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Sample records for agc viiia protein

  1. Myotonin protein-kinase [AGC]n trinucleotide repeat in seven nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Novelli, G.; Sineo, L.; Pontieri, E. [Catholic Univ. of Rome (Italy)]|[Univ. of Milan (Italy)]|[Univ. Florence (Italy)] [and others

    1994-09-01

    Myotonic dystrophy (DM) is due to a genomic instability of a trinucleotide [AGC]n motif, located at the 3{prime} UTR region of a protein-kinase gene (myotonin protein kinase, MT-PK). The [AGC] repeat is meiotically and mitotically unstable, and it is directly related to the manifestations of the disorder. Although a gene dosage effect of the MT-PK has been demonstrated n DM muscle, the mechanism(s) by which the intragenic repeat expansion leads to disease is largely unknown. This non-standard mutational event could reflect an evolutionary mechanism widespread among animal genomes. We have isolated and sequenced the complete 3{prime}UTR region of the MT-PK gene in seven primates (macaque, orangutan, gorilla, chimpanzee, gibbon, owl monkey, saimiri), and examined by comparative sequence nucleotide analysis the [AGC]n intragenic repeat and the surrounding nucleotides. The genomic organization, including the [AGC]n repeat structure, was conserved in all examined species, excluding the gibbon (Hylobates agilis), in which the [AGC]n upstream sequence (GGAA) is replaced by a GA dinucleotide. The number of [AGC]n in the examined species ranged between 7 (gorilla) and 13 repeats (owl monkeys), with a polymorphism informative content (PIC) similar to that observed in humans. These results indicate that the 3{prime}UTR [AGC] repeat within the MT-PK gene is evolutionarily conserved, supporting that this region has important regulatory functions.

  2. Autoregulation of kinase dephosphorylation by ATP binding in AGC protein kinases.

    Science.gov (United States)

    Chan, Tung O; Pascal, John M; Armen, Roger S; Rodeck, Ulrich

    2012-02-01

    AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non- ATP-competitive kinase inhibitors that discriminate within and between protein kinase families.

  3. Autoregulation of kinase dephosphorylation by ATP binding to AGC protein kinases

    Science.gov (United States)

    Pascal, John M; Armen, Roger S

    2012-01-01

    AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non-ATP-competitive kinase inhibitors that discriminate within and between protein kinase families. PMID:22262182

  4. The wheat AGC kinase TaAGC1 is a positive contributor to host resistance to the necrotrophic pathogen Rhizoctonia cerealis.

    Science.gov (United States)

    Zhu, Xiuliang; Yang, Kun; Wei, Xuening; Zhang, Qiaofeng; Rong, Wei; Du, Lipu; Ye, Xingguo; Qi, Lin; Zhang, Zengyan

    2015-11-01

    Considerable progress has been made in understanding the roles of AGC kinases in mammalian systems. However, very little is known about the roles of AGC kinases in wheat (Triticum aestivum). The necrotrophic fungus Rhizoctonia cerealis is the major pathogen of the destructive disease sharp eyespot of wheat. In this study, the wheat AGC kinase gene TaAGC1, responding to R. cerealis infection, was isolated, and its properties and role in wheat defence were characterized. R. cerealis-resistant wheat lines expressed TaAGC1 at higher levels than susceptible wheat lines. Sequence and phylogenetic analyses showed that the TaAGC1 protein is a serine/threonine kinase belonging to the NDR (nuclear Dbf2-related) subgroup of AGC kinases. Kinase activity assays proved that TaAGC1 is a functional kinase and the Asp-239 residue located in the conserved serine/threonine kinase domain of TaAGC1 is required for the kinase activity. Subcellular localization assays indicated that TaAGC1 localized in the cytoplasm and nucleus. Virus-induced TaAGC1 silencing revealed that the down-regulation of TaAGC1 transcripts significantly impaired wheat resistance to R. cerealis. The molecular characterization and responses of TaAGC1 overexpressing transgenic wheat plants indicated that TaAGC1 overexpression significantly enhanced resistance to sharp eyespot and reduced the accumulation of reactive oxygen species (ROS) in wheat plants challenged with R. cerealis. Furthermore, ROS-scavenging and certain defence-associated genes were up-regulated in resistant plants overexpressing TaAGC1 but down-regulated in susceptible knock-down plants. These results suggested that the kinase TaAGC1 positively contributes to wheat immunity to R. cerealis through regulating expression of ROS-related and defence-associated genes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Evolutionary adaptations of plant AGC kinases: from light signaling to cell polarity regulation

    Directory of Open Access Journals (Sweden)

    Eike Hendrik Rademacher

    2012-11-01

    Full Text Available Signaling and trafficking over membranes involves a plethora of transmembrane proteins that control the flow of compounds or relay specific signaling events. Next to external cues internal stimuli can modify the activity or abundance of these proteins at the plasma membrane. One such regulatory mechanism is protein phosphorylation by membrane-associated kinases and phosphatases. The AGC kinase family is one of seven kinase families that are conserved in all eukaryotic genomes. In plants evolutionary adaptations introduced specific structural changes within the plant AGC kinases that most likely allow for sensing of external stimuli (i.e. light through controlled modification of kinase activity.Starting from the well-defined structural basis common to all AGC kinases we review the current knowledge on the structure-function relationship in plant AGC kinases. Nine of the 39 Arabidopsis AGC kinases have now been shown to be involved in the regulation of auxin transport. In particular, AGC kinase-mediated phosphorylation of the auxin transporters ABCB1 and ABCB19 has been shown to regulate their activity, while auxin transporters of the PIN family are located to different positions at the plasma membrane depending on their phosphorylation status, which is a result of counteracting AGC kinase and PP2A phosphatase activities. We therefore focus on regulation of AGC kinase activity in this context. Identified structural adaptations of the involved AGC kinases may provide new insight into AGC kinase functionality and demonstrate their position as central hubs in the cellular network controlling plant development and growth.

  6. AGC-2 Disassembly Report

    Energy Technology Data Exchange (ETDEWEB)

    William Windes

    2014-05-01

    The Next Generation Nuclear Plant (NGNP) Graphite Research and Development (R&D) Program is currently measuring irradiated material properties for predicting the behavior and operating performance of new nuclear graphite grades available for use within the cores of new very high temperature reactor designs. The Advanced Graphite Creep (AGC) experiment, consisting of six irradiation capsules, will generate irradiated graphite performance data for NGNP reactor operating conditions. The AGC experiment is designed to determine the changes to specific material properties such as thermal diffusivity, thermal expansion, elastic modulus, mechanical strength, irradiation induced dimensional change rate, and irradiation creep for a wide variety of nuclear grade graphite types over a range of high temperature, and moderate doses. A series of six capsules containing graphite test specimens will be used to expose graphite test samples to a dose range from 1 to 7 dpa at three different temperatures (600, 900, and 1200°C) as described in the Graphite Technology Development Plan. Since irradiation induced creep within graphite components is considered critical to determining the operational life of the graphite core, some of the samples will also be exposed to an applied load to determine the creep rate for each graphite type under both temperature and neutron flux. All six AGC capsules in the experiment will be irradiated in the Advanced Test Reactor (ATR). AGC-1 and AGC-2 will be irradiated in the south flux trap and AGC-3–AGC-6 will be irradiated in the east flux trap. The change in flux traps is due to NGNP irradiation priorities requiring the AGC experiment to be moved to accommodate Fuel irradiation experiments. After irradiation, all six AGC capsules will be cooled in the ATR Canal, sized for shipment, and shipped to the Materials and Fuels Complex (MFC) where the capsule will be disassembled in the Hot Fuel Examination Facility (HFEF). During disassembly, the metallic

  7. Peningkatan Aktivitas, Motivasi dan Hasil Belajar IPA Biologi Peserta Didik Kelas VIIIA-1 MTsN Watampone melalui Model Pembelajaran Inkuiri Terbimbing

    Directory of Open Access Journals (Sweden)

    Pujiati Pujiati

    2016-02-01

    Full Text Available ABSTRAKPenelitian ini bertujuan untuk mengetahui peningkatan aktivitas belajar, motivasi belajar dan hasil belajar IPA Biologi peserta didik kelas VIIIA-1 MTsN 1 Watampone melalui model pembelajaran inkuiri terbimbing. Penelitian ini merupakan penelitian tindakan kelas yang dilaksanakan di MTsN  1 Watampone Kabupaten Bone. Subjek  penelitian ini adalah peserta didik kelas VIIIA-1 dengan jumlah peserta didik 32 orang. Penelitian ini dilakukan pada semester genap tahun pelajaran 2015/2016, bulan Januari sampai bulan April 2016. Hasil penelitian menunjukkan bahwa (1 aktivitas belajar IPA Biologi peserta didik kelas VIIIA-1 MTsN 1 Watampone meningkat dari  62,25% menjadi 87,5% melalui model pembelajaran inkuiri terbimbing (2 motivasi  belajar IPA Biologi peserta didik kelas VIIIA-1 MTsN 1 Watampone meningkat dari 85,71% menjadi 87,06%  melalui model pembelajaran inkuri terbimbing (3 . Hasil   belajar IPA Biologi peserta didik kelas VIIIA-1 MTsN 1 Watampone meningkat dari 59,37% menjadi 87,5%  melalui model pembelajaran inkuri terbimbing.Kata kunci: pendekatan saintifik, keterampilan proses sains, hasil belajar kognitif biologi.ABSTRACTThis study aims to determine the increase activity, motivation and learning outcomes of science biology for VIIIA-1 Class of MTsN 1 Watampone through guided inquiry learning model. This study is classroom action research conducted in MTsN 1 Watampone, Bone. The subjects were students of Class of VIIIA-1 with the number of students is 32. This research was conducted in the second semester of 2015/2016 academic year, January to April 2016. Results showed that (1 the activity of students to learn science biology of VIIIA-1 Class of MTsN 1 Watampone increased from 62.25% to 87.5% through the inquiry guided learning model, (2 motivation to learn science biology of Students of VIIIA-1 Class of MTsN 1 Watampone increased from 85.71% to 87.06% through the inquiry guided learning model, (3 Biological science learning

  8. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)

    2008-06-03

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  9. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.

    2008-01-01

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  10. AGC-2 Graphite Preirradiation Data Analysis Report

    Energy Technology Data Exchange (ETDEWEB)

    William Windes; W. David Swank; David Rohrbaugh; Joseph Lord

    2013-08-01

    This report described the specimen loading order and documents all pre-irradiation examination material property measurement data for the graphite specimens contained within the second Advanced Graphite Capsule (AGC-2) irradiation capsule. The AGC-2 capsule is the second in six planned irradiation capsules comprising the Advanced Graphite Creep (AGC) test series. The AGC test series is used to irradiate graphite specimens allowing quantitative data necessary for predicting the irradiation behavior and operating performance of new nuclear graphite grades to be generated which will ascertain the in-service behavior of the graphite for pebble bed and prismatic Very High Temperature Reactor (VHTR) designs. Similar to the AGC-1 specimen pre-irradiation examination report, material property tests were conducted on specimens from 18 nuclear graphite types but on an increased number of specimens (512) prior to loading into the AGC-2 irradiation assembly. All AGC-2 specimen testing was conducted at Idaho National Laboratory (INL) from October 2009 to August 2010. This report also details the specimen loading methodology for the graphite specimens inside the AGC-2 irradiation capsule. The AGC-2 capsule design requires “matched pair” creep specimens that have similar dose levels above and below the neutron flux profile mid-plane to provide similar specimens with and without an applied load. This document utilized the neutron flux profile calculated for the AGC-2 capsule design, the capsule dimensions, and the size (length) of the selected graphite and silicon carbide samples to create a stacking order that can produce “matched pairs” of graphite samples above and below the AGC-2 capsule elevation mid-point to provide specimens with similar neutron dose levels.

  11. AGC-3 Graphite Preirradiation Data Analysis Report

    Energy Technology Data Exchange (ETDEWEB)

    William Windes; David Swank; David Rohrbaugh; Joseph Lord

    2013-09-01

    This report describes the specimen loading order and documents all pre-irradiation examination material property measurement data for the graphite specimens contained within the third Advanced Graphite Capsule (AGC-3) irradiation capsule. The AGC-3 capsule is third in six planned irradiation capsules comprising the Advanced Graphite Creep (AGC) test series. The AGC test series is used to irradiate graphite specimens allowing quantitative data necessary for predicting the irradiation behavior and operating performance of new nuclear graphite grades to be generated which will ascertain the in-service behavior of the graphite for pebble bed and prismatic Very High Temperature Reactor (VHTR) designs. The general design of AGC-3 test capsule is similar to the AGC-2 test capsule, material property tests were conducted on graphite specimens prior to loading into the AGC-3 irradiation assembly. However the 6 major nuclear graphite grades in AGC-2 were modified; two previous graphite grades (IG-430 and H-451) were eliminated and one was added (Mersen’s 2114 was added). Specimen testing from three graphite grades (PCEA, 2114, and NBG-17) was conducted at Idaho National Laboratory (INL) and specimen testing for two grades (IG-110 and NBG-18) were conducted at Oak Ridge National Laboratory (ORNL) from May 2011 to July 2013. This report also details the specimen loading methodology for the graphite specimens inside the AGC-3 irradiation capsule. The AGC-3 capsule design requires "matched pair" creep specimens that have similar dose levels above and below the neutron flux profile mid-plane to provide similar specimens with and without an applied load. This document utilized the neutron flux profile calculated for the AGC-3 capsule design, the capsule dimensions, and the size (length) of the selected graphite and silicon carbide samples to create a stacking order that can produce "matched pairs" of graphite samples above and below the AGC-3 capsule elevation mid-point to

  12. AGC kinases, mechanisms of regulation ‎and innovative drug development.

    Science.gov (United States)

    Leroux, Alejandro E; Schulze, Jörg O; Biondi, Ricardo M

    2018-02-01

    The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signalling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation. In the present review, we update the knowledge of the mechanisms of regulation of different AGC kinases. The conformation of the catalytic domain of many AGC kinases is regulated allosterically through the modulation of the conformation of a regulatory site on the small lobe of the kinase domain, the PIF-pocket. The PIF-pocket acts like an ON-OFF switch in AGC kinases with different modes of regulation, i.e. PDK1, PKB/Akt, LATS and Aurora kinases. In this review, we make emphasis on how the knowledge of the molecular mechanisms of regulation can guide the discovery and development of small allosteric modulators. Molecular probes stabilizing the PIF-pocket in the active conformation are activators, while compounds stabilizing the disrupted site are allosteric inhibitors. One challenge for the rational development of allosteric modulators is the lack of complete structural information of the inhibited forms of full-length AGC kinases. On the other hand, we suggest that the available information derived from molecular biology and biochemical studies can already guide screening strategies for the identification of innovative mode of action molecular probes and the development of selective allosteric drugs for the treatment of human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Dwarfism in homozygous Agc1CreERT mice is associated with decreased expression of aggrecan.

    Science.gov (United States)

    Rashid, Harunur; Chen, Haiyan; Hassan, Quamarul; Javed, Amjad

    2017-10-01

    Aggrecan (Acan), a large proteoglycan is abundantly expressed in cartilage tissue. Disruption of Acan gene causes dwarfism and perinatal lethality of homozygous mice. Because of sustained expression of Acan in the growth plate and articular cartilage, Agc Cre model has been developed for the regulated ablation of target gene in chondrocytes. In this model, the IRES-CreERT-Neo-pgk transgene is knocked-in the 3'UTR of the Acan gene. We consistently noticed variable weight and size among the Agc Cre littermates, prompting us to examine the cause of this phenotype. Wild-type, Cre-heterozygous (Agc +/Cre ), and Cre-homozygous (Agc Cre/Cre ) littermates were indistinguishable at birth. However, by 1-month, Agc Cre/Cre mice showed a significant reduction in body weight (18-27%) and body length (19-22%). Low body weight and dwarfism was sustained through adulthood and occurred in both genders. Compared with wild-type and Agc +/Cre littermates, long bones and vertebrae were shorter in Agc Cre/Cre mice. Histological analysis of Agc Cre/Cre mice revealed a significant reduction in the length of the growth plate and the thickness of articular cartilage. The amount of proteoglycan deposited in the cartilage of Agc Cre/Cre mice was nearly half of the WT littermates. Analysis of gene expression indicates impaired differentiation of chondrocyte in hyaline cartilage of Agc Cre/Cre mice. Notably, both Acan mRNA and protein was reduced by 50% in Agc Cre/Cre mice. A strong correlation was noted between the level of Acan mRNA and the body length. Importantly, Agc +/Cre mice showed no overt skeletal phenotype. Thus to avoid misinterpretation of data, only the Agc +/Cre mice should be used for conditional deletion of a target gene in the cartilage tissue. © 2017 Wiley Periodicals, Inc.

  14. Is AGC beneficial in hearing aids?

    Science.gov (United States)

    King, A B; Martin, M C

    1984-02-01

    Three different functions of Automatic Gain Control (AGC) circuits in hearing aids are distinguished and the evidence for their benefits is considered. The value of AGC's function as a relatively distortion-free means of limiting output has been well established. With regard to compression, the benefit of short-term or 'syllabic' compression has not been demonstrated convincingly. Most evaluations of this type of AGC have looked for increase in speech intelligibility, but theoretical predictions of its effect do not appear to take account of the acoustic cues to consonant contrasts actually used by hearing impaired people, and empirical studies have often used listening conditions which do not give a realistic test of benefit. Relatively little attention has been paid to long-term compression, or to the effect of AGC on comfort rather than intelligibility. Listening tests carried out at the RNID and reported here have shown that AGC can benefit hearing aid users by allowing them to listen to a wider range of sound levels without either strain or discomfort, and, if time constants are well chosen, without adverse effects on speech intelligibility in quiet or in noise.

  15. AGC-2 Graphite Preirradiation Data Package

    Energy Technology Data Exchange (ETDEWEB)

    David Swank; Joseph Lord; David Rohrbaugh; William Windes

    2012-10-01

    The NGNP Graphite R&D program is currently establishing the safe operating envelope of graphite core components for a Very High Temperature Reactor (VHTR) design. The program is generating quantitative data necessary for predicting the behavior and operating performance of the new nuclear graphite grades. To determine the in-service behavior of the graphite for pebble bed and prismatic designs, the Advanced Graphite Creep (AGC) experiment is underway. This experiment is examining the properties and behavior of nuclear grade graphite over a large spectrum of temperatures, neutron fluences and compressive loads. Each experiment consists of over 400 graphite specimens that are characterized prior to irradiation and following irradiation. Six experiments are planned with the first, AGC-1, currently being irradiated in the Advanced Test Reactor (ATR) and pre-irradiation characterization of the second, AGC-2, completed. This data package establishes the readiness of 512 specimens for assembly into the AGC-2 capsule.

  16. Investigation of an AGC for Audio Applications

    DEFF Research Database (Denmark)

    Haerizadeh, Seyediman; Jørgensen, Ivan Harald Holger; Marker-Villumsen, Niels

    2015-01-01

    An investigation of an amplifier with discrete time Automatic Gain Control (AGC) which is intended for implementation in hearing aid is performed. The aim of this investigation is to find the AGC’s minimum gain step size for which the glitches become inaudible. Such AGCs produce undesirable...

  17. performance evaluation of evolutionary designed conventional AGC ...

    African Journals Online (AJOL)

    In this context, the tuning of a multi-area automatic generation control (AGC) system after deregulation and furthermore, the effect of reheat turbines dynamics in the power system performance, are not yet ... The performances of the tuned two–area AGC system are obtained using appropriate Matlab/Simulink models. Finally ...

  18. AGC-2 Specimen Post Irradiation Data Package Report

    Energy Technology Data Exchange (ETDEWEB)

    Windes, William Enoch [Idaho National Lab. (INL), Idaho Falls, ID (United States); Swank, W. David [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rohrbaugh, David T. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cottle, David L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-08-01

    This report documents results of the post-irradiation examination material property testing of the creep, control, and piggyback specimens from the irradiation creep capsule Advanced Graphite Creep (AGC)-2 are reported. This is the second of a series of six irradiation test trains planned as part of the AGC experiment to fully characterize the neutron irradiation effects and radiation creep behavior of current nuclear graphite grades. The AGC-2 capsule was irradiated in the Idaho National Laboratory Advanced Test Reactor at a nominal temperature of 600°C and to a peak dose of 5 dpa (displacements per atom). One-half of the creep specimens were subjected to mechanical stresses (an applied stress of either 13.8, 17.2, or 20.7 MPa) to induce irradiation creep. All post-irradiation testing and measurement results are reported with the exception of the irradiation mechanical strength testing, which is the last destructive testing stage of the irradiation testing program. Material property tests were conducted on specimens from 15 nuclear graphite grades using a similar loading configuration as the first AGC capsule (AGC-1) to provide easy comparison between the two capsules. However, AGC-2 contained an increased number of specimens (i.e., 487 total specimens irradiated) and replaced specimens of the minor grade 2020 with the newer grade 2114. The data reported include specimen dimensions for both stressed and unstressed specimens to establish the irradiation creep rates, mass and volume data necessary to derive density, elastic constants (Young’s modulus, shear modulus, and Poisson’s ratio) from ultrasonic time-of-flight velocity measurements, Young’s modulus from the fundamental frequency of vibration, electrical resistivity, and thermal diffusivity and thermal expansion data from 100–500°C. No data outliers were determined after all measurements were completed. A brief statistical analysis was performed on the irradiated data and a limited comparison between

  19. PRELIMINARY RESULTS OF THE AGC-4 IRRADIATION IN THE ADVANCED TEST REACTOR AND DESIGN OF AGC-5 (HTR16-18469)

    Energy Technology Data Exchange (ETDEWEB)

    Davenport, Michael; Petti, D. A.

    2016-11-01

    The United States Department of Energy’s Advanced Reactor Technologies (ART) Program will irradiate up to six nuclear graphite creep experiments in the Advanced Test Reactor (ATR) located at the Idaho National Laboratory (INL). The graphite experiments are being irradiated over an approximate eight year period to support development of a graphite irradiation performance data base on the new nuclear grade graphites now available for use in high temperature gas reactors. The goals of the irradiation experiments are to obtain irradiation performance data, including irradiation creep, at different temperatures and loading conditions to support design of the Very High Temperature Gas Reactor (VHTR), as well as other future gas reactors. The experiments each consist of a single capsule that contain six stacks of graphite specimens, with half of the graphite specimens in each stack under a compressive load, while the other half of the specimens are not be subjected to a compressive load during irradiation. The six stacks have differing compressive loads applied to the top half of diametrically opposite pairs of specimen stacks. A seventh specimen stack in the center of the capsule does not have a compressive load. The specimens are being irradiated in an inert sweep gas atmosphere with on-line temperature and compressive load monitoring and control. There are also samples taken of the sweep gas effluent to measure any oxidation or off-gassing of the specimens that may occur during initial start-up of the experiment. The first experiment, AGC-1, started its irradiation in September 2009, and the irradiation was completed in January 2011. The second experiment, AGC-2, started its irradiation in April 2011 and completed its irradiation in May 2012. The third experiment, AGC-3, started its irradiation in late November 2012 and completed in the April of 2014. AGC-4 is currently being irradiated in the ATR. This paper will briefly discuss the preliminary irradiation results

  20. AGC-3 Experiment Irradiation Monitoring Data Qualification Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Hull, Laurence C. [Idaho National Lab. (INL), Idaho Falls, ID (United States). VHTR Technology Development Office

    2014-08-01

    The Graphite Technology Development Program will run a series of six experiments to quantify the effects of irradiation on nuclear-grade graphite. The third experiment, Advanced Graphite Creep 3 (AGC-3), began with Advanced Test Reactor (ATR) Cycle 152B on November 27, 2012, and ended with ATR Cycle 155B on April 23, 2014. This report documents qualification of AGC-3 experiment irradiation monitoring data for use by the Very High Temperature Reactor (VHTR) Technology Development Office (TDO) Program for research and development activities required to design and license the first VHTR nuclear plant. Qualified data meet the requirements for data collection and use as described in the experiment planning and quality assurance documents. Failed data do not meet the requirements. Trend data may not meet the requirements, but may still provide some useable information. The report documents qualification of AGC-3 experiment irradiation monitoring data following MCP-2691. This report also documents whether AGC-3 experiment irradiation monitoring data meet the requirements for data collection as specified in technical and functional requirements documents and quality assurance (QA) plans. Data handling is described showing how data are passed from the data collection experiment to the Nuclear Data Management and Analysis System (NDMAS) team. The data structure is described, including data batches, components, attributes, and response variables. The description of the approach to data qualification includes the steps taken to qualify the data and the specific tests used to verify that the data meet requirements. Finally, the current status of the data received by NDMAS from the AGC-3 experiment is presented with summarized information on test results and resolutions. This report addresses all of the irradiation monitoring data collected during the AGC-3 experiment.

  1. Comparison of dual-time-constant and fast-acting automatic gain control (AGC) systems in cochlear implants.

    Science.gov (United States)

    Boyle, Patrick J; Büchner, Andreas; Stone, Michael A; Lenarz, Thomas; Moore, Brian C J

    2009-04-01

    Cochlear implants usually employ an automatic gain control (AGC) system as a first stage of processing. AGC1 was a fast-acting (syllabic) compressor. AGC2 was a dual-time-constant system; it usually performed as a slow-acting compressor, but incorporated an additional fast-acting system to provide protection from sudden increases in sound level. Six experienced cochlear-implant users were tested in a counterbalanced order, receiving one-month of experience with a given AGC type before switching to the other type. Performance was evaluated shortly after provision of a given AGC type and after one-month of experience with that AGC type. Questionnaires, mainly relating to listening in quiet situations, did not reveal significant differences between the two AGC types. However, fixed-level and roving-level tests of sentence identification in noise both revealed significantly better performance for AGC2. It is suggested that the poorer performance for AGC1 occurred because AGC1 introduced cross-modulation between the target speech and background noise, which made perceptual separation of the target and background more difficult.

  2. AGC-3 Experiment Irradiation Monitoring Data Qualification Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Laurence Hull

    2014-10-01

    The Graphite Technology Development Program will run a series of six experiments to quantify the effects of irradiation on nuclear grade graphite. The third experiment, Advanced Graphite Creep 3 (AGC 3), began with Advanced Test Reactor (ATR) Cycle 152B on November 27, 2012, and ended with ATR Cycle 155B on April 23, 2014. This report documents qualification of AGC 3 experiment irradiation monitoring data for use by the Very High Temperature Reactor (VHTR) Technology Development Office (TDO) Program for research and development activities required to design and license the first VHTR nuclear plant. Qualified data meet the requirements for data collection and use as described in the experiment planning and quality assurance documents. Failed data do not meet the requirements. Trend data may not meet the requirements, but may still provide some useable information. All thermocouples (TCs) functioned throughout the AGC 3 experiment. There was one interval between December 18, 2012, and December 20, 2012, where 10 NULL values were reported for various TCs. These NULL values were deleted from the Nuclear Data Management and Analysis System database. All temperature data are Qualified for use by the VHTR TDO Program. Argon, helium, and total gas flow data were within expected ranges and are Qualified for use by the VHTR TDO Program. Total gas flow was approximately 50 sccm through the AGC 3 experiment capsule. Helium gas flow was briefly increased to 100 sccm during ATR shutdowns. At the start of the AGC 3 experiment, moisture in the outflow gas line was stuck at a constant value of 335.6174 ppmv for the first cycle (Cycle 152B). When the AGC 3 experiment capsule was reinstalled in ATR for Cycle 154B, a new moisture filter was installed. Moisture data from Cycle 152B are Failed. All moisture data from the final three cycles (Cycles 154B, 155A, and 155B) are Qualified for use by the VHTR TDO Program.

  3. Designing Structure-Dependent MPC-Based AGC Schemes Considering Network Topology

    Directory of Open Access Journals (Sweden)

    Young-Sik Jang

    2015-04-01

    Full Text Available This paper presents the important features of structure-dependent model predictive control (MPC-based approaches for automatic generation control (AGC considering network topology. Since power systems have various generators under different topologies, it is necessary to reflect the characteristics of generators in power networks and the control system structures in order to improve the dynamic performance of AGC. Specifically, considering control system structures is very important because not only can the topological problems be reduced, but also a computing system for AGC in a bulk-power system can be realized. Based on these considerations, we propose new schemes in the proposed controller for minimizing inadvertent line flows and computational burden, which strengthen the advantages of MPC-based approach for AGC. Analysis and simulation results in the IEEE 39-bus model system show different dynamic behaviors among structure-dependent control schemes and possible improvements in computational burden via the proposed control scheme while system operators in each balancing area consider physical load reference ramp constraints among generators.

  4. A sensitive glucose biosensor based on Ag@C core–shell matrix

    International Nuclear Information System (INIS)

    Zhou, Xuan; Dai, Xingxin; Li, Jianguo; Long, Yumei; Li, Weifeng; Tu, Yifeng

    2015-01-01

    Nano-Ag particles were coated with colloidal carbon (Ag@C) to improve its biocompatibility and chemical stability for the preparation of biosensor. The core–shell structure was evidenced by transmission electron microscope (TEM) and the Fourier transfer infrared (FTIR) spectra revealed that the carbon shell is rich of function groups such as − OH and − COOH. The as-prepared Ag@C core–shell structure can offer favorable microenvironment for immobilizing glucose oxidase and the direct electrochemistry process of glucose oxidase (GOD) at Ag@C modified glassy carbon electrode (GCE) was realized. The modified electrode exhibited good response to glucose. Under optimum experimental conditions the biosensor linearly responded to glucose concentration in the range of 0.05–2.5 mM, with a detection limit of 0.02 mM (S/N = 3). The apparent Michaelis–Menten constant (K M app ) of the biosensor is calculated to be 1.7 mM, suggesting high enzymatic activity and affinity toward glucose. In addition, the GOD-Ag@C/Nafion/GCE shows good reproducibility and long-term stability. These results suggested that core–shell structured Ag@C is an ideal matrix for the immobilization of the redox enzymes and further the construction of the sensitive enzyme biosensor. - Highlights: • Enhanced direct electrochemistry of GOD was achieved at Ag@C modified electrode. • A novel glucose biosensor based on Ag@C core–shell structure was developed. • The designed GOD-Ag@C/Nafion/GCE biosensor showed favorable analysis properties. • The biosensor is easy to prepare and can be applied for real sample assay

  5. A sensitive glucose biosensor based on Ag@C core–shell matrix

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xuan; Dai, Xingxin; Li, Jianguo [College of Chemistry, Chemical engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123 (China); Long, Yumei, E-mail: yumeilong@suda.edu.cn [College of Chemistry, Chemical engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123 (China); The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou (China); Li, Weifeng, E-mail: liweifeng@suda.edu.cn [College of Chemistry, Chemical engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123 (China); Tu, Yifeng [College of Chemistry, Chemical engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123 (China); The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou (China)

    2015-04-01

    Nano-Ag particles were coated with colloidal carbon (Ag@C) to improve its biocompatibility and chemical stability for the preparation of biosensor. The core–shell structure was evidenced by transmission electron microscope (TEM) and the Fourier transfer infrared (FTIR) spectra revealed that the carbon shell is rich of function groups such as − OH and − COOH. The as-prepared Ag@C core–shell structure can offer favorable microenvironment for immobilizing glucose oxidase and the direct electrochemistry process of glucose oxidase (GOD) at Ag@C modified glassy carbon electrode (GCE) was realized. The modified electrode exhibited good response to glucose. Under optimum experimental conditions the biosensor linearly responded to glucose concentration in the range of 0.05–2.5 mM, with a detection limit of 0.02 mM (S/N = 3). The apparent Michaelis–Menten constant (K{sub M}{sup app}) of the biosensor is calculated to be 1.7 mM, suggesting high enzymatic activity and affinity toward glucose. In addition, the GOD-Ag@C/Nafion/GCE shows good reproducibility and long-term stability. These results suggested that core–shell structured Ag@C is an ideal matrix for the immobilization of the redox enzymes and further the construction of the sensitive enzyme biosensor. - Highlights: • Enhanced direct electrochemistry of GOD was achieved at Ag@C modified electrode. • A novel glucose biosensor based on Ag@C core–shell structure was developed. • The designed GOD-Ag@C/Nafion/GCE biosensor showed favorable analysis properties. • The biosensor is easy to prepare and can be applied for real sample assay.

  6. AGC-2 Irradiation Data Qualification Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Laurence C. Hull

    2012-07-01

    The Graphite Technology Development Program will run a series of six experiments to quantify the effects of irradiation on nuclear grade graphite. The second Advanced Graphite Creep (AGC) experiment (AGC-2) began with Advanced Test Reactor (ATR) Cycle 149A on April 12, 2011, and ended with ATR Cycle 151B on May 5, 2012. The purpose of this report is to qualify AGC-2 irradiation monitoring data following INL Management and Control Procedure 2691, Data Qualification. Data that are Qualified meet the requirements for data collection and use as described in the experiment planning and quality assurance documents. Data that do not meet the requirements are Failed. Some data may not quite meet the requirements, but may still provide some useable information. These data are labeled as Trend. No Trend data were identified for the AGC-2 experiment. All thermocouples functioned throughout the AGC-2 experiment. There was one instance where spurious signals or instrument power interruption resulted in a recorded temperature value being well outside physical reality. This value was identified and labeled as Failed data. All other temperature data are Qualified. All helium and argon gas flow data are within expected ranges. Total gas flow was approximately 50 sccm through the capsule. Helium gas flow was briefly increased to 100 sccm during reactor shutdown. All gas flow data are Qualified. At the start of the experiment, moisture in the outflow gas line increased to 200 ppmv then declined to less than 10 ppmv over a period of 5 days. This increase in moisture coincides with the initial heating of the experiment and drying of the system. Moisture slightly exceeded 10 ppmv three other times during the experiment. While these moisture values exceed the 10 ppmv threshold value, the reported measurements are considered accurate and to reflect moisture conditions in the capsule. All moisture data are Qualified. Graphite creep specimens are subjected to one of three loads, 393 lbf

  7. A Robust Distributed Multipoint Fiber Optic Gas Sensor System Based on AGC Amplifier Structure.

    Science.gov (United States)

    Zhu, Cunguang; Wang, Rende; Tao, Xuechen; Wang, Guangwei; Wang, Pengpeng

    2016-07-28

    A harsh environment-oriented distributed multipoint fiber optic gas sensor system realized by automatic gain control (AGC) technology is proposed. To improve the photoelectric signal reliability, the electronic variable gain can be modified in real time by an AGC closed-loop feedback structure to compensate for optical transmission loss which is caused by the fiber bend loss or other reasons. The deviation of the system based on AGC structure is below 4.02% when photoelectric signal decays due to fiber bending loss for bending radius of 5 mm, which is 20 times lower than the ordinary differential system. In addition, the AGC circuit with the same electric parameters can keep the baseline intensity of signals in different channels of the distributed multipoint sensor system at the same level. This avoids repetitive calibrations and streamlines the installation process.

  8. DC magnetron sputtering prepared Ag-C thin film anode for thin film lithium ion microbatteries

    International Nuclear Information System (INIS)

    Li, Y.; Tu, J.P.; Shi, D.Q.; Huang, X.H.; Wu, H.M.; Yuan, Y.F.; Zhao, X.B.

    2007-01-01

    An Ag-C thin film was prepared by DC magnetron co-sputtering, using pure silver and graphite as the targets. The microstructure and morphology of the deposited thin film were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Electrochemical performances of the Ag-C thin film anode were investigated by means of discharge/charge and cyclic voltammogram (CV) tests in model cells. The electrochemical impedance spectrum (EIS) characteristics and the chemical diffusion coefficient, D Li of the Ag-C thin film electrode at different discharging states were discussed. It was believed that the excellent cycling performance of the Ag-C electrode was ascribed to the good conductivity of silver and the volume stability of the thin film

  9. ALFALFA DISCOVERY OF THE MOST METAL-POOR GAS-RICH GALAXY KNOWN: AGC 198691

    Energy Technology Data Exchange (ETDEWEB)

    Hirschauer, Alec S.; Salzer, John J.; Rhode, Katherine L., E-mail: ash@astro.indiana.edu, E-mail: slaz@astro.indiana.edu, E-mail: krhode@indiana.edu [Department of Astronomy, Indiana University, 727 East Third Street, Bloomington, IN 47405 (United States); and others

    2016-05-10

    We present spectroscopic observations of the nearby dwarf galaxy AGC 198691. This object is part of the Survey of H i in Extremely Low-Mass Dwarfs project, which is a multi-wavelength study of galaxies with H i masses in the range of 10{sup 6}–10{sup 7.2} M {sub ⊙}, discovered by the Arecibo Legacy Fast ALFA (ALFALFA) survey. We have obtained spectra of the lone H ii region in AGC 198691 with the new high-throughput KPNO Ohio State Multi-Object Spectrograph on the Mayall 4 m, as well as with the Blue Channel spectrograph on the MMT 6.5 m telescope. These observations enable the measurement of the temperature-sensitive [O iii] λ 4363 line and hence the determination of a “direct” oxygen abundance for AGC 198691. We find this system to be an extremely metal-deficient (XMD) system with an oxygen abundance of 12+log(O/H) = 7.02 ± 0.03, making AGC 198691 the lowest-abundance star-forming galaxy known in the local universe. Two of the five lowest-abundance galaxies known have been discovered by the ALFALFA blind H i survey; this high yield of XMD galaxies represents a paradigm shift in the search for extremely metal-poor galaxies.

  10. Regulation of planar growth by the Arabidopsis AGC protein kinase UNICORN.

    Science.gov (United States)

    Enugutti, Balaji; Kirchhelle, Charlotte; Oelschner, Maxi; Torres Ruiz, Ramón Angel; Schliebner, Ivo; Leister, Dario; Schneitz, Kay

    2012-09-11

    The spatial coordination of growth is of central importance for the regulation of plant tissue architecture. Individual layers, such as the epidermis, are clonally propagated and structurally maintained by symmetric cell divisions that are oriented along the plane of the layer. The developmental control of this process is poorly understood. The simple cellular basis and sheet-like structure of Arabidopsis integuments make them an attractive model system to address planar growth. Here we report on the characterization of the Arabidopsis UNICORN (UCN) gene. Analysis of ucn integuments reveals localized distortion of planar growth, eventually resulting in an ectopic multicellular protrusion. In addition, ucn mutants exhibit ectopic growth in filaments and petals, as well as aberrant embryogenesis. We further show that UCN encodes an active AGC VIII kinase. Genetic, biochemical, and cell biological data suggest that UCN suppresses ectopic growth in integuments by directly repressing the KANADI transcription factor ABERRANT TESTA SHAPE. Our findings indicate that UCN represents a unique plant growth regulator that maintains planar growth of integuments by repressing a developmental regulator involved in the control of early integument growth and polarity.

  11. Exceptional disfavor for proline at the P + 1 position among AGC and CAMK kinases establishes reciprocal specificity between them and the proline-directed kinases.

    Science.gov (United States)

    Zhu, Guozhi; Fujii, Koichi; Belkina, Natalya; Liu, Yin; James, Michael; Herrero, Juan; Shaw, Stephen

    2005-03-18

    To precisely regulate critical signaling pathways, two kinases that phosphorylate distinct sites on the same protein substrate must have mutually exclusive specificity. Evolution could assure this by designing families of kinase such as basophilic kinases and proline-directed kinase with distinct peptide specificity; their reciprocal peptide specificity would have to be very complete, since recruitment of substrate allows phosphorylation of even rather poor phosphorylation sites in a protein. Here we report a powerful evolutionary strategy that assures distinct substrates for basophilic kinases (PKA, PKG and PKC (AGC) and calmodulin-dependent protein kinase (CAMK)) and proline-directed kinase, namely by the presence or absence of proline at the P + 1 position in substrates. Analysis of degenerate and non-degenerate peptides by in vitro kinase assays reveals that proline at the P + 1 position in substrates functions as a "veto" residue in substrate recognition by AGC and CAMK kinases. Furthermore, analysis of reported substrates of two typical basophilic kinases, protein kinase C and protein kinase A, shows the lowest occurrence of proline at the P + 1 position. Analysis of crystal structures and sequence conservation provides a molecular basis for this disfavor and illustrate its generality.

  12. Performance comparison of TCSC with TCPS and SSSC controllers in AGC of realistic interconnected multi-source power system

    Directory of Open Access Journals (Sweden)

    Javad Morsali

    2016-03-01

    Full Text Available The primary goals of employing series flexible ac transmission system (FACTS in automatic generation control (AGC studies of interconnected power systems are mitigating area frequency and tie-line power oscillations. This paper compares dynamic performance of thyristor controlled series capacitor (TCSC as damping controller with thyristor controlled phase shifter (TCPS and static synchronous series compensator (SSSC which are series FACTS damping controllers. Commonly used lead-lag controllers are used in structure of damping controllers. The effect of TCSC in tie-line power exchange is modeled mathematically based on the Taylor series expansion for small-signal load disturbance. The performance of the proposed TCSC controller in coordination with integral AGC is compared with cases of TCPS–AGC and SSSC–AGC. An improved particle swarm optimization (IPSO algorithm and integral of time multiplied squared error (ITSE performance index are used to design the damping controllers. A two-area power system having generations from reheat thermal, hydro, and gas units in each area is evaluated regarding nonlinearity effects of generation rate constraint (GRC and governor dead band (GDB. The simulations results in MATLAB/SIMULINK environment show that the proposed TCSC–AGC yields superior performance than others in damping of area frequencies and tie-line oscillations. Furthermore, sensitivity analyses are performed to show greater robustness of TCSC–AGC.

  13. Plasma membrane proteins Slm1 and Slm2 mediate activation of the AGC kinase Ypk1 by TORC2 and sphingolipids in S. cerevisiae.

    Science.gov (United States)

    Niles, Brad J; Powers, Ted

    2012-10-15

    The PH domain-containing proteins Slm1 and Slm2 were originally identified as substrates of the rapamycin-insensitive TOR complex 2 (TORC2) and as mediators of signaling by the lipid second messenger phosphatidyl-inositol-4,5-bisphosphate (PI4,5P2) in budding yeast S. cerevisiae. More recently, these proteins have been identified as critical effectors that facilitate phosphorylation and activation of the AGC kinases Ypk1 and Ypk2 by TORC2. Here, we review the molecular basis for this regulation as well as place it within the context of recent findings that have revealed Slm1/2 and TORC2-dependent phosphorylation of Ypk1 is coupled to the biosynthesis of complex sphingolipids and to their levels within the plasma membrane (PM) as well as other forms of PM stress. Together, these studies reveal the existence of an intricate homeostatic feedback mechanism, whereby the activity of these signaling components is linked to the biosynthesis of PM lipids according to cellular need.

  14. Zen law and features of liquidus-solidus curves in binary state diagrams based on elements VIIIA and IB of the periodic table

    Science.gov (United States)

    Potekaev, A. I.; Kondratyuk, A. A.; Porobova, S. A.; Klopotov, A. A.; Markova, T. N.; Kakushkin, Yu A.; Klopotov, V. D.

    2016-11-01

    The paper presents the analysis of binary state diagrams based on elements VIIIA and IB of the periodic table and crystal geometry parameters of solid solutions and intermetallic compositions. The analysis shows an explicit correlation between the type of the evolution of phase diagrams classified by Lebedev depending on the nature of atomic volume deviations observed in solid solutions and intermetallic compounds from Zen law.

  15. Binary phase diagrams based on elements VIIIA and IB periods of the D.I. Mendeleev’s table and features of crystallographic parameters

    Science.gov (United States)

    Potekaev, A. I.; Klopotov, A. A.; Porobova, S. A.; Klopotov, V. D.; Markova, T. N.; Imanaliev, M. I.

    2017-01-01

    The data obtained as a result of the analysis of crystallogeometric parameters and the structure of state diagrams of binary systems from elements VIIIA and IB periods of the D.I. Mendeleev’s table are presented. It is shown that the classification of the evolution of phase diagrams of binary systems by types, proposed by T.A. Lebedev, correlates with features of concentration dependences of the deviation of atomic volumes in solid solutions from Zen law.

  16. Hubble Space Telescope Imaging of the Ultra-compact High Velocity Cloud AGC 226067: A Stripped Remnant in the Virgo Cluster

    Energy Technology Data Exchange (ETDEWEB)

    Sand, D. J.; Crnojević, D. [Texas Tech University, Physics and Astronomy Department, Box 41051, Lubbock, TX 79409-1051 (United States); Seth, A. C. [Department of Physics and Astronomy, University of Utah, Salt Lake City, UT 84112 (United States); Spekkens, K. [Royal Military College of Canada, Department of Physics, P.O. Box 17000, Station Forces, Kingston, Ontario, K7K 7B4 (Canada); Strader, J. [Center for Data Intensive and Time Domain Astronomy, Department of Physics and Astronomy, Michigan State University, 567 Wilson Road, East Lansing, MI 48824 (United States); Adams, E. A. K. [ASTRON, Netherlands Institute for Radio Astronomy, Postbus 2, 7900 AA Dwingeloo (Netherlands); Caldwell, N.; Randall, S. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Guhathakurta, P. [UCO/Lick Observatory, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (United States); Kenney, J. [Yale University Astronomy Department, P.O. Box 208101, New Haven, CT 06520-8101 (United States); Simon, J. D. [Observatories of the Carnegie Institution for Science, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Toloba, E. [Department of Physics, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211 (United States); Willman, B., E-mail: david.sand@ttu.edu [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States)

    2017-07-10

    We analyze the optical counterpart to the ultra-compact high velocity cloud AGC 226067, utilizing imaging taken with the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope . The color–magnitude diagram of the main body of AGC 226067 reveals an exclusively young stellar population, with an age of ∼7–50 Myr, and is consistent with a metallicity of [Fe/H] ∼ −0.3 as previous work has measured via H ii region spectroscopy. Additionally, the color–magnitude diagram is consistent with a distance of D ≈ 17 Mpc, suggesting an association with the Virgo cluster. A secondary stellar system located ∼1.′6 (∼8 kpc) away in projection has a similar stellar population. The lack of an old red giant branch (≳5 Gyr) is contrasted with a serendipitously discovered Virgo dwarf in the ACS field of view (Dw J122147+132853), and the total diffuse light from AGC 226067 is consistent with the luminosity function of the resolved ∼7–50 Myr stellar population. The main body of AGC 226067 has a M {sub V} = −11.3 ± 0.3, or M {sub stars} = 5.4 ± 1.3 × 10{sup 4} M {sub ⊙} given the stellar population. We searched 20 deg{sup 2} of imaging data adjacent to AGC 226067 in the Virgo Cluster, and found two similar stellar systems dominated by a blue stellar population, far from any massive galaxy counterpart—if this population has star-formation properties that are similar to those of AGC 226067, it implies ∼0.1 M {sub ⊙} yr{sup −1} in Virgo intracluster star formation. Given its unusual stellar population, AGC 226067 is likely a stripped remnant and is plausibly the result of compressed gas from the ram pressure stripped M86 subgroup (∼350 kpc away in projection) as it falls into the Virgo Cluster.

  17. Genetic algorithm based PID controller design for a multi-area AGC ...

    African Journals Online (AJOL)

    user

    conventional AGC model the variations of frequency and tie-line power exchanges are ... Simulation results show that the proposed. GAPID Controller complies with NERC's standards. The performance studies have been carried out by using the MATLAB ..... The Indian power system is in the process of restructuring.

  18. Sensitive electrochemical sensor of tryptophan based on Ag-C core–shell nanocomposite modified glassy carbon electrode

    International Nuclear Information System (INIS)

    Mao Shuxian; Li Weifeng; Long Yumei; Tu Yifeng; Deng, Anping

    2012-01-01

    Graphical abstract: Ag-C and Colloidal carbon sphere modified glassy carbon electrodes were prepared. It was clear that the Ag-C/GCE exhibited enhanced electrocatalytic activity towards Trp, which could result from the synergistic effect between Ag core and carbon shell. The Ag-C/GCE showed excellent analytical properties in the determination of Trp. Highlights: ► The electrochemical behavior of Ag-C core–shell nanocomposite was firstly proposed. ► Ag-C/GC electrode exhibited favorable electrocatalytic properties towards Trp. ► The good electrocatalysis was due to the synergistic effect of Ag-core and C-shell. ► The Ag-C/GC electrode displayed excellent analytical properties in determining Trp. - Abstract: We here reported a simple electrochemical method for the detection of tryptophan (Trp) based on the Ag-C modified glassy carbon (Ag-C/GC) electrode. The Ag-C core–shell structured nanoparticles were synthesized using one-pot hydrothermal method and characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), and Fourier transform-infrared spectroscopy (FTIR). The electrochemical behaviors of Trp on Ag-C/GC electrode were investigated and exhibited a direct electrochemical process. The favorable electrochemical properties of Ag-C/GC electrode were attributed to the synergistic effect of the Ag core and carbon shell. The carbon shell cannot only protect Ag core but also contribute to the enhanced substrate accessibility and Trp-substrate interactions, while nano-Ag core can display good electrocatalytic activity to Trp at the same time. Under the optimum experimental conditions the oxidation peak current was linearly dependent on the Trp concentration in the range of 1.0 × 10 −7 to 1.0 × 10 −4 M with a detection limit of 4.0 × 10 −8 M (S/N = 3). In addition, the proposed electrode was applied for the determination of Trp concentration in real samples and satisfactory results were obtained. The technique offers

  19. Economic assessment model architecture for AGC/AVLIS selection

    International Nuclear Information System (INIS)

    Hoglund, R.L.

    1984-01-01

    The economic assessment model architecture described provides the flexibility and completeness in economic analysis that the selection between AGC and AVLIS demands. Process models which are technology-specific will provide the first-order responses of process performance and cost to variations in process parameters. The economics models can be used to test the impacts of alternative deployment scenarios for a technology. Enterprise models provide global figures of merit for evaluating the DOE perspective on the uranium enrichment enterprise, and business analysis models compute the financial parameters from the private investor's viewpoint

  20. Sensitive electrochemical sensor of tryptophan based on Ag-C core-shell nanocomposite modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Mao Shuxian [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123 (China); Li Weifeng, E-mail: liweifeng@suda.edu.cn [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123 (China); Long Yumei, E-mail: yumeilong@suda.edu.cn [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123 (China); Tu Yifeng; Deng, Anping [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123 (China)

    2012-08-13

    Graphical abstract: Ag-C and Colloidal carbon sphere modified glassy carbon electrodes were prepared. It was clear that the Ag-C/GCE exhibited enhanced electrocatalytic activity towards Trp, which could result from the synergistic effect between Ag core and carbon shell. The Ag-C/GCE showed excellent analytical properties in the determination of Trp. Highlights: Black-Right-Pointing-Pointer The electrochemical behavior of Ag-C core-shell nanocomposite was firstly proposed. Black-Right-Pointing-Pointer Ag-C/GC electrode exhibited favorable electrocatalytic properties towards Trp. Black-Right-Pointing-Pointer The good electrocatalysis was due to the synergistic effect of Ag-core and C-shell. Black-Right-Pointing-Pointer The Ag-C/GC electrode displayed excellent analytical properties in determining Trp. - Abstract: We here reported a simple electrochemical method for the detection of tryptophan (Trp) based on the Ag-C modified glassy carbon (Ag-C/GC) electrode. The Ag-C core-shell structured nanoparticles were synthesized using one-pot hydrothermal method and characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), and Fourier transform-infrared spectroscopy (FTIR). The electrochemical behaviors of Trp on Ag-C/GC electrode were investigated and exhibited a direct electrochemical process. The favorable electrochemical properties of Ag-C/GC electrode were attributed to the synergistic effect of the Ag core and carbon shell. The carbon shell cannot only protect Ag core but also contribute to the enhanced substrate accessibility and Trp-substrate interactions, while nano-Ag core can display good electrocatalytic activity to Trp at the same time. Under the optimum experimental conditions the oxidation peak current was linearly dependent on the Trp concentration in the range of 1.0 Multiplication-Sign 10{sup -7} to 1.0 Multiplication-Sign 10{sup -4} M with a detection limit of 4.0 Multiplication-Sign 10{sup -8} M (S/N = 3). In addition

  1. Genetic analysis of ectopic growth suppression during planar growth of integuments mediated by the Arabidopsis AGC protein kinase UNICORN

    Directory of Open Access Journals (Sweden)

    Enugutti Balaji

    2013-01-01

    Full Text Available Abstract Background The coordination of growth within a tissue layer is of critical importance for tissue morphogenesis. For example, cells within the epidermis undergo stereotypic cell divisions that are oriented along the plane of the layer (planar growth, thereby propagating the layered epidermal structure. Little is known about the developmental control that regulates such planar growth in plants. Recent evidence suggested that the Arabidopsis AGC VIII protein kinase UNICORN (UCN maintains planar growth by suppressing the formation of ectopic multicellular protrusions in several floral tissues including integuments. In the current model UCN controls this process during integument development by directly interacting with the ABERRANT TESTA SHAPE (ATS protein, a member of the KANADI (KAN family of transcription factors, thereby repressing its activity. Here we report on the further characterization of the UCN mechanism. Results Phenotypic analysis of flowers of ucn-1 plants impaired in floral homeotic gene activity revealed that any of the four floral whorls could produce organs carrying ucn-1 protrusions. The ectopic outgrowths of ucn integuments did not accumulate detectable signals of the auxin and cytokinin reporters DR5rev::GFP and ARR5::GUS, respectively. Furthermore, wild-type and ucn-1 seedlings showed similarly strong callus formation upon in vitro culture on callus-inducing medium. We also show that ovules of ucn-1 plants carrying the dominant ats allele sk21-D exhibited more pronounced protrusion formation. Finally ovules of ucn-1 ett-1 double mutants and ucn-1 ett-1 arf4-1 triple mutants displayed an additive phenotype. Conclusions These data deepen the molecular insight into the UCN-mediated control of planar growth during integument development. The presented evidence indicates that UCN downstream signaling does not involve the control of auxin or cytokinin homeostasis. The results also reveal that UCN interacts with ATS

  2. Genetic analysis of ectopic growth suppression during planar growth of integuments mediated by the Arabidopsis AGC protein kinase UNICORN.

    Science.gov (United States)

    Enugutti, Balaji; Schneitz, Kay

    2013-01-02

    The coordination of growth within a tissue layer is of critical importance for tissue morphogenesis. For example, cells within the epidermis undergo stereotypic cell divisions that are oriented along the plane of the layer (planar growth), thereby propagating the layered epidermal structure. Little is known about the developmental control that regulates such planar growth in plants. Recent evidence suggested that the Arabidopsis AGC VIII protein kinase UNICORN (UCN) maintains planar growth by suppressing the formation of ectopic multicellular protrusions in several floral tissues including integuments. In the current model UCN controls this process during integument development by directly interacting with the ABERRANT TESTA SHAPE (ATS) protein, a member of the KANADI (KAN) family of transcription factors, thereby repressing its activity. Here we report on the further characterization of the UCN mechanism. Phenotypic analysis of flowers of ucn-1 plants impaired in floral homeotic gene activity revealed that any of the four floral whorls could produce organs carrying ucn-1 protrusions. The ectopic outgrowths of ucn integuments did not accumulate detectable signals of the auxin and cytokinin reporters DR5rev::GFP and ARR5::GUS, respectively. Furthermore, wild-type and ucn-1 seedlings showed similarly strong callus formation upon in vitro culture on callus-inducing medium. We also show that ovules of ucn-1 plants carrying the dominant ats allele sk21-D exhibited more pronounced protrusion formation. Finally ovules of ucn-1 ett-1 double mutants and ucn-1 ett-1 arf4-1 triple mutants displayed an additive phenotype. These data deepen the molecular insight into the UCN-mediated control of planar growth during integument development. The presented evidence indicates that UCN downstream signaling does not involve the control of auxin or cytokinin homeostasis. The results also reveal that UCN interacts with ATS independently of an ATS/ETT complex required for integument

  3. Design and realization of an AEC&AGC system for the CCD aerial camera

    Science.gov (United States)

    Liu, Hai ying; Feng, Bing; Wang, Peng; Li, Yan; Wei, Hao yun

    2015-08-01

    An AEC and AGC(Automatic Exposure Control and Automatic Gain Control) system was designed for a CCD aerial camera with fixed aperture and electronic shutter. The normal AEC and AGE algorithm is not suitable to the aerial camera since the camera always takes high-resolution photographs in high-speed moving. The AEC and AGE system adjusts electronic shutter and camera gain automatically according to the target brightness and the moving speed of the aircraft. An automatic Gamma correction is used before the image is output so that the image is better for watching and analyzing by human eyes. The AEC and AGC system could avoid underexposure, overexposure, or image blurring caused by fast moving or environment vibration. A series of tests proved that the system meet the requirements of the camera system with its fast adjusting speed, high adaptability, high reliability in severe complex environment.

  4. A novel quasi-oppositional harmony search algorithm for AGC optimization of three-area multi-unit power system after deregulation

    Directory of Open Access Journals (Sweden)

    Chandan Kumar Shiva

    2016-03-01

    Full Text Available The present work addresses a decentralized, well tested three-area multi-unit power system for its automatic generation control (AGC after deregulation which is characterized by price-based market operation. To match with the actual deregulated environment, as prevailing in the real one, the market structure is kept generic enough enabling to capture all possibilities occurring in real-time day-to-day power environment. In accordance to the modifications, as done in the investigated three-area power system model, the concerned objective is to intensify the deregulated AGC operation followed by load disturbances. At the present platform, three different classes of case study results are postulated for the studied test system. The first two illustrate the behavior of unilateral and bilateral based power contract transactions while the third one considers the contract violation case as it exists in present time. The contractual agreement, instituted by DISCO participation matrix, is initialized to address the power transaction contracts. In this work, a novel quasi-oppositional harmony search (QOHS algorithm is explored and presented its significances in deregulated AGC operation. In the second phase of investigation, fast acting Sugeno fuzzy logic technique is explored for on-line, off-nominal operating conditions. For analysis purpose, both the qualitative and the quantitative aspects of the proposed QOHS are presented in reference to genetic algorithm (GA. Additionally, the sensitivity analysis is also performed to evaluate the performance of the proposed QOHS based controller. Simulation work reveals that the proposed QOHS may be, effectively, worked out to order to improve the deregulated AGC performance. It is also being observed that the proposed QOHS outperforms the GA in sense of deregulated AGC operation of power system.

  5. PEMBELAJARAN LAY UP SHOOT MENGGUNAKAN MEDIA AUDIO VISUAL BASIC LAY UP SHOOT UNTUK MENINGKATKAN HASILBELAJAR LAY UP SHOOT PADA SISWA KELAS VIIIA SMP KANISIUS PATI TAHUN 2013/2014

    Directory of Open Access Journals (Sweden)

    Frendy Nurochwan Febryanto

    2015-01-01

    Full Text Available The purpose of this study was to determine the learning lay up shoot using basic audiovisual media shoot lay ups can improve learning outcomes shoot lay ups in class VIIIA Starch Canisius junior year 2013/2014 . This study uses Classroom Action Research ( CAR. The technique of collecting data through observation and assessment of learning outcomes shoot basketball lay up. Data analysis techniques used in this research is descriptive . At the end of the first cycle activity of teachers in teaching basic techniques lay up shoot using audio-visual media reaches 76.19%, whereas at the end of the first cycle of student activity during the learning process lay up shoot using audio-visualmediareaches78.57%. At the end of the second cycle of activity of teachers in teaching basic techniques lay up shoot using audio-visual media reaches 85.71%, whereas at the end of the second cycle of activity of students during the learning process lay up shoot using audio-visual media reaches 92.86%. Based on the results of the study it can be concluded that learning the lay-up shoot using basic audiovisual media shoot lay ups can improve student learning outcomes at Canisius junior class VIIIA Pati year 2013/2014.

  6. Inhibition of secretary PLA₂--VRV-PL-VIIIa of Russell's viper venom by standard aqueous stem bark extract of Mangifera indica L.

    Science.gov (United States)

    Dhananjaya, B L; Sudarshan, S

    2015-03-01

    The aqueous extract of Mangifera indica is known to possess anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic phospholipases A2s, which are the most toxic and lethal component of snake venom is still unknown. Therefore, this study was carried out to evaluate the modulatory effect of standard aqueous bark extract of M. indica on VRV-PL-VIIIa of Indian Russells viper venom. Mangifera indica extract dose dependently inhibited the GIIB sPLA2 (VRV-PL-VIIIa) activity with an IC50 value of 6.8±0.3 μg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 96% at ~40 μg/ml concentration. Further, M. indica extract at different concentrations (0-50 μg/ml) inhibited the edema formed in a dose dependent manner. It was found that there was no relieve of inhibitory effect of the extract when examined as a function of increased substrate and calcium concentration. The inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inducing activities. As the inhibition is independent of substrate, calcium concentration and was irreversible, it can be concluded that M. indica extracts mode of inhibition could be due to direct interaction of components present in the extract with PLA2 enzyme. In conclusion, the aqueous extract of M. indica effectively inhibits svPLA2 (Snake venom phospholipase A2) enzymatic and its associated toxic activities, which substantiate its anti-snake venom properties. Further in-depth studies are interesting to known on the role and mechanism of the principal inhibitory constituents present in the extract, so as to develop them into potent anti-snake venom and as an anti-inflammatory agent.

  7. AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Yu [Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Department of General Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang 832008 (China); Niu, Jianhua [Department of General Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang 832008 (China); Shen, Yun [Department of Gastroenterology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang 832008 (China); Li, Dongmei [Department of Biochemistry and Molecular Biology, School of Medicine, Shihezi University, Shihezi, Xinjiang 832008 (China); Peng, Xinyu, E-mail: pppengxinyu@sina.com [Department of General Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang 832008 (China); Wu, Xiangwei, E-mail: wuxiangweiys@126.com [Department of General Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang 832008 (China)

    2016-09-09

    The AGC kinase family is important cell proliferation and survival. Dysregulation of this family contributes to gastric cancer progression. Here, we evaluated the potential activity of AT13148, a first-in-class multi-AGC kinase inhibitor, against gastric cancer cells. Our results showed that AT13148 exerted potent cytotoxic and anti-proliferative activities against a panel human gastric cancer cell lines (HGC-27, AGS, SNU-601, N87 and MKN-28), possibly via inducing cancer cell apoptotic death. Apoptosis inhibition by the Caspase blockers dramatically attenuated AT13148-caused cytotoxicity against gastric cancer cells. Intriguingly, same AT13148 treatment was not cytotoxic/pro-apoptotic to the non-cancerous human gastric epithelial GEC-1 cells. At the signaling level, AT13148 treatment in gastric cancer cells dramatically suppressed activation of multiple AGC kinases, including Akt (at p-Thr-308), p70S6 kinase (p70S6K), glycogen synthase kinase 3β (GSK-3β) and p90 ribosomal S6 kinase (RSK). Our in vivo studies demonstrated that daily oral gavage of AT13148 at well-tolerated doses significantly inhibited HGC27 xenograft tumor growth in nude mice. AGC activity was also dramatically decreased in AT13148-administrated HGC27 tumors. Therefore, targeting AGC kinases by AT13148 demonstrates superior anti-gastric cancer activity both in vitro and in vivo. The preclinical results of this study support the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. - Highlights: • AT13148 is cytotoxic and anti-proliferative to human gastric cancer cells. • AT13148 induces gastric cancer cell apoptotic death, inhibited by Caspase inhibitors. • AT13148 inactivates multiple AGC kinases in human gastric cancer cells. • AT13148 oral administration suppresses HGC27 xenograft growth in nude mice. • AT13148 oral administration inhibits multiple AGC kinases in HGC27 xenograft tumors.

  8. Optimized multi area AGC simulation in restructured power systems

    International Nuclear Information System (INIS)

    Bhatt, Praghnesh; Roy, Ranjit; Ghoshal, S.P.

    2010-01-01

    In this paper, the traditional automatic generation control loop with modifications is incorporated for simulating automatic generation control (AGC) in restructured power system. Federal energy regulatory commission (FERC) encourages an open market system for price based operation. FERC has issued a notice for proposed rulemaking of various ancillary services. One of these ancillary services is load following with frequency control which comes broadly under Automatic Generation Control in deregulated regime. The concept of DISCO participation matrix is used to simulate the bilateral contracts in the three areas and four area diagrams. Hybrid particle swarm optimization is used to obtain optimal gain parameters for optimal transient performance. (author)

  9. Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation

    DEFF Research Database (Denmark)

    Hauge, Camilla; Antal, Torben L; Hirschberg, Daniel

    2007-01-01

    investigated the role of the third, so-called turn motif phosphate, also located in the tail, in the AGC kinases PKB, S6K, RSK, MSK, PRK and PKC. We report cooperative action of the HM phosphate and the turn motif phosphate, because it binds a phosphoSer/Thr-binding site above the glycine-rich loop within...

  10. AGC-4 Experiment Irradiation Monitoring Data Qualification Interim Report

    International Nuclear Information System (INIS)

    Hull, Laurence Charles

    2016-01-01

    The Graphite Technology Development Program is running a series of six experiments to quantify the effects of irradiation on nuclear grade graphite. The fourth experiment, Advanced Graphite Creep 4 (AGC 4), began with Advanced Test Reactor (ATR) cycle 157D on May 30, 2015, and has been irradiated for two cycles. The capsule was removed from the reactor after ATR cycle 158A, which ended on January 2, 2016, due to interference with another experiment. Irradiation will resume when the interfering experiment is removed from the reactor. This report documents qualification of AGC 4 experiment irradiation monitoring data for use by the Advanced Reactor Technologies (ART) Technology Development Office (TDO) Program for research and development activities required to design and license the first HTR nuclear plant. Qualified data meet the requirements for use as described in the experiment planning and quality assurance documents. Failed data do not meet the requirements and provide no useable information. Trend data may not meet all requirements, but still provide some useable information. Use of Trend data requires assessment of how any deficiencies affect a particular use of the data. All thermocouples (TCs) have functioned throughout the AGC-4 experiment. All temperature data are Qualified for use by the ART TDO Program. Argon, helium, and total gas flow data were within expected ranges and are Qualified for use by the ART TDO Program. Discharge gas line moisture values were consistently low during cycle 157D. At the start of cycle 158A, gas moisture briefly spiked to over 600 ppmv and then declined throughout the cycle. Moisture values are within the measurement range of the instrument and are Qualified for use by the ART TDO Program. Graphite creep specimens were subjected to one of three loads, 393, 491, or 589 lbf. For a brief period during cycle 157D between 12:19 on June 2, 2015 and 08:23 on June 11, 2015 the load cells were wired incorrectly resulting in missing

  11. AGC-4 Experiment Irradiation Monitoring Data Qualification Interim Report

    Energy Technology Data Exchange (ETDEWEB)

    Hull, Laurence Charles [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-08-01

    The Graphite Technology Development Program is running a series of six experiments to quantify the effects of irradiation on nuclear grade graphite. The fourth experiment, Advanced Graphite Creep 4 (AGC 4), began with Advanced Test Reactor (ATR) cycle 157D on May 30, 2015, and has been irradiated for two cycles. The capsule was removed from the reactor after ATR cycle 158A, which ended on January 2, 2016, due to interference with another experiment. Irradiation will resume when the interfering experiment is removed from the reactor. This report documents qualification of AGC 4 experiment irradiation monitoring data for use by the Advanced Reactor Technologies (ART) Technology Development Office (TDO) Program for research and development activities required to design and license the first HTR nuclear plant. Qualified data meet the requirements for use as described in the experiment planning and quality assurance documents. Failed data do not meet the requirements and provide no useable information. Trend data may not meet all requirements, but still provide some useable information. Use of Trend data requires assessment of how any deficiencies affect a particular use of the data. All thermocouples (TCs) have functioned throughout the AGC-4 experiment. All temperature data are Qualified for use by the ART TDO Program. Argon, helium, and total gas flow data were within expected ranges and are Qualified for use by the ART TDO Program. Discharge gas line moisture values were consistently low during cycle 157D. At the start of cycle 158A, gas moisture briefly spiked to over 600 ppmv and then declined throughout the cycle. Moisture values are within the measurement range of the instrument and are Qualified for use by the ART TDO Program. Graphite creep specimens were subjected to one of three loads, 393, 491, or 589 lbf. For a brief period during cycle 157D between 12:19 on June 2, 2015 and 08:23 on June 11, 2015 the load cells were wired incorrectly resulting in missing

  12. [Effect of American Ginseng Capsule on the liver oxidative injury and the Nrf2 protein expression in rats exposed by electromagnetic radiation of frequency of cell phone].

    Science.gov (United States)

    Luo, Ya-ping; Ma, Hui-Rong; Chen, Jing-Wei; Li, Jing-Jing; Li, Chun-xiang

    2014-05-01

    To observe the effect of American Ginseng Capsule (AGC) on the liver oxidative injury and the Nrf2 protein expression in the liver tissue of rats exposed by 900 MHz cell phone electromagnetic radiation. Totally 40 male SD rats were randomly divided into the normal control group, the model group, the Shuifei Jibin Capsule (SJC) group, and the AGC group,10 in each group. Rats in the normal control group were not irradiated. Rats in the rest three groups were exposed by imitated 900 MHz cellular phone for 4 h in 12 consecutive days. Meanwhile, rats in the SJC group and the AGC group were intragastrically administrated with suspension of SJC and AGC (1 mL/200 g body weight) respectively. Normal saline was administered to rats in the normal control group and the model group. The histolomorphological changes of the liver tissue were observed by HE staining. Contents of malonic dialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX)were detected by colorimetry. The Nrf2 protein expression of hepatocytes was detected by immunohistochemical assay and Western blot. Compared with the normal control group, hepatocyte nucleus was atrophied or partially disappeared, the contents of liver MDA and Nrf2 protein obviously increased (P electromagnetic radiation induced by 900 MHz cell phone could affect the expression of Nrf2 protein, induce oxidative injury, and induce abnormal morphology of liver cells. SJC and AGC could promote the morphological recovery of the liver cells. Its mechanism might be related to affecting the expression of Nrf2 protein and attenuating oxidative damage of liver cells.

