Scientists and professionals from all around the world in Karlsruhe. Frederic Joliot/Otto Hahn summer school 2013 on nuclear reactors 'Physics, Fuels and Systems'

Energy Technology Data Exchange (ETDEWEB)

Sanchez-Espinoza, V.H.; Fischer, U. [Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen (Germany). Scientific Secretariat FJOHSS

2014-02-15

Every 2 years the Karlsruhe Institute of Technology (KIT) organizes the Frederic Joliot/Otto Hahn (FJOH) Summer School together with the Commissariat a l'-Energie Atomique (CEA) since 1999. In 2013, the FJOH Summer School took place in Karlsruhe from 21 to 30 August. The topic of this year's school was 'Advanced Nuclear Systems with Transuranium Fuels'. Experts from internationally well recognized research institutions and Universities from USA, Japan, Asia and Europe gave lectures about the current status and trends on the related fields. (orig.)

Scientists from all over the world attended the 'Frederic Joliot/Otto Hahn Summer School 2011' at the Karlsruhe Institute of Technology (KIT); Wissenschaftler aus aller Welt bei der 'Frederic Joliot/Otto Hahn Summer School 2011' am Karlsruhe Institute of Technology (KIT)

Energy Technology Data Exchange (ETDEWEB)

Sanchez, Victor H.; Fischer, Ulrich [Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen (DE). Inst. for Neutron Physics and Reactor Technology (INR)

2011-12-15

The Karlsruhe Institute of Technology (KIT) and the Commissariat r leEnergie Atomique et Aux Energies Alternatives (CEA), Cadarache, alternate in organizing the annual 'Frederic Joliot/Otto Hahn Summer School.' This year's event, the 17th since its inception, was held in Karlsruhe, Germany on August 25 to September 3. Its topic was 'High-fidelity Modeling for Nuclear Reactors: Challenges and Prospects.' Here is a list of the subjects covered: - Status and perspectives of modeling and its role in design, operation, and safety. - Thermal hydraulics of nuclear reactors and simulation of 2 phase flows. - Structural mechanics, structure? fluid interaction, and seismic safety. - Advanced simulation in neutronics and reactor physics. - Progress in simulating fuel and materials behavior. - Multiphysics and uncertainty analysis methods. Experts from eight leading international research institutions and universities presented, and discussed with the 59 participants from 19 countries, the current state of the art and most recent development trends in the subjects listed above. (orig.)

Scientists from all over the world attend the ''Frederic Joliot/Otto Hahn Summer School 2009'' at the Karlsruhe Institute of Technology (KIT)

International Nuclear Information System (INIS)

Sanchez Espinoza, Victor Hugo; Fischer, Ulrich

2009-01-01

The ''Frederic Joliot/Otto Hahn Summer School'' is organized each year alternately by the Karlsruhe Institute of Technology and the Commissariat a l'Energie Atomique (CEA), Cadarache. This year's Summer School, the 15th since its foundation, was run at the Advanced Training Center (FTU) of KIT Campus Nord on August 26 to September 4. The key topic this year was ''The Challenges in Implementing Fast Reactor Technology.'' These are the items discussed: Principles and challenges of future fast reactor designs, Fuels, fuel cycle, and recycling of minor actinides, Innovative cladding tube and structural materials, Special aspects of coolants and the challenges they pose, Fast reactor safety. Experts from 8 leading international research establishments and universities presented and discussed with the 58 participants from 16 countries the current state of the art and the latest development trends in the topics listed above. (orig.)

Scientists from all over the world attend the ''Frederic Joliot/Otto Hahn Summer School 2009'' at the Karlsruhe Institute of Technology (KIT); Wissenschaftler aus aller Welt bei der ''Frederic Joliot/Otto Hahn Summer School 2009'' am Karlsruhe Institute of Technologie (KIT)

Energy Technology Data Exchange (ETDEWEB)

Sanchez Espinoza, Victor Hugo; Fischer, Ulrich [Karlsruhe Inst. of Tech. (KIT), Campus Nord/Inst. for Neutron Physics and Reactor Tech. (INR), Eggenstein-Leopoldshafen (Germany)

2009-11-15

The ''Frederic Joliot/Otto Hahn Summer School'' is organized each year alternately by the Karlsruhe Institute of Technology and the Commissariat a l'Energie Atomique (CEA), Cadarache. This year's Summer School, the 15th since its foundation, was run at the Advanced Training Center (FTU) of KIT Campus Nord on August 26 to September 4. The key topic this year was ''The Challenges in Implementing Fast Reactor Technology.'' These are the items discussed: Principles and challenges of future fast reactor designs, Fuels, fuel cycle, and recycling of minor actinides, Innovative cladding tube and structural materials, Special aspects of coolants and the challenges they pose, Fast reactor safety. Experts from 8 leading international research establishments and universities presented and discussed with the 58 participants from 16 countries the current state of the art and the latest development trends in the topics listed above. (orig.)

Scientists from all over the world attended the 'Frederic Joliot/Otto Hahn Summer School 2011' at the Karlsruhe Institute of Technology (KIT)

International Nuclear Information System (INIS)

Sanchez, Victor H.; Fischer, Ulrich

2011-01-01

The Karlsruhe Institute of Technology (KIT) and the Commissariat r leEnergie Atomique et Aux Energies Alternatives (CEA), Cadarache, alternate in organizing the annual 'Frederic Joliot/Otto Hahn Summer School.' This year's event, the 17th since its inception, was held in Karlsruhe, Germany on August 25 to September 3. Its topic was 'High-fidelity Modeling for Nuclear Reactors: Challenges and Prospects.' Here is a list of the subjects covered: - Status and perspectives of modeling and its role in design, operation, and safety. - Thermal hydraulics of nuclear reactors and simulation of 2 phase flows. - Structural mechanics, structure? fluid interaction, and seismic safety. - Advanced simulation in neutronics and reactor physics. - Progress in simulating fuel and materials behavior. - Multiphysics and uncertainty analysis methods. Experts from eight leading international research institutions and universities presented, and discussed with the 59 participants from 19 countries, the current state of the art and most recent development trends in the subjects listed above. (orig.)

Annual report 1972

International Nuclear Information System (INIS)

1972-01-01

The report deals with the development of Geesthacht research centre, the research facilities (NS 'Otto Hahn', FRG-1 and FRG-2, ANEX), research and development projects, cooperation with industry and other research facilities, as well as with publications and lectures of 1972. (orig./AK) [de

The su(2)α Hahn oscillator and a discrete Fourier-Hahn transform

International Nuclear Information System (INIS)

Jafarov, E I; Stoilova, N I; Van der Jeugt, J

2011-01-01

We define the quadratic algebra su(2) α which is a one-parameter deformation of the Lie algebra su(2) extended by a parity operator. The odd-dimensional representations of su(2) (with representation label j, a positive integer) can be extended to representations of su(2) α . We investigate a model of the finite one-dimensional harmonic oscillator based upon this algebra su(2) α . It turns out that in this model the spectrum of the position and momentum operator can be computed explicitly, and that the corresponding (discrete) wavefunctions can be determined in terms of Hahn polynomials. The operation mapping position wavefunctions into momentum wavefunctions is studied, and this so-called discrete Fourier-Hahn transform is computed explicitly. The matrix of this discrete Fourier-Hahn transform has many interesting properties, similar to those of the traditional discrete Fourier transform. (paper)

Development and testing of control rod drives for ship reactors

International Nuclear Information System (INIS)

Bruelheide, K.; Mundt, D.; Peters, C.-H.; Manthey, H.-J.

1978-01-01

The following paper deals with the development and testings of a new control rod drive design for marine reactors. Starting from the good operating experience with the advanced pressurized water reactor (FDR) of the NS OTTO HAHN a control rod drive system with an hermetically sealed drive principle was developed. A prototype control rod drive system was put through extensive tests and developed ready for standard production at the 'Gesellschaft fuer Kernenergieverwertung in Schiffbau und Schiffahrt'

Civilian nuclear ships

International Nuclear Information System (INIS)

Oelgaard, P.L.

1993-03-01

This report contains a review of the information available on nuclear powered ships, built for civilian purposes. In the introduction a short discussion is given of the reasons for the limited use of nuclear ships for these purposes. In the second section a brief review is presented of data for the three experimental/merchant ships build by the United States, Germany and Japan, i.e. NS Savannah, NS Otto Hahn and NS Mutsu. In the third section the Soviet/Russian icebreaker NS Lenin is considered. Its design, operational experience and the introduction of a new nuclear propulsion plant is reviewed. In the fourth section the newer Soviet/Russian icebreakers with nuclear propulsion are considered. Finally design of the Soviet/Russian icebreaker transport/container ship NS Sevmorput is reviewed in the fifth section. The future Russian plans for nuclear vessels for the arctic waters are briefly discussed. (au)

40 years of nuclear fission

International Nuclear Information System (INIS)

Koch, H.

