MCF-7 and MDA-MB-231 breast cancer cells into nude mice. Subsequently, western blot analysis was performed to investigate the expression of tristetraprolin (TTP), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in the xenograft tumors, and cell cultures. Tablet cloning, Transwell and wound healing assays revealed that DADS treatment significantly inhibited the proliferation, invasion and migration of breast cancer cells. In addition, DADS treatment led to significant downregulation of uPA and MMP-9 protein expression, but significantly upregulated TTP expression in vivo and in vitro . Knocking down TTP expression using small interfering RNA reversed the aforementioned effects of DADS, which suggests TTP is a key target of DADS in inhibiting the progression of breast cancer.

  17. A high pressure x-ray diffraction study of titanium disulfide

    International Nuclear Information System (INIS)

    Aksoy, Resul; Selvi, Emre; Knudson, Russell; Ma Yanzhang

    2009-01-01

    A high pressure angle dispersive synchrotron x-ray diffraction study of titanium disulfide (TiS 2 ) was carried out to pressures of 45.5 GPa in a diamond-anvil cell. We observed a phase transformation of TiS 2 beginning at about 20.7 GPa. The structure of the high pressure phase needs further identification. By fitting the pressure-volume data to the third-order Birch-Murnaghan equation of state, the bulk modulus, K 0T , was determined to be 45.9 ± 0.7 GPa with its pressure derivative, K' 0T , being 9.5 ± 0.3 at pressures lower than 17.8 GPa. It was found that the compression behavior of TiS 2 is anisotropic along the different axes. The compression ratio of the c-axis is about nine times larger than the a-axis when pressures are lower than 1 GPa. It suddenly decreases to three times larger at pressures of about 3 GPa. This ratio shows a linear decrease with a slope of negative 0.048 at pressures below phase transformation.

  18. Ferroelectric transistors with monolayer molybdenum disulfide and ultra-thin aluminum-doped hafnium oxide

    Science.gov (United States)

    Yap, Wui Chung; Jiang, Hao; Liu, Jialun; Xia, Qiangfei; Zhu, Wenjuan

    2017-07-01

    In this letter, we demonstrate ferroelectric memory devices with monolayer molybdenum disulfide (MoS2) as the channel material and aluminum (Al)-doped hafnium oxide (HfO2) as the ferroelectric gate dielectric. Metal-ferroelectric-metal capacitors with 16 nm thick Al-doped HfO2 are fabricated, and a remnant polarization of 3 μC/cm2 under a program/erase voltage of 5 V is observed. The capability of potential 10 years data retention was estimated using extrapolation of the experimental data. Ferroelectric transistors based on embedded ferroelectric HfO2 and MoS2 grown by chemical vapor deposition are fabricated. Clockwise hysteresis is observed at low program/erase voltages due to slow bulk traps located near the 2D/dielectric interface, while counterclockwise hysteresis is observed at high program/erase voltages due to ferroelectric polarization. In addition, the endurances of the devices are tested, and the effects associated with ferroelectric materials, such as the wake-up effect and polarization fatigue, are observed. Reliable writing/reading in MoS2/Al-doped HfO2 ferroelectric transistors over 2 × 104 cycles is achieved. This research can potentially lead to advances of two-dimensional (2D) materials in low-power logic and memory applications.

  19. Morphological Evolution of Vertically Standing Molybdenum Disulfide Nanosheets by Chemical Vapor Deposition.

    Science.gov (United States)

    Zhang, Song; Liu, Jiajia; Ruiz, Karla Hernandez; Tu, Rong; Yang, Meijun; Li, Qizhong; Shi, Ji; Li, Haiwen; Zhang, Lianmeng; Goto, Takashi

    2018-04-20

    In this study, we demonstrated the chemical vapor deposition (CVD) of vertically standing molybdenum disulfide (MoS₂) nanosheets, with an unconventional combination of molybdenum hexacarbonyl (Mo(CO)₆) and 1,2-ethanedithiol (C₂H₆S₂) as the novel kind of Mo and S precursors respectively. The effect of the distance between the precursor’s outlet and substrates (denoted as d ) on the growth characteristics of MoS₂, including surface morphology and nanosheet structure, was investigated. Meanwhile, the relationship between the structure characteristics of MoS₂ nanosheets and their catalytic performance for hydrogen evolution reaction (HER) was elucidated. The formation of vertically standing nanosheets was analyzed and verified by means of an extrusion growth model. The crystallinity, average length, and average depth between peak and valley ( R z) of MoS₂ nanosheets differed depending on the spatial location of the substrate. Good crystalized MoS₂ nanosheets grown at d = 5.5 cm with the largest average length of 440 nm, and the highest R z of 162 nm contributed to a better HER performance, with a respective Tafel slope and exchange current density of 138.9 mV/decade, and 22.6 μA/cm² for raw data (127.8 mV/decade and 19.3 μA/cm² for iR-corrected data).

  20. Two-dimensional tantalum disulfide: controlling structure and properties via synthesis

    Science.gov (United States)

    Zhao, Rui; Grisafe, Benjamin; Krishna Ghosh, Ram; Holoviak, Stephen; Wang, Baoming; Wang, Ke; Briggs, Natalie; Haque, Aman; Datta, Suman; Robinson, Joshua

    2018-04-01

    Tantalum disulfide (TaS2) is a transition metal dichalcogenide (TMD) that exhibits phase transition induced electronic property modulation at low temperature. However, the appropriate phase must be grown to enable the semiconductor/metal transition that is of interest for next generation electronic applications. In this work, we demonstrate direct and controllable synthesis of ultra-thin 1T-TaS2 and 2H-TaS2 on a variety of substrates (sapphire, SiO2/Si, and graphene) via powder vapor deposition. The synthesis process leads to single crystal domains ranging from 20 to 200 nm thick and 1-10 µm on a side. The TaS2 phase (1T or 2H) is controlled by synthesis temperature, which subsequently is shown to control the electronic properties. Furthermore, this work constitutes the first demonstration of a metal-insulator phase transition in directly synthesized 1T-TaS2 films and domains by electronic means.

  1. Synthesis of novel disulfide and sulfone hybrid scaffolds as potent β-glucuronidase inhibitor.

    Science.gov (United States)

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Wadood, Abdul; Rahim, Fazal; Al Muqarrabin, Laode Muhammad Ramadhan; Zaki, Hamizah Mohd; Ahmat, Norizan; Nasir, Abdul; Khan, Fahad

    2016-10-01

    Novel series of disulfide and sulfone hybrid analogs (1-20) were synthesized and characterized through EI-MS and (1)H NMR and evaluated for β-glucuronidase inhibitory potential. All synthesized analogs except 13 and 15 showed excellent β-glucuronidase inhibitory potential with IC50 value ranging in between 2.20-88.16μM as compared to standard d-saccharic acid 1,4 lactone (48.4±1.25μM). Analogs 19, 16, 4, 1, 17, 6, 10, 3, 18, 2, 11, 14 and 5 showed many fold potent activity against β-glucuronidase inhibitor. Structure activity relationship showed that substitution of electron withdrawing groups at ortho as well as para position on phenyl ring increase potency. Electron withdrawing groups at meta position on phenyl ring showed slightly low potency as compared to ortho and para position. The binding interactions were confirmed through molecular docking studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Cytotoxicity and Efflux Pump Inhibition Induced by Molybdenum Disulfide and Boron Nitride Nanomaterials with Sheetlike Structure.