  13. Flexible Ag-C60 nano-biosensors based on surface plasmon coupled emission for clinical and forensic applications.

    Science.gov (United States)

    Mulpur, Pradyumna; Yadavilli, Sairam; Mulpur, Praharsha; Kondiparthi, Neeharika; Sengupta, Bishwambhar; Rao, Apparao M; Podila, Ramakrishna; Kamisetti, Venkataramaniah

    2015-10-14

    The relatively low sensitivity of fluorescence detection schemes, which are mainly limited by the isotropic nature of fluorophore emission, can be overcome by utilizing surface plasmon coupled emission (SPCE). In this study, we demonstrate directional emission from fluorophores on flexible Ag-C60 SPCE sensor platforms for point-of-care sensing, in healthcare and forensic sensing scenarios, with at least 10 times higher sensitivity than traditional fluorescence sensing schemes. Adopting the highly sensitive Ag-C60 SPCE platform based on glass and novel low-cost flexible substrates, we report the unambiguous detection of acid-fast Mycobacterium tuberculosis (Mtb) bacteria at densities as low as 20 Mtb mm(-2); from non-acid-fast bacteria (e.g., E. coli and S. aureus), and the specific on-site detection of acid-fast sperm cells in human semen samples. In combination with the directional emission and high-sensitivity of SPCE platforms, we also demonstrate the utility of smartphones that can replace expensive and cumbersome detectors to enable rapid hand-held detection of analytes in resource-limited settings; a much needed critical advance to biosensors, for developing countries.

  14. AGC-2 Irradiation Report

    Energy Technology Data Exchange (ETDEWEB)

    Rohrbaugh, David Thomas [Idaho National Lab. (INL), Idaho Falls, ID (United States); Windes, William [Idaho National Lab. (INL), Idaho Falls, ID (United States); Swank, W. David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-06-01

    components longer useful lifetimes within the core. Determining the irradiation creep rates of nuclear grade graphites is critical for determining the useful lifetime of graphite components and is a major component of the Advanced Graphite Creep (AGC) experiment.

  15. La liberalización educativa en el marco del AGCS/GATS: Analizando el estado actual de las negociaciones. Educational liberalization under the AGCS/GATS: Analyzing the current state of negotiations

    Directory of Open Access Journals (Sweden)

    Antoni Verger

    2006-03-01

    Full Text Available En este artículo se analizan los factores que inciden en la liberalización comercial del sector de servicios educativos en el marco del Acuerdo General de Comercio Servicios (AGCS. Para ello se examina con detalle la metodología de la negociación del Acuerdo y se revisan los compromisos consolidados por los países miembros de la OMC en materia de servicios educativos. También se analizan los resultados provisionales de la vigente ronda de servicios (GATS2000 la cual se encuentra todavía en proceso de negociación. Las fuentes de datos primarias a partir de las cuales se interpretan los resultados de las negociaciones del AGCS consisten en entrevistas a diferentes delegaciones de los países miembros de la OMC, documentos de posición de algunas delegaciones y documentos de análisis del Consejo de Comercio de Servicios de la OMC The aim of this article is to analyze the factors that influence the commercial liberalization of educational services in the General Agreement of Trade in Services (GATS framework. First at all, we examine closely the negotiation methodology of the Agreement, as well as we check the commitments of the WTO members in the educational sector. On the other hand we analyze the provisional results of the last round of services (GATS2000 which is still being negotiated. The primary data sources are interviews to different delegations of the countries members of the WTO, documents of position of some delegations and documents of analysis of the “Council of Trade in Services” of the WTO.

  16. Double-differential recording and AGC using microcontrolled variable gain ASIC.

    Science.gov (United States)

    Rieger, Robert; Deng, Shin-Liang

    2013-01-01

    Low-power wearable recording of biopotentials requires acquisition front-ends with high common-mode rejection for interference suppression and adjustable gain to provide an optimum signal range to a cascading analogue-to-digital stage. A microcontroller operated double-differential (DD) recording setup and automatic gain control circuit (AGC) are discussed which reject common-mode interference and provide tunable gain, thus compensating for imbalance and variation in electrode interface impedance. Custom-designed variable gain amplifiers (ASIC) are used as part of the recording setup. The circuit gain and balance is set by the timing of microcontroller generated clock signals. Measured results are presented which confirm that improved common-mode rejection is achieved compared to a single differential amplifier in the presence of input network imbalance. Practical measured examples further validate gain control suitable for biopotential recording and power-line rejection for wearable ECG and EMG recording. The prototype front-end consumes 318 μW including amplifiers and microcontroller.

  17. AGC of a multi-area power system under deregulated environment using redox flow batteries and interline power flow controller

    Directory of Open Access Journals (Sweden)

    Tulasichandra Sekhar Gorripotu

    2015-12-01

    Full Text Available In this paper, Proportional Integral Derivative with Filter (PIDF is proposed for Automatic Generation Control (AGC of a multi-area power system in deregulated environment. Initially, a two area four units thermal system without any physical constraints is considered and the gains of the PIDF controller are optimized employing Differential Evolution (DE algorithm using ITAE criterion. The superiority of proposed DE optimized PIDF controller over Fuzzy Logic controller is demonstrated. Then, to further improve the system performance, an Interline Power Flow Controller (IPFC is placed in the tie-line and Redox Flow Batteries (RFB is considered in the first area and the controller parameters are tuned. Additionally, to get an accurate insight of the AGC problem, important physical constraints such as Time Delay (TD and Generation Rate Constraints (GRC are considered and the controller parameters are retuned. The performance of proposed controller is evaluated under different operating conditions that take place in a deregulated power market. Further, the proposed approach is extended to a two area six units hydro thermal system. Finally, sensitivity analysis is performed by varying the system parameters and operating load conditions from their nominal values.

  18. The power grid AGC frequency bias coefficient online identification method based on wide area information

    Science.gov (United States)

    Wang, Zian; Li, Shiguang; Yu, Ting

    2015-12-01

    This paper propose online identification method of regional frequency deviation coefficient based on the analysis of interconnected grid AGC adjustment response mechanism of regional frequency deviation coefficient and the generator online real-time operation state by measured data through PMU, analyze the optimization method of regional frequency deviation coefficient in case of the actual operation state of the power system and achieve a more accurate and efficient automatic generation control in power system. Verify the validity of the online identification method of regional frequency deviation coefficient by establishing the long-term frequency control simulation model of two-regional interconnected power system.

  19. AGC controlled scintillation probe for industrial application; Sonda scyntylacyjna do zastosowan przemyslowych stabilizowana ukladem ARW

    Energy Technology Data Exchange (ETDEWEB)

    Mirowicz, J.; Machaj, B.

    1997-12-31

    The instrument to measure Am-241 and Cs-137 radiation consisting of scintillation probe, two measuring channels and a photomultiplier automatic gain control circuit was investigated in respect to its operating stability and measuring errors. The instability of the count rate does not exceed 0.15 % of the PM gain variation {+-}50 % relative to nominal one. The effective time constant of the AGC loop {<=}1 sec, and after the mains is interrupted and switched again the instrument restarts its operation and stabilizes the PM gain in the period not longer than 10 sec since the moment the mains is switched on. (author). 3 refs, 7 figs, 7 tabs.

  20. Dissociation of activated protein C functions by elimination of protein S cofactor enhancement.

    LENUS (Irish Health Repository)

    Harmon, Shona

    2008-11-07

    Activated protein C (APC) plays a critical anticoagulant role in vivo by inactivating procoagulant factor Va and factor VIIIa and thus down-regulating thrombin generation. In addition, APC bound to the endothelial cell protein C receptor can initiate protease-activated receptor-1 (PAR-1)-mediated cytoprotective signaling. Protein S constitutes a critical cofactor for the anticoagulant function of APC but is not known to be involved in regulating APC-mediated protective PAR-1 signaling. In this study we utilized a site-directed mutagenesis strategy to characterize a putative protein S binding region within the APC Gla domain. Three single amino acid substitutions within the APC Gla domain (D35T, D36A, and A39V) were found to mildly impair protein S-dependent anticoagulant activity (<2-fold) but retained entirely normal cytoprotective activity. However, a single amino acid substitution (L38D) ablated the ability of protein S to function as a cofactor for this APC variant. Consequently, in assays of protein S-dependent factor Va proteolysis using purified proteins or in the plasma milieu, APC-L38D variant exhibited minimal residual anticoagulant activity compared with wild type APC. Despite the location of Leu-38 in the Gla domain, APC-L38D interacted normally with endothelial cell protein C receptor and retained its ability to trigger PAR-1 mediated cytoprotective signaling in a manner indistinguishable from that of wild type APC. Consequently, elimination of protein S cofactor enhancement of APC anticoagulant function represents a novel and effective strategy by which to separate the anticoagulant and cytoprotective functions of APC for potential therapeutic gain.

  1. A CMOS low power, process/temperature variation tolerant RSSI with an integrated AGC loop

    International Nuclear Information System (INIS)

    Lei Qianqian; Lin Min; Shi Yin

    2013-01-01

    A low voltage low power CMOS limiter and received signal strength indicator (RSSI) with an integrated automatic gain control (AGC) loop for a short-distance receiver are implemented in SMIC 0.13 μm CMOS technology. The RSSI has a dynamic range of more than 60 dB and the RSSI linearity error is within ±0.5 dB for an input power from −65 to −8 dBm. The RSSI output voltage is from 0.15 to 1 V and the slope of the curve is 14.17 mV/dB while consuming 1.5 mA (I and Q paths) from a 1.2 V supply. Auto LNA gain mode selection with a combined RSSI function is also presented. Furthermore, with the compensation circuit, the proposed RSSI shows good temperature-independent and good robustness against process variation characteristics. (semiconductor integrated circuits)

  2. ARALAR/AGC1 deficiency, a neurodevelopmental disorder with severe impairment of neuronal mitochondrial respiration, does not produce a primary increase in brain lactate.

    Science.gov (United States)

    Juaristi, Inés; García-Martín, María L; Rodrigues, Tiago B; Satrústegui, Jorgina; Llorente-Folch, Irene; Pardo, Beatriz

    2017-07-01

    ARALAR/AGC1 (aspartate-glutamate mitochondrial carrier 1) is an important component of the NADH malate-aspartate shuttle (MAS). AGC1-deficiency is a rare disease causing global cerebral hypomyelination, developmental arrest, hypotonia, and epilepsy (OMIM ID #612949); the aralar-KO mouse recapitulates the major findings in humans. This study was aimed at understanding the impact of ARALAR-deficiency in brain lactate levels as a biomarker. We report that lactate was equally abundant in wild-type and aralar-KO mouse brain in vivo at postnatal day 17. We find that lactate production upon mitochondrial blockade depends on up-regulation of lactate formation in astrocytes rather than in neurons. However, ARALAR-deficiency decreased cell respiration in neurons, not astrocytes, which maintained unchanged respiration and lactate production. As the primary site of ARALAR-deficiency is neuronal, this explains the lack of accumulation of brain lactate in ARALAR-deficiency in humans and mice. On the other hand, we find that the cytosolic and mitochondrial components of the glycerol phosphate shuttle are present in astrocytes with similar activities. This suggests that glycerol phosphate shuttle is the main NADH shuttle in astrocytes and explains the absence of effects of ARALAR-deficiency in these cells. © 2017 International Society for Neurochemistry.

  3. Tightness and suitability evaluation of abandoned salt caverns served as hydrocarbon energies storage under adverse geological conditions (AGC)

    International Nuclear Information System (INIS)

    Wei, Liu; Jie, Chen; Deyi, Jiang; Xilin, Shi; Yinping, Li; Daemen, J.J.K.; Chunhe, Yang

    2016-01-01

    Highlights: • Tightness conditions are set to assess use of old caverns for hydrocarbons storage. • Gas seepage and tightness around caverns are numerically simulated under AGC. • κ of interlayers act as a key factor to affect the tightness and use of salt cavern. • The threshold upper permeability of interlayers is proposed for storing oil and gas. • Three types of real application are introduced by using the tightness conditions. - Abstract: In China, the storage of hydrocarbon energies is extremely insufficient partially due to the lack of storage space, but on the other side the existence of a large number of abandoned salt caverns poses a serious threat to safety and geological environments. Some of these caverns, defined as abandoned caverns under adverse geological conditions (AGC), are expected to store hydrocarbon energies (natural gas or crude oil) to reduce the risk of potential disasters and simultaneously support the national strategic energy reserve of China. Herein, a series of investigations primarily related to the tightness and suitability of the caverns under AGC is performed. Laboratory measurements to determine the physical and mechanical properties as well as porosity and permeability of bedded salt cores from a near target cavern are implemented to determine the petro-mechanical properties and basic parameters for further study. The results show that the mechanical properties of the bedded rock salts are satisfactory for the stability of caverns. The interface between the salt and interlayers exhibits mechanical properties that are between those of rock salt and interlayers and in particular is not a weak zone. The silty mudstone interlayers have relatively high porosity and permeability, likely due to their low content of clay minerals and the presence of halite-filled cracks. The conditions for evaluating the tightness and suitability of a cavern for storing hydrocarbons are proposed, including “No tensile stress,”

  4. Direct electrochemistry and electrocatalytic behavior of hemoglobin entrapped in Ag@C nanocables/gold nanoparticles nanocomposites film.

    Science.gov (United States)

    Hu, Xiao-Wei; Mao, Chang-Jie; Song, Ji-Ming; Niu, He-Lin; Zhang, Sheng-Yi; Cui, Rong-Jing

    2012-10-01

    Direct electrochemistry of hemoglobin (Hb) was successfully fabricated by immobilizing Hb on the nanocomposites containing of Ag@C nanocables and Au nanoparticles (AuNPs) modified glassy carbon electrode (GCE). The immobilized Hb retained its biological activity and shown high catalytic activities to the reduction of H2O2 by circular dicroism (CD) spectrum, fourier transform infrared (FT-IR) spectrum and cyclic voltammetry (CV). Experimental conditions such as scan rate and pH Value were studied and optimized. The results indicated that the resulting biosensor are linear to the concentrations of H2O2 in the ranges of 6.67 x 10(-7)-2.40 x 10(5) M, and the detection limit is 2.02 x 10(-7) M. The electrochemical biosensor has also high stability and good reproducibility.

  5. Structure of Human G Protein-Coupled Receptor Kinase 2 in Complex with the Kinase Inhibitor Balanol

    Energy Technology Data Exchange (ETDEWEB)

    Tesmer, John J.G.; Tesmer, Valerie M.; Lodowski, David T.; Steinhagen, Henning; Huber, Jochen (Sanofi); (Michigan); (Texas)

    2010-07-19

    G protein-coupled receptor kinase 2 (GRK2) is a pharmaceutical target for the treatment of cardiovascular diseases such as congestive heart failure, myocardial infarction, and hypertension. To better understand how nanomolar inhibition and selectivity for GRK2 might be achieved, we have determined crystal structures of human GRK2 in complex with G{beta}{gamma} in the presence and absence of the AGC kinase inhibitor balanol. The selectivity of balanol among human GRKs is assessed.

  6. 尝试使用AGC600DID-C2H2气相色谱仪分析粗氪氙中的氪、氙%Trial use of AGC600DID-C2H2 gas chromatograph to analyze krypton and xenon in crude krypton and xenon

    Institute of Scientific and Technical Information of China (English)

    龙雨

    2013-01-01

    使用现有的AGC600DID-C2H2气相色谱仪,对鄂钢制氧厂KDON-35000/40600型空分设备生产的粗氪氙产品质量的检测进行了一次成功的尝试.介绍分析仪的配置、对气路的改进措施和检测调试情况,阐述为提高检测的准确性而在仪器和分析方法上需做的改进建议.

  7. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

    DEFF Research Database (Denmark)

    Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas

    2009-01-01

    of numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites......, the activation loop and the Z/TM in the C-terminal extension. We provide evidence that phosphorylation of the Z/TM site of PRK2 inhibits its interaction with PDK1. Our studies further provide a mechanistic model to explain different steps in the docking interaction and regulation. Interestingly, we found...... that the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2 and do...

  8. Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression.

    Science.gov (United States)

    Isakov, Noah

    2018-02-01

    The AGC family of serine/threonine kinases (PKA, PKG, PKC) includes more than 60 members that are critical regulators of numerous cellular functions, including cell cycle and differentiation, morphogenesis, and cell survival and death. Mutation and/or dysregulation of AGC kinases can lead to malignant cell transformation and contribute to the pathogenesis of many human diseases. Members of one subgroup of AGC kinases, the protein kinase C (PKC), have been singled out as critical players in carcinogenesis, following their identification as the intracellular receptors of phorbol esters, which exhibit tumor-promoting activities. This observation attracted the attention of researchers worldwide and led to intense investigations on the role of PKC in cell transformation and the potential use of PKC as therapeutic drug targets in cancer diseases. Studies demonstrated that many cancers had altered expression and/or mutation of specific PKC genes. However, the causal relationships between the changes in PKC gene expression and/or mutation and the direct cause of cancer remain elusive. Independent studies in normal cells demonstrated that activation of PKC is essential for the induction of cell activation and proliferation, differentiation, motility, and survival. Based on these observations and the general assumption that PKC isoforms play a positive role in cell transformation and/or cancer progression, many PKC inhibitors have entered clinical trials but the numerous attempts to target PKC in cancer has so far yielded only very limited success. More recent studies demonstrated that PKC function as tumor suppressors, and suggested that future clinical efforts should focus on restoring, rather than inhibiting, PKC activity. The present manuscript provides some historical perspectives on the tumor promoting function of PKC, reviewing some of the observations linking PKC to cancer progression, and discusses the role of PKC in the pathogenesis of cancer diseases and its

  9. Problemática jurídica en torno a los principios fundamentales del Sistema Multilateral de Comercio, en el Acuerdo General sobre el Comercio de Servicios, AGCS

    OpenAIRE

    Velasteguí Ayala, Ximena del Rocío

    2013-01-01

    El Acuerdo General sobre el Comercio de Servicios, AGCS, negociado en la Ronda de Uruguay, constituye en el primer acopio de normas internacionales en materia de comercio internacional de servicios, sector que evidencia un crecimiento acelerado en respuesta al rápido crecimiento de la economía mundial, producto de la evolución de las comunicaciones. Con el presente trabajo de investigación se pretende conocer la problemática jurídica que surge en torno a los principales princip...

  10. Comparison of intelligent fuzzy based AGC coordinated PID controlled and PSS controlled AVR system

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, V. [Department of Electrical Engineering, Asansol Engineering College, Asansol, West Bengal (India); Ghoshal, S.P. [Department of Electrical Engineering, National Institute of Technology, Durgapur, West Bengal (India)

    2007-11-15

    This paper attempts to investigate the performance of intelligent fuzzy based coordinated control of the Automatic Generation Control (AGC) loop and the excitation loop equipped with Proportional Integral Derivative (PID) controlled Automatic Voltage Regulator (AVR) system and Power System Stabilizer (PSS) controlled AVR system. The work establishes that PSS controlled AVR system is much more robust in dynamic performance of the system over a wide range of system operating configurations. Thus, it is revealed that PSS equipped AVR is much more superior than PID equipped AVR in damping the oscillation resulting in improved transient response. The paper utilizes a novel class of Particle Swarm Optimization (PSO) termed as Craziness based Particle Swarm Optimization (CRPSO) as optimizing tool to get optimal tuning of PSS parameters as well as the gains of PID controllers. For on-line, off-nominal operating conditions Takagi Sugeno Fuzzy Logic (TSFL) has been applied to obtain the off-nominal optimal gains of PID controllers and parameters of PSS. Implementation of TSFL helps to achieve very fast dynamic response. Fourth order model of generator with AVR and high gain thyristor excitation system is considered for PSS controlled system while normal gain exciter is considered for PID controlled system. Simulation study also reveals that with high gain exciter, PID control is not at all effective. Transient responses are achieved by using modal analysis. (author)

  11. L-malate enhances the gene expression of carried proteins and antioxidant enzymes in liver of aged rats.

    Science.gov (United States)

    Zeng, X; Wu, J; Wu, Q; Zhang, J

    2015-01-01

    Previous studies in our laboratory reported L-malate as a free radical scavenger in aged rats. To investigate the antioxidant mechanism of L-malate in the mitochondria, we analyzed the change in gene expression of two malate-aspartate shuttle (MAS)-related carried proteins (AGC, aspartate/glutamate carrier and OMC, oxoglutarate/malate carrier) in the inner mitochondrial membrane, and three antioxidant enzymes (CAT, SOD, and GSH-Px) in the mitochondria. The changes in gene expression of these proteins and enzymes were examined by real-time RT-PCR in the heart and liver of aged rats treated with L-malate. L-malate was orally administered in rats continuously for 30 days using a feeding atraumatic needle. We found that the gene expression of OMC and GSH-Px mRNA in the liver increased by 39 % and 38 %, respectively, in the 0.630 g/kg L-malate treatment group than that in the control group. The expression levels of SOD mRNA in the liver increased by 39 %, 56 %, and 78 % in the 0.105, 0.210, and 0.630 g/kg L-malate treatment groups, respectively. No difference were observed in the expression levels of AGC, OMC, CAT, SOD, and GSH-Px mRNAs in the heart of rats between the L-malate treatment and control groups. These results predicted that L-malate may increase the antioxidant capacity of mitochondria by enhancing the expression of mRNAs involved in the MAS and the antioxidant enzymes.

  12. Aptamer Recognition Induced Target-Bridged Strategy for Proteins Detection Based on Magnetic Chitosan and Silver/Chitosan Nanoparticles Using Surface-Enhanced Raman Spectroscopy.

    Science.gov (United States)

    He, Jincan; Li, Gongke; Hu, Yuling

    2015-11-03

    Poor selectivity and biocompability remain problems in applying surface-enhanced Raman spectroscopy (SERS) for direct detection of proteins due to similar spectra of most proteins and overlapping Raman bands in complex mixtures. To solve these problems, an aptamer recognition induced target-bridged strategy based on magnetic chitosan (MCS) and silver/chitosan nanoparticles (Ag@CS NPs) using SERS was developed for detection of protein benefiting from specific affinity of aptamers and biocompatibility of chitosan (CS). In this process, one aptamer (or antibody) modified MCS worked as capture probes through the affinity binding site of protein. The other aptamer modified Raman report molecules encapsulated Ag@CS NPs were used as SERS sensing probes based on the other binding site of protein. The sandwich complexes of aptamer (antibody)/protein/aptamer were separated easily with a magnet from biological samples, and the concentration of protein was indirectly reflected by the intensity variation of SERS signal of Raman report molecules. To explore the universality of the strategy, three different kinds of proteins including thrombin, platelet derived growth factor BB (PDGF BB) and immunoglobulin E (lgE) were investigated. The major advantages of this aptamer recognition induced target-bridged strategy are convenient operation with a magnet, stable signal expressing resulting from preventing loss of report molecules with the help of CS shell, and the avoidance of slow diffusion-limited kinetics problems occurring on a solid substrate. To demonstrate the feasibility of the proposed strategy, the method was applied to detection of PDGF BB in clinical samples. The limit of detection (LOD) of PDGF BB was estimated to be 3.2 pg/mL. The results obtained from human serum of healthy persons and cancer patients using the proposed strategy showed good agreement with that of the ELISA method but with wider linear range, more convenient operation, and lower cost. The proposed

  13. Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1

    DEFF Research Database (Denmark)

    Hindie, Valerie; Stroba, Adriana; Zhang, Hua

    2009-01-01

    -dependent activation of AGC kinases. The AGC kinase PDK1 is activated by the docking of a phosphorylated motif from substrates. Here we present the crystallography of PDK1 bound to a rationally developed low-molecular-weight activator and describe the conformational changes induced by small compounds in the crystal...... molecular details of the allosteric changes induced by small compounds that trigger the activation of PDK1 through mimicry of phosphorylation-dependent conformational changes....

  14. Radioiodinated 5-iodothienyl-2-substituted long chain fatty acids for myocardial imaging

    International Nuclear Information System (INIS)

    Goodman, M.M.; Knapp, F.F. Jr.; Kirsch, G.; Owen, B.A.

    1984-01-01

    Thienyl-2-alkyl derivatives undergo facile iodination regiospecifically at the 5-position of the thiophene ring and are alternatives to iodophenyl agents. /sup 125/I-labeled 2-(17-oxoheptadecanoly)-5-iodothiophene (VIIIa) and /sup 125/I-labeled 2-(13-oxotridecanoyl)-5-iodothiophene (VIIIb) were prepared as model agents. The substrate was 2-(17-oxoheptadecanoyl)thiophene (VIa), in which the thiophene ring was attached to the terminal position of heptadecanoic acid. (VIa) was prepared by Friedel-Crafts condensation of 16-iodohexadecanoyl chloride, with thiophene followed by -I + CN/sup -/ → -CN; Wolff-Kishner reduction; -CN + OH/sup -/ → -COOH (VI). Regiospecific rho-[bis-(trifluoroacety 1)] thallation of (VIa), followed by treatment with KI gave 2-(17-oxoheptadecanoyl)-5-iodothiophene (VIIIa). Compound VIIIb was prepared in the same manner. Compounds Ia, b-VIIIa,b, were analyzed by TLC, IR, MS, NMR, and CandH. I-125-labeled (VIIIa) and (VIIIb) were prepared in the same manner. I-125 (VIIIb) showed high myocardial uptake in rats (4/group). Iodothienyl fatty acids may represent alternatives to iodophenyl substituted fatty acids for myocardial imaging

  15. Valoración de la intervención en alumnado de secundaria con alteraciones graves de conducta (AGC

    Directory of Open Access Journals (Sweden)

    Manuel Espada Largo

    2017-01-01

    Full Text Available Los problemas de comportamiento en centros educativos son objeto de numerosas investigaciones (Mayorga y Oliver, 2006; Olweus, 1973a; Sela-Shayovitz, 2009; Sellman, 2011; Torrego y Galán, 2008. El objetivo de este estudio es describir cómo se interviene con alumnado con Alteraciones Graves de Conducta (AGC en los institutos públicos de la provincia de Toledo (España. El plan de investigación corresponde a un estudio de caso único de tipo intrínseco. Las técnicas de recogida y análisis de datos son cuantitativas vs. cualitativas complementariamente. Se diseñaron categorías de análisis prefiguradas a partir del marco teórico del estudio y se recogieron categorías emergentes. El instrumento utilizado fue un cuestionario de entrevista semiestructurada diseñado ad hoc. Los resultados indicaron que la intervención que se está desarrollando en los institutos públicos de la provincia de Toledo con este tipo de alumnado debería ser revisada. Existen diferencias importantes entre los criterios básicos de prevención, la atención desde un planteamiento integral de mejora de la convivencia y el nivel de aplicación real en los centros. Se aportan propuestas de mejora.

  16. Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

    Science.gov (United States)

    Toyota, Kazuhiro; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Nakagawa, Naoya; Takahashi, Shinya; Sueda, Taijiro

    2018-05-01

    Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

  17. BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo

    DEFF Research Database (Denmark)

    Sapkota, Gopal P; Cummings, Lorna; Newell, Felicity S

    2007-01-01

    ), which then mediate many of the physiological processes that are regulated by these extracellular agonists. It can be difficult to assess the individual functions of each AGC kinase because their substrate specificities are similar. Here we describe the small molecule BI-D1870, which inhibits RSK1, RSK2......, RSK3 and RSK4 in vitro with an IC(50) of 10-30 nM, but does not signi-ficantly inhibit ten other AGC kinase members and over 40 other protein kinases tested at 100-fold higher concentrations. BI-D1870 is cell permeant and prevents the RSK-mediated phorbol ester- and EGF (epidermal growth factor......)-induced phosphoryl-ation of glycogen synthase kinase-3beta and LKB1 in human embry-onic kidney 293 cells and Rat-2 cells. In contrast, BI-D1870 does not affect the agonist-triggered phosphorylation of substrates for six other AGC kinases. Moreover, BI-D1870 does not suppress the phorbol ester- or EGF...

  18. Mechanistic Framework for Establishment, Maintenance, and Alteration of Cell Polarity in Plants

    Directory of Open Access Journals (Sweden)

    Pankaj Dhonukshe

    2012-01-01

    Full Text Available Cell polarity establishment, maintenance, and alteration are central to the developmental and response programs of nearly all organisms and are often implicated in abnormalities ranging from patterning defects to cancer. By residing at the distinct plasma membrane domains polar cargoes mark the identities of those domains, and execute localized functions. Polar cargoes are recruited to the specialized membrane domains by directional secretion and/or directional endocytic recycling. In plants, auxin efflux carrier PIN proteins display polar localizations in various cell types and play major roles in directional cell-to-cell transport of signaling molecule auxin that is vital for plant patterning and response programs. Recent advanced microscopy studies applied to single cells in intact plants reveal subcellular PIN dynamics. They uncover the PIN polarity generation mechanism and identified important roles of AGC kinases for polar PIN localization. AGC kinase family members PINOID, WAG1, and WAG2, belonging to the AGC-3 subclass predominantly influence the polar localization of PINs. The emerging mechanism for AGC-3 kinases action suggests that kinases phosphorylate PINs mainly at the plasma membrane after initial symmetric PIN secretion for eventual PIN internalization and PIN sorting into distinct ARF-GEF-regulated polar recycling pathways. Thus phosphorylation status directs PIN translocation to different cell sides. Based on these findings a mechanistic framework evolves that suggests existence of cell side-specific recycling pathways in plants and implicates AGC3 kinases for differential PIN recruitment among them for eventual PIN polarity establishment, maintenance, and alteration.

  19. PENINGKATAN AKTIVITAS DAN HASIL BELAJAR BENTUK PASAR DENGAN METODE COURSE REVIEW HORAY (CRH BERBANTUAN MEDIA GAMBAR KELAS VIII SMP N 1 BULU KABUPATEN SUKOHARJO

    Directory of Open Access Journals (Sweden)

    Setyaningsih Setyaningsih

    2013-11-01

    Full Text Available Penelitian ini bertujuan untuk meningkatkan aktivitas dan hasil belajar siswa pada materi bentuk pasar dengan metode Course Review Horay (CRH berbantuan media gambar kelas VIII SMP N 1 Bulu Kabupaten Sukoharjo. Jenis penelitian ini adalah penelitian tindakan kelas yang terdiri dari dua siklus. Setiap siklus memiliki empat tahap yaitu perencanaan, pelaksanaan, pengamatan, dan refleksi. Subjek penelitian ini adalah siswa kelas VIIIA SMP N 1 Bulu. Data aktivitas siswa dan guru diperoleh dari lembar observasi. Data hasil belajar diperoleh dari soal evaluasi siklus I dan siklus II. Berdasarkan hasil penelitian diperoleh aktivitas siswa siklus I sebesar 70,83% meningkat menjadi 87,50% pada siklus II. Sedangkan aktivitas guru dalam siklus I sebesar 71,86% meningkat menjadi 90,6% pada siklus II. Rata-rata hasil belajar kognitif menunjukkan pada siklus I sebesar 72,67 meningkat menjadi 83,20 pada siklus II. Sedangkan ketuntasan klasikal pada siklus I sebesar 70% meningkat menjadi 83,33% pada siklus II. Dari hasil penelitian tersebut dapat disimpulkan bahwa terjadi peningkatan aktivitas dan hasil belajar siswa pada materi bentuk pasar dengan metode Course Review Horay (CRH berbantuan media gambar siswa kelas VIIIA SMP N 1 Bulu Kabupaten Sukoharjo. This research is aimed to increasing activity and student learning results in the subject matter of market forms material by using Course Review Horay (CRH method and image as media in VIIIA class of SMP N 1 Bulu. The design is Classroom Action Research (CAR consisting of two cycles, each cycle including planning, action, observation and reflection. The subjects of research were 30 students of the VIIIA class of SMP N 1 Bulu. Student and teacher activity data were obtained from observation sheet. Results learning data were obtained from test evaluation of the first cycle and second cycle. Based on the results research was obtained in the first cycle of student activities at 70,83% increased to 87,50 in the

  20. Functional characterization of the protein C A267T mutation: evidence for impaired secretion due to defective intracellular transport

    Directory of Open Access Journals (Sweden)

    Tjeldhorn Lena

    2010-09-01

    Full Text Available Abstract Background Activated protein C (PC is a serine protease that regulates blood coagulation by inactivating coagulation factors Va and VIIIa. PC deficiency is an autosomally inherited disorder associated with a high risk of recurrent venous thrombosis. The aim of the study was to explore the mechanisms responsible for severe PC deficiency in a patient with the protein C A267T mutation by in-vitro expression studies. Results Huh7 and CHO-K1 cells were transiently transfected with expression vectors containing wild-type (WT PC and mutated PC (A267T PC cDNAs. PC mRNA levels were assessed by qRT-PCR and the PC protein levels were measured by ELISA. The mRNA levels of WT PC and A267T PC were similar, while the intracellular protein level of A267T PC was moderately decreased compared to WT PC. The secretion of A267T PC into the medium was severely impaired. No differences in molecular weights were observed between WT and A267T PC before and after treatment with endo-β-N-acetylglucosaminidase. Proteasomal and lysosomal degradations were examined using lactacystin and bafilomycin, respectively, and revealed that A267T PC was slightly more susceptible for proteasomal degradation than WT PC. Intracellular co-localization analysis indicated that A267T PC was mainly located in the endoplasmic reticulum (ER, whereas WT PC was observed in both ER and Golgi. Conclusions In contrast to what has been reported for other PC mutants, intracellular degradation of A267T PC was not the main/dominant mechanism underlying the reduced intracellular and secretion levels of PC. Our results indicate that the A267T mutation most likely caused misfolding of PC, which might lead to increased retention of the mutated PC in ER.

  1. Latexin is involved in bone morphogenetic protein-2-induced chondrocyte differentiation

    International Nuclear Information System (INIS)

    Kadouchi, Ichiro; Sakamoto, Kei; Tangjiao, Liu; Murakami, Takashi; Kobayashi, Eiji; Hoshino, Yuichi; Yamaguchi, Akira

    2009-01-01

    Latexin is the only known carboxypeptidase A inhibitor in mammals. We previously demonstrated that BMP-2 significantly induced latexin expression in Runx2-deficient mesenchymal cells (RD-C6 cells), during chondrocyte and osteoblast differentiation. In this study, we investigated latexin expression in the skeleton and its role in chondrocyte differentiation. Immunohistochemical studies revealed that proliferating and prehypertrophic chondrocytes expressed latexin during skeletogenesis and bone fracture repair. In the early phase of bone fracture, latexin mRNA expression was dramatically upregulated. BMP-2 upregulated the expression of the mRNAs of latexin, Col2a1, and the gene encoding aggrecan (Agc1) in a micromass culture of C3H10T1/2 cells. Overexpression of latexin additively stimulated the BMP-2-induced expression of the mRNAs of Col2a, Agc1, and Col10a1. BMP-2 treatment upregulated Sox9 expression, and Sox9 stimulated the promoter activity of latexin. These results indicate that latexin is involved in BMP-2-induced chondrocyte differentiation and plays an important role in skeletogenesis and skeletal regeneration.

  2. Clinical application of immune-enhanced enteral nutrition in patients with advanced gastric cancer after total gastrectomy.

    Science.gov (United States)

    Liu, Hua; Ling, Wei; Shen, Zhi Yong; Jin, Xin; Cao, Hui

    2012-08-01

    To determine whether immune-enhanced enteral nutrition (EN) was effective on nutritional status, immune function, surgical outcomes and days of hospitalization after total gastrectomy for patients with advanced gastric cancer (AGC). From August 2005 to May 2011, 78 patients with AGC who underwent a total gastrectomy were enrolled and divided randomly into three groups: immune-enhanced EN (EN + glutamine [Gln]) group, standard EN group and control group. Serum parameters including total protein, albumin, proalbumin and transferrin were examined on preoperative day 1, postoperative day 2 and day 12. Levels of immunoglobulin M (IgM), immunoglobulin G (IgG), natural killer (NK) cells, CD4⁺ and CD8⁺ T cells were also compared. The formulas were tolerated well in all the patients except 5 with mild complications. The EN + Gln and EN groups showed a faster onset of flatus and shorter hospitalization duration than the control group. On postoperative day 12, serum total protein, albumin, proalbumin and transferrin levels of the EN + Gln and EN groups were significantly higher than those of the control group (P nutritional status and immune function for the patients with AGC after total gastrectomy. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

  3. Firefly algorithm optimized fuzzy PID controller for AGC of multi-area multi-source power systems with UPFC and SMES

    Directory of Open Access Journals (Sweden)

    Pratap Chandra Pradhan

    2016-03-01

    Full Text Available In this paper, a Firefly Algorithm (FA optimized fuzzy PID controller is proposed for Automatic Generation Control (AGC of multi-area multi-source power system. Initially, a two area six units power system is used and the gains of the fuzzy PID controller are optimized employing FA optimization technique using an ITAE criterion. The superiority of the proposed FA optimized fuzzy PID controller has been demonstrated by comparing the results with some recently published approaches such as optimal control and Differential Evolution (DE optimized PID controller for the identical interconnected power system. Then, physical constraints such as Time Delay (TD, reheat turbine and Generation Rate Constraint (GRC are included in the system model and the superiority of FA is demonstrated by comparing the results over DE, Gravitational Search Algorithm (GSA and Genetic Algorithm (GA optimization techniques for the same interconnected power system. Additionally, a Unified Power Flow Controller (UPFC is placed in the tie-line and Superconducting Magnetic Energy Storage (SMES units are considered in both areas. Simulation results show that the system performances are improved significantly with the proposed UPFC and SMES units. Sensitivity analysis of the system is performed by varying the system parameters and operating load conditions from their nominal values. It is observed that the optimum gains of the proposed controller need not be reset even if the system is subjected to wide variation in loading condition and system parameters. Finally, the effectiveness of the proposed controller design is verified by considering different types of load patterns.

  4. The Cellient automated cell block system is useful in the differential diagnosis of atypical glandular cells in Papanicolaou tests.

    Science.gov (United States)

    Xing, Wei; Hou, April Y; Fischer, Andrew; Owens, Christopher L; Jiang, Zhong

    2014-01-01

    Atypical glandular cells (AGC) is a very important diagnosis in gynecological cytology. In the current study, the authors investigated the usefulness of Cellient cell blocks (CB) for characterizing AGC on Papanicolaou (Pap) tests. A total of 148 patients with an AGC diagnosis based on Pap tests by cytotechnologists and referred to cytopathologists were studied. Among these patients, there were 68 patients with CB preparations and 80 patients with Pap tests only (TP-AGC group). Follow-up results by Pap tests or biopsies were obtained in 117 of 148 patients. The median follow-up was 13 months (range, 1 month-36 months). Of the 68 patients with CBs, 31 (46%) were reclassified as negative for dysplasia or low-grade intraepithelial lesion; 30 patients (44%) retained a diagnosis of AGC (CB-AGC group); and 7 patients (10%) were given specific diagnoses of high-grade intraepithelial lesion (3 patients), endocervical adenocarcinoma in situ (1 patient), and invasive adenocarcinoma (3 patients). On follow-up, the CB-AGC group was found to have a significantly lower rate of negative/low-grade squamous intraepithelial lesion diagnoses compared with the TP-AGC group (55% vs 85%; P= .006). The CB-AGC group had a significantly higher rate of endocervical or endometrial adenocarcinoma compared with the TP-AGC group (36% vs 8%; P= .003) at the time of follow-up. The rates of high-grade squamous intraepithelial lesion were not found to be statistically different between these 2 groups (9% vs 7%; P= .66). The Cellient CB is a useful technique to further categorize a diagnosis of AGC on Pap tests. Using the Cellient CB system, the pathologist has the ability to improve the diagnostic accuracy of AGC so that unnecessary colposcopic evaluation or biopsies can be avoided. © 2013 American Cancer Society.

  5. Landscape-scale analysis of aboveground tree carbon stocks affected by mountain pine beetles in Idaho

    International Nuclear Information System (INIS)

    Bright, B C; Hicke, J A; Hudak, A T

    2012-01-01

    Bark beetle outbreaks kill billions of trees in western North America, and the resulting tree mortality can significantly impact local and regional carbon cycling. However, substantial variability in mortality occurs within outbreak areas. Our objective was to quantify landscape-scale effects of beetle infestations on aboveground carbon (AGC) stocks using field observations and remotely sensed data across a 5054 ha study area that had experienced a mountain pine beetle outbreak. Tree mortality was classified using multispectral imagery that separated green, red, and gray trees, and models relating field observations of AGC to LiDAR data were used to map AGC. We combined mortality and AGC maps to quantify AGC in beetle-killed trees. Thirty-nine per cent of the forested area was killed by beetles, with large spatial variability in mortality severity. For the entire study area, 40–50% of AGC was contained in beetle-killed trees. When considered on a per-hectare basis, 75–89% of the study area had >25% AGC in killed trees and 3–6% of the study area had >75% of the AGC in killed trees. Our results show that despite high variability in tree mortality within an outbreak area, bark beetle epidemics can have a large impact on AGC stocks at the landscape scale. (letter)

  6. Measuring and modelling above-ground carbon and tree allometry along a tropical elevation gradient

    DEFF Research Database (Denmark)

    Marshall, A.R.; Willcock, S.; Platts, P.J.

    2012-01-01

    of physical, climatic and edaphic predictors of AGC and tree stature. AGC estimates using stem diameter, height and wood density, gave a mean value of 174.6 t ha−1, compared with 229.6 t ha−1 when height was excluded. Regression models revealed that stems were tallest for a given diameter at mid......:benefit of different measurements and recommend a tiered approach to AGC monitoring, depending on available resources. AGC assessments in African forests could exclude small stems, but should aim to record disturbance, topography and species. Stem height is vital for AGC estimation and valuation; when excluding height...... our 55 t ha−1 over-estimation of AGC would have over-valued the carbon resource by 24% (US$3300 ha−1)....

  7. Atypical endometrial cells and atypical glandular cells favor endometrial origin in Papanicolaou cervicovaginal tests: Correlation with histologic follow-up and abnormal clinical presentations

    Directory of Open Access Journals (Sweden)

    Longwen Chen

    2014-01-01

    Full Text Available The 2001 Bethesda system recommends further classifying atypical glandular cells (AGCs as either endocervical or endometrial origin. Numerous studies have investigated the clinical significance of AGC. In this study, we investigated the incidence of clinically significant lesions among women with liquid-based Papanicolaou cervicovaginal (Pap interpretations of atypical endometrial cells (AEMs or AGC favor endometrial origin (AGC-EM. More importantly, we correlated patients of AEM or AGC-EM with their clinical presentations to determine if AEM/AGC-EM combined with abnormal vaginal bleeding is associated with a higher incidence of significant endometrial pathology. All liquid-based Pap tests with an interpretation of AEM and AGC-EM from July, 2004 through June, 2009 were retrieved from the database. Women with an interpretation of atypical endocervical cells, AGC, favor endocervical origin or AGC, favor neoplastic were not included in the study. The most severe subsequent histologic diagnoses were recorded for each patient. During this 5-year period, we accessioned 332,470 Pap tests of which 169 (0.05% were interpreted as either AEM or AGC-EM. Of the 169 patients, 133 had histologic follow-up within the health care system. The patients ranged in age from 21 to 71 years old (mean 49.7. On follow-up histology, 27 (20.3% had neoplastic/preneoplastic uterine lesions. Among them, 20 patients were diagnosed with adenocarcinoma (18 endometrial, 1 endocervical, and 1 metastatic colorectal, 3 with atypical endometrial hyperplasia, and 4 with endometrial hyperplasia without atypia. All patients with significant endometrial pathology, except one, were over 40 years old, and 22 of 25 patients reported abnormal vaginal bleeding at the time of endometrial biopsy or curettage. This study represents a large series of women with liquid-based Pap test interpretations of AEM and AGC-EM with clinical follow-up. Significant preneoplastic or neoplastic endometrial

  8. Combined effect of pulse density and grid cell size on predicting and mapping aboveground carbon in fast-growing Eucalyptus forest plantation using airborne LiDAR data.

    Science.gov (United States)

    Silva, Carlos Alberto; Hudak, Andrew Thomas; Klauberg, Carine; Vierling, Lee Alexandre; Gonzalez-Benecke, Carlos; de Padua Chaves Carvalho, Samuel; Rodriguez, Luiz Carlos Estraviz; Cardil, Adrián

    2017-12-01

    LiDAR remote sensing is a rapidly evolving technology for quantifying a variety of forest attributes, including aboveground carbon (AGC). Pulse density influences the acquisition cost of LiDAR, and grid cell size influences AGC prediction using plot-based methods; however, little work has evaluated the effects of LiDAR pulse density and cell size for predicting and mapping AGC in fast-growing Eucalyptus forest plantations. The aim of this study was to evaluate the effect of LiDAR pulse density and grid cell size on AGC prediction accuracy at plot and stand-levels using airborne LiDAR and field data. We used the Random Forest (RF) machine learning algorithm to model AGC using LiDAR-derived metrics from LiDAR collections of 5 and 10 pulses m -2 (RF5 and RF10) and grid cell sizes of 5, 10, 15 and 20 m. The results show that LiDAR pulse density of 5 pulses m -2 provides metrics with similar prediction accuracy for AGC as when using a dataset with 10 pulses m -2 in these fast-growing plantations. Relative root mean square errors (RMSEs) for the RF5 and RF10 were 6.14 and 6.01%, respectively. Equivalence tests showed that the predicted AGC from the training and validation models were equivalent to the observed AGC measurements. The grid cell sizes for mapping ranging from 5 to 20 also did not significantly affect the prediction accuracy of AGC at stand level in this system. LiDAR measurements can be used to predict and map AGC across variable-age Eucalyptus plantations with adequate levels of precision and accuracy using 5 pulses m -2 and a grid cell size of 5 m. The promising results for AGC modeling in this study will allow for greater confidence in comparing AGC estimates with varying LiDAR sampling densities for Eucalyptus plantations and assist in decision making towards more cost effective and efficient forest inventory.

  9. Células glandulares atípicas em esfregaços cervicovaginais: significância e aspectos atuais Atypical glandular cells in cervical smears: significance and current aspects

    Directory of Open Access Journals (Sweden)

    Adriana Bittencourt Campaner

    2007-02-01

    Full Text Available Células glandulares atípicas (AGC em esfregaços cervicovaginais são achados citológicos raros, porém de significado representativo. Sua incidência varia, na literatura, de 0,08% a 0,81%. O sistema Bethesda de 2001 classifica estas lesões glandulares como AGCs sem outras especificações, AGCs provavelmente neoplásicas, adenocarcinoma cervical in situ (AIS e adenocarcinoma invasivo. Das mulheres portadoras de AGC, grande parte não apresentará qualquer tipo de alteração histológica em avaliação subseqüente. Entretanto, em 17,4% a 62,2% dos casos serão encontradas lesões histológicas significativas, como neoplasias intra-epiteliais cervicais, AIS, neoplasias escamosas e glandulares, cervicais e endometriais, bem como neoplasias de outras localizações. O risco de doença significativa está relacionado à subdivisão de AGC encontrada. Em virtude da elevada probabilidade de anormalidades histológicas significativas em casos de AGC, a simples repetição citológica é insuficiente para o seguimento dessa condição. Esta atualização descreve a epidemiologia, a avaliação e a conduta das pacientes portadoras dessa anormalidade citológica.Atypical glandular cells (AGC on cervical smears are unusual but important cytologic diagnosis. The incidence of AGC ranges from 0.08% to 0.81 % of all cervical smears tests. The 2001 Bethesda System nomenclature classifies these glandular lesions as AGC not otherwise specified, AGC favor neoplasia, endocervical adenocarcinoma in situ (AIS and invasive adenocarcinoma. Of women with AGC smears, a great number will have no histologic abnormalities on further evaluation. However, 17.4% to 62.2% are found to have significant histologic lesions such as cervical intraepithelial neoplasia, AIS, squamous and glandular cancers from sites farther the cervix and endometrium. The risk of significant disease is related to the AGC subclassification that was found. Because of the high likelihood that AGC

  10. Hemophilia B with mutations at glycine-48 of factor IX exhibited delayed activation by the factor VIIa-tissue factor complex.

    Science.gov (United States)

    Wu, P C; Hamaguchi, N; Yu, Y S; Shen, M C; Lin, S W

    2000-10-01

    Gly-48 is in the conserved DGDQC sequence (residues 47-51 of human factor IX) of the first EGF (EGF-1)-like domain of factor IX. The importance of the Gly-48 is manifested by two hemophilia B patients; factor IXTainan and factor IXMalmo27, with Gly-48 replaced by arginine (designated IXG48R) and valine (IXG48V), respectively. Both patients were CRM+ exhibiting mild hemophilic episodes with 25% (former) and 19% (latter) normal clotting activities. We characterize both factor IX variants to show the roles of Gly-48 and the conservation of the DGDQC sequence in factor IX. Purified plasma and recombinant factor IX variants exhibited approximately 26%-27% normal factor IX's clotting activities with G48R or G48V mutation. Both variants depicted normal quenching of the intrinsic fluorescence by increasing concentrations of calcium ions and Tb3+, indicating that arginine and valine substitution for Gly-48 did not perturb the calcium site in the EGF-1 domain. Activation of both mutants by factor XIa appeared normal. The reduced clotting activity of factors IXG48R and IXG48V was attributed to the failure of both mutants to cleavage factor X: in the presence of only phospholipids and calcium ions, both mutants showed a 4 to approximately 7-fold elevation in Km, and by adding factor VIIIa to the system, although factor VIIIa potentiated the activation of factor X by the mutants factor IXaG48R and factor IXaG48V, a 2 to approximately 3-fold decrease in the catalytic function was observed with the mutant factor IXa's, despite that they bound factor VIIIa on the phospholipid vesicles with only slightly reduced affinity when compared to wild-type factor IXa. The apparent Kd for factor VIIIa binding was 0.83 nM for normal factor IXa, 1.74 nM for IXaG48R and 1.4 nM for IXaG48V. Strikingly, when interaction with the factor VIIa-TF complex was examined, both mutations were barely activated by the VIIa-TF complex and they also showed abnormal interaction with VIIa-TF in bovine

  11. Coordination of Heat Pumps, Electric Vehicles and AGC for Efficient LFC in a Smart Hybrid Power System via SCA-Based Optimized FOPID Controllers

    Directory of Open Access Journals (Sweden)

    Rahmat Khezri

    2018-02-01

    Full Text Available Due to the high price of fossil fuels, the increased carbon footprint in conventional generation units and the intermittent functionality of renewable units, alternative sources must contribute to the load frequency control (LFC of the power system. To tackle the challenge, dealing with controllable loads, the ongoing study aims at efficient LFC in smart hybrid power systems. To achieve this goal, heat pumps (HPs and electric vehicles (EVs are selected as the most effective controllable loads to contribute to the LFC issue. In this regard, the EVs can be controlled in a bidirectional manner as known charging and discharging states under a smart structure. In addition, regarding the HPs, the power consumption is controllable. As the main task, this paper proposes a fractional order proportional integral differential (FOPID controller for coordinated control of power consumption in HPs, the discharging state in EVs and automatic generation control (AGC. The parameters of the FOPID controllers are optimized simultaneously by the sine cosine algorithm (SCA, which is a new method for optimization problems. In the sequel, four scenarios, including step and random load changes, aggregated intermittent generated power from wind turbines, a random load change scenario and a sensitivity analysis scenario, are selected to demonstrate the efficiency of the proposed SCA-based FOPID controllers in a hybrid two-area power system.

  12. Navigating the conformational landscape of G protein-coupled receptor kinases during allosteric activation.

    Science.gov (United States)

    Yao, Xin-Qiu; Cato, M Claire; Labudde, Emily; Beyett, Tyler S; Tesmer, John J G; Grant, Barry J

    2017-09-29

    G protein-coupled receptors (GPCRs) are essential for transferring extracellular signals into carefully choreographed intracellular responses controlling diverse aspects of cell physiology. The duration of GPCR-mediated signaling is primarily regulated via GPCR kinase (GRK)-mediated phosphorylation of activated receptors. Although many GRK structures have been reported, the mechanisms underlying GRK activation are not well-understood, in part because it is unknown how these structures map to the conformational landscape available to this enzyme family. Unlike most other AGC kinases, GRKs rely on their interaction with GPCRs for activation and not phosphorylation. Here, we used principal component analysis of available GRK and protein kinase A crystal structures to identify their dominant domain motions and to provide a framework that helps evaluate how close each GRK structure is to being a catalytically competent state. Our results indicated that disruption of an interface formed between the large lobe of the kinase domain and the regulator of G protein signaling homology domain (RHD) is highly correlated with establishment of the active conformation. By introducing point mutations in the GRK5 RHD-kinase domain interface, we show with both in silico and in vitro experiments that perturbation of this interface leads to higher phosphorylation activity. Navigation of the conformational landscape defined by this bioinformatics-based study is likely common to all GPCR-activated GRKs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Spectroscopic characterization of the effect of gamma radiation on the physical parameters of biosynthesized silver/chitosan nano-particles and their antimicrobial activity

    Science.gov (United States)

    Osman, Mohamed E.; Eid, May M.; Khattab, Om kolthoum H.; El-Hallouty, Salwa M.; El-Marakby, Seham M.; Mahmoud, Doaa A.

    2015-09-01

    Studying the effect of pH on the biosynthesis of silver/chitosan nanoparticles (Ag/CS NPs) using Aspergillus deflectus and Penicillium pinophilum as reducing agents, showed very weak surface plasmon resonance (SPR) of Ag/CS NPs at certain pH. In this paper, the effect of irradiation on the synthesis of Ag/CS at non-optimum pH was evaluated and thereby, the antimicrobial effect of the biosynthesized Ag/CS NPs. The SPR of the AgNPs was analyzed by UV-visible spectroscopy. The active groups responsible for the reduction and capping of the AgNPs were analyzed by Fourier transform infrared (FTIR), and their shape and size were determined via high resolution transmission electron microscopy (HRTEM) and the dynamic light scattering (DLS) technique. UV/Visible spectroscopy confirmed the appearance of AgNPs’ SPR. Additionally, the FTIR spectroscopy confirmed the Ag/CS NP formation. Data also revealed that increasing both the pH and irradiation dose resulted in a decrease of the Ag/CS NPs’ size. DLS and HRTEM results showed that the best pH for biosynthesis of Ag/Cs is 7.5 at 50 kGy considering the particle size and crystallinity. Also, pH 8.5 gave the best antimicrobial activity of the Ag/CS NPs from Penicillium against both S. aureus and E. coli, while 8.5 and 7.5 were the best in the same order, for Ag/CS from Aspergillus.

  14. Regulation of ABCB1/PGP1-catalysed auxin transport by linker phosphorylation

    DEFF Research Database (Denmark)

    Henrichs, Sina; Wang, Bangjun; Fukao, Yoichiro

    2012-01-01

    Polar transport of the plant hormone auxin is controlled by PIN-and ABCB/PGP-efflux catalysts. PIN polarity is regulated by the AGC protein kinase, PINOID (PID), while ABCB activity was shown to be dependent on interaction with the FKBP42, TWISTED DWARF1 (TWD1). Using co-immunoprecipitation (co-I...

  15. Assess and Predict Automatic Generation Control Performances for Thermal Power Generation Units Based on Modeling Techniques

    Science.gov (United States)

    Zhao, Yan; Yang, Zijiang; Gao, Song; Liu, Jinbiao

    2018-02-01

    Automatic generation control(AGC) is a key technology to maintain real time power generation and load balance, and to ensure the quality of power supply. Power grids require each power generation unit to have a satisfactory AGC performance, being specified in two detailed rules. The two rules provide a set of indices to measure the AGC performance of power generation unit. However, the commonly-used method to calculate these indices is based on particular data samples from AGC responses and will lead to incorrect results in practice. This paper proposes a new method to estimate the AGC performance indices via system identification techniques. In addition, a nonlinear regression model between performance indices and load command is built in order to predict the AGC performance indices. The effectiveness of the proposed method is validated through industrial case studies.

  16. Molecular-targeted therapy for chemotherapy-refractory gastric cancer: a case report and literature review.

    Science.gov (United States)

    Kuo, Hung-Yang; Yeh, Kun-Huei

    2014-07-01

    The prognosis of advanced gastric cancer (AGC) remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. However, malnutrition and poor performance of AGC in late stages usually preclude such patients from intensive treatment. Many targeted-therapies failed to show a significant survival benefit in AGC, but have regained attention after the positive result of ramucirumab was announced last year. Among all targeted agents, only trastuzumab, a monoclonal antibody against Human epidermal growth factor receptor-2 (HER2) protein, has been proven as having survival benefit by addition to first-line chemotherapy. Herein we reported a patient who benefited from adding trastuzumab to the same second-line combination chemotherapy (paclitaxel, 5-fluorouracil, and leucovorin) upon progression of bulky liver metastases. At least five months of progression-free survival were achieved without any additional toxicity. We also reviewed literature of molecularly-targeted therapy for chemotherapy-refractory gastric cancer, including several large phase III trials (REGARD, GRANITE-1, EXPAND, and REAL-3) published in 2013-2014. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Real power regulation for the utility power grid via responsive loads

    Science.gov (United States)

    McIntyre, Timothy J [Knoxville, TN; Kirby, Brendan J [Knoxville, TN; Kisner, Roger A

    2009-05-19

    A system for dynamically managing an electrical power system that determines measures of performance and control criteria for the electric power system, collects at least one automatic generation control (AGC) input parameter to at least one AGC module and at least one automatic load control (ALC) input parameter to at least one ALC module, calculates AGC control signals and loads as resources (LAR) control signals in response to said measures of performance and control criteria, propagates AGC control signals to power generating units in response to control logic in AGC modules, and propagates LAR control signals to at least one LAR in response to control logic in ALC modules.

  18. An fMRI Study of Intra-Individual Functional Topography in the Human Cerebellum

    Directory of Open Access Journals (Sweden)

    Catherine J. Stoodley

    2010-01-01

    Full Text Available Neuroimaging studies report cerebellar activation during both motor and non-motor paradigms, and suggest a functional topography within the cerebellum. Sensorimotor tasks activate the anterior lobe, parts of lobule VI, and lobule VIII, whereas higher-level tasks activate lobules VI and VII in the posterior lobe. To determine whether these activation patterns are evident at a single-subject level, we conducted functional magnetic resonance imaging (fMRI during five tasks investigating sensorimotor (finger tapping, language (verb generation, spatial (mental rotation, working memory (N-back, and emotional processing (viewing images from the International Affective Picture System. Finger tapping activated the ipsilateral anterior lobe (lobules IV-V as well as lobules VI and VIII. Activation during verb generation was found in right lobules VII and VIIIA. Mental rotation activated left-lateralized clusters in lobules VII-VIIIA, VI-Crus I, and midline VIIAt. The N-back task showed bilateral activation in right lobules VI-Crus I and left lobules VIIB-VIIIA. Cerebellar activation was evident bilaterally in lobule VI while viewing arousing vs. neutral images. This fMRI study provides the first proof of principle demonstration that there is topographic organization of motor execution vs. cognitive/emotional domains within the cerebellum of a single individual, likely reflecting the anatomical specificity of cerebro-cerebellar circuits underlying different task domains. Inter-subject variability of motor and non-motor topography remains to be determined.

  19. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    Directory of Open Access Journals (Sweden)

    Guhyun Kang

    Full Text Available Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC, whereas the prognosis of patients with advanced gastric cancer (AGC remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes and AGCs (3104 genes. A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010. The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  20. Calcium-regulation of mitochondrial respiration maintains ATP homeostasis and requires ARALAR/AGC1-malate aspartate shuttle in intact cortical neurons.

    Science.gov (United States)

    Llorente-Folch, Irene; Rueda, Carlos B; Amigo, Ignacio; del Arco, Araceli; Saheki, Takeyori; Pardo, Beatriz; Satrústegui, Jorgina

    2013-08-28

    Neuronal respiration is controlled by ATP demand and Ca2+ but the roles played by each are unknown, as any Ca2+ signal also impacts on ATP demand. Ca2+ can control mitochondrial function through Ca2+-regulated mitochondrial carriers, the aspartate-glutamate and ATP-Mg/Pi carriers, ARALAR/AGC1 and SCaMC-3, respectively, or in the matrix after Ca2+ transport through the Ca2+ uniporter. We have studied the role of Ca2+ signaling in the regulation of mitochondrial respiration in intact mouse cortical neurons in basal conditions and in response to increased workload caused by increases in [Na+]cyt (veratridine, high-K+ depolarization) and/or [Ca2+]cyt (carbachol). Respiration in nonstimulated neurons on 2.5-5 mm glucose depends on ARALAR-malate aspartate shuttle (MAS), with a 46% drop in aralar KO neurons. All stimulation conditions induced increased OCR (oxygen consumption rate) in the presence of Ca2+, which was prevented by BAPTA-AM loading (to preserve the workload), or in Ca2+-free medium (which also lowers cell workload). SCaMC-3 limits respiration only in response to high workloads and robust Ca2+ signals. In every condition tested Ca2+ activation of ARALAR-MAS was required to fully stimulate coupled respiration by promoting pyruvate entry into mitochondria. In aralar KO neurons, respiration was stimulated by veratridine, but not by KCl or carbachol, indicating that the Ca2+ uniporter pathway played a role in the first, but not in the second condition, even though KCl caused an increase in [Ca2+]mit. The results suggest a requirement for ARALAR-MAS in priming pyruvate entry in mitochondria as a step needed to activate respiration by Ca2+ in response to moderate workloads.

  1. Presence of variations in ribosomal protein L16 corresponding to susceptibility of enterococci to oligosaccharides (avilamycin and evernimicin)

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Jensen, Lars Bogø

    2000-01-01

    .faecium isolates had sequences that were similar to those of the type strains. All resistant E.faecalis isolates contained the same base pair variation [CGT (Arg-56) --> CAT (His-56)]. The same variation and two additional variations [ATC (Ile-52) --> ACC (Thr-52) and ATC (Ile-52) --> AGC (Ser-52)] were found...

  2. Matching Automatic Gain Control Across Devices in Bimodal Cochlear Implant Users.

    Science.gov (United States)

    Veugen, Lidwien C E; Chalupper, Josef; Snik, Ad F M; Opstal, A John van; Mens, Lucas H M

    2016-01-01

    The purpose of this study was to improve bimodal benefit in listeners using a cochlear implant (CI) and a hearing aid (HA) in contralateral ears, by matching the time constants and the number of compression channels of the automatic gain control (AGC) of the HA to the CI. Equivalent AGC was hypothesized to support a balanced loudness for dynamically changing signals like speech and improve bimodal benefit for speech understanding in quiet and with noise presented from the side(s) at 90 degree. Fifteen subjects participated in the study, all using the same Advanced Bionics Harmony CI processor and HA (Phonak Naida S IX UP). In a 3-visit crossover design with 4 weeks between sessions, performance was measured using a HA with a standard AGC (syllabic multichannel compression with 1 ms attack time and 50 ms release time) or an AGC that was adjusted to match that of the CI processor (dual AGC broadband compression, 3 and 240 msec attack time, 80 and 1500 msec release time). In all devices, the AGC was activated above the threshold of 63 dB SPL. The authors balanced loudness across the devices for soft and loud input sounds in 3 frequency bands (0 to 548, 548 to 1000, and >1000 Hz). Speech understanding was tested in free field in quiet and in noise for three spatial speaker configurations, with target speech always presented from the front. Single-talker noise was either presented from the CI side or the HA side, or uncorrelated stationary speech-weighted noise or single-talker noise was presented from both sides. Questionnaires were administered to assess differences in perception between the two bimodal fittings. Significant bimodal benefit over the CI alone was only found for the AGC-matched HA for the speech tests with single-talker noise. Compared with the standard HA, matched AGC characteristics significantly improved speech understanding in single-talker noise by 1.9 dB when noise was presented from the HA side. AGC matching increased bimodal benefit

  3. Who owns the Brazilian carbon?

    Science.gov (United States)

    Freitas, Flavio L M; Englund, Oskar; Sparovek, Gerd; Berndes, Göran; Guidotti, Vinicius; Pinto, Luís F G; Mörtberg, Ulla

    2018-05-01

    Brazil is one of the major contributors to land-use change emissions, mostly driven by agricultural expansion for food, feed, and bioenergy feedstock. Policies to avoid deforestation related to private commitments, economic incentives, and other support schemes are expected to improve the effectiveness of current command and control mechanisms increasingly. However, until recently, land tenure was unknown for much of the Brazilian territory, which has undermined the governance of native vegetation and challenged support and incentive mechanisms for avoiding deforestation. We assess the total extent of public governance mechanisms protecting aboveground carbon (AGC) stocks. We constructed a land tenure dataset for the entire nation and modeled the effects and uncertainties of major land-use acts on protecting AGC stocks. Roughly 70% of the AGC stock in Brazil is estimated to be under legal protection, and an additional 20% is expected to be protected after areas in the Amazon with currently undesignated land undergo a tenure regularization. About 30% of the AGC stock is on private land, of which roughly two-thirds are protected. The Cerrado, Amazon, and Caatinga biomes hold about 40%, 30%, and 20% of the unprotected AGC, respectively. Effective conservation of protected and unprotected carbon will depend on successful implementation of the Forest Act, and regularization of land tenure in the Amazon. Policy development that prioritizes unprotected AGC stocks is warranted to promote conservation of native vegetation beyond the legal requirements. However, different biomes and land tenure structures may require different policy settings considering local and regional specifics. Finally, the fate of current AGC stocks relies upon effective implementation of command and control mechanisms, considering that unprotected AGC in native vegetation on private land only accounts for 6.5% of the total AGC stock. © 2017 John Wiley & Sons Ltd.

  4. Molecular targeted therapy for advanced gastric cancer.

    Science.gov (United States)

    Kim, Jong Gwang

    2013-03-01

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.

  5. Prolonged action potential duration in cardiac ablation of PDK1 mice.

    Science.gov (United States)

    Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

    2015-01-01

    The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

  6. Commutated automatic gain control system

    Science.gov (United States)

    Yost, S. R.

    1982-01-01

    A commutated automatic gain control (AGC) system was designed and built for a prototype Loran C receiver. The receiver uses a microcomputer to control a memory aided phase-locked loop (MAPLL). The microcomputer also controls the input/output, latitude/longitude conversion, and the recently added AGC system. The circuit designed for the AGC is described, and bench and flight test results are presented. The AGC circuit described actually samples starting at a point 40 microseconds after a zero crossing determined by the software lock pulse ultimately generated by a 30 microsecond delay and add network in the receiver front end envelope detector.

  7. Texas A and M University, Nuclear Science Center: Twenty-fourth progress report, January 1, 1987-December 31, 1987

    International Nuclear Information System (INIS)

    Crawford, K.C.; Davis, J.W.; Krohn, J.L.; Meyer, C.M.; Petesch, J.E.; Stasny, G.S.

    1988-03-01

    Utilization of the reactor (NSCR Reactor) during 1987 increased slightly over that in 1986. The main activity is shifting from isotope tracer production to testing and exposure irradiations. Core VIII-A, operational since March 1986, was used throughout 1987

  8. Removal of phenol from radioactive waste solutions using activated granular Carbon and activated vermiculite

    International Nuclear Information System (INIS)

    Ezz El-Din, M.R.; Atta, E.R.

    2006-01-01

    The efficiency of both activated granular carbon (AGC) and activated vermiculite (AV) in removal of phenol from aqueous waste solutions is of great interest. The aim of the present study is to compare the absorbance capacities of both AGC and AV for the removal of phenol from radioactive waste solutions and to identify the factors affecting the sorption process. The experimental results were in the form of batch sorption measurements for the removal of phenol at ambient temperature (29 ± 1 degree C) and for times up to 40 min and 180 min for AGC and AV, respectively. The results indicated that activated carbon has good efficiency to adsorb phenol. Freundlich equation has been fitted to both AGC and AV for the contaminant removal. The adsorption capacities of both AGC and AV to phenol were 17.4 mg g-1 and 4.5 mg g-1, respectively. The maximum desorption percent of phenol from both loaded AGC and loaded AV were 9 % and 0 %, respectively, and it attained within about 200 min. accordingly, it is recommended that activated carbon is preferred in the applied field for removing phenol from radioactive aqueous wastes

  9. Software and hardware platform for testing of Automatic Generation Control algorithms

    Directory of Open Access Journals (Sweden)

    Vasiliev Alexey

    2017-01-01

    Full Text Available Development and implementation of new Automatic Generation Control (AGC algorithms requires testing them on a model that adequately simulates primary energetic, information and control processes. In this article an implementation of a test platform based on HRTSim (Hybrid Real Time Simulator and SCADA CK-2007 (which is widely used by the System Operator of Russia is proposed. Testing of AGC algorithms on the test platform based on the same SCADA system that is used in operation allows to exclude errors associated with the transfer of AGC algorithms and settings from the test platform to a real power system. A power system including relay protection, automatic control systems and emergency control automatics can be accurately simulated on HRTSim. Besides the information commonly used by conventional AGC systems HRTSim is able to provide a resemblance of Phasor Measurement Unit (PMU measurements (information about rotor angles, magnitudes and phase angles of currents and voltages etc.. The additional information significantly expands the number of possible AGC algorithms so the test platform is useful in modern AGC system developing. The obtained test results confirm that the proposed system is applicable for the tasks mentioned above.

  10. Journal of Chemical Sciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    , global hardness and softness are reported for a representative set of spherically confined atoms of IA, IIA, VA and VIIIA series in the periodic table. The atomic electrons are confined within the impenetrable spherical cavity defined by a given ...

  11. Coevolving MAPK and PID phosphosites indicate an ancient environmental control of PIN auxin transporters in land plants.