1979-01-01

On the occasion of both the 100th birthday of the discoverer of nuclear fission, Otto Hahn, and the 40th anniversary of this outstanding scientific discovery the historical development is described, which led to nuclear fission. Aspects of scientific life in Berlin and in the whole world at that time are presented, and relations between scientists are characterized by quotations. In particular, stress is laid on the life and activities of Otto Hahn as a human being and as a scientist, and his outstanding scientific achievements are appreciated. (author)

Continuous and discrete best polynomial degree reduction with Jacobi and Hahn weights

KAUST Repository

Ait-Haddou, Rachid

2016-03-02

We show that the weighted least squares approximation of Bézier coefficients with Hahn weights provides the best polynomial degree reduction in the Jacobi L2L2-norm. A discrete analogue of this result is also provided. Applications to Jacobi and Hahn orthogonal polynomials are presented.

Port entry of nuclear ships differences, procedures and conditions

International Nuclear Information System (INIS)

McMichael, D.; Bianchi, H.

1978-01-01

There are about 250 nuclear propelled ships, only 2 of them are merchant ships: the US freighter Savannah and the bulk carrier Otto Hahn of the Federal Republic of Germany. This paper is restricted to the experience with both of these ships, showing partly similar and partly different procedures for port entry. They have called at 107 ports in 40 countries. The Savannah was operated in the periods from 1962 - 1971 and the Otto Hahn is still in operation. The endeavours of the OECD and IMCO to review and to harmonize international rules for nuclear merchant ships should be supported and continued

An Inconvenient History: the Nuclear-Fission Display in the Deutsches Museum

Science.gov (United States)

Sime, Ruth Lewin

2010-06-01

One of the longstanding attractions of the Deutsches Museum in Munich, Germany, has been its display of the apparatus associated with the discovery of nuclear fission. Although the discovery involved three scientists, Otto Hahn, Lise Meitner, and Fritz Strassmann, the fission display was designated for over 30 years as the Arbeitstisch von Otto Hahn (Otto Hahn’s Worktable), with Strassmann mentioned peripherally and Meitner not at all, and it was not until the early 1990s that the display was revised to include all three codiscoverers more equitably. I examine the creation of the fission display in the context of the postwar German culture of silencing the National Socialist past, and trace the eventual transformation of the display into a contemporary exhibit that more accurately represents the scientific history of the fission discovery.

A set of sums for continuous dual q-2-Hahn polynomials

International Nuclear Information System (INIS)

Gade, R. M.

2009-01-01

An infinite set {τ (l) (y;r,z)} r,lisanelementofN 0 of linear sums of continuous dual q -2 -Hahn polynomials with prefactors depending on a complex parameter z is studied. The sums τ (l) (y;r,z) have an interpretation in context with tensor product representations of the quantum affine algebra U q ' (sl(2)) involving both a positive and a negative discrete series representation. For each l>0, the sum τ (l) (y;r,z) can be expressed in terms of the sum τ (0) (y;r,z), continuous dual q 2 -Hahn polynomials, and their associated polynomials. The sum τ (0) (y;r,z) is obtained as a combination of eight basic hypergeometric series. Moreover, an integral representation is provided for the sums τ (l) (y;r,z) with the complex parameter restricted by |zq| -2 -Hahn polynomials.

A high-order q-difference equation for q-Hahn multiple orthogonal polynomials

DEFF Research Database (Denmark)

Arvesú, J.; Esposito, Chiara

2012-01-01

A high-order linear q-difference equation with polynomial coefficients having q-Hahn multiple orthogonal polynomials as eigenfunctions is given. The order of the equation coincides with the number of orthogonality conditions that these polynomials satisfy. Some limiting situations when are studie....... Indeed, the difference equation for Hahn multiple orthogonal polynomials given in Lee [J. Approx. Theory (2007), ), doi: 10.1016/j.jat.2007.06.002] is obtained as a limiting case....

Uniform Smoothness Entails Hahn-Banach | Albius | Quaestiones ...

African Journals Online (AJOL)

the Axiom of Choice), and we denote by ZFC set theory with the Axiom of Choice. Our paper deals with the role of the Axiom of. Choice in functional analysis, and more particularly, with the necessity of using the Axiom of Choice when invoking some consequence of the following Hahn-Banach axiom HB. Mathematics ...

As Voltas do Pentágono de Hahn

Directory of Open Access Journals (Sweden)

Maria Augusta Vilalba Nunes

2012-09-01

Full Text Available http://dx.doi.org/10.5007/2176-8552.2011nesp2p109 O conto Pentágono de Hahn do escritor pernambucano Osman Lins se constrói como uma espécie de sistema, em que cinco micronarrativas se embaralham em trinta e dois parágrafos. Cada micronarrativa é designada por um sinal gráfico diferente e cada uma possui um narrador-personagem, sendo que a presença paquidérmica de Senhorita Hahn, uma elefanta que chega à cidade com um circo, é a única coisa que une cada uma das histórias. Este ensaio faz uma leitura do uso dos sinais gráficos dentro da fragmentação narrativa do conto, que, como sugere o título, se constrói aludindo à figura geométrica de um pentágono. Para ilustrar o sistema de Osman, criei uma figura pentagonal em forma de estrela que tem em cada uma de suas pontas um sinal gráfico, o que significa que cada uma das pontas representa uma das micronarrativas. Ao centro, unindo cada ponta da estrela, e, consequentemente, sendo o elo entre as micronarrativas, temos Hahn, a elefanta. A partir dessa figura pentagonal, faço um estudo do possível funcionamento dos sinais gráficos dentro do texto, sendo que minha leitura, no entanto, não procura desvendar o sistema criado por Osman, mas apenas levantar algumas possibilidades.

OTTO - the analysing system for spectra ver 9.0

International Nuclear Information System (INIS)

Menningen, M.

1989-10-01

OTTO is an interactive command system for the analysis of one-dimensional spectra. OTTO includes basic functions for spectra handling, interactive arithmetic with variables and arrays (formula interpreter), as well as numerous graphic functions. In combination with the general functions more complex dedicated routines (physical routines) are available, e.g. to prepare the measured data or to transform them. There are several program versions including different physical routines. The most important feature of OTTO is a very variable fitting routine (least square fit). A large number of fitting functions is available. Additional functions may be supplied by the user. All operations may be executed also in procedures (command files). The procedure processor is capable of a set of control instructions (jumps, loops, if's). Thus extended procedures may be written in the OTTO command-language. OTTO is written in FORTRAN and was impelemented at VAX computers. (orig.) [de

Method of resonating groups in the Faddeev-Hahn equation formalism for three-body nuclear problem

CERN Document Server

Nasirov, M Z

2002-01-01

The Faddeev-Hahn equation formalism for three-body nuclear problem is considered. For solution of the equations the method of resonant groups have applied. The calculations of tritium binding energy and doublet nd-scattering length have been carried out. The results obtained shows that Faddeev-Hahn equation formalism is very simple and effective. (author)

The Brussels Nuclear Ship Convention and its impact on the German Atomic Energy Act

International Nuclear Information System (INIS)

Bernaerts, A.

1976-01-01

Although the Brussels Nuclear Ship Liability Convention of 1962, whose incorporation into German law was agreed upon by the German Federal Parliament (the Bundestag) in 1975, will have only minor international significance once it has entered into force, it will yet provide a new legal basis for the nuclear liability of the German vessel N.S. 'Otto Hahn' for the periods of her stay within the Federal Republic of Germany. However, there is no smooth concurrence of the Brussels Convention and the German Atomic Energy Act adapted to the Paris Liability Convention in 1975. This means that a number of questions still need to be resolved with respect to the protection of victims and the liability of shipowners. (orig.) [de

Wolfgang Pauli at the 6th meeting of the Nobel Prize laureates

CERN Multimedia

Franz Thorbecke, Lindau

1956-01-01

From left to right : ?, Max Born, Paul Adrien Maurice Dirac, Adolf Friedrich Johann Butenandt, ?, Otto Hahn, Wolfgang Pauli, Franca Pauli, Sir Chandrasekhara Venkata Raman, Isidor Isaac Rabi, and Leopold Ruzicka

NS OTTO HAHN - test report no. 27 for the period from 5-8-1976 to 25-8-1977

International Nuclear Information System (INIS)

1977-01-01

Several voyages to Rio de Janeiro, Montevideo, and Durban are reported on as well as stays in the shipyard. In these reports, the programme of operation is explained, and the technical incidents are described. For the period between August 25th, 1976, and June 17th, 1977, the development of thermal power is given in the form of power histograms. (UA) [de

Experience with W3Re/W25Re thermocouples in fuel pins of NS Otto Hahn's two cores

International Nuclear Information System (INIS)

Kolb, M.