    Science.gov (United States)

    Liu, Su; Shen, Zhuoyan; Wu, Bing; Yu, Yue; Hou, Hui; Zhang, Xu-Xiang; Ren, Hong-Qiang

    2017-09-19

    Sheetlike molybdenum disulfide (MoS 2 ) and boron nitride (BN) nanomaterials have attracted attention in the past few years due to their unique material properties. However, information on adverse effects and their underlying mechanisms for sheetlike MoS 2 and BN nanomaterials is rare. In this study, cytotoxicities of sheetlike MoS 2 and BN nanomaterials on human hepatoma HepG2 cells were systematically investigated at different toxic end points. Results showed that MoS 2 and BN nanomaterials decreased cell viability at 30 μg/mL and induced adverse effects on intracellular ROS generation (≥2 μg/mL), mitochondrial depolarization (≥4 μg/mL), and membrane integrity (≥8 μg/mL for MoS 2 and ≥2 μg/mL for BN). Furthermore, this study first found that low exposure concentrations (0.2-2 μg/mL) of MoS 2 and BN nanomaterials could increase plasma membrane fluidity and inhibit transmembrane ATP binding cassette (ABC) efflux transporter activity, which make both nanomaterials act as a chemosensitizer (increasing arsenic toxicity). Damage to plasma membrane and release of soluble Mo or B species might be two reasons that both nanomaterials inhibit efflux pump activities. This study provides a systematic understanding of the cytotoxicity of sheetlike MoS 2 and BN nanomaterials at different exposure levels, which is important for their safe use.

  3. Contact research strategy for emerging molybdenum disulfide and other two-dimensional field-effect transistors

    Directory of Open Access Journals (Sweden)

    Yuchen Du

    2014-09-01

    Full Text Available Layered two-dimensional (2D semiconducting transition metal dichalcogenides (TMDs have been widely isolated, synthesized, and characterized recently. Numerous 2D materials are identified as the potential candidates as channel materials for future thin film technology due to their high mobility and the exhibiting bandgaps. While many TMD filed-effect transistors (FETs have been widely demonstrated along with a significant progress to clearly understand the device physics, large contact resistance at metal/semiconductor interface still remain a challenge. From 2D device research point of view, how to minimize the Schottky barrier effects on contacts thus reduce the contact resistance of metals on 2D materials is very critical for the further development of the field. Here, we present a review of contact research on molybdenum disulfide and other TMD FETs from the fundamental understanding of metal-semiconductor interfaces on 2D materials. A clear contact research strategy on 2D semiconducting materials is developed for future high-performance 2D FETs with aggressively scaled dimensions.

  4. In-plane and cross-plane thermal conductivities of molybdenum disulfide

    International Nuclear Information System (INIS)

    Ding, Zhiwei; Pei, Qing-Xiang; Zhang, Yong-Wei; Jiang, Jin-Wu

    2015-01-01

    We investigate the in-plane and cross-plane thermal conductivities of molybdenum disulfide (MoS 2 ) using non-equilibrium molecular dynamics simulations. We find that the in-plane thermal conductivity of monolayer MoS 2 is about 19.76 W mK −1 . Interestingly, the in-plane thermal conductivity of multilayer MoS 2 is insensitive to the number of layers, which is in strong contrast to the in-plane thermal conductivity of graphene where the interlayer interaction strongly affects the in-plane thermal conductivity. This layer number insensitivity is attributable to the finite energy gap in the phonon spectrum of MoS 2 , which makes the phonon–phonon scattering channel almost unchanged with increasing layer number. For the cross-plane thermal transport, we find that the cross-plane thermal conductivity of multilayer MoS 2 can be effectively tuned by applying cross-plane strain. More specifically, a 10% cross-plane compressive strain can enhance the thermal conductivity by a factor of 10, while a 5% cross-plane tensile strain can reduce the thermal conductivity by 90%. Our findings are important for thermal management in MoS 2 based nanodevices and for thermoelectric applications of MoS 2 . (paper)

  5. High-damage-resistant tungsten disulfide saturable absorber mirror for passively Q-switched fiber laser.

    Science.gov (United States)

    Chen, Hao; Chen, YuShan; Yin, Jinde; Zhang, Xuejun; Guo, Tuan; Yan, Peiguang

    2016-07-25

    In this paper, we demonstrate a high-damage-resistant tungsten disulfide saturable absorber mirror (WS2-SAM) fabricated by magnetron sputtering technique. The WS2-SAM has an all-fiber-integrated configuration and high-damage-resistant merit because the WS2 layer is protected by gold film so as to avoid being oxidized and destroyed at high pump power. Employing the WS2-SAM in an Erbium-doped fiber laser (EDFL) with linear cavity, the stable Q-switching operation is achieved at central wavelength of 1560 nm, with the repetition rates ranging from 29.5 kHz to 367.8 kHz and the pulse duration ranging from 1.269 μs to 154.9 ns. For the condition of the maximum pump power of 600 mW, the WS2-SAM still works stably with an output power of 25.2 mW, pulse energy of 68.5 nJ, and signal-noise-ratio of 42 dB. The proposed WS2-SAM configuration provides a promising solution for advanced pulsed fiber lasers with the characteristics of high damage resistance, high output energy, and wide tunable frequency.

  6. Fiber-integrated tungsten disulfide saturable absorber (mirror) for pulsed fiber lasers

    Science.gov (United States)

    Chen, Hao; Li, Irene Ling; Ruan, Shuangchen; Guo, Tuan; Yan, Peiguang

    2016-08-01

    We propose two schemes for achieving tungsten disulfide (WS2)-based saturable absorber (SA) and saturable absorber mirror (SAM). By utilizing the pulsed laser deposition method, we grow the WS2 film on microfiber to form an evanescent field interaction SA device. Incorporating this SA device into a common ring-cavity erbium-doped fiber (EDF) laser, stably passive mode-locking can be achieved with pulse duration of 395 fs and signal-to-noise ratio of 64 dB. We also produce a fiber tip integrated WS2-SAM by utilizing the magnetron sputtering technique (MST). This new type of SAM combines the WS2 layer as SA and gold mirror as high reflective mirror. By employing the WS2-SAM, we construct the linear-cavity EDF lasers, and achieve passive mode-locking operation with pulse duration of ˜1 ns and SNR of ˜61 dB. We further achieve stably passive Q-switching operation with pulse duration of ˜160 ns and pulse energy of 54.4 nJ. These fiber-integrated SAs and SAMs have merits of compactness and reliability, paving the way for the development of new photonic devices such as SAs for pulsed laser technology.