    Science.gov (United States)

    Dory, Magdalena; Hatzimasoura, Elizabeth; Kállai, Brigitta M; Nagy, Szilvia K; Jäger, Katalin; Darula, Zsuzsanna; Nádai, Tímea V; Mészáros, Tamás; López-Juez, Enrique; Barnabás, Beáta; Palme, Klaus; Bögre, László; Ditengou, Franck A; Dóczi, Róbert

    2018-01-01

    Plant growth flexibly adapts to environmental conditions, implying cross-talk between environmental signalling and developmental regulation. Here, we show that the PIN auxin efflux carrier family possesses three highly conserved putative mitogen-activated protein kinase (MAPK) sites adjacent to the phosphorylation sites of the well-characterised AGC kinase PINOID, which regulates the polar localisation of PINs and directional auxin transport, thereby underpinning organ growth. The conserved sites of PIN1 are phosphorylated in vitro by two environmentally activated MAPKs, MPK4 and MPK6. In contrast to AGC kinases, MAPK-mediated phosphorylation of PIN1 at adjacent sites leads to a partial loss of the plasma membrane localisation of PIN1. MAPK-mediated modulation of PIN trafficking may participate in environmental adjustment of plant growth. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  12. An output amplitude configurable wideband automatic gain control with high gain step accuracy

    International Nuclear Information System (INIS)

    He Xiaofeng; Ye Tianchun; Mo Taishan; Ma Chengyan

    2012-01-01

    An output amplitude configurable wideband automatic gain control (AGC) with high gain step accuracy for the GNSS receiver is presented. The amplitude of an AGC is configurable in order to cooperate with baseband chips to achieve interference suppression and be compatible with different full range ADCs. And what's more, the gain-boosting technology is introduced and the circuit is improved to increase the step accuracy. A zero, which is composed by the source feedback resistance and the source capacity, is introduced to compensate for the pole. The AGC is fabricated in a 0.18 μm CMOS process. The AGC shows a 62 dB gain control range by 1 dB each step with a gain error of less than 0.2 dB. The AGC provides 3 dB bandwidth larger than 80 MHz and the overall power consumption is less than 1.8 mA, and the die area is 800 × 300 μm 2 . (semiconductor integrated circuits)

  13. Flexural Behavior of RC Members Using Externally Bonded Aluminum-Glass Fiber Composite Beams

    Directory of Open Access Journals (Sweden)

    Ki-Nam Hong

    2014-03-01

    Full Text Available This study concerns improvement of flexural stiffness/strength of concrete members reinforced with externally bonded, aluminum-glass fiber composite (AGC beams. An experimental program, consisting of seven reinforced concrete slabs and seven reinforced concrete beams strengthened in flexure with AGC beams, was initiated under four-point bending in order to evaluate three parameters: the cross-sectional shape of the AGC beam, the glass fiber fabric array, and the installation of fasteners. The load-deflection response, strain distribution along the longitudinal axis of the beam, and associated failure modes of the tested specimens were recorded. It was observed that the AGC beam led to an increase of the initial cracking load, yielding load of the tension steels and peak load. On the other hand, the ductility of some specimens strengthened was reduced by more than 50%. The A-type AGC beam was more efficient in slab specimens than in beam specimens and the B-type was more suitable for beam specimens than for slabs.

  14. Crystal structures of PRK1 in complex with the clinical compounds lestaurtinib and tofacitinib reveal ligand induced conformational changes.

    Directory of Open Access Journals (Sweden)

    Philip Chamberlain

    Full Text Available Protein kinase C related kinase 1 (PRK1 is a component of Rho-GTPase, androgen receptor, histone demethylase and histone deacetylase signaling pathways implicated in prostate and ovarian cancer. Herein we describe the crystal structure of PRK1 in apo form, and also in complex with a panel of literature inhibitors including the clinical candidates lestaurtinib and tofacitinib, as well as the staurosporine analog Ro-31-8220. PRK1 is a member of the AGC-kinase class, and as such exhibits the characteristic regulatory sequence at the C-terminus of the catalytic domain--the 'C-tail'. The C-tail fully encircles the catalytic domain placing a phenylalanine in the ATP-binding site. Our inhibitor structures include examples of molecules which both interact with, and displace the C-tail from the active site. This information may assist in the design of inhibitors targeting both PRK and other members of the AGC kinase family.

  15. Cervical screening with Luviva machine for early detection of ...

    African Journals Online (AJOL)

    Cervical screening with Luviva machine for early detection of cervical dysplasia: ... glandular cell (AGC), Atypical glandular cell favouring neoplasia (AGC-FN), ... in low grade squamous intraepithelial lesion was recorded among the patients.

  16. 78 FR 5179 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

    Science.gov (United States)

    2013-01-24

    ... Healthcare Corporation; Lakewood IPA, Inc.; Tenet Healthcare Corporation. 20130401 G Apax VIII-A L.P.; Nike.... Lucas; The Walt Disney Company. 20130208 G Liberty Interactive Corporation; TripAdvisor, Inc.; Liberty... Investment Management Corp. 20130258 G U.S. Bancorp; FSV Payment Systems, Inc.; U.S. Bancorp. 20130260 G...

  17. A clinicopathological study of asymptomatic gastric cancer.

    OpenAIRE

    Matsukuma, A.; Furusawa, M.; Tomoda, H.; Seo, Y.

    1996-01-01

    The clinicopathological profiles of 419 patients with asymptomatic gastric cancer (AGC) first detected by gastric screening, were reviewed and compared with those of the 1727 patients with symptomatic gastric cancer (SGC). The incidence of AGC increased gradually and has amounted to 30% of the total resected cases in recent years. About 75% of AGC cases were of early cancer and 84% were negative for lymph node metastases. In contrast, only 33% of SGC cases were of early cancer and 57% were no...

  18. Enhancing pattern of gastric carcinoma at dynamic incremental CT: correlation with gross and histologic findings

    International Nuclear Information System (INIS)

    Shin, Hong Seop; Lee, Dong Ho; Kim, Yoon Hwa; Ko, Young Tae; Lim, Joo Won; Yoon, Yup

    1996-01-01

    To evaluate the enhancing pattern of gastric carcinomas at dynamic incremental CT and to correlate it with pathologic findings. We retrospectively evaluated the enhancement pattern of stomach cancer on dynamic incremental CT of the 78 patients. All the lesions had been pathologically proved after surgery. The enhancement pattern was categorized as good or poor in the early phase;homogeneous, heterogeneous or ring enhancement;the presence or absence of delayed enhancement. There were 16 cases of early gastric cancer (EGC), and 62 cases of advanced gastric cancer(AGC). The Borrmann type of AGC were 1(n=1), 2(n=20), 3=(n=32), 4(n=8) and 5(n=1). The histologic patterns of AGC were tubular(n=49), signet ring cell(n=10), and mucinous(n=3). The enhancing patterns were compared with gross and histologic findings and delayed enhancement was correlated with pathologic evidence of desmoplasia. Good enhancement of tumor was seen in 24/41cases (58.5%) with AGC Borrmann type 3-5, in 6/21(28.6%) with AGC Borrmann type 1-2, and in 3/16(18.8%) with EGC (P<.05). By histologic pattern, good enhancement of tumor was seen in 8/10(80%) with signet ring cell type, in 21/49(42.9%) with tubular type, and in 1/3(33.3%) with mucinous type(P<.05). EGC was homogeneously enhanced in 14/16cases (87.5%), but AGC was heterogeneously enhanced in 33/62(53.2%), respectively(P<.01). There was no significant correlation between delayed enhancement and the presence of desmoplasia. AGC Borrmann type 3-5 and signet ring cell type have a tendency to show good enhancement and EGC is more homogeneously enhanced at dynamic incremental CT

  19. Aboveground carbon loss in natural and managed tropical forests from 2000 to 2012

    International Nuclear Information System (INIS)

    Tyukavina, A; Hansen, M C; Potapov, P V; Krylov, A M; Turubanova, S; Baccini, A; Houghton, R A; Goetz, S J; Stehman, S V

    2015-01-01

    Tropical forests provide global climate regulation ecosystem services and their clearing is a significant source of anthropogenic greenhouse gas (GHG) emissions and resultant radiative forcing of climate change. However, consensus on pan-tropical forest carbon dynamics is lacking. We present a new estimate that employs recommended good practices to quantify gross tropical forest aboveground carbon (AGC) loss from 2000 to 2012 through the integration of Landsat-derived tree canopy cover, height, intactness and forest cover loss and GLAS-lidar derived forest biomass. An unbiased estimate of forest loss area is produced using a stratified random sample with strata derived from a wall-to-wall 30 m forest cover loss map. Our sample-based results separate the gross loss of forest AGC into losses from natural forests (0.59 PgC yr −1 ) and losses from managed forests (0.43 PgC yr −1 ) including plantations, agroforestry systems and subsistence agriculture. Latin America accounts for 43% of gross AGC loss and 54% of natural forest AGC loss, with Brazil experiencing the highest AGC loss for both categories at national scales. We estimate gross tropical forest AGC loss and natural forest loss to account for 11% and 6% of global year 2012 CO 2 emissions, respectively. Given recent trends, natural forests will likely constitute an increasingly smaller proportion of tropical forest GHG emissions and of global emissions as fossil fuel consumption increases, with implications for the valuation of co-benefits in tropical forest conservation. (letter)

  20. A novel analog/digital reconfigurable automatic gain control with a novel DC offset cancellation circuit

    Energy Technology Data Exchange (ETDEWEB)

    He Xiaofeng; Ye Tianchun [Institute of Microelectronics, Chinese Academy of Science, Beijing 100029 (China); Mo Taishan; Ma Chengyan, E-mail: hexiaofeng@casic.ac.cn [Hangzhou Zhongke Microelectronics Co, Ltd, Hangzhou 310053 (China)

    2011-02-15

    An analog/digital reconfigurable automatic gain control (AGC) circuit with a novel DC offset cancellation circuit for a direct-conversion receiver is presented. The AGC is analog/digital reconfigurable in order to be compatible with different baseband chips. What's more, a novel DC offset cancellation (DCOC) circuit with an HPCF (high pass cutoff frequency) less than 10 kHz is proposed. The AGC is fabricated by a 0.18 {mu}m CMOS process. Under analog control mode, the AGC achieves a 70 dB dynamic range with a 3 dB-bandwidth larger than 60 MHz. Under digital control mode, through a 5-bit digital control word, the AGC shows a 64 dB gain control range by 2 dB each step with a gain error of less than 0.3 dB. The DC offset cancellation circuits can suppress the output DC offset voltage to be less than 1.5 mV, while the offset voltage of 40 mV is introduced into the input. The overall power consumption is less than 3.5 mA, and the die area is 800 x 300 {mu}m{sup 2}. (semiconductor integrated circuits)

  1. Removal of cadmium(II) from aqueous solution by corn stalk graft copolymers.

    Science.gov (United States)

    Zheng, Liuchun; Dang, Zhi; Zhu, Chaofei; Yi, Xiaoyun; Zhang, Hui; Liu, Congqiang

    2010-08-01

    Corn stalk was modified using graft copolymerization to produce absorbent (AGCS), which was characterized by elemental analysis, fourier transform infrared, X-ray diffraction, solid-state CP/MAS (13)C NMR spectra, thermogravimetric analysis and differential scanning calorimeter. AGCS, having cyano group (-CN) after grafted successfully, exhibits more high adsorption potential for Cd(II) than unmodified forms. The efficiency of AGCS for removal of cadmium ions was evaluated. Factors affecting Cd(II) adsorption such as pH value and adsorbent dosage were investigated. More than 90% removal was achieved at pH 3.0-7.0 and the adsorption increased from 16.0% to 99.2% with increase of adsorbent dose. In addition, two isotherm models, namely, Langmuir and Freunlich were also analyzed to determine the best fit equation for adsorption of Cd(II) on AGCS. (c) 2010 Elsevier Ltd. All rights reserved.

  2. Conditional Expression of the Androgen Receptor Increases Susceptibility of Bladder Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Daniel T Johnson

    Full Text Available Bladder cancer represents a significant human tumor burden, accounting for about 7.7% and 2.4% of all cancer cases in males and females, respectively. While men have a higher risk of developing bladder cancer, women tend to present at a later stage of disease and with more aggressive tumors. Previous studies have suggested a promotional role of androgen signaling in enhancing bladder cancer development. To directly assess the role of androgens in bladder tumorigenesis, we have developed a novel transgenic mouse strain, R26hARLoxP/+:Upk3aGCE/+, in which the human AR transgene is conditionally expressed in bladder urothelium. Intriguingly, both male and female R26hARLoxP/+:Upk3aGCE/+ mice display a higher incidence of urothelial cell carcinoma (UCC than the age and sex matched control littermates in response to the carcinogen, N-butyl-N-(4-hydroxybutyl nitrosamine (BBN. We detect expression of the human AR transgene in CK5-positive and p63-positive basal cells in bladder urothelium. Further analyses of UCC tissues from R26hARLoxP/+:Upk3aGCE/+ mice showed that the majority of tumor cells are of urothelial basal cell origin. Positive immunostaining of transgenic AR protein was observed in the majority of tumor cells of the transgenic mice, providing a link between transgenic AR expression and oncogenic transformation. We observed an increase in Ki67 positive cells within the UCC lesions of transgenic AR mice. Manipulating endogenous androgen levels by castration and androgen supplementation directly affected bladder tumor development in male and female R26hARLoxP/+:Upk3aGCE/+ mice, respectively. Taken together, our data demonstrate for the first time that conditional activation of transgenic AR expression in bladder urothelium enhances carciongen-induced bladder tumor formation in mice. This new AR transgenic mouse line mimics certain features of human bladder cancer and can be used to study bladder tumorigenesis and for drug development.

  3. Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

    Science.gov (United States)

    Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

    2017-12-01

    The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

  4. 77 FR 29322 - Updating State Residential Building Energy Efficiency Codes

    Science.gov (United States)

    2012-05-17

    ... Glass Company North America (AGC). However, DOE notes that PNA/AGC's comment was received late. Although... following. Steel-framed wall insulation Air barrier location Changes whose effect is unclear: Fenestration... code's primary regulation of a home's envelope thermal resistance, or the resistance of the ceilings...

  5. In Vitro Evaluation of Colloidal Silver on Immune Function: Anti lymphoproliferative Activity

    International Nuclear Information System (INIS)

    Franco-Molina, M. A.; Mendoza-Gamboa, E.; Zarate-Trivino, D. G.; Coronado-Cerda, E.E.; Alcocer-Gonzalez, J. M.; Resendez-Perez, D.; Rodriguez-Salazar, M.C.; Rivera-Morales, L.G.; Tamez-Guerra, R.; Rodriguez-Padilla, C.

    2016-01-01

    Colloidal silver (AgC) is currently used by humans and it can be internalized through inhalation, injection, ingestion, and dermal contact. However, there is limited information about immunological activity; more investigations using colloidal silver are needed. In the present study, the effects of AgC (17.5 ng/m L) on immunological parameters (proliferation and immuno phenotyping) using human peripheral blood mononuclear cells (PBMC) and macrophages (phagocytosis) and cytotoxicity on leukemia and lymphoma cancer cell lines (1.75 to 17.5 ng/m L) were investigated. AgC was observed to significantly ρ) decrease interleukin-2 (I L-2) production and proliferation induced by phytohemagglutinin or concanavalin A in PBMC without affecting its cell viability but with cytotoxic effect on cancer cells. IL-2, IL-4, IL-6, IL-10, INF-γ, and IL_-17 A cytokines production and CD3"+, CD3"-CD19"+, CD3"+CD4"+, CD3"+CD8"+, and CD16"+CD56"+ PBMC phenotypes were not affected by AgC. The present study demonstrates that colloidal silver is harmless and nontoxic to the immune system cells and its ability to interfere with the immune response by decreasing cell proliferation when stimulated with mitogens demonstrated the anti lymphoproliferative potential of AgC

  6. In Vitro Evaluation of Colloidal Silver on Immune Function: Antilymphoproliferative Activity

    Directory of Open Access Journals (Sweden)

    M. A. Franco-Molina

    2016-01-01

    Full Text Available Colloidal silver (AgC is currently used by humans and it can be internalized through inhalation, injection, ingestion, and dermal contact. However, there is limited information about immunological activity; more investigations using colloidal silver are needed. In the present study, the effects of AgC (17.5 ng/mL on immunological parameters (proliferation and immunophenotyping using human peripheral blood mononuclear cells (PBMC and macrophages (phagocytosis and cytotoxicity on leukemia and lymphoma cancer cell lines (1.75 to 17.5 ng/mL were investigated. AgC was observed to significantly (p<0.05 decrease interleukin-2 (IL-2 production and proliferation induced by phytohemagglutinin or concanavalin A in PBMC without affecting its cell viability but with cytotoxic effect on cancer cells. IL-2, IL-4, IL-6, IL-10, INF-γ, and IL-17A cytokines production and CD3+, CD3−CD19+, CD3+CD4+, CD3+CD8+, and CD16+CD56+ PBMC phenotypes were not affected by AgC. The present study demonstrates that colloidal silver is harmless and nontoxic to the immune system cells and its ability to interfere with the immune response by decreasing cell proliferation when stimulated with mitogens demonstrated the antilymphoproliferative potential of AgC.

  7. PENGARUH PENGGUNAAN MODEL COOPERATIVE LEARNING TIPE GROUP INVESTIGATION (GI TERHADAP HASIL BELAJAR IPS TERPADU KELAS VIII SEMESTER GENAP SMPYPI 1 BANDAR MATARAM LAMPUNG TENGAH T.P 2015/2016

    Directory of Open Access Journals (Sweden)

    Desi Fatmawati Maryatun

    2016-05-01

    Full Text Available Metode cooperative learning tipe group investigation merupakan model pembelajaran kooperatif yang dapat melibatkan peserta didik secara aktif dalam kegiatan pembelajaran mulai dari merencanakan topik-topik yang akan dipelajari, bagaimana melaksanakan investigasinya, hingga melakukan presentasi kelompok dan evaluasi. Tujuan penelitian ini adalah untuk mengetahui adanya pengaruh penggunaan model pembelajaran cooperative learning tipe Group Investigation terhadap hasil belajar IPS Terpadu peserta didik kelas VIII semester genap SMP YPI 1 Bandar Mataram  Lampung Tengah tahun pelajaran 2015/2016. Hipotesis yang penulis ajukan adalah “Ada pengaruh yang positif pada model pembelajaran cooperative learning tipe Group Investigation terhadap hasil belajar IPS Terpadu peserta didik kelas VIII semester genap SMP YPI 1 Bandar Mataram  Lampung Tengah tahun pelajaran 2015/2016. Populasi dalam penelitian ini adalah siswa kelas VIII SMP YPI 1 Bandar Mataram Lampung Tengah Tahun Pelajaran 2015/2016 yaitu berjumlah 48 orang siswa dan diantaranya terdiri dari 2 kelas. Dan yang menjadi sampel dalam penelitian ini adalah kelas VIIIa dan VIIIb. Kelas VIIIa sebagai kelas eksperimen dan kelas VIIIb sebagai kelas control, sampel diambil menggunakan teknik purposive sampling, Eksperimen dilaksanakan pada siswa kelas VIIIa Semester Genap SMP YPI 1 Bandar Mataram Lampung Tengah Tahun Pelajaran 2015/2016 yang berjumlah 24 peserta didik. Data penelitian ini dikumpulkan dengan menggunakan  metode observasi, wawancara, dokumentasi, dan tes. Sedangkan untuk mengetahui tingkat validitas dan reliabilitas penulis menggunakan rumus K-R 20. Kemudian untuk menguji/membuktikan hipotesis digunakan rumus Regresi Linier Sederhana yaitu  Ŷ = a + bx. Nilai Ŷ = 73,33+ 0,5 X yang dilanjutkan dengan rumus thitung > ttabel.pada daftar signifikan 5% yaitu 4 > 1,72  dan pada taraf signifikan 1% yaitu 4 > 2,52. Dengan demikian hipotesisnya diterima karena ada pengaruh yang positif

  8. Rictor forms a complex with Cullin-1 to promote SGK1 ubiquitination and destruction

    Science.gov (United States)

    Gao, Daming; Wan, Lixin; Inuzuka, Hiroyuki; Berg, Anders H.; Tseng, Alan; Zhai, Bo; Shaik, Shavali; Bennett, Eric; Tron, Adriana E.; Gasser, Jessica A.; Lau, Alan; Gygi, Steven; Harper, J. Wade; DeCaprio, James A.; Toker, Alex; Wei, Wenyi

    2010-01-01

    Summary The Rictor/mTOR complex (also known as mTORC2) plays a critical role in cellular homeostasis by phosphorylating AGC kinases such as Akt and SGK at their hydrophobic motifs to activate downstream signaling. However, the regulation of mTORC2 and whether it has additional function(s), remains largely unknown. Here we report that Rictor associates with Cullin-1 to form a functional E3 ubiquitin ligase. Rictor, but not Raptor or mTOR alone promotes SGK1 ubiquitination. Loss of Rictor/Cullin-1-mediated ubiquitination leads to increased SGK1 protein levels as detected in Rictor null cells. Moreover, as part of a feedback mechanism, phosphorylation of Rictor at T1135 by multiple AGC kinases disrupts the interaction between Rictor and Cullin-1 to impair SGK1 ubiquitination. These findings indicate that the Rictor/Cullin-1 E3 ligase activity is regulated by a specific signal relay cascade and that misregulation of this mechanism may contribute to the frequent overexpression of SGK1 in various human cancers. PMID:20832730

  9. Improving Frequency Stability Based on Distributed Control of Multiple Load Aggregators

    DEFF Research Database (Denmark)

    Hu, Jianqiang; Cao, Jinde; Guerrero, Josep M.

    2017-01-01

    into the traditional centralized proportional-integral-based automatic generation control (AGC) framework, which has formed the coupled secondary frequency control structure. It has been shown that the total power mismatch in each control area is shared with both AGC units and load aggregators, and the system...

  10. A program for assisting automatic generation control of the ELETRONORTE using artificial neural network; Um programa para assistencia ao controle automatico de geracao da Eletronorte usando rede neuronal artificial

    Energy Technology Data Exchange (ETDEWEB)

    Brito Filho, Pedro Rodrigues de; Nascimento Garcez, Jurandyr do [Para Univ., Belem, PA (Brazil). Centro Tecnologico; Charone, Junior, Wady [Centrais Eletricas do Nordeste do Brasil S.A. (ELETRONORTE), Belem, PA (Brazil)

    1994-12-31

    This work presents an application of artificial neural network as a support to decision making in the automatic generation control (AGC) of the ELETRONORTE. It uses a software to auxiliary in the decisions in real time of the AGC. (author) 2 refs., 6 figs., 1 tab.

  11. Anomalous diffusion of a probe in a bath of active granular chains

    Science.gov (United States)

    Jerez, Michael Jade Y.; Confesor, Mark Nolan P.; Carpio-Bernido, M. Victoria; Bernido, Christopher C.

    2017-08-01

    We investigate the dynamics of a passive probe particle in a bath of active granular chains (AGC). The bath and the probe are enclosed in an experimental compartment with a sinusoidal boundary to prevent AGC congestion along the boundary while connected to an electrodynamic shaker. Single AGC trajectory analysis reveals a persistent type of motion compared to a purely Brownian motion as seen in its mean squared displacement (MSD). It was found that at small concentration, Φ ≤ 0.44, the MSD exhibits two dynamical regimes characterized by two different scaling exponents. For small time scales, the dynamics is superdiffusive (1.32-1.63) with the MSD scaling exponent increasing monotonically with increasing AGC concentration. On the other hand, at long time, we recover the Brownian dynamics regime, MSD = DΔt, where the mobility D ∝ Φ. We quantify the probe dynamics at short time scale by modeling it as a fractional Brownian motion. The analytical form of the MSD agrees with experimental results.

  12. Automated Assume-Guarantee Reasoning for Omega-Regular Systems and Specifications

    Science.gov (United States)

    Chaki, Sagar; Gurfinkel, Arie

    2010-01-01

    We develop a learning-based automated Assume-Guarantee (AG) reasoning framework for verifying omega-regular properties of concurrent systems. We study the applicability of non-circular (AGNC) and circular (AG-C) AG proof rules in the context of systems with infinite behaviors. In particular, we show that AG-NC is incomplete when assumptions are restricted to strictly infinite behaviors, while AG-C remains complete. We present a general formalization, called LAG, of the learning based automated AG paradigm. We show how existing approaches for automated AG reasoning are special instances of LAG.We develop two learning algorithms for a class of systems, called infinite regular systems, that combine finite and infinite behaviors. We show that for infinity-regular systems, both AG-NC and AG-C are sound and complete. Finally, we show how to instantiate LAG to do automated AG reasoning for infinite regular, and omega-regular, systems using both AG-NC and AG-C as proof rules

  13. Drug diffusion and biological responses of arteries using a drug-eluting stent with nonuniform coating

    Directory of Open Access Journals (Sweden)

    Saito N

    2016-03-01

    Full Text Available Noboru Saito, Yuhei Mori, Sayaka Uchiyama Terumo Corporation R&D Center, Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan Abstract: The purpose of this study was to determine the effect of a nonuniform coating, abluminal-gradient coating (AGC, which leaves the abluminal surface of the curves and links parts of the stent free from the drug coating, on the diffusion direction of the drug and the biological responses of the artery to drug-eluting stent (DES by comparing the AGC-sirolimus stent and the conventional full-surface coating (CFC sirolimus stent. The study aimed to verify whether the AGC approach was appropriate for the development of a safer DES, minimizing the risks of stent thrombosis due to delayed endothelialization by the drug and distal embolization due to cracking of the coating layer on the hinge parts of the DES on stent expansion. In the in vitro local drug diffusion study, we used rhodamine B as a model drug, and rhodamine B released from the AGC stent diffused predominantly into the abluminal side of the alginate artery model. Conversely, rhodamine B released from the CFC stent quickly spread to the luminal side of the artery model, where endothelial cell regeneration is required. In the biological responses study, the luminal surface of the iliac artery implanted with the AGC-sirolimus stent in a rabbit iliac artery for 2 weeks was completely covered with endothelial-like cells. On the other hand, the luminal surface of the iliac artery implanted with the CFC-sirolimus stent for 2 weeks only showed partial coverage with endothelial-like cells. While thrombosis was observed in two of the three CFC-sirolimus stents, it was observed in only one of the three AGC-sirolimus stents. Taken together, these findings indicate that the designed nonuniform coating (AGC is an appropriate approach to ensure a safer DES. However, the number of studies is limited and a larger study should be conducted to reach a statistically

  14. Mechanical and microstructural characterization of aluminum reinforced with carbon-coated silver nanoparticles

    International Nuclear Information System (INIS)

    Martinez-Sanchez, R.; Reyes-Gasga, J.; Caudillo, R.; Garcia-Gutierrez, D.I.; Marquez-Lucero, A.; Estrada-Guel, I.; Mendoza-Ruiz, D.C.; Jose Yacaman, M.

    2007-01-01

    Composites of pure aluminum with carbon-coated silver nanoparticles (Ag-C NP) of 10 nm in size were prepared by the mechanical milling process. Transmission electron microscopy showed that the Ag-C NP are homogeneously dispersed into the Al matrix, silver nanoparticles do not coalesce, grow or dissolve in the aluminum matrix due the carbon shell. The values of yield strength (σ y ), maximum strength (σ max ) and micro-hardness Vickers (HVN) of the composites were evaluated and reported as a function of Ag-C NP content. It has been found that the introduction of this type of particles in aluminum strengthen it, increasing all the previous parameters

  15. Molecular Mechanism of Selectivity among G Protein-Coupled Receptor Kinase 2 Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Thal, David M.; Yeow, Raymond Y.; Schoenau, Christian; Huber, Jochen; Tesmer, John J.G. (Sanofi); (Michigan)

    2012-07-11

    G protein-coupled receptors (GPCRs) are key regulators of cell physiology and control processes ranging from glucose homeostasis to contractility of the heart. A major mechanism for the desensitization of activated GPCRs is their phosphorylation by GPCR kinases (GRKs). Overexpression of GRK2 is strongly linked to heart failure, and GRK2 has long been considered a pharmaceutical target for the treatment of cardiovascular disease. Several lead compounds developed by Takeda Pharmaceuticals show high selectivity for GRK2 and therapeutic potential for the treatment of heart failure. To understand how these drugs achieve their selectivity, we determined crystal structures of the bovine GRK2-G{beta}{gamma} complex in the presence of two of these inhibitors. Comparison with the apoGRK2-G{beta}{gamma} structure demonstrates that the compounds bind in the kinase active site in a manner similar to that of the AGC kinase inhibitor balanol. Both balanol and the Takeda compounds induce a slight closure of the kinase domain, the degree of which correlates with the potencies of the inhibitors. Based on our crystal structures and homology modeling, we identified five amino acids surrounding the inhibitor binding site that we hypothesized could contribute to inhibitor selectivity. However, our results indicate that these residues are not major determinants of selectivity among GRK subfamilies. Rather, selectivity is achieved by the stabilization of a unique inactive conformation of the GRK2 kinase domain.

  16. Tree species diversity promotes aboveground carbon storage through functional diversity and functional dominance.

    Science.gov (United States)

    Mensah, Sylvanus; Veldtman, Ruan; Assogbadjo, Achille E; Glèlè Kakaï, Romain; Seifert, Thomas

    2016-10-01

    The relationship between biodiversity and ecosystem function has increasingly been debated as the cornerstone of the processes behind ecosystem services delivery. Experimental and natural field-based studies have come up with nonconsistent patterns of biodiversity-ecosystem function, supporting either niche complementarity or selection effects hypothesis. Here, we used aboveground carbon (AGC) storage as proxy for ecosystem function in a South African mistbelt forest, and analyzed its relationship with species diversity, through functional diversity and functional dominance. We hypothesized that (1) diversity influences AGC through functional diversity and functional dominance effects; and (2) effects of diversity on AGC would be greater for functional dominance than for functional diversity. Community weight mean (CWM) of functional traits (wood density, specific leaf area, and maximum plant height) were calculated to assess functional dominance (selection effects). As for functional diversity (complementarity effects), multitrait functional diversity indices were computed. The first hypothesis was tested using structural equation modeling. For the second hypothesis, effects of environmental variables such as slope and altitude were tested first, and separate linear mixed-effects models were fitted afterward for functional diversity, functional dominance, and both. Results showed that AGC varied significantly along the slope gradient, with lower values at steeper sites. Species diversity (richness) had positive relationship with AGC, even when slope effects were considered. As predicted, diversity effects on AGC were mediated through functional diversity and functional dominance, suggesting that both the niche complementarity and the selection effects are not exclusively affecting carbon storage. However, the effects were greater for functional diversity than for functional dominance. Furthermore, functional dominance effects were strongly transmitted by CWM of

  17. Deep Learning-Based Data Forgery Detection in Automatic Generation Control

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Fengli [Univ. of Arkansas, Fayetteville, AR (United States); Li, Qinghua [Univ. of Arkansas, Fayetteville, AR (United States)

    2017-10-09

    Automatic Generation Control (AGC) is a key control system in the power grid. It is used to calculate the Area Control Error (ACE) based on frequency and tie-line power flow between balancing areas, and then adjust power generation to maintain the power system frequency in an acceptable range. However, attackers might inject malicious frequency or tie-line power flow measurements to mislead AGC to do false generation correction which will harm the power grid operation. Such attacks are hard to be detected since they do not violate physical power system models. In this work, we propose algorithms based on Neural Network and Fourier Transform to detect data forgery attacks in AGC. Different from the few previous work that rely on accurate load prediction to detect data forgery, our solution only uses the ACE data already available in existing AGC systems. In particular, our solution learns the normal patterns of ACE time series and detects abnormal patterns caused by artificial attacks. Evaluations on the real ACE dataset show that our methods have high detection accuracy.

  18. Visualizing MCNP Tally Segment Geometry and Coupling Results with ABAQUS

    International Nuclear Information System (INIS)

    J. R. Parry; J. A. Galbraith

    2007-01-01

    The Advanced Graphite Creep test, AGC-1, is planned for irradiation in the Advanced Test Reactor (ATR) in support of the Next Generation Nuclear Plant program. The experiment requires very detailed neutronics and thermal hydraulics analyses to show compliance with programmatic and ATR safety requirements. The MCNP model used for the neutronics analysis required hundreds of tally regions to provide the desired detail. A method for visualizing the hundreds of tally region geometries and the tally region results in 3 dimensions has been created to support the AGC-1 irradiation. Additionally, a method was created which would allow ABAQUS to access the results directly for the thermal analysis of the AGC-1 experiment

  19. FUEL-FLEXIBLE GASIFICATION-COMBUSTION TECHNOLOGY FOR PRODUCTION OF H2 AND SEQUESTRATION-READY CO2

    Energy Technology Data Exchange (ETDEWEB)

    George Rizeq; Janice West; Arnaldo Frydman; Vladimir Zamansky; Linda Denton; Hana Loreth; Tomasz Wiltowski

    2001-07-01

    It is expected that in the 21st century the Nation will continue to rely on fossil fuels for electricity, transportation, and chemicals. It will be necessary to improve both the thermodynamic efficiency and environmental impact performance of fossil fuel utilization. General Electric Energy and Environmental Research Corporation (GE EER) has developed an innovative fuel-flexible Advanced Gasification-Combustion (AGC) concept to produce H{sub 2} and sequestration-ready CO{sub 2} from solid fuels. The AGC module offers potential for reduced cost and increased energy efficiency relative to conventional gasification and combustion systems. GE EER was awarded a Vision-21 program from U.S. DOE NETL to develop the AGC technology. Work on this three-year program started on October 1, 2000. The project team includes GE EER, California Energy Commission, Southern Illinois University at Carbondale, and T. R. Miles, Technical Consultants, Inc. In the AGC technology, coal/opportunity fuels and air are simultaneously converted into separate streams of (1) pure hydrogen that can be utilized in fuel cells, (2) sequestration-ready CO{sub 2}, and (3) high temperature/pressure oxygen-depleted air to produce electricity in a gas turbine. The process produces near-zero emissions and, based on preliminary modeling work in the first quarter of this program, has an estimated process efficiency of approximately 67% based on electrical and H{sub 2} energy outputs relative to the higher heating value of coal. The three-year R&D program will determine the operating conditions that maximize separation of CO{sub 2} and pollutants from the vent gas, while simultaneously maximizing coal conversion efficiency and hydrogen production. The program integrates lab-, bench- and pilot-scale studies to demonstrate the AGC concept. This is the third quarterly technical progress report for the Vision-21 AGC program supported by U.S. DOE NETL (Contract: DE-FC26-00FT40974). This report summarizes program

  20. Clinicopathological study of asymptomatic gastric cancer and symptomatic gastric cancer

    International Nuclear Information System (INIS)

    Sato, Toshiteru

    2008-01-01

    Gastric cancer can be classified into two categories based on the absence or presence of symptoms at diagnosis. Differences in clinicopathological features and prognoses between asymptomatic gastric cancer (ACG) and symptomatic gastric cancer (SGC) can be used to inform diagnosis strategies and ultimately improve survival rates. All cases of gastric cancer (239 AGC, 323 SGC) diagnosed in our hospital between 1997 and 1999 were used in this study. ACG patients showed significantly higher frequency of males, cases of early cancer, cases found by a mass screening program, cases treated by endoscopic resection, cases treated by curative operation, cases of type 0 macroscopic finding, cases of histologically-differentiated type, and stage I cases. By contrast, SGC patients showed significantly higher numbers of cases treated by chemotherapy alone or best support care, cases of type 2, 3, and 4 macroscopic findings, cases occupying the whole stomach, and cases of stage II, III, IV. Statistically significant differences were also found for the 5-year survival rate (83.3% in AGC, 41.2% in SGC), the incidence of early cancer (90.1% in AGC, 83.7% in SGC), and for advanced cancer (38.7% in AGC, 22.7% in SGC). The higher incidence of advanced cases in SGC than in AGC (40.0% vs. 13.0%), coupled with the low 5-year survival rate of advanced SGC (22.7%), provides strong evidence of the importance of diagnosing gastric cancer during its asymptomatic period. (author)

  1. FUEL-FLEXIBLE GASIFICATION-COMBUSTION TECHNOLOGY FOR PRODUCTION OF H2 AND SEQUESTRATION-READY CO2

    International Nuclear Information System (INIS)

    George Rizeq; Ravi Kumar; Janice West; Vitali Lissianski; Neil Widmer; Vladimir Zamansky

    2001-01-01

    It is expected that in the 21st century the Nation will continue to rely on fossil fuels for electricity, transportation, and chemicals. It will be necessary to improve both the thermodynamic efficiency and environmental impact performance of fossil fuel utilization. General Electric Energy and Environmental Research Corporation (GE-EER) has developed an innovative fuel-flexible Advanced Gasification-Combustion (AGC) concept to produce H(sub 2) and sequestration-ready CO(sub 2) from solid fuels. The AGC module offers potential for reduced cost and increased energy efficiency relative to conventional gasification and combustion systems. GE-EER was awarded a Vision-21 program from U.S. DOE NETL to develop the AGC technology. Work on this three-year program started on October 1, 2000. The project team includes GE-EER, California Energy Commission, Southern Illinois University at Carbondale, and T. R. Miles, Technical Consultants, Inc. In the AGC technology, coal/opportunity fuels and air are simultaneously converted into separate streams of (1) pure hydrogen that can be utilized in fuel cells, (2) sequestration-ready CO(sub 2), and (3) high temperature/pressure oxygen depleted air to produce electricity in a gas turbine. The process produces near-zero emissions and, based on preliminary modeling work in the first quarter of this program, has an estimated process efficiency of approximately 67% based on electrical and H(sub 2) energy outputs relative to the higher heating value of coal. The three-year R and D program will determine the operating conditions that maximize separation of CO(sub 2) and pollutants from the vent gas, while simultaneously maximizing coal conversion efficiency and hydrogen production. The program integrates lab-, bench- and pilot-scale studies to demonstrate the AGC concept. This is the 1st quarterly progress report for the Vision-21 AGC program supported by U.S. DOE NETL (Contract: DE-FC26-00FT40974). This report summarizes program

  2. Adaptive automatic generation control with superconducting magnetic energy storage in power systems

    International Nuclear Information System (INIS)

    Tripathy, S.C.; Balasubramanian, R.; Nair, P.S.C.

    1992-01-01

    An improved automatic generation control (AGC) employing self-tuning adaptive control for both main AGC loop and superconducting magnetic energy storage (SMES) is presented in this paper. Computer simulations on a two-area interconnected power system show that the proposed adaptive control scheme is very effective in damping out oscillations caused by load disturbances and its performance is quite insensitive to controller gain parameter changes of SMES. A comprehensive comparative performance evaluation of control schemes using adaptive and non-adaptive controllers in the main AGC and in the SMES control loops is presented. The improvement in performance brought in by the adaptive scheme is particularly pronounced for load changes of random magnitude and duration. The proposed controller can be easily implemented using microprocessors

  3. Modeling And Control Of Excitation And Governor Based On PSO For MHPP

    Directory of Open Access Journals (Sweden)

    Adi Soeprijanto

    2013-07-01

    Full Text Available This paper presents the modeling and control of the excitation system via the automatic voltage regulator (AVR and governor system through the automatic generation control (AGC or frequency load control (FLC to improve stability on a micro hydro power plant (MHPP. Three main parts of the generation system are synchronous generator, AVR/excitation, AGC modelled linearly. Generator is modelled by a single machine connected to infinite bus (SMIB which is equipped by AVR and excitation linear model. Excitation control system made ??by optimizing the gain of the AVR (KA and the governor with the gain of the AGC (Ki. Optimization is done using the method improved particle swam optimization (IPSO. The main purpose of setting the gain of the AVR-AGC is to stabilize the oscillation frequency of the MHPP is connected to an infinite bus. Simulations are conducted by inputting step function with 5% load fluctuations as a representation of dynamic load. The simulation results show that the proposed method effectively raises the level  of electromechanical damping oscillations the SMIB by generating the comprehensive damping index (CDI is minimum.

  4. THE EFFECTIVENESS OF USING CLUSTER CONNECTION TOWARDS STUDENTS’ VOCABULARY MASTERY AT THE EIGHTH GRADE OF MTs DARUL IHSAN DURI

    Directory of Open Access Journals (Sweden)

    setiawati setiawati

    2017-12-01

    Full Text Available Penelitian ini bertujuan mengetahui keefektifan penggunaan cluster connection terhadap penguasaan kosakata siswa pada siswa kelas 8 MTs Darul Ihsan Duri. Behubungan dengan objek penelitian, peneliti menggunakan metode eksperimen. Model penelitiannya adalah kelompok pretest--post test untuk kelas control dan eksperimen. Penelitian ini diadakan pada MTs Darul Ihsan Duri pada tahun akademik 2015/2016. Populasi penelitian ini adalah kelas 8 MTs Darul Ihsan Duri pada tahun akademik 2015/2016. Total populasi penelitian adalah 62 siswa. Sampel penelitian ini adalah kelas VIII.A sebagai kelas kontrol, dan VIII.B sebagai kelas eksperimen. Kelas VIII.A terdiri atas 31 siswa. Kelas VIII.B terdiri atas 31 siswa. Dalam menganalisis data peneliti menggunakan Independent Sample T-Test. T-Test digunakan untuk mengetahui apakah teknik cluster connection effektif terhadap penguasaaan kosakata siswa. Hasil penelitian menunjukan bahwa penggunaan teknik cluster connection efektif terhadap penguasaaan kosakata siswa. Berdasarkan perhitungan statistic dalam menganalisis data peneliti memberikan tafsiran skor postest pada kelas eksperimen dan kelas kontrol. Dari perhitungan, t-test adalah 2.627 dan t-table adalah 2.00. karena nilai t-test (2.627 lebih tinggi dari pada t-table (2.00. Berdasarkan hasil penelitian, dapat disimpulkan bahwa alternative hipotesis (Ha diterima dan hipotesis null (Ho ditolak. Ini berarti pengajaran kosakata dengan teknik cluster connection adalah efektif.   This study aimed to know The Effectiveness of Using Cluster Connection Towards The Students’ VocabularyMastery at The Eighth Graders at MTs Darul Ihsan Duri. Related to the object of the research, the researcher used experimental method. The design of the research was control and experiment group; pretest – posttest design. The research was conducted at MTs. Daru lIhsan Duri in the academic year 2015/2016. The population of this research was the eighth grade students of MTs Darul Ihsan

  5. The economic burden of advanced gastric cancer in Taiwan.

    Science.gov (United States)

    Hong, Jihyung; Tsai, Yiling; Novick, Diego; Hsiao, Frank Chi-Huang; Cheng, Rebecca; Chen, Jen-Shi

    2017-09-16

    Gastric cancer is one of the leading causes of cancer-related deaths in both sexes worldwide, especially in Eastern Asia. This study aimed to estimate the economic burden of advanced gastric cancer (AGC) in Taiwan. The costs of AGC in 2013 were estimated using resource use data from a chart review study (n = 122 with AGC) and national statistics. Annual per-patient costs, where patients' follow-up periods were adjusted for, were estimated with 82 patients who had complete resource use data. The costs were composed of direct medical costs, direct non-medical costs (healthcare travel and caregiver costs), morbidity costs, and mortality costs. Relevant unit costs were retrieved mainly from literature and national statistics, and applied to the resource use data. A broad definition of morbidity and mortality costs was employed to value the productivity loss in patients with unpaid employment, economically inactive and unemployed as well as the life years after the age of retirement. Their narrow definitions were also used in sensitivity analyses, using age- and/or sex-specific employment rates. Forgone future earnings/productivity loss were discounted at 3%. Annual per-patient costs were projected to estimate the total costs of AGC at the national level with an estimated number of patients with AGC (N = 2611) in Taiwan in 2013. The mean age of the 82 patients was 59.3 (SD: 11.9) years, and 67.1% were male. Per-patient costs were US$26,431 for direct medical costs, US$4669 for direct non-medical costs, US$5758 for morbidity costs, and US$145,990 for mortality costs (per death). These per-patient costs were projected to incur total AGC costs of US$423 million at the national-level. Mortality costs accounted for 77.3% of the total costs, followed by direct medical costs (16.3%), morbidity costs (3.6%), and direct non-medical costs (2.9%). AGC was found to exert a significant economic burden in Taiwan, incurring US$423 million in 2013. This represents about 0.08% of

  6. A wide range and high speed automatic gain control

    International Nuclear Information System (INIS)

    Tacconi, E.; Christiansen, C.

    1993-05-01

    Automatic gain control (AGC) techniques have been largely used since the beginning of electronics, but in most of the applications the dynamic response is slow compared with the carrier frequency. The problem of developing an automatic gain control with high dynamic response and wide control range simultaneously is analyzed in this work. An ideal gain control law, with the property that the total loop gain remains constant independent of the carrier amplitude, is obtained. The resulting AGC behavior is compared by computer simulations with a linear multiplier AGC. The ideal gain control law can be approximated using a transconductance amplifier. A practical circuit that has been used at CERN in the radio frequency loops of the Booster Synchrotron is presented. The circuit has high speed and 80-dB gain control range

  7. Analysis of Wind Speed Forecasting Error Effects on Automatic Generation Control Performance

    Directory of Open Access Journals (Sweden)

    H. Rajabi Mashhadi

    2014-09-01

    Full Text Available The main goal of this paper is to study statistical indices and evaluate AGC indices in power system which has large penetration of the WTGs. Increasing penetration of wind turbine generations, needs to study more about impacts of it on power system frequency control. Frequency control is changed with unbalancing real-time system generation and load . Also wind turbine generations have more fluctuations and make system more unbalance. Then AGC loop helps to adjust system frequency and the scheduled tie-line powers. The quality of AGC loop is measured by some indices. A good index is a proper measure shows the AGC performance just as the power system operates. One of well-known measures in literature which was introduced by NERC is Control Performance Standards(CPS. Previously it is claimed that a key factor in CPS index is related to standard deviation of generation error, installed power and frequency response. This paper focuses on impact of a several hours-ahead wind speed forecast error on this factor. Furthermore evaluation of conventional control performances in the power systems with large-scale wind turbine penetration is studied. Effects of wind speed standard deviation and also degree of wind farm penetration are analyzed and importance of mentioned factor are criticized. In addition, influence of mean wind speed forecast error on this factor is investigated. The study system is a two area system which there is significant wind farm in one of those. The results show that mean wind speed forecast error has considerable effect on AGC performance while the mentioned key factor is insensitive to this mean error.

  8. Genome-Wide Identification and Evolutionary Analysis of Sarcocystis neurona Protein Kinases.

    Science.gov (United States)

    Murungi, Edwin K; Kariithi, Henry M

    2017-03-21

    The apicomplexan parasite Sarcocystis neurona causes equine protozoal myeloencephalitis (EPM), a degenerative neurological disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions, such as host cell invasion, cell cycle progression and host immune response evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans. We identified 97 putative PKs clustering within the various eukaryotic kinase groups. Although containing the universally-conserved PKA (AGC group), S. neurona kinome was devoid of PKB and PKC. Moreover, the kinome contains the six-conserved apicomplexan CDPKs (CAMK group). Several OPK atypical kinases, including ROPKs 19A, 27, 30, 33, 35 and 37 were identified. Notably, S. neurona is devoid of the virulence-associated ROPKs 5, 6, 18 and 38, as well as the Alpha and RIO kinases. Two out of the three S. neurona CK1 enzymes had high sequence similarities to Toxoplasma gondii TgCK1-α and TgCK1-β and the Plasmodium PfCK1. Further experimental studies on the S. neurona putative PKs identified in this study are required to validate the functional roles of the PKs and to understand their involvement in mechanisms that regulate various cellular processes and host-parasite interactions. Given the essentiality of apicomplexan PKs in the survival of apicomplexans, the current study offers a platform for future development of novel therapeutics for EPM, for instance via application of PK inhibitors to block parasite invasion and development in their host.

  9. Genome-Wide Identification and Evolutionary Analysis of Sarcocystis neurona Protein Kinases

    Directory of Open Access Journals (Sweden)

    Edwin K. Murungi

    2017-03-01

    Full Text Available The apicomplexan parasite Sarcocystis neurona causes equine protozoal myeloencephalitis (EPM, a degenerative neurological disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs have been implicated in a myriad of critical functions, such as host cell invasion, cell cycle progression and host immune response evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans. We identified 97 putative PKs clustering within the various eukaryotic kinase groups. Although containing the universally-conserved PKA (AGC group, S. neurona kinome was devoid of PKB and PKC. Moreover, the kinome contains the six-conserved apicomplexan CDPKs (CAMK group. Several OPK atypical kinases, including ROPKs 19A, 27, 30, 33, 35 and 37 were identified. Notably, S. neurona is devoid of the virulence-associated ROPKs 5, 6, 18 and 38, as well as the Alpha and RIO kinases. Two out of the three S. neurona CK1 enzymes had high sequence similarities to Toxoplasma gondii TgCK1-α and TgCK1-β and the Plasmodium PfCK1. Further experimental studies on the S. neurona putative PKs identified in this study are required to validate the functional roles of the PKs and to understand their involvement in mechanisms that regulate various cellular processes and host-parasite interactions. Given the essentiality of apicomplexan PKs in the survival of apicomplexans, the current study offers a platform for future development of novel therapeutics for EPM, for instance via application of PK inhibitors to block parasite invasion and development in their host.

  10. Application of GA optimization for automatic generation control design in an interconnected power system

    International Nuclear Information System (INIS)

    Golpira, H.; Bevrani, H.; Golpira, H.

    2011-01-01

    Highlights: → A realistic model for automatic generation control (AGC) design is proposed. → The model considers GRC, Speed governor dead band, filters and time delay. → The model provides an accurate model for the digital simulations. -- Abstract: This paper addresses a realistic model for automatic generation control (AGC) design in an interconnected power system. The proposed scheme considers generation rate constraint (GRC), dead band, and time delay imposed to the power system by governor-turbine, filters, thermodynamic process, and communication channels. Simplicity of structure and acceptable response of the well-known integral controller make it attractive for the power system AGC design problem. The Genetic algorithm (GA) is used to compute the decentralized control parameters to achieve an optimum operating point. A 3-control area power system is considered as a test system, and the closed-loop performance is examined in the presence of various constraints scenarios. It is shown that neglecting above physical constraints simultaneously or in part, leads to impractical and invalid results and may affect the system security, reliability and integrity. Taking to account the advantages of GA besides considering a more complete dynamic model provides a flexible and more realistic AGC system in comparison of existing conventional schemes.

  11. Cost-effectiveness Analysis of Fluorouracil, Leucovorin, and Irinotecan versus Epirubicin, Cisplatin, and Capecitabine in Patients with Advanced Gastric Adenocarcinoma

    Science.gov (United States)

    Wen, Feng; Zheng, Hanrui; Wu, Yifan; Wheeler, John; Zeng, Xiaoxi; Fu, Ping; Li, Qiu

    2016-01-01

    No standard treatment has been accepted widely for the first-/second-line therapy for advanced gastric cancer (AGC). The current study aimed to determine a preferred strategy between FOLFIRI (fluorouracil, leucovorin, and irinotecan) and ECX (epirubicin, cisplatin,and capecitabine) for AGC from the cost-effectiveness perspective. According to a French intergroup study, two groups (ECX arm and FOLFIRI arm) and three health states (progression-free survival (PFS), progressive disease (PD) and death) were analyzed in the current Markov model. All the medical costs were calculated from a Chinese societal perspective. Although FOLFIRI was an acceptable first-line therapy in the treatment of AGC with a better time-to treatment failure (TTF) compared to ECX, ECX arm (ECX followed by FOLFIRI) gained 0.08 quality-adjusted life months (QALMs) more effectiveness benefit compared with FOLFIRI arm (FOLFIRI followed by ECX). Additionally, a lower cost was found in ECX arm ($23,813.13 versus $24,983.70). Hence, the strategy of FOLFIRI arm is dominated by ECX arm ($4,125.8 per QALM in FOLIRI arm; $3,879.724 per QALM in ECX arm). ECX followed by FOLFIRI was a preferred strategy with more effectiveness and lower cost compared with FOLFIRI followed by ECX for the treatment of AGC. PMID:27824060

  12. Application of GA optimization for automatic generation control design in an interconnected power system

    Energy Technology Data Exchange (ETDEWEB)

    Golpira, H., E-mail: hemin.golpira@uok.ac.i [Department of Electrical and Computer Engineering, University of Kurdistan, Sanandaj, PO Box 416, Kurdistan (Iran, Islamic Republic of); Bevrani, H. [Department of Electrical and Computer Engineering, University of Kurdistan, Sanandaj, PO Box 416, Kurdistan (Iran, Islamic Republic of); Golpira, H. [Department of Industrial Engineering, Islamic Azad University, Sanandaj Branch, PO Box 618, Kurdistan (Iran, Islamic Republic of)

    2011-05-15

    Highlights: {yields} A realistic model for automatic generation control (AGC) design is proposed. {yields} The model considers GRC, Speed governor dead band, filters and time delay. {yields} The model provides an accurate model for the digital simulations. -- Abstract: This paper addresses a realistic model for automatic generation control (AGC) design in an interconnected power system. The proposed scheme considers generation rate constraint (GRC), dead band, and time delay imposed to the power system by governor-turbine, filters, thermodynamic process, and communication channels. Simplicity of structure and acceptable response of the well-known integral controller make it attractive for the power system AGC design problem. The Genetic algorithm (GA) is used to compute the decentralized control parameters to achieve an optimum operating point. A 3-control area power system is considered as a test system, and the closed-loop performance is examined in the presence of various constraints scenarios. It is shown that neglecting above physical constraints simultaneously or in part, leads to impractical and invalid results and may affect the system security, reliability and integrity. Taking to account the advantages of GA besides considering a more complete dynamic model provides a flexible and more realistic AGC system in comparison of existing conventional schemes.

  13. daptive Filter Used as a Dynamic Compensator in Automatic Gauge Control of Strip Rolling Processes

    Directory of Open Access Journals (Sweden)

    N. ROMAN

    2010-12-01

    Full Text Available The paper deals with a control structure of the strip thickness in a rolling mill of quarto type (AGC – Automatic Gauge Control. It performs two functions: the compensation of errors induced by unideal dynamics of the tracking systems lead by AGC system and the control adaptation to the change of dynamic properties of the tracking systems. The compensation of dynamical errors is achieved through inverse models of the tracking system, implemented as adaptive filters.

  14. Intelligent control schemes applied to Automatic Generation Control

    Directory of Open Access Journals (Sweden)

    Dingguo Chen

    2016-04-01

    Full Text Available Integrating ever increasing amount of renewable generating resources to interconnected power systems has created new challenges to the safety and reliability of today‟s power grids and posed new questions to be answered in the power system modeling, analysis and control. Automatic Generation Control (AGC must be extended to be able to accommodate the control of renewable generating assets. In addition, AGC is mandated to operate in accordance with the NERC‟s Control Performance Standard (CPS criteria, which represent a greater flexibility in relaxing the control of generating resources and yet assuring the stability and reliability of interconnected power systems when each balancing authority operates in full compliance. Enhancements in several aspects to the traditional AGC must be made in order to meet the aforementioned challenges. It is the intention of this paper to provide a systematic, mathematical formulation for AGC as a first attempt in the context of meeting the NERC CPS requirements and integrating renewable generating assets, which has not been seen reported in the literature to the best knowledge of the authors. Furthermore, this paper proposes neural network based predictive control schemes for AGC. The proposed controller is capable of handling complicated nonlinear dynamics in comparison with the conventional Proportional Integral (PI controller which is typically most effective to handle linear dynamics. The neural controller is designed in such a way that it has the capability of controlling the system generation in the relaxed manner so the ACE is controlled to a desired range instead of driving it to zero which would otherwise increase the control effort and cost; and most importantly the resulting system control performance meets the NERC CPS requirements and/or the NERC Balancing Authority’s ACE Limit (BAAL compliance requirements whichever are applicable.

  15. Does damming of the Colorado River affect the nursery area of blue shrimp Litopenaeus stylirostris (Decapoda: Penaeidae in the Upper Gulf of California?

    Directory of Open Access Journals (Sweden)

    Eugenio Alberto Aragón-Noriega

    2000-12-01

    Full Text Available After damming the Colorado River the freshwater flow was reduced to 1 % of its virgin flow to the Upper Gulf of California (UGC. The ecological effects need to be properly documented. The UGC is the nursery area for Litopenaeus stylirostris, the most profitable fishery in the zone. In order to know the relative abundance of L. stylirostris postlarval stage we conducted a sampled survey every 14 days in 1993, 1994 and 1997, plus an intensive sampling during a complete tide cycle in July 1995 and 1996. We did 10 min trawls each hour during the flood tide. Relative abundance of postlarvae was higher (pEl represamiento del Río Colorado ha ocasionado que el flujo de agua dulce sobre el Alto Golfo de California (AGC se haya reducido hasta el 1 % del flujo original. Se ha documentado el efecto de la reducción de agua dulce sobre las condiciones hidrográficas del AGC, pero las repercusiones ecológicas no se han descrito apropiadamente. El AGC ha sido área de crianza para especies comerciales como el camarón Litopenaeus stylirostris. Se hicieron recolectas de postlarvas de L. stylirostris en el AGC durante cinco años consecutivos. Los muestreos fueron catorcenalmente en los años de 1993, 1994 y 1997 y se realizó una recolecta diaria durante 15 días consecutivos en los años 1995 y 1996. Para ello se arrastró una red de plancton de 505 µ durante 10 min cada hora durante el flujo de marea. La abundancia relativa de las postlarvas de camarón en esta zona viaria considerablemente en años cuando el flujo de agua dulce incrementa. La abundancia es mayor hasta en un 200 % (p < 0.05 cuando existe descarga de agua dulce al AGC.

  16. Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-β in patients with advanced gastric cancer: A randomized clinical trial

    Science.gov (United States)

    YAMASHITA, KEISHI; SAKURAMOTO, SHINICHI; MIENO, HIROAKI; NEMOTO, MASAYUKI; SHIBATA, TOMOTAKA; KATADA, NATSUYA; OHTSUKI, SHIGEAKI; SAKAMOTO, YASUTOSHI; HOSHI, KEIKA; WANG, GUOQIN; HEMMI, OSAMU; SATOH, TOSHIHIKO; KIKUCHI, SHIRO; WATANABE, MASAHIKO

    2015-01-01

    Systemic abrogation of TGF-β signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide-Kureha (PSK) into tumor-bearing mice also showed tumor regression with reduced TGF-β. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF-β. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF-β was measured pre- and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF-β ranged from 1.85–43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly-differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF-β (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF-β remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF-β between groups A and B (P=0.019). PSK reduced the plasma TGF-β in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF-β by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC. PMID:26137253

  17. Prospective Evaluation of Changes in Tumor Size and Tumor Metabolism in Patients with Advanced Gastric Cancer Undergoing Chemotherapy: Association and Clinical Implication.

    Science.gov (United States)

    Park, Seongyeol; Ha, Seunggyun; Kwon, Hyun Woo; Kim, Woo Hyoung; Kim, Tae-Yong; Oh, Do-Youn; Cheon, Gi Jeong; Bang, Yung-Jue

    2017-06-01

    A change in tumor size is a well-validated and commonly used value for evaluating response to chemotherapy in cancer. Metabolic changes induced by chemotherapy are related to prognosis in several tumor types. However, the clinical implication of metabolic changes in patients with advanced gastric cancer (AGC) undergoing chemotherapy remains unclear. We aimed to evaluate response of tumor size and metabolism in AGC during chemotherapy and to reveal the relationship between them in view of their impact on patient survival. Methods: We prospectively enrolled patients with AGC before the initiation of first-line palliative chemotherapy. Using baseline and follow-up contrast-enhanced CT and 18 F-FDG PET, we assessed the tumor diameter, SUV max , and total lesion glycolysis in each lesion and their changes during chemotherapy at the same time. We included all lesions with the maximal longest diameters over 1 cm on CT, and each lesion was evaluated by matched 18 F-FDG PET. We analyzed the association between changes in tumor metabolism and tumor size and performed outcome analysis on overall survival (OS) and progression-free survival (PFS). Results: Seventy-four patients were enrolled, and the number of all lesions included in this study was 620. Compared with adenocarcinomas, poorly cohesive carcinomas demonstrated lower SUV max irrespective of tumor size ( P chemotherapy had a linear correlation with the changes in tumor size of each lesion, and a 30% tumor size reduction was associated with a 50% SUV max reduction ( P chemotherapy correlated with changes in tumor size in AGC. Considering both changes in metabolism and size could help predict a more accurate prognosis for AGC patients undergoing chemotherapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  18. Optimization of mass spectrometric parameters improve the identification performance of capillary zone electrophoresis for single-shot bottom-up proteomics analysis.

    Science.gov (United States)

    Zhang, Zhenbin; Dovichi, Norman J

    2018-02-25

    The effects of MS1 injection time, MS2 injection time, dynamic exclusion time, intensity threshold, and isolation width were investigated on the numbers of peptide and protein identifications for single-shot bottom-up proteomics analysis using CZE-MS/MS analysis of a Xenopus laevis tryptic digest. An electrokinetically pumped nanospray interface was used to couple a linear-polyacrylamide coated capillary to a Q Exactive HF mass spectrometer. A sensitive method that used a 1.4 Th isolation width, 60,000 MS2 resolution, 110 ms MS2 injection time, and a top 7 fragmentation produced the largest number of identifications when the CZE loading amount was less than 100 ng. A programmable autogain control method (pAGC) that used a 1.4 Th isolation width, 15,000 MS2 resolution, 110 ms MS2 injection time, and top 10 fragmentation produced the largest number of identifications for CZE loading amounts greater than 100 ng; 7218 unique peptides and 1653 protein groups were identified from 200 ng by using the pAGC method. The effect of mass spectrometer conditions on the performance of UPLC-MS/MS was also investigated. A fast method that used a 1.4 Th isolation width, 30,000 MS2 resolution, 45 ms MS2 injection time, and top 12 fragmentation produced the largest number of identifications for 200 ng UPLC loading amount (6025 unique peptides and 1501 protein groups). This is the first report where the identification number for CZE surpasses that of the UPLC at the 200 ng loading level. However, more peptides (11476) and protein groups (2378) were identified by using UPLC-MS/MS when the sample loading amount was increased to 2 μg with the fast method. To exploit the fast scan speed of the Q-Exactive HF mass spectrometer, higher sample loading amounts are required for single-shot bottom-up proteomics analysis using CZE-MS/MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Wolf pack hunting strategy for automatic generation control of an islanding smart distribution network

    International Nuclear Information System (INIS)

    Xi, Lei; Zhang, Zeyu; Yang, Bo; Huang, Linni; Yu, Tao

    2016-01-01

    Highlights: • A mixed homogeneous and heterogeneous multi-agent based wolf pack hunting (WPH) method is proposed. • WPH can effectively handle the ever-increasing penetration of renewable energy in smart grid. • An AGC power dispatch, coordinated control, and electric power autonomy of an ISDN is achieved. - Abstract: As the conventional centralized automatic generation control (AGC) is inadequate to handle the ever-increasing penetration of renewable energy and the requirement of plug-and-play of smart grid, this paper proposes a mixed homogeneous and heterogeneous multi-agent based wolf pack hunting (WPH) strategy to achieve a fast AGC power dispatch, optimal coordinated control, and electric power autonomy of an islanding smart distribution network (ISDN). A virtual consensus variable is employed to deal with the topology variation resulted from the excess of power limits and to achieve the plug-and-play of AGC units. Then an integrated objective of frequency deviation and short-term economic dispatch is developed, such that all units can maintain an optimal operation in the presence of load disturbances. Four case studies are undertaken to an ISDN with various distributed generations and microgrids. Simulation results demonstrate that WPH has a greater robustness and a faster dynamic optimization than that of conventional approaches, which can increase the utilization rate of the renewable energy and effectively resolve the coordination and electric power autonomy of ISDN.

  20. Proteomic profiling of an undefined microbial consortium cultured in fermented dairy manure: Methods development.

    Science.gov (United States)

    Hanson, Andrea J; Paszczynski, Andrzej J; Coats, Erik R

    2016-03-01

    The production of polyhydroxyalkanoates (PHA; bioplastics) from waste or surplus feedstocks using mixed microbial consortia (MMC) and aerobic dynamic feeding (ADF) is a growing field within mixed culture biotechnology. This study aimed to optimize a 2DE workflow to investigate the proteome dynamics of an MMC synthesizing PHA from fermented dairy manure. To mitigate the challenges posed to effective 2DE by this complex sample matrix, the bacterial biomass was purified using Accudenz gradient centrifugation (AGC) before protein extraction. The optimized 2DE method yielded high-quality gels suitable for quantitative comparative analysis and subsequent protein identification by LC-MS/MS. The optimized 2DE method could be adapted to other proteomic investigations involving MMC in complex organic or environmental matrices. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Kemampuan Representasi Matematis Luas dan Keliling Lingkaran Berdasarkan Teori Bruner di SMPN 9 Pontianak

    OpenAIRE

    Safitri, Eka; Hartoyo, Agung; Bistari

    2015-01-01

    This study is aimed to determine the ability and factors that caused the mathematical representation according to students' competence level in solving problems of area and perimeter of a circle. The method used was descriptive research in case study design. The subjects of research were students of grade VIIIA of SMPN 9 Pontianak. The results showed that the factors that caused low capacity of representation as follows: (1) Student who had a high competency level in enactive representation i...

  2. Application of ANN-SCE model on the evaluation of automatic generation control performance

    Energy Technology Data Exchange (ETDEWEB)

    Chang-Chien, L.R.; Lo, C.S.; Lee, K.S. [National Cheng Kung Univ., Tainan, Taiwan (China)

    2005-07-01

    An accurate evaluation of load frequency control (LFC) performance is needed to balance minute-to-minute electricity generation and demand. In this study, an artificial neural network-based system control error (ANN-SCE) model was used to assess the performance of automatic generation controls (AGC). The model was used to identify system dynamics for control references in supplementing AGC logic. The artificial neural network control error model was used to track a single area's LFC dynamics in Taiwan. The model was used to gauge the impacts of regulation control. Results of the training, evaluating, and projecting processes showed that the ANN-SCE model could be algebraically decomposed into components corresponding to different impact factors. The SCE information obtained from testing of various AGC gains provided data for the creation of a new control approach. The ANN-SCE model was used in conjunction with load forecasting and scheduled generation data to create an ANN-SCE identifier. The model successfully simulated SCE dynamics. 13 refs., 10 figs.

  3. Lipodistrofia em indivíduos vivendo com HIV/AIDS: fatores de risco para lipoatrofia e acúmulo de gordura corporal e associação com síndrome metabólica. Um estudo de coorte

    OpenAIRE

    Oliveira, Thais Gelenske Braga e

    2014-01-01

    O presente estudo teve como objetivo determinar as densidades de incidência e fatores associados com lipoatrofia(LA) e acúmulo de gordura corporal (AGC), determinar a densidade de incidência de síndrome metabólica (SM) de acordo com três critérios diferentes [American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI), International Diabetes Federation (IDF) e Harmonizing Metabolic Syndrome: a Joint Interim Statement (JIS)] e verificar a associação de LA e AGC com o desenv...

  4. Desflurane usage during anesthesia with and without N2O using FLOW-i Automatic Gas Control with three different wash-in speeds.

    Science.gov (United States)

    De Medts, Robrecht; Carette, Rik; De Wolf, Andre M; Hendrickx, Jan F A

    2017-06-09

    AGC ® (Automatic Gas Control) is the FLOW-i's automated low flow tool (Maquet, Solna, Sweden) that target controls the inspired O 2 (F I O 2 ) and end-expired desflurane concentration (F A des) while (by design) exponentially decreasing fresh gas flow (FGF) during wash-in to a maintenance default FGF of 300 mL min -1 . It also offers a choice of wash-in speeds for the inhaled agents. We examined AGC performance and hypothesized that the use of lower wash-in speeds and N 2 O both reduce desflurane usage (Vdes). After obtaining IRB approval and patient consent, 78 ASA I-II patients undergoing abdominal surgery were randomly assigned to 1 of 6 groups (n = 13 each), depending on carrier gas (O 2 /air or O 2 /N 2 O) and wash-in speed (AGC speed 2, 4, or 6) of desflurane, resulting in groups air/2, air/4, air/6, N 2 O/2, N 2 O/4, and N 2 O/6. The target for F I O 2 was set at 35%, while the F A des target was selected so that the AGC displayed 1.3 MAC (corrected for the additive affect of N 2 O if used). AGC was activated upon starting mechanical ventilation. Varvel's criteria were used to describe performance of achieving the targets. Patient demographics, end-expired N 2 O concentration, MAC, FGF, and Vdes were compared using ANOVA. Data are presented as mean ± standard deviation, except for Varvel's criteria (median ± quartiles). Patient demographics did not differ among the groups. Median performance error was -2-0% for F I O 2 and -3-1% for F A des; median absolute performance error was 1-2% for F I O 2 and 0-3% for F A des. MAC increased faster in N 2 O groups, but total MAC decreased 0.1-0.25 MAC below that in the O 2 /air groups after 60 min. The effect of wash-in speed on Vdes faded over time. N 2 O decreased Vdes by 62%. AGC performance for O 2 and desflurane targeting is excellent. After 1 h, the wash-in speeds tested are unlikely to affect desflurane usage. N 2 O usage decreases Vdes proportionally with its reduction in F A tdes.