1976-01-01

The paper first deals with the installation of 18 and 9 high-temperature sheathed thermocouples in fuel rods of the cores FDR-1 and FDR-2, respectively. The measured fuel rod centerline temperatures could be related to the local linear rod power at any given time by means of the densities of fission products with different half-lives obtained from fuel rod γ-scans. The fuel temperatures show then already an increase with the burn-up of the FDR-1 which becomes steeper when taking into account the decrease of the EMF measured at irradiated thermocouples taken from the fuel rods. Finally, the determination of effective thermocouple time constants and of fuel rod heat transfer time constants is demonstrated by utilizing the reactor noise to measure the transfer function between neutron flux and fuel temperature signal. (orig.) [de

Otto Graf Lambsdorff in memoriam / Wolter von Tiesenhausen

Index Scriptorium Estoniae

Tiesenhausen, Wolter von

2010-01-01

Baltisaksa päritolu liberaalsest saksa poliitikust Otto Graf Lambsdorff'ist, kes täitis mitmel korral Saksamaa majandusministri kohuseid. Lisaks baltisaksa päritolule olid tal Baltimaadega isiklikud poliitilised seosed, vend Hagen töötas Saksa saatkonnas Riias ja poeg Nikolaus teenis diplomaadina Tallinnas. President Lennart Meri omistas Otto Graf Lambsdorffile Maarjamaa risti I klassi teenetemärgi

Waiting for the ice to thaw

International Nuclear Information System (INIS)

Jager, W.; Schroeder, E.

1976-01-01

The prospects for the economical operation of nuclear ships is discussed. The basis for this is the hitherto successful operation of the 'Otto Hahn'. Planning aims at a 80,000 shp container ship. (UA) [de

Decline of Hesperia ottoe (Lepidoptera: Hesperiidae in Northern Tallgrass Prairie Preserves

Directory of Open Access Journals (Sweden)

Ann B. Swengel

2013-11-01

Full Text Available We counted butterflies on transect surveys during Hesperia ottoe flight period in 1988–2011 at tallgrass prairie preserves in four states (Illinois, Iowa, Minnesota, Wisconsin, divided into units cross-referenced to vegetation type and management history. H. ottoe occurred only in dry and sand prairie types, and was significantly more abundant in undegraded than semi-degraded prairie, and in discontinuous sod (with numerous unvegetated areas due to bare sand and/or rock outcrops than in continuous sod. This skipper was significantly more abundant in small sites compared to medium and large sites, even when the analysis was limited to undegraded prairie analyzed separately by sod type. H. ottoe was significantly under-represented in year-burn 0 (the first growing season after fire compared to an expected distribution proportional to survey effort. However, H. ottoe was also over-represented in fire-managed units compared to non-fire-managed units. However, by far most units and sites were in fire management and most populations declined to subdetection during this study. Peak abundance post-fire occurred in a later year-burn in discontinuous sod and was much higher than in continuous sod. We also analyze H. ottoe status and trend in midwestern prairie preserves by compiling a dataset of our and others’ butterfly surveys from 1974 to 2011. Only 1/9 sites with continuous sod had detectable H. ottoe in recent year(s. In discontinuous sod, 2/6 did, with two sites lacking data for the last few years. The number of years H. ottoe was still detectable after preservation and the number of years to consistent non-detection were both significantly higher in discontinuous than continuous sod. Both measures of population persistence averaged over twice as long in discontinuous than continuous sod, and correlated negatively with prairie size. The year when consistent non-detection began varied over several decades among sites. Despite the currently urgent

Decline of Hesperia ottoe (Lepidoptera: Hesperiidae) in Northern Tallgrass Prairie Preserves.

Science.gov (United States)

Swengel, Ann B; Swengel, Scott R

2013-11-20

We counted butterflies on transect surveys during Hesperia ottoe flight period in 1988-2011 at tallgrass prairie preserves in four states (Illinois, Iowa, Minnesota, Wisconsin), divided into units cross-referenced to vegetation type and management history. H. ottoe occurred only in dry and sand prairie types, and was significantly more abundant in undegraded than semi-degraded prairie, and in discontinuous sod (with numerous unvegetated areas due to bare sand and/or rock outcrops) than in continuous sod. This skipper was significantly more abundant in small sites compared to medium and large sites, even when the analysis was limited to undegraded prairie analyzed separately by sod type. H. ottoe was significantly under-represented in year-burn 0 (the first growing season after fire) compared to an expected distribution proportional to survey effort. However, H. ottoe was also over-represented in fire-managed units compared to non-fire-managed units. However, by far most units and sites were in fire management and most populations declined to subdetection during this study. Peak abundance post-fire occurred in a later year-burn in discontinuous sod and was much higher than in continuous sod. We also analyze H. ottoe status and trend in midwestern prairie preserves by compiling a dataset of our and others' butterfly surveys from 1974 to 2011. Only 1/9 sites with continuous sod had detectable H. ottoe in recent year(s). In discontinuous sod, 2/6 did, with two sites lacking data for the last few years. The number of years H. ottoe was still detectable after preservation and the number of years to consistent non-detection were both significantly higher in discontinuous than continuous sod. Both measures of population persistence averaged over twice as long in discontinuous than continuous sod, and correlated negatively with prairie size. The year when consistent non-detection began varied over several decades among sites. Despite the currently urgent need to identify

Lise Meitner and fission: Fallout from the discovery

International Nuclear Information System (INIS)

Sime, R.L.

1991-01-01

Much has been written about Lise Meitner, but she remains on the periphery. Of her pioneering work in nuclear physics, little is said; she is remembered primarily for nuclear fission, a discovery in which she did not share. Especially in Germany the staging seldom varies: Otto Hahn in the spotlight, Fritz Strassmann in his shadow, Lise Meitner in the wings, dimly outlined in reflected light. Her role is open to speculation. One writer sees her work 'crowned by the Nobel Prize for Otto Hahn', another, once director of an institute that bears her name, portrays her as the physicist who obstructed the discovery from the start. Often she is cast as Hahn's Mitarbeiterin; sometimes she is completely invisible, as in one of the world's great science museums, which for 30 years displayed the fission apparatus-equipment assembled by Lise Meitner on a table in her laboratory in her physics section of the Kaiser-Wilhelm-Institut fuer Chemie - without ever mentioning her name. The principals themselves do not agree. In his memoirs, Hahn has remarkably little to say of this closest colleague and friend. From Lise Meitner herself we have no autobiography. Available, however, is the large collection of letters and documents she has left behind, and these make it possible for us to learn much more. (orig./BBR)

Lise Meitner and fission: Fallout from the discovery

Energy Technology Data Exchange (ETDEWEB)

Sime, R.L. (Sacramento City Coll., CA (United States). Dept. of Chemistry)

1991-08-01

Much has been written about Lise Meitner, but she remains on the periphery. Of her pioneering work in nuclear physics, little is said; she is remembered primarily for nuclear fission, a discovery in which she did not share. Especially in Germany the staging seldom varies: Otto Hahn in the spotlight, Fritz Strassmann in his shadow, Lise Meitner in the wings, dimly outlined in reflected light. Her role is open to speculation. One writer sees her work 'crowned by the Nobel Prize for Otto Hahn', another, once director of an institute that bears her name, portrays her as the physicist who obstructed the discovery from the start. Often she is cast as Hahn's Mitarbeiterin; sometimes she is completely invisible, as in one of the world's great science museums, which for 30 years displayed the fission apparatus-equipment assembled by Lise Meitner on a table in her laboratory in her physics section of the Kaiser-Wilhelm-Institut fuer Chemie - without ever mentioning her name. The principals themselves do not agree. In his memoirs, Hahn has remarkably little to say of this closest colleague and friend. From Lise Meitner herself we have no autobiography. Available, however, is the large collection of letters and documents she has left behind, and these make it possible for us to learn much more. (orig./BBR).

Isotype by Otto Neurath

Directory of Open Access Journals (Sweden)

Malysheva O. A.

2016-04-01

Full Text Available the article deals with the theoretical basis of the infographic and its practical impact on the person’s attention by the example of the book of Otto Neurath's about the international pictorial language. This shows the relevance of design methods of Isotype system and its influence on modern infographic.

Lise Meitner

International Nuclear Information System (INIS)

2014-01-01

This paper is a collection of articles concerning the biography of Lise Meitner with special regards to her cooperation with Otto Hahn in the discovery of nuclear fission, whereby the role of women in science, especially physics, are considered. (HSI)

Lise Meitner; Lise Meitner

Energy Technology Data Exchange (ETDEWEB)

NONE

2014-11-15

This paper is a collection of articles concerning the biography of Lise Meitner with special regards to her cooperation with Otto Hahn in the discovery of nuclear fission, whereby the role of women in science, especially physics, are considered. (HSI)

Dr. Otto Heinrich Warburg—Survivor of Ethical Storms

Directory of Open Access Journals (Sweden)

George M. Weisz

2015-11-01

Full Text Available Otto Heinrich Warburg (1883–1970; not to be confused with the Zionist of the same name was a member of an illustrious Jewish family, known for some five centuries. From humble beginnings, the family became prominent in the world for their contributions to all aspects of society. The son of a German mother and a Jewish (converted father, Otto H. Warburg became a major contributor to medical science in the field of cancer research. Considered for Nobel Prize more than once, he finally received it in 1931 for his discovery of the nature and mode of action of the cellular respiratory enzyme. Warburg’s personality was controversial: he was intolerant of opposing scientific views yet tolerant toward Nazi abuses. Accused of collaboration under the Nazi regime, Otto H. Warburg was nevertheless readmitted to the global scientific community after World War II. His contribution to cancer research remains influential to this day and has been superseded by discoveries that have built upon his work.