  7. Oscillatory motion in layered materials: graphene, boron nitride, and molybdenum disulfide

    International Nuclear Information System (INIS)

    Ye, Zhijiang; Martini, Ashlie; Otero-de-la-Roza, Alberto; Johnson, Erin R

    2015-01-01

    Offset-driven self-retraction and oscillatory motion of bilayer graphene has been observed experimentally and is potentially relevant for nanoscale technological applications. In a previous article, we showed that friction between laterally offset graphene layers is controlled by roughness and proposed a simple reduced-order model based on density-functional theory (DFT) and molecular dynamics (MD) data, with which predictions on the experimental size-scale could be made. In this article, we extend our study to other layered materials, with emphasis on boron nitride (BN) and molybdenum disulfide (MoS 2 ). Using MD and DFT simulations of these systems and a generalized version of the reduced-order model, we predict that BN will exhibit behavior similar to graphene (heavily-damped oscillation with a decay rate that increases with roughness) and that MoS 2 shows no oscillatory behavior even in the absence of roughness. This is attributed to the higher energy barrier for sliding in MoS 2 as well as the surface structure. Our generalized reduced-order model provides a guide to predicting and tuning experimental oscillation behavior using a few parameters that can be derived from simulation data. (paper)

  8. Photoelectrochemical Cell of Hybrid Regioregular POLY(3-HEXYLTHIOPHENE-2,5-DIYL) and Molybdenum Disulfide Film

    Science.gov (United States)

    Abdelmola, Fatmaelzahraa M.; Ram, Manoj K.; Takshi, Arash; Stafanakos, Elias; Kumar, Ashok; Goswami, D. Yogi

    The photoelectrochemical cell attracts attention worldwide due to conversion of optical energy into electricity, production of hydrogen through water splitting and use in photodetector and photo-sensor applications. We have been working on the photochemical cell based on regioregular polyhexylthiophenes hybrid-structured films for photoelectrochemical and photovoltaic applications. This paper discusses the hybrid film studies on regioregular poly(3-hexylthiophene-2,5-diyl) (P3HT) with 2D molybdenum disulfide (MoS2) for photoelectrochemical cell. The hybrid P3HT/MoS2 films deposited over indium tin oxide (ITO)-coated glass plate or n-type silicon substrates were characterized using FTIR, UV/vis, electrochemical and scanning electron microscopy (SEM) techniques. The optical measurements showed a higher absorption magnitude with low reflection properties of P3HT/MoS2 hybrid films revealing a superior photocurrent compared to both P3HT and MoS2 films. The P3HT/MoS2 hybrid-based photoelectrochemical cell yielded a short-circuit current (Isc) of 183.16μAṡcm-2, open-circuit voltage (Voc) of 0.92V, fill factor (FF) of 25% and power conversion efficiency (η) of 0.18% under the light intensity of 242Wṡm-2. The estimated power conversion efficiency and fill factor are comparable to organic-based photovoltaic devices.

  9. An olfactory subsystem that detects carbon disulfide and mediates food-related social learning.

    Science.gov (United States)

    Munger, Steven D; Leinders-Zufall, Trese; McDougall, Lisa M; Cockerham, Renee E; Schmid, Andreas; Wandernoth, Petra; Wennemuth, Gunther; Biel, Martin; Zufall, Frank; Kelliher, Kevin R

    2010-08-24

    Olfactory signals influence social interactions in a variety of species. In mammals, pheromones and other social cues can promote mating or aggression behaviors; can communicate information about social hierarchies, genetic identity and health status; and can contribute to associative learning. However, the molecular, cellular, and neural mechanisms underlying many olfactory-mediated social interactions remain poorly understood. Here, we report that a specialized olfactory subsystem that includes olfactory sensory neurons (OSNs) expressing the receptor guanylyl cyclase GC-D, the cyclic nucleotide-gated channel subunit CNGA3, and the carbonic anhydrase isoform CAII (GC-D(+) OSNs) is required for the acquisition of socially transmitted food preferences (STFPs) in mice. Using electrophysiological recordings from gene-targeted mice, we show that GC-D(+) OSNs are highly sensitive to the volatile semiochemical carbon disulfide (CS(2)), a component of rodent breath and a known social signal mediating the acquisition of STFPs. Olfactory responses to CS(2) are drastically reduced in mice lacking GC-D, CNGA3, or CAII. Disruption of this sensory transduction cascade also results in a failure to acquire STFPs from either live or surrogate demonstrator mice or to exhibit hippocampal correlates of STFP retrieval. Our findings indicate that GC-D(+) OSNs detect chemosignals that facilitate food-related social interactions. Copyright 2010 Elsevier Ltd. All rights reserved.

  10. Evaluation of ion-sputtered molybdenum disulfide bearings for spacecraft gimbals

    Science.gov (United States)

    Loewenthal, S. H.; Chou, R. G.; Hopple, G. B.; Wenger, W. L.

    1994-07-01

    High-density, sputtered molybdenum disulfide films (MoS2) were investigated as lubricants for the next generation of spacecraft gimbal bearings where low torque signatures and long life are required. Low friction in a vacuum environment, virturally no out-gassing, insensitivity to low temperature, and radiation resistance of these lubricant films are valued in such applications. One hundred and twenty five thousand hours of acumulated bearing test time were obtained on 24 pairs of flight-quality bearings ion-sputtered with three types of advanced MoS2 films. Life tests were conducted in a vacuum over a simulated duty cycle for a space payload gimbal. Optimum retainer and ball material composition were investigated. Comparisions were made with test bearings lubricated with liquid space lubricants. Self-lubricating PTFE retainers were required for long life, i.e., greater than 40 million gimbal cycles. Bearings with polyimide retainers, silicon nitride ceramic balls, or steel balls sputtered with MoS2 film suffered early torque failure, irrespective of the type of race-sputtered MoS2 film. Failure generally resulted from excess film or retainer debris deposited in the ball track which tended to jam the bearing. Both grease lubricated and the better MoS2 film lubricated bearings produced long lives, although the torque with liquid lubricants was lower and less irregular.

  11. Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

    Science.gov (United States)

    Gong, Zhen-Hua; Tian, Guo-Li; Huang, Qi-Wei; Wang, Yan-Min; Xu, Hong-Ping

    2017-07-20

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 μmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 μmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

  12. Chemical vapor deposition based tungsten disulfide (WS2) thin film transistor

    KAUST Repository

    Hussain, Aftab M.

    2013-04-01

    Tungsten disulfide (WS2) is a layered transition metal dichalcogenide with a reported band gap of 1.8 eV in bulk and 1.32-1.4 eV in its thin film form. 2D atomic layers of metal dichalcogenides have shown changes in conductivity with applied electric field. This makes them an interesting option for channel material in field effect transistors (FETs). Therefore, we show a highly manufacturable chemical vapor deposition (CVD) based simple process to grow WS2 directly on silicon oxide in a furnace and then its transistor action with back gated device with room temperature field effect mobility of 0.1003 cm2/V-s using the Schottky barrier contact model. We also show the semiconducting behavior of this WS2 thin film which is more promising than thermally unstable organic materials for thin film transistor application. Our direct growth method on silicon oxide also holds interesting opportunities for macro-electronics applications. © 2013 IEEE.