  5. The alfalfa “almost darks” campaign: Pilot VLA HI observations of five high mass-to-light ratio systems

    International Nuclear Information System (INIS)

    Cannon, John M.; Martinkus, Charlotte P.; Leisman, Lukas; Haynes, Martha P.; Giovanelli, Riccardo; Hallenbeck, Gregory; Jones, Michael

    2015-01-01

    We present new Very Large Array (VLA) H i spectral line imaging of five sources discovered by the ALFALFA extragalactic survey. These targets are drawn from a larger sample of systems that were not uniquely identified with optical counterparts during ALFALFA processing, and as such have unusually high H i mass to light ratios. The candidate “Almost Dark” objects fall into four broad categories: (1) objects with nearby H i neighbors that are likely of tidal origin; (2) objects that appear to be part of a system of multiple H i sources, but which may not be tidal in origin; (3) objects isolated from nearby ALFALFA H i detections, but located near a gas-poor early type galaxy; (4) apparently isolated sources, with no object of coincident redshift within ∼400 kpc. Roughly 75% of the 200 objects without identified counterparts in the α.40 database (Haynes et al. 2011) fall into category 1 (likely tidal), and were not considered for synthesis follow-up observations. The pilot sample presented here (AGC193953, AGC208602, AGC208399, AGC226178, and AGC233638) contains the first five sources observed as part of a larger effort to characterize H i sources with no readily identifiable optical counterpart at single dish resolution (3.′5). These objects span a range of H i mass [7.41 < log(M Hi ) < 9.51] and H i mass to B-band luminosity ratios (3 < M Hi /L B < 9). We compare the H i total intensity and velocity fields to optical imaging drawn from the Sloan Digital Sky Survey and to ultraviolet imaging drawn from archival GALEX observations. Four of the sources with uncertain or no optical counterpart in the ALFALFA data are identified with low surface brightness optical counterparts in Sloan Digital Sky Survey imaging when compared with VLA H i intensity maps, and appear to be galaxies with clear signs of ordered rotation in the H i velocity fields. Three of these are detected in far-ultraviolet GALEX images, a likely indication of star formation within the last few

  6. Comparison of FOLFOX and DOF regimens as first-line treatment in East Asian patients with advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu M

    2018-01-01

    Full Text Available Mengyao Liu,1,2 Guofang Hu,2 Yuan Wang,2 Jun Guo,2 Liyan Liu,2 Xiao Han,2 Zhehai Wang2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, 2Department of Oncology, Shandong Cancer Hospital, affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China Background: Our study retrospectively assesses the safety and efficacy of the FOLFOX (oxaliplatin, fluorouracil, and leucovorin versus DOF (docetaxel, oxaliplatin, and fluorouracil regimens in untreated locally advanced gastric cancer (AGC.Patients and methods: A total of 108 patients underwent DOF (N=58 and FOLFOX (N=50 regimens. The end points were overall response rate (ORR, survival, and toxicity. Kaplan–Meier curve was used to estimate overall survival (OS and progression-free survival (PFS and Cox regression for multivariate analysis.Results: The ORRs were 50% for DOF and 30% for FOLFOX groups (P<0.05, and disease control rates were 91.4% and 72%, respectively. The median PFS and OS in DOF group were significantly better than FOLFOX group (8.2 versus 6.4 months, P<0.05; 16.3 versus 11.2 months, P<0.001. Both groups showed acceptable toxicity; all grades and grade 3–4 toxicity had no significant differences (P=0.071; P=0.247. However, the incidence of grade 3–4 peripheral neuropathy was significantly higher in DOF group (10.3% versus 2%, P<0.05. In the subgroup analysis for elderly AGC patients (≥65 years, administration of DOF also resulted in a superior PFS (8.5 versus 5.9 months; P=0.038 and OS (15.3 versus 9.8 months; P=0.004 compared with FOLFOX. However, DOF regimen was associated with more neutropenia (67% versus 30%; P<0.05, thrombocytopenia (61% versus 52%; P<0.05, and peripheral neuropathy (49% versus 22%; P<0.05.Conclusion: DOF regimen was more effective than FOLFOX for AGC, both in younger and older patients. The adverse effects of the two regimens were

  7. Can lymphovascular invasion be predicted by preoperative multiphasic dynamic CT in patients with advanced gastric cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Zelan; Liang, Cuishan; Huang, Xiaomei; Liu, Zaiyi [Southern Medical University, Guangzhou, Guangdong (China); Guangdong General Hospital, Guangdong Academy of Medical Sciences, Department of Radiology, Guangzhou, Guangdong Province (China); Liang, Changhong; Huang, Yanqi [Guangdong General Hospital, Guangdong Academy of Medical Sciences, Department of Radiology, Guangzhou, Guangdong Province (China); He, Lan [Guangdong General Hospital, Guangdong Academy of Medical Sciences, Department of Radiology, Guangzhou, Guangdong Province (China); South China University of Technology, School of Medicine, Guangzhou, Guangdong (China); Chen, Xin [The Affiliated Guangzhou First People' Hospital, Guangzhou Medical University, Department of Radiology, Guangzhou, Guangdong (China); Xiong, Yabing [Southern Medical University, Guangzhou, Guangdong (China)

    2017-08-15

    To determine whether multiphasic dynamic CT can preoperatively predict lymphovascular invasion (LVI) in advanced gastric cancer (AGC). 278 patients with AGC who underwent preoperative multiphasic dynamic CT were retrospectively recruited. Tumour CT attenuation difference between non-contrast and arterial (Δ{sub AP}), portal (Δ{sub PP}) and delayed phase (Δ{sub DP}), tumour-spleen attenuation difference in the portal phase (Δ{sub T-S}), tumour contrast enhancement ratios (CERs), tumour-to-spleen ratio (TSR) and tumour volumes were obtained. All CT-derived parameters and clinicopathological variables associated with LVI were analysed by univariate analysis, followed by multivariate and receiver operator characteristics (ROC) analysis. Associations between CT predictors for LVI and histopathological characteristics were evaluated by the chi-square test. Δ{sub PP} (OR, 1.056; 95% CI: 1.032-1.080) and Δ{sub T-S} (OR, 1.043; 95% CI: 1.020-1.066) are independent predictors for LVI in AGC. Δ{sub PP}, Δ{sub T-S} and their combination correctly predicted LVI in 74.8% (AUC, 0.775; sensitivity, 88.6%; specificity, 54.1%), 68.7% (AUC, 0.747; sensitivity, 68.3%; specificity, 69.4%) and 71.7% (AUC, 0.800; sensitivity, 67.6%; specificity, 77.8%), respectively. There were significant associations between CT predictors for LVI with tumour histological differentiation and Lauren classification. Multiphasic dynamic CT provides a non-invasive method to predict LVI in AGC through quantitative enhancement measurement. (orig.)

  8. Chemical and physiological aspects of isomers of conjugated fatty acids Aspectos químicos e fisiológicos de isômeros conjugados de ácidos graxos

    Directory of Open Access Journals (Sweden)

    Eliane Bonifácio Teixeira de Carvalho

    2010-06-01

    Full Text Available Conjugated fatty acid (CFA is the general term to describe the positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds. The CFAs of linoleic acid (CLAs are found naturally in foods derived from ruminant animals, meat, or dairy products. The CFAs of α-linolenic acid (CLNAs are found exclusively in various types of seed oils of plants. There are many investigations to assess the effects to health from CFAs consumption, which have been associated with physiological processes that are involved with non transmissible chronic diseases such as cancer, atherosclerosis, inflammation, and obesity. Conclusive studies about the CFAs effects in the body are still scarce and further research about their participation in physiological processes are necessary. This review aimed to discuss the influence of conjugated fatty acids on physiological processes in animal organism.Ácido graxo conjugado (AGC é o termo geral usado para descrever os isômeros posicionais e geométricos dos ácidos graxos poliinsaturados com duplas ligações conjugadas. Os AGCs do ácido linoléico (ALCs são encontrados naturalmente em alimentos derivados de animais ruminantes, carnes e produtos lácteos. Os AGCs do ácido α-linolênico (ALNCs são encontrados exclusivamente em óleos de sementes de vários tipos de plantas. Desenvolvem-se muitas investigações com o objetivo de avaliar os efeitos do consumo de AGCs para a saúde, já que estes têm sido associados a processos fisiológicos relacionados com doenças crônicas não transmissíveis como câncer, aterosclerose, inflamação e obesidade. Estudos conclusivos sobre os efeitos dos AGCs no organismo humano ainda são raros e mais pesquisas sobre sua atuação em processos fisiológicos são necessárias. O objetivo desta revisão é discutir a influência dos ácidos graxos conjugados sobre os processos fisiológicos.

  9. AGC 2 Irradiated Material Properties Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Rohrbaugh, David Thomas [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-05-01

    The Advanced Reactor Technologies Graphite Research and Development Program is conducting an extensive graphite irradiation experiment to provide data for licensing of a high temperature reactor (HTR) design. In past applications, graphite has been used effectively as a structural and moderator material in both research and commercial high temperature gas cooled reactor designs. , Nuclear graphite H 451, used previously in the United States for nuclear reactor graphite components, is no longer available. New nuclear graphite grades have been developed and are considered suitable candidates for new HTR reactor designs. To support the design and licensing of HTR core components within a commercial reactor, a complete properties database must be developed for these current grades of graphite. Quantitative data on in service material performance are required for the physical, mechanical, and thermal properties of each graphite grade, with a specific emphasis on data accounting for the life limiting effects of irradiation creep on key physical properties of the HTR candidate graphite grades. Further details on the research and development activities and associated rationale required to qualify nuclear grade graphite for use within the HTR are documented in the graphite technology research and development plan.

  10. Target of rapamycin complex 2 signals to downstream effector yeast protein kinase 2 (Ypk2) through adheres-voraciously-to-target-of-rapamycin-2 protein 1 (Avo1) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Liao, Hsien-Ching; Chen, Mei-Yu

    2012-02-24

    The conserved Ser/Thr kinase target of rapamycin (TOR) serves as a central regulator in controlling cell growth-related functions. There exist two distinct TOR complexes, TORC1 and TORC2, each coupling to specific downstream effectors and signaling pathways. In Saccharomyces cerevisiae, TORC2 is involved in regulating actin organization and maintaining cell wall integrity. Ypk2 (yeast protein kinase 2), a member of the cAMP-dependent, cGMP-dependent, and PKC (AGC) kinase family, is a TORC2 substrate known to participate in actin and cell wall regulation. Employing avo3(ts) mutants with defects in TORC2 functions that are suppressible by active Ypk2, we investigated the molecular interactions involved in mediating TORC2 signaling to Ypk2. GST pulldown assays in yeast lysates demonstrated physical interactions between Ypk2 and components of TORC2. In vitro binding assays revealed that Avo1 directly binds to Ypk2. In avo3(ts) mutants, the TORC2-Ypk2 interaction was reduced and could be restored by AVO1 overexpression, highlighting the important role of Avo1 in coupling TORC2 to Ypk2. The interaction was mapped to an internal region (amino acids 600-840) of Avo1 and a C-terminal region of Ypk2. Ypk2(334-677), a truncated form of Ypk2 containing the Avo1-interacting region, was able to interfere with Avo1-Ypk2 interaction in vitro. Overexpressing Ypk2(334-677) in yeast cells resulted in a perturbation of TORC2 functions, causing defective cell wall integrity, aberrant actin organization, and diminished TORC2-dependent Ypk2 phosphorylation evidenced by the loss of an electrophoretic mobility shift. Together, our data support the conclusion that the direct Avo1-Ypk2 interaction is crucial for TORC2 signaling to the downstream Ypk2 pathway.

  11. Economically important species dominate aboveground carbon storage in forests of southwestern Amazonia

    Directory of Open Access Journals (Sweden)

    N. Galia Selaya

    2017-06-01

    Full Text Available Tree species in tropical forests provide economically important goods and ecosystem services. In submontane forests of southwestern Amazonia, we investigated the degree to which tree species important for subsistence and trade contribute to aboveground carbon storage (AGC. We used 41 1-hectare plots to determine the species abundance, basal area, and AGC of stems > 10 cm diameter at breast height (dbh. Economically important taxa were classified using ethnobotanical studies and according to their stem density. These taxa (n = 263 accounted for 45% of total stems, 53% of total basal area, and 56% of total AGC, significantly more than taxa with minor or unknown uses (Welch test at p 40 cm and few stems in regeneration classes of dbh < 10 to 20 cm (e.g., Bertholletia excelsa, Cariniana spp., Cedrelinga spp., Ceiba spp., Dipteryx spp., whereas dominant Tetragastris spp., and Pseudolmedia spp. had most stems in low diameter classes and a median diameter of < 30 cm. Bertholletia excelsa, with 1.5 stems per hectare, showed the highest basal area of any species and accounted for 9% of AGC (11 Mg/ha, twice that of the second-ranking species. Our study shows that economic importance and carbon stocks in trees are closely linked in southwestern Amazonia. Unplanned harvests can disrupt synergistic dual roles altering carbon stocks temporally or permanently. Precautionary measures based on species ecology, demography, and regeneration traits should be at the forefront of REDD+ to reconcile maximum harvesting limits, biodiversity conservation, and sustainable forest management.

  12. PI2 controller based coordinated control with Redox Flow Battery and Unified Power Flow Controller for improved Restoration Indices in a deregulated power system

    Directory of Open Access Journals (Sweden)

    R. Thirunavukarasu

    2016-12-01

    Full Text Available The nature of power system restoration problem involves status assessment, optimization of generation capability and load pickup. This paper proposes the evaluation of Power System Restoration Indices (PSRI based on the Automatic Generation Control (AGC assessment of interconnected power system in a deregulated environment. The PSRI are useful for system planners to prepare the power system restoration plans and to improve the efficiency of the physical operation of the power system with the increased transmission capacity in the network. The stabilization of frequency and tie-line power oscillations in an interconnected power system becomes challenging when implemented in the future competitive environment. This paper also deals with the concept of AGC in two-area reheat power system having coordinated control action with Redox Flow Battery (RFB and Unified Power Flow Controller (UPFC are capable of controlling the network performance in a very fast manner and improve power transfer limits in order to have a better restoration. In addition to that a new Proportional–Double Integral (PI2 controller is designed and implemented in AGC loop and controller parameters are optimized through Bacterial Foraging Optimization (BFO algorithm. Simulation results reveal that the proposed PI2 controller is that it has good stability during load variations, excellent transient and dynamic responses when compared with the system comprising PI controller. Moreover the AGC loop with RFB coordinated with UPFC has greatly improved the dynamic response and it reduces the control input requirements, to ensure improved PSRI in order to provide the reduced restoration time, thereby improving the system reliability.

  13. The alfalfa “almost darks” campaign: Pilot VLA HI observations of five high mass-to-light ratio systems

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, John M.; Martinkus, Charlotte P. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Leisman, Lukas; Haynes, Martha P.; Giovanelli, Riccardo; Hallenbeck, Gregory; Jones, Michael, E-mail: jcannon@macalester.edu, E-mail: cmartink@macalester.edu, E-mail: leisman@astro.cornell.edu, E-mail: haynes@astro.cornell.edu, E-mail: riccardo@astro.cornell.edu, E-mail: hallenbg@union.edu, E-mail: jonesmg@astro.cornell.edu [Center for Radiophysics and Space Research, Space Sciences Building, Cornell University, Ithaca, NY 14853 (United States); and others

    2015-02-01

    We present new Very Large Array (VLA) H i spectral line imaging of five sources discovered by the ALFALFA extragalactic survey. These targets are drawn from a larger sample of systems that were not uniquely identified with optical counterparts during ALFALFA processing, and as such have unusually high H i mass to light ratios. The candidate “Almost Dark” objects fall into four broad categories: (1) objects with nearby H i neighbors that are likely of tidal origin; (2) objects that appear to be part of a system of multiple H i sources, but which may not be tidal in origin; (3) objects isolated from nearby ALFALFA H i detections, but located near a gas-poor early type galaxy; (4) apparently isolated sources, with no object of coincident redshift within ∼400 kpc. Roughly 75% of the 200 objects without identified counterparts in the α.40 database (Haynes et al. 2011) fall into category 1 (likely tidal), and were not considered for synthesis follow-up observations. The pilot sample presented here (AGC193953, AGC208602, AGC208399, AGC226178, and AGC233638) contains the first five sources observed as part of a larger effort to characterize H i sources with no readily identifiable optical counterpart at single dish resolution (3.′5). These objects span a range of H i mass [7.41 < log(M{sub Hi}) < 9.51] and H i mass to B-band luminosity ratios (3 < M{sub Hi}/L{sub B} < 9). We compare the H i total intensity and velocity fields to optical imaging drawn from the Sloan Digital Sky Survey and to ultraviolet imaging drawn from archival GALEX observations. Four of the sources with uncertain or no optical counterpart in the ALFALFA data are identified with low surface brightness optical counterparts in Sloan Digital Sky Survey imaging when compared with VLA H i intensity maps, and appear to be galaxies with clear signs of ordered rotation in the H i velocity fields. Three of these are detected in far-ultraviolet GALEX images, a likely indication of star formation within

  14. PKA and Apicomplexan Parasite Diseases.

    Science.gov (United States)

    Haidar, M; Ramdani, G; Kennedy, E J; Langsley, G

    2017-04-01

    The cAMP-dependent protein kinase PKA is a well-characterized member of the serine-threonine protein AGC kinase family and is the effector kinase of cAMP signaling. As such, PKA is involved in the control of a wide variety of cellular processes including metabolism, cell growth, gene expression and apoptosis. cAMP-dependent PKA signaling pathways play important roles during infection and virulence of various pathogens. Since fluxes in cAMP are involved in multiple intracellular functions, a variety of different pathological infectious processes can be affected by PKA signaling pathways. Here, we highlight some features of cAMP-PKA signaling that are relevant to Plasmodium falciparum -infection of erythrocytes and present an update on AKAP targeting of PKA in PGE2 signaling via EP4 in Theileria annulata -infection of leukocytes and discuss cAMP-PKA signling in Toxoplasma. © Georg Thieme Verlag KG Stuttgart · New York.

  15. A Time-Varying Potential-Based Demand Response Method for Mitigating the Impacts of Wind Power Forecasting Errors

    Directory of Open Access Journals (Sweden)

    Jia Ning

    2017-11-01

    Full Text Available The uncertainty of wind power results in wind power forecasting errors (WPFE which lead to difficulties in formulating dispatching strategies to maintain the power balance. Demand response (DR is a promising tool to balance power by alleviating the impact of WPFE. This paper offers a control method of combining DR and automatic generation control (AGC units to smooth the system’s imbalance, considering the real-time DR potential (DRP and security constraints. A schematic diagram is proposed from the perspective of a dispatching center that manages smart appliances including air conditioner (AC, water heater (WH, electric vehicle (EV loads, and AGC units to maximize the wind accommodation. The presented model schedules the AC, WH, and EV loads without compromising the consumers’ comfort preferences. Meanwhile, the ramp constraint of generators and power flow transmission constraint are considered to guarantee the safety and stability of the power system. To demonstrate the performance of the proposed approach, simulations are performed in an IEEE 24-node system. The results indicate that considerable benefits can be realized by coordinating the DR and AGC units to mitigate the WPFE impacts.

  16. United States advanced technologies

    International Nuclear Information System (INIS)

    Longenecker, J.R.

    1985-01-01

    In the United States, the advanced technologies have been applied to uranium enrichment as a means by which it can be assured that nuclear fuel cost will remain competitive in the future. The United States is strongly committed to the development of advanced enrichment technology, and has brought both advanced gas centrifuge (AGC) and atomic vapor laser isotope separation (AVLIS) programs to a point of significant technical refinement. The ability to deploy advanced technologies is the basis for the confidence in competitive future price. Unfortunately, the development of advanced technologies is capital intensive. The year 1985 is the key year for advanced technology development in the United States, since the decision on the primary enrichment technology for the future, AGC or AVLIS, will be made shortly. The background on the technology selection process, the highlights of AGC and AVLIS programs and the way to proceed after the process selection are described. The key objective is to maximize the sales volume and minimize the operating cost. This will help the utilities in other countries supply low cost energy on a reliable, long term basis. (Kako, I.)

  17. AGC 2 Irradiation Creep Strain Data Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Windes, William E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rohrbaugh, David T. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Swank, W. David [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-08-01

    The Advanced Reactor Technologies Graphite Research and Development Program is conducting an extensive graphite irradiation experiment to provide data for licensing of a high temperature reactor (HTR) design. In past applications, graphite has been used effectively as a structural and moderator material in both research and commercial high temperature gas cooled reactor designs. Nuclear graphite H-451, used previously in the United States for nuclear reactor graphite components, is no longer available. New nuclear graphite grades have been developed and are considered suitable candidates for new HTR reactor designs. To support the design and licensing of HTR core components within a commercial reactor, a complete properties database must be developed for these current grades of graphite. Quantitative data on in service material performance are required for the physical, mechanical, and thermal properties of each graphite grade, with a specific emphasis on data accounting for the life limiting effects of irradiation creep on key physical properties of the HTR candidate graphite grades. Further details on the research and development activities and associated rationale required to qualify nuclear grade graphite for use within the HTR are documented in the graphite technology research and development plan.

  18. AGC 2 Irradiation Creep Strain Data Analysis

    International Nuclear Information System (INIS)

    Windes, William E.; Rohrbaugh, David T.; Swank, W. David

    2016-01-01

    The Advanced Reactor Technologies Graphite Research and Development Program is conducting an extensive graphite irradiation experiment to provide data for licensing of a high temperature reactor (HTR) design. In past applications, graphite has been used effectively as a structural and moderator material in both research and commercial high temperature gas cooled reactor designs. Nuclear graphite H-451, used previously in the United States for nuclear reactor graphite components, is no longer available. New nuclear graphite grades have been developed and are considered suitable candidates for new HTR reactor designs. To support the design and licensing of HTR core components within a commercial reactor, a complete properties database must be developed for these current grades of graphite. Quantitative data on in service material performance are required for the physical, mechanical, and thermal properties of each graphite grade, with a specific emphasis on data accounting for the life limiting effects of irradiation creep on key physical properties of the HTR candidate graphite grades. Further details on the research and development activities and associated rationale required to qualify nuclear grade graphite for use within the HTR are documented in the graphite technology research and development plan.

  19. THE EFFECTIVENESS OF USING CLUSTER CONNECTION TOWARDS STUDENTS’ VOCABULARY MASTERY AT THE EIGHTH GRADE OF MTs DARUL IHSAN DURI

    Directory of Open Access Journals (Sweden)

    Setiawati

    2017-12-01

    Full Text Available This study aimed to know The Effectiveness of Using Cluster Connection Towards The Students’ VocabularyMastery at The Eighth Graders at MTs Darul Ihsan Duri. Related to the object of the research, the researcher used experimental method. The design of the research was control and experiment group; pretest – posttest design. The research was conducted at MTs. Daru lIhsan Duri in the academic year 2015/2016. The population of this research was the eighth grade students of MTs Darul Ihsan Duri. The total population was 62 students. The sample of the research was class VIII.A as control class and class VIII.B as experimental class. Class VIII.A consisted of 31 students. Class VIII.B consisted of 31 students. In analyzing the research data, the researcher used Independent sampleT-Test. T-Test was used to know whether cluster connection technique is effective toward the students’ vocabulary mastery. The result of the research showed that using cluster connection technique was effective toward the students’ vocabulary mastery. Based on statistical calculation in data analysis, the researcher gave interpretation of posttest score in experiment class and the control class. From the calculation, t-test value was 2.627 and t-table was 2.00. Because t-test value (2.627 was higher than t-table (2.00, it could be concluded that alternative hypothesis (Ha was accepted and the null hypothesis (Ho was rejected. It means that teaching vocabulary by using cluster connection is effective

  20. Radiation therapy and arterial infusion chemotherapy for advanced gallbladder cancer

    International Nuclear Information System (INIS)

    Hokodate, Hirofumi; Saito, Hiroya; Takeuchi, Shuhei; Horikawa, Masahiro; Takamura, Akio

    2009-01-01

    The standard therapy is not yet established for the unresectable advanced gallbladder cancer (AGC). Here described is the outcome of authors' therapeutic protocol for AGC during the time Jan., 1989-Dec., 2008. Subjects are 73 patients (M 32/F 41, average age 65 y) with AGC of Stage IV. One shot arterial infusion (AI) of EEP regimen (etoposide (VP16)/4'epiadriamycin (EPIR)/cisplatin (CDDP)) is conducted via hepatic artery proper or common at the first angiography and one week later, external radiation therapy (RT), with about 30-50 Gy/6 fractions (actually, 12-61.6 Gy). AI is weekly done with FP regimen (CDDP/5-fluorouracil (FU)) through the reservoir indwelled in the gastroduodenal artery for 6 months where a metal stent for the stegnosis of bile duct is used if necessary after RT, and in recent days, additionally with biweekly CDDP/gemcitabin (GEM) regimen depending on patient's state after FP. As a result, RT is conducted to 62 cases (RT alone 8 cases), AI, 64 (alone, 10), and RT+AI, 54. Response is found to be 49% (CR 7 cases and PR, 28). Survivals 1- and 3-year are 39 and 6%, respectively, and average survival time, 408 days. Survival rate in (RT+AI) is significantly superior to that in AI alone and in RT alone. Prognosis in patients with jaundice, hepatic or duodenal invasion is significantly inferior to those without the symptom, and in non-responded cases, to responded cases. Complications like hepatic abscess are seen in 4 cases at 6 months after treatment. Four actual case-reports are presented in details with their images. Combination of RT+AI is suggested to be of utility for AGC, of which multi-center trial is awaited with addition of newer anti-cancers developed recently. (K.T.)

  1. Multidetector CT of Locally Invasive Advanced Gastric Cancer: Value of Oblique Coronal Reconstructed Images for the Assessment of Local Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jin Hee; Kim, Ah Yong; Kim, Hye Jin; Yook, Jeong Hwan; Yu, Eun Sil; Jang, Yoon Jin; Park, Seong Ho; Shin, Yong Moon; Ha, Hyun Kwon [Asan Medical Center, Seoul (Korea, Republic of)

    2010-01-15

    To evaluate the diagnostic value of oblique coronal reconstructed CT images to determine the local invasion of advanced gastric cancer (AGC). Thirty-four consecutive patients, who were suspected to have locally invasive advanced gastric cancer (more than T3 stage) on a preoperative MDCT scan and underwent a diagnostic or curative laparotomy, were enrolled in this study. Two reviewers performed an independent blind review of three series of MDCT images in random order; axial (AXI), conventional coronal (CCI), and oblique coronal (OCI) (parallel to long axis of gastric body and pancreas) images. In assessing the local invasion, the reader's confidence for the local invasion of AGC was graded using a five point scale (1 = definitely negative, 5 = definitely positive: T4). With surgical findings and histopathological proofs as reference standards, the diagnostic performance of the three different plans of CT images was employed for the verification of local invasion of AGC on a preoperative CT scan using the receiver operating characteristic (ROC) method. Agreements between the two reviewers were analyzed using weighted kappa statistics. Results: In 19 out of 34 patients, local invasion was confirmed surgically or histopathologically (13 pancreas invasion, 6 liver invasion, 4 major vascular invasion, 3 colon and mesocolon invasion, and 2 spleen invasion). The diagnostic performance of OCI was superior to AXI or CCI in the local invasion of AGC. The differences in the area under the curve of AXI (0.770 {+-} 0.087, 0.700 {+-} 0.094), CCI (0.884 {+-} 0.058, 0.958 {+-} 0.038), and OCI (0.954 {+-} 0.050, 0.956 {+-} 0.049), were statistically significant for both reviewers. Inter-observer agreement was excellent for OCI ({kappa}= .973), which was greater than CCI (({kappa}= .839), and AXI (({kappa}= .763). On a CT scan, OCI might be a useful imaging technique in evaluating locally invasive advanced gastric cancer.

  2. National-scale estimation of gross forest aboveground carbon loss: a case study of the Democratic Republic of the Congo

    International Nuclear Information System (INIS)

    Tyukavina, A; Potapov, P V; Turubanova, S A; Hansen, M C; Stehman, S V; Baccini, A; Goetz, S J; Laporte, N T; Houghton, R A

    2013-01-01

    Recent advances in remote sensing enable the mapping and monitoring of carbon stocks without relying on extensive in situ measurements. The Democratic Republic of the Congo (DRC) is among the countries where national forest inventories (NFI) are either non-existent or out of date. Here we demonstrate a method for estimating national-scale gross forest aboveground carbon (AGC) loss and associated uncertainties using remotely sensed-derived forest cover loss and biomass carbon density data. Lidar data were used as a surrogate for NFI plot measurements to estimate carbon stocks and AGC loss based on forest type and activity data derived using time-series multispectral imagery. Specifically, DRC forest type and loss from the FACET (Forêts d’Afrique Centrale Evaluées par Télédétection) product, created using Landsat data, were related to carbon data derived from the Geoscience Laser Altimeter System (GLAS). Validation data for FACET forest area loss were created at a 30-m spatial resolution and compared to the 60-m spatial resolution FACET map. We produced two gross AGC loss estimates for the DRC for the last decade (2000–2010): a map-scale estimate (53.3 ± 9.8 Tg C yr −1 ) accounting for whole-pixel classification errors in the 60-m resolution FACET forest cover change product, and a sub-grid estimate (72.1 ± 12.7 Tg C yr −1 ) that took into account 60-m cells that experienced partial forest loss. Our sub-grid forest cover and AGC loss estimates, which included smaller-scale forest disturbances, exceed published assessments. Results raise the issue of scale in forest cover change mapping and validation, and subsequent impacts on remotely sensed carbon stock change estimation, particularly for smallholder dominated systems such as the DRC. (letter)

  3. Aboveground Biomass and Carbon in a South African Mistbelt Forest and the Relationships with Tree Species Diversity and Forest Structures

    Directory of Open Access Journals (Sweden)

    Sylvanus Mensah

    2016-04-01

    Full Text Available Biomass and carbon stocks are key information criteria to understand the role of forests in regulating global climate. However, for a bio-rich continent like Africa, ground-based measurements for accurate estimation of carbon are scarce, and the variables affecting the forest carbon are not well understood. Here, we present the first biomass study conducted in South Africa Mistbelt forests. Using data from a non-destructive sampling of 59 trees of four species, we (1 evaluated the accuracy of multispecies aboveground biomass (AGB models, using predictors such as diameter at breast height (DBH, total height (H and wood density; (2 estimated the amount of biomass and carbon stored in the aboveground compartment of Mistbelt forests and (3 explored the variation of aboveground carbon (AGC in relation to tree species diversity and structural variables. We found significant effects of species on wood density and AGB. Among the candidate models, the model that incorporated DBH and H as a compound variable (DBH2 × H was the best fitting. AGB and AGC values were highly variable across all plots, with average values of 358.1 Mg·ha−1 and 179.0 Mg·C·ha−1, respectively. Few species contributed 80% of AGC stock, probably as a result of selection effect. Stand basal area, basal area of the ten most important species and basal area of the largest trees were the most influencing variables. Tree species richness was also positively correlated with AGC, but the basal area of smaller trees was not. These results enable insights into the role of biodiversity in maintaining carbon storage and the possibilities for sustainable strategies for timber harvesting without risk of significant biomass decline.

  4. A low power automatic gain control loop for a receiver

    Energy Technology Data Exchange (ETDEWEB)

    Li Guofeng; Geng Zhiqing; Wu Nanjian, E-mail: nanjian@red.semi.ac.c [State Key Laboratory for Super lattices and Microstructures, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083 (China)

    2010-09-15

    This paper proposes a new structure to lower the power consumption of a variable gain amplifier (VGA) and keep the linearity of the VGA unchanged. The structure is used in a high rate amplitude-shift keying (ASK) based IF-stage. It includes an automatic gain control (AGC) loop and ASK demodulator. The AGC mainly consists of six-stage VGAs. The IF-stage is realized in 0.18 {mu}m CMOS technology. The measurement results show that the power consumption of the whole system is very low. The system consumes 730 {mu}A while operating at 1.8 V. The minimum ASK signal the system could detect is 0.7 mV (peak to peak amplitude). (semiconductor integrated circuits)

  5. Examining spectral properties of Landsat 8 OLI for predicting above-ground carbon of Labanan Forest, Berau

    Science.gov (United States)

    Suhardiman, A.; Tampubolon, B. A.; Sumaryono, M.

    2018-04-01

    Many studies revealed significant correlation between satellite image properties and forest data attributes such as stand volume, biomass or carbon stock. However, further study is still relevant due to advancement of remote sensing technology as well as improvement on methods of data analysis. In this study, the properties of three vegetation indices derived from Landsat 8 OLI were tested upon above-ground carbon stock data from 50 circular sample plots (30-meter radius) from ground survey in PT. Inhutani I forest concession in Labanan, Berau, East Kalimantan. Correlation analysis using Pearson method exhibited a promising results when the coefficient of correlation (r-value) was higher than 0.5. Further regression analysis was carried out to develop mathematical model describing the correlation between sample plots data and vegetation index image using various mathematical models.Power and exponential model were demonstrated a good result for all vegetation indices. In order to choose the most adequate mathematical model for predicting Above-ground Carbon (AGC), the Bayesian Information Criterion (BIC) was applied. The lowest BIC value (i.e. -376.41) shown by Transformed Vegetation Index (TVI) indicates this formula, AGC = 9.608*TVI21.54, is the best predictor of AGC of study area.

  6. Adaptive Neuro-Fuzzy Based Gain Controller for Erbium-Doped Fiber Amplifiers

    Directory of Open Access Journals (Sweden)

    YUCEL, M.

    2017-02-01

    Full Text Available Erbium-doped fiber amplifiers (EDFA must have a flat gain profile which is a very important parameter such as wavelength division multiplexing (WDM and dense WDM (DWDM applications for long-haul optical communication systems and networks. For this reason, it is crucial to hold a stable signal power per optical channel. For the purpose of overcoming performance decline of optical networks and long-haul optical systems, the gain of the EDFA must be controlled for it to be fixed at a high speed. In this study, due to the signal power attenuation in long-haul fiber optic communication systems and non-equal signal amplification in each channel, an automatic gain controller (AGC is designed based on the adaptive neuro-fuzzy inference system (ANFIS for EDFAs. The intelligent gain controller is implemented and the performance of this new electronic control method is demonstrated. The proposed ANFIS-based AGC-EDFA uses the experimental dataset to produce the ANFIS-based sets and the rule base. Laser diode currents are predicted within the accuracy rating over 98 percent with the proposed ANFIS-based system. Upon comparing ANFIS-based AGC-EDFA and experimental results, they were found to be very close and compatible.

  7. Layer-by-layer construction of graphene/cobalt phthalocyanine composite film on activated GCE for application as a nitrite sensor

    International Nuclear Information System (INIS)

    Cui, Lili; Pu, Tao; Liu, Ying; He, Xingquan

    2013-01-01

    Graphical abstract: A novel nitrite sensor was prepared by using LBL technique which for the first time used the activated positively charged glassy carbon electrode (A-GCE) as the substrate. The nitrite sensor shows super stability for consecutive CV testing and rather low detection limit. -- Abstract: In this paper, a novel graphene/cobalt phthalocyanine composite film was prepared by layer-by-layer (LBL) technique which for the first time used the activated positively charged glassy carbon electrode (A-GCE) as the substrate. The surface morphology of graphene/cobalt phthalocyanine composite film was characterized by scanning electron microscopy (SEM) and atomic force microscope (AFM). It is found that graphene/cobalt phthalocyanine composite film modified GCE exhibits good catalytic activity toward the oxidation of nitrite. The oxidation current barely decreases in consecutive CV test. Furthermore, the modified GCE shows long-term stability after 70 days. The super good stability can be attributed to the immobilization and dispersion of electroactive cobalt phthalocyanine by graphene, and using A-GCE as substrate which can enhance the interaction force between GCE and electroactive cobalt phthalocyanine. The nitrite sensor shows rather low detection limit of 0.084 μM at a signal-to-noise ratio = 3 (S/N = 3)

  8. Wind power integration into the automatic generation control of power systems with large-scale wind power

    Directory of Open Access Journals (Sweden)

    Abdul Basit

    2014-10-01

    Full Text Available Transmission system operators have an increased interest in the active participation of wind power plants (WPP in the power balance control of power systems with large wind power penetration. The emphasis in this study is on the integration of WPPs into the automatic generation control (AGC of the power system. The present paper proposes a coordinated control strategy for the AGC between combined heat and power plants (CHPs and WPPs to enhance the security and the reliability of a power system operation in the case of a large wind power penetration. The proposed strategy, described and exemplified for the future Danish power system, takes the hour-ahead regulating power plan for generation and power exchange with neighbouring power systems into account. The performance of the proposed strategy for coordinated secondary control is assessed and discussed by means of simulations for different possible future scenarios, when wind power production in the power system is high and conventional production from CHPs is at a minimum level. The investigation results of the proposed control strategy have shown that the WPPs can actively help the AGC, and reduce the real-time power imbalance in the power system, by down regulating their production when CHPs are unable to provide the required response.

  9. Applying fractional order PID to design TCSC-based damping controller in coordination with automatic generation control of interconnected multi-source power system

    Directory of Open Access Journals (Sweden)

    Javad Morsali

    2017-02-01

    Full Text Available In this paper, fractional order proportional-integral-differential (FOPID controller is employed in the design of thyristor controlled series capacitor (TCSC-based damping controller in coordination with the secondary integral controller as automatic generation control (AGC loop. In doing so, the contribution of the TCSC in tie-line power exchange is extracted mathematically for small load disturbance. Adjustable parameters of the proposed FOPID-based TCSC damping controller and the AGC loop are optimized concurrently via an improved particle swarm optimization (IPSO algorithm which is reinforced by chaotic parameter and crossover operator to obtain a globally optimal solution. The powerful FOMCON toolbox is used along with MATLAB for handling fractional order modeling and control. An interconnected multi-source power system is simulated regarding the physical constraints of generation rate constraint (GRC nonlinearity and governor dead band (GDB effect. Simulation results using FOMCON toolbox demonstrate that the proposed FOPID-based TCSC damping controller achieves the greatest dynamic performance under different load perturbation patterns in comparison with phase lead-lag and classical PID-based TCSC damping controllers, all in coordination with the integral AGC. Moreover, sensitivity analyses are performed to show the robustness of the proposed controller under various uncertainty scenarios.

  10. Automated Gain Control and Internal Calibration With External Ion Accumulation Capillary liquid chromatography-electrospray ionization-fourier transform ion cyclotron resonance.

    Energy Technology Data Exchange (ETDEWEB)

    Belov, Mikhail E.(VISITORS); Zhang, Rui (BATTELLE (PACIFIC NW LAB)); Strittmatter, Eric F.(BATTELLE (PACIFIC NW LAB)); Prior, David C.(BATTELLE (PACIFIC NW LAB)); Tang, Keqi (BATTELLE (PACIFIC NW LAB)); Smith, Richard D.(BATTELLE (PACIFIC NW LAB))

    2003-08-15

    When combined with capillary LC separations, Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ESI-FTICR MS) has increasingly been applied for advanced characterization of proteolytic digests. Incorporation of external (to the ICR cell) ion accumulation multipoles with FTICR for ion pre selection and accumulation has enhanced the dynamic range, sensitivity and duty cycle of measurements. However, the highly variable ion production rate from an LC separation can result in overfilling of the external trap, resulting in m/z discrimination and fragmentation of peptide ions. An excessive space charge trapped in the ICR cell causes significant shifts in the detected ion cyclotron frequencies, reducing the achievable mass measurement accuracy (MMA) for protein identification. To eliminate m/z discrimination in the external ion trap, further increase the duty cycle and improve MMA, we developed a capability for data-dependent adjustment of ion accumulation times in the course of an LC separation, referred to as Automated Gain Control (AGC), in combination with low kinetic energy gated ion trapping and internal calibration using a dual-channel electrodynamic ion funnel. The system was initially evaluated in the analysis of a 0.5 mg/mL tryptic digest of bovine serum albumin. The implementation of LC/ESI/AGC/FTICR with internal calibration gave rise to a {approx} 10-fold increase in the number of identified tryptic peptides within mass measurement accuracy of 2 ppm as compared to that detected during the conventional LC/FTICR run with a fixed ion accumulation time and external calibration.

  11. Comparing side chain packing in soluble proteins, protein-protein interfaces, and transmembrane proteins.

    Science.gov (United States)

    Gaines, J C; Acebes, S; Virrueta, A; Butler, M; Regan, L; O'Hern, C S

    2018-05-01

    We compare side chain prediction and packing of core and non-core regions of soluble proteins, protein-protein interfaces, and transmembrane proteins. We first identified or created comparable databases of high-resolution crystal structures of these 3 protein classes. We show that the solvent-inaccessible cores of the 3 classes of proteins are equally densely packed. As a result, the side chains of core residues at protein-protein interfaces and in the membrane-exposed regions of transmembrane proteins can be predicted by the hard-sphere plus stereochemical constraint model with the same high prediction accuracies (>90%) as core residues in soluble proteins. We also find that for all 3 classes of proteins, as one moves away from the solvent-inaccessible core, the packing fraction decreases as the solvent accessibility increases. However, the side chain predictability remains high (80% within 30°) up to a relative solvent accessibility, rSASA≲0.3, for all 3 protein classes. Our results show that ≈40% of the interface regions in protein complexes are "core", that is, densely packed with side chain conformations that can be accurately predicted using the hard-sphere model. We propose packing fraction as a metric that can be used to distinguish real protein-protein interactions from designed, non-binding, decoys. Our results also show that cores of membrane proteins are the same as cores of soluble proteins. Thus, the computational methods we are developing for the analysis of the effect of hydrophobic core mutations in soluble proteins will be equally applicable to analyses of mutations in membrane proteins. © 2018 Wiley Periodicals, Inc.

  12. Protein docking prediction using predicted protein-protein interface

    Directory of Open Access Journals (Sweden)

    Li Bin

    2012-01-01

    Full Text Available Abstract Background Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. Results We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm, is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. Conclusion We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

  13. Protein docking prediction using predicted protein-protein interface.

    Science.gov (United States)

    Li, Bin; Kihara, Daisuke

    2012-01-10

    Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm), is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

  14. Design of an optimal SMES for automatic generation control of two-area thermal power system using Cuckoo search algorithm

    Directory of Open Access Journals (Sweden)

    Sabita Chaine

    2015-05-01

    Full Text Available This work presents a methodology adopted in order to tune the controller parameters of superconducting magnetic energy storage (SMES system in the automatic generation control (AGC of a two-area thermal power system. The gains of integral controllers of AGC loop, proportional controller of SMES loop and gains of the current feedback loop of the inductor in SMES are optimized simultaneously in order to achieve a desired performance. Recently proposed intelligent technique based algorithm known as Cuckoo search algorithm (CSA is applied for optimization. Sensitivity and robustness of the tuned gains tested at different operating conditions prove the effectiveness of fast acting energy storage devices like SMES in damping out oscillations in power system when their controllers are properly tuned.

  15. Fabrication of oxide layer on zirconium by micro-arc oxidation: Structural and antimicrobial characteristics.

    Science.gov (United States)

    Fidan, S; Muhaffel, F; Riool, M; Cempura, G; de Boer, L; Zaat, S A J; Filemonowicz, A Czyrska-; Cimenoglu, H

    2017-02-01

    The aim of this study was to cover the surfaces of zirconium (Zr) with an antimicrobial layer for biomedical applications. For this purpose, the micro-arc oxidation (MAO) process was employed in a sodium silicate and sodium hydroxide containing base electrolyte with and without addition of silver acetate (AgC 2 H 3 O 2 ). In general, synthesized MAO layers were composed of zirconium oxide (ZrO 2 ) and zircon (ZrSiO 4 ). Addition of AgC 2 H 3 O 2 into the base electrolyte caused homogenous precipitation of silver-containing particles in the MAO layer, which exhibited excellent antibacterial efficiency against methicillin-resistant Staphylococcus aureus (MRSA) as compared to the untreated and MAO-treated Zr. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Performance of automatic generation control mechanisms with large-scale wind power

    Energy Technology Data Exchange (ETDEWEB)

    Ummels, B.C.; Gibescu, M.; Paap, G.C. [Delft Univ. of Technology (Netherlands); Kling, W.L. [Transmission Operations Department of TenneT bv (Netherlands)

    2007-11-15

    The unpredictability and variability of wind power increasingly challenges real-time balancing of supply and demand in electric power systems. In liberalised markets, balancing is a responsibility jointly held by the TSO (real-time power balancing) and PRPs (energy programs). In this paper, a procedure is developed for the simulation of power system balancing and the assessment of AGC performance in the presence of large-scale wind power, using the Dutch control zone as a case study. The simulation results show that the performance of existing AGC-mechanisms is adequate for keeping ACE within acceptable bounds. At higher wind power penetrations, however, the capabilities of the generation mix are increasingly challenged and additional reserves are required at the same level. (au)

  17. Prediction of Protein-Protein Interactions Related to Protein Complexes Based on Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Peng Liu

    2015-01-01

    Full Text Available A method for predicting protein-protein interactions based on detected protein complexes is proposed to repair deficient interactions derived from high-throughput biological experiments. Protein complexes are pruned and decomposed into small parts based on the adaptive k-cores method to predict protein-protein interactions associated with the complexes. The proposed method is adaptive to protein complexes with different structure, number, and size of nodes in a protein-protein interaction network. Based on different complex sets detected by various algorithms, we can obtain different prediction sets of protein-protein interactions. The reliability of the predicted interaction sets is proved by using estimations with statistical tests and direct confirmation of the biological data. In comparison with the approaches which predict the interactions based on the cliques, the overlap of the predictions is small. Similarly, the overlaps among the predicted sets of interactions derived from various complex sets are also small. Thus, every predicted set of interactions may complement and improve the quality of the original network data. Meanwhile, the predictions from the proposed method replenish protein-protein interactions associated with protein complexes using only the network topology.

  18. Temporal dynamics of visual working memory.

    Science.gov (United States)

    Sobczak-Edmans, M; Ng, T H B; Chan, Y C; Chew, E; Chuang, K H; Chen, S H A

    2016-01-01

    The involvement of the human cerebellum in working memory has been well established in the last decade. However, the cerebro-cerebellar network for visual working memory is not as well defined. Our previous fMRI study showed superior and inferior cerebellar activations during a block design visual working memory task, but specific cerebellar contributions to cognitive processes in encoding, maintenance and retrieval have not yet been established. The current study examined cerebellar contributions to each of the components of visual working memory and presence of cerebellar hemispheric laterality was investigated. 40 young adults performed a Sternberg visual working memory task during fMRI scanning using a parametric paradigm. The contrast between high and low memory load during each phase was examined. We found that the most prominent activation was observed in vermal lobule VIIIb and bilateral lobule VI during encoding. Using a quantitative laterality index, we found that left-lateralized activation of lobule VIIIa was present in the encoding phase. In the maintenance phase, there was bilateral lobule VI and right-lateralized lobule VIIb activity. Changes in activation in right lobule VIIIa were present during the retrieval phase. The current results provide evidence that superior and inferior cerebellum contributes to visual working memory, with a tendency for left-lateralized activations in the inferior cerebellum during encoding and right-lateralized lobule VIIb activations during maintenance. The results of the study are in agreement with Baddeley's multi-component working memory model, but also suggest that stored visual representations are additionally supported by maintenance mechanisms that may employ verbal coding. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Enhanced Electrochemical Performance of Electrospun Ag/Hollow Glassy Carbon Nanofibers as Free-standing Li-ion Battery Anode

    International Nuclear Information System (INIS)

    Shilpa; Sharma, Ashutosh

    2015-01-01

    Silver with a high theoretical capacity for lithium storage is an attractive alloy based anode for Li-ion batteries, but large volume changes associated with AgLi x alloy formation leads to electrode cracking, pulverization and rapid capacity fading. A buffer matrix, like the electrospun hollow carbon nanofibers, can reduce this problem to a great extent. Herein, we demonstrate the facile synthesis of a free-standing, binder free Ag-C hybrid electrode through co-axial electrospinning, where well dispersed Ag nanoparticles are embedded in hollow carbon nanofibers. Using this approach, the long cycle life of carbon is complemented with the high lithium storage capacity of Ag, resulting in a high performance anode. The Ag-C composite electrode delivers a capacity of 739 mAh g −1 (>conventional graphite anodes) at 50 mA g −1 , with ∼85% capacity retention after 100 cycles. In addition, the Ag-C composite nanofibers are highly porous and exhibit a large accessible surface area (∼726.9 m 2 g −1 ) with an average pore diameter of ∼6.07 nm. The encapsulation of Ag in the hollow interiors not only provides additional lithium storage sites but also enhances the electronic conductivity, which combined with the reduced lithium diffusion path lengths in the nanofibers result in faster charge-discharge kinetics and hence a high rate performance

  20. Cost-Effectiveness of Five Commonly Used Prosthesis Brands for Total Knee Replacement in the UK: A Study Using the NJR Dataset.

    Directory of Open Access Journals (Sweden)

    Mark Pennington

    Full Text Available There is a lack of evidence on the effectiveness or cost-effectiveness of alternative brands of prosthesis for total knee replacement (TKR. We compared patient-reported outcomes, revision rates, and costs, and estimated the relative cost-effectiveness of five frequently used cemented brands of unconstrained prostheses with fixed bearings (PFC Sigma, AGC Biomet, Nexgen, Genesis 2, and Triathlon.We used data from three national databases for patients who had a TKR between 2003 and 2012, to estimate the effect of prosthesis brand on post-operative quality of life (QOL (EQ-5D-3L in 53 126 patients at six months. We compared TKR revision rates by brand over 10 years for 239 945 patients. We used a fully probabilistic Markov model to estimate lifetime costs and quality-adjusted life years (QALYs, incremental cost effectiveness ratios (ICERs, and the probability that each prosthesis brand is the most cost effective at alternative thresholds of willingness-to-pay for a QALY gain.Revision rates were lowest with the Nexgen and PFC Sigma (2.5% after 10 years in 70-year-old women. Average lifetime costs were lowest with the AGC Biomet (£9 538; mean post-operative QOL was highest with the Nexgen, which was the most cost-effective brand across all patient subgroups. For example, for 70-year-old men and women, the ICERs for the Nexgen compared to the AGC Biomet were £2 300 per QALY. At realistic cost per QALY thresholds (£10 000 to £30 000, the probabilities that the Nexgen is the most cost-effective brand are about 98%. These results were robust to alternative modelling assumptions.AGC Biomet prostheses are the least costly cemented unconstrained fixed brand for TKR but Nexgen prostheses lead to improved patient outcomes, at low additional cost. These results suggest that Nexgen should be considered as a first choice prosthesis for patients with osteoarthritis who require a TKR.

  1. Coexistence of enriched and modern-like 142Nd signatures in Archean igneous rocks of the eastern Kaapvaal Craton, southern Africa

    Science.gov (United States)

    Schneider, Kathrin P.; Hoffmann, J. Elis; Boyet, Maud; Münker, Carsten; Kröner, Alfred

    2018-04-01

    The short-lived 146Sm-142Nd isotope system is an important tool for tracing Hadean crust-mantle differentiation processes and constraining their imprint on much younger rocks from Archean cratons. We report the first comprehensive set of high-precision 142Nd analyses for granitoids and amphibolites of the Ancient Gneiss Complex (AGC; Swaziland) and the oldest metavolcanic units of the Barberton Greenstone Belt (BGB; South Africa). The investigated samples span an age range from 3.66 Ga to 3.22 Ga and are representative of major geological units of the AGC and the lower Onverwacht Group of the BGB. Measured samples yielded μ142Nd values in the range from -8 ppm to +3 ppm relative to the JNdi-1 terrestrial standard, with typical errors smaller than 4.4 ppm. The distribution of the μ142Nd values for these 17 measured samples is bimodal with ten samples showing a tendency towards slightly negative μ142Nd anomalies, whereas seven samples have 142Nd similar to the terrestrial reference. The only confidently resolvable μ142Nd anomalies were found in a 3.44 Ga Ngwane Gneiss sample and in amphibolites of the ca. 3.45 Ga Dwalile Greenstone Remnant, revealing μ142Nd values ranging from - 7.9 ± 4.4 to - 6.1 ± 4.3 ppm. The μ142Nd deficits do not correlate with age, lithological unit, or sample locality. Instead, our results reveal that two distinct mantle domains were involved in the formation of the AGC crust. The two reservoirs can be distinguished by their μ142Nd signatures. Mantle-derived rocks tapped the enriched reservoir with negative μ142Nd at least until 3.46 Ga, whereas the granitoids preserved a negative μ142Nd signature that formed by incorporation of older AGC crust at least until 3.22 Ga. The oldest gneisses with no μ142Nd anomaly are up to 3.64 Ga in age, indicating that a modern terrestrial 142Nd reservoir was already present by early Archean times.

  2. Laparoscopy versus open surgery for advanced and resectable gastric cancer: a meta-analysis Laparoscopia versus cirugía abierta en el cáncer gástrico avanzado y resecable: una meta-análisis

    Directory of Open Access Journals (Sweden)

    David Martínez-Ramos

    2011-03-01

    Full Text Available Background: there are few studies in the literature comparing laparoscopic versus open Gastrectomy, predominantly for advanced gastric cancer (AGC. Most of the available studies and meta-analysis compare both approaches in the early gastric cancer. The meta-analysis, here presented, compares the clinical outcomes between these two procedures for AGC. Objectives: to evaluate the current status of both partial and total laparoscopic gastrectomy (LG, with regard to its short and long-term outcomes by comparing it to conventional open gastrectomy (OG for AGC. Data sources and review methods: original articles published in English language from January 1991 to October 2009 were searched in the Medline, Embase, Current Contents, Science Citation Index databases and Cochrane Controlled Trials Register. All articles comparing LG and OG for AGC were included, and those comparing outcomes only for early gastric cancer (EGC were excluded. Clinical appraisal and data extraction were conducted independently by 3 reviewers. Statistical analysis was carried out following the DerSimonian-Laird random effects model. Results: out of 2,344 studies, 7 studies were selected. One prospective randomized controlled trial, one comparative prospective study and five comparative retrospective studies were analyzed. These studies include a total of 452 patients with gastric cancer, 174 patients in the LG and 278 in the OG. The analyzed result variables were operative time, operative blood loss, hospital postoperative stay, number of dissected lymph nodes and cancer-related mortality risk. Compared to OG, LG was a longer procedure: weighted mean difference (WMD 44 minutes; 95% confidence interval (CI 20 to 69; I-squared = 91.6%, but was associated with a lower blood loss (WMD -122 cc; 95% CI -208 to -37; I-squared = 90.8%; this was more significant for hospital operative stay (WMD -6.2 days; 95% CI -9.4 to -2.8; I-squared = 67.8%. Moreover there were no significant

  3. Oligomeric protein structure networks: insights into protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Brinda KV

    2005-12-01

    Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

  4. Protein nanoparticles for therapeutic protein delivery.

    Science.gov (United States)

    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  5. AGC-1 Experiment and Final Preliminary Design Report

    Energy Technology Data Exchange (ETDEWEB)

    Robert L. Bratton; Tim Burchell

    2006-08-01

    This report details the experimental plan and design as of the preliminary design review for the Advanced Test Reactor Graphite Creep-1 graphite compressive creep capsule. The capsule will contain five graphite grades that will be irradiated in the Advanced Test Reactor at the Idaho National Laboratory to determine the irradiation induced creep constants. Seven other grades of graphite will be irradiated to determine irradiated physical properties. The capsule will have an irradiation temperature of 900 C and a peak irradiation dose of 5.8 x 10{sup 21} n/cm{sup 2} [E > 0.1 MeV], or 4.2 displacements per atom.

  6. Protein-protein interactions: an application of Tus-Ter mediated protein microarray system.

    Science.gov (United States)

    Sitaraman, Kalavathy; Chatterjee, Deb K

    2011-01-01

    In this chapter, we present a novel, cost-effective microarray strategy that utilizes expression-ready plasmid DNAs to generate protein arrays on-demand and its use to validate protein-protein interactions. These expression plasmids were constructed in such a way so as to serve a dual purpose of synthesizing the protein of interest as well as capturing the synthesized protein. The microarray system is based on the high affinity binding of Escherichia coli "Tus" protein to "Ter," a 20 bp DNA sequence involved in the regulation of DNA replication. The protein expression is carried out in a cell-free protein synthesis system, with rabbit reticulocyte lysates, and the target proteins are detected either by labeled incorporated tag specific or by gene-specific antibodies. This microarray system has been successfully used for the detection of protein-protein interaction because both the target protein and the query protein can be transcribed and translated simultaneously in the microarray slides. The utility of this system for detecting protein-protein interaction is demonstrated by a few well-known examples: Jun/Fos, FRB/FKBP12, p53/MDM2, and CDK4/p16. In all these cases, the presence of protein complexes resulted in the localization of fluorophores at the specific sites of the immobilized target plasmids. Interestingly, during our interactions studies we also detected a previously unknown interaction between CDK2 and p16. Thus, this Tus-Ter based system of protein microarray can be used for the validation of known protein interactions as well as for identifying new protein-protein interactions. In addition, it can be used to examine and identify targets of nucleic acid-protein, ligand-receptor, enzyme-substrate, and drug-protein interactions.

  7. Truly Absorbed Microbial Protein Synthesis, Rumen Bypass Protein, Endogenous Protein, and Total Metabolizable Protein from Starchy and Protein-Rich Raw Materials

    NARCIS (Netherlands)

    Parand, Ehsan; Vakili, Alireza; Mesgaran, Mohsen Danesh; Duinkerken, Van Gert; Yu, Peiqiang

    2015-01-01

    This study was carried out to measure truly absorbed microbial protein synthesis, rumen bypass protein, and endogenous protein loss, as well as total metabolizable protein, from starchy and protein-rich raw feed materials with model comparisons. Predictions by the DVE2010 system as a more

  8. Influence of β-galacto-oligosaccharide on growth performance and ...

    African Journals Online (AJOL)

    Malik Gee

    2017-08-07

    Aug 7, 2017 ... reduced acidic goblet cells (AGCs) in the ileum of the HSCT group compared with ... oligosaccharides that enrich the innate microbial ecosystem of the host. ..... parenchyma of lymphoid organs during heat stress might have ...

  9. Download this PDF file

    African Journals Online (AJOL)

    Mr Olusoji

    favouring neoplasia (AGC-FN), Atypical glandular cell of ... Screening for cervical dysplasia is critical for early detection in order to reverse this trend. ... of43.9% in low grade squamous intraepithelial lesion was recorded among the patients.

  10. Composition of Overlapping Protein-Protein and Protein-Ligand Interfaces.

    Directory of Open Access Journals (Sweden)

    Ruzianisra Mohamed

    Full Text Available Protein-protein interactions (PPIs play a major role in many biological processes and they represent an important class of targets for therapeutic intervention. However, targeting PPIs is challenging because often no convenient natural substrates are available as starting point for small-molecule design. Here, we explored the characteristics of protein interfaces in five non-redundant datasets of 174 protein-protein (PP complexes, and 161 protein-ligand (PL complexes from the ABC database, 436 PP complexes, and 196 PL complexes from the PIBASE database and a dataset of 89 PL complexes from the Timbal database. In all cases, the small molecule ligands must bind at the respective PP interface. We observed similar amino acid frequencies in all three datasets. Remarkably, also the characteristics of PP contacts and overlapping PL contacts are highly similar.

  11. First-line chemotherapy with S-1 alone or S-1 plus cisplatin for elderly patients with advanced gastric cancer: a multicenter propensity score matched study.

    Science.gov (United States)

    Makiyama, Akitaka; Kunieda, Kenji; Noguchi, Masaaki; Kajiwara, Takeshi; Tamura, Takao; Takeda, Koji; Sugiyama, Junko; Minashi, Keiko; Moriwaki, Toshikazu; Sugimoto, Naotoshi; Nagase, Michitaka; Negoro, Yuji; Tsuda, Takashi; Shimodaira, Hideki; Okano, Naohiro; Tsuji, Akihito; Sakai, Daisuke; Yanagihara, Kazuhiro; Ueda, Shinya; Tamura, Shingo; Otsu, Satoshi; Honda, Takuya; Matsushita, Yuzo; Okuno, Tatsuya; Kashiwada, Tomomi; Nozaki, Akira; Ebi, Masahide; Okuda, Hiroyuki; Shimokawa, Mototsugu; Hironaka, Shuichi; Hyodo, Ichinosuke; Baba, Eishi; Boku, Narikazu; Muro, Kei; Esaki, Taito

    2018-01-20

    Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability. In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors. PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients' characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p strategy and explore applicability of the geriatric assessment for these patients.

  12. Silver-based getters for 129I removal from low-activity waste

    International Nuclear Information System (INIS)

    Asmussen, R. Matthew; Neeway, James J.; Lawter, Amanda R.; Wilson, Andrew; Qafoku, Nikolla P.

    2016-01-01

    A prominent radionuclide of concern in nuclear wastes, 129 I, is present in low-activity wastes (LAW) at the Hanford site. Several Ag-containing materials were tested as immobilization agents, or ''getters'', for I (as iodide, I - ) removal from deionized (DI) water and a liquid LAW simulant: Ag impregnated activate carbon (Ag-C), Ag exchanged zeolite (Ag-Z), and argentite. In anoxic batch experiments with DI water, the Ag-C and argentite were most effective, with maximum K d values of 6.2 x 10 5 mL/g for the Ag-C and 3.7 x 10 5 mL/g for the argentite after 15 days. Surface area and Ag content were found to influence the performance of the getters in DI water. In the anoxic batch experiments with LAW simulant, Ag-Z vastly outperformed the other getters with K d values of 2.2 x 10 4 mL/g at 2 h, which held steady until 15 days, compared with 1.8 x 10 3 mL/g reached at 15 days by the argentite. All getters were stable over long periods of time (i.e. 40 days) in DI water, while the Ag-Z and argentite were also stable in the LAW simulant. Ag-Z was found to have consistent I removal upon crushing to a smaller particle size and in the presence of O 2 , making it a strong candidate for the treatment of LAW containing I.

  13. Balancing Acts Between Ancient and Modern Cities: The Ancient Greek Cities Project of C. A. Doxiadis

    Directory of Open Access Journals (Sweden)

    Mantha Zarmakoupi

    2015-12-01

    Full Text Available This paper examines the inception and development of the Ancient Greek Cities (AGC research project (1963–77 of Constantinos A. Doxiadis and addresses the novelty of its methodological approach to the study of classical urbanism. With the AGC project, Doxiadis launched a comprehensive study of the ancient Greek built environment to provide an overview of the factors involved in its shaping. The project produced 24 published volumes — the first two laying out the historical and methodological parameters of the ensuing 22 monographs with case studies — as well as 12 unpublished manuscripts, and through international conferences initiated a wider dialogue on ancient cities beyond the classical Greek world. It was the first interdisciplinary study that attempted to tackle the environmental factors, together with the social and economic ones, underpinning the creation, development and operation of ancient Greek cities. Doxiadis’s innovative approach to the analysis of the ancient city was indebted to his practice as an architect and town planner and was informed by his theory of Ekistics. His purpose was to identify the urban planning principles of ancient Greek settlements in order to employ them in his projects. This paper examines the concept and methodology of the AGC project as well as the ways in which Doxiadis used the study of ancient cities in relation to his contemporary urban/architectural agendas, and explains this important moment in the historiography of ancient Greek urbanism.

  14. Untargeted Metabolomic Analysis of Capsicum spp. by GC-MS.

    Science.gov (United States)

    Aranha, Bianca Camargo; Hoffmann, Jessica Fernanda; Barbieri, Rosa Lia; Rombaldi, Cesar Valmor; Chaves, Fábio Clasen

    2017-09-01

    In order to conserve the biodiversity of Capsicum species and find genotypes with potential to be utilised commercially, Embrapa Clima Temperado maintains an active germplasm collection (AGC) that requires characterisation, enabling genotype selection and support for breeding programmes. The objective of this study was to characterise pepper accessions from the Embrapa Clima Temperado AGC and differentiate species based on their metabolic profile using an untargeted metabolomics approach. Cold (-20°C) methanol extraction residue of freeze-dried fruit samples was partitioned into water/methanol (A) and chloroform (B) fractions. The polar fraction (A) was derivatised and both fractions (A and B) were analysed by gas chromatography coupled to mass spectrometry (GC-MS). Data from each fraction was analysed using a multivariate principal component analysis (PCA) with XCMS software. Amino acids, sugars, organic acids, capsaicinoids, and hydrocarbons were identified. Outlying accessions including P116 (C. chinense), P46, and P76 (C. annuum) were observed in a PCA plot mainly due to their high sucrose and fructose contents. PCA also indicated a separation of P221 (C. annuum) and P200 (C. chinense), because of their high dihydrocapsaicin content. Although the metabolic profiling did not allow for grouping by species, it permitted the simultaneous identification and quantification of several compounds complementing and expanding the metabolic database of the studied Capsicum spp. in the AGC. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Protein- protein interaction detection system using fluorescent protein microdomains

    Science.gov (United States)

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2010-02-23

    The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (.beta.-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (.beta.-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GFP amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.

  16. A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

    Directory of Open Access Journals (Sweden)

    Qian Li

    Full Text Available BACKGROUND: Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. METHODOLOGY: We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671 between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. CONCLUSIONS: This article proposes a network-based multi-target computational estimation

  17. A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

    Science.gov (United States)

    Li, Qian; Li, Xudong; Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

    2011-03-22

    Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by

  18. A case of advanced gastric cancer resected for rebleeding after palliative radiotherapy for hemostasis

    International Nuclear Information System (INIS)

    Muneoka, Yusuke; Ichikawa, Hiroshi; Ishikawa, Takashi

    2016-01-01

    We report a case of advanced gastric cancer (AGC) that was resected for rebleeding after palliative radiotherapy for hemostasis. A 74-year-old man with Stage IV gastric cancer received chemotherapy and achieved stable disease. After 23 months, he experienced continuous bleeding from the tumor due to regrowth. Palliative radiotherapy was conducted to control the bleeding, and the tumor successfully achieved hemostasis. However, 6 weeks later, the patient experienced rebleeding and developed hemostatic shock. We then performed a successful emergency gastrectomy. Bleeding negatively affects quality of life in patients with AGC and is potentially lethal. Although palliative radiotherapy for bleeding of gastric cancer is a safe and useful treatment within a short time frame in cases of rebleeding, emergency gastrectomy may be necessary. Therefore, when we select this treatment, the possibility of subsequent surgical treatment must be considered. (author)

  19. The preparation of highly active antimicrobial silver nanoparticles by an organometallic approach

    International Nuclear Information System (INIS)

    Fernandez, Eduardo J; Garcia-Barrasa, Jorge; Lopez-de-Luzuriaga, Jose M; Monge, Miguel; Laguna, Antonio; Torres, Carmen

    2008-01-01

    Silver nanoparticles of small size with a high surface to volume ratio have been prepared using an organometallic approach. For this, the complex NBu 4 [Ag(C 6 F 5 ) 2 ] has been treated with AgClO 4 in a 1:1 molar ratio, giving rise to the nanoparticle precursor [Ag(C 6 F 5 )] in solution. Addition of one equivalent of hexadecylamine (HDA) and 5 h of reflux in toluene leads to a deep yellow solution containing monodisperse silver nanoparticles (Ag NPs) of ca. 10 nm. This approach leads to nanoparticles with almost uncontaminated surfaces which make them very reactive. Antimicrobial studies show that these nanoparticles are very active as antimicrobial agents. Very low concentrations between 12 and 25 μg ml -1 of Ag NPs are enough to produce bacteriostatic and bactericidal effectiveness

  20. Wind power integration into the automatic generation control of power systems with large-scale wind power

    DEFF Research Database (Denmark)

    Basit, Abdul; Hansen, Anca Daniela; Altin, Müfit

    2014-01-01

    Transmission system operators have an increased interest in the active participation of wind power plants (WPP) in the power balance control of power systems with large wind power penetration. The emphasis in this study is on the integration of WPPs into the automatic generation control (AGC......) of the power system. The present paper proposes a coordinated control strategy for the AGC between combined heat and power plants (CHPs) and WPPs to enhance the security and the reliability of a power system operation in the case of a large wind power penetration. The proposed strategy, described...... and exemplified for the future Danish power system, takes the hour-ahead regulating power plan for generation and power exchange with neighbouring power systems into account. The performance of the proposed strategy for coordinated secondary control is assessed and discussed by means of simulations for different...

  1. Automatic generation control of an interconnected hydrothermal power system considering superconducting magnetic energy storage

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, Rajesh Joseph; Das, D.; Patra, Amit [Department of Electrical Engineering, Indian Institute of Technology, Kharagpur 721 302 (India)

    2007-10-15

    This paper presents the analysis of automatic generation control (AGC) of an interconnected hydrothermal power system in the presence of generation rate constraints (GRCs). The improvement of AGC with the addition of a small capacity superconducting magnetic energy storage (SMES) unit in either, as well as in both the areas are studied. Time domain simulations are used to study the performance of the power system and control logic. The optimal values of the integral gain settings are obtained using integral squared error (ISE) technique by minimising a quadratic performance index. Suitable method for controlling the SMES unit is described. Analysis reveals that SMES unit fitted in either of the areas is as effective as SMES units fitted in both the areas and improves the dynamic performances to a considerable extent following a load disturbance in either of the areas. (author)

  2. Application of automatic gain control for radiometer diagnostic in SST-1 tokamak.

    Science.gov (United States)

    Makwana, Foram R; Siju, Varsha; Edappala, Praveenlal; Pathak, S K

    2017-12-01

    This paper describes the characterisation of a negative feedback type of automatic gain control (AGC) circuit that will be an integral part of the heterodyne radiometer system operating at a frequency range of 75-86 GHz at SST-1 tokamak. The developed AGC circuit is a combination of variable gain amplifier and log amplifier which provides both gain and attenuation typically up to 15 dB and 45 dB, respectively, at a fixed set point voltage and it has been explored for the first time in tokamak radiometry application. The other important characteristics are that it exhibits a very fast response time of 390 ns to understand the fast dynamics of electron cyclotron emission and can operate at very wide input RF power dynamic range of around 60 dB that ensures signal level within the dynamic range of the detection system.

  3. Identification of Protein-Protein Interactions with Glutathione-S-Transferase (GST) Fusion Proteins.

    Science.gov (United States)

    Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

    2007-08-01

    INTRODUCTIONGlutathione-S-transferase (GST) fusion proteins have had a wide range of applications since their introduction as tools for synthesis of recombinant proteins in bacteria. GST was originally selected as a fusion moiety because of several desirable properties. First and foremost, when expressed in bacteria alone, or as a fusion, GST is not sequestered in inclusion bodies (in contrast to previous fusion protein systems). Second, GST can be affinity-purified without denaturation because it binds to immobilized glutathione, which provides the basis for simple purification. Consequently, GST fusion proteins are routinely used for antibody generation and purification, protein-protein interaction studies, and biochemical analysis. This article describes the use of GST fusion proteins as probes for the identification of protein-protein interactions.

  4. On the application of bezier surfaces for GA-Fuzzy controller design for use in automatic generation control

    CSIR Research Space (South Africa)

    Boesack, CD

    2012-03-01

    Full Text Available Automatic Generation Control (AGC) of large interconnected power systems are typically controlled by a PI or PID type control law. Recently intelligent control techniques such as GA-Fuzzy controllers have been widely applied within the power...

  5. Protein-protein interaction network-based detection of functionally similar proteins within species.

    Science.gov (United States)

    Song, Baoxing; Wang, Fen; Guo, Yang; Sang, Qing; Liu, Min; Li, Dengyun; Fang, Wei; Zhang, Deli

    2012-07-01

    Although functionally similar proteins across species have been widely studied, functionally similar proteins within species showing low sequence similarity have not been examined in detail. Identification of these proteins is of significant importance for understanding biological functions, evolution of protein families, progression of co-evolution, and convergent evolution and others which cannot be obtained by detection of functionally similar proteins across species. Here, we explored a method of detecting functionally similar proteins within species based on graph theory. After denoting protein-protein interaction networks using graphs, we split the graphs into subgraphs using the 1-hop method. Proteins with functional similarities in a species were detected using a method of modified shortest path to compare these subgraphs and to find the eligible optimal results. Using seven protein-protein interaction networks and this method, some functionally similar proteins with low sequence similarity that cannot detected by sequence alignment were identified. By analyzing the results, we found that, sometimes, it is difficult to separate homologous from convergent evolution. Evaluation of the performance of our method by gene ontology term overlap showed that the precision of our method was excellent. Copyright © 2012 Wiley Periodicals, Inc.