Five years of proton therapy of tumours of the eye at Hahn-Meitner Institute, Berlin; Fuenf Jahre Protonentherapie von Augentumoren am Hahn-Meitner-Institut Berlin

Energy Technology Data Exchange (ETDEWEB)

Heufelder, J.; Cordini, D.; Heese, J.; Homeyer, H.; Kluge, H.; Morgenstern, H. [Hahn-Meitner-Inst. Berlin, Augentumortherapie (Germany); Fuchs, H. [Hahn-Meitner-Inst. Berlin, Augentumortherapie (Germany); Augenklinik, Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin (Germany); Hoecht, S.; Nausner, M.; Hinkelbein, W. [Klinik fuer Radioonkologie und Strahlentherapie, Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin (Germany); Bechrakis, N.E.; Foerster, M.H. [Augenklinik, Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin (Germany)

2004-07-01

Eye tumors (choroidal melanomas, iris melanomas, and choroidal hemangiomas) are being treated with 68 MeV protons since 1998 at the Ion Beam Laboratory of the Hahn-Meitner Institute of Berlin (Germany's first proton therapy center), in cooperation with the Charite University Hospital in Berlin, Campus Benjamin Franklin. The proton beam, generated via a combination of Van de Graaff accelerator and cyclotron, is prepared by passive shaping for conformal tumor irradiation. A digital X-ray verification of the tumor location with the patient in sitting position limits the position uncertainties to a maximum of 0,3 mm. The treatment planning is performed using the program EYEPLAN. OCTOPUS, a CT-based planning program developed in cooperation with the German Cancer Research Center of Heidelberg, is under pre-clinical testing. Thus far, more than 400 patients have been irradiated. The first results are comparable to those obtained in other proton therapy centers. At the end of 2002, the University Hospital of Essen has also become a cooperation partner of the Hahn-Meitner Institute. (orig.) [German] Seit 1998 werden am Ionenstrahllabor des Hahn-Meitner-Instituts Berlin (Deutschlands erster Einrichtung zur Protonentherapie) im Rahmen eines Kooperationsvertrages mit der Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin, Augentumoren (Aderhautmelanome, Irismelanome und Aderhauthaemangiome) mit 68-MeV-Protonen bestrahlt. Der mittels einer Kombination aus Van de Graaff-Beschleuniger und Zyklotron erzeugte Protonenstrahl wird passiv fuer eine konformale Bestrahlung des Tumors aufbereitet. Eine digitale Roentgenkontrolle der Lagerung des sitzenden Patienten beschraenkt die Lagerungsunsicherheit auf maximal 0,3 mm. Fuer die Bestrahlungsplanung wird das modellbasierte Planungsprogramm EYEPLAN verwendet. In vorklinischer Erprobung befindet sich das mit dem Deutschen Krebsforschungszentrum Heidelberg entwickelte CT-basierte Planungsprogramm OCTOPUS. Bisher wurden

The discovery of nuclear fission and the responsibility of the scientist

International Nuclear Information System (INIS)

Staab, H.A.

1989-01-01

The history of the discovery of nuclear fission is placed in historical context and the responsibility of the scientists involved for the subsequent military uses is discussed. It is explained that the deep things in science are not found because they are useful; they are found because it is possible to find them. If Otto Hahn and his co-workers had not discovered nuclear fission someone else in the late 1930s or early 1940s would have done so. It was decisions outside science which set the course for the nuclear fission research once the basic principle had been understood. The question how far does the scientists responsibility extend for unknown and unintended consequences of research and for misuses of his findings by others is discussed. Scientists have a duty to understand the applications of their work and to warn of misuse or hazards, as did Otto Hahn. (UK)

Hahn-Meitner-Institut Berlin. Annual report 1993

International Nuclear Information System (INIS)

1994-01-01

This report describes the activities of the Hahn-Meitner-Institute (HMI) on four special subjects: 1. Nuclear physics (nuclear reactions, nuclear structure, VICKSI accelerator development), 2. photochemical energy conversion (basic and material research, radiation chemistry), 3. structure research (theory of many-body systems, solid-state physics, neutron scattering, highly stressed metallic materials, trace nutrients in health and nutrition), and 4. information technics (software, real time systems, semiconductor subassembly). The following is presented for every special subject: a) The topics worked on in 1993, b) selected results and c) publications, lectures, theses submitted for diplomas and doctoral theses. (orig.) [de

Continuous and discrete best polynomial degree reduction with Jacobi and Hahn weights

KAUST Repository

Ait-Haddou, Rachid

2016-01-01

We show that the weighted least squares approximation of Bézier coefficients with Hahn weights provides the best polynomial degree reduction in the Jacobi L2L2-norm. A discrete analogue of this result is also provided. Applications to Jacobi

Power Peaking Effect of OTTO Fuel Scheme Pebble Bed Reactor

Science.gov (United States)

Setiadipura, T.; Suwoto; Zuhair; Bakhri, S.; Sunaryo, G. R.

2018-02-01

Pebble Bed Reactor (PBR) type of Hight Temperature Gas-cooled Reactor (HTGR) is a very interesting nuclear reactor design to fulfill the growing electricity and heat demand with a superior passive safety features. Effort to introduce the PBR design to the market can be strengthen by simplifying its system with the Once-through-then-out (OTTO) cycle PBR in which the pebble fuel only pass the core once. Important challenge in the OTTO fuel scheme is the power peaking effect which limit the maximum nominal power or burnup of the design. Parametric survey is perform in this study to investigate the contribution of different design parameters to power peaking effect of OTTO cycle PBR. PEBBED code is utilized in this study to perform the equilibrium PBR core analysis for different design parameter and fuel scheme. The parameters include its core diameter, height-per-diameter (H/D), power density, and core nominal power. Results of this study show that diameter and H/D effectsare stronger compare to the power density and nominal core power. Results of this study might become an importance guidance for design optimization of OTTO fuel scheme PBR.

GKSS annual report 1980

International Nuclear Information System (INIS)

1981-01-01

This annual report of the GKSS-Research Centre Geesthacht GmbH contains a survey of the research- and development work done in the year of the report and a survey on the organisation and situation of the society. The R and D programme can be divided in two parts: utilization of nuclear energy; utilization of the sea and the coasts. The first part concerns tasks on the sector of reactor safety compiled to a project which is fully integrated into the programme Reactor Safety of the Federal Ministy for Research and Technology. Development of nuclear-energy propelled vessels is continued to a smaller extent than before. The NS OTTO HAHN stopped operations in 1979. In 1980 a waste-disposed concept for the nuclear waste was developed, on the basis of which the GKSS received permission to put the ship out of service. (orig./RW) [de

Otto von Habsburg : III maailmasõda on läbi / Otto von Habsburg ; interv. Marianne Mikko

Index Scriptorium Estoniae

Habsburg, Otto von, 1912-2011

2002-01-01

Otto von Habsburg vastab küsimustele, mis puudutavad Euroopa konvendi presidendi teadet, et Türgi koht ei ole EL-is, Iraagi võimalikku ründamist, Hiina ja Venemaa suhteid, Tšetšeeniat, tshetsheene ja terrorismi, Venemaa, EL-i ja USA suhteid, III maailmasõda, Eesti Vabariigi tulevikku

'Pflanze, Otto, Bismarck'

OpenAIRE

Burgaud, Stéphanie

2013-01-01

La somme que l’historien américain O.P. consacra au ministre prussien puis chancelier d’Empire, Otto von Bismarck, parut en 1990, fruit de plusieurs décennies de travail. Traduite en allemand en 1997 chez Beck, elle connut un immense succès académique. La posture de l’auteur, en retrait des débats historiographiques sur le Sonderweg, son impartialité affichée, et surtout l’analyse équilibrée qu’il menait entre période prussienne et impériale (particulièrement lisible dans la version allemande...

Evaluating Otto the Auto: Does Engagement in an Interactive Website Improve Young Children's Transportation Safety?

Science.gov (United States)

Schwebel, David C; Johnston, Anna; Shen, Jiabin; Li, Peng

2017-07-19

Transportation-related injuries are a leading cause of pediatric death, and effective interventions are limited. Otto the Auto is a website offering engaging, interactive activities. We evaluated Otto among a sample of sixty-nine 4- and 5-year-old children, who participated in a randomized parallel group design study. Following baseline evaluation, children engaged with either Otto or a control website for 2 weeks and then were re-evaluated. Children who used Otto failed to show increases in transportation safety knowledge or behavior compared to the control group, although there was a dosage effect whereby children who engaged in the website more with parents gained safer behavior patterns. We conclude Otto may have some efficacy when engaged by children with their parents, but continued efforts to develop and refine engaging, effective, theory-driven strategies to teach children transportation safety, including via internet, should be pursued.

Lise Meitner (1878-1968) 'Mother of nuclear structure physics'

International Nuclear Information System (INIS)

Armbruster, P.