  13. Rationalising predictors of child sexual exploitation and sex-trading.

    Science.gov (United States)

    Klatt, Thimna; Cavner, Della; Egan, Vincent

    2014-02-01

    Although there is evidence for specific risk factors leading to child sexual exploitation and prostitution, these influences overlap and have rarely been examined concurrently. The present study examined case files for 175 young persons who attended a voluntary organization in Leicester, United Kingdom, which supports people who are sexually exploited or at risk of sexual exploitation. Based on the case files, the presence or absence of known risk factors for becoming a sex worker was coded. Data were analyzed using t-test, logistic regression, and smallest space analysis. Users of the voluntary organization's services who had been sexually exploited exhibited a significantly greater number of risk factors than service users who had not been victims of sexual exploitation. The logistic regression produced a significant model fit. However, of the 14 potential predictors--many of which were associated with each other--only four variables significantly predicted actual sexual exploitation: running away, poverty, drug and/or alcohol use, and having friends or family members in prostitution. Surprisingly, running away was found to significantly decrease the odds of becoming involved in sexual exploitation. Smallest space analysis of the data revealed 5 clusters of risk factors. Two of the clusters, which reflected a desperation and need construct and immature or out-of-control lifestyles, were significantly associated with sexual exploitation. Our research suggests that some risk factors (e.g. physical and emotional abuse, early delinquency, and homelessness) for becoming involved in sexual exploitation are common but are part of the problematic milieu of the individuals affected and not directly associated with sex trading itself. Our results also indicate that it is important to engage with the families and associates of young persons at risk of becoming (or remaining) a sex worker if one wants to reduce the numbers of persons who engage in this activity. Copyright

  14. An efficient algorithmic approach for mass spectrometry-based disulfide connectivity determination using multi-ion analysis

    Directory of Open Access Journals (Sweden)

    Yen Ten-Yang

    2011-02-01

    Full Text Available Abstract Background Determining the disulfide (S-S bond pattern in a protein is often crucial for understanding its structure and function. In recent research, mass spectrometry (MS based analysis has been applied to this problem following protein digestion under both partial reduction and non-reduction conditions. However, this paradigm still awaits solutions to certain algorithmic problems fundamental amongst which is the efficient matching of an exponentially growing set of putative S-S bonded structural alternatives to the large amounts of experimental spectrometric data. Current methods circumvent this challenge primarily through simplifications, such as by assuming only the occurrence of certain ion-types (b-ions and y-ions that predominate in the more popular dissociation methods, such as collision-induced dissociation (CID. Unfortunately, this can adversely impact the quality of results. Method We present an algorithmic approach to this problem that can, with high computational efficiency, analyze multiple ions types (a, b, bo, b*, c, x, y, yo, y*, and z and deal with complex bonding topologies, such as inter/intra bonding involving more than two peptides. The proposed approach combines an approximation algorithm-based search formulation with data driven parameter estimation. This formulation considers only those regions of the search space where the correct solution resides with a high likelihood. Putative disulfide bonds thus obtained are finally combined in a globally consistent pattern to yield the overall disulfide bonding topology of the molecule. Additionally, each bond is associated with a confidence score, which aids in interpretation and assimilation of the results. Results The method was tested on nine different eukaryotic Glycosyltransferases possessing disulfide bonding topologies of varying complexity. Its performance was found to be characterized by high efficiency (in terms of time and the fraction of search space

  15. Meaning, function and methods of the recultivation in mining exploitation

    OpenAIRE

    Dambov, Risto; Ljatifi, Ejup

    2015-01-01

    With the exploitation of mineral resources is performed degradation and deformation of the relief and the general part of surface of the Earth's crust. Depending on the type of open pit mine, this degradation can be expressed to a lesser or greater extent, and sometimes in several square kilometers. The exploitation of mineral resources is with unbreakable link with the environment. Very often it is said that mining is „enemy No. 1“ for environment. With exploitation comes to degradation of h...

  16. The possibilities of exploitation of Serbian thermomineral waters

    International Nuclear Information System (INIS)

    Jovanovic, L.

    2002-01-01

    Global ecological problem of petrol resources deficit caused an intensive search of alternative energy sources. Deficit of conventional energy fluids in Yugoslavia requires serious efforts to create a program of alternative energy sources exploitation. Geothermal energy represents an important energetic source for the countries with poor energy resources. Geothermal energy can become the basis for economic development. At present these geothermal resources are not being exploited in Yugoslavia. The possibilities of effective exploitation of thermal and thermomineral water resources in Yugoslavia are presented in this paper

  17. Imouraren mining exploitation : Complementary studies Synthetic report Volum B - Mines

    International Nuclear Information System (INIS)

    1980-01-01

    The object of the current study is to determine the main technical characteristics of the reference project of a mine that can supply the necessary ore quantity at a production of 3000 tonnes uranium per year, along 10 years. The project is one of the possible solutions for exploiting the mine. The current study permits to establish : investment and functioning cost estimation, overall project of the mining exploitation program, necessary strength estimation, average ore grades evaluation and variations of these grades, utilities needs, production vizing program, main exploitation methods and necessary materials. Reference project study of the mine serves as base to the economics studies and studies optimization [fr

  18. Virtual Geophysics Laboratory: Exploiting the Cloud and Empowering Geophysicsts

    Science.gov (United States)

    Fraser, Ryan; Vote, Josh; Goh, Richard; Cox, Simon

    2013-04-01

    Over the last five decades geoscientists from Australian state and federal agencies have collected and assembled around 3 Petabytes of geoscience data sets under public funding. As a consequence of technological progress, data is now being acquired at exponential rates and in higher resolution than ever before. Effective use of these big data sets challenges the storage and computational infrastructure of most organizations. The Virtual Geophysics Laboratory (VGL) is a scientific workflow portal addresses some of the resulting issues by providing Australian geophysicists with access to a Web 2.0 or Rich Internet Application (RIA) based integrated environment that exploits eResearch tools and Cloud computing technology, and promotes collaboration between the user community. VGL simplifies and automates large portions of what were previously manually intensive scientific workflow processes, allowing scientists to focus on the natural science problems, rather than computer science and IT. A number of geophysical processing codes are incorporated to support multiple workflows. For example a gravity inversion can be performed by combining the Escript/Finley codes (from the University of Queensland) with the gravity data registered in VGL. Likewise, tectonic processes can also be modeled by combining the Underworld code (from Monash University) with one of the various 3D models available to VGL. Cloud services provide scalable and cost effective compute resources. VGL is built on top of mature standards-compliant information services, many deployed using the Spatial Information Services Stack (SISS), which provides direct access to geophysical data. A large number of data sets from Geoscience Australia assist users in data discovery. GeoNetwork provides a metadata catalog to store workflow results for future use, discovery and provenance tracking. VGL has been developed in collaboration with the research community using incremental software development practices and open

  19. Conflicts Related to Natural Resources Exploitation: A Case Study of ...

    African Journals Online (AJOL)

    Conflicts Related to Natural Resources Exploitation: A Case Study of Oil Crisis in Nigeria's Niger Delta Region and its Socio-Political and Economic Implications. ... on the environment leading to pollution of land, rivers, creeks and waterways.