  6. Protein-Protein Docking in Drug Design and Discovery.

    Science.gov (United States)

    Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

    2018-01-01

    Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

  7. IPP: Annual report 1982

    International Nuclear Information System (INIS)

    1982-01-01

    This report presents a detailed outline of the work accomplished within the framework of the Tokamak projects ASDEX and ASDEX Upgrade and the JET and NET projects, the stellarator projects VIII-A, VII-AS and VII-X, and of stellarator reactor system studies. The various scientific research departments, such as Experimental Plasma Physics 1, 2 and 3, Theoretical Plasma Physics 1 and 2, Plasma-Wall. Interactions, and Information Sciences give an account of the results of their research and development work. Further reports on the 1982 activities deal with a) the organisational structure of the IPP, b) administrative and business items, c) scientific publications and conference proceedings, and with d) IPP-supported projects at universities. (GG) [de

  8. Radioisotopic and synthetic studies related to caroxazone metabolism in man

    International Nuclear Information System (INIS)

    Bernardi, L.; Coda, S.; Nicolella, V.; Vicario, G.P.; Gioia, B.; Minghetti, A.; Vigevani, A.; Arcamone, F.

    1979-01-01

    Labelled 2-oxo-2H-1,3-benzoxazine-3(4H)-acetamide (caroxazone), has been synthesized by condensing N-(2-hydroxylbenzyl) glycinamide with 14 C phosgene. Metabolic studies were performed administering the labelled drug to man and recovering metabolites were identified and confirmed by synthesis, namely (3,4-dihydro - 3-carboxamidomethyl-2-oxo-2H - 1,3-benzoxazin-4-yl) urea (IX), N-carboxamidomethyl o-hydroxymethylphenyl carbamate (V), 4-methoxy-2-oxo-2H - 1,3-benzoxazine-3(4H) acetamide (VIIIa), 2-oxo-2H - 1,3-benzoxazine-3(4H) acetic acid (III) and 4-hydroxy-2-oxo-2H-1,3-benzoxazine-3(4H) acetamide (IV). (orig.) 891 AJ/orig. 892 GR [de

  9. Evolution of protein-protein interactions

    Indian Academy of Sciences (India)

    Evolution of protein-protein interactions · Our interests in protein-protein interactions · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20.

  10. Protein function prediction using neighbor relativity in protein-protein interaction network.

    Science.gov (United States)

    Moosavi, Sobhan; Rahgozar, Masoud; Rahimi, Amir

    2013-04-01

    There is a large gap between the number of discovered proteins and the number of functionally annotated ones. Due to the high cost of determining protein function by wet-lab research, function prediction has become a major task for computational biology and bioinformatics. Some researches utilize the proteins interaction information to predict function for un-annotated proteins. In this paper, we propose a novel approach called "Neighbor Relativity Coefficient" (NRC) based on interaction network topology which estimates the functional similarity between two proteins. NRC is calculated for each pair of proteins based on their graph-based features including distance, common neighbors and the number of paths between them. In order to ascribe function to an un-annotated protein, NRC estimates a weight for each neighbor to transfer its annotation to the unknown protein. Finally, the unknown protein will be annotated by the top score transferred functions. We also investigate the effect of using different coefficients for various types of functions. The proposed method has been evaluated on Saccharomyces cerevisiae and Homo sapiens interaction networks. The performance analysis demonstrates that NRC yields better results in comparison with previous protein function prediction approaches that utilize interaction network. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Protein Structure Prediction by Protein Threading

    Science.gov (United States)

    Xu, Ying; Liu, Zhijie; Cai, Liming; Xu, Dong

    The seminal work of Bowie, Lüthy, and Eisenberg (Bowie et al., 1991) on "the inverse protein folding problem" laid the foundation of protein structure prediction by protein threading. By using simple measures for fitness of different amino acid types to local structural environments defined in terms of solvent accessibility and protein secondary structure, the authors derived a simple and yet profoundly novel approach to assessing if a protein sequence fits well with a given protein structural fold. Their follow-up work (Elofsson et al., 1996; Fischer and Eisenberg, 1996; Fischer et al., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et al., 1992) on protein fold recognition led to the development of a new brand of powerful tools for protein structure prediction, which we now term "protein threading." These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many of the proteins encoded in the hundreds of genomes that have been sequenced up to now.

  12. Specificity and affinity quantification of protein-protein interactions.

    Science.gov (United States)

    Yan, Zhiqiang; Guo, Liyong; Hu, Liang; Wang, Jin

    2013-05-01

    Most biological processes are mediated by the protein-protein interactions. Determination of the protein-protein structures and insight into their interactions are vital to understand the mechanisms of protein functions. Currently, compared with the isolated protein structures, only a small fraction of protein-protein structures are experimentally solved. Therefore, the computational docking methods play an increasing role in predicting the structures and interactions of protein-protein complexes. The scoring function of protein-protein interactions is the key responsible for the accuracy of the computational docking. Previous scoring functions were mostly developed by optimizing the binding affinity which determines the stability of the protein-protein complex, but they are often lack of the consideration of specificity which determines the discrimination of native protein-protein complex against competitive ones. We developed a scoring function (named as SPA-PP, specificity and affinity of the protein-protein interactions) by incorporating both the specificity and affinity into the optimization strategy. The testing results and comparisons with other scoring functions show that SPA-PP performs remarkably on both predictions of binding pose and binding affinity. Thus, SPA-PP is a promising quantification of protein-protein interactions, which can be implemented into the protein docking tools and applied for the predictions of protein-protein structure and affinity. The algorithm is implemented in C language, and the code can be downloaded from http://dl.dropbox.com/u/1865642/Optimization.cpp.

  13. Tuningless Load Frequency Control Through Active Engagement of Distributed Resources

    DEFF Research Database (Denmark)

    Prostejovsky, Alexander; Marinelli, Mattia; Rezkalla, Michel M.N.

    2017-01-01

    system dynamics. Second, primary resources are actively involved in frequency restoration by systematic adjustment of their frequency reference setpoints. In contrast to the commonly used Automatic Generation Control (AGC), the proposed Direct Load Frequency Control (DLFC) does not require an integrator...

  14. Understanding Cervical Changes: A Health Guide for Women

    Science.gov (United States)

    Explains abnormal Pap test, HPV test, and Pap/HPV cotest results. Treatment and follow-up care for abnormal cervical cancer screening results including ASC-US, AGC, LSIL, ASC-H, HSIL, AIS. Learn about colposcopy, types of biopsies, CIN, and HPV vaccine.

  15. Detection of protein complex from protein-protein interaction network using Markov clustering

    International Nuclear Information System (INIS)

    Ochieng, P J; Kusuma, W A; Haryanto, T

    2017-01-01

    Detection of complexes, or groups of functionally related proteins, is an important challenge while analysing biological networks. However, existing algorithms to identify protein complexes are insufficient when applied to dense networks of experimentally derived interaction data. Therefore, we introduced a graph clustering method based on Markov clustering algorithm to identify protein complex within highly interconnected protein-protein interaction networks. Protein-protein interaction network was first constructed to develop geometrical network, the network was then partitioned using Markov clustering to detect protein complexes. The interest of the proposed method was illustrated by its application to Human Proteins associated to type II diabetes mellitus. Flow simulation of MCL algorithm was initially performed and topological properties of the resultant network were analysed for detection of the protein complex. The results indicated the proposed method successfully detect an overall of 34 complexes with 11 complexes consisting of overlapping modules and 20 non-overlapping modules. The major complex consisted of 102 proteins and 521 interactions with cluster modularity and density of 0.745 and 0.101 respectively. The comparison analysis revealed MCL out perform AP, MCODE and SCPS algorithms with high clustering coefficient (0.751) network density and modularity index (0.630). This demonstrated MCL was the most reliable and efficient graph clustering algorithm for detection of protein complexes from PPI networks. (paper)

  16. Coarse-grain modelling of protein-protein interactions

    NARCIS (Netherlands)

    Baaden, Marc; Marrink, Siewert J.

    2013-01-01

    Here, we review recent advances towards the modelling of protein-protein interactions (PPI) at the coarse-grained (CG) level, a technique that is now widely used to understand protein affinity, aggregation and self-assembly behaviour. PPI models of soluble proteins and membrane proteins are

  17. Predictive value of pretreatment metabolic activity measured by fluorodeoxyglucose positron emission tomography in patients with metastatic advanced gastric cancer: the maximal SUV of the stomach is a prognostic factor

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun Chul; Cheoi, Kungseok; Chung, Hyunsoo; Lee, Hyuk; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan [Yonsei University College of Medicine, Department of Internal Medicine and Institute of Gastroenterology, Seoul (Korea, Republic of); Lee, Jae-Hoon; Yun, Mi Jin [Yonsei University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of)

    2012-07-15

    Few studies have evaluated metabolic activity by {sup 18}F-FDG PET as a prognostic factor in advanced gastric cancer (AGC). We investigated its prognostic role in metastatic AGC. We enrolled 82 patients with metastatic AGC, who were treatment-naive and underwent pretreatment {sup 18}F-FDG PET/CT scanning. In each patient, the maximal standardized uptake value (SUVmax) was measured in each target lesion. Stomach{sub SUVmax} was defined as SUVmax in the stomach, while Total{sub SUVmax} was defined as the highest SUVmax among all the target lesions. The stomach was the organ most frequently displaying the highest SUVmax among all the target lesions (in 67.1 % of patients). A Total{sub SUVmax} value of 11.5 was the value with the maximum sum of sensitivity and specificity from receiver-operating characteristic curves for progression-free survival (PFS). PFS was significantly longer in patients with a Total{sub SUVmax} value <11.5 than in those with a Total{sub SUVmax} value {>=}11.5 (P = 0.023); however, overall survival (OS) was not (P = 0.055). A Stomach{sub SUVmax} value of 6.0 was derived by similar methods. PFS and OS were significantly longer in those with a Stomach{sub SUVmax} value <6.0 than in those with a Stomach{sub SUVmax} value {>=}6.0 (P = 0.001 and P = 0.006, respectively). Furthermore, those with a low Total{sub SUVmax} and those with a low Stomach{sub SUVmax} showed better chemotherapeutic responses (P = 0.016 and P = 0.034, respectively). Among patients with histologically undifferentiated carcinomas, those with lower Total{sub SUVmax} and those with lower Stomach{sub SUVmax} showed longer median PFS (P = 0.027 and P = 0.005, respectively) and OS (P = 0.009 and P <0.001, respectively). Multivariate analysis demonstrated Stomach{sub SUVmax} as an independent predictor of PFS (P = 0.002) and OS (P = 0.038). Pretreatment metabolic activity may be a useful prognostic marker in patients with metastatic AGC undergoing palliative chemotherapy. Notably

  18. Prevalence of H. pylori Infection and Atrophic Gastritis in a Population-based Screening with Serum Biomarker Panel (GastroPanel®) in St. Petersburg.

    Science.gov (United States)

    Roman, Laslo D; Lukyanchuk, Ruslan; Sablin, Oleg A; Araslanova, Elena I; Eklund, Carita; Hendolin, Panu; Paloheimo, Lea; Syrjänen, Kari

    2016-08-01

    Russian Federation is among the high-incidence countries for gastric cancer (GC), with the incidence being projected to continue increasing. Using a non-invasive blood test with four stomach-specific biomarkers (pepsinogen-I (PG-I) and -II (PG-II), amidated gastrin-17 (G-17) and Helicobacter pylori (HP) IgG antibodies) in a hospital-based screening setting, we aimed to determine the prevalence of GC risk conditions: HP-infection and atrophic gastritis (AG). A population-derived cohort of 918 asymptomatic subjects (646 women and 272 men) with a mean age of 51.8 years (range=26-83) was examined with the GastroPanel® (GP) test. GP results were verified by gastroscopy and biopsies (the Updated Sydney System (USS) classification for all test-positive AG cases and for random 5% test-negatives (n=263) to correct for the verification bias. Of the 918 subjects, only 199 (21.7%) tested completely normal, while 76.7% (704/918) had HP-infection. Altogether, in 99 subjects (10.8%), GP suggested AG: atrophic gastritis in the antrum (AGA) (n=21), atrophic gastritis in the corpus (AGC) (n=69) or atrophic pangastritis (AGpan) (n=9). The overall concordance between GP and USS classification was 82.5% (217/263) with weighted kappa intra-class correlation coefficient (ICC)=0.875 (95% confidence interval (CI)=0.840-0.901). The sensitivity/specificity balance in receiver operating characteristic (ROC) analysis for PG-I as a marker of moderate/severe AGC (AGC2+) had area under the curve (AUC)=0.895 (95%CI=0.837-0.953). Using the AGC2+ end-point, verification bias-corrected specificity of PGI reached 96.4% (95%CI=94.7-97.9) and that of PGI/PGII ratio 94.6% (95%CI=92.6-96.3), with inevitable erosion in sensitivities. While capable of detecting the subjects at risk for GC (HP and/or AG), GP should be the cost-effective means to break the current ominous trend in GC incidence in Russian Federation. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios

  19. Detection of protein-protein interactions by ribosome display and protein in situ immobilisation.

    Science.gov (United States)

    He, Mingyue; Liu, Hong; Turner, Martin; Taussig, Michael J

    2009-12-31

    We describe a method for identification of protein-protein interactions by combining two cell-free protein technologies, namely ribosome display and protein in situ immobilisation. The method requires only PCR fragments as the starting material, the target proteins being made through cell-free protein synthesis, either associated with their encoding mRNA as ribosome complexes or immobilised on a solid surface. The use of ribosome complexes allows identification of interacting protein partners from their attached coding mRNA. To demonstrate the procedures, we have employed the lymphocyte signalling proteins Vav1 and Grb2 and confirmed the interaction between Grb2 and the N-terminal SH3 domain of Vav1. The method has promise for library screening of pairwise protein interactions, down to the analytical level of individual domain or motif mapping.

  20. International Journal of Engineering, Science and Technology - Vol ...

    African Journals Online (AJOL)

    Application of computational intelligence in emerging power systems · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT ... Allocation of optimal distributed generation using GA for minimum system losses in radial distribution networks ... performance evaluation of evolutionary designed conventional AGC controllers for ...

  1. Immobilization of lysozyme-cellulose amide-linked conjugates on cellulose i and ii cotton nanocrystalline preparations

    Science.gov (United States)

    Lysozyme was attached through an amide linkage between some of the protein’s aspartate and glutamate residues to amino-glycine-cellulose (AGC), which was prepared by esterification of glycine to preparations of cotton nanocrystals (CNC). The nanocrystalline preparations were produced through acid h...

  2. DQA2

    Indian Academy of Sciences (India)

    mukesh

    , GGT, CCC, TCT, GGC, CAG, TAC, ACC, CAG, GAA, TTT, GAT, GGA, GAC, GAG, ATG, TTT, TAT, GTG, GAC, CTG, GGG, AAG, AAG, GAG, ACT, GTC, TGG, AGG, CTG, CCT, ATG, TTT, AGC, CAG, TTT, GCA, GGT, TTT, GAC, CCA, CAG, GCT ...

  3. Coevolution study of mitochondria respiratory chain proteins: toward the understanding of protein--protein interaction.

    Science.gov (United States)

    Yang, Ming; Ge, Yan; Wu, Jiayan; Xiao, Jingfa; Yu, Jun

    2011-05-20

    Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein--protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using "Mirror tree" method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein--protein interaction in intra-complex and the binary protein--protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test, p-value = 4.4 × 10(-6)). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein--protein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study. Copyright © 2011. Published by Elsevier Ltd.

  4. A Novel Approach for Protein-Named Entity Recognition and Protein-Protein Interaction Extraction

    Directory of Open Access Journals (Sweden)

    Meijing Li

    2015-01-01

    Full Text Available Many researchers focus on developing protein-named entity recognition (Protein-NER or PPI extraction systems. However, the studies about these two topics cannot be merged well; then existing PPI extraction systems’ Protein-NER still needs to improve. In this paper, we developed the protein-protein interaction extraction system named PPIMiner based on Support Vector Machine (SVM and parsing tree. PPIMiner consists of three main models: natural language processing (NLP model, Protein-NER model, and PPI discovery model. The Protein-NER model, which is named ProNER, identifies the protein names based on two methods: dictionary-based method and machine learning-based method. ProNER is capable of identifying more proteins than dictionary-based Protein-NER model in other existing systems. The final discovered PPIs extracted via PPI discovery model are represented in detail because we showed the protein interaction types and the occurrence frequency through two different methods. In the experiments, the result shows that the performances achieved by our ProNER and PPI discovery model are better than other existing tools. PPIMiner applied this protein-named entity recognition approach and parsing tree based PPI extraction method to improve the performance of PPI extraction. We also provide an easy-to-use interface to access PPIs database and an online system for PPIs extraction and Protein-NER.

  5. Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency.

    Science.gov (United States)

    Saheki, Takeyori; Inoue, Kanako; Ono, Hiromi; Fujimoto, Yuki; Furuie, Sumie; Yamamura, Ken-Ichi; Kuroda, Eishi; Ushikai, Miharu; Asakawa, Akihiro; Inui, Akio; Eto, Kazuhiro; Kadowaki, Takashi; Moriyama, Mitsuaki; Sinasac, David S; Yamamoto, Takashi; Furukawa, Tatsuhiko; Kobayashi, Keiko

    2017-04-01

    Mice carrying simultaneous homozygous mutations in the genes encoding citrin, the mitochondrial aspartate-glutamate carrier 2 (AGC2) protein, and mitochondrial glycerol-3-phosphate dehydrogenase (mGPD), are a phenotypically representative model of human citrin (a.k.a., AGC2) deficiency. In this study, we investigated the voluntary oral intake and preference for sucrose, glycerol or ethanol solutions by wild-type, citrin (Ctrn)-knockout (KO), mGPD-KO, and Ctrn/mGPD double-KO mice; all substances that are known or suspected precipitating factors in the pathogenesis of human citrin deficiency. The double-KO mice showed clear suppressed intake of sucrose, consuming less with progressively higher concentrations compared to the other mice. Similar observations were made when glycerol or ethanol were given. The preference of Ctrn-KO and mGPD-KO mice varied with the different treatments; essentially no differences were observed for sucrose, while an intermediate intake or similar to that of the double-KO mice was observed for glycerol and ethanol. We next examined the hepatic glycerol 3-phosphate, citrate, citrulline, lysine, glutamate and adenine nucleotide levels following forced enteral administration of these solutions. A strong correlation between the simultaneous increased hepatic glycerol 3-phosphate and decreased ATP or total adenine nucleotide content and observed aversion of the mice during evaluation of their voluntary preferences was found. Overall, our results suggest that the aversion observed in the double-KO mice to these solutions is initiated and/or mediated by hepatic metabolic perturbations, resulting in a behavioral response to increased hepatic cytosolic NADH and a decreased cellular adenine nucleotide pool. These findings may underlie the dietary predilections observed in human citrin deficient patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Design of a wideband CMOS impedance spectroscopy ASIC analog front-end for multichannel biosensor interfaces.

    Science.gov (United States)

    Valente, Virgilio; Dai Jiang; Demosthenous, Andreas

    2015-08-01

    This paper presents the preliminary design and simulation of a flexible and programmable analog front-end (AFE) circuit with current and voltage readout capabilities for electric impedance spectroscopy (EIS). The AFE is part of a fully integrated multifrequency EIS platform. The current readout comprises of a transimpedance stage and an automatic gain control (AGC) unit designed to accommodate impedance changes larger than 3 order of magnitude. The AGC is based on a dynamic peak detector that tracks changes in the input current over time and regulates the gain of a programmable gain amplifier in order to optimise the signal-to-noise ratio. The system works up to 1 MHz. The voltage readout consists of a 2 stages of fully differential current-feedback instrumentation amplifier which provide 100 dB of CMRR and a programmable gain up to 20 V/V per stage with a bandwidth in excess of 10MHz.

  7. Protein complex prediction in large ontology attributed protein-protein interaction networks.

    Science.gov (United States)

    Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian; Li, Yanpeng; Xu, Bo

    2013-01-01

    Protein complexes are important for unraveling the secrets of cellular organization and function. Many computational approaches have been developed to predict protein complexes in protein-protein interaction (PPI) networks. However, most existing approaches focus mainly on the topological structure of PPI networks, and largely ignore the gene ontology (GO) annotation information. In this paper, we constructed ontology attributed PPI networks with PPI data and GO resource. After constructing ontology attributed networks, we proposed a novel approach called CSO (clustering based on network structure and ontology attribute similarity). Structural information and GO attribute information are complementary in ontology attributed networks. CSO can effectively take advantage of the correlation between frequent GO annotation sets and the dense subgraph for protein complex prediction. Our proposed CSO approach was applied to four different yeast PPI data sets and predicted many well-known protein complexes. The experimental results showed that CSO was valuable in predicting protein complexes and achieved state-of-the-art performance.

  8. Protein surface shielding agents in protein crystallization

    International Nuclear Information System (INIS)

    Hašek, J.

    2011-01-01

    The crystallization process can be controlled by protein surface shielding agents blocking undesirable competitive adhesion modes during non-equilibrium processes of deposition of protein molecules on the surface of growing crystalline blocks. The hypothesis is based on a number of experimental proofs from diffraction experiments and also retrieved from the Protein Data Bank. The molecules adhering temporarily on the surface of protein molecules change the propensity of protein molecules to deposit on the crystal surface in a definite position and orientation. The concepts of competitive adhesion modes and protein surface shielding agents acting on the surface of molecules in a non-equilibrium process of protein crystallization provide a useful platform for the control of crystallization. The desirable goal, i.e. a transient preference of a single dominating adhesion mode between protein molecules during crystallization, leads to uniform deposition of proteins in a crystal. This condition is the most important factor for diffraction quality and thus also for the accuracy of protein structure determination. The presented hypothesis is a generalization of the experimentally well proven behaviour of hydrophilic polymers on the surface of protein molecules of other compounds

  9. The Development of Protein Microarrays and Their Applications in DNA-Protein and Protein-Protein Interaction Analyses of Arabidopsis Transcription Factors

    Science.gov (United States)

    Gong, Wei; He, Kun; Covington, Mike; Dinesh-Kumar, S. P.; Snyder, Michael; Harmer, Stacey L.; Zhu, Yu-Xian; Deng, Xing Wang

    2009-01-01

    We used our collection of Arabidopsis transcription factor (TF) ORFeome clones to construct protein microarrays containing as many as 802 TF proteins. These protein microarrays were used for both protein-DNA and protein-protein interaction analyses. For protein-DNA interaction studies, we examined AP2/ERF family TFs and their cognate cis-elements. By careful comparison of the DNA-binding specificity of 13 TFs on the protein microarray with previous non-microarray data, we showed that protein microarrays provide an efficient and high throughput tool for genome-wide analysis of TF-DNA interactions. This microarray protein-DNA interaction analysis allowed us to derive a comprehensive view of DNA-binding profiles of AP2/ERF family proteins in Arabidopsis. It also revealed four TFs that bound the EE (evening element) and had the expected phased gene expression under clock-regulation, thus providing a basis for further functional analysis of their roles in clock regulation of gene expression. We also developed procedures for detecting protein interactions using this TF protein microarray and discovered four novel partners that interact with HY5, which can be validated by yeast two-hybrid assays. Thus, plant TF protein microarrays offer an attractive high-throughput alternative to traditional techniques for TF functional characterization on a global scale. PMID:19802365

  10. Platinated DNA oligonucleotides: new probes forming ultrastable conjugates with graphene oxide

    Science.gov (United States)

    Wang, Feng; Liu, Juewen

    2014-05-01

    Metal containing polymers have expanded the property of polymers by involving covalently associated metal complexes. DNA is a special block copolymer. While metal ions are known to influence DNA, little is explored on its polymer property when strong metal complexes are associated. In this work, we study cisplatin modified DNA as a new polymer and probe. Out of the complexes formed between cisplatin-A15, HAuCl4-A15, Hg2+-T15 and Ag+-C15, only the cisplatin adduct is stable under the denaturing gel electrophoresis condition. Each Pt-nucleobase bond gives a positive charge and thus makes DNA a zwitterionic polymer. This allows ultrafast adsorption of DNA by graphene oxide (GO) and the adsorbed complex is highly stable. Non-specific DNA, protein, surfactants and thiolated compounds cannot displace platinated DNA from GO, while non-modified DNA is easily displaced in most cases. The stable GO/DNA conjugate is further tested for surface hybridization. This is the first demonstration of using metallated DNA as a polymeric material for interfacing with nanoscale materials.Metal containing polymers have expanded the property of polymers by involving covalently associated metal complexes. DNA is a special block copolymer. While metal ions are known to influence DNA, little is explored on its polymer property when strong metal complexes are associated. In this work, we study cisplatin modified DNA as a new polymer and probe. Out of the complexes formed between cisplatin-A15, HAuCl4-A15, Hg2+-T15 and Ag+-C15, only the cisplatin adduct is stable under the denaturing gel electrophoresis condition. Each Pt-nucleobase bond gives a positive charge and thus makes DNA a zwitterionic polymer. This allows ultrafast adsorption of DNA by graphene oxide (GO) and the adsorbed complex is highly stable. Non-specific DNA, protein, surfactants and thiolated compounds cannot displace platinated DNA from GO, while non-modified DNA is easily displaced in most cases. The stable GO/DNA conjugate

  11. Protein sequence comparison and protein evolution

    Energy Technology Data Exchange (ETDEWEB)

    Pearson, W.R. [Univ. of Virginia, Charlottesville, VA (United States). Dept. of Biochemistry

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. This tutorial examines how the information conserved during the evolution of a protein molecule can be used to infer reliably homology, and thus a shared proteinfold and possibly a shared active site or function. The authors start by reviewing a geological/evolutionary time scale. Next they look at the evolution of several protein families. During the tutorial, these families will be used to demonstrate that homologous protein ancestry can be inferred with confidence. They also examine different modes of protein evolution and consider some hypotheses that have been presented to explain the very earliest events in protein evolution. The next part of the tutorial will examine the technical aspects of protein sequence comparison. Both optimal and heuristic algorithms and their associated parameters that are used to characterize protein sequence similarities are discussed. Perhaps more importantly, they survey the statistics of local similarity scores, and how these statistics can both be used to improve the selectivity of a search and to evaluate the significance of a match. They them examine distantly related members of three protein families, the serine proteases, the glutathione transferases, and the G-protein-coupled receptors (GCRs). Finally, the discuss how sequence similarity can be used to examine internal repeated or mosaic structures in proteins.

  12. On the analysis of protein-protein interactions via knowledge-based potentials for the prediction of protein-protein docking

    DEFF Research Database (Denmark)

    Feliu, Elisenda; Aloy, Patrick; Oliva, Baldo

    2011-01-01

    Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions for s...... and with independence of the partner. This information is encoded at the residue level and could be easily incorporated in the initial grid scoring for Fast Fourier Transform rigid-body docking methods.......Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions...... for selecting rigid-body docking poses. These potentials include the energetic component that provides the residues with a particular secondary structure and surface accessibility. These scoring functions have been tested on a state-of-art benchmark dataset and on a decoy dataset of permanent interactions. Our...

  13. Proteins interacting with cloning scars: a source of false positive protein-protein interactions.

    Science.gov (United States)

    Banks, Charles A S; Boanca, Gina; Lee, Zachary T; Florens, Laurence; Washburn, Michael P

    2015-02-23

    A common approach for exploring the interactome, the network of protein-protein interactions in cells, uses a commercially available ORF library to express affinity tagged bait proteins; these can be expressed in cells and endogenous cellular proteins that copurify with the bait can be identified as putative interacting proteins using mass spectrometry. Control experiments can be used to limit false-positive results, but in many cases, there are still a surprising number of prey proteins that appear to copurify specifically with the bait. Here, we have identified one source of false-positive interactions in such studies. We have found that a combination of: 1) the variable sequence of the C-terminus of the bait with 2) a C-terminal valine "cloning scar" present in a commercially available ORF library, can in some cases create a peptide motif that results in the aberrant co-purification of endogenous cellular proteins. Control experiments may not identify false positives resulting from such artificial motifs, as aberrant binding depends on sequences that vary from one bait to another. It is possible that such cryptic protein binding might occur in other systems using affinity tagged proteins; this study highlights the importance of conducting careful follow-up studies where novel protein-protein interactions are suspected.

  14. The effect of protein-protein and protein-membrane interactions on membrane fouling in ultrafiltration

    NARCIS (Netherlands)

    Huisman, I.H.; Prádanos, P.; Hernández, A.

    2000-01-01

    It was studied how protein-protein and protein-membrane interactions influence the filtration performance during the ultrafiltration of protein solutions over polymeric membranes. This was done by measuring flux, streaming potential, and protein transmission during filtration of bovine serum albumin

  15. Fluorogen-activating proteins: beyond classical fluorescent proteins

    Directory of Open Access Journals (Sweden)

    Shengnan Xu

    2018-05-01

    Full Text Available Fluorescence imaging is a powerful technique for the real-time noninvasive monitoring of protein dynamics. Recently, fluorogen activating proteins (FAPs/fluorogen probes for protein imaging were developed. Unlike the traditional fluorescent proteins (FPs, FAPs do not fluoresce unless bound to their specific small-molecule fluorogens. When using FAPs/fluorogen probes, a washing step is not required for the removal of free probes from the cells, thus allowing rapid and specific detection of proteins in living cells with high signal-to-noise ratio. Furthermore, with different fluorogens, living cell multi-color proteins labeling system was developed. In this review, we describe about the discovery of FAPs, the design strategy of FAP fluorogens, the application of the FAP technology and the advances of FAP technology in protein labeling systems. KEY WORDS: Fluorogen activating proteins, Fluorogens, Genetically encoded sensors, Fluorescence imaging, Molecular imaging

  16. VOLTAMMETRIC DETERMINATION OF NICOTINE IN CIGARETTE ...

    African Journals Online (AJOL)

    Preferred Customer

    determination of nicotine in two brands of commercial cigarettes and ... to disruption of arteries and cardiovascular risk factors [8, 9]. Smoking .... e d. Figure 2. Cyclic voltammetric response (scan rate of 100 mV/s) of 1.0 mM nicotine at AGCE in.

  17. Protein immobilization strategies for protein biochips

    NARCIS (Netherlands)

    Rusmini, F.; Rusmini, Federica; Zhong, Zhiyuan; Feijen, Jan

    2007-01-01

    In the past few years, protein biochips have emerged as promising proteomic and diagnostic tools for obtaining information about protein functions and interactions. Important technological innovations have been made. However, considerable development is still required, especially regarding protein

  18. Protein Molecular Structures, Protein SubFractions, and Protein Availability Affected by Heat Processing: A Review

    International Nuclear Information System (INIS)

    Yu, P.

    2007-01-01

    The utilization and availability of protein depended on the types of protein and their specific susceptibility to enzymatic hydrolysis (inhibitory activities) in the gastrointestine and was highly associated with protein molecular structures. Studying internal protein structure and protein subfraction profiles leaded to an understanding of the components that make up a whole protein. An understanding of the molecular structure of the whole protein was often vital to understanding its digestive behavior and nutritive value in animals. In this review, recently obtained information on protein molecular structural effects of heat processing was reviewed, in relation to protein characteristics affecting digestive behavior and nutrient utilization and availability. The emphasis of this review was on (1) using the newly advanced synchrotron technology (S-FTIR) as a novel approach to reveal protein molecular chemistry affected by heat processing within intact plant tissues; (2) revealing the effects of heat processing on the profile changes of protein subfractions associated with digestive behaviors and kinetics manipulated by heat processing; (3) prediction of the changes of protein availability and supply after heat processing, using the advanced DVE/OEB and NRC-2001 models, and (4) obtaining information on optimal processing conditions of protein as intestinal protein source to achieve target values for potential high net absorbable protein in the small intestine. The information described in this article may give better insight in the mechanisms involved and the intrinsic protein molecular structural changes occurring upon processing.

  19. Analgecine, the extracts of Vaccinia-inoculated rabbit skin, effectively alleviates the chronic low back pain with little side effect – A randomized multi-center double-blind placebo-controlled phase 3 clinical trial

    Directory of Open Access Journals (Sweden)

    Jian Dong

    2016-04-01

    Conclusion: Analgecine (AGC, 8 units twice daily effectively alleviates chronic low back pain due to degenerative vertebral disorders when compared to placebo and is well tolerated by tested individuals, and can be considered as a first-line treatment for chronic low pain due to degenerative vertebral diseases.

  20. High grade serous ovarian carcinoma with serous tubal intraepithelial carcinoma in a case presented with atypical glandular cell favor neoplasm cervical cytology and dermatomyositis

    Directory of Open Access Journals (Sweden)

    Mun-Kun Hong

    2015-04-01

    Conclusion: The patient had serous carcinoma of the ovary with tubal STIC, which presented as dermatomyositis. The AGC-FN identified from a Pap smear hinted at a diagnosis of ovarian carcinoma. These presentations point to an occult malignancy in the genital tract and demand careful diagnostic workup.

  1. 78 FR 17598 - Program Integrity Issues

    Science.gov (United States)

    2013-03-22

    ... College and Higher Education (TEACH) Grant Program, the Federal Pell Grant Program, and the Academic Competitiveness Grant (AGC) and National Science and Mathematics Access to Retain Talent Grant (National Smart... is most likely to be obtained. As the primary function of admissions representatives is to serve as...

  2. Application of energy storage units in an interconnected hydro ...

    African Journals Online (AJOL)

    The main objective of Automatic Generation Control (AGC) is to balance the total system generation against system load and losses so that the desired frequency and power interchange with neighbouring systems are maintained. Any mismatch between generation and demand causes the system frequency to deviate from ...

  3. Information assessment on predicting protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Gerstein Mark

    2004-10-01

    Full Text Available Abstract Background Identifying protein-protein interactions is fundamental for understanding the molecular machinery of the cell. Proteome-wide studies of protein-protein interactions are of significant value, but the high-throughput experimental technologies suffer from high rates of both false positive and false negative predictions. In addition to high-throughput experimental data, many diverse types of genomic data can help predict protein-protein interactions, such as mRNA expression, localization, essentiality, and functional annotation. Evaluations of the information contributions from different evidences help to establish more parsimonious models with comparable or better prediction accuracy, and to obtain biological insights of the relationships between protein-protein interactions and other genomic information. Results Our assessment is based on the genomic features used in a Bayesian network approach to predict protein-protein interactions genome-wide in yeast. In the special case, when one does not have any missing information about any of the features, our analysis shows that there is a larger information contribution from the functional-classification than from expression correlations or essentiality. We also show that in this case alternative models, such as logistic regression and random forest, may be more effective than Bayesian networks for predicting interactions. Conclusions In the restricted problem posed by the complete-information subset, we identified that the MIPS and Gene Ontology (GO functional similarity datasets as the dominating information contributors for predicting the protein-protein interactions under the framework proposed by Jansen et al. Random forests based on the MIPS and GO information alone can give highly accurate classifications. In this particular subset of complete information, adding other genomic data does little for improving predictions. We also found that the data discretizations used in the

  4. Mapping Protein-Protein Interactions by Quantitative Proteomics

    DEFF Research Database (Denmark)

    Dengjel, Joern; Kratchmarova, Irina; Blagoev, Blagoy

    2010-01-01

    spectrometry (MS)-based proteomics in combination with affinity purification protocols has become the method of choice to map and track the dynamic changes in protein-protein interactions, including the ones occurring during cellular signaling events. Different quantitative MS strategies have been used...... to characterize protein interaction networks. In this chapter we describe in detail the use of stable isotope labeling by amino acids in cell culture (SILAC) for the quantitative analysis of stimulus-dependent dynamic protein interactions.......Proteins exert their function inside a cell generally in multiprotein complexes. These complexes are highly dynamic structures changing their composition over time and cell state. The same protein may thereby fulfill different functions depending on its binding partners. Quantitative mass...

  5. Fabrication of oxide layer on zirconium by micro-arc oxidation: Structural and antimicrobial characteristics

    International Nuclear Information System (INIS)

    Fidan, S.; Muhaffel, F.; Riool, M.; Cempura, G.; Boer, L. de; Zaat, S.A.J.; Filemonowicz, A. Czyrska -; Cimenoglu, H.

    2017-01-01

    The aim of this study was to cover the surfaces of zirconium (Zr) with an antimicrobial layer for biomedical applications. For this purpose, the micro-arc oxidation (MAO) process was employed in a sodium silicate and sodium hydroxide containing base electrolyte with and without addition of silver acetate (AgC 2 H 3 O 2 ). In general, synthesized MAO layers were composed of zirconium oxide (ZrO 2 ) and zircon (ZrSiO 4 ). Addition of AgC 2 H 3 O 2 into the base electrolyte caused homogenous precipitation of silver-containing particles in the MAO layer, which exhibited excellent antibacterial efficiency against methicillin-resistant Staphylococcus aureus (MRSA) as compared to the untreated and MAO-treated Zr. - Highlights: • Micro-arc oxidation process was applied on zirconium in an electrolyte containing silver acetate. • Silver incorporated in the oxide layer in the form of nanoparticles. • 0.45 wt.% silver incorporation provided excellent antibacterial activity.

  6. A crystallographically isolated dimeric hydrolyzed chlorophosphazene dianion

    Directory of Open Access Journals (Sweden)

    Matthew J. Panzner

    2009-01-01

    Full Text Available Single crystals of the title compound bis[bis(1-ethyl-3-methyl-imidazol-2-ylidenesilver(I] 1,5,5,7,11,11-hexachloro-2,8-dioxa-4,6,10,12,13,14-hexaaza-1λ5,3,5λ5,7λ5,9,11λ5-hexaphosphatricyclo[7.3.1.13,7]tetradeca-1(13,4,7(14,10-tetraene-6,12-diide 3,9-dioxide, [Ag(C6H10N22](Cl6N6O4P60.5, were isolated from the reaction of the silver N-heteocyclic carbene complex [Ag(C6H10N22]Cl and hexachlorocyclotriphosphazene [NPCl2]3 in the presence of water. The asymmetric unit contains one silver carbene cation with the carbene ligands bound to the Ag(I in an almost linear arrangement and one half of a hydrolyzed phosphazene dianion. The second cation and additional half of the anion are generated by an inversion center.

  7. Empirical multichannel power consumption model for erbium-doped fiber amplifiers

    DEFF Research Database (Denmark)

    Saldaña Cercos, Silvia; de Paiva, Getulio E. R.; Argentato, Marcio Colazza

    2015-01-01

    In this paper we report on the first experimental power consumption analysis and model of single and multi-stage booster erbium-doped fiber amplifiers (EDFAs) with automatic gain control (AGC), accounting for channel number dependency. Results show that the amount of channels being amplified simu......-users, it is relevant to study channel number dependent power consumption for devising EDFA power efficient control and design.......In this paper we report on the first experimental power consumption analysis and model of single and multi-stage booster erbium-doped fiber amplifiers (EDFAs) with automatic gain control (AGC), accounting for channel number dependency. Results show that the amount of channels being amplified...... simultaneously contributes significantly, up to 48%, to the total power consumption due to the circuitry used for controlling the EDFA. As the number of simultaneous amplified WDM channels in high capacity long and medium reach transmission links reflects closely traffic patterns generated by end...

  8. Does attention redirection contribute to the effectiveness of attention bias modification on social anxiety?

    Science.gov (United States)

    Yao, Nisha; Yu, Hongyu; Qian, Mingyi; Li, Songwei

    2015-12-01

    Attention bias modification (ABM) is designed to modify threat-related attention bias and thus alleviate anxiety. The current research examined whether consistently directing attention towards targeted goals per se contributes to ABM efficacy. We randomly assigned 68 non-clinical college students with elevated social anxiety to non-valence-specific attend-to-geometrics (AGC), attention modification (AMC), or attention control (ACC) conditions. We assessed subjective, behavioral, and physiological reactivity to a speech task and self-reported social anxiety symptoms. After training, participants in the AMC exhibited an attention avoidance from threat, and those in the AGC responded more rapidly toward targeted geometrics. There was a significant pre- to post-reduction in subjective speech distress across groups, but behavioral and physiological reactivity to speech, as well as self-report social anxiety symptoms, remained unchanged. These results lead to questions concerning effectiveness of ABM training for reducing social anxiety. Further examination of the current ABM protocol is required. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Template-free fabrication and morphology regulation of Ag@carbon composite structure

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenyan, E-mail: zhangwenyan8531@gmail.com [College of Material Engineering, Jinling Institute of Technology, Nanjing (China); Hao, Lingyun; Lin, Qin [College of Material Engineering, Jinling Institute of Technology, Nanjing (China); Lu, Chunhua; Xu, Zhongzi [College of Materials Science and Engineering, Nanjing Technology University, Nanjing (China); Chen, Xiaoyu [College of Material Engineering, Jinling Institute of Technology, Nanjing (China)

    2014-12-15

    Graphical abstract: - Highlights: • A simple and low-cost method to prepare Ag@C composite material. • AgNO{sub 3} plays an important role in tuning size and functional groups of products. • HTC reaction time is also a key factor for regulating the Ag@C structure. - Abstract: Ag–carbon composite materials were prepared without any template by hydrothermal carbonization of solvable starch. The composite materials are composed of Ag cores and carbonaceous shell to form a core–shell (Ag@carbon) structure. During the hydrothermal carbonization process, the aromatization and carbonization of solvable starch endowed the Ag@carbon composite structure with abundant aromatic, hydroxyl and carbonyl groups. The AgNO{sub 3} concentration and HTC reaction time are two important factors for regulating the size, morphology and functional groups of the composite material. With the increasing of AgNO{sub 3} concentration, morphologies of the composite material turned from spheres to wires.

  10. Jingle-bell-shaped ferrite hollow sphere with a noble metal core: Simple synthesis and their magnetic and antibacterial properties

    Science.gov (United States)

    Li, Siheng; Wang, Enbo; Tian, Chungui; Mao, Baodong; Kang, Zhenhui; Li, Qiuyu; Sun, Guoying

    2008-07-01

    In this paper, a simple strategy is developed for rational fabrication of a class of jingle-bell-shaped hollow structured nanomaterials marked as Ag@ MFe 2O 4 ( M=Ni, Co, Mg, Zn), consisting of ferrite hollow shells and metal nanoparticle cores, using highly uniform colloidal Ag@C microspheres as template. The final composites were obtained by direct adsorption of metal cations Fe 3+ and M 2+ on the surface of the Ag@C spheres followed by calcination process to remove the middle carbon shell and transform the metal ions into pure phase ferrites. The as-prepared composites were characterized by X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray analysis (EDX), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-vis spectroscopy and SQUID magnetometer. The results showed that the composites possess the magnetic property of the ferrite shell and the optical together with antibacterial property of the Ag core.

  11. Automatic generation control of TCPS based hydrothermal system under open market scenario: A fuzzy logic approach

    Energy Technology Data Exchange (ETDEWEB)

    Rao, C. Srinivasa [EEE Department, G. Pulla Reddy Engineering College, Kurnool, Andhra Pradesh (India); Nagaraju, S. Siva [EEE Department, J.N.T.U College of Engg., Kakinada, Andhra Pradesh (India); Raju, P. Sangameswara [EEE Department, S.V. University, Tirupati, Andhra Pradesh (India)

    2009-09-15

    This paper presents the analysis of automatic generation control of a two-area interconnected thyristor controlled phase shifter based hydrothermal system in the continuous mode using fuzzy logic controller under open market scenario. Open transmission access and the evolving of more socialized companies for generation, transmission and distribution affects the formulation of AGC problem. So the traditional AGC two-area system is modified to take into account the effect of bilateral contracts on the dynamics. It is possible to stabilize the system frequency and tie-power oscillations by controlling the phase angle of TCPS which is expected to provide a new ancillary service for the future power systems. A control strategy using TCPS is proposed to provide active control of system frequency. Further dynamic responses for small perturbation considering fuzzy logic controller and PI controller (dual mode controller) have been observed and the superior performance of fuzzy logic controller has been reported analytically and also through simulation. (author)

  12. ProDis-ContSHC: learning protein dissimilarity measures and hierarchical context coherently for protein-protein comparison in protein database retrieval.

    Science.gov (United States)

    Wang, Jingyan; Gao, Xin; Wang, Quanquan; Li, Yongping

    2012-05-08

    The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity/similarity measure for comparing a pair of proteins. This kind of pairwise measures suffer from the limitation of neglecting the distribution of other proteins and thus cannot satisfy the need for high accuracy of the retrieval systems. Recent work in the machine learning community has shown that exploiting the global structure of the database and learning the contextual dissimilarity/similarity measures can improve the retrieval performance significantly. However, most existing contextual dissimilarity/similarity learning algorithms work in an unsupervised manner, which does not utilize the information of the known class labels of proteins in the database. In this paper, we propose a novel protein-protein dissimilarity learning algorithm, ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij by considering the contextual information of the proteins. The context of a protein is defined by its neighboring proteins. The basic idea is, for a pair of proteins (i, j), if their context N(i) and N(j) is similar to each other, the two proteins should also have a high similarity. We implement this idea by regularizing dij by a factor learned from the context N(i) and N(j).Moreover, we divide the context to hierarchial sub-context and get the contextual dissimilarity vector for each protein pair. Using the class label information of the proteins, we select the relevant (a pair of proteins that has the same class labels) and irrelevant (with different labels) protein pairs, and train an SVM model to distinguish between their contextual dissimilarity vectors. The SVM model is further used to learn a supervised regularizing factor. Finally, with the new Supervised learned Dissimilarity measure, we update the Protein Hierarchial

  13. Biophysics of protein evolution and evolutionary protein biophysics

    Science.gov (United States)

    Sikosek, Tobias; Chan, Hue Sun

    2014-01-01

    The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence–structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by ‘hidden’ conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution. PMID:25165599

  14. High quality protein microarray using in situ protein purification

    Directory of Open Access Journals (Sweden)

    Fleischmann Robert D

    2009-08-01

    Full Text Available Abstract Background In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC. This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. Results Two slide surfaces were examined, chelated Cu2+ slides suspended on a polyethylene glycol (PEG coating and chelated Ni2+ slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu2+ slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents

  15. Can infrared spectroscopy provide information on protein-protein interactions?

    Science.gov (United States)

    Haris, Parvez I

    2010-08-01

    For most biophysical techniques, characterization of protein-protein interactions is challenging; this is especially true with methods that rely on a physical phenomenon that is common to both of the interacting proteins. Thus, for example, in IR spectroscopy, the carbonyl vibration (1600-1700 cm(-1)) associated with the amide bonds from both of the interacting proteins will overlap extensively, making the interpretation of spectral changes very complicated. Isotope-edited infrared spectroscopy, where one of the interacting proteins is uniformly labelled with (13)C or (13)C,(15)N has been introduced as a solution to this problem, enabling the study of protein-protein interactions using IR spectroscopy. The large shift of the amide I band (approx. 45 cm(-1) towards lower frequency) upon (13)C labelling of one of the proteins reveals the amide I band of the unlabelled protein, enabling it to be used as a probe for monitoring conformational changes. With site-specific isotopic labelling, structural resolution at the level of individual amino acid residues can be achieved. Furthermore, the ability to record IR spectra of proteins in diverse environments means that isotope-edited IR spectroscopy can be used to structurally characterize difficult systems such as protein-protein complexes bound to membranes or large insoluble peptide/protein aggregates. In the present article, examples of application of isotope-edited IR spectroscopy for studying protein-protein interactions are provided.

  16. Protein and protein hydrolysates in sports nutrition.

    Science.gov (United States)

    van Loon, Luc J C; Kies, Arie K; Saris, Wim H M

    2007-08-01

    With the increasing knowledge about the role of nutrition in increasing exercise performance, it has become clear over the last 2 decades that amino acids, protein, and protein hydrolysates can play an important role. Most of the attention has been focused on their effects at a muscular level. As these nutrients are ingested, however, it also means that gastrointestinal digestibility and absorption can modulate their efficacy significantly. Therefore, discussing the role of amino acids, protein, and protein hydrolysates in sports nutrition entails holding a discussion on all levels of the metabolic route. On May 28-29, 2007, a small group of researchers active in the field of exercise science and protein metabolism presented an overview of the different aspects of the application of protein and protein hydrolysates in sports nutrition. In addition, they were asked to share their opinions on the future progress in their fields of research. In this overview, an introduction to the workshop and a short summary of its outcome is provided.

  17. ProDis-ContSHC: Learning protein dissimilarity measures and hierarchical context coherently for protein-protein comparison in protein database retrieval

    KAUST Repository

    Wang, Jim Jing-Yan

    2012-05-08

    Background: The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity/similarity measure for comparing a pair of proteins. This kind of pairwise measures suffer from the limitation of neglecting the distribution of other proteins and thus cannot satisfy the need for high accuracy of the retrieval systems. Recent work in the machine learning community has shown that exploiting the global structure of the database and learning the contextual dissimilarity/similarity measures can improve the retrieval performance significantly. However, most existing contextual dissimilarity/similarity learning algorithms work in an unsupervised manner, which does not utilize the information of the known class labels of proteins in the database.Results: In this paper, we propose a novel protein-protein dissimilarity learning algorithm, ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij by considering the contextual information of the proteins. The context of a protein is defined by its neighboring proteins. The basic idea is, for a pair of proteins (i, j), if their context N (i) and N (j) is similar to each other, the two proteins should also have a high similarity. We implement this idea by regularizing dij by a factor learned from the context N (i) and N (j). Moreover, we divide the context to hierarchial sub-context and get the contextual dissimilarity vector for each protein pair. Using the class label information of the proteins, we select the relevant (a pair of proteins that has the same class labels) and irrelevant (with different labels) protein pairs, and train an SVM model to distinguish between their contextual dissimilarity vectors. The SVM model is further used to learn a supervised regularizing factor. Finally, with the new Supervised learned Dissimilarity measure, we update

  18. Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy.

    Science.gov (United States)

    Wang, Zhi-Hui; Li, Dong-Dong; Chen, Wei-Lin; You, Qi-Dong; Guo, Xiao-Ke

    2018-01-15

    The mixed lineage leukemia protein-1 (MLL1), as a lysine methyltransferase, predominantly regulates the methylation of histone H3 lysine 4 (H3K4) and functions in hematopoietic stem cell (HSC) self-renewal. MLL1 gene fuses with partner genes that results in the generation of MLL1 fusion proteins (MLL1-FPs), which are frequently detected in acute leukemia. In the progress of leukemogenesis, a great deal of proteins cooperate with MLL1 to form multiprotein complexes serving for the dysregulation of H3K4 methylation, the overexpression of homeobox (HOX) cluster genes, and the consequent generation of leukemia. Hence, disrupting the interactions between MLL1 and the reciprocal proteins has been considered to be a new treatment strategy for leukemia. Here, we reviewed potential protein-protein interactions (PPIs) between MLL1 and its reciprocal proteins, and summarized the inhibitors to target MLL1 PPIs. The druggability of MLL1 PPIs for leukemia were also discussed. Copyright © 2017. Published by Elsevier Ltd.

  19. Protein kinase substrate identification on functional protein arrays

    Directory of Open Access Journals (Sweden)

    Zhou Fang

    2008-02-01

    Full Text Available Abstract Background Over the last decade, kinases have emerged as attractive therapeutic targets for a number of different diseases, and numerous high throughput screening efforts in the pharmaceutical community are directed towards discovery of compounds that regulate kinase function. The emerging utility of systems biology approaches has necessitated the development of multiplex tools suitable for proteomic-scale experiments to replace lower throughput technologies such as mass spectroscopy for the study of protein phosphorylation. Recently, a new approach for identifying substrates of protein kinases has applied the miniaturized format of functional protein arrays to characterize phosphorylation for thousands of candidate protein substrates in a single experiment. This method involves the addition of protein kinases in solution to arrays of immobilized proteins to identify substrates using highly sensitive radioactive detection and hit identification algorithms. Results To date, the factors required for optimal performance of protein array-based kinase substrate identification have not been described. In the current study, we have carried out a detailed characterization of the protein array-based method for kinase substrate identification, including an examination of the effects of time, buffer compositions, and protein concentration on the results. The protein array approach was compared to standard solution-based assays for assessing substrate phosphorylation, and a correlation of greater than 80% was observed. The results presented here demonstrate how novel substrates for protein kinases can be quickly identified from arrays containing thousands of human proteins to provide new clues to protein kinase function. In addition, a pooling-deconvolution strategy was developed and applied that enhances characterization of specific kinase-substrate relationships and decreases reagent consumption. Conclusion Functional protein microarrays are an

  20. Protein kinesis: The dynamics of protein trafficking and stability

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    The purpose of this conference is to provide a multidisciplinary forum for exchange of state-of-the-art information on protein kinesis. This volume contains abstracts of papers in the following areas: protein folding and modification in the endoplasmic reticulum; protein trafficking; protein translocation and folding; protein degradation; polarity; nuclear trafficking; membrane dynamics; and protein import into organelles.

  1. LEVELS OF METALS IN COMMERCIALLY AVAILABLE ETHIOPIAN ...

    African Journals Online (AJOL)

    Preferred Customer

    Tea, one of the most popular beverages in the world, is an infusion of the leaves of .... the local market of Ethiopia and (ii) the three tea brands represent the three different tea ..... Kumar, A.; Nair, A.G.C.; Reddy, A.V.R.; Garg, A.N. Food Chem.

  2. 78 FR 57798 - Program Integrity Issues

    Science.gov (United States)

    2013-09-20

    ... Competitiveness Grant (AGC) and the National Science and Mathematics Access to Retain Talent Grant (National Smart... Federal Register. Free Internet access to the official edition of the Federal Register and the Code of... of title 34 of the Code of Federal Regulations as follows: PART 668--STUDENT ASSISTANCE GENERAL...

  3. HKC: An Algorithm to Predict Protein Complexes in Protein-Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Xiaomin Wang

    2011-01-01

    Full Text Available With the availability of more and more genome-scale protein-protein interaction (PPI networks, research interests gradually shift to Systematic Analysis on these large data sets. A key topic is to predict protein complexes in PPI networks by identifying clusters that are densely connected within themselves but sparsely connected with the rest of the network. In this paper, we present a new topology-based algorithm, HKC, to detect protein complexes in genome-scale PPI networks. HKC mainly uses the concepts of highest k-core and cohesion to predict protein complexes by identifying overlapping clusters. The experiments on two data sets and two benchmarks show that our algorithm has relatively high F-measure and exhibits better performance compared with some other methods.

  4. Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial.

    Science.gov (United States)

    Hu, Yanfeng; Huang, Changming; Sun, Yihong; Su, Xiangqian; Cao, Hui; Hu, Jiankun; Xue, Yingwei; Suo, Jian; Tao, Kaixiong; He, Xianli; Wei, Hongbo; Ying, Mingang; Hu, Weiguo; Du, Xiaohui; Chen, Pingyan; Liu, Hao; Zheng, Chaohui; Liu, Fenglin; Yu, Jiang; Li, Ziyu; Zhao, Gang; Chen, Xinzu; Wang, Kuan; Li, Ping; Xing, Jiadi; Li, Guoxin

    2016-04-20

    The safety and efficacy of radical laparoscopic distal gastrectomy (LG) with D2 lymphadenectomy for the treatment of advanced gastric cancer (AGC) remain controversial. We conducted a randomized controlled trial to compare laparoscopic and conventional open distal gastrectomy with D2 lymph node dissections for AGC. Between September 2012 and December 2014, 1,056 patients with clinical stage T2-4aN0-3M0 gastric cancer were eligible for inclusion. They were randomly assigned to either the LG with D2 lymphadenectomy group (n = 528) or the open gastrectomy (OG) with D2 lymphadenectomy group (n = 528). Fifteen experienced surgeons from 14 institutions in China participated in the study. The morbidity and mortality within 30 days after surgery between the LG (n = 519) and the OG (n = 520) groups were compared on the basis of the modified intention-to-treat principle. Postoperative complications were stratified according to the Clavien-Dindo classification. The compliance rates of D2 lymphadenectomy were similar between the LG and OG groups (99.4% v 99.6%; P = .845). The postoperative morbidity was 15.2% in the LG group and 12.9% in OG group with no significant difference (difference, 2.3%; 95% CI, -1.9 to 6.6; P = .285). The mortality rate was 0.4% for the LG group and zero for the OG group (difference, 0.4%; 95% CI, -0.4 to 1.4; P = .249). The distribution of severity was similar between the two groups (P = .314). Experienced surgeons can safely perform LG with D2 lymphadenectomy for AGC. © 2016 by American Society of Clinical Oncology.

  5. Efficacy of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer: the protocol of the KLASS-02 multicenter randomized controlled clinical trial

    International Nuclear Information System (INIS)

    Hur, Hoon; Lee, Hyun Yong; Lee, Hyuk-Joon; Kim, Min Chan; Hyung, Woo Jin; Park, Young Kyu; Kim, Wook; Han, Sang-Uk

    2015-01-01

    Despite the well-described benefits of laparoscopic surgery such as lower operative blood loss and enhanced postoperative recovery in gastric cancer surgery, the application of laparoscopic surgery in patients with locally advanced gastric cancer (AGC) remains elusive owing to a lack of clinical evidence. Recently, the Korean Laparoscopic Surgical Society Group launched a new multicenter randomized clinical trial (RCT) to compare laparoscopic and open D2 lymphadenectomy for patients with locally AGC. Here, we introduce the protocol of this clinical trial. This trial is an investigator-initiated, randomized, controlled, parallel group, non-inferiority trial. Gastric cancer patients diagnosed with primary tumors that have invaded into the muscle propria and not into an adjacent organ (cT2–cT4a) in preoperative studies are recruited. Another criterion for recruitment is no lymph node metastasis or limited perigastric lymph node (including lymph nodes around the left gastric artery) metastasis. A total 1,050 patients in both groups are required to statistically show non-inferiority of the laparoscopic approach with respect to the primary end-point, relapse-free survival of 3 years. Secondary outcomes include postoperative morbidity and mortality, postoperative recovery, quality of life, and overall survival. Surgeons who are validated through peer-review of their surgery videos can participate in this clinical trial. This clinical trial was designed to maintain the principles of a surgical clinical trial with internal validity for participating surgeons. Through the KLASS-02 RCT, we hope to show the efficacy of laparoscopic D2 lymphadenectomy in AGC patients compared with the open procedure. ClinicalTrial.gov, https://www.clinicaltrials.gov/ct2/show/NCT01456598?term

  6. Historical forest baselines reveal potential for continued carbon sequestration

    Science.gov (United States)

    Rhemtulla, Jeanine M.; Mladenoff, David J.; Clayton, Murray K.

    2009-01-01

    One-third of net CO2 emissions to the atmosphere since 1850 are the result of land-use change, primarily from the clearing of forests for timber and agriculture, but quantifying these changes is complicated by the lack of historical data on both former ecosystem conditions and the extent and spatial configuration of subsequent land use. Using fine-resolution historical survey records, we reconstruct pre-EuroAmerican settlement (1850s) forest carbon in the state of Wisconsin, examine changes in carbon after logging and agricultural conversion, and assess the potential for future sequestration through forest recovery. Results suggest that total above-ground live forest carbon (AGC) fell from 434 TgC before settlement to 120 TgC at the peak of agricultural clearing in the 1930s and has since recovered to approximately 276 TgC. The spatial distribution of AGC, however, has shifted significantly. Former savanna ecosystems in the south now store more AGC because of fire suppression and forest ingrowth, despite the fact that most of the region remains in agriculture, whereas northern forests still store much less carbon than before settlement. Across the state, continued sequestration in existing forests has the potential to contribute an additional 69 TgC. Reforestation of agricultural lands, in particular, the formerly high C-density forests in the north-central region that are now agricultural lands less optimal than those in the south, could contribute 150 TgC. Restoring historical carbon stocks across the landscape will therefore require reassessing overall land-use choices, but a range of options can be ranked and considered under changing needs for ecosystem services. PMID:19369213

  7. Comparison of RECIST version 1.0 and 1.1 in assessment of tumor response by computed tomography in advanced gastric cancer.

    Science.gov (United States)

    Jang, Gil-Su; Kim, Min-Jeong; Ha, Hong-Il; Kim, Jung Han; Kim, Hyeong Su; Ju, Sung Bae; Zang, Dae Young

    2013-12-01

    Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0 (RECIST 1.0) was proposed as a new guideline for evaluating tumor response and has been widely accepted as a standardized measure. With a number of issues being raised on RECIST 1.0, however, a revised RECIST guideline version 1.1 (RECIST 1.1) was proposed by the RECIST Working Group in 2009. This study was conducted to compare CT tumor response based on RECIST 1.1 vs. RECIST 1.0 in patients with advanced gastric cancer (AGC). We reviewed 61 AGC patients with measurable diseases by RECIST 1.0 who were enrolled in other clinical trials between 2008 and 2010. These patients were retrospectively re-analyzed to determine the concordance between the two response criteria using the κ statistic. The number and sum of tumor diameters of the target lesions by RECIST 1.1 were significantly lower than those by RECIST 1.0 (P<0.0001). However, there was excellent agreement in tumor response between RECIST 1.1 and RECIST 1.0 (κ=0.844). The overall response rates (ORRs) according to RECIST 1.0 and RECIST 1.1 were 32.7% (20/61) and 34.5% (20/58), respectively. One patient with partial response (PR) based on RECIST 1.0 was reclassified as stable disease (SD) by RECIST 1.1. Of two patients with SD by RECIST 1.0, one was downgraded to progressive disease and the other was upgraded to PR by RECIST 1.1. RECIST 1.1 provided almost perfect agreement with RECIST 1.0 in the CT assessment of tumor response of AGC.

  8. Molecular tweezers modulate 14-3-3 protein-protein interactions

    Science.gov (United States)

    Bier, David; Rose, Rolf; Bravo-Rodriguez, Kenny; Bartel, Maria; Ramirez-Anguita, Juan Manuel; Dutt, Som; Wilch, Constanze; Klärner, Frank-Gerrit; Sanchez-Garcia, Elsa; Schrader, Thomas; Ottmann, Christian

    2013-03-01

    Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins—a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)—in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions.

  9. Changes in protein composition and protein phosphorylation during ...

    African Journals Online (AJOL)

    Changes in protein profiles and protein phosphorylation were studied in various stages of germinating somatic and zygotic embryos. Many proteins, which were expressed in cotyledonary stage somatic embryos, were also present in the zygotic embryos obtained from mature dry seed. The intensity of 22 kDa protein was ...

  10. An ontology-based search engine for protein-protein interactions.

    Science.gov (United States)

    Park, Byungkyu; Han, Kyungsook

    2010-01-18

    Keyword matching or ID matching is the most common searching method in a large database of protein-protein interactions. They are purely syntactic methods, and retrieve the records in the database that contain a keyword or ID specified in a query. Such syntactic search methods often retrieve too few search results or no results despite many potential matches present in the database. We have developed a new method for representing protein-protein interactions and the Gene Ontology (GO) using modified Gödel numbers. This representation is hidden from users but enables a search engine using the representation to efficiently search protein-protein interactions in a biologically meaningful way. Given a query protein with optional search conditions expressed in one or more GO terms, the search engine finds all the interaction partners of the query protein by unique prime factorization of the modified Gödel numbers representing the query protein and the search conditions. Representing the biological relations of proteins and their GO annotations by modified Gödel numbers makes a search engine efficiently find all protein-protein interactions by prime factorization of the numbers. Keyword matching or ID matching search methods often miss the interactions involving a protein that has no explicit annotations matching the search condition, but our search engine retrieves such interactions as well if they satisfy the search condition with a more specific term in the ontology.

  11. Water-Protein Interactions: The Secret of Protein Dynamics

    Directory of Open Access Journals (Sweden)

    Silvia Martini

    2013-01-01

    Full Text Available Water-protein interactions help to maintain flexible conformation conditions which are required for multifunctional protein recognition processes. The intimate relationship between the protein surface and hydration water can be analyzed by studying experimental water properties measured in protein systems in solution. In particular, proteins in solution modify the structure and the dynamics of the bulk water at the solute-solvent interface. The ordering effects of proteins on hydration water are extended for several angstroms. In this paper we propose a method for analyzing the dynamical properties of the water molecules present in the hydration shells of proteins. The approach is based on the analysis of the effects of protein-solvent interactions on water protons NMR relaxation parameters. NMR relaxation parameters, especially the nonselective (R1NS and selective (R1SE spin-lattice relaxation rates of water protons, are useful for investigating the solvent dynamics at the macromolecule-solvent interfaces as well as the perturbation effects caused by the water-macromolecule interactions on the solvent dynamical properties. In this paper we demonstrate that Nuclear Magnetic Resonance Spectroscopy can be used to determine the dynamical contributions of proteins to the water molecules belonging to their hydration shells.

  12. Two Chimeric Regulators of G-protein Signaling (RGS) Proteins Differentially Modulate Soybean Heterotrimeric G-protein Cycle*

    Science.gov (United States)

    Roy Choudhury, Swarup; Westfall, Corey S.; Laborde, John P.; Bisht, Naveen C.; Jez, Joseph M.; Pandey, Sona

    2012-01-01

    Heterotrimeric G-proteins and the regulator of G-protein signaling (RGS) proteins, which accelerate the inherent GTPase activity of Gα proteins, are common in animals and encoded by large gene families; however, in plants G-protein signaling is thought to be more limited in scope. For example, Arabidopsis thaliana contains one Gα, one Gβ, three Gγ, and one RGS protein. Recent examination of the Glycine max (soybean) genome reveals a larger set of G-protein-related genes and raises the possibility of more intricate G-protein networks than previously observed in plants. Stopped-flow analysis of GTP-binding and GDP/GTP exchange for the four soybean Gα proteins (GmGα1–4) reveals differences in their kinetic properties. The soybean genome encodes two chimeric RGS proteins with an N-terminal seven transmembrane domain and a C-terminal RGS box. Both GmRGS interact with each of the four GmGα and regulate their GTPase activity. The GTPase-accelerating activities of GmRGS1 and -2 differ for each GmGα, suggesting more than one possible rate of the G-protein cycle initiated by each of the Gα proteins. The differential effects of GmRGS1 and GmRGS2 on GmGα1–4 result from a single valine versus alanine difference. The emerging picture suggests complex regulation of the G-protein cycle in soybean and in other plants with expanded G-protein networks. PMID:22474294

  13. Alignment of non-covalent interactions at protein-protein interfaces.

    Directory of Open Access Journals (Sweden)

    Hongbo Zhu

    Full Text Available BACKGROUND: The study and comparison of protein-protein interfaces is essential for the understanding of the mechanisms of interaction between proteins. While there are many methods for comparing protein structures and protein binding sites, so far no methods have been reported for comparing the geometry of non-covalent interactions occurring at protein-protein interfaces. METHODOLOGY/PRINCIPAL FINDINGS: Here we present a method for aligning non-covalent interactions between different protein-protein interfaces. The method aligns the vector representations of van der Waals interactions and hydrogen bonds based on their geometry. The method has been applied to a dataset which comprises a variety of protein-protein interfaces. The alignments are consistent to a large extent with the results obtained using two other complementary approaches. In addition, we apply the method to three examples of protein mimicry. The method successfully aligns respective interfaces and allows for recognizing conserved interface regions. CONCLUSIONS/SIGNIFICANCE: The Galinter method has been validated in the comparison of interfaces in which homologous subunits are involved, including cases of mimicry. The method is also applicable to comparing interfaces involving non-peptidic compounds. Galinter assists users in identifying local interface regions with similar patterns of non-covalent interactions. This is particularly relevant to the investigation of the molecular basis of interaction mimicry.

  14. The Ser/Thr Protein Kinase Protein-Protein Interaction Map of M. tuberculosis.

    Science.gov (United States)

    Wu, Fan-Lin; Liu, Yin; Jiang, He-Wei; Luan, Yi-Zhao; Zhang, Hai-Nan; He, Xiang; Xu, Zhao-Wei; Hou, Jing-Li; Ji, Li-Yun; Xie, Zhi; Czajkowsky, Daniel M; Yan, Wei; Deng, Jiao-Yu; Bi, Li-Jun; Zhang, Xian-En; Tao, Sheng-Ce

    2017-08-01

    Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, the leading cause of death among all infectious diseases. There are 11 eukaryotic-like serine/threonine protein kinases (STPKs) in Mtb, which are thought to play pivotal roles in cell growth, signal transduction and pathogenesis. However, their underlying mechanisms of action remain largely uncharacterized. In this study, using a Mtb proteome microarray, we have globally identified the binding proteins in Mtb for all of the STPKs, and constructed the first STPK protein interaction (KPI) map that includes 492 binding proteins and 1,027 interactions. Bioinformatics analysis showed that the interacting proteins reflect diverse functions, including roles in two-component system, transcription, protein degradation, and cell wall integrity. Functional investigations confirmed that PknG regulates cell wall integrity through key components of peptidoglycan (PG) biosynthesis, e.g. MurC. The global STPK-KPIs network constructed here is expected to serve as a rich resource for understanding the key signaling pathways in Mtb, thus facilitating drug development and effective control of Mtb. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Protein-protein interaction site predictions with three-dimensional probability distributions of interacting atoms on protein surfaces.