2001-03-01

A biography of Lise Meitner is given. Especially her work in cooperation with Otto Hahn concerning the discoveries of 207 Tl and 234 Pa by means of recoil separation and β-spectrometry as well as the discovery of fission is described. Furthermore her confrontations with racism and sexism are considered. (HSI)

Lise Meitner A Life in Physics

CERN Document Server

Sime, Ruth Lewin

1996-01-01

Lise Meitner (1878-1968) was a pioneer of nuclear physics and co-discoverer, with Otto Hahn and Fritz Strassmann, of nuclear fission. Braving the sexism of the scientific world, she joined the prestigious Kaiser Wilhelm Institute for Chemistry and became a prominent member of the international physics community. Of Jewish origin, Meitner fled Nazi Germany for Stockholm in 1938 and later moved to Cambridge, England. Her career was shattered when she fled Germany, and her scientific reputation was damaged when Hahn took full credit-and the 1944 Nobel Prize-for the work they had done together on

Kaks maastikuvaadet Karl Otto Gerhard von Kügelgenilt: romantismi kaja biidermeierlikus sarmis = Two Landscape Views by Otto Gerhard von Kügelgen: Echo of Romanticism in Biedermeier Charm / Kadi Polli

Index Scriptorium Estoniae

Polli, Kadi, 1973-

2011-01-01

2010. aastal Frankfurdis H. W. Fichteri kunstigaleriis müüki tulnud kümnest kunstiteosest, sh. Eesti Kunstimuuseumi poolt omandatud kahest Karl Otto Gerhard von Kügelgeni tööst. Franz Gerhard von Kügelgeni noorema poja Karl Otto Gerhard von Kügelgeni elust, loomingust ja tema akvarellidest "Perekond Vinni mõisas" ja "Rändur metsas"

Otto Lanz, surgeon and art collector

NARCIS (Netherlands)

van Gulik, T. M.; Brummelkamp, W. H.

1988-01-01

Otto Lanz (1865-1935) was educated in Switzerland, where he was trained in the surgical clinic of Theodore Kocher. In 1902, he was appointed as a professor of surgery in Amsterdam, remaining there until his death. He was wellknown for his surgery of the thyroid gland and for his studies on the

Quantum degeneracy effect on performance of irreversible Otto cycle with ideal Bose gas

International Nuclear Information System (INIS)

Wu Feng; Chen Lingen; Sun Fengrui; Wu Chih; Guo Fangzhong; Li Qing

2006-01-01

An Otto cycle working with an ideal Bose gas is called a Bose Otto cycle. The internal irreversibility of the cycle is included in the factors of internal irreversibility degree. The quantum degeneracy effect on the performance of the cycle is investigated based on quantum statistical mechanics and thermodynamics. Variations of the maximum work output ratio R W and the efficiency ratio y with temperature ratio τ are examined, which reveal the influence of the quantum degeneracy of the working substance on the performance of a Bose Otto cycle. It is shown that the results obtained herein are valid under both classical and quantum ideal gas conditions

Lise Meitner (1878-1968) 'Mother of nuclear structure physics'

Energy Technology Data Exchange (ETDEWEB)

Armbruster, P.

2001-03-01

A biography of Lise Meitner is given. Especially her work in cooperation with Otto Hahn concerning the discoveries of{sup 207}Tl and {sup 234}Pa by means of recoil separation and {beta}-spectrometry as well as the discovery of fission is described. Furthermore her confrontations with racism and sexism are considered. (HSI)

Preliminary thermodynamic study of regenerative Otto based cycles with zero NOx emissions operating with adiabatic and polytropic expansion

International Nuclear Information System (INIS)

Garcia, Ramon Ferreiro; Carril, Jose Carbia; Romero Gomez, Javier; Romero Gomez, Manuel

2016-01-01

Highlights: • Efficient polytropic expansion based Otto cycle. • Thermal efficiency is due to the inherent regeneration. • Low temperature combustion with zero NOx emissions. - Abstract: The aim of the paper is to demonstrate that a regenerative Otto cycle with adiabatic or polytropic expansion can achieve improved performance over traditional Otto engines, even exceeding the Carnot factor. Thus, the work deals with a novel regenerative Otto based internal combustion engine which differs from the conventional Otto thermal cycles in that the process of heat conversion into mechanical work is performed obeying a polytropic path function instead of the conventional adiabatic expansion without regeneration. Design characteristics concern the fact that combustion at constant volume is carried out undergoing large air excess so that the top combustion temperature is significantly lower than in conventional Otto cycles and consequently NOx emissions are neglected. Furthermore, during the polytropic expansion based path function, heat is absorbed by being submitted to a controlled heat flow rate, to achieve the desired polytropic expansion. The analysis of the regenerative Otto based on polytropic expansion is presented and results are compared with a regenerative Otto based on the adiabatic expansion and CF. The results show that a relevant advantage of the proposed regenerative Otto with polytropic expansion over the regenerative Otto cycle with adiabatic expansion involves performance enhancement within a wide range of combustion pressures, temperatures and regeneration capacities. Thus, thermal efficiency and specific work as function of the top combustion pressure ranges are of 71.95–58.43% and 143.5–173.6 kJ/kg respectively, when combustion pressures vary between 105 kPa and 200 kPa and CF is 60.8% (lower than the thermal efficiency). The successful results involving a compact engine structure, technically and economically viable, promises a new generation

Preliminary Neutronic Design of High Burnup OTTO Cycle Pebble Bed Reactor

OpenAIRE

Setiadipura, T; Irwanto, D; Zuhair, Zuhair

2015-01-01

The pebble bed type High Temperature Gas-cooled Reactor (HTGR) is among the interesting nuclear reactor designs in terms of safety and flexibility for co-generation applications. In addition, the strong inherent safety characteristics of the pebble bed reactor (PBR) which is based on natural mechanisms improve the simplicity of the PBR design, in particular for the Once-Through-Then-Out (OTTO) cycle PBR design. One of the important challenges of the OTTO cycle PBR design, and nuclear reactor ...

Shielding analysis method applied to nuclear ship 'MUTSU' and its evaluation based on experimental analyses

International Nuclear Information System (INIS)

Yamaji, Akio; Miyakoshi, Jun-ichi; Iwao, Yoshiaki; Tsubosaka, Akira; Saito, Tetsuo; Fujii, Takayoshi; Okumura, Yoshihiro; Suzuoki, Zenro; Kawakita, Takashi.

1984-01-01

Procedures of shielding analysis are described which were used for the shielding modification design of the Nuclear Ship ''MUTSU''. The calculations of the radiation distribution on board were made using Sn codes ANISN and TWOTRAN, a point kernel code QAD and a Monte Carlo code MORSE. The accuracies of these calculations were investigated through the analysis of various shielding experiments: the shield tank experiment of the Nuclear Ship ''Otto Hahn'', the shielding mock-up experiment for ''MUTSU'' performed in JRR-4, the shielding benchmark experiment using the 16 N radiation facility of AERE Harwell and the shielding effect experiment of the ship structure performed in the training ship ''Shintoku-Maru''. The values calculated by the ANISN agree with the data measured at ''Otto Hahn'' within a factor of 2 for fast neutrons and within a factor of 3 for epithermal and thermal neutrons. The γ-ray dose rates calculated by the QAD agree with the measured values within 30% for the analysis of the experiment in JRR-4. The design values for ''MUTSU'' were determined in consequence of these experimental analyses. (author)

Otto Toeplitz Memorial Conference

International Nuclear Information System (INIS)

Ball, J.A.

1981-01-01

A conference in operator theory and its applications commemorating the 100th anniversary of the birth of the distinguished German mathematician Otto Toeplitz, organized by the University of Tel Aviv together with German Mathematical Society, took place in Tel Aviv, Israel, from May 11th to 15th, 1981. I give here a broad very subjective overview of the proceedings of the conference for the benefit of readers of TTSP; for those interested in further details, a forthcoming volume in the Birkhaeuser series Operator Theory: Advances and Applications will consist of expanded written versions of most of the talks given at the conference

Micro-/nanoscaled irreversible Otto engine cycle with friction loss and boundary effects and its performance characteristics

International Nuclear Information System (INIS)

Nie, Wenjie; Liao, Qinghong; Zhang, ChunQiang; He, Jizhou

2010-01-01

An irreversible cycle model of the micro-/nanoscaled Otto engine cycle with internal friction loss is established. The general expressions of the work output and efficiency of the cycle are calculated based on the finite system thermodynamic theory, in which the quantum boundary effect of gas particles as working substance and the mechanical Casimir effect of gas system are considered. It is found that, for a micro-/nanoscaled Otto cycle devices, the work output W and efficiency η of the cycle can be expressed as the functions of the temperature ratio τ of the two heat reservoirs, the volume ratio r V and the surface area ratio r A of the two isochoric processes, the dimensionless thermal wavelength λ and other parameters of cycle, while for a macroscaled Otto cycle devices, the work output W 0 and efficiency η 0 of the cycle are independent of the surface area ratio r A and the dimensionless thermal wavelength λ. Further, the influence of boundary of cycle on the performance characteristics of the micro-/nanoscaled Otto cycle are analyzed in detail by introducing the output ratio W/W 0 and efficiency ratio η/η 0 . The results present the general performance characteristics of a micro-/nanoscaled Otto cycle and may serve as the basis for the design of a realistic Otto cycle device in micro-/nanoscale.