  20. Exploitation of unconventional protein sources in the feed of weaner ...

    African Journals Online (AJOL)

    Exploitation of unconventional protein sources in the feed of weaner rabbits ... as protein sources for feeding ruminants but rarely considered as feed for micro ... 26.88 g/100g DM in Centrosema pubescens and Moringa oleifera, respectively.

  1. Exploiting Formation Flying for Fuel Saving Supersonic Oblique Wing Aircraft

    Science.gov (United States)

    2007-07-01

    used and developed during recent wing / winglet / morphing design programmes (Refs.13-14). By exploiting this method, we have assessed the aerodynamics ...parameters, Propulsion Issues, Size Issues, Aero-elastic effects 15. SUBJECT TERMS EOARD, Control System, Aerodynamics 16...

  2. Human trafficking and exploitation: A global health concern.

    Science.gov (United States)

    Zimmerman, Cathy; Kiss, Ligia

    2017-11-01

    In this collection review, Cathy Zimmerman and colleague introduce the PLOS Medicine Collection on Human Trafficking, Exploitation and Health, laying out the magnitude of the global trafficking problem and offering a public health policy framework to guide responses to trafficking.

  3. Uncertainty avoidance and the exploration-exploitation trade-off

    NARCIS (Netherlands)

    Broekhuizen, Thijs; Giarratana, Marco S.; Torres, Anna

    2017-01-01

    Purpose - This study aims to investigate how a firm's uncertainty avoidance - as indicated by the headquarters' national culture - impacts firm performance by affecting exploratory (product innovation) and exploitative (brand trademark protection) activities. It aims to show that firms characterized

  4. Enhanced surrogate models for statistical design exploiting space mapping technology

    DEFF Research Database (Denmark)

    Koziel, Slawek; Bandler, John W.; Mohamed, Achmed S.

    2005-01-01

    We present advances in microwave and RF device modeling exploiting Space Mapping (SM) technology. We propose new SM modeling formulations utilizing input mappings, output mappings, frequency scaling and quadratic approximations. Our aim is to enhance circuit models for statistical analysis...

  5. Trajectories and cycles of sexual exploitation and trafficking for sexual exploitation of women in the Peruvian Amazon

    OpenAIRE

    Mujica, Jaris

    2015-01-01

    The commercial sexual exploitation is a constant activity in the Peruvian Amazon. Around the river port of Pucallpa in ucayali region, the practice appears systematically: teenage attend taverns around the port, and those dedicated to the work of cooking camps logging, are victims of constant exploitation and many also of trafficking. this article aims to reconstruct the path of life and reproductive cycle of the forms of exploitation in a sample of 20 women, and focuses on: (i) evidence of s...

  6. Escaping from the exploitation trap by shaping the digital future

    OpenAIRE

    Füzes, Péter; Gódor, Zoltán; Szabó, Zsolt Roland

    2017-01-01

    Even Fortune 500 firms can disappear quickly, because many of them falls into an exploitation trap. Examples show that certain organizations – that manifest ambidextrous features – can avoid the exploitation trap. But, how can they do it? Authors tracked the digital transformation of a Fortune 500 company in order to understand the strategic and organizational challenges and solutions to become resilient and prosperous. A cutting edge example is shown in the paper about how an industry leader...

  7. The concept of exploitation in international human trafficking law

    OpenAIRE

    von der Pütten, Tuija Kaarina

    2017-01-01

    Human trafficking is commonly known as a criminal practice that takes place in the framework of sex trade: women and children are trafficked within a state, or from one state to another, for the purpose of sexual exploitation. Similarly, the early 20th century international conventions aimed to tackle ‘white slave traffic’, trafficking of women and children for sexual exploitation. However, it is misleading to see trafficking only within this context. People are trafficked so that they can be...

  8. Valley- and spin-switch effects in molybdenum disulfide superconducting spin valve

    Science.gov (United States)

    Majidi, Leyla; Asgari, Reza

    2014-10-01

    We propose a hole-doped molybdenum disulfide (MoS2) superconducting spin valve (F/S/F) hybrid structure in which the Andreev reflection process is suppressed for all incoming waves with a determined range of the chemical potential in ferromagnetic (F) region and the cross-conductance in the right F region depends crucially on the configuration of magnetizations in the two F regions. Using the scattering formalism, we find that the transport is mediated purely by elastic electron cotunneling (CT) process in a parallel configuration and changes to the pure crossed Andreev reflection (CAR) process in the low-energy regime, without fixing of a unique parameter, by reversing the direction of magnetization in the right F region. This suggests both valley- and spin-switch effects between the perfect elastic CT and perfect CAR processes and makes the nonlocal charge current to be fully valley- and spin-polarized inside the right F region where the type of the polarizations can be changed by reversing the magnetization direction in the right F region. We further demonstrate that the presence of the strong spin-orbit interaction λ and an additional topological term (β ) in the Hamiltonian of MoS2 result in an enhancement of the charge conductance of the CT and CAR processes and make them to be present for long lengths of the superconducting region. Besides, we find that the thermal conductance of the structure with a small length of the highly doped superconducting region exhibits linear dependence on the temperature at low temperatures, whereas it enhances exponentially at higher temperatures. In particular, we demonstrate that the thermal conductance versus the strength of the exchange field (h ) in F region displays a maximum value at h <λ , which moves towards larger exchange fields by increasing the temperature.

  9. Tribological properties of adaptive phosphate composite coatings with addition of silver and molybdenum disulfide

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Cancan [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China); University of Chinese Academy of Sciences, Beijing (China); Chen, Lei, E-mail: chenlei@lzb.ac.cn [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China); Zhou, Jiansong, E-mail: jszhou@licp.cas.cn [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China); Zhou, Huidi; Chen, Jianmin [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China)

    2014-05-01

    Highlights: • A new kind of adaptive coatings was fabricated using relatively simple spraying techniques. • The tribological properties of Ag/MoS{sub 2} phosphate composite coatings were investigated at the temperature from 20 °C to 700 °C. • The composition and wear mechanisms of Ag/MoS{sub 2} phosphate composite coatings were also discussed. • The Ag/MoS{sub 2} phosphate composite coatings have self-repairing capability in the rubbing process at 700 °C. - Abstract: Adaptive phosphate composite coatings with addition of solid lubricants of molybdenum disulfide (MoS{sub 2}) and silver (Ag) using aluminum chromium phosphate as the binder were fabricated on high-temperature steel. The tribological properties of phosphate composite coatings were evaluated from room temperature (RT) to 700 °C. The phase composition and microstructure were investigated according to the characterization by power X-ray diffraction (XRD), Raman spectroscopy and scanning electron microscopy (SEM). The results show that the composite coating with the Ag/MoS{sub 2} mass ratio of 2:1 exhibits the stable and low friction coefficients from RT to 700 °C and relative low wear rates at all testing temperatures. The tribo-chemical reaction between Ag and MoS{sub 2} occurred in the rubbing process to form silver molybdates compounds lubricating film. The temperature-adaptive tribological properties were attributed to the formation of lubricating films composed of lubricants silver, MoS{sub 2} and silver molybdates phases on the worn surfaces of the composites coatings in a wide-temperature range.