    Directory of Open Access Journals (Sweden)

    Ching-Tai Chen

    Full Text Available Protein-protein interactions are key to many biological processes. Computational methodologies devised to predict protein-protein interaction (PPI sites on protein surfaces are important tools in providing insights into the biological functions of proteins and in developing therapeutics targeting the protein-protein interaction sites. One of the general features of PPI sites is that the core regions from the two interacting protein surfaces are complementary to each other, similar to the interior of proteins in packing density and in the physicochemical nature of the amino acid composition. In this work, we simulated the physicochemical complementarities by constructing three-dimensional probability density maps of non-covalent interacting atoms on the protein surfaces. The interacting probabilities were derived from the interior of known structures. Machine learning algorithms were applied to learn the characteristic patterns of the probability density maps specific to the PPI sites. The trained predictors for PPI sites were cross-validated with the training cases (consisting of 432 proteins and were tested on an independent dataset (consisting of 142 proteins. The residue-based Matthews correlation coefficient for the independent test set was 0.423; the accuracy, precision, sensitivity, specificity were 0.753, 0.519, 0.677, and 0.779 respectively. The benchmark results indicate that the optimized machine learning models are among the best predictors in identifying PPI sites on protein surfaces. In particular, the PPI site prediction accuracy increases with increasing size of the PPI site and with increasing hydrophobicity in amino acid composition of the PPI interface; the core interface regions are more likely to be recognized with high prediction confidence. The results indicate that the physicochemical complementarity patterns on protein surfaces are important determinants in PPIs, and a substantial portion of the PPI sites can be predicted

  16. Protein-Protein Interaction Site Predictions with Three-Dimensional Probability Distributions of Interacting Atoms on Protein Surfaces

    Science.gov (United States)

    Chen, Ching-Tai; Peng, Hung-Pin; Jian, Jhih-Wei; Tsai, Keng-Chang; Chang, Jeng-Yih; Yang, Ei-Wen; Chen, Jun-Bo; Ho, Shinn-Ying; Hsu, Wen-Lian; Yang, An-Suei

    2012-01-01

    Protein-protein interactions are key to many biological processes. Computational methodologies devised to predict protein-protein interaction (PPI) sites on protein surfaces are important tools in providing insights into the biological functions of proteins and in developing therapeutics targeting the protein-protein interaction sites. One of the general features of PPI sites is that the core regions from the two interacting protein surfaces are complementary to each other, similar to the interior of proteins in packing density and in the physicochemical nature of the amino acid composition. In this work, we simulated the physicochemical complementarities by constructing three-dimensional probability density maps of non-covalent interacting atoms on the protein surfaces. The interacting probabilities were derived from the interior of known structures. Machine learning algorithms were applied to learn the characteristic patterns of the probability density maps specific to the PPI sites. The trained predictors for PPI sites were cross-validated with the training cases (consisting of 432 proteins) and were tested on an independent dataset (consisting of 142 proteins). The residue-based Matthews correlation coefficient for the independent test set was 0.423; the accuracy, precision, sensitivity, specificity were 0.753, 0.519, 0.677, and 0.779 respectively. The benchmark results indicate that the optimized machine learning models are among the best predictors in identifying PPI sites on protein surfaces. In particular, the PPI site prediction accuracy increases with increasing size of the PPI site and with increasing hydrophobicity in amino acid composition of the PPI interface; the core interface regions are more likely to be recognized with high prediction confidence. The results indicate that the physicochemical complementarity patterns on protein surfaces are important determinants in PPIs, and a substantial portion of the PPI sites can be predicted correctly with

  17. Bioinformatic Prediction of WSSV-Host Protein-Protein Interaction

    Directory of Open Access Journals (Sweden)

    Zheng Sun

    2014-01-01

    Full Text Available WSSV is one of the most dangerous pathogens in shrimp aquaculture. However, the molecular mechanism of how WSSV interacts with shrimp is still not very clear. In the present study, bioinformatic approaches were used to predict interactions between proteins from WSSV and shrimp. The genome data of WSSV (NC_003225.1 and the constructed transcriptome data of F. chinensis were used to screen potentially interacting proteins by searching in protein interaction databases, including STRING, Reactome, and DIP. Forty-four pairs of proteins were suggested to have interactions between WSSV and the shrimp. Gene ontology analysis revealed that 6 pairs of these interacting proteins were classified into “extracellular region” or “receptor complex” GO-terms. KEGG pathway analysis showed that they were involved in the “ECM-receptor interaction pathway.” In the 6 pairs of interacting proteins, an envelope protein called “collagen-like protein” (WSSV-CLP encoded by an early virus gene “wsv001” in WSSV interacted with 6 deduced proteins from the shrimp, including three integrin alpha (ITGA, two integrin beta (ITGB, and one syndecan (SDC. Sequence analysis on WSSV-CLP, ITGA, ITGB, and SDC revealed that they possessed the sequence features for protein-protein interactions. This study might provide new insights into the interaction mechanisms between WSSV and shrimp.

  18. The findings and the role of axial CT imaging and 3D imaging of gastric lesion by spiral CT

    International Nuclear Information System (INIS)

    Lee, Dong Ho; Ko, Young Tae

    1996-01-01

    The purpose of this study is to assess the efficacy of axial CT imaging and 3D imaging by spiral CT in the detection and evaluation of gastric lesion. Seventy-seven patients with pathologically-proven gastric lesions underwent axial CT and 3D imaging by spiral CT. There were 49 cases of advanced gastric carcinoma(AGC), 21 of early gastric carcinoma (EGC), three of benign ulcers, three of leiomyomas, and one case of lymphoma. Spiral CT was performed with 3-mm collimation, 4.5mm/sec table feed, and 1-1.5-mm reconstruction interval after the ingestion of gas. 3D imaging was obtained using the SSD technique, and on analysis a grade was given(excellent, good, poor). Axial CT scan was performed with 5-mm collimation, 7mm/sec table feed, and 5-mm reconstruction interval after the ingestion of water. Among 49 cases of AGC, excellent 3D images were obtained in seven patients (14.3%), good 3D images in 30(61.2%), and poor 3D images in 12(24.5%). Among the 12 patients with poor images, the cancers were located at the pyloric antrum in eight cases, were AGC Borrmann type 4 in three cases, and EGC-mimicking lesion in one case. Using axial CT scan alone, Borrmann's classification based tumor morphology were accurately identified in 67.3% of cases, but using 3D imaging, the corresponding figure was 85.7%. In 33 cases receiving surgery, good correlation between axial CT scan and pathology occurred in 72.7% of T class, and 69.7% of N class. Among 21 cases of EGC, excellent 3D images were obtained in three patients (14.3%), good 3D images in 14 (66.7%), and poor 3D images in two (9.5%). The other two cases of EGC were not detected. By axial CT scan, no tumor was detected in four cases, and there were two doubtful cases. 3D images of three benign ulcers were excellent in one case and good in two. 3D images of three leiomyomas and one lymphoma were excellent. Combined axial CT imaging and 3D imaging by spiral CT has the potential to accurately diagnose gastric lesions other than AGC

  19. Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Jesus R.; Becker, Christopher J.; Blackledge, Charles W.; Duquenne, Celine; Feng, Yanhong; Grant, Seth W.; Heerding, Dirk; Li, William H.; Miller, William H.; Romeril, Stuart P.; Scherzer, Daryl; Shu, Arthur; Bobko, Mark A.; Chadderton, Antony R.; Dumble, Melissa; Gardiner, Christine M.; Gilbert, Seth; Liu, Qi; Rabindran, Sridhar K.; Sudakin, Valery; Xiang, Hong; Brady, Pat G.; Campobasso, Nino; Ward, Paris; Axten, Jeffrey M. (GSKPA)

    2014-10-02

    Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

  20. Protein subcellular localization assays using split fluorescent proteins

    Science.gov (United States)

    Waldo, Geoffrey S [Santa Fe, NM; Cabantous, Stephanie [Los Alamos, NM

    2009-09-08

    The invention provides protein subcellular localization assays using split fluorescent protein systems. The assays are conducted in living cells, do not require fixation and washing steps inherent in existing immunostaining and related techniques, and permit rapid, non-invasive, direct visualization of protein localization in living cells. The split fluorescent protein systems used in the practice of the invention generally comprise two or more self-complementing fragments of a fluorescent protein, such as GFP, wherein one or more of the fragments correspond to one or more beta-strand microdomains and are used to "tag" proteins of interest, and a complementary "assay" fragment of the fluorescent protein. Either or both of the fragments may be functionalized with a subcellular targeting sequence enabling it to be expressed in or directed to a particular subcellular compartment (i.e., the nucleus).

  1. Human cancer protein-protein interaction network: a structural perspective.

    Directory of Open Access Journals (Sweden)

    Gozde Kar

    2009-12-01

    Full Text Available Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network. The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%. We illustrate the interface related affinity properties of two cancer-related hub

  2. Localization of oestrogen hormone receptors in the reproductive ...

    African Journals Online (AJOL)

    Primers sequence used were the forward and reverse β oestrogen primer which was designed to detect the expression of the gene encoding oestrogen receptor in the reproductive tract of the giant African Land Snail (Archachatina marginata) were: Forward: 5'-GCT TCG AGC TCA GCC TG-3' Reverse: 5'-AGG ATC ATG ...

  3. 76 FR 65773 - Petition for Waiver of the Terms of the Order Limiting Scheduled Operations at LaGuardia Airport...

    Science.gov (United States)

    2011-10-24

    ... respective airport. Eligible participating carriers also may not be subsidiaries, either partially or wholly... post a running tally of bids for each slot bundle at http://www.faa.gov/about/office_org/headquarters.../office_org/headquarters_offices/agc/ReAllocation . The FAA also will post all other bid information with...

  4. Hot-spot analysis for drug discovery targeting protein-protein interactions.

    Science.gov (United States)

    Rosell, Mireia; Fernández-Recio, Juan

    2018-04-01

    Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.

  5. Interaction between plate make and protein in protein crystallisation screening.

    Directory of Open Access Journals (Sweden)

    Gordon J King

    Full Text Available BACKGROUND: Protein crystallisation screening involves the parallel testing of large numbers of candidate conditions with the aim of identifying conditions suitable as a starting point for the production of diffraction quality crystals. Generally, condition screening is performed in 96-well plates. While previous studies have examined the effects of protein construct, protein purity, or crystallisation condition ingredients on protein crystallisation, few have examined the effect of the crystallisation plate. METHODOLOGY/PRINCIPAL FINDINGS: We performed a statistically rigorous examination of protein crystallisation, and evaluated interactions between crystallisation success and plate row/column, different plates of same make, different plate makes and different proteins. From our analysis of protein crystallisation, we found a significant interaction between plate make and the specific protein being crystallised. CONCLUSIONS/SIGNIFICANCE: Protein crystal structure determination is the principal method for determining protein structure but is limited by the need to produce crystals of the protein under study. Many important proteins are difficult to crystallize, so that identification of factors that assist crystallisation could open up the structure determination of these more challenging targets. Our findings suggest that protein crystallisation success may be improved by matching a protein with its optimal plate make.

  6. Protein Charge and Mass Contribute to the Spatio-temporal Dynamics of Protein-Protein Interactions in a Minimal Proteome

    Science.gov (United States)

    Xu, Yu; Wang, Hong; Nussinov, Ruth; Ma, Buyong

    2013-01-01

    We constructed and simulated a ‘minimal proteome’ model using Langevin dynamics. It contains 206 essential protein types which were compiled from the literature. For comparison, we generated six proteomes with randomized concentrations. We found that the net charges and molecular weights of the proteins in the minimal genome are not random. The net charge of a protein decreases linearly with molecular weight, with small proteins being mostly positively charged and large proteins negatively charged. The protein copy numbers in the minimal genome have the tendency to maximize the number of protein-protein interactions in the network. Negatively charged proteins which tend to have larger sizes can provide large collision cross-section allowing them to interact with other proteins; on the other hand, the smaller positively charged proteins could have higher diffusion speed and are more likely to collide with other proteins. Proteomes with random charge/mass populations form less stable clusters than those with experimental protein copy numbers. Our study suggests that ‘proper’ populations of negatively and positively charged proteins are important for maintaining a protein-protein interaction network in a proteome. It is interesting to note that the minimal genome model based on the charge and mass of E. Coli may have a larger protein-protein interaction network than that based on the lower organism M. pneumoniae. PMID:23420643

  7. Prediction of heterodimeric protein complexes from weighted protein-protein interaction networks using novel features and kernel functions.

    Directory of Open Access Journals (Sweden)

    Peiying Ruan

    Full Text Available Since many proteins express their functional activity by interacting with other proteins and forming protein complexes, it is very useful to identify sets of proteins that form complexes. For that purpose, many prediction methods for protein complexes from protein-protein interactions have been developed such as MCL, MCODE, RNSC, PCP, RRW, and NWE. These methods have dealt with only complexes with size of more than three because the methods often are based on some density of subgraphs. However, heterodimeric protein complexes that consist of two distinct proteins occupy a large part according to several comprehensive databases of known complexes. In this paper, we propose several feature space mappings from protein-protein interaction data, in which each interaction is weighted based on reliability. Furthermore, we make use of prior knowledge on protein domains to develop feature space mappings, domain composition kernel and its combination kernel with our proposed features. We perform ten-fold cross-validation computational experiments. These results suggest that our proposed kernel considerably outperforms the naive Bayes-based method, which is the best existing method for predicting heterodimeric protein complexes.

  8. NMR Studies of Protein Hydration and Protein-Ligand Interactions

    Science.gov (United States)

    Chong, Yuan

    Water on the surface of a protein is called hydration water. Hydration water is known to play a crucial role in a variety of biological processes including protein folding, enzymatic activation, and drug binding. Although the significance of hydration water has been recognized, the underlying mechanism remains far from being understood. This dissertation employs a unique in-situ nuclear magnetic resonance (NMR) technique to study the mechanism of protein hydration and the role of hydration in alcohol-protein interactions. Water isotherms in proteins are measured at different temperatures via the in-situ NMR technique. Water is found to interact differently with hydrophilic and hydrophobic groups on the protein. Water adsorption on hydrophilic groups is hardly affected by the temperature, while water adsorption on hydrophobic groups strongly depends on the temperature around 10 C, below which the adsorption is substantially reduced. This effect is induced by the dramatic decrease in the protein flexibility below 10 C. Furthermore, nanosecond to microsecond protein dynamics and the free energy, enthalpy, and entropy of protein hydration are studied as a function of hydration level and temperature. A crossover at 10 C in protein dynamics and thermodynamics is revealed. The effect of water at hydrophilic groups on protein dynamics and thermodynamics shows little temperature dependence, whereas water at hydrophobic groups has stronger effect above 10 C. In addition, I investigate the role of water in alcohol binding to the protein using the in-situ NMR detection. The isotherms of alcohols are first measured on dry proteins, then on proteins with a series of controlled hydration levels. The free energy, enthalpy, and entropy of alcohol binding are also determined. Two distinct types of alcohol binding are identified. On the one hand, alcohols can directly bind to a few specific sites on the protein. This type of binding is independent of temperature and can be

  9. Mapping monomeric threading to protein-protein structure prediction.

    Science.gov (United States)

    Guerler, Aysam; Govindarajoo, Brandon; Zhang, Yang

    2013-03-25

    The key step of template-based protein-protein structure prediction is the recognition of complexes from experimental structure libraries that have similar quaternary fold. Maintaining two monomer and dimer structure libraries is however laborious, and inappropriate library construction can degrade template recognition coverage. We propose a novel strategy SPRING to identify complexes by mapping monomeric threading alignments to protein-protein interactions based on the original oligomer entries in the PDB, which does not rely on library construction and increases the efficiency and quality of complex template recognitions. SPRING is tested on 1838 nonhomologous protein complexes which can recognize correct quaternary template structures with a TM score >0.5 in 1115 cases after excluding homologous proteins. The average TM score of the first model is 60% and 17% higher than that by HHsearch and COTH, respectively, while the number of targets with an interface RMSD benchmark proteins. Although the relative performance of SPRING and ZDOCK depends on the level of homology filters, a combination of the two methods can result in a significantly higher model quality than ZDOCK at all homology thresholds. These data demonstrate a new efficient approach to quaternary structure recognition that is ready to use for genome-scale modeling of protein-protein interactions due to the high speed and accuracy.

  10. DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network.

    Science.gov (United States)

    Mistry, Divya; Wise, Roger P; Dickerson, Julie A

    2017-01-01

    Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be

  11. A credit-card library approach for disrupting protein-protein interactions.

    Science.gov (United States)

    Xu, Yang; Shi, Jin; Yamamoto, Noboru; Moss, Jason A; Vogt, Peter K; Janda, Kim D

    2006-04-15

    Protein-protein interfaces are prominent in many therapeutically important targets. Using small organic molecules to disrupt protein-protein interactions is a current challenge in chemical biology. An important example of protein-protein interactions is provided by the Myc protein, which is frequently deregulated in human cancers. Myc belongs to the family of basic helix-loop-helix leucine zipper (bHLH-ZIP) transcription factors. It is biologically active only as heterodimer with the bHLH-ZIP protein Max. Herein, we report a new strategy for the disruption of protein-protein interactions that has been corroborated through the design and synthesis of a small parallel library composed of 'credit-card' compounds. These compounds are derived from a planar, aromatic scaffold and functionalized with four points of diversity. From a 285 membered library, several hits were obtained that disrupted the c-Myc-Max interaction and cellular functions of c-Myc. The IC50 values determined for this small focused library for the disruption of Myc-Max dimerization are quite potent, especially since small molecule antagonists of protein-protein interactions are notoriously difficult to find. Furthermore, several of the compounds were active at the cellular level as shown by their biological effects on Myc action in chicken embryo fibroblast assays. In light of our findings, this approach is considered a valuable addition to the armamentarium of new molecules being developed to interact with protein-protein interfaces. Finally, this strategy for disrupting protein-protein interactions should prove applicable to other families of proteins.

  12. Protein Correlation Profiles Identify Lipid Droplet Proteins with High Confidence*

    Science.gov (United States)

    Krahmer, Natalie; Hilger, Maximiliane; Kory, Nora; Wilfling, Florian; Stoehr, Gabriele; Mann, Matthias; Farese, Robert V.; Walther, Tobias C.

    2013-01-01

    Lipid droplets (LDs) are important organelles in energy metabolism and lipid storage. Their cores are composed of neutral lipids that form a hydrophobic phase and are surrounded by a phospholipid monolayer that harbors specific proteins. Most well-established LD proteins perform important functions, particularly in cellular lipid metabolism. Morphological studies show LDs in close proximity to and interacting with membrane-bound cellular organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and endosomes. Because of these close associations, it is difficult to purify LDs to homogeneity. Consequently, the confident identification of bona fide LD proteins via proteomics has been challenging. Here, we report a methodology for LD protein identification based on mass spectrometry and protein correlation profiles. Using LD purification and quantitative, high-resolution mass spectrometry, we identified LD proteins by correlating their purification profiles to those of known LD proteins. Application of the protein correlation profile strategy to LDs isolated from Drosophila S2 cells led to the identification of 111 LD proteins in a cellular LD fraction in which 1481 proteins were detected. LD localization was confirmed in a subset of identified proteins via microscopy of the expressed proteins, thereby validating the approach. Among the identified LD proteins were both well-characterized LD proteins and proteins not previously known to be localized to LDs. Our method provides a high-confidence LD proteome of Drosophila cells and a novel approach that can be applied to identify LD proteins of other cell types and tissues. PMID:23319140

  13. ProteinShop: A tool for interactive protein manipulation and steering

    Energy Technology Data Exchange (ETDEWEB)

    Crivelli, Silvia; Kreylos, Oliver; Max, Nelson; Hamann, Bernd; Bethel, Wes

    2004-05-25

    We describe ProteinShop, a new visualization tool that streamlines and simplifies the process of determining optimal protein folds. ProteinShop may be used at different stages of a protein structure prediction process. First, it can create protein configurations containing secondary structures specified by the user. Second, it can interactively manipulate protein fragments to achieve desired folds by adjusting the dihedral angles of selected coil regions using an Inverse Kinematics method. Last, it serves as a visual framework to monitor and steer a protein structure prediction process that may be running on a remote machine. ProteinShop was used to create initial configurations for a protein structure prediction method developed by a team that competed in CASP5. ProteinShop's use accelerated the process of generating initial configurations, reducing the time required from days to hours. This paper describes the structure of ProteinShop and discusses its main features.

  14. Prioritizing disease candidate proteins in cardiomyopathy-specific protein-protein interaction networks based on "guilt by association" analysis.

    Directory of Open Access Journals (Sweden)

    Wan Li

    Full Text Available The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial. Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on "guilt by association" analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on "guilt by association" analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.

  15. Modular protein switches derived from antibody mimetic proteins.

    Science.gov (United States)

    Nicholes, N; Date, A; Beaujean, P; Hauk, P; Kanwar, M; Ostermeier, M

    2016-02-01

    Protein switches have potential applications as biosensors and selective protein therapeutics. Protein switches built by fusion of proteins with the prerequisite input and output functions are currently developed using an ad hoc process. A modular switch platform in which existing switches could be readily adapted to respond to any ligand would be advantageous. We investigated the feasibility of a modular protein switch platform based on fusions of the enzyme TEM-1 β-lactamase (BLA) with two different antibody mimetic proteins: designed ankyrin repeat proteins (DARPins) and monobodies. We created libraries of random insertions of the gene encoding BLA into genes encoding a DARPin or a monobody designed to bind maltose-binding protein (MBP). From these libraries, we used a genetic selection system for β-lactamase activity to identify genes that conferred MBP-dependent ampicillin resistance to Escherichia coli. Some of these selected genes encoded switch proteins whose enzymatic activity increased up to 14-fold in the presence of MBP. We next introduced mutations into the antibody mimetic domain of these switches that were known to cause binding to different ligands. To different degrees, introduction of the mutations resulted in switches with the desired specificity, illustrating the potential modularity of these platforms. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Protein-protein interactions and cancer: targeting the central dogma.

    Science.gov (United States)

    Garner, Amanda L; Janda, Kim D

    2011-01-01

    Between 40,000 and 200,000 protein-protein interactions have been predicted to exist within the human interactome. As these interactions are of a critical nature in many important cellular functions and their dysregulation is causal of disease, the modulation of these binding events has emerged as a leading, yet difficult therapeutic arena. In particular, the targeting of protein-protein interactions relevant to cancer is of fundamental importance as the tumor-promoting function of several aberrantly expressed proteins in the cancerous state is directly resultant of its ability to interact with a protein-binding partner. Of significance, these protein complexes play a crucial role in each of the steps of the central dogma of molecular biology, the fundamental processes of genetic transmission. With the many important discoveries being made regarding the mechanisms of these genetic process, the identification of new chemical probes are needed to better understand and validate the druggability of protein-protein interactions related to the central dogma. In this review, we provide an overview of current small molecule-based protein-protein interaction inhibitors for each stage of the central dogma: transcription, mRNA splicing and translation. Importantly, through our analysis we have uncovered a lack of necessary probes targeting mRNA splicing and translation, thus, opening up the possibility for expansion of these fields.

  17. Targeting protein-protein interactions for parasite control.

    Directory of Open Access Journals (Sweden)

    Christina M Taylor

    2011-04-01

    Full Text Available Finding new drug targets for pathogenic infections would be of great utility for humanity, as there is a large need to develop new drugs to fight infections due to the developing resistance and side effects of current treatments. Current drug targets for pathogen infections involve only a single protein. However, proteins rarely act in isolation, and the majority of biological processes occur via interactions with other proteins, so protein-protein interactions (PPIs offer a realm of unexplored potential drug targets and are thought to be the next-generation of drug targets. Parasitic worms were chosen for this study because they have deleterious effects on human health, livestock, and plants, costing society billions of dollars annually and many sequenced genomes are available. In this study, we present a computational approach that utilizes whole genomes of 6 parasitic and 1 free-living worm species and 2 hosts. The species were placed in orthologous groups, then binned in species-specific orthologous groups. Proteins that are essential and conserved among species that span a phyla are of greatest value, as they provide foundations for developing broad-control strategies. Two PPI databases were used to find PPIs within the species specific bins. PPIs with unique helminth proteins and helminth proteins with unique features relative to the host, such as indels, were prioritized as drug targets. The PPIs were scored based on RNAi phenotype and homology to the PDB (Protein DataBank. EST data for the various life stages, GO annotation, and druggability were also taken into consideration. Several PPIs emerged from this study as potential drug targets. A few interactions were supported by co-localization of expression in M. incognita (plant parasite and B. malayi (H. sapiens parasite, which have extremely different modes of parasitism. As more genomes of pathogens are sequenced and PPI databases expanded, this methodology will become increasingly

  18. ProteinHistorian: tools for the comparative analysis of eukaryote protein origin.

    Directory of Open Access Journals (Sweden)

    John A Capra

    Full Text Available The evolutionary history of a protein reflects the functional history of its ancestors. Recent phylogenetic studies identified distinct evolutionary signatures that characterize proteins involved in cancer, Mendelian disease, and different ontogenic stages. Despite the potential to yield insight into the cellular functions and interactions of proteins, such comparative phylogenetic analyses are rarely performed, because they require custom algorithms. We developed ProteinHistorian to make tools for performing analyses of protein origins widely available. Given a list of proteins of interest, ProteinHistorian estimates the phylogenetic age of each protein, quantifies enrichment for proteins of specific ages, and compares variation in protein age with other protein attributes. ProteinHistorian allows flexibility in the definition of protein age by including several algorithms for estimating ages from different databases of evolutionary relationships. We illustrate the use of ProteinHistorian with three example analyses. First, we demonstrate that proteins with high expression in human, compared to chimpanzee and rhesus macaque, are significantly younger than those with human-specific low expression. Next, we show that human proteins with annotated regulatory functions are significantly younger than proteins with catalytic functions. Finally, we compare protein length and age in many eukaryotic species and, as expected from previous studies, find a positive, though often weak, correlation between protein age and length. ProteinHistorian is available through a web server with an intuitive interface and as a set of command line tools; this allows biologists and bioinformaticians alike to integrate these approaches into their analysis pipelines. ProteinHistorian's modular, extensible design facilitates the integration of new datasets and algorithms. The ProteinHistorian web server, source code, and pre-computed ages for 32 eukaryotic genomes are

  19. Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

    Science.gov (United States)

    He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

    2012-07-01

    Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

  20. Annotating the protein-RNA interaction sites in proteins using evolutionary information and protein backbone structure.

    Science.gov (United States)

    Li, Tao; Li, Qian-Zhong

    2012-11-07

    RNA-protein interactions play important roles in various biological processes. The precise detection of RNA-protein interaction sites is very important for understanding essential biological processes and annotating the function of the proteins. In this study, based on various features from amino acid sequence and structure, including evolutionary information, solvent accessible surface area and torsion angles (φ, ψ) in the backbone structure of the polypeptide chain, a computational method for predicting RNA-binding sites in proteins is proposed. When the method is applied to predict RNA-binding sites in three datasets: RBP86 containing 86 protein chains, RBP107 containing 107 proteins chains and RBP109 containing 109 proteins chains, better sensitivities and specificities are obtained compared to previously published methods in five-fold cross-validation tests. In order to make further examination for the efficiency of our method, the RBP107 dataset is used as training set, RBP86 and RBP109 datasets are used as the independent test sets. In addition, as examples of our prediction, RNA-binding sites in a few proteins are presented. The annotated results are consistent with the PDB annotation. These results show that our method is useful for annotating RNA binding sites of novel proteins.

  1. The role of the Jacobi last multiplier and isochronous systems

    Indian Academy of Sciences (India)

    The authors wish to thank Sergej Flach and Basil Grammaticos for their valuable constructive remarks. AGC wishes to acknowledge the support provided by the S.N. Bose National Centre for Basic Sciences, Kolkata in the form of an Associateship. References. [1] C G J Jacobi, Sul principio dell'ultimo moltiplicatore, e suo ...

  2. On interface dipole layers between C60 and Ag or Au

    NARCIS (Netherlands)

    Veenstra, Sjoerd; Heeres, A.; Hadziioannou, G.; Sawatzky, G.A.; Jonkman, H.T.

    2002-01-01

    C60 layers on polycrystalline Ag and Au are studied by photoelectron spectroscopy. At these metal/C60 interfaces an electron transfer occurs from the metal to the lowest unoccupied orbital of C60. We found in the case of the polycrystalline Ag/C60 interface a dipolar layer with its associated

  3. Evolutionary diversification of protein-protein interactions by interface add-ons.

    Science.gov (United States)

    Plach, Maximilian G; Semmelmann, Florian; Busch, Florian; Busch, Markus; Heizinger, Leonhard; Wysocki, Vicki H; Merkl, Rainer; Sterner, Reinhard

    2017-10-03

    Cells contain a multitude of protein complexes whose subunits interact with high specificity. However, the number of different protein folds and interface geometries found in nature is limited. This raises the question of how protein-protein interaction specificity is achieved on the structural level and how the formation of nonphysiological complexes is avoided. Here, we describe structural elements called interface add-ons that fulfill this function and elucidate their role for the diversification of protein-protein interactions during evolution. We identified interface add-ons in 10% of a representative set of bacterial, heteromeric protein complexes. The importance of interface add-ons for protein-protein interaction specificity is demonstrated by an exemplary experimental characterization of over 30 cognate and hybrid glutamine amidotransferase complexes in combination with comprehensive genetic profiling and protein design. Moreover, growth experiments showed that the lack of interface add-ons can lead to physiologically harmful cross-talk between essential biosynthetic pathways. In sum, our complementary in silico, in vitro, and in vivo analysis argues that interface add-ons are a practical and widespread evolutionary strategy to prevent the formation of nonphysiological complexes by specializing protein-protein interactions.

  4. The interface of protein structure, protein biophysics, and molecular evolution

    Science.gov (United States)

    Liberles, David A; Teichmann, Sarah A; Bahar, Ivet; Bastolla, Ugo; Bloom, Jesse; Bornberg-Bauer, Erich; Colwell, Lucy J; de Koning, A P Jason; Dokholyan, Nikolay V; Echave, Julian; Elofsson, Arne; Gerloff, Dietlind L; Goldstein, Richard A; Grahnen, Johan A; Holder, Mark T; Lakner, Clemens; Lartillot, Nicholas; Lovell, Simon C; Naylor, Gavin; Perica, Tina; Pollock, David D; Pupko, Tal; Regan, Lynne; Roger, Andrew; Rubinstein, Nimrod; Shakhnovich, Eugene; Sjölander, Kimmen; Sunyaev, Shamil; Teufel, Ashley I; Thorne, Jeffrey L; Thornton, Joseph W; Weinreich, Daniel M; Whelan, Simon

    2012-01-01

    Abstract The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction. PMID:22528593

  5. Racemic & quasi-racemic protein crystallography enabled by chemical protein synthesis.

    Science.gov (United States)

    Kent, Stephen Bh

    2018-04-04

    A racemic protein mixture can be used to form centrosymmetric crystals for structure determination by X-ray diffraction. Both the unnatural d-protein and the corresponding natural l-protein are made by total chemical synthesis based on native chemical ligation-chemoselective condensation of unprotected synthetic peptide segments. Racemic protein crystallography is important for structure determination of the many natural protein molecules that are refractory to crystallization. Racemic mixtures facilitate the crystallization of recalcitrant proteins, and give diffraction-quality crystals. Quasi-racemic crystallization, using a single d-protein molecule, can facilitate the determination of the structures of a series of l-protein analog molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. General protein-protein cross-linking.

    Science.gov (United States)

    Alegria-Schaffer, Alice

    2014-01-01

    This protocol describes a general protein-to-protein cross-linking procedure using the water-soluble amine-reactive homobifunctional BS(3) (bis[sulfosuccinimidyl] suberate); however, the protocol can be easily adapted using other cross-linkers of similar properties. BS(3) is composed of two sulfo-NHS ester groups and an 11.4 Å linker. Sulfo-NHS ester groups react with primary amines in slightly alkaline conditions (pH 7.2-8.5) and yield stable amide bonds. The reaction releases N-hydroxysuccinimide (see an application of NHS esters on Labeling a protein with fluorophores using NHS ester derivitization). © 2014 Elsevier Inc. All rights reserved.

  7. Quality control methodology for high-throughput protein-protein interaction screening.

    Science.gov (United States)

    Vazquez, Alexei; Rual, Jean-François; Venkatesan, Kavitha

    2011-01-01

    Protein-protein interactions are key to many aspects of the cell, including its cytoskeletal structure, the signaling processes in which it is involved, or its metabolism. Failure to form protein complexes or signaling cascades may sometimes translate into pathologic conditions such as cancer or neurodegenerative diseases. The set of all protein interactions between the proteins encoded by an organism constitutes its protein interaction network, representing a scaffold for biological function. Knowing the protein interaction network of an organism, combined with other sources of biological information, can unravel fundamental biological circuits and may help better understand the molecular basics of human diseases. The protein interaction network of an organism can be mapped by combining data obtained from both low-throughput screens, i.e., "one gene at a time" experiments and high-throughput screens, i.e., screens designed to interrogate large sets of proteins at once. In either case, quality controls are required to deal with the inherent imperfect nature of experimental assays. In this chapter, we discuss experimental and statistical methodologies to quantify error rates in high-throughput protein-protein interactions screens.

  8. Quantifying the molecular origins of opposite solvent effects on protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Vincent Vagenende

    Full Text Available Although the nature of solvent-protein interactions is generally weak and non-specific, addition of cosolvents such as denaturants and osmolytes strengthens protein-protein interactions for some proteins, whereas it weakens protein-protein interactions for others. This is exemplified by the puzzling observation that addition of glycerol oppositely affects the association constants of two antibodies, D1.3 and D44.1, with lysozyme. To resolve this conundrum, we develop a methodology based on the thermodynamic principles of preferential interaction theory and the quantitative characterization of local protein solvation from molecular dynamics simulations. We find that changes of preferential solvent interactions at the protein-protein interface quantitatively account for the opposite effects of glycerol on the antibody-antigen association constants. Detailed characterization of local protein solvation in the free and associated protein states reveals how opposite solvent effects on protein-protein interactions depend on the extent of dewetting of the protein-protein contact region and on structural changes that alter cooperative solvent-protein interactions at the periphery of the protein-protein interface. These results demonstrate the direct relationship between macroscopic solvent effects on protein-protein interactions and atom-scale solvent-protein interactions, and establish a general methodology for predicting and understanding solvent effects on protein-protein interactions in diverse biological environments.

  9. Our interests in protein-protein interactions

    Indian Academy of Sciences (India)

    protein interactions. Evolution of P-P partnerships. Evolution of P-P structures. Evolutionary dynamics of P-P interactions. Dynamics of P-P interaction network. Host-pathogen interactions. CryoEM mapping of gigantic protein assemblies.

  10. A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions

    Science.gov (United States)

    Hostetler, Jessica B.; Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.; Fairhurst, Rick M.; Rayner, Julian C.

    2015-01-01

    Background A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. Methodology/Principal Findings We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further

  11. [Detection of protein-protein interactions by FRET and BRET methods].

    Science.gov (United States)

    Matoulková, E; Vojtěšek, B

    2014-01-01

    Nowadays, in vivo protein-protein interaction studies have become preferable detecting meth-ods that enable to show or specify (already known) protein interactions and discover their inhibitors. They also facilitate detection of protein conformational changes and discovery or specification of signaling pathways in living cells. One group of in vivo methods enabling these findings is based on fluorescent resonance energy transfer (FRET) and its bio-luminescent modification (BRET). They are based on visualization of protein-protein interactions via light or enzymatic excitation of fluorescent or bio-luminescent proteins. These methods allow not only protein localization within the cell or its organelles (or small animals) but they also allow us to quantify fluorescent signals and to discover weak or strong interaction partners. In this review, we explain the principles of FRET and BRET, their applications in the characterization of protein-protein interactions and we describe several findings using these two methods that clarify molecular and cellular mechanisms and signals related to cancer biology.

  12. Protein degradation and protein synthesis in long-term memory formation

    Directory of Open Access Journals (Sweden)

    Timothy J Jarome

    2014-06-01

    Full Text Available Long-term memory (LTM formation requires transient changes in the activity of intracellular signaling cascades that are thought to regulate new gene transcription and de novo protein synthesis in the brain. Consistent with this, protein synthesis inhibitors impair LTM for a variety of behavioral tasks when infused into the brain around the time of training or following memory retrieval, suggesting that protein synthesis is a critical step in LTM storage in the brain. However, evidence suggests that protein degradation mediated by the ubiquitin-proteasome system may also be a critical regulator of LTM formation and stability following retrieval. This requirement for increased protein degradation has been shown in the same brain regions in which protein synthesis is required for LTM storage. Additionally, increases in the phosphorylation of proteins involved in translational control parallel increases in protein polyubiquitination and the increased demand for protein degradation is regulated by intracellular signaling molecules thought to regulate protein synthesis during LTM formation. In some cases inhibiting proteasome activity can rescue memory impairments that result from pharmacological blockade of protein synthesis, suggesting that protein degradation may control the requirement for protein synthesis during the memory storage process. Results such as these suggest that protein degradation and synthesis are both critical for LTM formation and may interact to properly consolidate and store memories in the brain. Here, we review the evidence implicating protein synthesis and degradation in LTM storage and highlight the areas of overlap between these two opposing processes. We also discuss evidence suggesting these two processes may interact to properly form and store memories. LTM storage likely requires a coordinated regulation between protein degradation and synthesis at multiple sites in the mammalian brain.

  13. Evolutionary reprograming of protein-protein interaction specificity.

    Science.gov (United States)

    Akiva, Eyal; Babbitt, Patricia C

    2015-10-22

    Using mutation libraries and deep sequencing, Aakre et al. study the evolution of protein-protein interactions using a toxin-antitoxin model. The results indicate probable trajectories via "intermediate" proteins that are promiscuous, thus avoiding transitions via non-interactions. These results extend observations about other biological interactions and enzyme evolution, suggesting broadly general principles. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Protein Annotation from Protein Interaction Networks and Gene Ontology

    OpenAIRE

    Nguyen, Cao D.; Gardiner, Katheleen J.; Cios, Krzysztof J.

    2011-01-01

    We introduce a novel method for annotating protein function that combines Naïve Bayes and association rules, and takes advantage of the underlying topology in protein interaction networks and the structure of graphs in the Gene Ontology. We apply our method to proteins from the Human Protein Reference Database (HPRD) and show that, in comparison with other approaches, it predicts protein functions with significantly higher recall with no loss of precision. Specifically, it achieves 51% precis...

  15. Protein supplementation with sports protein bars in renal patients.

    Science.gov (United States)

    Meade, Anthony

    2007-05-01

    Malnutrition prevalence in patients on dialysis is well established. The protein requirements for both hemodialysis and peritoneal dialysis have been documented elsewhere, including the Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Nutrition in Chronic Renal Failure. The clinical challenge is to assist patients in meeting these targets, especially in those with anorexia. Traditional supplements have included fluid, which is an issue for patients who are fluid restricted. The study objectives were to (1) investigate the range of sports protein supplements that may be suitable for patients on hemodialysis to use and (2) trial nonfluid protein supplements in patients on hemodialysis. Known manufacturers of sports protein bars and other sports supplements available in Australia were contacted for the nutrient breakdown of high-protein products, specifically potassium, protein, and phosphorus contents. As a result, selected high-protein sports bars (Protein FX, Aussie Bodies, Port Melbourne, Victoria, Australia) were used as an alternative to the more commonly used renal-specific fluid supplements (Nepro, Abbott Laboratories, Abbott Park, IL; Novasource Renal, Novartis Nutrition Corporation, Fremont, MI; and Renilon, Nutricia, Wiltshire, UK) in patients with poor nutritional status requiring supplementation. Patient satisfaction and clinical nutrition markers were investigated. The study took place at inpatient, in-center, and satellite hemodialysis settings in Adelaide, South Australia. A total of 32 patients (16 females and 16 males) with an average age of 62.9 years (range 32-86 years) undergoing hemodialysis (acute and maintenance) were included. Subjects were selected by the author as part of routine clinical nutrition care. Patients trialed sports protein bars as a protein supplement alone or in conjunction with other supplementary products. All patients were in favor of the trial, with 22 of 32 patients continuing with the protein

  16. Protein enriched pasta: structure and digestibility of its protein network.

    Science.gov (United States)

    Laleg, Karima; Barron, Cécile; Santé-Lhoutellier, Véronique; Walrand, Stéphane; Micard, Valérie

    2016-02-01

    Wheat (W) pasta was enriched in 6% gluten (G), 35% faba (F) or 5% egg (E) to increase its protein content (13% to 17%). The impact of the enrichment on the multiscale structure of the pasta and on in vitro protein digestibility was studied. Increasing the protein content (W- vs. G-pasta) strengthened pasta structure at molecular and macroscopic scales but reduced its protein digestibility by 3% by forming a higher covalently linked protein network. Greater changes in the macroscopic and molecular structure of the pasta were obtained by varying the nature of protein used for enrichment. Proteins in G- and E-pasta were highly covalently linked (28-32%) resulting in a strong pasta structure. Conversely, F-protein (98% SDS-soluble) altered the pasta structure by diluting gluten and formed a weak protein network (18% covalent link). As a result, protein digestibility in F-pasta was significantly higher (46%) than in E- (44%) and G-pasta (39%). The effect of low (55 °C, LT) vs. very high temperature (90 °C, VHT) drying on the protein network structure and digestibility was shown to cause greater molecular changes than pasta formulation. Whatever the pasta, a general strengthening of its structure, a 33% to 47% increase in covalently linked proteins and a higher β-sheet structure were observed. However, these structural differences were evened out after the pasta was cooked, resulting in identical protein digestibility in LT and VHT pasta. Even after VHT drying, F-pasta had the best amino acid profile with the highest protein digestibility, proof of its nutritional interest.

  17. HIV protein sequence hotspots for crosstalk with host hub proteins.

    Directory of Open Access Journals (Sweden)

    Mahdi Sarmady

    Full Text Available HIV proteins target host hub proteins for transient binding interactions. The presence of viral proteins in the infected cell results in out-competition of host proteins in their interaction with hub proteins, drastically affecting cell physiology. Functional genomics and interactome datasets can be used to quantify the sequence hotspots on the HIV proteome mediating interactions with host hub proteins. In this study, we used the HIV and human interactome databases to identify HIV targeted host hub proteins and their host binding partners (H2. We developed a high throughput computational procedure utilizing motif discovery algorithms on sets of protein sequences, including sequences of HIV and H2 proteins. We identified as HIV sequence hotspots those linear motifs that are highly conserved on HIV sequences and at the same time have a statistically enriched presence on the sequences of H2 proteins. The HIV protein motifs discovered in this study are expressed by subsets of H2 host proteins potentially outcompeted by HIV proteins. A large subset of these motifs is involved in cleavage, nuclear localization, phosphorylation, and transcription factor binding events. Many such motifs are clustered on an HIV sequence in the form of hotspots. The sequential positions of these hotspots are consistent with the curated literature on phenotype altering residue mutations, as well as with existing binding site data. The hotspot map produced in this study is the first global portrayal of HIV motifs involved in altering the host protein network at highly connected hub nodes.

  18. Different protein-protein interface patterns predicted by different machine learning methods.

    Science.gov (United States)

    Wang, Wei; Yang, Yongxiao; Yin, Jianxin; Gong, Xinqi

    2017-11-22

    Different types of protein-protein interactions make different protein-protein interface patterns. Different machine learning methods are suitable to deal with different types of data. Then, is it the same situation that different interface patterns are preferred for prediction by different machine learning methods? Here, four different machine learning methods were employed to predict protein-protein interface residue pairs on different interface patterns. The performances of the methods for different types of proteins are different, which suggest that different machine learning methods tend to predict different protein-protein interface patterns. We made use of ANOVA and variable selection to prove our result. Our proposed methods taking advantages of different single methods also got a good prediction result compared to single methods. In addition to the prediction of protein-protein interactions, this idea can be extended to other research areas such as protein structure prediction and design.

  19. Molecular simulations of lipid-mediated protein-protein interactions

    NARCIS (Netherlands)

    de Meyer, F.J.M.; Venturoli, M.; Smit, B.

    2008-01-01

    Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may be important in determining the protein topology after insertion in the membrane, in regulating the protein activity, in protein aggregation and in signal transduction. To gain insight into the

  20. Detecting protein-protein interactions in living cells

    DEFF Research Database (Denmark)

    Gottschalk, Marie; Bach, Anders; Hansen, Jakob Lerche

    2009-01-01

    to the endogenous C-terminal peptide of the NMDA receptor, as evaluated by a cell-free protein-protein interaction assay. However, it is important to address both membrane permeability and effect in living cells. Therefore a bioluminescence resonance energy transfer (BRET) assay was established, where the C......-terminal of the NMDA receptor and PDZ2 of PSD-95 were fused to green fluorescent protein (GFP) and Renilla luciferase (Rluc) and expressed in COS7 cells. A robust and specific BRET signal was obtained by expression of the appropriate partner proteins and subsequently, the assay was used to evaluate a Tat......The PDZ domain mediated interaction between the NMDA receptor and its intracellular scaffolding protein, PSD-95, is a potential target for treatment of ischemic brain diseases. We have recently developed a number of peptide analogues with improved affinity for the PDZ domains of PSD-95 compared...

  1. Personalizing Protein Nourishment

    Science.gov (United States)

    DALLAS, DAVID C.; SANCTUARY, MEGAN R.; QU, YUNYAO; KHAJAVI, SHABNAM HAGHIGHAT; VAN ZANDT, ALEXANDRIA E.; DYANDRA, MELISSA; FRESE, STEVEN A.; BARILE, DANIELA; GERMAN, J. BRUCE

    2016-01-01

    Proteins are not equally digestible—their proteolytic susceptibility varies by their source and processing method. Incomplete digestion increases colonic microbial protein fermentation (putrefaction), which produces toxic metabolites that can induce inflammation in vitro and have been associated with inflammation in vivo. Individual humans differ in protein digestive capacity based on phenotypes, particularly disease states. To avoid putrefaction-induced intestinal inflammation, protein sources and processing methods must be tailored to the consumer’s digestive capacity. This review explores how food processing techniques alter protein digestibility and examines how physiological conditions alter digestive capacity. Possible solutions to improving digestive function or matching low digestive capacity with more digestible protein sources are explored. Beyond the ileal digestibility measurements of protein digestibility, less invasive, quicker and cheaper techniques for monitoring the extent of protein digestion and fermentation are needed to personalize protein nourishment. Biomarkers of protein digestive capacity and efficiency can be identified with the toolsets of peptidomics, metabolomics, microbial sequencing and multiplexed protein analysis of fecal and urine samples. By monitoring individual protein digestive function, the protein component of diets can be tailored via protein source and processing selection to match individual needs to minimize colonic putrefaction and, thus, optimize gut health. PMID:26713355

  2. A scored human protein-protein interaction network to catalyze genomic interpretation

    DEFF Research Database (Denmark)

    Li, Taibo; Wernersson, Rasmus; Hansen, Rasmus B

    2017-01-01

    Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (InWeb_InBioMap,......Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (In...

  3. Transduction proteins of olfactory receptor cells: identification of guanine nucleotide binding proteins and protein kinase C

    International Nuclear Information System (INIS)

    Anholt, R.R.H.; Mumby, S.M.; Stoffers, D.A.; Girard, P.R.; Kuo, J.F.; Snyder, S.H.

    1987-01-01

    The authors have analyzed guanine nucleotide binding proteins (G-proteins) in the olfactory epithelium of Rana catesbeiana using subunit-specific antisera. The olfactory epithelium contained the α subunits of three G-proteins, migrating on polyacrylamide gels in SDS with apparent molecular weights of 45,000, 42,000, and 40,000, corresponding to G/sub s/, G/sub i/, and G/sub o/, respectively. A single β subunit with an apparent molecular weight of 36,000 was detected. An antiserum against the α subunit of retinal transducin failed to detect immunoreactive proteins in olfactory cilia detached from the epithelium. The olfactory cilia appeared to be enriched in immunoreactive G/sub sα/ relative to G/sub ichemical bond/ and G/sub ochemical bond/ when compared to membranes prepared from the olfactory epithelium after detachment of the cilia. Bound antibody was detected by autoradiography after incubation with [ 125 I]protein. Immunohistochemical studies using an antiserum against the β subunit of G-proteins revealed intense staining of the ciliary surface of the olfactory epithelium and of the axon bundles in the lamina propria. In contrast, an antiserum against a common sequence of the α subunits preferentially stained the cell membranes of the olfactory receptor cells and the acinar cells of Bowman's glands and the deep submucosal glands. In addition to G-proteins, they have identified protein kinase C in olfactory cilia via a protein kinase C specific antiserum and via phorbol ester binding. However, in contrast to the G-proteins, protein kinase C occurred also in cilia isolated from respiratory epithelium

  4. Progression and regression of cervical pap test lesions in an urban AIDS clinic in the combined antiretroviral therapy era: a longitudinal, retrospective study.

    Science.gov (United States)

    Lofgren, Sarah M; Tadros, Talaat; Herring-Bailey, Gina; Birdsong, George; Mosunjac, Marina; Flowers, Lisa; Nguyen, Minh Ly

    2015-05-01

    Our objective was to evaluate the progression and regression of cervical dysplasia in human immunodeficiency virus (HIV)-positive women during the late antiretroviral era. Risk factors as well as outcomes after treatment of cancerous or precancerous lesions were examined. This is a longitudinal retrospective review of cervical Pap tests performed on HIV-infected women with an intact cervix between 2004 and 2011. Subjects needed over two Pap tests for at least 2 years of follow-up. Progression was defined as those who developed a squamous intraepithelial lesion (SIL), atypical glandular cells (AGC), had low-grade SIL (LSIL) followed by atypical squamous cells-cannot exclude high-grade SIL (ASC-H) or high-grade SIL (HSIL), or cancer. Regression was defined as an initial SIL with two or more subsequent normal Pap tests. Persistence was defined as having an SIL without progression or regression. High-risk human papillomavirus (HPV) testing started in 2006 on atypical squamous cells of undetermined significance (ASCUS) Pap tests. AGC at enrollment were excluded from progression analysis. Of 1,445 screened, 383 patients had over two Pap tests for a 2-year period. Of those, 309 had an intact cervix. The median age was 40 years and CD4+ cell count was 277 cells/mL. Four had AGC at enrollment. A quarter had persistently normal Pap tests, 64 (31%) regressed, and 50 (24%) progressed. Four developed cancer. The only risk factor associated with progression was CD4 count. In those with treated lesions, 24 (59%) had negative Pap tests at the end of follow-up. More studies are needed to evaluate follow-up strategies of LSIL patients, potentially combined with HPV testing. Guidelines for HIV-seropositive women who are in care, have improved CD4, and have persistently negative Pap tests could likely lengthen the follow-up interval.

  5. First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study.

    Science.gov (United States)

    Tomasello, Gianluca; Valeri, Nicola; Ghidini, Michele; Smyth, Elizabeth C; Liguigli, Wanda; Toppo, Laura; Mattioli, Rodolfo; Curti, Alessandra; Hahne, Jens C; Negri, Federica M; Panni, Stefano; Ratti, Margherita; Lazzarelli, Silvia; Gerevini, Fabiana; Colombi, Chiara; Panni, Andrea; Rovatti, Massimo; Treccani, Leonardo; Martinotti, Mario; Passalacqua, Rodolfo

    2017-12-19

    Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy. HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d 1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4 cycles received panitumumab until progression. From 05/2010 to 01/2014, 52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%; 96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI, 8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not associated with any significant clinical benefit from treatment. Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity profile of this limits further development. Further research on predictive biomarkers for treatment efficacy in AGC is required.Clinical trial information: 2009-016962-10.

  6. The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

    International Nuclear Information System (INIS)

    Lee, Kang Nyeong; Choi, Ho Soon; Yang, Sun Young; Park, Hyun Ki; Lee, Young Yiul; Lee, Oh Young; Yoon, Byung Chul; Hahm, Joon Soo; Paik, Seung Sam

    2014-01-01

    Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways

  7. A novel approach for the detection of early gastric cancer: fluorescence spectroscopy of gastric juice.

    Science.gov (United States)

    Deng, Kai; Zhou, Li Ya; Lin, San Ren; Li, Yuan; Chen, Mo; Geng, Qiu Ming; Li, Yu Wen

    2013-06-01

    This study aimed to investigate the efficacy of fluorescence spectroscopy of gastric juice for early gastric cancer (EGC) screening. Gastric juice was collected from 101 participants who underwent endoscopy in the Outpatient Endoscopy Center of Peking University Third Hospital. The participants were divided into three groups: the normal mucosa or chronic non-atrophic gastritis (NM-CNAG) group (n = 35), advanced gastric cancer (AGC) group (n = 33) and EGC group (n = 33). Fluorescence spectroscopic analysis was performed in all the gastric juice samples and the maximum fluorescence intensity of the first peak (P1 FI) was measured. The mean fluorescence intensity of P1 FI of gastric juice in AGC (92.1 ± 10.7) and EGC (90.8 ± 12.0) groups was significantly higher than that in the NM-CNAG group (55.7 ± 7.5) (AGC vs NM-CNAG, P = 0.006 and EGC vs NM-CNAG, P = 0.015, respectively). The areas under the receiver operating characteristic curves for the detection of AGC and EGC were 0.681 (95% confidence interval [CI] 0.553-0.810, P = 0.010) and 0.655 (95% CI 0.522-0.787, P = 0.028). With the P1 FI of ≥47.7, the sensitivity, specificity and accuracy for detecting EGC were 69.7%, 57.1% and 63.2%, respectively. The enhancement of P1 FI of gastric juice occurs at the early stage of gastric cancer. Fluorescence spectroscopy of gastric juice may be used as a novel screening tool for the early detection of gastric cancer. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  8. Greenness and Carbon Stocks of Mangroves: A climate-driven Effect

    Science.gov (United States)

    Lule, A. V.; Colditz, R. R.; Herrera-Silveira, J.; Guevara, M.; Rodriguez-Zuniga, M. T.; Cruz, I.; Ressl, R.; Vargas, R.

    2017-12-01

    Mangroves cover less than 1% of the earth's surface and are one o­­­f the most productive ecosystems of the world. They are highly vulnerable to climate variability due to their sensitivity to environmental changes; therefore, there are scientific and societal needs to designed frameworks to assess mangrove's vulnerability. We study the relationship between climate drivers, canopy greenness and carbon stocks to quantify a potential climate-driven effect on mangrove carbon dynamics. We identify greenness trends and their relationships with climate drivers and carbon stocks throughout 15 years (2001-2015) across mangrove forests of Mexico. We defined several categories for mangroves: a) Arid mangroves with superficial water input (ARsw); b) Humid mangroves with interior or underground water input (HUiw); and c) Humid mangroves with superficial water input (HUsw). We found a positive significant trend of greenness for ARsw and HUsw categories (pmangrove's categories (pmangrove categories showed higher greenness values during winter; which is likely driven by temperature with a lag of -3 to -5 months (r2 > 0.69). Precipitation and temperature drive canopy greenness only across HUsw. Regarding carbon stocks, the HUiw shows the lower amount of aboveground carbon (AGC; 12.7 Mg C ha-1) and the higher belowground carbon (BGC; 219 Mg C ha-1). The HUsw shows the higher amount of AGC (169.5 Mg C ha-1) and the ARsw the lower of BGC (92.4 Mg C ha-1). Climate drivers are better related with canopy greenness and AGC for both humid mangrove categories (r2 > 0.48), while the relationship of BGC and canopy greenness is lower for all categories (r2 mangrove's ecosystem function and environmental services, as well as their potential vulnerability to climate variability.

  9. Mapping aboveground carbon stocks using LiDAR data in Eucalyptus spp. plantations in the state of Sao Paulo, Brazil

    Science.gov (United States)

    Carlos Alberto Silva; Carine Klauberg; Samuel de Padua Chaves e Carvalho; Andrew T. Hudak; e Luiz Carlos Estraviz. Rodriguez

    2014-01-01

    Fast growing plantation forests provide a low-cost means to sequester carbon for greenhouse gas abatement. The aim of this study was to evaluate airborne LiDAR (Light Detection And Ranging) to predict aboveground carbon (AGC) stocks in Eucalyptus spp. plantations. Biometric parameters (tree height (Ht) and diameter at breast height (DBH)) were collected from...

  10. Preliminary genetic linkage map of Indian major carp, Labeo rohita ...

    Indian Academy of Sciences (India)

    R: TGC TGC GGG TCA TTA GTA TTC ATC. F: TTCACGGACAGATTTGACCCAG. R: AGTCTTTTCAGGAGATTAGCAG. F: TGA GAT GTT CAG CAG GAG CTC. R: GAG CGT CGA GTGGCG TTT C. F: GAT CCC AGC AGA GGC TGT G. R: AGT CTG TGC TCT CTG GAG TG. F: TGCACA CCT CGA GGT TAG CAA C. R: TCA GCT ...

  11. Diffusion of Integral Membrane Proteins in Protein-Rich Membranes

    DEFF Research Database (Denmark)

    Javanainen, Matti; Martinez-Seara, Hector; Metzler, Ralf

    2017-01-01

    of being protein-poor, native cell membranes are extremely crowded with proteins. On the basis of extensive molecular simulations, we here demonstrate that protein crowding of the membrane at physiological levels leads to deviations from the SD relation and to the emergence of a stronger Stokes......-like dependence D ∝ 1/R. We propose that this 1/R law mainly arises due to geometrical factors: smaller proteins are able to avoid confinement effects much better than their larger counterparts. The results highlight that the lateral dynamics in the crowded setting found in native membranes is radically different......The lateral diffusion of embedded proteins along lipid membranes in protein-poor conditions has been successfully described in terms of the Saffman-Delbrück (SD) model, which predicts that the protein diffusion coefficient D is weakly dependent on its radius R as D ∝ ln(1/R). However, instead...

  12. Competitive Protein Adsorption - Multilayer Adsorption and Surface Induced Protein Aggregation

    DEFF Research Database (Denmark)

    Holmberg, Maria; Hou, Xiaolin

    2009-01-01

    In this study, competitive adsorption of albumin and IgG (immunoglobulin G) from human serum solutions and protein mixtures onto polymer surfaces is studied by means of radioactive labeling. By using two different radiolabels (125I and 131I), albumin and IgG adsorption to polymer surfaces...... is monitored simultaneously and the influence from the presence of other human serum proteins on albumin and IgG adsorption, as well as their mutual influence during adsorption processes, is investigated. Exploring protein adsorption by combining analysis of competitive adsorption from complex solutions...... of high concentration with investigation of single protein adsorption and interdependent adsorption between two specific proteins enables us to map protein adsorption sequences during competitive protein adsorption. Our study shows that proteins can adsorb in a multilayer fashion onto the polymer surfaces...

  13. Protein leverage effects of beef protein on energy intake in humans.

    Science.gov (United States)

    Martens, Eveline A; Tan, Sze-Yen; Dunlop, Mandy V; Mattes, Richard D; Westerterp-Plantenga, Margriet S

    2014-06-01

    The protein leverage hypothesis requires specific evidence that protein intake is regulated more strongly than energy intake. The objective was to determine ad libitum energy intake, body weight changes, appetite profile, and nitrogen balance in response to 3 diets with different protein-to-carbohydrate + fat ratios over 12 consecutive days, with beef as a source of protein. A 3-arm, 12-d randomized crossover study was performed in 30 men and 28 women [mean ± SD age: 33 ± 16 y; body mass index (in kg/m²): 24.4 ± 4.0] with the use of diets containing 5%, 15%, and 30% of energy (En%) from protein, predominantly from beef. Energy intake was significantly lower in the 30En%-protein condition (8.73 ± 1.93 MJ/d) than in the 5En%-protein (9.48 ± 1.67 MJ/d) and 15En%-protein (9.30 ± 1.62 MJ/d) conditions (P = 0.001), stemming largely from lower energy intake during meals (P = 0.001). Hunger (P = 0.001) and desire to eat (P = 0.001) ratings were higher and fullness ratings were lower (P = 0.001) in the 5En%-protein condition than in the 15En%-protein and 30En%-protein conditions. Nitrogen excretion was lower in the 5En%-protein condition (4.7 ± 1.5 g/24 h; P = 0.001) and was higher in the 30En%-protein condition (15.3 ± 8.7 g/24 h; P = 0.001) compared with the 15En%-protein condition (10.0 ± 5.2 g/24 h). Nitrogen balance was maintained in the 5En%-protein condition and was positive in the 15En%- and 30En%-protein conditions (P = 0.001). Complete protein leverage did not occur because subjects did not consume to a common protein amount at the expense of energy balance. Individuals did underconsume relative to energy requirements from high-protein diets. The lack of support for protein leverage effects on a low-protein diet may stem from the fact that protein intake was sufficient to maintain nitrogen balance over the 12-d trial. © 2014 American Society for Nutrition.

  14. The clinical expression of hereditary protein C and protein S deficiency: : a relation to clinical thrombotic risk-factors and to levels of protein C and protein S

    NARCIS (Netherlands)

    Henkens, C. M. A.; van der Meer, J.; Hillege, J. L.; Bom, V. J. J.; Halie, M. R.; van der Schaaf, W.

    We investigated 103 first-degree relatives of 13 unrelated protein C or protein S deficient patients to assess the role of additional thrombotic risk factors and of protein C and protein S levels in the clinical expression of hereditary protein C and protein S deficiency. Fifty-seven relatives were

  15. Laparoscopic subtotal gastrectomy for advanced gastric cancer: technical aspects and surgical, nutritional and oncological outcomes.

    Science.gov (United States)

    Nakauchi, Masaya; Suda, Koichi; Nakamura, Kenichi; Shibasaki, Susumu; Kikuchi, Kenji; Nakamura, Tetsuya; Kadoya, Shinichi; Ishida, Yoshinori; Inaba, Kazuki; Taniguchi, Keizo; Uyama, Ichiro

    2017-11-01

    Higher morbidity in total gastrectomy than in distal gastrectomy has been reported, but laparoscopic subtotal gastrectomy (LsTG) has been reported to be safe and feasible in early gastric cancer (GC). We determined the surgical, nutritional and oncological outcomes of LsTG for advanced gastric cancer (AGC). Of the 816 consecutive patients with GC who underwent radical gastrectomy at our institution between 2008 and 2012, 253 who underwent curative laparoscopic gastrectomy (LG) for AGC were enrolled. LsTG was indicated for patients with upper stomach third tumors, who hoped to avoid total gastrectomy, nutritional status were primarily assessed. Of 253 patients, the morbidity (Clavien-Dindo classification grade ≥ III) was 17.0% (43 patients). The 3-year overall survival and 3-year recurrence-free survival rates were 80.2 and 73.5%, respectively. LcDG, LsTG and LTG were performed in 121, 27 and 105 patients, individually. Morbidity was strongly associated with LTG (P = 0.001). Postoperative loss of body weight was significantly greater after LTG in comparison with LcDG or LsTG (P nutritional point of view.

  16. Low Cost, Lightweight Gravity Coring and Improved Epoxy Impregnation Applied to Laminated Maar Sediment in Vietnam

    Directory of Open Access Journals (Sweden)

    Jan P. Schimmelmann

    2018-05-01

    Full Text Available In response to the need for lightweight and affordable sediment coring and high-resolution structural documentation of unconsolidated sediment, we developed economical and fast methods for (i recovering short sediment cores with undisturbed topmost sediment, without the need for a firmly anchored coring platform, and (ii rapid epoxy-impregnation of crayon-shaped subcores in preparation for thin-sectioning, with minimal use of solvents and epoxy resin. The ‘Autonomous Gravity Corer’ (AGC can be carried to remote locations and deployed from an inflatable or makeshift raft. Its utility was tested on modern unconsolidated lacustrine sediment from a ~21 m deep maar lake in Vietnam’s Central Highlands near Pleiku. The sedimentary fabric fidelity of the epoxy-impregnation method was demonstrated for finely laminated artificial flume sediment. Our affordable AGC is attractive not only for work in developing countries, but lends itself broadly for coring in remote regions where challenging logistics prevent the use of heavy coring equipment. The improved epoxy-impregnation technique saves effort and costly chemical reagents, while at the same time preserving the texture of the sediment.

  17. PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

    Science.gov (United States)

    Dunn, Henry A; Ferguson, Stephen S G

    2015-10-01

    G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and

  18. Measuring protein breakdown rate in individual proteins in vivo

    DEFF Research Database (Denmark)

    Holm, Lars; Kjaer, Michael

    2010-01-01

    To outline different approaches of how protein breakdown can be quantified and to present a new approach to determine the fractional breakdown rate of individual slow turnover proteins in vivo.......To outline different approaches of how protein breakdown can be quantified and to present a new approach to determine the fractional breakdown rate of individual slow turnover proteins in vivo....

  19. Novel Technology for Protein-Protein Interaction-based Targeted Drug Discovery

    Directory of Open Access Journals (Sweden)

    Jung Me Hwang

    2011-12-01

    Full Text Available We have developed a simple but highly efficient in-cell protein-protein interaction (PPI discovery system based on the translocation properties of protein kinase C- and its C1a domain in live cells. This system allows the visual detection of trimeric and dimeric protein interactions including cytosolic, nuclear, and/or membrane proteins with their cognate ligands. In addition, this system can be used to identify pharmacological small compounds that inhibit specific PPIs. These properties make this PPI system an attractive tool for screening drug candidates and mapping the protein interactome.

  20. A new essential protein discovery method based on the integration of protein-protein interaction and gene expression data

    Directory of Open Access Journals (Sweden)

    Li Min

    2012-03-01

    Full Text Available Abstract Background Identification of essential proteins is always a challenging task since it requires experimental approaches that are time-consuming and laborious. With the advances in high throughput technologies, a large number of protein-protein interactions are available, which have produced unprecedented opportunities for detecting proteins' essentialities from the network level. There have been a series of computational approaches proposed for predicting essential proteins based on network topologies. However, the network topology-based centrality measures are very sensitive to the robustness of network. Therefore, a new robust essential protein discovery method would be of great value. Results In this paper, we propose a new centrality measure, named PeC, based on the integration of protein-protein interaction and gene expression data. The performance of PeC is validated based on the protein-protein interaction network of Saccharomyces cerevisiae. The experimental results show that the predicted precision of PeC clearly exceeds that of the other fifteen previously proposed centrality measures: Degree Centrality (DC, Betweenness Centrality (BC, Closeness Centrality (CC, Subgraph Centrality (SC, Eigenvector Centrality (EC, Information Centrality (IC, Bottle Neck (BN, Density of Maximum Neighborhood Component (DMNC, Local Average Connectivity-based method (LAC, Sum of ECC (SoECC, Range-Limited Centrality (RL, L-index (LI, Leader Rank (LR, Normalized α-Centrality (NC, and Moduland-Centrality (MC. Especially, the improvement of PeC over the classic centrality measures (BC, CC, SC, EC, and BN is more than 50% when predicting no more than 500 proteins. Conclusions We demonstrate that the integration of protein-protein interaction network and gene expression data can help improve the precision of predicting essential proteins. The new centrality measure, PeC, is an effective essential protein discovery method.

  1. The Proteins API: accessing key integrated protein and genome information.

    Science.gov (United States)

    Nightingale, Andrew; Antunes, Ricardo; Alpi, Emanuele; Bursteinas, Borisas; Gonzales, Leonardo; Liu, Wudong; Luo, Jie; Qi, Guoying; Turner, Edd; Martin, Maria

    2017-07-03

    The Proteins API provides searching and programmatic access to protein and associated genomics data such as curated protein sequence positional annotations from UniProtKB, as well as mapped variation and proteomics data from large scale data sources (LSS). Using the coordinates service, researchers are able to retrieve the genomic sequence coordinates for proteins in UniProtKB. This, the LSS genomics and proteomics data for UniProt proteins is programmatically only available through this service. A Swagger UI has been implemented to provide documentation, an interface for users, with little or no programming experience, to 'talk' to the services to quickly and easily formulate queries with the services and obtain dynamically generated source code for popular programming languages, such as Java, Perl, Python and Ruby. Search results are returned as standard JSON, XML or GFF data objects. The Proteins API is a scalable, reliable, fast, easy to use RESTful services that provides a broad protein information resource for users to ask questions based upon their field of expertise and allowing them to gain an integrated overview of protein annotations available to aid their knowledge gain on proteins in biological processes. The Proteins API is available at (http://www.ebi.ac.uk/proteins/api/doc). © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Multiple protonation equilibria in electrostatics of protein-protein binding.