The night of the physicists. Heisenberg, Hahn, Weizsaecker, and the German bomb; Die Nacht der Physiker. Heisenberg, Hahn, Weizsaecker und die deutsche Bombe

Energy Technology Data Exchange (ETDEWEB)

Schirach, Richard von

2014-07-01

Finally the German atomic physicists around Heisenberg, von Weizsaecker, and Hahn worked on their ''uranium machine'' in a Swabian beer-cellar - and took themselves for the world elite of nuclear research. In imprisonment they heared from the dropping of the Hiroshima bomb - a shock. Richard von Schirach shows the hindered ''fathers of the German atomic bomb'' in close-up, their eagerness, their hybris, their true importance, and their attempts to give after the war a new interpretation of their own role. A book, which raises in the sense of Duerrenmatt the question for the responsibility of science.

Preliminary neutronic design of high burnup OTTO cycle pebble bed reactor

International Nuclear Information System (INIS)

Setiadipura, T.; Zuhair; Irwanto, D.

2015-01-01

The pebble bed type High Temperature Gas-cooled Reactor (HTGR) is among the interesting nuclear reactor designs in terms of safety and flexibility for co-generation applications. In addition, the strong inherent safety characteristics of the pebble bed reactor (PBR) which is based on natural mechanisms improve the simplicity of the PBR design, in particular for the Once-Through-Then-Out (OTTO) cycle PBR design. One of the important challenges of the OTTO cycle PBR design, and nuclear reactor design in general, is improving the nuclear fuel utilization which is shown by attaining a higher burnup value. This study performed a preliminary neutronic design study of a 200 MWt OTTO cycle PBR with high burnup while fulfilling the safety criteria of the PBR design.The safety criteria of the design was represented by the per-fuel-pebble maximum power generation of 4.5 kW/pebble. The maximum burnup value was also limited by the tested maximum burnup value which maintained the integrity of the pebble fuel. Parametric surveys were performed to obtain the optimized parameters used in this study, which are the fuel enrichment, per-pebble heavy metal (HM) loading, and the average axial speed of the fuel. An optimum design with burnup value of 131.1 MWd/Kg-HM was achieved in this study which is much higher compare to the burnup of the reference design HTR-MODUL and a previously proposed OTTO-cycle PBR design. This optimum design uses 17% U-235 enrichment with 4 g HM-loading per fuel pebble. (author)

Preliminary Neutronic Design of High Burnup OTTO Cycle Pebble Bed Reactor

Directory of Open Access Journals (Sweden)

T. Setiadipura

2015-04-01

Full Text Available The pebble bed type High Temperature Gas-cooled Reactor (HTGR is among the interesting nuclear reactor designs in terms of safety and flexibility for co-generation applications. In addition, the strong inherent safety characteristics of the pebble bed reactor (PBR which is based on natural mechanisms improve the simplicity of the PBR design, in particular for the Once-Through-Then-Out (OTTO cycle PBR design. One of the important challenges of the OTTO cycle PBR design, and nuclear reactor design in general, is improving the nuclear fuel utilization which is shown by attaining a higher burnup value. This study performed a preliminary neutronic design study of a 200 MWt OTTO cycle PBR with high burnup while fulfilling the safety criteria of the PBR design.The safety criteria of the design was represented by the per-fuel-pebble maximum power generation of 4.5 kW/pebble. The maximum burnup value was also limited by the tested maximum burnup value which maintained the integrity of the pebble fuel. Parametric surveys were performed to obtain the optimized parameters used in this study, which are the fuel enrichment, per-pebble heavy metal (HM loading, and the average axial speed of the fuel. An optimum design with burnup value of 131.1 MWd/Kg-HM was achieved in this study which is much higher compare to the burnup of the reference design HTR-MODUL and a previously proposed OTTO-cycle PBR design. This optimum design uses 17% U-235 enrichment with 4 g HM-loading per fuel pebble

40 CFR 86.008-10 - Emission standards for 2008 and later model year Otto-cycle heavy-duty engines and vehicles.

Science.gov (United States)

2010-07-01

... model year Otto-cycle heavy-duty engines and vehicles. 86.008-10 Section 86.008-10 Protection of... Otto-cycle HDE. (d) Every manufacturer of new motor vehicle engines subject to the standards prescribed... production of heavy-duty Otto-cycle motor vehicle engines for model year 2008, except as explicitly allowed...

40 CFR 86.098-10 - Emission standards for 1998 and later model year Otto-cycle heavy-duty engines and vehicles.

Science.gov (United States)

2010-07-01

... model year Otto-cycle heavy-duty engines and vehicles. 86.098-10 Section 86.098-10 Protection of..., exhaust emissions from new 1998 and later model year Otto-cycle heavy-duty engines shall not exceed: (i) For Otto-cycle heavy-duty engines fueled with either gasoline or liquefied petroleum gas, and intended...

Laguerre-Freud equations for the recurrence coefficients of the Laguerre-Hahn orthogonal polynomials on special nonuniform lattices

International Nuclear Information System (INIS)

Bangerezako, Gaspard; Foupouagnigni, Mama

2003-10-01

We give an algorithmic derivation of the Laguerre-Freud equations for the recurrence coefficients β n and γ n of the Laguerre-Hahn orthogonal polynomials on special nonuniform lattices. This algorithm is the most general one since it is valid for the Laguerre-Hahn orthogonal polynomials of any class k, on the special nonuniform lattices including the continuous (limiting cases), linear, q-linear and the q-nonlinear ones. Moreover, the algorithm allows to deduce an upper bound for the order of the equations in β n and γ n , which is respectively 2 k + 2 and 2 k + 3 when k is even, or 2 k + 3 and 2 k + 2 when k is odd. Finally, as applications, we discuss explicitly these equations for k = 1 in the continuous and linear cases, and k = 2 in the continuous symmetric one. (author)

Passage of nuclear powered ships in territorial waters and their stay in harbours

International Nuclear Information System (INIS)

Lucchini, L.; Voelckel, M.

1975-01-01

The specificity of rules governing entry of nuclear ships in the territorial waters of a State and their liability are reviewed. The concept of innocent passage prevailing for navigation in territorial waters is examined as are the protective measures taken by the Host State, in particular the prior authorisation characterizing thate State's discretionary powers of acceptance or refusal to admit the nuclear ship and the control over it. Liability rules and the nature of liability are analysed on the basis of agreements on the Savannah and the Otto Hahn. The importance of State intervention is demonstrated in its relationship with the operator particularly regarding control of operation and financial assistance. Also mentioned is liability for breach of the rules of procedure laid down in bilateral agreements, and in this context, a study is made of the rules of conduct for nuclear ships in territorial waters set out in the Savannah and Otto Hahn agreements. The liability of the coastal State is reviewed from the viewpoint of its grounds and possibilities of extension, given the development of nuclear navigation and the importance attached to protection against marine environmental pollution [fr

Two-state approximation of the Fadeev-Hahn equations

International Nuclear Information System (INIS)

Brener, S.E.

1993-01-01

The equations have been chosen which allow both to solve the scattering problems and to calculate the parameters of bound states of three particles with Coulomb interaction when the system energy is below the decay to three separate particles. The method of constructing of equations which are most suitable for concrete problems is considered. Different numerical schemes to calculate the low energy scattering cross sections with two-particle clusterization in 'in' and 'out' collision's channels have been developed. The bounds of applied approaches were determined and the peculiarities connected with differently defined reaction amplitudes under these approaches have been considered. The interpretation of obtained results at different definitions of reaction amplitudes was demonstrated, and the elastic, inelastic cross sections and muon transfer rates in hydrogen isotope mesic atom collisions have been calculated using Fadeev-Hahn equations. (author)

Five years of proton therapy of tumours of the eye at Hahn-Meitner Institute, Berlin

International Nuclear Information System (INIS)

Heufelder, J.; Cordini, D.; Heese, J.; Homeyer, H.; Kluge, H.; Morgenstern, H.; Fuchs, H.; Hoecht, S.; Nausner, M.; Hinkelbein, W.; Bechrakis, N.E.; Foerster, M.H.

2004-01-01

Eye tumors (choroidal melanomas, iris melanomas, and choroidal hemangiomas) are being treated with 68 MeV protons since 1998 at the Ion Beam Laboratory of the Hahn-Meitner Institute of Berlin (Germany's first proton therapy center), in cooperation with the Charite University Hospital in Berlin, Campus Benjamin Franklin. The proton beam, generated via a combination of Van de Graaff accelerator and cyclotron, is prepared by passive shaping for conformal tumor irradiation. A digital X-ray verification of the tumor location with the patient in sitting position limits the position uncertainties to a maximum of 0,3 mm. The treatment planning is performed using the program EYEPLAN. OCTOPUS, a CT-based planning program developed in cooperation with the German Cancer Research Center of Heidelberg, is under pre-clinical testing. Thus far, more than 400 patients have been irradiated. The first results are comparable to those obtained in other proton therapy centers. At the end of 2002, the University Hospital of Essen has also become a cooperation partner of the Hahn-Meitner Institute. (orig.) [de

50 years of nuclear fission

International Nuclear Information System (INIS)

Hilscher, D.