  10. Molybdenum disulfide nanoflower-chitosan-Au nanoparticles composites based electrochemical sensing platform for bisphenol A determination

    International Nuclear Information System (INIS)

    Huang, Ke-Jing; Liu, Yu-Jie; Liu, Yan-Ming; Wang, Ling-Ling

    2014-01-01

    Highlights: • This work constructs a novel electrochemical biosensor for bisphenol A detection. • Flower-like MoS 2 are prepared by a simple hydrothermal procedure. • AuNPs are assembled on MoS 2 nanoflowers modified electrode for signal amplification. • The developed sensor exhibits low detection limit and wide linear range. - Abstract: Two-dimensional transition metal dichalcogenide are attracting increasing attention in electrochemical sensing due to their unique electronic properties. In this work, flower-like molybdenum disulfide (MoS 2 ) was prepared by a simple hydrothermal method. The scanning electron microscopy and transmission electron microscopy images showed the MoS 2 nanoflower had sizes with diameter of about 200 nm and was constructed with many irregular sheets as a petal-like structure with thickness of several nanometers. A novel electrochemical sensor was constructed for the determination of bisphenol A (BPA) based on MoS 2 and chitosan-gold nanoparticles composites modified electrode. The sensor showed an efficient electrocatalytic role for the oxidation of BPA, and the oxidation overpotentials of BPA decreased significantly and the peak current increased greatly compared with bare GCE and other modified electrode. A good linear relationship between the oxidation peak current and BPA concentration was obtained in the range from 0.05 to 100 μM with a detection limit of 5.0 × 10 −9 M (S/N = 3). The developed sensor exhibited high sensitivity and long-term stability, and it was successfully applied for the determination of BPA in different samples. This work indicated MoS 2 nanoflowers were promising in electrochemical sensing and catalytic applications

  11. Syntheses, spectroscopic characterization, crystal structure and natural rubber vulcanization activity of new disulfides derived from sulfonyldithiocarbimates

    Science.gov (United States)

    Alves, Leandro de Carvalho; Rubinger, Mayura Marques Magalhães; Tavares, Eder do Couto; Janczak, Jan; Pacheco, Elen Beatriz Acordi Vasques; Visconte, Leila Lea Yuan; Oliveira, Marcelo Ribeiro Leite

    2013-09-01

    The compounds (Bu4N)2[(4-RC6H4SO2NCS2)2] [Bu4N = tetrabutylammonium cation; R = H (1), F (2), Cl (3) and Br (4)] and (Ph4P)2[(4-RC6H4SO2NCS2)2]ṡH2O [Ph4P = tetraphenylphosphonium cation and R = I (5)] were synthesized by the reaction of the potassium dithiocarbimates (4-RC6H4SO2NCS2K2ṡ2H2O) with I2 and Bu4NBr or Ph4PCl. The IR data were consistent with the formation of the dithiocarbimatodisulfides anions. The NMR spectra showed the expected signals for the cations and anions in a 2:1 proportion. The structures of compounds 1-5 were determined by the single crystal X-ray diffraction. The compounds 2, 3 and 4 are isostructural and crystallise in the centrosymmetric space group C2/c of the monoclinic system. Compound 1 crystallises in the monoclinic system in the space group of P21/n and the compound 5 crystallises in the centrosymmetric space group P-1 of the triclinic system. The complex anions of compounds 2, 3 and 4 exhibit similar conformations having twofold symmetry, while in 1 and 5 the anions exhibit C1 symmetry. The activity of the new compounds in the vulcanization of the natural rubber was evaluated and compared to the commercial accelerators ZDMC, TBBS and TMTD. These studies confirm that the sulfonyldithiocarbimato disulfides anions are new vulcanization accelerators, being slower than the commercial accelerators, but producing a greater degree of crosslinking, and scorch time values compatible with good processing safety for industrial applications. The mechanical properties, stress and tear resistances were determined and compared to those obtained with the commercial accelerators.

  12. Graphene-Molybdenum Disulfide-Graphene Tunneling Junctions with Large-Area Synthesized Materials.

    Science.gov (United States)

    Joiner, Corey A; Campbell, Philip M; Tarasov, Alexey A; Beatty, Brian R; Perini, Chris J; Tsai, Meng-Yen; Ready, William J; Vogel, Eric M

    2016-04-06

    Tunneling devices based on vertical heterostructures of graphene and other 2D materials can overcome the low on-off ratios typically observed in planar graphene field-effect transistors. This study addresses the impact of processing conditions on two-dimensional materials in a fully integrated heterostructure device fabrication process. In this paper, graphene-molybdenum disulfide-graphene tunneling heterostructures were fabricated using only large-area synthesized materials, unlike previous studies that used small exfoliated flakes. The MoS2 tunneling barrier is either synthesized on a sacrificial substrate and transferred to the bottom-layer graphene or synthesized directly on CVD graphene. The presence of graphene was shown to have no impact on the quality of the grown MoS2. The thickness uniformity of MoS2 grown on graphene and SiO2 was found to be 1.8 ± 0.22 nm. XPS and Raman spectroscopy are used to show how the MoS2 synthesis process introduces defects into the graphene structure by incorporating sulfur into the graphene. The incorporation of sulfur was shown to be greatly reduced in the absence of molybdenum suggesting molybdenum acts as a catalyst for sulfur incorporation. Tunneling simulations based on the Bardeen transfer Hamiltonian were performed and compared to the experimental tunneling results. The simulations show the use of MoS2 as a tunneling barrier suppresses contributions to the tunneling current from the conduction band. This is a result of the observed reduction of electron conduction within the graphene sheets.