    Science.gov (United States)

    Piłat, Zofia; Antosiewicz, Jan M

    2008-11-27

    All proteins contain groups capable of exchanging protons with their environment. We present here an approach, based on a rigorous thermodynamic cycle and the partition functions for energy levels characterizing protonation states of the associating proteins and their complex, to compute the electrostatic pH-dependent contribution to the free energy of protein-protein binding. The computed electrostatic binding free energies include the pH of the solution as the variable of state, mutual "polarization" of associating proteins reflected as changes in the distribution of their protonation states upon binding and fluctuations between available protonation states. The only fixed property of both proteins is the conformation; the structure of the monomers is kept in the same conformation as they have in the complex structure. As a reference, we use the electrostatic binding free energies obtained from the traditional Poisson-Boltzmann model, computed for a single macromolecular conformation fixed in a given protonation state, appropriate for given solution conditions. The new approach was tested for 12 protein-protein complexes. It is shown that explicit inclusion of protonation degrees of freedom might lead to a substantially different estimation of the electrostatic contribution to the binding free energy than that based on the traditional Poisson-Boltzmann model. This has important implications for the balancing of different contributions to the energetics of protein-protein binding and other related problems, for example, the choice of protein models for Brownian dynamics simulations of their association. Our procedure can be generalized to include conformational degrees of freedom by combining it with molecular dynamics simulations at constant pH. Unfortunately, in practice, a prohibitive factor is an enormous requirement for computer time and power. However, there may be some hope for solving this problem by combining existing constant pH molecular dynamics

  3. Texturized dairy proteins.

    Science.gov (United States)

    Onwulata, Charles I; Phillips, John G; Tunick, Michael H; Qi, Phoebi X; Cooke, Peter H

    2010-03-01

    Dairy proteins are amenable to structural modifications induced by high temperature, shear, and moisture; in particular, whey proteins can change conformation to new unfolded states. The change in protein state is a basis for creating new foods. The dairy products, nonfat dried milk (NDM), whey protein concentrate (WPC), and whey protein isolate (WPI) were modified using a twin-screw extruder at melt temperatures of 50, 75, and 100 degrees C, and moistures ranging from 20 to 70 wt%. Viscoelasticity and solubility measurements showed that extrusion temperature was a more significant (P extruded dairy protein ranged from rigid (2500 N) to soft (2.7 N). Extruding at or above 75 degrees C resulted in increased peak force for WPC (138 to 2500 N) and WPI (2.7 to 147.1 N). NDM was marginally texturized; the presence of lactose interfered with its texturization. WPI products extruded at 50 degrees C were not texturized; their solubility values ranged from 71.8% to 92.6%. A wide possibility exists for creating new foods with texturized dairy proteins due to the extensive range of states achievable. Dairy proteins can be used to boost the protein content in puffed snacks made from corn meal, but unmodified, they bind water and form doughy pastes with starch. To minimize the water binding property of dairy proteins, WPI, or WPC, or NDM were modified by extrusion processing. Extrusion temperature conditions were adjusted to 50, 75, or 100 degrees C, sufficient to change the structure of the dairy proteins, but not destroy them. Extrusion modified the structures of these dairy proteins for ease of use in starchy foods to boost nutrient levels. Dairy proteins can be used to boost the protein content in puffed snacks made from corn meal, but unmodified, they bind water and form doughy pastes with starch. To minimize the water binding property of dairy proteins, whey protein isolate, whey protein concentrate, or nonfat dried milk were modified by extrusion processing. Extrusion

  4. Protein annotation from protein interaction networks and Gene Ontology.

    Science.gov (United States)

    Nguyen, Cao D; Gardiner, Katheleen J; Cios, Krzysztof J

    2011-10-01

    We introduce a novel method for annotating protein function that combines Naïve Bayes and association rules, and takes advantage of the underlying topology in protein interaction networks and the structure of graphs in the Gene Ontology. We apply our method to proteins from the Human Protein Reference Database (HPRD) and show that, in comparison with other approaches, it predicts protein functions with significantly higher recall with no loss of precision. Specifically, it achieves 51% precision and 60% recall versus 45% and 26% for Majority and 24% and 61% for χ²-statistics, respectively. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Dietary Protein Intake in Dutch Elderly People: A Focus on Protein Sources

    Directory of Open Access Journals (Sweden)

    Michael Tieland

    2015-11-01

    Full Text Available Introduction: Sufficient high quality dietary protein intake is required to prevent or treat sarcopenia in elderly people. Therefore, the intake of specific protein sources as well as their timing of intake are important to improve dietary protein intake in elderly people. Objectives: to assess the consumption of protein sources as well as the distribution of protein sources over the day in community-dwelling, frail and institutionalized elderly people. Methods: Habitual dietary intake was evaluated using 2- and 3-day food records collected from various studies involving 739 community-dwelling, 321 frail and 219 institutionalized elderly people. Results: Daily protein intake averaged 71 ± 18 g/day in community-dwelling, 71 ± 20 g/day in frail and 58 ± 16 g/day in institutionalized elderly people and accounted for 16% ± 3%, 16% ± 3% and 17% ± 3% of their energy intake, respectively. Dietary protein intake ranged from 10 to 12 g at breakfast, 15 to 23 g at lunch and 24 to 31 g at dinner contributing together over 80% of daily protein intake. The majority of dietary protein consumed originated from animal sources (≥60% with meat and dairy as dominant sources. Thus, 40% of the protein intake in community-dwelling, 37% in frail and 29% in institutionalized elderly originated from plant based protein sources with bread as the principle source. Plant based proteins contributed for >50% of protein intake at breakfast and between 34% and 37% at lunch, with bread as the main source. During dinner, >70% of the protein intake originated from animal protein, with meat as the dominant source. Conclusion: Daily protein intake in these older populations is mainly (>80% provided by the three main meals, with most protein consumed during dinner. More than 60% of daily protein intake consumed is of animal origin, with plant based protein sources representing nearly 40% of total protein consumed. During dinner, >70% of the protein intake originated from

  6. Introduction to current and future protein therapeutics: a protein engineering perspective.

    Science.gov (United States)

    Carter, Paul J

    2011-05-15

    Protein therapeutics and its enabling sister discipline, protein engineering, have emerged since the early 1980s. The first protein therapeutics were recombinant versions of natural proteins. Proteins purposefully modified to increase their clinical potential soon followed with enhancements derived from protein or glycoengineering, Fc fusion or conjugation to polyethylene glycol. Antibody-based drugs subsequently arose as the largest and fastest growing class of protein therapeutics. The rationale for developing better protein therapeutics with enhanced efficacy, greater safety, reduced immunogenicity or improved delivery comes from the convergence of clinical, scientific, technological and commercial drivers that have identified unmet needs and provided strategies to address them. Future protein drugs seem likely to be more extensively engineered to improve their performance, e.g., antibodies and Fc fusion proteins with enhanced effector functions or extended half-life. Two old concepts for improving antibodies, namely antibody-drug conjugates and bispecific antibodies, have advanced to the cusp of clinical success. As for newer protein therapeutic platform technologies, several engineered protein scaffolds are in early clinical development and offer differences and some potential advantages over antibodies. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Exploration of the dynamic properties of protein complexes predicted from spatially constrained protein-protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Eric A Yen

    2014-05-01

    Full Text Available Protein complexes are not static, but rather highly dynamic with subunits that undergo 1-dimensional diffusion with respect to each other. Interactions within protein complexes are modulated through regulatory inputs that alter interactions and introduce new components and deplete existing components through exchange. While it is clear that the structure and function of any given protein complex is coupled to its dynamical properties, it remains a challenge to predict the possible conformations that complexes can adopt. Protein-fragment Complementation Assays detect physical interactions between protein pairs constrained to ≤8 nm from each other in living cells. This method has been used to build networks composed of 1000s of pair-wise interactions. Significantly, these networks contain a wealth of dynamic information, as the assay is fully reversible and the proteins are expressed in their natural context. In this study, we describe a method that extracts this valuable information in the form of predicted conformations, allowing the user to explore the conformational landscape, to search for structures that correlate with an activity state, and estimate the abundance of conformations in the living cell. The generator is based on a Markov Chain Monte Carlo simulation that uses the interaction dataset as input and is constrained by the physical resolution of the assay. We applied this method to an 18-member protein complex composed of the seven core proteins of the budding yeast Arp2/3 complex and 11 associated regulators and effector proteins. We generated 20,480 output structures and identified conformational states using principle component analysis. We interrogated the conformation landscape and found evidence of symmetry breaking, a mixture of likely active and inactive conformational states and dynamic exchange of the core protein Arc15 between core and regulatory components. Our method provides a novel tool for prediction and

  8. BLAST-based structural annotation of protein residues using Protein Data Bank.

    Science.gov (United States)

    Singh, Harinder; Raghava, Gajendra P S

    2016-01-25

    In the era of next-generation sequencing where thousands of genomes have been already sequenced; size of protein databases is growing with exponential rate. Structural annotation of these proteins is one of the biggest challenges for the computational biologist. Although, it is easy to perform BLAST search against Protein Data Bank (PDB) but it is difficult for a biologist to annotate protein residues from BLAST search. A web-server StarPDB has been developed for structural annotation of a protein based on its similarity with known protein structures. It uses standard BLAST software for performing similarity search of a query protein against protein structures in PDB. This server integrates wide range modules for assigning different types of annotation that includes, Secondary-structure, Accessible surface area, Tight-turns, DNA-RNA and Ligand modules. Secondary structure module allows users to predict regular secondary structure states to each residue in a protein. Accessible surface area predict the exposed or buried residues in a protein. Tight-turns module is designed to predict tight turns like beta-turns in a protein. DNA-RNA module developed for predicting DNA and RNA interacting residues in a protein. Similarly, Ligand module of server allows one to predicted ligands, metal and nucleotides ligand interacting residues in a protein. In summary, this manuscript presents a web server for comprehensive annotation of a protein based on similarity search. It integrates number of visualization tools that facilitate users to understand structure and function of protein residues. This web server is available freely for scientific community from URL http://crdd.osdd.net/raghava/starpdb .

  9. Integral UBL domain proteins: a family of proteasome interacting proteins

    DEFF Research Database (Denmark)

    Hartmann-Petersen, Rasmus; Gordon, Colin

    2004-01-01

    The family of ubiquitin-like (UBL) domain proteins (UDPs) comprises a conserved group of proteins involved in a multitude of different cellular activities. However, recent studies on UBL-domain proteins indicate that these proteins appear to share a common property in their ability to interact...

  10. Modulation of mitogen-activated protein kinase-activated protein kinase 3 by hepatitis C virus core protein

    DEFF Research Database (Denmark)

    Ngo, HT; Pham, Long; Kim, JW

    2013-01-01

    Hepatitis C virus (HCV) is highly dependent on cellular proteins for its own propagation. In order to identify the cellular factors involved in HCV propagation, we performed protein microarray assays using the HCV core protein as a probe. Of ~9,000 host proteins immobilized in a microarray...... inducers. Binding of HCV core to MAPKAPK3 was confirmed by in vitro pulldown assay and further verified by coimmunoprecipitation assay. HCV core protein interacted with MAPKAPK3 through amino acid residues 41 to 75 of core and the N-terminal half of kinase domain of MAPKAPK3. In addition, both RNA...... increased HCV IRES-mediated translation and MAPKAPK3-dependent HCV IRES activity was further increased by core protein. These data suggest that HCV core may modulate MAPKAPK3 to facilitate its own propagation....

  11. DQA1

    Indian Academy of Sciences (India)

    mukesh

    2, GAC, CAC, ATT, GGC, ACC, TAT, GGC, GTA, AGC, TTC, TAC, CAC, TCT, TAT, GGT, CCC, TCT, GGC, TAC, TAT, ATC, CAT, GAA, TTT, GAT, GGA, GAT, GAA, GAG, TTT, TAT, GTG, GAC, CTG, GAG, AAG, AGG, GAG, ACT, GTC, TGG, CAT, CTG, CCT, GTG, TTT, AGT, GAA, TTT, GCA, AGT, TTT, GAC, CCT, CAG, GAT, GGG ...

  12. Development of an Advanced, Automatic, Ultrasonic NDE Imaging System via Adaptive Learning Network Signal Processing Techniques

    Science.gov (United States)

    1981-03-13

    UNCLASSIFIED SECURITY CLAS,:FtfC ’i OF TH*!’ AGC W~ct P- A* 7~9r1) 0. ABSTRACT (continued) onuing in concert with a sophisticated detector has...and New York, 1969. Whalen, M.F., L.J. O’Brien, and A.N. Mucciardi, "Application of Adaptive Learning Netowrks for the Characterization of Two

  13. Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV replication.

    Directory of Open Access Journals (Sweden)

    Ji'an Pan

    Full Text Available Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12 provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.

  14. Protein engineering techniques gateways to synthetic protein universe

    CERN Document Server

    Poluri, Krishna Mohan

    2017-01-01

    This brief provides a broad overview of protein-engineering research, offering a glimpse of the most common experimental methods. It also presents various computational programs with applications that are widely used in directed evolution, computational and de novo protein design. Further, it sheds light on the advantages and pitfalls of existing methodologies and future perspectives of protein engineering techniques.

  15. Topology-function conservation in protein-protein interaction networks.

    Science.gov (United States)

    Davis, Darren; Yaveroğlu, Ömer Nebil; Malod-Dognin, Noël; Stojmirovic, Aleksandar; Pržulj, Nataša

    2015-05-15

    Proteins underlay the functioning of a cell and the wiring of proteins in protein-protein interaction network (PIN) relates to their biological functions. Proteins with similar wiring in the PIN (topology around them) have been shown to have similar functions. This property has been successfully exploited for predicting protein functions. Topological similarity is also used to guide network alignment algorithms that find similarly wired proteins between PINs of different species; these similarities are used to transfer annotation across PINs, e.g. from model organisms to human. To refine these functional predictions and annotation transfers, we need to gain insight into the variability of the topology-function relationships. For example, a function may be significantly associated with specific topologies, while another function may be weakly associated with several different topologies. Also, the topology-function relationships may differ between different species. To improve our understanding of topology-function relationships and of their conservation among species, we develop a statistical framework that is built upon canonical correlation analysis. Using the graphlet degrees to represent the wiring around proteins in PINs and gene ontology (GO) annotations to describe their functions, our framework: (i) characterizes statistically significant topology-function relationships in a given species, and (ii) uncovers the functions that have conserved topology in PINs of different species, which we term topologically orthologous functions. We apply our framework to PINs of yeast and human, identifying seven biological process and two cellular component GO terms to be topologically orthologous for the two organisms. © The Author 2015. Published by Oxford University Press.

  16. Functional Versatility of AGY Serine Codons in Immunoglobulin Variable Region Genes

    Directory of Open Access Journals (Sweden)

    Thiago Detanico

    2016-11-01

    Full Text Available In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ag often arise by somatic hypermutation (SHM that converts AGT and AGC (AGY Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes. Because AGC is a preferred target for SHM by activation-induced cytidine deaminase (AID, we asked whether the AGY abundance was solely due to a selection pressure to conserve high mutability in CDRs regardless of codon context but found that this was not the case. Instead, AGY triplets were selectively enriched in the Ser codon reading frame. Motivated by reports implicating a functional role for poly/autoreactive specificities in anti-viral antibodies, we also analyzed mutations at AGY in antibodies directed against a number of different viruses, and found that mutations producing Arg codons in anti-viral antibodies were indeed frequent. Unexpectedly, however, we also found that AGY codons mutated often to encode nearly all of the amino acids that are reported to provide the most frequent contacts with antigen (Ag. In many cases, mutations producing codons for these alternative amino acids in anti-viral antibodies were more frequent than those producing Arg codons. Mutations producing each of these key amino acids required only single-base changes in AGY. AGY is the only codon group in which 2/3rds of random mutations generate codons for these key residues. Finally, by directly analyzing x-ray structures of immune complexes from the RCSB protein database, we found that Ag-contact residues generated via somatic hypermutation occurred more often at AGY than at any other codon group. Thus, preservation of

  17. Protein space: a natural method for realizing the nature of protein universe.

    Science.gov (United States)

    Yu, Chenglong; Deng, Mo; Cheng, Shiu-Yuen; Yau, Shek-Chung; He, Rong L; Yau, Stephen S-T

    2013-02-07

    Current methods cannot tell us what the nature of the protein universe is concretely. They are based on different models of amino acid substitution and multiple sequence alignment which is an NP-hard problem and requires manual intervention. Protein structural analysis also gives a direction for mapping the protein universe. Unfortunately, now only a minuscule fraction of proteins' 3-dimensional structures are known. Furthermore, the phylogenetic tree representations are not unique for any existing tree construction methods. Here we develop a novel method to realize the nature of protein universe. We show the protein universe can be realized as a protein space in 60-dimensional Euclidean space using a distance based on a normalized distribution of amino acids. Every protein is in one-to-one correspondence with a point in protein space, where proteins with similar properties stay close together. Thus the distance between two points in protein space represents the biological distance of the corresponding two proteins. We also propose a natural graphical representation for inferring phylogenies. The representation is natural and unique based on the biological distances of proteins in protein space. This will solve the fundamental question of how proteins are distributed in the protein universe. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Transverse feedback: high intensity operation, AGC, IGC, lessons for 2012

    CERN Document Server

    Höfle, W

    2012-01-01

    The transverse damper system (ADT) plays an important role in the preservation of the beam transverse emittance and for damping of oscillations driven by the coupled bunch instability. An overview of the ADT system will be presented with an emphasis on the important feedback loop parameters as they change from injection through the ramp into collision. The dedicated setting - up procedure required for the different bunch intensities and bunch spacings will be explained. During the 2011 run the injection and abort gap cleaning became operational at injection energy. Preparations for cleaning at 3.5 TeV as well as batch selective transverse blow - up were completed and preliminarily tested. Plans for 2012 include study and potential improvement of the system impulse response to improve the 'selectivity' of the cleaning and blow - up facility. The ADT also provides bunch - by - bunch observation, which was extensively used during the run and MDs, and will be further upgraded during the next year.

  19. Protein intake does not increase vastus lateralis muscle protein synthesis during cycling

    DEFF Research Database (Denmark)

    Hulston, CJ; Wolsk, Emil; Grøndahl, Thomas Sahl

    2011-01-01

    PURPOSE: This study aimed to investigate the effect of protein ingestion on leg protein turnover and vastus lateralis muscle protein synthesis during bicycle exercise and recovery. METHODS: Eight healthy males participated in two experiments in which they ingested either a carbohydrate solution...... sampling, and blood flow measurements. Muscle protein synthesis was calculated from the incorporation of l-[ring-C6]phenylalanine into protein. RESULTS: Consuming protein during exercise increased leg protein synthesis and decreased net leg protein breakdown; however, protein ingestion did not increase...... protein synthesis within the highly active vastus lateralis muscle (0.029%·h(-1), ± 0.004%·h(-1), and 0.030%·h(-1), ± 0.003%·h(-1), in CHO and CHO + P, respectively; P = 0.88). In contrast, consuming protein, during exercise and recovery, increased postexercise vastus lateralis muscle protein synthesis...

  20. Regulation of protein kinase C-related kinase (PRK) signalling by the TPα and TPβ isoforms of the human thromboxane A2 receptor: Implications for thromboxane- and androgen- dependent neoplastic and epigenetic responses in prostate cancer.

    Science.gov (United States)

    O'Sullivan, Aine G; Mulvaney, Eamon P; Kinsella, B Therese

    2017-04-01

    The prostanoid thromboxane (TX) A 2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA 2 /TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA 2 -TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC. Hence the aim of the current study was to investigate whether TXA 2 /TP-induced PRK activation can mimic and/or enhance AR-mediated cellular responses in the model androgen-responsive prostate adenocarcinoma LNCaP cell line. We reveal that TXA 2 /TP signalling can act as a neoplastic- and epigenetic-regulator, promoting and enhancing both AR-associated chromatin remodelling (H3Thr11 phosphorylation, WDR5 recruitment and acetylation of histone H4 at lysine 16) and AR-mediated transcriptional activation (e.g of the KLK3/prostate-specific antigen and TMPRSS2 genes) through mechanisms involving TPα/TPβ mediated-PRK1 and PRK2, but not PRK3, signalling complexes. Overall, these data demonstrate that TPα/TPβ can act as neoplastic and epigenetic regulators by mimicking and/or enhancing the actions of androgens within the prostate and provides further mechanistic insights into the role of the TXA 2 /TP signalling axis in PCa, including potentially in CRPC. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Mitochondrial protein acetylation mediates nutrient sensing of mitochondrial protein synthesis and mitonuclear protein balance.

    Science.gov (United States)

    Di Domenico, Antonella; Hofer, Annette; Tundo, Federica; Wenz, Tina

    2014-11-01

    Changes in nutrient supply require global metabolic reprogramming to optimize the utilization of the nutrients. Mitochondria as a central component of the cellular metabolism play a key role in this adaptive process. Since mitochondria harbor their own genome, which encodes essential enzymes, mitochondrial protein synthesis is a determinant of metabolic adaptation. While regulation of cytoplasmic protein synthesis in response to metabolic challenges has been studied in great detail, mechanisms which adapt mitochondrial translation in response to metabolic challenges remain elusive. Our results suggest that the mitochondrial acetylation status controlled by Sirt3 and its proposed opponent GCN5L1 is an important regulator of the metabolic adaptation of mitochondrial translation. Moreover, both proteins modulate regulators of cytoplasmic protein synthesis as well as the mitonuclear protein balance making Sirt3 and GCN5L1 key players in synchronizing mitochondrial and cytoplasmic translation. Our results thereby highlight regulation of mitochondrial translation as a novel component in the cellular nutrient sensing scheme and identify mitochondrial acetylation as a new regulatory principle for the metabolic competence of mitochondrial protein synthesis. © 2014 International Union of Biochemistry and Molecular Biology.

  2. Understanding Protein-Protein Interactions Using Local Structural Features

    DEFF Research Database (Denmark)

    Planas-Iglesias, Joan; Bonet, Jaume; García-García, Javier

    2013-01-01

    Protein-protein interactions (PPIs) play a relevant role among the different functions of a cell. Identifying the PPI network of a given organism (interactome) is useful to shed light on the key molecular mechanisms within a biological system. In this work, we show the role of structural features...... interacting and non-interacting protein pairs to classify the structural features that sustain the binding (or non-binding) behavior. Our study indicates that not only the interacting region but also the rest of the protein surface are important for the interaction fate. The interpretation...... to score the likelihood of the interaction between two proteins and to develop a method for the prediction of PPIs. We have tested our method on several sets with unbalanced ratios of interactions and non-interactions to simulate real conditions, obtaining accuracies higher than 25% in the most unfavorable...

  3. MetaGO: Predicting Gene Ontology of Non-homologous Proteins Through Low-Resolution Protein Structure Prediction and Protein-Protein Network Mapping.

    Science.gov (United States)

    Zhang, Chengxin; Zheng, Wei; Freddolino, Peter L; Zhang, Yang

    2018-03-10

    Homology-based transferal remains the major approach to computational protein function annotations, but it becomes increasingly unreliable when the sequence identity between query and template decreases below 30%. We propose a novel pipeline, MetaGO, to deduce Gene Ontology attributes of proteins by combining sequence homology-based annotation with low-resolution structure prediction and comparison, and partner's homology-based protein-protein network mapping. The pipeline was tested on a large-scale set of 1000 non-redundant proteins from the CAFA3 experiment. Under the stringent benchmark conditions where templates with >30% sequence identity to the query are excluded, MetaGO achieves average F-measures of 0.487, 0.408, and 0.598, for Molecular Function, Biological Process, and Cellular Component, respectively, which are significantly higher than those achieved by other state-of-the-art function annotations methods. Detailed data analysis shows that the major advantage of the MetaGO lies in the new functional homolog detections from partner's homology-based network mapping and structure-based local and global structure alignments, the confidence scores of which can be optimally combined through logistic regression. These data demonstrate the power of using a hybrid model incorporating protein structure and interaction networks to deduce new functional insights beyond traditional sequence homology-based referrals, especially for proteins that lack homologous function templates. The MetaGO pipeline is available at http://zhanglab.ccmb.med.umich.edu/MetaGO/. Copyright © 2018. Published by Elsevier Ltd.

  4. A Mesoscopic Model for Protein-Protein Interactions in Solution

    OpenAIRE

    Lund, Mikael; Jönsson, Bo

    2003-01-01

    Protein self-association may be detrimental in biological systems, but can be utilized in a controlled fashion for protein crystallization. It is hence of considerable interest to understand how factors like solution conditions prevent or promote aggregation. Here we present a computational model describing interactions between protein molecules in solution. The calculations are based on a molecular description capturing the detailed structure of the protein molecule using x-ray or nuclear ma...

  5. A PQL (protein quantity loci) analysis of mature pea seed proteins identifies loci determining seed protein composition.

    Science.gov (United States)

    Bourgeois, Michael; Jacquin, Françoise; Cassecuelle, Florence; Savois, Vincent; Belghazi, Maya; Aubert, Grégoire; Quillien, Laurence; Huart, Myriam; Marget, Pascal; Burstin, Judith

    2011-05-01

    Legume seeds are a major source of dietary proteins for humans and animals. Deciphering the genetic control of their accumulation is thus of primary significance towards their improvement. At first, we analysed the genetic variability of the pea seed proteome of three genotypes over 3 years of cultivation. This revealed that seed protein composition variability was under predominant genetic control, with as much as 60% of the spots varying quantitatively among the three genotypes. Then, by combining proteomic and quantitative trait loci (QTL) mapping approaches, we uncovered the genetic architecture of seed proteome variability. Protein quantity loci (PQL) were searched for 525 spots detected on 2-D gels obtained for 157 recombinant inbred lines. Most protein quantity loci mapped in clusters, suggesting that the accumulation of the major storage protein families was under the control of a limited number of loci. While convicilin accumulation was mainly under the control of cis-regulatory regions, vicilins and legumins were controlled by both cis- and trans-regulatory regions. Some loci controlled both seed protein composition and protein content and a locus on LGIIa appears to be a major regulator of protein composition and of protein in vitro digestibility. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Using modified soy protein to enhance foaming of egg white protein.

    Science.gov (United States)

    Wang, Guang; Troendle, Molly; Reitmeier, Cheryll A; Wang, Tong

    2012-08-15

    It is well known that the foaming properties of egg white protein are significantly reduced when a small amount of yolk is mixed in the white. To improve foaming properties of yolk-contaminated egg white protein, soy protein isolate (SPI) and egg proteins were modified to make basic proteins, and effects of these modified proteins on egg white foaming were evaluated in a model and an angel cake system. SPI and egg yolk proteins were modified to have an isoelectric point of 10, and sonication was used to increase protein dispersibility after the ethyl esterification reaction. However, only the addition of sonicated and modified SPI (SMSPI) showed improvement of foaming in the 5% egg protein model system with 0.4% yolk addition. SMSPI was then used in making angel food cake to examine whether the cake performance reduction due to yolk contamination of the white would be restored by such alkaline protein. Cake performance was improved when cream of tartar was used together with SMSPI. Basic soy protein can be made and used to improve egg white foaming properties and cake performance. Copyright © 2012 Society of Chemical Industry.

  7. Yeast ribosomal proteins

    International Nuclear Information System (INIS)

    Otaka, E.; Kobata, K.

    1978-01-01

    The cytoplasmic 80s ribosomal proteins from the cells of yeast Saccharomyces cerevisiae were analyzed by SDS two-dimensional polyacrylamide gel electrophoresis. Seventyfour proteins were identified and consecutively numbered from 1 to 74. Upon oxidation of the 80s proteins with performic acid, ten proteins (no. 15, 20, 35, 40, 44, 46, 49, 51, 54 and 55) were dislocated on the gel without change of the total number of protein spots. Five proteins (no. 8, 14, 16, 36 and 74) were phosphorylated in vivo as seen in 32 P-labelling experiments. The large and small subunits separated in low magnesium medium were analyzed by the above gel electrophoresis. At least forty-five and twenty-eight proteins were assumed to be in the large and small subunits, respectively. All proteins found in the 80s ribosomes, except for no. 3, were detected in either subunit without appearance of new spots. The acidic protein no. 3 seems to be lost during subunit dissociation. (orig.) [de

  8. Specificity of molecular interactions in transient protein-protein interaction interfaces.

    Science.gov (United States)

    Cho, Kyu-il; Lee, KiYoung; Lee, Kwang H; Kim, Dongsup; Lee, Doheon

    2006-11-15

    In this study, we investigate what types of interactions are specific to their biological function, and what types of interactions are persistent regardless of their functional category in transient protein-protein heterocomplexes. This is the first approach to analyze protein-protein interfaces systematically at the molecular interaction level in the context of protein functions. We perform systematic analysis at the molecular interaction level using classification and feature subset selection technique prevalent in the field of pattern recognition. To represent the physicochemical properties of protein-protein interfaces, we design 18 molecular interaction types using canonical and noncanonical interactions. Then, we construct input vector using the frequency of each interaction type in protein-protein interface. We analyze the 131 interfaces of transient protein-protein heterocomplexes in PDB: 33 protease-inhibitors, 52 antibody-antigens, 46 signaling proteins including 4 cyclin dependent kinase and 26 G-protein. Using kNN classification and feature subset selection technique, we show that there are specific interaction types based on their functional category, and such interaction types are conserved through the common binding mechanism, rather than through the sequence or structure conservation. The extracted interaction types are C(alpha)-- H...O==C interaction, cation...anion interaction, amine...amine interaction, and amine...cation interaction. With these four interaction types, we achieve the classification success rate up to 83.2% with leave-one-out cross-validation at k = 15. Of these four interaction types, C(alpha)--H...O==C shows binding specificity for protease-inhibitor complexes, while cation-anion interaction is predominant in signaling complexes. The amine ... amine and amine...cation interaction give a minor contribution to the classification accuracy. When combined with these two interactions, they increase the accuracy by 3.8%. In the case of

  9. Protein-protein interactions in the regulation of WRKY transcription factors.

    Science.gov (United States)

    Chi, Yingjun; Yang, Yan; Zhou, Yuan; Zhou, Jie; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

    2013-03-01

    It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all analyzed WRKY proteins recognize the TTGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcription factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biological processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.

  10. Functional structural motifs for protein-ligand, protein-protein, and protein-nucleic acid interactions and their connection to supersecondary structures.

    Science.gov (United States)

    Kinjo, Akira R; Nakamura, Haruki

    2013-01-01

    Protein functions are mediated by interactions between proteins and other molecules. One useful approach to analyze protein functions is to compare and classify the structures of interaction interfaces of proteins. Here, we describe the procedures for compiling a database of interface structures and efficiently comparing the interface structures. To do so requires a good understanding of the data structures of the Protein Data Bank (PDB). Therefore, we also provide a detailed account of the PDB exchange dictionary necessary for extracting data that are relevant for analyzing interaction interfaces and secondary structures. We identify recurring structural motifs by classifying similar interface structures, and we define a coarse-grained representation of supersecondary structures (SSS) which represents a sequence of two or three secondary structure elements including their relative orientations as a string of four to seven letters. By examining the correspondence between structural motifs and SSS strings, we show that no SSS string has particularly high propensity to be found interaction interfaces in general, indicating any SSS can be used as a binding interface. When individual structural motifs are examined, there are some SSS strings that have high propensity for particular groups of structural motifs. In addition, it is shown that while the SSS strings found in particular structural motifs for nonpolymer and protein interfaces are as abundant as in other structural motifs that belong to the same subunit, structural motifs for nucleic acid interfaces exhibit somewhat stronger preference for SSS strings. In regard to protein folds, many motif-specific SSS strings were found across many folds, suggesting that SSS may be a useful description to investigate the universality of ligand binding modes.

  11. Prediction of protein–protein interactions: unifying evolution and structure at protein interfaces

    International Nuclear Information System (INIS)

    Tuncbag, Nurcan; Gursoy, Attila; Keskin, Ozlem

    2011-01-01

    The vast majority of the chores in the living cell involve protein–protein interactions. Providing details of protein interactions at the residue level and incorporating them into protein interaction networks are crucial toward the elucidation of a dynamic picture of cells. Despite the rapid increase in the number of structurally known protein complexes, we are still far away from a complete network. Given experimental limitations, computational modeling of protein interactions is a prerequisite to proceed on the way to complete structural networks. In this work, we focus on the question 'how do proteins interact?' rather than 'which proteins interact?' and we review structure-based protein–protein interaction prediction approaches. As a sample approach for modeling protein interactions, PRISM is detailed which combines structural similarity and evolutionary conservation in protein interfaces to infer structures of complexes in the protein interaction network. This will ultimately help us to understand the role of protein interfaces in predicting bound conformations

  12. Shotgun protein sequencing.

    Energy Technology Data Exchange (ETDEWEB)

    Faulon, Jean-Loup Michel; Heffelfinger, Grant S.

    2009-06-01

    A novel experimental and computational technique based on multiple enzymatic digestion of a protein or protein mixture that reconstructs protein sequences from sequences of overlapping peptides is described in this SAND report. This approach, analogous to shotgun sequencing of DNA, is to be used to sequence alternative spliced proteins, to identify post-translational modifications, and to sequence genetically engineered proteins.

  13. Protein-protein interactions within late pre-40S ribosomes.

    Directory of Open Access Journals (Sweden)

    Melody G Campbell

    2011-01-01

    Full Text Available Ribosome assembly in eukaryotic organisms requires more than 200 assembly factors to facilitate and coordinate rRNA transcription, processing, and folding with the binding of the ribosomal proteins. Many of these assembly factors bind and dissociate at defined times giving rise to discrete assembly intermediates, some of which have been partially characterized with regards to their protein and RNA composition. Here, we have analyzed the protein-protein interactions between the seven assembly factors bound to late cytoplasmic pre-40S ribosomes using recombinant proteins in binding assays. Our data show that these factors form two modules: one comprising Enp1 and the export adaptor Ltv1 near the beak structure, and the second comprising the kinase Rio2, the nuclease Nob1, and a regulatory RNA binding protein Dim2/Pno1 on the front of the head. The GTPase-like Tsr1 and the universally conserved methylase Dim1 are also peripherally connected to this second module. Additionally, in an effort to further define the locations for these essential proteins, we have analyzed the interactions between these assembly factors and six ribosomal proteins: Rps0, Rps3, Rps5, Rps14, Rps15 and Rps29. Together, these results and previous RNA-protein crosslinking data allow us to propose a model for the binding sites of these seven assembly factors. Furthermore, our data show that the essential kinase Rio2 is located at the center of the pre-ribosomal particle and interacts, directly or indirectly, with every other assembly factor, as well as three ribosomal proteins required for cytoplasmic 40S maturation. These data suggest that Rio2 could play a central role in regulating cytoplasmic maturation steps.

  14. 3DProIN: Protein-Protein Interaction Networks and Structure Visualization.

    Science.gov (United States)

    Li, Hui; Liu, Chunmei

    2014-06-14

    3DProIN is a computational tool to visualize protein-protein interaction networks in both two dimensional (2D) and three dimensional (3D) view. It models protein-protein interactions in a graph and explores the biologically relevant features of the tertiary structures of each protein in the network. Properties such as color, shape and name of each node (protein) of the network can be edited in either 2D or 3D views. 3DProIN is implemented using 3D Java and C programming languages. The internet crawl technique is also used to parse dynamically grasped protein interactions from protein data bank (PDB). It is a java applet component that is embedded in the web page and it can be used on different platforms including Linux, Mac and Window using web browsers such as Firefox, Internet Explorer, Chrome and Safari. It also was converted into a mac app and submitted to the App store as a free app. Mac users can also download the app from our website. 3DProIN is available for academic research at http://bicompute.appspot.com.

  15. Racemic protein crystallography.

    Science.gov (United States)

    Yeates, Todd O; Kent, Stephen B H

    2012-01-01

    Although natural proteins are chiral and are all of one "handedness," their mirror image forms can be prepared by chemical synthesis. This opens up new opportunities for protein crystallography. A racemic mixture of the enantiomeric forms of a protein molecule can crystallize in ways that natural proteins cannot. Recent experimental data support a theoretical prediction that this should make racemic protein mixtures highly amenable to crystallization. Crystals obtained from racemic mixtures also offer advantages in structure determination strategies. The relevance of these potential advantages is heightened by advances in synthetic methods, which are extending the size limit for proteins that can be prepared by chemical synthesis. Recent ideas and results in the area of racemic protein crystallography are reviewed.

  16. Modularity in protein structures: study on all-alpha proteins.

    Science.gov (United States)

    Khan, Taushif; Ghosh, Indira

    2015-01-01

    Modularity is known as one of the most important features of protein's robust and efficient design. The architecture and topology of proteins play a vital role by providing necessary robust scaffolds to support organism's growth and survival in constant evolutionary pressure. These complex biomolecules can be represented by several layers of modular architecture, but it is pivotal to understand and explore the smallest biologically relevant structural component. In the present study, we have developed a component-based method, using protein's secondary structures and their arrangements (i.e. patterns) in order to investigate its structural space. Our result on all-alpha protein shows that the known structural space is highly populated with limited set of structural patterns. We have also noticed that these frequently observed structural patterns are present as modules or "building blocks" in large proteins (i.e. higher secondary structure content). From structural descriptor analysis, observed patterns are found to be within similar deviation; however, frequent patterns are found to be distinctly occurring in diverse functions e.g. in enzymatic classes and reactions. In this study, we are introducing a simple approach to explore protein structural space using combinatorial- and graph-based geometry methods, which can be used to describe modularity in protein structures. Moreover, analysis indicates that protein function seems to be the driving force that shapes the known structure space.

  17. Emergence of modularity and disassortativity in protein-protein interaction networks.

    Science.gov (United States)

    Wan, Xi; Cai, Shuiming; Zhou, Jin; Liu, Zengrong

    2010-12-01

    In this paper, we present a simple evolution model of protein-protein interaction networks by introducing a rule of small-preference duplication of a node, meaning that the probability of a node chosen to duplicate is inversely proportional to its degree, and subsequent divergence plus nonuniform heterodimerization based on some plausible mechanisms in biology. We show that our model cannot only reproduce scale-free connectivity and small-world pattern, but also exhibit hierarchical modularity and disassortativity. After comparing the features of our model with those of real protein-protein interaction networks, we believe that our model can provide relevant insights into the mechanism underlying the evolution of protein-protein interaction networks. © 2010 American Institute of Physics.

  18. HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy.

    Science.gov (United States)

    Yan, Yumeng; Zhang, Di; Zhou, Pei; Li, Botong; Huang, Sheng-You

    2017-07-03

    Protein-protein and protein-DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, here we have presented HDOCK, a novel web server of our hybrid docking algorithm of template-based modeling and free docking, in which cases with misleading templates can be rescued by the free docking protocol. The server supports protein-protein and protein-DNA/RNA docking and accepts both sequence and structure inputs for proteins. The docking process is fast and consumes about 10-20 min for a docking run. Tested on the cases with weakly homologous complexes of server. The HDOCK web server is available at http://hdock.phys.hust.edu.cn/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Aquaporin Protein-Protein Interactions

    Directory of Open Access Journals (Sweden)

    Jennifer Virginia Roche

    2017-10-01

    Full Text Available Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently regulated by gating or trafficking, allowing for the cell to control membrane permeability in a specific manner. Protein–protein interactions play crucial roles in both regulatory processes and also mediate alternative functions such as cell adhesion. In this review, we summarize recent knowledge about aquaporin protein–protein interactions; dividing the interactions into three types: (1 interactions between aquaporin tetramers; (2 interactions between aquaporin monomers within a tetramer (hetero-tetramerization; and (3 transient interactions with regulatory proteins. We particularly focus on the structural aspects of the interactions, discussing the small differences within a conserved overall fold that allow for aquaporins to be differentially regulated in an organism-, tissue- and trigger-specific manner. A deep knowledge about these differences is needed to fully understand aquaporin function and regulation in many physiological processes, and may enable design of compounds targeting specific aquaporins for treatment of human disease.

  20. A method for investigating protein-protein interactions related to Salmonella typhimurium pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, Saiful M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Shi, Liang [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Yoon, Hyunjin [Dartmouth College, Hanover, NH (United States); Ansong, Charles [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rommereim, Leah M. [Dartmouth College, Hanover, NH (United States); Norbeck, Angela D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Auberry, Kenneth J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moore, R. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Adkins, Joshua N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Heffron, Fred [Oregon Health and Science Univ., Portland, OR (United States); Smith, Richard D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-02-10

    We successfully modified an existing method to investigate protein-protein interactions in the pathogenic bacterium Salmonella typhimurium (STM). This method includes i) addition of a histidine-biotin-histidine tag to the bait proteins via recombinant DNA techniques; ii) in vivo cross-linking with formaldehyde; iii) tandem affinity purification of bait proteins under fully denaturing conditions; and iv) identification of the proteins cross-linked to the bait proteins by liquid-chromatography in conjunction with tandem mass-spectrometry. In vivo cross-linking stabilized protein interactions permitted the subsequent two-step purification step conducted under denaturing conditions. The two-step purification greatly reduced nonspecific binding of non-cross-linked proteins to bait proteins. Two different negative controls were employed to reduce false-positive identification. In an initial demonstration of this approach, we tagged three selected STM proteins- HimD, PduB and PhoP- with known binding partners that ranged from stable (e.g., HimD) to transient (i.e., PhoP). Distinct sets of interacting proteins were identified with each bait protein, including the known binding partners such as HimA for HimD, as well as anticipated and unexpected binding partners. Our results suggest that novel protein-protein interactions may be critical to pathogenesis by Salmonella typhimurium. .

  1. Exceptional heat stability of high protein content dispersions containing whey protein particles

    NARCIS (Netherlands)

    Saglam, D.; Venema, P.; Vries, de R.J.; Linden, van der E.

    2014-01-01

    Due to aggregation and/or gelation during thermal treatment, the amount of whey proteins that can be used in the formulation of high protein foods e.g. protein drinks, is limited. The aim of this study was to replace whey proteins with whey protein particles to increase the total protein content and

  2. Directed Evolution of Proteins through In Vitro Protein Synthesis in Liposomes

    Directory of Open Access Journals (Sweden)

    Takehiro Nishikawa

    2012-01-01

    Full Text Available Directed evolution of proteins is a technique used to modify protein functions through “Darwinian selection.” In vitro compartmentalization (IVC is an in vitro gene screening system for directed evolution of proteins. IVC establishes the link between genetic information (genotype and the protein translated from the information (phenotype, which is essential for all directed evolution methods, by encapsulating both in a nonliving microcompartment. Herein, we introduce a new liposome-based IVC system consisting of a liposome, the protein synthesis using recombinant elements (PURE system and a fluorescence-activated cell sorter (FACS used as a microcompartment, in vitro protein synthesis system, and high-throughput screen, respectively. Liposome-based IVC is characterized by in vitro protein synthesis from a single copy of a gene in a cell-sized unilamellar liposome and quantitative functional evaluation of the synthesized proteins. Examples of liposome-based IVC for screening proteins such as GFP and β-glucuronidase are described. We discuss the future directions for this method and its applications.

  3. Categorizing Biases in High-Confidence High-Throughput Protein-Protein Interaction Data Sets*

    Science.gov (United States)

    Yu, Xueping; Ivanic, Joseph; Memišević, Vesna; Wallqvist, Anders; Reifman, Jaques

    2011-01-01

    We characterized and evaluated the functional attributes of three yeast high-confidence protein-protein interaction data sets derived from affinity purification/mass spectrometry, protein-fragment complementation assay, and yeast two-hybrid experiments. The interacting proteins retrieved from these data sets formed distinct, partially overlapping sets with different protein-protein interaction characteristics. These differences were primarily a function of the deployed experimental technologies used to recover these interactions. This affected the total coverage of interactions and was especially evident in the recovery of interactions among different functional classes of proteins. We found that the interaction data obtained by the yeast two-hybrid method was the least biased toward any particular functional characterization. In contrast, interacting proteins in the affinity purification/mass spectrometry and protein-fragment complementation assay data sets were over- and under-represented among distinct and different functional categories. We delineated how these differences affected protein complex organization in the network of interactions, in particular for strongly interacting complexes (e.g. RNA and protein synthesis) versus weak and transient interacting complexes (e.g. protein transport). We quantified methodological differences in detecting protein interactions from larger protein complexes, in the correlation of protein abundance among interacting proteins, and in their connectivity of essential proteins. In the latter case, we showed that minimizing inherent methodology biases removed many of the ambiguous conclusions about protein essentiality and protein connectivity. We used these findings to rationalize how biological insights obtained by analyzing data sets originating from different sources sometimes do not agree or may even contradict each other. An important corollary of this work was that discrepancies in biological insights did not

  4. With Protein Foods, Variety Is Key: 10 Tips for Choosing Protein

    Science.gov (United States)

    ... Dietary Guidelines Communicator’s Guide 10 Tips: Vary Your Protein Routine You are here Home 10 Tips: Vary ... Protein Routine Print Share 10 Tips: Vary Your Protein Routine Protein foods include both animal (meat, poultry, ...

  5. Protein complex prediction based on k-connected subgraphs in protein interaction network

    OpenAIRE

    Habibi, Mahnaz; Eslahchi, Changiz; Wong, Limsoon

    2010-01-01

    Abstract Background Protein complexes play an important role in cellular mechanisms. Recently, several methods have been presented to predict protein complexes in a protein interaction network. In these methods, a protein complex is predicted as a dense subgraph of protein interactions. However, interactions data are incomplete and a protein complex does not have to be a complete or dense subgraph. Results We propose a more appropriate protein complex prediction method, CFA, that is based on ...

  6. Karakteristik Protein dan Nitrogen Non Protein Daging Ikan Cucut Lanyam (Charcharhinus limbatus (Characteristics of Protein and Non Protein Nitrogen in Lanyam Shark Muscle

    Directory of Open Access Journals (Sweden)

    Yuspihana Fitrial

    2017-02-01

    Based on protein solubility of Lanyam muscle at pH 1.5 to 12 obtained two points which is minimum solubility at pH 4.5 and pH 9. Based on the classification Osborn, Lanyam muscle contained albumin (28.64%, globulin (13:44%, prolamin (03.29%, glutelin (33.70%. Observation of non-protein nitrogen levels indicated that the washing process was very effective to reduce non-protein nitrogen levels up to 62.34% and urea levels up to 58% . Differential Scanning Calorimetry Study of Lanyam mince showed two types of protein that has a different stability to heat and after added 2.5% NaCl formed a peak which is a fusion of both these proteins

  7. On the role of electrostatics on protein-protein interactions

    Science.gov (United States)

    Zhang, Zhe; Witham, Shawn; Alexov, Emil

    2011-01-01

    The role of electrostatics on protein-protein interactions and binding is reviewed in this article. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and basic electrostatic effects occurring upon the formation of the complex are discussed. The role of the salt concentration and pH of the water phase on protein-protein binding free energy is demonstrated and indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge-charge interactions across the interface. It is pointed out that the pH-optimum (pH of optimal binding affinity) varies among the protein-protein complexes, and perhaps is a result of their adaptation to particular subcellular compartment. At the end, the similarities and differences between hetero- and homo-complexes are outlined and discussed with respect to the binding mode and charge complementarity. PMID:21572182

  8. PIPE: a protein-protein interaction prediction engine based on the re-occurring short polypeptide sequences between known interacting protein pairs

    Directory of Open Access Journals (Sweden)

    Greenblatt Jack

    2006-07-01

    Full Text Available Abstract Background Identification of protein interaction networks has received considerable attention in the post-genomic era. The currently available biochemical approaches used to detect protein-protein interactions are all time and labour intensive. Consequently there is a growing need for the development of computational tools that are capable of effectively identifying such interactions. Results Here we explain the development and implementation of a novel Protein-Protein Interaction Prediction Engine termed PIPE. This tool is capable of predicting protein-protein interactions for any target pair of the yeast Saccharomyces cerevisiae proteins from their primary structure and without the need for any additional information or predictions about the proteins. PIPE showed a sensitivity of 61% for detecting any yeast protein interaction with 89% specificity and an overall accuracy of 75%. This rate of success is comparable to those associated with the most commonly used biochemical techniques. Using PIPE, we identified a novel interaction between YGL227W (vid30 and YMR135C (gid8 yeast proteins. This lead us to the identification of a novel yeast complex that here we term vid30 complex (vid30c. The observed interaction was confirmed by tandem affinity purification (TAP tag, verifying the ability of PIPE to predict novel protein-protein interactions. We then used PIPE analysis to investigate the internal architecture of vid30c. It appeared from PIPE analysis that vid30c may consist of a core and a secondary component. Generation of yeast gene deletion strains combined with TAP tagging analysis indicated that the deletion of a member of the core component interfered with the formation of vid30c, however, deletion of a member of the secondary component had little effect (if any on the formation of vid30c. Also, PIPE can be used to analyse yeast proteins for which TAP tagging fails, thereby allowing us to predict protein interactions that are not

  9. Consumption of Milk Protein or Whey Protein Results in a Similar Increase in Muscle Protein Synthesis in Middle Aged Men.

    Science.gov (United States)

    Mitchell, Cameron J; McGregor, Robin A; D'Souza, Randall F; Thorstensen, Eric B; Markworth, James F; Fanning, Aaron C; Poppitt, Sally D; Cameron-Smith, David

    2015-10-21

    The differential ability of various milk protein fractions to stimulate muscle protein synthesis (MPS) has been previously described, with whey protein generally considered to be superior to other fractions. However, the relative ability of a whole milk protein to stimulate MPS has not been compared to whey. Sixteen healthy middle-aged males ingested either 20 g of milk protein (n = 8) or whey protein (n = 8) while undergoing a primed constant infusion of ring (13)C₆ phenylalanine. Muscle biopsies were obtained 120 min prior to consumption of the protein and 90 and 210 min afterwards. Resting myofibrillar fractional synthetic rates (FSR) were 0.019% ± 0.009% and 0.021% ± 0.018% h(-1) in the milk and whey groups respectively. For the first 90 min after protein ingestion the FSR increased (p whey groups respectively with no difference between groups (p = 0.810). FSR returned to baseline in both groups between 90 and 210 min after protein ingestion. Despite evidence of increased rate of digestion and leucine availability following the ingestion of whey protein, there was similar activation of MPS in middle-aged men with either 20 g of milk protein or whey protein.

  10. Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes.

    Science.gov (United States)

    Nillegoda, Nadinath B; Stank, Antonia; Malinverni, Duccio; Alberts, Niels; Szlachcic, Anna; Barducci, Alessandro; De Los Rios, Paolo; Wade, Rebecca C; Bukau, Bernd

    2017-05-15

    Hsp70 participates in a broad spectrum of protein folding processes extending from nascent chain folding to protein disaggregation. This versatility in function is achieved through a diverse family of J-protein cochaperones that select substrates for Hsp70. Substrate selection is further tuned by transient complexation between different classes of J-proteins, which expands the range of protein aggregates targeted by metazoan Hsp70 for disaggregation. We assessed the prevalence and evolutionary conservation of J-protein complexation and cooperation in disaggregation. We find the emergence of a eukaryote-specific signature for interclass complexation of canonical J-proteins. Consistently, complexes exist in yeast and human cells, but not in bacteria, and correlate with cooperative action in disaggregation in vitro. Signature alterations exclude some J-proteins from networking, which ensures correct J-protein pairing, functional network integrity and J-protein specialization. This fundamental change in J-protein biology during the prokaryote-to-eukaryote transition allows for increased fine-tuning and broadening of Hsp70 function in eukaryotes.

  11. Globular and disordered-the non-identical twins in protein-protein interactions

    DEFF Research Database (Denmark)

    Teilum, Kaare; Olsen, Johan Gotthardt; Kragelund, Birthe Brandt

    2015-01-01

    as a strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those...... of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1)....

  12. Neuromuscular electrical stimulation prior to presleep protein feeding stimulates the use of protein-derived amino acids for overnight muscle protein synthesis.

    Science.gov (United States)

    Dirks, Marlou L; Groen, Bart B L; Franssen, Rinske; van Kranenburg, Janneau; van Loon, Luc J C

    2017-01-01

    Short periods of muscle disuse result in substantial skeletal muscle atrophy. Recently, we showed that both neuromuscular electrical stimulation (NMES) as well as presleep dietary protein ingestion represent effective strategies to stimulate muscle protein synthesis rates. In this study, we test our hypothesis that NMES can augment the use of presleep protein-derived amino acids for overnight muscle protein synthesis in older men. Twenty healthy, older [69 ± 1 (SE) yr] men were subjected to 24 h of bed rest, starting at 8:00 AM. In the evening, volunteers were subjected to 70-min 1-legged NMES, while the other leg served as nonstimulated control (CON). Immediately following NMES, 40 g of intrinsically l-[1- 13 C]-phenylalanine labeled protein was ingested prior to sleep. Blood samples were taken throughout the night, and muscle biopsies were obtained from both legs in the evening and the following morning (8 h after protein ingestion) to assess dietary protein-derived l-[1- 13 C]-phenylalanine enrichments in myofibrillar protein. Plasma phenylalanine concentrations and plasma l-[1- 13 C]-phenylalanine enrichments increased significantly following protein ingestion and remained elevated for up to 6 h after protein ingestion (P protein-bound l-[1- 13 C]-phenylalanine enrichments (MPE) increased to a greater extent in the stimulated compared with the control leg (0.0344 ± 0.0019 vs. 0.0297 ± 0.0016 MPE, respectively; P protein-derived amino acids in the NMES compared with CON leg. In conclusion, application of NMES prior to presleep protein feeding stimulates the use of dietary protein-derived amino acids for overnight muscle protein synthesis in older men. Neuromuscular electrical stimulation (NMES) as well as presleep dietary protein ingestion represent effective strategies to stimulate muscle protein synthesis rates. Here we demonstrate that in older men after a day of bed rest, the application of NMES prior to presleep protein feeding stimulates the use of

  13. A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein.

    Science.gov (United States)

    Agrawal, Neeraj J; Helk, Bernhard; Trout, Bernhardt L

    2014-01-21

    Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. ProDis-ContSHC: Learning protein dissimilarity measures and hierarchical context coherently for protein-protein comparison in protein database retrieval

    KAUST Repository

    Wang, Jim Jing-Yan; Gao, Xin; Wang, Quanquan; Li, Yongping

    2012-01-01

    Background: The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity

  15. Current strategies for protein production and purification enabling membrane protein structural biology.

    Science.gov (United States)

    Pandey, Aditya; Shin, Kyungsoo; Patterson, Robin E; Liu, Xiang-Qin; Rainey, Jan K

    2016-12-01

    Membrane proteins are still heavily under-represented in the protein data bank (PDB), owing to multiple bottlenecks. The typical low abundance of membrane proteins in their natural hosts makes it necessary to overexpress these proteins either in heterologous systems or through in vitro translation/cell-free expression. Heterologous expression of proteins, in turn, leads to multiple obstacles, owing to the unpredictability of compatibility of the target protein for expression in a given host. The highly hydrophobic and (or) amphipathic nature of membrane proteins also leads to challenges in producing a homogeneous, stable, and pure sample for structural studies. Circumventing these hurdles has become possible through the introduction of novel protein production protocols; efficient protein isolation and sample preparation methods; and, improvement in hardware and software for structural characterization. Combined, these advances have made the past 10-15 years very exciting and eventful for the field of membrane protein structural biology, with an exponential growth in the number of solved membrane protein structures. In this review, we focus on both the advances and diversity of protein production and purification methods that have allowed this growth in structural knowledge of membrane proteins through X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM).

  16. Fragment-based quantum mechanical calculation of protein-protein binding affinities.

    Science.gov (United States)

    Wang, Yaqian; Liu, Jinfeng; Li, Jinjin; He, Xiao

    2018-04-29

    The electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method has been successfully utilized for efficient linear-scaling quantum mechanical (QM) calculation of protein energies. In this work, we applied the EE-GMFCC method for calculation of binding affinity of Endonuclease colicin-immunity protein complex. The binding free energy changes between the wild-type and mutants of the complex calculated by EE-GMFCC are in good agreement with experimental results. The correlation coefficient (R) between the predicted binding energy changes and experimental values is 0.906 at the B3LYP/6-31G*-D level, based on the snapshot whose binding affinity is closest to the average result from the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculation. The inclusion of the QM effects is important for accurate prediction of protein-protein binding affinities. Moreover, the self-consistent calculation of PB solvation energy is required for accurate calculations of protein-protein binding free energies. This study demonstrates that the EE-GMFCC method is capable of providing reliable prediction of relative binding affinities for protein-protein complexes. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  17. PROTEIN FRACTIONS AND IN VITRO FERMENTATION OF PROTEIN FEEDS FOR RUMINANTS

    Directory of Open Access Journals (Sweden)

    Angel L. Guevara-Mesa

    2011-05-01

    Full Text Available The objective of this study was to evaluate 20 protein feeds grouped in forages, vegetal by- products and animal by-products used for ruminant diets. Protein fractions (PF: A, non-protein nitrogen (NPN; B1, buffer-soluble protein; B2, buffer-insoluble, NDF-soluble protein; B3, NDF-insoluble, ADF-soluble protein; and C, ADF-insoluble protein, were determined for each ingredient.  Protein composition was correlated with total gas production in vitro (GP, gas production rate (S, lag time (L, DM disappearance (DMDIV and residual protein (RPIV. The completely randomised designed was analysed using mixed proc. and Tukey contrasts. Forages contained 18.29, 7.86, 66.00, 2.96, 4.89% of fractions A, B1, B2, B3 and C, respectively. Vegetable by-products contained 22.55, 4.55, 59.51, 8.84, 4.55% of each fraction, in the same order. Animal by-products contained 19.13, 4.52, 70.24, 3.74, 2.37% of each fraction, in the same order. Vetch, wheat bran and poultry litter had the greatest Vmax in each group. Vmax was correlated (P≤0.01 with total protein (r = -0.45, ADF (r = 0.27 and DMDIV (r = 0.61. In conclusion, there were differences in protein composition and kinetics of in vitro gas production among ingredients.

  18. Selection of peptides interfering with protein-protein interaction.

    Science.gov (United States)

    Gaida, Annette; Hagemann, Urs B; Mattay, Dinah; Räuber, Christina; Müller, Kristian M; Arndt, Katja M

    2009-01-01

    Cell physiology depends on a fine-tuned network of protein-protein interactions, and misguided interactions are often associated with various diseases. Consequently, peptides, which are able to specifically interfere with such adventitious interactions, are of high interest for analytical as well as medical purposes. One of the most abundant protein interaction domains is the coiled-coil motif, and thus provides a premier target. Coiled coils, which consist of two or more alpha-helices wrapped around each other, have one of the simplest interaction interfaces, yet they are able to confer highly specific homo- and heterotypic interactions involved in virtually any cellular process. While there are several ways to generate interfering peptides, the combination of library design with a powerful selection system seems to be one of the most effective and promising approaches. This chapter guides through all steps of such a process, starting with library options and cloning, detailing suitable selection techniques and ending with purification for further down-stream characterization. Such generated peptides will function as versatile tools to interfere with the natural function of their targets thereby illuminating their down-stream signaling and, in general, promoting understanding of factors leading to specificity and stability in protein-protein interactions. Furthermore, peptides interfering with medically relevant proteins might become important diagnostics and therapeutics.

  19. Phthalic Acid Chemical Probes Synthesized for Protein-Protein Interaction Analysis

    Directory of Open Access Journals (Sweden)

    Chin-Jen Wu

    2013-06-01

    Full Text Available Plasticizers are additives that are used to increase the flexibility of plastic during manufacturing. However, in injection molding processes, plasticizers cannot be generated with monomers because they can peel off from the plastics into the surrounding environment, water, or food, or become attached to skin. Among the various plasticizers that are used, 1,2-benzenedicarboxylic acid (phthalic acid is a typical precursor to generate phthalates. In addition, phthalic acid is a metabolite of diethylhexyl phthalate (DEHP. According to Gene_Ontology gene/protein database, phthalates can cause genital diseases, cardiotoxicity, hepatotoxicity, nephrotoxicity, etc. In this study, a silanized linker (3-aminopropyl triethoxyslane, APTES was deposited on silicon dioxides (SiO2 particles and phthalate chemical probes were manufactured from phthalic acid and APTES–SiO2. These probes could be used for detecting proteins that targeted phthalic acid and for protein-protein interactions. The phthalic acid chemical probes we produced were incubated with epithelioid cell lysates of normal rat kidney (NRK-52E cells to detect the interactions between phthalic acid and NRK-52E extracted proteins. These chemical probes interacted with a number of chaperones such as protein disulfide-isomerase A6, heat shock proteins, and Serpin H1. Ingenuity Pathways Analysis (IPA software showed that these chemical probes were a practical technique for protein-protein interaction analysis.

  20. Protein-protein docking using region-based 3D Zernike descriptors.

    Science.gov (United States)

    Venkatraman, Vishwesh; Yang, Yifeng D; Sael, Lee; Kihara, Daisuke

    2009-12-09

    Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-alphaRMSD 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods.

  1. Predicting protein complexes from weighted protein-protein interaction graphs with a novel unsupervised methodology: Evolutionary enhanced Markov clustering.

    Science.gov (United States)

    Theofilatos, Konstantinos; Pavlopoulou, Niki; Papasavvas, Christoforos; Likothanassis, Spiros; Dimitrakopoulos, Christos; Georgopoulos, Efstratios; Moschopoulos, Charalampos; Mavroudi, Seferina

    2015-03-01

    Proteins are considered to be the most important individual components of biological systems and they combine to form physical protein complexes which are responsible for certain molecular functions. Despite the large availability of protein-protein interaction (PPI) information, not much information is available about protein complexes. Experimental methods are limited in terms of time, efficiency, cost and performance constraints. Existing computational methods have provided encouraging preliminary results, but they phase certain disadvantages as they require parameter tuning, some of them cannot handle weighted PPI data and others do not allow a protein to participate in more than one protein complex. In the present paper, we propose a new fully unsupervised methodology for predicting protein complexes from weighted PPI graphs. The proposed methodology is called evolutionary enhanced Markov clustering (EE-MC) and it is a hybrid combination of an adaptive evolutionary algorithm and a state-of-the-art clustering algorithm named enhanced Markov clustering. EE-MC was compared with state-of-the-art methodologies when applied to datasets from the human and the yeast Saccharomyces cerevisiae organisms. Using public available datasets, EE-MC outperformed existing methodologies (in some datasets the separation metric was increased by 10-20%). Moreover, when applied to new human datasets its performance was encouraging in the prediction of protein complexes which consist of proteins with high functional similarity. In specific, 5737 protein complexes were predicted and 72.58% of them are enriched for at least one gene ontology (GO) function term. EE-MC is by design able to overcome intrinsic limitations of existing methodologies such as their inability to handle weighted PPI networks, their constraint to assign every protein in exactly one cluster and the difficulties they face concerning the parameter tuning. This fact was experimentally validated and moreover, new

  2. Escherichia coli cell-free protein synthesis and isotope labeling of mammalian proteins.

    Science.gov (United States)

    Terada, Takaho; Yokoyama, Shigeyuki

    2015-01-01

    This chapter describes the cell-free protein synthesis method, using an Escherichia coli cell extract. This is a cost-effective method for milligram-scale protein production and is particularly useful for the production of mammalian proteins, protein complexes, and membrane proteins that are difficult to synthesize by recombinant expression methods, using E. coli and eukaryotic cells. By adjusting the conditions of the cell-free method, zinc-binding proteins, disulfide-bonded proteins, ligand-bound proteins, etc., may also be produced. Stable isotope labeling of proteins can be accomplished by the cell-free method, simply by using stable isotope-labeled amino acid(s) in the cell-free reaction. Moreover, the cell-free protein synthesis method facilitates the avoidance of stable isotope scrambling and dilution over the recombinant expression methods and is therefore advantageous for amino acid-selective stable isotope labeling. Site-specific stable isotope labeling is also possible with a tRNA molecule specific to the UAG codon. By the cell-free protein synthesis method, coupled transcription-translation is performed from a plasmid vector or a PCR-amplified DNA fragment encoding the protein. A milligram quantity of protein can be produced with a milliliter-scale reaction solution in the dialysis mode. More than a thousand solution structures have been determined by NMR spectroscopy for uniformly labeled samples of human and mouse functional domain proteins, produced by the cell-free method. Here, we describe the practical aspects of mammalian protein production by the cell-free method for NMR spectroscopy. © 2015 Elsevier Inc. All rights reserved.

  3. A selection that reports on protein-protein interactions within a thermophilic bacterium.

    Science.gov (United States)

    Nguyen, Peter Q; Silberg, Jonathan J

    2010-07-01

    Many proteins can be split into fragments that exhibit enhanced function upon fusion to interacting proteins. While this strategy has been widely used to create protein-fragment complementation assays (PCAs) for discovering protein-protein interactions within mesophilic organisms, similar assays have not yet been developed for studying natural and engineered protein complexes at the temperatures where thermophilic microbes grow. We describe the development of a selection for protein-protein interactions within Thermus thermophilus that is based upon growth complementation by fragments of Thermotoga neapolitana adenylate kinase (AK(Tn)). Complementation studies with an engineered thermophile (PQN1) that is not viable above 75 degrees C because its adk gene has been replaced by a Geobacillus stearothermophilus ortholog revealed that growth could be restored at 78 degrees C by a vector that coexpresses polypeptides corresponding to residues 1-79 and 80-220 of AK(Tn). In contrast, PQN1 growth was not complemented by AK(Tn) fragments harboring a C156A mutation within the zinc-binding tetracysteine motif unless these fragments were fused to Thermotoga maritima chemotaxis proteins that heterodimerize (CheA and CheY) or homodimerize (CheX). This enhanced complementation is interpreted as arising from chemotaxis protein-protein interactions, since AK(Tn)-C156A fragments having only one polypeptide fused to a chemotaxis protein did not complement PQN1 to the same extent. This selection increases the maximum temperature where a PCA can be used to engineer thermostable protein complexes and to map protein-protein interactions.

  4. InSilico Proteomics System: Integration and Application of Protein and Protein-Protein Interaction Data using Microsoft .NET

    Directory of Open Access Journals (Sweden)

    Straßer Wolfgang

    2006-12-01

    Full Text Available In the last decades, biological databases became the major knowledge resource for researchers in the field of molecular biology. The distribution of information among these databases is one of the major problems. An overview about the subject area of data access and representation of protein and protein-protein interaction data within public biological databases is described. For a comprehensive and consistent way of searching and analysing integrated protein and protein-protein interaction data, the InSilico Proteomics (ISP project has been initiated. Its three main objectives are (1 to provide an integrated knowledge pool for data investigation and global network analysis functions for a better understanding of a cell’s interactome, (2 employment of public data for plausibility analysis and validation of in-house experimental data and (3 testing the applicability of Microsoft’s .NET architecture for bioinformatics applications. Data integrated into the ISP database can be queried through the Web portal PRIMOS (PRotein Interaction and MOlecule Search which is freely available at http://biomis.fh-hagenberg.at/isp/primos.

  5. Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

    DEFF Research Database (Denmark)

    Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah

    2016-01-01

    ’s disease (PD), Alzheimer’s disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other......In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post......-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially...

  6. Detecting protein complexes based on a combination of topological and biological properties in protein-protein interaction network

    Directory of Open Access Journals (Sweden)

    Pooja Sharma

    2018-06-01

    Full Text Available Protein complexes are known to play a major role in controlling cellular activity in a living being. Identifying complexes from raw protein protein interactions (PPIs is an important area of research. Earlier work has been limited mostly to yeast. Such protein complex identification methods, when applied to large human PPIs often give poor performance. We introduce a novel method called CSC to detect protein complexes. The method is evaluated in terms of positive predictive value, sensitivity and accuracy using the datasets of the model organism, yeast and humans. CSC outperforms several other competing algorithms for both organisms. Further, we present a framework to establish the usefulness of CSC in analyzing the influence of a given disease gene in a complex topologically as well as biologically considering eight major association factors. Keywords: Protein complex, Connectivity, Semantic similarity, Contribution

  7. Protein complex prediction based on k-connected subgraphs in protein interaction network

    Directory of Open Access Journals (Sweden)

    Habibi Mahnaz

    2010-09-01

    Full Text Available Abstract Background Protein complexes play an important role in cellular mechanisms. Recently, several methods have been presented to predict protein complexes in a protein interaction network. In these methods, a protein complex is predicted as a dense subgraph of protein interactions. However, interactions data are incomplete and a protein complex does not have to be a complete or dense subgraph. Results We propose a more appropriate protein complex prediction method, CFA, that is based on connectivity number on subgraphs. We evaluate CFA using several protein interaction networks on reference protein complexes in two benchmark data sets (MIPS and Aloy, containing 1142 and 61 known complexes respectively. We compare CFA to some existing protein complex prediction methods (CMC, MCL, PCP and RNSC in terms of recall and precision. We show that CFA predicts more complexes correctly at a competitive level of precision. Conclusions Many real complexes with different connectivity level in protein interaction network can be predicted based on connectivity number. Our CFA program and results are freely available from http://www.bioinf.cs.ipm.ir/softwares/cfa/CFA.rar.

  8. Tau protein

    DEFF Research Database (Denmark)

    Frederiksen, Jette Lautrup Battistini; Kristensen, Kim; Bahl, Jmc

    2011-01-01

    Background: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. Objective: To investigate the association between tau protein concentration and 14......-3-3 protein in the cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON) versus patients with monosymptomatic onset who progressed to multiple sclerosis (MS). To evaluate results against data found in a complete literature review. Methods: A total of 66 patients with MS and/or ON from...... the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. Results: The study shows a significantly increased concentration of tau...

  9. Globular and disordered – the non-identical twins in protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Kaare eTeilum

    2015-07-01

    Full Text Available In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP’s bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol-1.

  10. Towards a map of the Populus biomass protein-protein interaction network

    Energy Technology Data Exchange (ETDEWEB)

    Beers, Eric [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Brunner, Amy [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Helm, Richard [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Dickerman, Allan [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States)

    2015-07-31

    Biofuels can be produced from a variety of plant feedstocks. The value of a particular feedstock for biofuels production depends in part on the degree of difficulty associated with the extraction of fermentable sugars from the plant biomass. The wood of trees is potentially a rich source fermentable sugars. However, the sugars in wood exist in a tightly cross-linked matrix of cellulose, hemicellulose, and lignin, making them largely recalcitrant to release and fermentation for biofuels production. Before breeders and genetic engineers can effectively develop plants with reduced recalcitrance to fermentation, it is necessary to gain a better understanding of the fundamental biology of the mechanisms responsible for wood formation. Regulatory, structural, and enzymatic proteins are required for the complicated process of wood formation. To function properly, proteins must interact with other proteins. Yet, very few of the protein-protein interactions necessary for wood formation are known. The main objectives of this project were to 1) identify new protein-protein interactions relevant to wood formation, and 2) perform in-depth characterizations of selected protein-protein interactions. To identify relevant protein-protein interactions, we cloned a set of approximately 400 genes that were highly expressed in the wood-forming tissue (known as secondary xylem) of poplar (Populus trichocarpa). We tested whether the proteins encoded by these biomass genes interacted with each other in a binary matrix design using the yeast two-hybrid (Y2H) method for protein-protein interaction discovery. We also tested a subset of the 400 biomass proteins for interactions with all proteins present in wood-forming tissue of poplar in a biomass library screen design using Y2H. Together, these two Y2H screens yielded over 270 interactions involving over 75 biomass proteins. For the second main objective we selected several interacting pairs or groups of interacting proteins for in

  11. Imaging protein-protein interactions in living cells

    NARCIS (Netherlands)

    Hink, M.A.; Bisseling, T.; Visser, A.J.W.G.

    2002-01-01

    The complex organization of plant cells makes it likely that the molecular behaviour of proteins in the test tube and the cell is different. For this reason, it is essential though a challenge to study proteins in their natural environment. Several innovative microspectroscopic approaches provide

  12. Protein - Which is Best?

    Science.gov (United States)

    Hoffman, Jay R; Falvo, Michael J

    2004-09-01

    Protein intake that exceeds the recommended daily allowance is widely accepted for both endurance and power athletes. However, considering the variety of proteins that are available much less is known concerning the benefits of consuming one protein versus another. The purpose of this paper is to identify and analyze key factors in order to make responsible recommendations to both the general and athletic populations. Evaluation of a protein is fundamental in determining its appropriateness in the human diet. Proteins that are of inferior content and digestibility are important to recognize and restrict or limit in the diet. Similarly, such knowledge will provide an ability to identify proteins that provide the greatest benefit and should be consumed. The various techniques utilized to rate protein will be discussed. Traditionally, sources of dietary protein are seen as either being of animal or vegetable origin. Animal sources provide a complete source of protein (i.e. containing all essential amino acids), whereas vegetable sources generally lack one or more of the essential amino acids. Animal sources of dietary protein, despite providing a complete protein and numerous vitamins and minerals, have some health professionals concerned about the amount of saturated fat common in these foods compared to vegetable sources. The advent of processing techniques has shifted some of this attention and ignited the sports supplement marketplace with derivative products such as whey, casein and soy. Individually, these products vary in quality and applicability to certain populations. The benefits that these particular proteins possess are discussed. In addition, the impact that elevated protein consumption has on health and safety issues (i.e. bone health, renal function) are also reviewed. Key PointsHigher protein needs are seen in athletic populations.Animal proteins is an important source of protein, however potential health concerns do exist from a diet of protein

  13. Combining random gene fission and rational gene fusion to discover near-infrared fluorescent protein fragments that report on protein-protein interactions.