1989-01-01

The article tells the story of the discovery of nuclear fission in Berlin 50 years ago by Otto Hahn and Fritz Strassmann in cooperation with Lise Meitner. 50 years later nuclear fission is still a subject of research. Some question remain unanswered. Selected new research results are used to discuss the dynamics of the collective movement of the elementary nuclear fission process. (orig.) [de

The Golden Anniversary of the Hahn-Strassmann experiment

International Nuclear Information System (INIS)

Fine, L.W.; Herrmann, G.

1988-01-01

Nearly fifty years have passed since chemical evidence of fission was first published in the January, 1939 issue of Naturwissenschaften, heralding the beginning of the nuclear age. News had reached America a few days earlier as Niels Bohr arrived in New York and visited with Fermi and others at Columbia. And so began one of the most exciting, dramatic, and profoundly important periods in all of the history of modern science. Although the history of these scientific events has been well-documented, it is appropriate in this Golden Anniversary period to once again record and review them. Making use of (1) the chronology provided by the essential list of publications that followed first publication, (2) eye-witness accounts of the principal participants (as excerpted from live interviews and recording made over the years on audio tapes - including Hahn himself), and (3) available photographic records, the flow of events and the contexts of the times are once again recalled

The night of the physicists. Heisenberg, Hahn, Weizsaecker, and the German bomb

International Nuclear Information System (INIS)

Schirach, Richard von

2014-01-01

Finally the German atomic physicists around Heisenberg, von Weizsaecker, and Hahn worked on their ''uranium machine'' in a Swabian beer-cellar - and took themselves for the world elite of nuclear research. In imprisonment they heared from the dropping of the Hiroshima bomb - a shock. Richard von Schirach shows the hindered ''fathers of the German atomic bomb'' in close-up, their eagerness, their hybris, their true importance, and their attempts to give after the war a new interpretation of their own role. A book, which raises in the sense of Duerrenmatt the question for the responsibility of science.

Results of the critical experiments concerning OTTO loading at the critical HTR-test facility KAHTER

International Nuclear Information System (INIS)

Drueke, V.; Litzow, W.; Paul, N.

1982-12-01

Critical experiments concerning OTTO loading are described. In the KAHTER facility an OTTO loading has been simulated, therefore the original KAHTER assembly was reconstructed. The determination of critical masses and reactivity worths of control rods and of additional absorber rods in the top reflector and in the upper cavity was of main interest for comparison with reactor following calculations. Besides this, reaction rates in different energy regions were measured in the upper part of the core, in the cavity and top reflector. (orig.) [de

75 years of the discovery of nuclear fission. A timeline; 75 Jahre Entdeckung der Kernspaltung. Eine Zeitlinie

Energy Technology Data Exchange (ETDEWEB)

Reinartz, Jerome [atw-Redaktion, Hattingen (Germany)

2013-12-15

The discovery of nuclear fission and the possibility of a self- sustaining chain reaction begins with modern atomic and nuclear physics at the end of the 19{sup th} century. Further key discoveries resulted as of 1900 with the fundamentals on the structure of matter. In 1938 Otto Hahn, Fritz Strassmann and Lise Meitner came to realise that neutrons were able to split uranium nuclei. Important milestones until 1938 and beyond are summarized. (orig.)

J. Randvere Ruth ja Otto Weiningeri Geschlecht und Charakter / Mirjam Hinrikus

Index Scriptorium Estoniae

Hinrikus, Mirjam, 1972-

2004-01-01

Naise kirjeldus J. Randvere "Ruthis" ja Otto Weiningeri "Geschlecht und Charakter'is". Andmed autori kohta lk. 202. Ilmunud ka kogumikus: J. Randvere "Ruth" 19.-20. sajandi vahetuse kultuuris / koost. Mirjam Hinrikus. Tallinn : Underi ja Tuglase Kirjanduskeskus, 2006, lk. 145-169

Award for Lise Meitner

International Nuclear Information System (INIS)

1967-01-01

It is a matter of history that the work in the 1930's of Lise Meitner, Otto Hahn and Fritz Strassmann played a great part in pointing the way to exploiting the possibilities of fission. One of the most interesting occasions the Agency has known came in 1963 when Lise Meitner paid a visit to talk about her life as a scientist, thus returning to the city where she had started her university career in 1901. Her account of a career which had brought her into contact with scientists such as Einstein, Planck, Rutherford, Bohr and many others took her listeners back to the birth of the atomic age. A photograph is shown taken at Dr. Meitner's home in Cambridge, UK, when she received the Enrico Fermi award for 1966, shared with Hahn and Strassmann

Interference of transcription across H-NS binding sites and repression by H-NS.

Science.gov (United States)

Rangarajan, Aathmaja Anandhi; Schnetz, Karin

2018-05-01

Nucleoid-associated protein H-NS represses transcription by forming extended DNA-H-NS complexes. Repression by H-NS operates mostly at the level of transcription initiation. Less is known about how DNA-H-NS complexes interfere with transcription elongation. In vitro H-NS has been shown to enhance RNA polymerase pausing and to promote Rho-dependent termination, while in vivo inhibition of Rho resulted in a decrease of the genome occupancy by H-NS. Here we show that transcription directed across H-NS binding regions relieves H-NS (and H-NS/StpA) mediated repression of promoters in these regions. Further, we observed a correlation of transcription across the H-NS-bound region and de-repression. The data suggest that the transcribing RNA polymerase is able to remodel the H-NS complex and/or dislodge H-NS from the DNA and thus relieve repression. Such an interference of transcription and H-NS mediated repression may imply that poorly transcribed AT-rich loci are prone to be repressed by H-NS, while efficiently transcribed loci escape repression. © 2018 John Wiley & Sons Ltd.

Liivimaa orientalisti Otto Friedrich Richteri õpiaastad / Indrek Jürjo

Index Scriptorium Estoniae

Jürjo, Indrek, 1956-2009

2006-01-01

Richteri koduõpetajaks oli kuulus Venemaa ajaloolane ja Tartu ülikooli kauaaegne rektor Gustav Ewers. Kõigepealt saadeti Otto prantsuse ja vene keele õppimise eesmärgil Moskva ülikooli (1808). 1809. aasta sügisest jätkus haridustee Heidelbergis, järgnes tavapärasest haridusteest eristuv erastuudium Viinis, mis kulges iseseisvate õpingute ja vahetu läbikäimise tähe all mitme tolleaegse vaimusuurusega

40 CFR 86.099-10 - Emission standards for 1999 and later model year Otto-cycle heavy-duty engines and vehicles.

Science.gov (United States)

2010-07-01

... model year Otto-cycle heavy-duty engines and vehicles. 86.099-10 Section 86.099-10 Protection of... to Otto-cycle engines used in such MDPVs, except as specified in subpart S of this part. The term... AND IN-USE HIGHWAY VEHICLES AND ENGINES General Provisions for Emission Regulations for 1977 and Later...

Multiple-state quantum Otto engine, 1D box system

Energy Technology Data Exchange (ETDEWEB)

Latifah, E., E-mail: enylatifah@um.ac.id [Laboratory of Theoretical Physics and Natural Philosophy, Physics Department, Institut Teknologi Sepuluh Nopember, ITS, Surabaya, Indonesia and Physics Department, Malang State University (Indonesia); Purwanto, A. [Laboratory of Theoretical Physics and Natural Philosophy, Physics Department, Institut Teknologi Sepuluh Nopember, ITS, Surabaya (Indonesia)

2014-03-24

Quantum heat engines produce work using quantum matter as their working substance. We studied adiabatic and isochoric processes and defined the general force according to quantum system. The processes and general force are used to evaluate a quantum Otto engine based on multiple-state of one dimensional box system and calculate the efficiency. As a result, the efficiency depends on the ratio of initial and final width of system under adiabatic processes.

From nuclear fission to nuclear energy

International Nuclear Information System (INIS)

Pocock, R.F.

1988-01-01

Otto Hahn, a German chemist, demonstrated the fission of the uranium nucleus in December 1938. Ten months later, basic physical theory had been modified to account for this phenomenon. It is suggested here that this great advance in radio-chemistry and physics was influenced considerably by political considerations. By the outbreak of the European War in September 1939, all the major scientific principles involved in the production of atomic weapons were well-known and were available in all industrial countries. (author)

Empire, Nationalism and the Jewish Question: Victor Adler and Otto Bauer

Directory of Open Access Journals (Sweden)

Wolfgang Maderthaner

2015-12-01

Full Text Available This paper uses the life and thought of two important figures in the history of Austrian socialism—Victor Adler and Otto Bauer—as a prism through which to examine the complex relationship between German nationalism, the Jewish Question and pro-Habsburgism among the early leadership of the Austrian Social Democratic Party.

NS19504

DEFF Research Database (Denmark)

Nausch, Bernhard; Rode, Frederik; Jørgensen, Susanne

2014-01-01

channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.0 ± 1.4 µM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization......19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 µM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 µ......M) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K(+) concentration consistent with a K(+) channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels...