  13. Modification of nanoelectrode ensembles by thiols and disulfides to prevent non specific adsorption of proteins

    Energy Technology Data Exchange (ETDEWEB)

    Silvestrini, M. [Department of Molecular Sciences and Nanosystems, University Ca' Foscari of Venice, Santa Marta 2137, 30123 Venice (Italy); Schiavuta, P.; Scopece, P. [Associazione CIVEN, via delle Industrie 5, 30175 Marghera - Venice (Italy); Pecchielan, G.; Moretto, L.M. [Department of Molecular Sciences and Nanosystems, University Ca' Foscari of Venice, Santa Marta 2137, 30123 Venice (Italy); Ugo, P., E-mail: ugo@unive.it [Department of Molecular Sciences and Nanosystems, University Ca' Foscari of Venice, Santa Marta 2137, 30123 Venice (Italy)

    2011-09-01

    Highlights: > Complex nanostructures are built on the gold surface of ensembles of nanoelectrodes. > Gold surface of nanoelectrodes was functionalized with SAM of organic sulphurs. > The polycarbonate surrounding nanoelectrodes was functionalized with proteins. > SAMs protect the nanoelectrodes from undesired proteins adsorption. - Abstract: The possibility to functionalize selectively with thiols or disulfides the surface of the gold nanoelectrodes of polycarbonate templated nanoelectrode ensembles (NEEs) is studied. It is shown that the Au nanoelectrodes can be coated by a self assembled monolayer (SAM) of thioctic acid (TA) or 2-mercaptoethanesulfonic (MES) acid. The study of the electrochemical behavior of SAM-modified NEEs by cyclic voltammetry (CV) at different solution pH, using ferrocenecarboxylate as an anionic redox probe (FcCOO{sup -}) and (ferrocenylmethyl)trimethylammonium (FA{sup +}) as a cationic redox probe, demonstrate that the SAM-modified nanoelectrodes are permselective, in that only cationic or neutral probes can access the SAM-coated nanoelectrode surface. CV, AFM and FTIR-ATR data indicate that proteins such as casein or bovine serum albumin, which are polyanionic at pH 7, adsorb on the surface of NEEs untreated with thiols, tending to block the electron transfer of the ferrocenyl redox probes. On the contrary, the pre-treatment of the NEE with an anionic SAM protects the nanoelectrodes from protein fouling, allowing the detection of well shaped voltammetric patterns for the redox probe. Experimental results indicate that, in the case of MES treated NEEs, the protein is bound only onto the polycarbonate surface which surrounds the nanoelectrodes, while the tips of the gold nanoelectrodes remain protein free.

  14. Attachment and entry of Chlamydia have distinct requirements for host protein disulfide isomerase.

    Directory of Open Access Journals (Sweden)

    Stephanie Abromaitis

    2009-04-01

    Full Text Available Chlamydia is an obligate intracellular pathogen that causes a wide range of diseases in humans. Attachment and entry are key processes in infectivity and subsequent pathogenesis of Chlamydia, yet the mechanisms governing these interactions are unknown. It was recently shown that a cell line, CHO6, that is resistant to attachment, and thus infectivity, of multiple Chlamydia species has a defect in protein disulfide isomerase (PDI N-terminal signal sequence processing. Ectopic expression of PDI in CHO6 cells led to restoration of Chlamydia attachment and infectivity; however, the mechanism leading to this recovery was not ascertained. To advance our understanding of the role of PDI in Chlamydia infection, we used RNA interference to establish that cellular PDI is essential for bacterial attachment to cells, making PDI the only host protein identified as necessary for attachment of multiple species of Chlamydia. Genetic complementation and PDI-specific inhibitors were used to determine that cell surface PDI enzymatic activity is required for bacterial entry into cells, but enzymatic function was not required for bacterial attachment. We further determined that it is a PDI-mediated reduction at the cell surface that triggers bacterial uptake. While PDI is necessary for Chlamydia attachment to cells, the bacteria do not appear to utilize plasma membrane-associated PDI as a receptor, suggesting that Chlamydia binds a cell surface protein that requires structural association with PDI. Our findings demonstrate that PDI has two essential and independent roles in the process of chlamydial infectivity: it is structurally required for chlamydial attachment, and the thiol-mediated oxido-reductive function of PDI is necessary for entry.

  15. Synergistic effect of tungsten disulfide and cenosphere combination on braking performance of composite friction materials

    International Nuclear Information System (INIS)

    Kachhap, Rakesh K.; Satapathy, Bhabani K.

    2014-01-01

    Graphical abstract: Graphical abstract showing correlation between enhanced frictional stability and enhanced visc-oelastic energy dissipation. - Highlights: • Developed new class of brake composites based on WS 2 and cenosphere. • Synergistic effect of WS 2 and cenosphere for enhanced friction stability. • Wear surface morphology revealed composition specific topography. • Friction fade-recovery performance remained optimal. - Abstract: Tungsten disulfide (WS 2 /TDS) based cenosphere (Cn) filled friction composites with varying cenosphere to WS 2 ratio (Cn/TDS) were fabricated by compression molding of phenolic resin based dry formulation mix and evaluated for their thermal, thermo-mechanical and tribological performances. The loss and revival of braking friction effectiveness due to heating or cooling of the disc termed as fade and recovery performance have been characterized on a Krauss friction testing machine following ECE R-90 industrial standards. The fade performance remained dependent on Cn/TDS, where enhanced fading could be correlated to lower Cn/TDS value accompanied with broader frictional fluctuations i.e. μ max –μ min . A decrease in the frictional-recovery response ensued with increase in Cn/TDS. Dynamic mechanical analysis revealed an increase in storage modulus till 2.5 wt.% of TDS loading followed by consistent decrease whereas two distinct peaks in loss modulus plots that are composition independent have been observed. Scanning electron microscopy revealed the worn surface morphology associated with the dynamics of contact patches formation and deformation vis-a-vis friction layer formation as integrally responsible for the observed friction performance. Energy dispersive analysis of X-rays (EDX) enabled compositional analysis of the friction layer viz. Fe, W, Si, and Al content which may have a mechanistic role in controlling phenomena like, disc rubbing, lubricity, porosity, and hardness of friction layer formed during braking

  16. Modification of nanoelectrode ensembles by thiols and disulfides to prevent non specific adsorption of proteins

    International Nuclear Information System (INIS)

    Silvestrini, M.; Schiavuta, P.; Scopece, P.; Pecchielan, G.; Moretto, L.M.; Ugo, P.

    2011-01-01

    Highlights: → Complex nanostructures are built on the gold surface of ensembles of nanoelectrodes. → Gold surface of nanoelectrodes was functionalized with SAM of organic sulphurs. → The polycarbonate surrounding nanoelectrodes was functionalized with proteins. → SAMs protect the nanoelectrodes from undesired proteins adsorption. - Abstract: The possibility to functionalize selectively with thiols or disulfides the surface of the gold nanoelectrodes of polycarbonate templated nanoelectrode ensembles (NEEs) is studied. It is shown that the Au nanoelectrodes can be coated by a self assembled monolayer (SAM) of thioctic acid (TA) or 2-mercaptoethanesulfonic (MES) acid. The study of the electrochemical behavior of SAM-modified NEEs by cyclic voltammetry (CV) at different solution pH, using ferrocenecarboxylate as an anionic redox probe (FcCOO - ) and (ferrocenylmethyl)trimethylammonium (FA + ) as a cationic redox probe, demonstrate that the SAM-modified nanoelectrodes are permselective, in that only cationic or neutral probes can access the SAM-coated nanoelectrode surface. CV, AFM and FTIR-ATR data indicate that proteins such as casein or bovine serum albumin, which are polyanionic at pH 7, adsorb on the surface of NEEs untreated with thiols, tending to block the electron transfer of the ferrocenyl redox probes. On the contrary, the pre-treatment of the NEE with an anionic SAM protects the nanoelectrodes from protein fouling, allowing the detection of well shaped voltammetric patterns for the redox probe. Experimental results indicate that, in the case of MES treated NEEs, the protein is bound only onto the polycarbonate surface which surrounds the nanoelectrodes, while the tips of the gold nanoelectrodes remain protein free.