    Science.gov (United States)

    Pandey, Naresh; Nobles, Christopher L; Zechiedrich, Lynn; Maresso, Anthony W; Silberg, Jonathan J

    2015-05-15

    Gene fission can convert monomeric proteins into two-piece catalysts, reporters, and transcription factors for systems and synthetic biology. However, some proteins can be challenging to fragment without disrupting function, such as near-infrared fluorescent protein (IFP). We describe a directed evolution strategy that can overcome this challenge by randomly fragmenting proteins and concomitantly fusing the protein fragments to pairs of proteins or peptides that associate. We used this method to create libraries that express fragmented IFP as fusions to a pair of associating peptides (IAAL-E3 and IAAL-K3) and proteins (CheA and CheY) and screened for fragmented IFP with detectable near-infrared fluorescence. Thirteen novel fragmented IFPs were identified, all of which arose from backbone fission proximal to the interdomain linker. Either the IAAL-E3 and IAAL-K3 peptides or CheA and CheY proteins could assist with IFP fragment complementation, although the IAAL-E3 and IAAL-K3 peptides consistently yielded higher fluorescence. These results demonstrate how random gene fission can be coupled to rational gene fusion to create libraries enriched in fragmented proteins with AND gate logic that is dependent upon a protein-protein interaction, and they suggest that these near-infrared fluorescent protein fragments will be suitable as reporters for pairs of promoters and protein-protein interactions within whole animals.

  14. Athoropometric measurements and plasma proteins in protein ...

    African Journals Online (AJOL)

    Athoropometric measurements and plasma proteins in protein energy malnutrition. MH Etukudo, EO Agbedana, OO Akinyinka, BOA Osifo. Abstract. No Abstract. Global Journal of Medical Sciences Vol. 5(1) 2006: 7-11. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD ...

  15. African Journal of Biotechnology Vol

    African Journals Online (AJOL)

    Gaga E Tonukari

    List of the random primers used, their nucleotide sequence and annealing temperatures. Primers. Sequence 5`- 3`. Annealing. Temperature. °C/time (s). 1. ATG ACG TTG A. 2. GGG CTA GGG T. 3. ACC GGG AAC G. 4. AGC AGG TGG A. 45/30. 5. AGG CCC CTG T. 6. ATG CCC CTG T. 7. AAA GCT GCG G. 8. ACC GCC GAA ...

  16. Characterization of specific random amplified polymorphic (RAPD ...

    African Journals Online (AJOL)

    toshiba

    2013-04-10

    Apr 10, 2013 ... GGG CCA CTG T. 8. 8. 0. 97. OPY-20. AGC CGT GGA A. 7. 7. 0. 98. OPZ-13. GAC TAA GCC C. 0. 0. 0 fingerprinting differentiation was combined with bulked segregant analysis (Michelmore, et al. 1991). A total of. 98 operon RAPD primers (Almaeda, USA) were used in the first step differential screening in ...

  17. Identification of membrane proteins by tandem mass spectrometry of protein ions

    Science.gov (United States)

    Carroll, Joe; Altman, Matthew C.; Fearnley, Ian M.; Walker, John E.

    2007-01-01

    The most common way of identifying proteins in proteomic analyses is to use short segments of sequence (“tags”) determined by mass spectrometric analysis of proteolytic fragments. The approach is effective with globular proteins and with membrane proteins with significant polar segments between membrane-spanning α-helices, but it is ineffective with other hydrophobic proteins where protease cleavage sites are either infrequent or absent. By developing methods to purify hydrophobic proteins in organic solvents and by fragmenting ions of these proteins by collision induced dissociation with argon, we have shown that partial sequences of many membrane proteins can be deduced easily by manual inspection. The spectra from small proteolipids (1–4 transmembrane α-helices) are dominated usually by fragment ions arising from internal amide cleavages, from which internal sequences can be obtained, whereas the spectra from larger membrane proteins (5–18 transmembrane α-helices) often contain fragment ions from N- and/or C-terminal parts yielding sequences in those regions. With these techniques, we have, for example, identified an abundant protein of unknown function from inner membranes of mitochondria that to our knowledge has escaped detection in proteomic studies, and we have produced sequences from 10 of 13 proteins encoded in mitochondrial DNA. They include the ND6 subunit of complex I, the last of its 45 subunits to be analyzed. The procedures have the potential to be developed further, for example by using newly introduced methods for protein ion dissociation to induce fragmentation of internal regions of large membrane proteins, which may remain partially folded in the gas phase. PMID:17720804

  18. Architectures and Functional Coverage of Protein-Protein Interfaces

    Science.gov (United States)

    Tuncbag, Nurcan; Gursoy, Attila; Guney, Emre; Nussinov, Ruth; Keskin, Ozlem

    2008-01-01

    The diverse range of cellular functions is performed by a limited number of protein folds existing in nature. One may similarly expect that cellular functional diversity would be covered by a limited number of protein-protein interface architectures. Here, we present 8205 interface clusters, each representing unique interface architecture. This dataset of protein-protein interfaces is analyzed and compared with older datasets. We observe that the number of both biological and crystal interfaces increase significantly compared to the number of PDB entries. Further, we find that the number of distinct interface architectures grows at a much faster rate than the number of folds and is yet to level off. We further analyze the growth trend of the functional coverage by constructing functional interaction networks from interfaces. The functional coverage is also found to steadily increase. Interestingly, we also observe that despite the diversity of interface architectures, some are more favorable and frequently used, and of particular interest, those are the ones which are also preferred in single chains. PMID:18620705

  19. Inferring high-confidence human protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Yu Xueping

    2012-05-01

    Full Text Available Abstract Background As numerous experimental factors drive the acquisition, identification, and interpretation of protein-protein interactions (PPIs, aggregated assemblies of human PPI data invariably contain experiment-dependent noise. Ascertaining the reliability of PPIs collected from these diverse studies and scoring them to infer high-confidence networks is a non-trivial task. Moreover, a large number of PPIs share the same number of reported occurrences, making it impossible to distinguish the reliability of these PPIs and rank-order them. For example, for the data analyzed here, we found that the majority (>83% of currently available human PPIs have been reported only once. Results In this work, we proposed an unsupervised statistical approach to score a set of diverse, experimentally identified PPIs from nine primary databases to create subsets of high-confidence human PPI networks. We evaluated this ranking method by comparing it with other methods and assessing their ability to retrieve protein associations from a number of diverse and independent reference sets. These reference sets contain known biological data that are either directly or indirectly linked to interactions between proteins. We quantified the average effect of using ranked protein interaction data to retrieve this information and showed that, when compared to randomly ranked interaction data sets, the proposed method created a larger enrichment (~134% than either ranking based on the hypergeometric test (~109% or occurrence ranking (~46%. Conclusions From our evaluations, it was clear that ranked interactions were always of value because higher-ranked PPIs had a higher likelihood of retrieving high-confidence experimental data. Reducing the noise inherent in aggregated experimental PPIs via our ranking scheme further increased the accuracy and enrichment of PPIs derived from a number of biologically relevant data sets. These results suggest that using our high

  20. Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures

    Directory of Open Access Journals (Sweden)

    Srinivasan Narayanaswamy

    2010-06-01

    Full Text Available Abstract Background Dengue virus along with the other members of the flaviviridae family has reemerged as deadly human pathogens. Understanding the mechanistic details of these infections can be highly rewarding in developing effective antivirals. During maturation of the virus inside the host cell, the coat proteins E and M undergo conformational changes, altering the morphology of the viral coat. However, due to low resolution nature of the available 3-D structures of viral assemblies, the atomic details of these changes are still elusive. Results In the present analysis, starting from Cα positions of low resolution cryo electron microscopic structures the residue level details of protein-protein interaction interfaces of dengue virus coat proteins have been predicted. By comparing the preexisting structures of virus in different phases of life cycle, the changes taking place in these predicted protein-protein interaction interfaces were followed as a function of maturation process of the virus. Besides changing the current notion about the presence of only homodimers in the mature viral coat, the present analysis indicated presence of a proline-rich motif at the protein-protein interaction interface of the coat protein. Investigating the conservation status of these seemingly functionally crucial residues across other members of flaviviridae family enabled dissecting common mechanisms used for infections by these viruses. Conclusions Thus, using computational approach the present analysis has provided better insights into the preexisting low resolution structures of virus assemblies, the findings of which can be made use of in designing effective antivirals against these deadly human pathogens.

  1. Protein degradation and protection against misfolded or damaged proteins

    Science.gov (United States)

    Goldberg, Alfred L.

    2003-12-01

    The ultimate mechanism that cells use to ensure the quality of intracellular proteins is the selective destruction of misfolded or damaged polypeptides. In eukaryotic cells, the large ATP-dependent proteolytic machine, the 26S proteasome, prevents the accumulation of non-functional, potentially toxic proteins. This process is of particular importance in protecting cells against harsh conditions (for example, heat shock or oxidative stress) and in a variety of diseases (for example, cystic fibrosis and the major neurodegenerative diseases). A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded.

  2. Drosophila protein interaction map (DPiM): a paradigm for metazoan protein complex interactions.

    Science.gov (United States)

    Guruharsha, K G; Obar, Robert A; Mintseris, Julian; Aishwarya, K; Krishnan, R T; Vijayraghavan, K; Artavanis-Tsakonas, Spyros

    2012-01-01

    Proteins perform essential cellular functions as part of protein complexes, often in conjunction with RNA, DNA, metabolites and other small molecules. The genome encodes thousands of proteins but not all of them are expressed in every cell type; and expressed proteins are not active at all times. Such diversity of protein expression and function accounts for the level of biological intricacy seen in nature. Defining protein-protein interactions in protein complexes, and establishing the when, what and where of potential interactions, is therefore crucial to understanding the cellular function of any protein-especially those that have not been well studied by traditional molecular genetic approaches. We generated a large-scale resource of affinity-tagged expression-ready clones and used co-affinity purification combined with tandem mass-spectrometry to identify protein partners of nearly 5,000 Drosophila melanogaster proteins. The resulting protein complex "map" provided a blueprint of metazoan protein complex organization. Here we describe how the map has provided valuable insights into protein function in addition to generating hundreds of testable hypotheses. We also discuss recent technological advancements that will be critical in addressing the next generation of questions arising from the map.

  3. MicroProteins

    DEFF Research Database (Denmark)

    Eguen, Teinai Ebimienere; Straub, Daniel; Graeff, Moritz

    2015-01-01

    MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. Recent bioinformatic attempts to identify miPs have resulted in a list of potential miPs, many of which lack the defining...... characteristics of a miP. In this opinion article, we clearly state the characteristics of a miP as evidenced by known proteins that fit the definition; we explain why modulatory proteins misrepresented as miPs do not qualify as true miPs. We also discuss the evolutionary history of miPs, and how the miP concept...

  4. Non-interacting surface solvation and dynamics in protein-protein interactions

    NARCIS (Netherlands)

    Visscher, Koen M.; Kastritis, Panagiotis L.|info:eu-repo/dai/nl/315886668; Bonvin, Alexandre M J J|info:eu-repo/dai/nl/113691238

    2015-01-01

    Protein-protein interactions control a plethora of cellular processes, including cell proliferation, differentiation, apoptosis, and signal transduction. Understanding how and why proteins interact will inevitably lead to novel structure-based drug design methods, as well as design of de novo

  5. Occurrence of protein disulfide bonds in different domains of life: a comparison of proteins from the Protein Data Bank.

    Science.gov (United States)

    Bošnjak, I; Bojović, V; Šegvić-Bubić, T; Bielen, A

    2014-03-01

    Disulfide bonds (SS bonds) are important post-translational modifications of proteins. They stabilize a three-dimensional (3D) structure (structural SS bonds) and also have the catalytic or regulatory functions (redox-active SS bonds). Although SS bonds are present in all groups of organisms, no comparative analyses of their frequency in proteins from different domains of life have been made to date. Using the Protein Data Bank, the number and subcellular locations of SS bonds in Archaea, Bacteria and Eukarya have been compared. Approximately three times higher frequency of proteins with SS bonds in eukaryotic secretory organelles (e.g. endoplasmic reticulum) than in bacterial periplasmic/secretory pathways was calculated. Protein length also affects the SS bond frequency: the average number of SS bonds is positively correlated with the length for longer proteins (>200 amino acids), while for the shorter and less stable proteins (proteins (250-350 amino acids) indicated a high number of SS bonds only in Archaea which could be explained by the need for additional protein stabilization in hyperthermophiles. The results emphasize higher capacity for the SS bond formation and isomerization in Eukarya when compared with Archaea and Bacteria.

  6. Kinetic parameters of protein metabolism in rats during protein-free feeding

    International Nuclear Information System (INIS)

    Krawielitzki, K.; Schadereit, R.; Wuensche, J.

    1987-01-01

    16 male rats of 100 g live weight were given 50 mg of a mixture containing 15 N-labelled amino acids as a single dose within a protein-free feeding period. Following this the 15 N excretion in feces and urine as well as the development of the 15 N excess in different organs and tissues were estimated over 3 days by slaughtering the animals within given 7 time intervals. Using a 3 pool model and the computer program for the interpretation of 15 N tracer experiments by Toewe et al. (1984), kinetic parameters such as the rate of protein synthesis, protein breakdown and the rate of reutilization were calculated. Despite a negative N balance (- 41.8 mg N/d) under protein-free conditions the protein metabolism of the rat shows high dynamics characterized by a high flux rate (225 mg N/d) and a high rate of body protein synthesis (181 mg/d). The reutilization was 85 %. Depending on time the 15 N excess in the tested organs and tissues showed significant differences and seems to demonstrate that under these conditions protein synthesis mainly takes place in the most important organs (e.g. intestinal tract, liver). Under protein-free feeding conditions protein synthesis and protein breakdown of the whole body seems to be slightly increased in comparison to N balanced feeding conditions. (author)

  7. The role of electrostatics in protein-protein interactions of a monoclonal antibody.

    Science.gov (United States)

    Roberts, D; Keeling, R; Tracka, M; van der Walle, C F; Uddin, S; Warwicker, J; Curtis, R

    2014-07-07

    Understanding how protein-protein interactions depend on the choice of buffer, salt, ionic strength, and pH is needed to have better control over protein solution behavior. Here, we have characterized the pH and ionic strength dependence of protein-protein interactions in terms of an interaction parameter kD obtained from dynamic light scattering and the osmotic second virial coefficient B22 measured by static light scattering. A simplified protein-protein interaction model based on a Baxter adhesive potential and an electric double layer force is used to separate out the contributions of longer-ranged electrostatic interactions from short-ranged attractive forces. The ionic strength dependence of protein-protein interactions for solutions at pH 6.5 and below can be accurately captured using a Deryaguin-Landau-Verwey-Overbeek (DLVO) potential to describe the double layer forces. In solutions at pH 9, attractive electrostatics occur over the ionic strength range of 5-275 mM. At intermediate pH values (7.25 to 8.5), there is a crossover effect characterized by a nonmonotonic ionic strength dependence of protein-protein interactions, which can be rationalized by the competing effects of long-ranged repulsive double layer forces at low ionic strength and a shorter ranged electrostatic attraction, which dominates above a critical ionic strength. The change of interactions from repulsive to attractive indicates a concomitant change in the angular dependence of protein-protein interaction from isotropic to anisotropic. In the second part of the paper, we show how the Baxter adhesive potential can be used to predict values of kD from fitting to B22 measurements, thus providing a molecular basis for the linear correlation between the two protein-protein interaction parameters.

  8. Scoring functions for protein-protein interactions.

    Science.gov (United States)

    Moal, Iain H; Moretti, Rocco; Baker, David; Fernández-Recio, Juan

    2013-12-01

    The computational evaluation of protein-protein interactions will play an important role in organising the wealth of data being generated by high-throughput initiatives. Here we discuss future applications, report recent developments and identify areas requiring further investigation. Many functions have been developed to quantify the structural and energetic properties of interacting proteins, finding use in interrelated challenges revolving around the relationship between sequence, structure and binding free energy. These include loop modelling, side-chain refinement, docking, multimer assembly, affinity prediction, affinity change upon mutation, hotspots location and interface design. Information derived from models optimised for one of these challenges can be used to benefit the others, and can be unified within the theoretical frameworks of multi-task learning and Pareto-optimal multi-objective learning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Pierced Lasso Proteins

    Science.gov (United States)

    Jennings, Patricia

    Entanglement and knots are naturally occurring, where, in the microscopic world, knots in DNA and homopolymers are well characterized. The most complex knots are observed in proteins which are harder to investigate, as proteins are heteropolymers composed of a combination of 20 different amino acids with different individual biophysical properties. As new-knotted topologies and new proteins containing knots continue to be discovered and characterized, the investigation of knots in proteins has gained intense interest. Thus far, the principle focus has been on the evolutionary origin of tying a knot, with questions of how a protein chain `self-ties' into a knot, what the mechanism(s) are that contribute to threading, and the biological relevance and functional implication of a knotted topology in vivo gaining the most insight. Efforts to study the fully untied and unfolded chain indicate that the knot is highly stable, remaining intact in the unfolded state orders of magnitude longer than first anticipated. The persistence of ``stable'' knots in the unfolded state, together with the challenge of defining an unfolded and untied chain from an unfolded and knotted chain, complicates the study of fully untied protein in vitro. Our discovery of a new class of knotted proteins, the Pierced Lassos (PL) loop topology, simplifies the knotting approach. While PLs are not easily recognizable by the naked eye, they have now been identified in many proteins in the PDB through the use of computation tools. PL topologies are diverse proteins found in all kingdoms of life, performing a large variety of biological responses such as cell signaling, immune responses, transporters and inhibitors (http://lassoprot.cent.uw.edu.pl/). Many of these PL topologies are secreted proteins, extracellular proteins, as well as, redox sensors, enzymes and metal and co-factor binding proteins; all of which provide a favorable environment for the formation of the disulphide bridge. In the PL

  10. The E5 Proteins

    OpenAIRE

    DiMaio, Daniel; Petti, Lisa

    2013-01-01

    The E5 proteins are short transmembrane proteins encoded by many animal and human papillomaviruses. These proteins display transforming activity in cultured cells and animals, and they presumably also play a role in the productive virus life cycle. The E5 proteins are thought to act by modulating the activity of cellular proteins. Here, we describe the biological activities of the best-studied E5 proteins and discuss the evidence implicating specific protein targets and pathways in mediating ...

  11. Analysis of the protein-protein interactions between the human acidic ribosomal P-proteins: evaluation by the two hybrid system

    DEFF Research Database (Denmark)

    Tchórzewski, M; Boldyreff, B; Issinger, O

    2000-01-01

    The surface acidic ribosomal proteins (P-proteins), together with ribosomal core protein P0 form a multimeric lateral protuberance on the 60 S ribosomal subunit. This structure, also called stalk, is important for efficient translational activity of the ribosome. In order to shed more light...... forms the 60 S ribosomal stalk: P0-(P1/P2)(2). Additionally, mutual interactions among human and yeast P-proteins were analyzed. Heterodimer formation could be observed between human P2 and yeast P1 proteins....

  12. Protein-protein interface detection using the energy centrality relationship (ECR characteristic of proteins.

    Directory of Open Access Journals (Sweden)

    Sanjana Sudarshan

    Full Text Available Specific protein interactions are responsible for most biological functions. Distinguishing Functionally Linked Interfaces of Proteins (FLIPs, from Functionally uncorrelated Contacts (FunCs, is therefore important to characterizing these interactions. To achieve this goal, we have created a database of protein structures called FLIPdb, containing proteins belonging to various functional sub-categories. Here, we use geometric features coupled with Kortemme and Baker's computational alanine scanning method to calculate the energetic sensitivity of each amino acid at the interface to substitution, identify hotspots, and identify other factors that may contribute towards an interface being FLIP or FunC. Using Principal Component Analysis and K-means clustering on a training set of 160 interfaces, we could distinguish FLIPs from FunCs with an accuracy of 76%. When these methods were applied to two test sets of 18 and 170 interfaces, we achieved similar accuracies of 78% and 80%. We have identified that FLIP interfaces have a stronger central organizing tendency than FunCs, due, we suggest, to greater specificity. We also observe that certain functional sub-categories, such as enzymes, antibody-heavy-light, antibody-antigen, and enzyme-inhibitors form distinct sub-clusters. The antibody-antigen and enzyme-inhibitors interfaces have patterns of physical characteristics similar to those of FunCs, which is in agreement with the fact that the selection pressures of these interfaces is differently evolutionarily driven. As such, our ECR model also successfully describes the impact of evolution and natural selection on protein-protein interfaces. Finally, we indicate how our ECR method may be of use in reducing the false positive rate of docking calculations.

  13. Variation in Protein and Calorie Consumption Following Protein Malnutrition in Rattus norvegicus

    Science.gov (United States)

    Jones, Donna C.; German, Rebecca Z.

    2013-01-01

    Simple Summary Catch-up growth following malnutrition is likely influenced by available protein and calories. We measured calorie and protein consumption following the removal of protein malnutrition after 40, 60 and 90 days, in laboratory rats. Following the transition in diet, animals self-selected fewer calories, implying elevated protein is sufficient to fuel catch-up growth, eventually resulting in body weights and bone lengths greater or equal to those of control animals. Rats rehabilitated at younger ages, had more drastic alterations in consumption. Variable responses in different ages and sex highlight the plasticity of growth and how nutrition affects body form. This work furthers our understanding of how humans and livestock can recover from protein-restriction malnutrition, which seems to employ different biological responses. Abstract Catch-up growth rates, following protein malnutrition, vary with timing and duration of insult, despite unlimited access to calories. Understanding changing patterns of post-insult consumption, relative rehabilitation timing, can provide insight into the mechanisms driving those differences. We hypothesize that higher catch-up growth rates will be correlated with increased protein consumption, while calorie consumption could remain stable. As catch-up growth rates decrease with age/malnutrition duration, we predict a dose effect in protein consumption with rehabilitation timing. We measured total and protein consumption, body mass, and long bone length, following an increase of dietary protein at 40, 60 and 90 days, with two control groups (chronic reduced protein or standard protein) for 150+ days. Immediately following rehabilitation, rats’ food consumption decreased significantly, implying that elevated protein intake is sufficient to fuel catch-up growth rates that eventually result in body weights and long bone lengths greater or equal to final measures of chronically fed standard (CT) animals. The duration of

  14. Protein domain recurrence and order can enhance prediction of protein functions

    KAUST Repository

    Abdel Messih, Mario A.

    2012-09-07

    Motivation: Burgeoning sequencing technologies have generated massive amounts of genomic and proteomic data. Annotating the functions of proteins identified in this data has become a big and crucial problem. Various computational methods have been developed to infer the protein functions based on either the sequences or domains of proteins. The existing methods, however, ignore the recurrence and the order of the protein domains in this function inference. Results: We developed two new methods to infer protein functions based on protein domain recurrence and domain order. Our first method, DRDO, calculates the posterior probability of the Gene Ontology terms based on domain recurrence and domain order information, whereas our second method, DRDO-NB, relies on the nave Bayes methodology using the same domain architecture information. Our large-scale benchmark comparisons show strong improvements in the accuracy of the protein function inference achieved by our new methods, demonstrating that domain recurrence and order can provide important information for inference of protein functions. The Author(s) 2012. Published by Oxford University Press.

  15. Impact of protein uptake and degradation on recombinant protein secretion in yeast

    DEFF Research Database (Denmark)

    Tyo, Keith E. J.; Liu, Zihe; Magnusson, Ylva

    2014-01-01

    Protein titers, a key bioprocessing metric, depend both on the synthesis of protein and the degradation of protein. Secreted recombinant protein production in Saccharomyces cerevisiae is an attractive platform as minimal media can be used for cultivation, thus reducing fermentation costs...... and transcriptomics, we identify metabolic and regulatory markers that are consistent with uptake of whole proteins by endocytosis, followed by intracellular degradation and catabolism of substituent amino acids. Uptake and degradation of recombinant protein products may be common in S. cerevisiae protein secretion...... and simplifying downstream purification, compared to other systems that require complex media. As such, engineering S. cerevisiae to improve titers has been then the subject of significant attention, but the majority of previous efforts have been focused on improving protein synthesis. Here, we characterize...

  16. Polymer Directed Protein Assemblies

    Directory of Open Access Journals (Sweden)

    Patrick van Rijn

    2013-05-01

    Full Text Available Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This “biopolymer” directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

  17. Nutritional geometry: gorillas prioritize non-protein energy while consuming surplus protein.

    Science.gov (United States)

    Rothman, Jessica M; Raubenheimer, David; Chapman, Colin A

    2011-12-23

    It is widely assumed that terrestrial food webs are built on a nitrogen-limited base and consequently herbivores must compensate through selection of high-protein foods and efficient nitrogen retention. Like many folivorous primates, gorillas' diet selection supports this assumption, as they apparently prefer protein-rich foods. Our study of mountain gorillas (Gorilla beringei) in Uganda revealed that, in some periods, carbohydrate-rich fruits displace a large portion of protein-rich leaves in their diet. We show that non-protein energy (NPE) intake was invariant throughout the year, whereas protein intake was substantially higher when leaves were the major portion of the diet. This pattern of macronutrient intake suggests that gorillas prioritize NPE and, to achieve this when leaves are the major dietary item, they over-eat protein. The concentrations of protein consumed in relation to energy when leaves were the major portion of the diet were close to the maximum recommended for humans and similar to high-protein human weight-loss diets. By contrast, the concentrations of protein in relation to energy when gorillas ate fruit-dominated diets were similar to those recommended for humans. Our results question the generality of nitrogen limitation in terrestrial herbivores and provide a fascinating contrast with human macronutrient intake.

  18. Nutritional geometry: gorillas prioritize non-protein energy while consuming surplus protein

    Science.gov (United States)

    Rothman, Jessica M.; Raubenheimer, David; Chapman, Colin A.

    2011-01-01

    It is widely assumed that terrestrial food webs are built on a nitrogen-limited base and consequently herbivores must compensate through selection of high-protein foods and efficient nitrogen retention. Like many folivorous primates, gorillas' diet selection supports this assumption, as they apparently prefer protein-rich foods. Our study of mountain gorillas (Gorilla beringei) in Uganda revealed that, in some periods, carbohydrate-rich fruits displace a large portion of protein-rich leaves in their diet. We show that non-protein energy (NPE) intake was invariant throughout the year, whereas protein intake was substantially higher when leaves were the major portion of the diet. This pattern of macronutrient intake suggests that gorillas prioritize NPE and, to achieve this when leaves are the major dietary item, they over-eat protein. The concentrations of protein consumed in relation to energy when leaves were the major portion of the diet were close to the maximum recommended for humans and similar to high-protein human weight-loss diets. By contrast, the concentrations of protein in relation to energy when gorillas ate fruit-dominated diets were similar to those recommended for humans. Our results question the generality of nitrogen limitation in terrestrial herbivores and provide a fascinating contrast with human macronutrient intake. PMID:21632622

  19. Detecting protein-protein interactions in the intact cell of Bacillus subtilis (ATCC 6633).

    Science.gov (United States)

    Winters, Michael S; Day, R A

    2003-07-01

    The salt bridge, paired group-specific reagent cyanogen (ethanedinitrile; C(2)N(2)) converts naturally occurring pairs of functional groups into covalently linked products. Cyanogen readily permeates cell walls and membranes. When the paired groups are shared between associated proteins, isolation of the covalently linked proteins allows their identity to be assigned. Examination of organisms of known genome sequence permits identification of the linked proteins by mass spectrometric techniques applied to peptides derived from them. The cyanogen-linked proteins were isolated by polyacrylamide gel electrophoresis. Digestion of the isolated proteins with proteases of known specificity afforded sets of peptides that could be analyzed by mass spectrometry. These data were compared with those derived theoretically from the Swiss Protein Database by computer-based comparisons (Protein Prospector; http://prospector.ucsf.edu). Identification of associated proteins in the ribosome of Bacillus subtilis strain ATCC 6633 showed that there is an association homology with the association patterns of the ribosomal proteins of Haloarcula marismortui and Thermus thermophilus. In addition, other proteins involved in protein biosynthesis were shown to be associated with ribosomal proteins.

  20. Hubungan antara konsumsi protein dengan produksi, protein dan laktosa susu kambing Peranakan Ettawa

    Directory of Open Access Journals (Sweden)

    Galuh Estu Prihatiningsih

    2015-09-01

    Full Text Available The study aimed to determine a correlation between crude protein intake, milk production, milk protein and milk lactose. This study used purposive sampling method. The sample used in this study were 35 Etawa crossbred goats with months of lactation 4-5 and lactation periods 2-3. Parameters observed were crude protein intake, milk production, milk protein and milk lactose. Data were analyzed using correlation analysis and simple linear regression. The result showed that crude protein intake, total milk production concentrations of milk protein and lactose were 0.77 kg/day; 0.30 kg/day; 0.196% and 3.32% respectively. There was a medium positive linear correlation between the crude protein intake with total milk production, protein and lactose content of milk. The correlation coefficient (r were 0.258; 0.254 and 0,255 respectively. It could be concluded that the higher crude protein intake would increase the amount of milk production, protein and lactose contents. Keywords: crude protein intake, total milk production, milk protein, milk lactose

  1. Protein-losing enteropathy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007338.htm Protein-losing enteropathy To use the sharing features on this page, please enable JavaScript. Protein-losing enteropathy is an abnormal loss of protein ...

  2. ProteinSplit: splitting of multi-domain proteins using prediction of ordered and disordered regions in protein sequences for virtual structural genomics

    International Nuclear Information System (INIS)

    Wyrwicz, Lucjan S; Koczyk, Grzegorz; Rychlewski, Leszek; Plewczynski, Dariusz

    2007-01-01

    The annotation of protein folds within newly sequenced genomes is the main target for semi-automated protein structure prediction (virtual structural genomics). A large number of automated methods have been developed recently with very good results in the case of single-domain proteins. Unfortunately, most of these automated methods often fail to properly predict the distant homology between a given multi-domain protein query and structural templates. Therefore a multi-domain protein should be split into domains in order to overcome this limitation. ProteinSplit is designed to identify protein domain boundaries using a novel algorithm that predicts disordered regions in protein sequences. The software utilizes various sequence characteristics to assess the local propensity of a protein to be disordered or ordered in terms of local structure stability. These disordered parts of a protein are likely to create interdomain spacers. Because of its speed and portability, the method was successfully applied to several genome-wide fold annotation experiments. The user can run an automated analysis of sets of proteins or perform semi-automated multiple user projects (saving the results on the server). Additionally the sequences of predicted domains can be sent to the Bioinfo.PL Protein Structure Prediction Meta-Server for further protein three-dimensional structure and function prediction. The program is freely accessible as a web service at http://lucjan.bioinfo.pl/proteinsplit together with detailed benchmark results on the critical assessment of a fully automated structure prediction (CAFASP) set of sequences. The source code of the local version of protein domain boundary prediction is available upon request from the authors

  3. Interplay between chaperones and protein disorder promotes the evolution of protein networks.

    Directory of Open Access Journals (Sweden)

    Sebastian Pechmann

    2014-06-01

    Full Text Available Evolution is driven by mutations, which lead to new protein functions but come at a cost to protein stability. Non-conservative substitutions are of interest in this regard because they may most profoundly affect both function and stability. Accordingly, organisms must balance the benefit of accepting advantageous substitutions with the possible cost of deleterious effects on protein folding and stability. We here examine factors that systematically promote non-conservative mutations at the proteome level. Intrinsically disordered regions in proteins play pivotal roles in protein interactions, but many questions regarding their evolution remain unanswered. Similarly, whether and how molecular chaperones, which have been shown to buffer destabilizing mutations in individual proteins, generally provide robustness during proteome evolution remains unclear. To this end, we introduce an evolutionary parameter λ that directly estimates the rate of non-conservative substitutions. Our analysis of λ in Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens sequences reveals how co- and post-translationally acting chaperones differentially promote non-conservative substitutions in their substrates, likely through buffering of their destabilizing effects. We further find that λ serves well to quantify the evolution of intrinsically disordered proteins even though the unstructured, thus generally variable regions in proteins are often flanked by very conserved sequences. Crucially, we show that both intrinsically disordered proteins and highly re-wired proteins in protein interaction networks, which have evolved new interactions and functions, exhibit a higher λ at the expense of enhanced chaperone assistance. Our findings thus highlight an intricate interplay of molecular chaperones and protein disorder in the evolvability of protein networks. Our results illuminate the role of chaperones in enabling protein evolution, and underline the

  4. Function and structure of GFP-like proteins in the protein data bank.

    Science.gov (United States)

    Ong, Wayne J-H; Alvarez, Samuel; Leroux, Ivan E; Shahid, Ramza S; Samma, Alex A; Peshkepija, Paola; Morgan, Alicia L; Mulcahy, Shawn; Zimmer, Marc

    2011-04-01

    The RCSB protein databank contains 266 crystal structures of green fluorescent proteins (GFP) and GFP-like proteins. This is the first systematic analysis of all the GFP-like structures in the pdb. We have used the pdb to examine the function of fluorescent proteins (FP) in nature, aspects of excited state proton transfer (ESPT) in FPs, deformation from planarity of the chromophore and chromophore maturation. The conclusions reached in this review are that (1) The lid residues are highly conserved, particularly those on the "top" of the β-barrel. They are important to the function of GFP-like proteins, perhaps in protecting the chromophore or in β-barrel formation. (2) The primary/ancestral function of GFP-like proteins may well be to aid in light induced electron transfer. (3) The structural prerequisites for light activated proton pumps exist in many structures and it's possible that like bioluminescence, proton pumps are secondary functions of GFP-like proteins. (4) In most GFP-like proteins the protein matrix exerts a significant strain on planar chromophores forcing most GFP-like proteins to adopt non-planar chromophores. These chromophoric deviations from planarity play an important role in determining the fluorescence quantum yield. (5) The chemospatial characteristics of the chromophore cavity determine the isomerization state of the chromophore. The cavities of highlighter proteins that can undergo cis/trans isomerization have chemospatial properties that are common to both cis and trans GFP-like proteins.

  5. Protein-protein docking with dynamic residue protonation states.

    Directory of Open Access Journals (Sweden)

    Krishna Praneeth Kilambi

    2014-12-01

    Full Text Available Protein-protein interactions depend on a host of environmental factors. Local pH conditions influence the interactions through the protonation states of the ionizable residues that can change upon binding. In this work, we present a pH-sensitive docking approach, pHDock, that can sample side-chain protonation states of five ionizable residues (Asp, Glu, His, Tyr, Lys on-the-fly during the docking simulation. pHDock produces successful local docking funnels in approximately half (79/161 the protein complexes, including 19 cases where standard RosettaDock fails. pHDock also performs better than the two control cases comprising docking at pH 7.0 or using fixed, predetermined protonation states. On average, the top-ranked pHDock structures have lower interface RMSDs and recover more native interface residue-residue contacts and hydrogen bonds compared to RosettaDock. Addition of backbone flexibility using a computationally-generated conformational ensemble further improves native contact and hydrogen bond recovery in the top-ranked structures. Although pHDock is designed to improve docking, it also successfully predicts a large pH-dependent binding affinity change in the Fc-FcRn complex, suggesting that it can be exploited to improve affinity predictions. The approaches in the study contribute to the goal of structural simulations of whole-cell protein-protein interactions including all the environmental factors, and they can be further expanded for pH-sensitive protein design.

  6. Protein scissors: Photocleavage of proteins at specific locations

    Indian Academy of Sciences (India)

    Unknown

    Binding of ligands to globular proteins at hydrophobic cavities while making specific ... ched to a PTI model A1010 monochromator. UV cut-off filter ..... >1:1 stoichiometry (protein to ligand), the binding equilibrium favors the thermo- dynamically ...

  7. Identifying Hierarchical and Overlapping Protein Complexes Based on Essential Protein-Protein Interactions and “Seed-Expanding” Method

    Directory of Open Access Journals (Sweden)

    Jun Ren

    2014-01-01

    Full Text Available Many evidences have demonstrated that protein complexes are overlapping and hierarchically organized in PPI networks. Meanwhile, the large size of PPI network wants complex detection methods have low time complexity. Up to now, few methods can identify overlapping and hierarchical protein complexes in a PPI network quickly. In this paper, a novel method, called MCSE, is proposed based on λ-module and “seed-expanding.” First, it chooses seeds as essential PPIs or edges with high edge clustering values. Then, it identifies protein complexes by expanding each seed to a λ-module. MCSE is suitable for large PPI networks because of its low time complexity. MCSE can identify overlapping protein complexes naturally because a protein can be visited by different seeds. MCSE uses the parameter λ_th to control the range of seed expanding and can detect a hierarchical organization of protein complexes by tuning the value of λ_th. Experimental results of S. cerevisiae show that this hierarchical organization is similar to that of known complexes in MIPS database. The experimental results also show that MCSE outperforms other previous competing algorithms, such as CPM, CMC, Core-Attachment, Dpclus, HC-PIN, MCL, and NFC, in terms of the functional enrichment and matching with known protein complexes.

  8. Defective Proteasome Delivery of Polyubiquitinated Proteins by Ubiquilin-2 Proteins Containing ALS Mutations.

    Directory of Open Access Journals (Sweden)

    Lydia Chang

    Full Text Available Ubiquilin proteins facilitate delivery of ubiquitinated proteins to the proteasome for degradation. Interest in the proteins has been heightened by the discovery that gene mutations in UBQLN2 cause dominant inheritance of amyotrophic lateral sclerosis (ALS. However, the mechanisms by which the mutations cause ALS are not known. Here we report on the underlying defect of ubiquilin-2 proteins containing ALS-linked mutations in affecting proteasome-mediated degradation. We found that overexpression of ubiquilin-2 proteins containing any one of five different ALS mutations slow degradation of Myc, a prototypic proteasome substrate. Examination of coprecipitating proteins indicated that the mutant proteins are generally capable of binding polyubiquitinated proteins, but defective in binding the proteasome. GST-pulldown studies revealed that many of the mutants bind weaker to the S5a subunit of the proteasome, compared with wild type (WT ubiquilin-2 protein. The results suggest the mutant proteins are unable to deliver their captured cargo to the proteasome for degradation, which presumably leads to toxicity. Quantification of cell death is consistent with this idea. Measurement of protein turnover further indicated the mutant proteins have longer half-lives than WT ubiquilin-2. Our studies provide novel insight into the mechanism by which ALS-linked mutations in UBQLN2 interfere with protein degradation.

  9. Analysis of protein folds using protein contact networks

    Indian Academy of Sciences (India)

    is a well-recognized classification system of proteins, which is based on manual in- ... can easily correspond to the information in the 2D matrix. ..... [7] U K Muppirala and Zhijun Li, Protein Engineering, Design & Selection 19, 265 (2006).

  10. Improved segmental isotope labeling of proteins and application to a larger protein

    International Nuclear Information System (INIS)

    Otomo, Takanori; Teruya, Kenta; Uegaki, Koichi; Yamazaki, Toshio; Kyogoku, Yoshimasa

    1999-01-01

    A new isotope labeling technique for peptide segments in a protein sample was recently established using the protein splicing element intein [Yamazaki et al. (1998) J. Am. Chem. Soc., 120, 5591-5592]. This method makes it possible to observe signals of a selected amino (N-) or carboxyl (C-) terminal region along a peptide chain. However, there is a problem with the yield of the segmentally labeled protein. In this paper, we report an increase in the yield of the protein that enables the production of sufficient amounts of segmentally 13 C/ 15 N-labeled protein samples. This was achieved by improvement of the expression level of the N-terminal fragment in cells and the efficiency of refolding into the active splicing conformation. The N-terminal fragment was expressed as a fused protein with the cellulose binding domain at its N-terminus, which was expressed as an insoluble peptide in cells and the expression level was increased. Incubation with 2.5 M urea and 50% glycerol increased the efficiency of the refolding greatly, thereby raising the final yields of the ligated proteins. The feasibility of application of the method to a high-molecular-weight protein was demonstrated by the results for a maltose binding protein consisting of 370 amino acids. All four examined joints in the maltose binding protein were successfully ligated to produce segmentally labeled protein samples

  11. Protein in diet

    Science.gov (United States)

    Diet - protein ... Protein foods are broken down into parts called amino acids during digestion. The human body needs a ... to eat animal products to get all the protein you need in your diet. Amino acids are ...

  12. An analysis pipeline for the inference of protein-protein interaction networks

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Ronald C.; Singhal, Mudita; Daly, Don S.; Gilmore, Jason M.; Cannon, William R.; Domico, Kelly O.; White, Amanda M.; Auberry, Deanna L.; Auberry, Kenneth J.; Hooker, Brian S.; Hurst, G. B.; McDermott, Jason E.; McDonald, W. H.; Pelletier, Dale A.; Schmoyer, Denise A.; Wiley, H. S.

    2009-12-01

    An analysis pipeline has been created for deployment of a novel algorithm, the Bayesian Estimator of Protein-Protein Association Probabilities (BEPro), for use in the reconstruction of protein-protein interaction networks. We have combined the Software Environment for BIological Network Inference (SEBINI), an interactive environment for the deployment and testing of network inference algorithms that use high-throughput data, and the Collective Analysis of Biological Interaction Networks (CABIN), software that allows integration and analysis of protein-protein interaction and gene-to-gene regulatory evidence obtained from multiple sources, to allow interactions computed by BEPro to be stored, visualized, and further analyzed. Incorporating BEPro into SEBINI and automatically feeding the resulting inferred network into CABIN, we have created a structured workflow for protein-protein network inference and supplemental analysis from sets of mass spectrometry bait-prey experiment data. SEBINI demo site: https://www.emsl.pnl.gov /SEBINI/ Contact: ronald.taylor@pnl.gov. BEPro is available at http://www.pnl.gov/statistics/BEPro3/index.htm. Contact: ds.daly@pnl.gov. CABIN is available at http://www.sysbio.org/dataresources/cabin.stm. Contact: mudita.singhal@pnl.gov.

  13. Link Performance Analysis and monitoring - A unified approach to divergent requirements

    Science.gov (United States)

    Thom, G. A.

    Link Performance Analysis and real-time monitoring are generally covered by a wide range of equipment. Bit Error Rate testers provide digital link performance measurements but are not useful during real-time data flows. Real-time performance monitors utilize the fixed overhead content but vary widely from format to format. Link quality information is also present from signal reconstruction equipment in the form of receiver AGC, bit synchronizer AGC, and bit synchronizer soft decision level outputs, but no general approach to utilizing this information exists. This paper presents an approach to link tests, real-time data quality monitoring, and results presentation that utilizes a set of general purpose modules in a flexible architectural environment. The system operates over a wide range of bit rates (up to 150 Mbs) and employs several measurement techniques, including P/N code errors or fixed PCM format errors, derived real-time BER from frame sync errors, and Data Quality Analysis derived by counting significant sync status changes. The architecture performs with a minimum of elements in place to permit a phased update of the user's unit in accordance with his needs.

  14. Switched Control Strategies of Aggregated Commercial HVAC Systems for Demand Response in Smart Grids

    Directory of Open Access Journals (Sweden)

    Kai Ma

    2017-07-01

    Full Text Available This work proposes three switched control strategies for aggregated heating, ventilation, and air conditioning (HVAC systems in commercial buildings to track the automatic generation control (AGC signal in smart grid. The existing control strategies include the direct load control strategy and the setpoint regulation strategy. The direct load control strategy cannot track the AGC signal when the state of charge (SOC of the aggregated thermostatically controlled loads (TCLs exceeds their regulation capacity, while the setpoint regulation strategy provides flexible regulation capacity, but causes larger tracking errors. To improve the tracking performance, we took the advantages of the two control modes and developed three switched control strategies. The control strategies switch between the direct load control mode and the setpoint regulation mode according to different switching indices. Specifically, we design a discrete-time controller and optimize the controller parameter for the setpoint regulation strategy using the Fibonacci optimization algorithm, enabling us to propose two switched control strategies across multiple time steps. Furthermore, we extend the switched control strategies by introducing a two-stage regulation in a single time step. Simulation results demonstrate that the proposed switched control strategies can reduce the tracking errors for frequency regulation.

  15. Performance of PCR-reverse blot hybridization assay for detection of rifampicin-resistant Mycobacterium leprae.

    Science.gov (United States)

    Wang, Hye-young; Kim, Hyunjung; Kim, Yeun; Bang, Hyeeun; Kim, Jong-Pill; Hwang, Joo Hwan; Cho, Sang-Nae; Kim, Tae Ue; Lee, Hyeyoung

    2015-10-01

    Drug resistance in Mycobacterium leprae is a significant problem in countries where leprosy is endemic. A sensitive, specific, and high-throughput reverse blot hybridization assay (REBA) for the detection of genotypic resistance to rifampicin (RIF) was designed and evaluated. It has been shown that resistance to RIF in M. leprae involves mutations in the rpoB gene encoding the -subunit of the RNA polymerase. The PCR-REBA simultaneously detects both 6 wild-type regions and 5 different mutations (507 AGC, 513 GTG, 516 TAT, 531 ATG, and 531 TTC) including the most prevalent mutations at positions 507 and 531. Thirty-one clinical isolates provided by Korea Institute of Hansen-s Disease were analyzed by PCR-REBA with RIF resistance of rpoB gene. As a result, missense mutations at codons 507 AGC and 531 ATG with 2-nucleotide substitutions were found in one sample, and a missense mutation at codon 516 TAT and ΔWT6 (deletion of 530-534) was found in another sample. These cases were confirmed by DNA sequence analysis. This rapid, simple, and highly sensitive assay provides a practical alternative to sequencing for genotypic evaluation of RIF resistance in M. leprae.

  16. [RS estimation of inventory parameters and carbon storage of moso bamboo forest based on synergistic use of object-based image analysis and decision tree].

    Science.gov (United States)

    Du, Hua Qiang; Sun, Xiao Yan; Han, Ning; Mao, Fang Jie

    2017-10-01

    By synergistically using the object-based image analysis (OBIA) and the classification and regression tree (CART) methods, the distribution information, the indexes (including diameter at breast, tree height, and crown closure), and the aboveground carbon storage (AGC) of moso bamboo forest in Shanchuan Town, Anji County, Zhejiang Province were investigated. The results showed that the moso bamboo forest could be accurately delineated by integrating the multi-scale ima ge segmentation in OBIA technique and CART, which connected the image objects at various scales, with a pretty good producer's accuracy of 89.1%. The investigation of indexes estimated by regression tree model that was constructed based on the features extracted from the image objects reached normal or better accuracy, in which the crown closure model archived the best estimating accuracy of 67.9%. The estimating accuracy of diameter at breast and tree height was relatively low, which was consistent with conclusion that estimating diameter at breast and tree height using optical remote sensing could not achieve satisfactory results. Estimation of AGC reached relatively high accuracy, and accuracy of the region of high value achieved above 80%.

  17. A new protein-protein interaction sensor based on tripartite split-GFP association.

    Science.gov (United States)

    Cabantous, Stéphanie; Nguyen, Hau B; Pedelacq, Jean-Denis; Koraïchi, Faten; Chaudhary, Anu; Ganguly, Kumkum; Lockard, Meghan A; Favre, Gilles; Terwilliger, Thomas C; Waldo, Geoffrey S

    2013-10-04

    Monitoring protein-protein interactions in living cells is key to unraveling their roles in numerous cellular processes and various diseases. Previously described split-GFP based sensors suffer from poor folding and/or self-assembly background fluorescence. Here, we have engineered a micro-tagging system to monitor protein-protein interactions in vivo and in vitro. The assay is based on tripartite association between two twenty amino-acids long GFP tags, GFP10 and GFP11, fused to interacting protein partners, and the complementary GFP1-9 detector. When proteins interact, GFP10 and GFP11 self-associate with GFP1-9 to reconstitute a functional GFP. Using coiled-coils and FRB/FKBP12 model systems we characterize the sensor in vitro and in Escherichia coli. We extend the studies to mammalian cells and examine the FK-506 inhibition of the rapamycin-induced association of FRB/FKBP12. The small size of these tags and their minimal effect on fusion protein behavior and solubility should enable new experiments for monitoring protein-protein association by fluorescence.

  18. Prediction of protein-protein interactions between viruses and human by an SVM model

    Directory of Open Access Journals (Sweden)

    Cui Guangyu

    2012-05-01

    Full Text Available Abstract Background Several computational methods have been developed to predict protein-protein interactions from amino acid sequences, but most of those methods are intended for the interactions within a species rather than for interactions across different species. Methods for predicting interactions between homogeneous proteins are not appropriate for finding those between heterogeneous proteins since they do not distinguish the interactions between proteins of the same species from those of different species. Results We developed a new method for representing a protein sequence of variable length in a frequency vector of fixed length, which encodes the relative frequency of three consecutive amino acids of a sequence. We built a support vector machine (SVM model to predict human proteins that interact with virus proteins. In two types of viruses, human papillomaviruses (HPV and hepatitis C virus (HCV, our SVM model achieved an average accuracy above 80%, which is higher than that of another SVM model with a different representation scheme. Using the SVM model and Gene Ontology (GO annotations of proteins, we predicted new interactions between virus proteins and human proteins. Conclusions Encoding the relative frequency of amino acid triplets of a protein sequence is a simple yet powerful representation method for predicting protein-protein interactions across different species. The representation method has several advantages: (1 it enables a prediction model to achieve a better performance than other representations, (2 it generates feature vectors of fixed length regardless of the sequence length, and (3 the same representation is applicable to different types of proteins.

  19. IGSF9 Family Proteins

    DEFF Research Database (Denmark)

    Hansen, Maria; Walmod, Peter Schledermann

    2013-01-01

    The Drosophila protein Turtle and the vertebrate proteins immunoglobulin superfamily (IgSF), member 9 (IGSF9/Dasm1) and IGSF9B are members of an evolutionarily ancient protein family. A bioinformatics analysis of the protein family revealed that invertebrates contain only a single IGSF9 family gene......, the longest isoforms of the proteins have the same general organization as the neural cell adhesion molecule family of cell adhesion molecule proteins, and like this family of proteins, IGSF9 family members are expressed in the nervous system. A review of the literature revealed that Drosophila Turtle...... facilitates homophilic cell adhesion. Moreover, IGSF9 family proteins have been implicated in the outgrowth and branching of neurites, axon guidance, synapse maturation, self-avoidance, and tiling. However, despite the few published studies on IGSF9 family proteins, reports on the functions of both Turtle...

  20. A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces

    NARCIS (Netherlands)

    Melo, Rita; Fieldhouse, Robert; Melo, André; Correia, João D G; Cordeiro, Maria Natália D S; Gümüş, Zeynep H; Costa, Joaquim; Bonvin, Alexandre M J J; de Sousa Moreira, Irina

    2016-01-01

    Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model

  1. Factor VII and protein C are phosphatidic acid-binding proteins.

    Science.gov (United States)

    Tavoosi, Narjes; Smith, Stephanie A; Davis-Harrison, Rebecca L; Morrissey, James H

    2013-08-20

    Seven proteins in the human blood clotting cascade bind, via their GLA (γ-carboxyglutamate-rich) domains, to membranes containing exposed phosphatidylserine (PS), although with membrane binding affinities that vary by 3 orders of magnitude. Here we employed nanodiscs of defined phospholipid composition to quantify the phospholipid binding specificities of these seven clotting proteins. All bound preferentially to nanobilayers in which PS headgroups contained l-serine versus d-serine. Surprisingly, however, nanobilayers containing phosphatidic acid (PA) bound substantially more of two of these proteins, factor VIIa and activated protein C, than did equivalent bilayers containing PS. Consistent with this finding, liposomes containing PA supported higher proteolytic activity by factor VIIa and activated protein C toward their natural substrates (factors X and Va, respectively) than did PS-containing liposomes. Moreover, treating activated human platelets with phospholipase D enhanced the rates of factor X activation by factor VIIa in the presence of soluble tissue factor. We hypothesize that factor VII and protein C bind preferentially to the monoester phosphate of PA because of its accessibility and higher negative charge compared with the diester phosphates of most other phospholipids. We further found that phosphatidylinositol 4-phosphate, which contains a monoester phosphate attached to its myo-inositol headgroup, also supported enhanced enzymatic activity of factor VIIa and activated protein C. We conclude that factor VII and protein C bind preferentially to monoester phosphates, which may have implications for the function of these proteases in vivo.

  2. High Dietary Protein Intake and Protein-Related Acid Load on Bone Health.

    Science.gov (United States)

    Cao, Jay J

    2017-12-01

    Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent clinical research assessing dietary protein on calcium metabolism and bone health. Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake. Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system.

  3. HomPPI: a class of sequence homology based protein-protein interface prediction methods

    Directory of Open Access Journals (Sweden)

    Dobbs Drena

    2011-06-01

    Full Text Available Abstract Background Although homology-based methods are among the most widely used methods for predicting the structure and function of proteins, the question as to whether interface sequence conservation can be effectively exploited in predicting protein-protein interfaces has been a subject of debate. Results We studied more than 300,000 pair-wise alignments of protein sequences from structurally characterized protein complexes, including both obligate and transient complexes. We identified sequence similarity criteria required for accurate homology-based inference of interface residues in a query protein sequence. Based on these analyses, we developed HomPPI, a class of sequence homology-based methods for predicting protein-protein interface residues. We present two variants of HomPPI: (i NPS-HomPPI (Non partner-specific HomPPI, which can be used to predict interface residues of a query protein in the absence of knowledge of the interaction partner; and (ii PS-HomPPI (Partner-specific HomPPI, which can be used to predict the interface residues of a query protein with a specific target protein. Our experiments on a benchmark dataset of obligate homodimeric complexes show that NPS-HomPPI can reliably predict protein-protein interface residues in a given protein, with an average correlation coefficient (CC of 0.76, sensitivity of 0.83, and specificity of 0.78, when sequence homologs of the query protein can be reliably identified. NPS-HomPPI also reliably predicts the interface residues of intrinsically disordered proteins. Our experiments suggest that NPS-HomPPI is competitive with several state-of-the-art interface prediction servers including those that exploit the structure of the query proteins. The partner-specific classifier, PS-HomPPI can, on a large dataset of transient complexes, predict the interface residues of a query protein with a specific target, with a CC of 0.65, sensitivity of 0.69, and specificity of 0.70, when homologs of

  4. Plant protein and animal proteins: do they differentially affect cardiovascular disease risk?

    Science.gov (United States)

    Richter, Chesney K; Skulas-Ray, Ann C; Champagne, Catherine M; Kris-Etherton, Penny M

    2015-11-01

    Proteins from plant-based compared with animal-based food sources may have different effects on cardiovascular disease (CVD) risk factors. Numerous epidemiologic and intervention studies have evaluated their respective health benefits; however, it is difficult to isolate the role of plant or animal protein on CVD risk. This review evaluates the current evidence from observational and intervention studies, focusing on the specific protein-providing foods and populations studied. Dietary protein is derived from many food sources, and each provides a different composite of nonprotein compounds that can also affect CVD risk factors. Increasing the consumption of protein-rich foods also typically results in lower intakes of other nutrients, which may simultaneously influence outcomes. Given these complexities, blanket statements about plant or animal protein may be too general, and greater consideration of the specific protein food sources and the background diet is required. The potential mechanisms responsible for any specific effects of plant and animal protein are similarly multifaceted and include the amino acid content of particular foods, contributions from other nonprotein compounds provided concomitantly by the whole food, and interactions with the gut microbiome. Evidence to date is inconclusive, and additional studies are needed to further advance our understanding of the complexity of plant protein vs. animal protein comparisons. Nonetheless, current evidence supports the idea that CVD risk can be reduced by a dietary pattern that provides more plant sources of protein compared with the typical American diet and also includes animal-based protein foods that are unprocessed and low in saturated fat. © 2015 American Society for Nutrition.

  5. Poxviral Ankyrin Proteins

    Directory of Open Access Journals (Sweden)

    Michael H. Herbert

    2015-02-01

    Full Text Available Multiple repeats of the ankyrin motif (ANK are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range.

  6. A high protein diet upregulated whole-body protein turnover during energy deficit

    Science.gov (United States)

    The effects of higher protein diets and sustained energy deficit (ED) on whole-body protein turnover (WBPTO) are not well described. This study examined whether dietary protein level influences whole-body protein breakdown (Ra), non-oxidative leucine disposal (NOLD), and oxidation (Ox) during ED. ...

  7. Detecting mutually exclusive interactions in protein-protein interaction maps.

    KAUST Repository

    Sánchez Claros, Carmen

    2012-06-08

    Comprehensive protein interaction maps can complement genetic and biochemical experiments and allow the formulation of new hypotheses to be tested in the system of interest. The computational analysis of the maps may help to focus on interesting cases and thereby to appropriately prioritize the validation experiments. We show here that, by automatically comparing and analyzing structurally similar regions of proteins of known structure interacting with a common partner, it is possible to identify mutually exclusive interactions present in the maps with a sensitivity of 70% and a specificity higher than 85% and that, in about three fourth of the correctly identified complexes, we also correctly recognize at least one residue (five on average) belonging to the interaction interface. Given the present and continuously increasing number of proteins of known structure, the requirement of the knowledge of the structure of the interacting proteins does not substantially impact on the coverage of our strategy that can be estimated to be around 25%. We also introduce here the Estrella server that embodies this strategy, is designed for users interested in validating specific hypotheses about the functional role of a protein-protein interaction and it also allows access to pre-computed data for seven organisms.

  8. Detecting mutually exclusive interactions in protein-protein interaction maps.

    KAUST Repository

    Sá nchez Claros, Carmen; Tramontano, Anna

    2012-01-01

    Comprehensive protein interaction maps can complement genetic and biochemical experiments and allow the formulation of new hypotheses to be tested in the system of interest. The computational analysis of the maps may help to focus on interesting cases and thereby to appropriately prioritize the validation experiments. We show here that, by automatically comparing and analyzing structurally similar regions of proteins of known structure interacting with a common partner, it is possible to identify mutually exclusive interactions present in the maps with a sensitivity of 70% and a specificity higher than 85% and that, in about three fourth of the correctly identified complexes, we also correctly recognize at least one residue (five on average) belonging to the interaction interface. Given the present and continuously increasing number of proteins of known structure, the requirement of the knowledge of the structure of the interacting proteins does not substantially impact on the coverage of our strategy that can be estimated to be around 25%. We also introduce here the Estrella server that embodies this strategy, is designed for users interested in validating specific hypotheses about the functional role of a protein-protein interaction and it also allows access to pre-computed data for seven organisms.

  9. Computational Protein Design

    DEFF Research Database (Denmark)

    Johansson, Kristoffer Enøe

    Proteins are the major functional group of molecules in biology. The impact of protein science on medicine and chemical productions is rapidly increasing. However, the greatest potential remains to be realized. The fi eld of protein design has advanced computational modeling from a tool of support...... to a central method that enables new developments. For example, novel enzymes with functions not found in natural proteins have been de novo designed to give enough activity for experimental optimization. This thesis presents the current state-of-the-art within computational design methods together...... with a novel method based on probability theory. With the aim of assembling a complete pipeline for protein design, this work touches upon several aspects of protein design. The presented work is the computational half of a design project where the other half is dedicated to the experimental part...

  10. Prediction of Protein-Protein Interactions by NanoLuc-Based Protein-Fragment Complementation Assay | Office of Cancer Genomics

    Science.gov (United States)

    The CTD2 Center at Emory has developed a new NanoLuc®-based protein-fragment complementation assay (NanoPCA) which allows the detection of novel protein-protein interactions (PPI). NanoPCA allows the study of PPI dynamics with reversible interactions.  Read the abstract. Experimental Approaches Read the detailed Experimetnal Approaches. 

  11. Protein carbonylation and metal-catalyzed protein oxidation in a cellular perspective

    DEFF Research Database (Denmark)

    Møller, Ian Max; Rogowska-Wrzesinska, Adelina; Rao, R S P

    2011-01-01

    Proteins can become oxidatively modified in many different ways, either by direct oxidation of amino acid side chains and protein backbone or indirectly by conjugation with oxidation products of polyunsaturated fatty acids and carbohydrates. While reversible oxidative modifications are thought...... to be relevant in physiological processes, irreversible oxidative modifications are known to contribute to cellular damage and disease. The most well-studied irreversible protein oxidation is carbonylation. In this work we first examine how protein carbonylation occurs via metal-catalyzed oxidation (MCO) in vivo...... and in vitro with an emphasis on cellular metal ion homeostasis and metal binding. We then review proteomic methods currently used for identifying carbonylated proteins and their sites of modification. Finally, we discuss the identified carbonylated proteins and the pattern of carbonylation sites in relation...

  12. Protein-protein docking using region-based 3D Zernike descriptors

    Directory of Open Access Journals (Sweden)

    Sael Lee

    2009-12-01

    Full Text Available Abstract Background Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. Results We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-αRMSD ≤ 2.5 Å within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. Conclusion We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for

  13. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  14. From nonspecific DNA-protein encounter complexes to the prediction of DNA-protein interactions.

    Directory of Open Access Journals (Sweden)

    Mu Gao

    2009-03-01

    Full Text Available DNA-protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA-protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA-protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA-protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA-protein interaction modes exhibit some similarity to specific DNA-protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Calpha deviation from native is up to 5 A from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA-protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein.

  15. Identification of a RAC/AKT-like gene in Leishmania parasites as a putative therapeutic target in leishmaniasis.

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    Varela-M, Rubén E; Ochoa, Rodrigo; Muskus, Carlos E; Muro, Antonio; Mollinedo, Faustino

    2017-10-10

    Leishmaniasis is one of the world's most neglected diseases caused by at least 20 different species of the protozoan parasite Leishmania. Although new drugs have become recently available, current therapy for leishmaniasis is still unsatisfactory. A subgroup of serine/threonine protein kinases named as related to A and C protein kinases (RAC), or protein kinase B (PKB)/AKT, has been identified in several organisms including Trypanosoma cruzi parasites. PKB/AKT plays a critical role in mammalian cell signaling promoting cell survival and is a major drug target in cancer therapy. However, the role of protozoan parasitic PKB/AKT remains to be elucidated. We have found that anti-human AKT antibodies recognized a protein of about 57 kDa in Leishmania spp. parasites. Anti-human phospho-AKT(Thr308) antibodies identified a protein in extracts from Leishmania spp. that was upregulated following parasite exposure to stressful conditions, such as nutrient deprivation or heat shock. Incubation of AKT inhibitor X with Leishmania spp. promastigotes under stressful conditions or with Leishmania-infected macrophages led to parasite cell death. We have identified and cloned a novel gene from Leishmania donovani named Ld-RAC/AKT-like gene, encoding a 510-amino acid protein of approximately 57.6 kDa that shows a 26.5% identity with mammalian AKT1. Ld-RAC/AKT-like protein contains major mammalian PKB/AKT hallmarks, including the typical pleckstrin, protein kinase and AGC kinase domains. Unlike mammalian AKT that contains key phosphorylation sites at Thr308 and Ser473 in the activation loop and hydrophobic motif, respectively, Ld-RAC/AKT-like protein has a Thr residue in both motifs. By domain sequence comparison, we classified AKT proteins from different origins in four major subcategories that included different parasites. Our data suggest that Ld-RAC/AKT-like protein represents a Leishmania orthologue of mammalian AKT involved in parasite stress response and survival, and

  16. Revisiting the description of Protein-Protein interfaces. Part II: Experimental study

    OpenAIRE

    Cazals , Frédéric; Proust , Flavien

    2006-01-01

    This paper provides a detailed experimental study of an interface model developed in the companion article F. Cazals and F. Proust, Revisiting the description of Protein-Protein interfaces. Part I: algorithms. Our experimental study is concerned with the usual database of protein-protein complexes, split into five families (Proteases, Immune system, Enzyme Complexes, Signal transduction, Misc.) Our findings, which bear some contradictions with usual statements are the following: (i)Connectivi...

  17. False positive reduction in protein-protein interaction predictions using gene ontology annotations

    Directory of Open Access Journals (Sweden)

    Lin Yen-Han

    2007-07-01

    Full Text Available Abstract Background Many crucial cellular operations such as metabolism, signalling, and regulations are based on protein-protein interactions. However, the lack of robust protein-protein interaction information is a challenge. One reason for the lack of solid protein-protein interaction information is poor agreement between experimental findings and computational sets that, in turn, comes from huge false positive predictions in computational approaches. Reduction of false positive predictions and enhancing true positive fraction of computationally predicted protein-protein interaction datasets based on highly confident experimental results has not been adequately investigated. Results Gene Ontology (GO annotations were used to reduce false positive protein-protein interactions (PPI pairs resulting from computational predictions. Using experimentally obtained PPI pairs as a training dataset, eight top-ranking keywords were extracted from GO molecular function annotations. The sensitivity of these keywords is 64.21% in the yeast experimental dataset and 80.83% in the worm experimental dataset. The specificities, a measure of recovery power, of these keywords applied to four predicted PPI datasets for each studied organisms, are 48.32% and 46.49% (by average of four datasets in yeast and worm, respectively. Based on eight top-ranking keywords and co-localization of interacting proteins a set of two knowledge rules were deduced and applied to remove false positive protein pairs. The 'strength', a measure of improvement provided by the rules was defined based on the signal-to-noise ratio and implemented to measure the applicability of knowledge rules applying to the predicted PPI datasets. Depending on the employed PPI-predicting methods, the strength varies between two and ten-fold of randomly removing protein pairs from the datasets. Conclusion Gene Ontology annotations along with the deduced knowledge rules could be implemented to partially

  18. Protein-anchoring therapy to target extracellular matrix proteins to their physiological destinations.

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    Ito, Mikako; Ohno, Kinji

    2018-02-20

    Endplate acetylcholinesterase (AChE) deficiency is a form of congenital myasthenic syndrome (CMS) caused by mutations in COLQ, which encodes collagen Q (ColQ). ColQ is an extracellular matrix (ECM) protein that anchors AChE to the synaptic basal lamina. Biglycan, encoded by BGN, is another ECM protein that binds to the dystrophin-associated protein complex (DAPC) on skeletal muscle, which links the actin cytoskeleton and ECM proteins to stabilize the sarcolemma during repeated muscle contractions. Upregulation of biglycan stabilizes the DPAC. Gene therapy can potentially ameliorate any disease that can be recapitulated in cultured cells. However, the difficulty of tissue-specific and developmental stage-specific regulated expression of transgenes, as well as the difficulty of introducing a transgene into all cells in a specific tissue, prevents us from successfully applying gene therapy to many human diseases. In contrast to intracellular proteins, an ECM protein is anchored to the target tissue via its specific binding affinity for protein(s) expressed on the cell surface within the target tissue. Exploiting this unique feature of ECM proteins, we developed protein-anchoring therapy in which a transgene product expressed even in remote tissues can be delivered and anchored to a target tissue using specific binding signals. We demonstrate the application of protein-anchoring therapy to two disease models. First, intravenous administration of adeno-associated virus (AAV) serotype 8-COLQ to Colq-deficient mice, resulting in specific anchoring of ectopically expressed ColQ-AChE at the NMJ, markedly improved motor functions, synaptic transmission, and the ultrastructure of the neuromuscular junction (NMJ). In the second example, Mdx mice, a model for Duchenne muscular dystrophy, were intravenously injected with AAV8-BGN. The treatment ameliorated motor deficits, mitigated muscle histopathologies, decreased plasma creatine kinase activities, and upregulated expression

  19. Automated protein structure modeling with SWISS-MODEL Workspace and the Protein Model Portal.

    Science.gov (United States)

    Bordoli, Lorenza; Schwede, Torsten

    2012-01-01

    Comparative protein structure modeling is a computational approach to build three-dimensional structural models for proteins using experimental structures of related protein family members as templates. Regular blind assessments of modeling accuracy have demonstrated that comparative protein structure modeling is currently the most reliable technique to model protein structures. Homology models are often sufficiently accurate to substitute for experimental structures in a wide variety of applications. Since the usefulness of a model for specific application is determined by its accuracy, model quality estimation is an essential component of protein structure prediction. Comparative protein modeling has become a routine approach in many areas of life science research since fully automated modeling systems allow also nonexperts to build reliable models. In this chapter, we describe practical approaches for automated protein structure modeling with SWISS-MODEL Workspace and the Protein Model Portal.

  20. Computational prediction of protein-protein interactions in Leishmania predicted proteomes.

    Directory of Open Access Journals (Sweden)

    Antonio M Rezende

    Full Text Available The Trypanosomatids parasites Leishmania braziliensis, Leishmania major and Leishmania infantum are important human pathogens. Despite of years of study and genome availability, effective vaccine has not been developed yet, and the chemotherapy is highly toxic. Therefore, it is clear just interdisciplinary integrated studies will have success in trying to search new targets for developing of vaccines and drugs. An essential part of this rationale is related to protein-protein interaction network (PPI study which can provide a better understanding of complex protein interactions in biological system. Thus, we modeled PPIs for Trypanosomatids through computational methods using sequence comparison against public database of protein or domain interaction for interaction prediction (Interolog Mapping and developed a dedicated combined system score to address the predictions robustness. The confidence evaluation of network prediction approach was addressed using gold standard positive and negative datasets and the AUC value obtained was 0.94. As result, 39,420, 43,531 and 45,235 interactions were predicted for L. braziliensis, L. major and L. infantum respectively. For each predicted network the top 20 proteins were ranked by MCC topological index. In addition, information related with immunological potential, degree of protein sequence conservation among orthologs and degree of identity compared to proteins of potential parasite hosts was integrated. This information integration provides a better understanding and usefulness of the predicted networks that can be valuable to select new potential biological targets for drug and vaccine development. Network modularity which is a key when one is interested in destabilizing the PPIs for drug or vaccine purposes along with multiple alignments of the predicted PPIs were performed revealing patterns associated with protein turnover. In addition, around 50% of hypothetical protein present in the networks