  17. Pushing the Performance Limit of Sub-100 nm Molybdenum Disulfide Transistors.

    Science.gov (United States)

    Liu, Yuan; Guo, Jian; Wu, Yecun; Zhu, Enbo; Weiss, Nathan O; He, Qiyuan; Wu, Hao; Cheng, Hung-Chieh; Xu, Yang; Shakir, Imran; Huang, Yu; Duan, Xiangfeng

    2016-10-12

    Two-dimensional semiconductors (2DSCs) such as molybdenum disulfide (MoS 2 ) have attracted intense interest as an alternative electronic material in the postsilicon era. However, the ON-current density achieved in 2DSC transistors to date is considerably lower than that of silicon devices, and it remains an open question whether 2DSC transistors can offer competitive performance. A high current device requires simultaneous minimization of the contact resistance and channel length, which is a nontrivial challenge for atomically thin 2DSCs, since the typical low contact resistance approaches for 2DSCs either degrade the electronic properties of the channel or are incompatible with the fabrication process for short channel devices. Here, we report a new approach toward high-performance MoS 2 transistors by using a physically assembled nanowire as a lift-off mask to create ultrashort channel devices with pristine MoS 2 channel and self-aligned low resistance metal/graphene hybrid contact. With the optimized contact in short channel devices, we demonstrate sub-100 nm MoS 2 transistor delivering a record high ON-current of 0.83 mA/μm at 300 K and 1.48 mA/μm at 20 K, which compares well with that of silicon devices. Our study, for the first time, demonstrates that the 2DSC transistors can offer comparable performance to the 2017 target for silicon transistors in International Technology Roadmap for Semiconductors (ITRS), marking an important milestone in 2DSC electronics.

  18. Noncovalently Functionalized Tungsten Disulfide Nanosheets for Enhanced Mechanical and Thermal Properties of Epoxy Nanocomposites.

    Science.gov (United States)

    Sahu, Megha; Narashimhan, Lakshmi; Prakash, Om; Raichur, Ashok M

    2017-04-26

    In the present study, noncovalently functionalized tungsten disulfide (WS 2 ) nanosheets were used as a toughening agent for epoxy nanocomposites. WS 2 was modified with branched polyethyleneimine (PEI) to increase the degree of interaction of nanosheets with the epoxy matrix and prevent restacking and agglomeration of the sheets in the epoxy matrix. The functionalization of WS 2 sheets was confirmed through Fourier transform infrared spectroscopy and thermogravimetric analysis. The exfoliation of the bulk WS 2 was confirmed through X-ray diffraction and various microscopic techniques. Epoxy nanocomposites containing up to 1 wt % of WS 2 -PEI nanosheets were fabricated. They showed a remarkable improvement in fracture toughness (K IC ). K IC increased from 0.94 to 1.72 MPa m -1/2 for WS 2 -PEI nanosheet loadings as low as 0.25 wt %. Compressive and flexural properties also showed a significant improvement as incorporation of 0.25 wt % of WS 2 -PEI nanosheets resulted in 43 and 65% increase in the compressive and flexural strengths of epoxy nanocomposites, respectively, compared with neat epoxy. Thermal stability and thermomechanical properties of the WS 2 -PEI-modified epoxy also showed a significant improvement. The simultaneous improvement in the mechanical and thermal properties could be attributed to the good dispersion of WS 2 -PEI nanosheets in the matrix, intrinsic high strength and thermal properties of the nanosheets, and improved interaction of the WS 2 nanosheets with the epoxy matrix owing to the presence of PEI molecules on the surface of the WS 2 nanosheets.

  19. Out-of-Plane Electromechanical Response of Monolayer Molybdenum Disulfide Measured by Piezoresponse Force Microscopy.

    Science.gov (United States)

    Brennan, Christopher J; Ghosh, Rudresh; Koul, Kalhan; Banerjee, Sanjay K; Lu, Nanshu; Yu, Edward T

    2017-09-13

    Two-dimensional (2D) materials have recently been theoretically predicted and experimentally confirmed to exhibit electromechanical coupling. Specifically, monolayer and few-layer molybdenum disulfide (MoS 2 ) have been measured to be piezoelectric within the plane of their atoms. This work demonstrates and quantifies a nonzero out-of-plane electromechanical response of monolayer MoS 2 and discusses its possible origins. A piezoresponse force microscope was used to measure the out-of-plane deformation of monolayer MoS 2 on Au/Si and Al 2 O 3 /Si substrates. Using a vectorial background subtraction technique, we estimate the effective out-of-plane piezoelectric coefficient, d 33 eff , for monolayer MoS 2 to be 1.03 ± 0.22 pm/V when measured on the Au/Si substrate and 1.35 ± 0.24 pm/V when measured on Al 2 O 3 /Si. This is on the same order as the in-plane coefficient d 11 reported for monolayer MoS 2 . Interpreting the out-of-plane response as a flexoelectric response, the effective flexoelectric coefficient, μ eff * , is estimated to be 0.10 nC/m. Analysis has ruled out the possibility of elastic and electrostatic forces contributing to the measured electromechanical response. X-ray photoelectron spectroscopy detected some contaminants on both MoS 2 and its substrate, but the background subtraction technique is expected to remove major contributions from the unwanted contaminants. These measurements provide evidence that monolayer MoS 2 exhibits an out-of-plane electromechanical response and our analysis offers estimates of the effective piezoelectric and flexoelectric coefficients.

  20. Hexa-histidin tag position influences disulfide structure but not binding behavior of in vitro folded N-terminal domain of rat corticotropin-releasing factor receptor type 2a

    OpenAIRE

    Klose, Jana; Wendt, Norbert; Kubald, Sybille; Krause, Eberhard; Fechner, Klaus; Beyermann, Michael; Bienert, Michael; Rudolph, Rainer; Rothemund, Sven

    2004-01-01

    The oxidative folding, particularly the arrangement of disulfide bonds of recombinant extracellular N-terminal domains of the corticotropin-releasing factor receptor type 2a bearing five cysteines (C2 to C6), was investigated. Depending on the position of a His-tag, two types of disulfide patterns were found. In the case of an N-terminal His-tag, the disulfide bonds C2–C3 and C4–C6 were found, leaving C5 free, whereas the C-terminal position of the His-tag led to the disulfide pattern C2–C5 a...