LA CTE "OTTO PARELLADA" (TALLAPIEDRA COMO BASE MATERIAL DE ESTUDIO

Directory of Open Access Journals (Sweden)

Alberto E Calvo González

2011-03-01

Full Text Available Se presenta el análisis de las posibilidades que tiene la CTE" Otto Parellada" como elemento fundamental en la formación de ingenieros electricistas, así como para otras especialidades.Se expone el modo en que actualmente se le aprovecha para la carrera de Ingeniería Eléctrica en ladisciplina de Centrales Termoeléctricas, así como para la carrera de Ingeniería Mecánica en la asignatura homónimadel 1er. año. Se exponen otras posibilidades de la planta que podrían ser explotadas aún por otras carreras comoArquitectura, al tener características que la avalan como Patrimonio Industrial.  In this paper is presented the analysis of the possibilities like fundamental element that Otto Parellada SteamPower Plant has for the electrical, as well as other specialties engineers' syllabus. The way that at present time isused for the electrical engineers education, in the thermal engineering subjects is exposed, as well as for themechanical engineering in the 1st year. Other possibilities of the plant that could still be exploited by otherscareers like architecture, due to the characteristic that endorse it as Industrial Patrimony are also exposed.

Otto von Guericke and 17th century cosmology

Science.gov (United States)

Knobloch, Eberhard

Otto von Guericke's scientific method was based on reason and experimental science. His cosmology was embedded in theology and can be interpreted as a refutation of Descartes' worldview. He used Nicolaus Cusanus' theory of quantities in order to characterize space. The notion of space has to be distinguished from that of world or heaven. Forces play a crucial role in this respect described by Athanasius Kircher in his "Celestial Journey". Guericke read this work very diligently. In spite of some obvious similarities between Guericke's and Newton's scientific aims and methods there are crucial differences between the scientific convictions and results of these scholars.

50 ns Backup Solution

CERN Document Server

Kain, V; Bartosik, H; Goddard, B; Höfle, W; Iadarola, G; Meddahi, M; Pieloni, T; Rumolo, G; Salvant, B; Wenninger, J

2014-01-01

The baseline bunch spacing for LHC high luminosity proton-proton operation after LS3 is 25 ns to maximize the integrated luminosity while keeping the pile-up low. The success of this mode of operation is not guaranteed. Electron cloud, UFOs, long-range beambeam, heating and other effects might make 25 ns operation in the LHC and/or the injectors difficult. This talk will review possible showstoppers in the LHC and injectors for 25 ns operation and discuss possible remedies. An alternative would be re-considering 50 ns operation. An estimate of the 50 ns performance will be given. The question of whether a different upgrade path would have to be chosen in case of 50 ns operation will also be addressed.

50 ns Backup Solution

International Nuclear Information System (INIS)

Kain, V; Arduini, G; Bartosik, H; Goddard, B; Höfle, W; Iadarola, G; Meddahi, M; Pieloni, T; Rumolo, G; Salvant, B; Wenninger, J

2014-01-01

The baseline bunch spacing for LHC high luminosity proton-proton operation after LS3 is 25 ns to maximize the integrated luminosity while keeping the pile-up low. The success of this mode of operation is not guaranteed. Electron cloud, UFOs, long-range beambeam, heating and other effects might make 25 ns operation in the LHC and/or the injectors difficult. This talk will review possible showstoppers in the LHC and injectors for 25 ns operation and discuss possible remedies. An alternative would be re-considering 50 ns operation. An estimate of the 50 ns performance will be given. The question of whether a different upgrade path would have to be chosen in case of 50 ns operation will also be addressed

Giant magnons under NS-NS and Melvin fields

International Nuclear Information System (INIS)

Huang, W.-H.

2006-01-01

The giant magnon is a rotating spiky string configuration which has the same dispersion relation between the energy and angular momentum as that of a spin magnon. In this paper we investigate the effects of the NS-NS and Melvin fields on the giant magnon. We first analyze the energy and angular momenta of the two-spin spiky D-string moving on the AdS 3 x S 1 with the NS-NS field. Due to the infinite boundary of the AdS spacetime the D-string solution will extend to infinity and it appears the divergences. After adding the counter terms we obtain the dispersion relation of the corresponding giant magnon. The result shows that there will appear a prefactor before the angular momentum, in addition to some corrections in the sine function. We also see that the spiky profile of a rotating D-string plays an important role in mapping it to a spin magnon. We next investigate the energy and angular momentum of the one-spin spiky fundamental string moving on the R x S 2 with the electric or magnetic Melvin field. The dispersion relation of the corresponding deformed giant magnon is also obtained. We discuss some properties of the correction terms and their relations to the spin chain with deformations

Conversion of cycle Diesel engines to Otto aiming the methane utilization as alternative fuel; Conversao de motores do ciclo diesel para Otto visando a utilizacao do metano como combustivel alternativo

Energy Technology Data Exchange (ETDEWEB)

Torres, J F; Venanzi, D [Sao Paulo Univ., Sao Carlos, SP (Brazil). Escola de Engenharia

1988-12-31

A diesel engine was converted in Otto engine for use methane as fuel, by modifications on compression ratio and on the induction system, and inclusion of a spark ignition system. The performance of dynamometer essays results in both cycles are compared and presented in overlapped curves. (author). 5 refs., 2 figs., 2 tabs

Host cell killing by the West Nile Virus NS2B-NS3 proteolytic complex: NS3 alone is sufficient to recruit caspase-8-based apoptotic pathway

International Nuclear Information System (INIS)

Ramanathan, Mathura P.; Chambers, Jerome A.; Pankhong, Panyupa; Chattergoon, Michael; Attatippaholkun, Watcharee; Dang, Kesen; Shah, Neelima; Weiner, David B.

2006-01-01

The West Nile Virus (WNV) non-structural proteins 2B and 3 (NS2B-NS3) constitute the proteolytic complex that mediates the cleavage and processing of the viral polyprotein. NS3 recruits NS2B and NS5 proteins to direct protease and replication activities. In an effort to investigate the biology of the viral protease, we cloned cDNA encoding the NS2B-NS3 proteolytic complex from brain tissue of a WNV-infected dead crow, collected from the Lower Merion area (Merion strain). Expression of the NS2B-NS3 gene cassette induced apoptosis within 48 h of transfection. Electron microscopic analysis of NS2B-NS3-transfected cells revealed ultra-structural changes that are typical of apoptotic cells including membrane blebbing, nuclear disintegration and cytoplasmic vacuolations. The role of NS3 or NS2B in contributing to host cell apoptosis was examined. NS3 alone triggers the apoptotic pathways involving caspases-8 and -3. Experimental results from the use of caspase-specific inhibitors and caspase-8 siRNA demonstrated that the activation of caspase-8 was essential to initiate apoptotic signaling in NS3-expressing cells. Downstream of caspase-3 activation, we observed nuclear membrane ruptures and cleavage of the DNA-repair enzyme, PARP in NS3-expressing cells. Nuclear herniations due to NS3 expression were absent in the cells treated with a caspase-3 inhibitor. Expression of protease and helicase domains themselves was sufficient to trigger apoptosis generating insight into the apoptotic pathways triggered by NS3 from WNV

A multi-stage-flash desalination plant of relative small performance with an integrated pressurized water reactor as a nuclear heat source

International Nuclear Information System (INIS)

Peltzer, M.; Petersen, G.

1976-01-01

In the Krupp-GKSS joint study MINIPLEX the requirements for seawater-desalination-plants with a performance in the range of 10,000 to 80,000 m 3 /d heated by a nuclear reactor are investigated. The reactor concept is similar to the integrated pressurized water reactor (IPWR) of the nuclear ship OTTO HAHN. The calculated costs of the desalinated water show, that due to the fuel cost advantages of reactors small and medium nuclear desalination plants are economically competetive with oil-fired plants since the steep rise of oil price in autumn 1973. (orig.) [de

Analysis of NMR spectra of sugar chains of glycolipids by multiple relayed COSY and 2D homonuclear Hartman-Hahn spectroscopy

International Nuclear Information System (INIS)

Inagaki, F.; Kohda, D.; Kodama, C.; Suzuki, A.

1987-01-01

The authors applied multiple relayed COSY and 2D homonuclear Hartman-Hahn spectroscopy to globoside, a glycolipid purified from human red blood cells. The subspectra corresponding to individual sugar components were extracted even from overlapping proton resonances by taking the cross sections of 2D spectra parallel to the F 2 axis at anomeric proton resonances, so that unambiguous assignments of sugar proton resonances were accomplished. (Auth.)

Pioneers of the Nuclear Sciences

International Nuclear Information System (INIS)

Bosch, P.; Bulbulian, S.; Fernandez, M.; Jimenez, M.; Segovia, N.; Solache, M.; Tejera, A.

1994-01-01

From 1896, date in which radioactivity is discovered, to 1942, when Fermi installed the first atomic pile, a small group of researchers got to the bottom of the atom, and proposed an appropriate structure to define it and to create a technology derived from their findings. There were four schools the protagonists of such studies: a French group (Becquerel, Curie and Joliet Curie), an anglo-saxon group (Chadwick, Rutherford and Thomson), an Italian group (Fermi) and finally, an Australian-German group (Frisch, Hahn, Meitner and Strassmann). The progress of the knowledge was very fast because the results were exchanged and discussed in congresses in a totally cosmopolitan ambient, with the knowledge as the only objective. The book is arranged in sections as follows: I. The discovery of natural radioactivity. II. Atomic structure. III. Artificial radioactivity. IV. Properties of thermal neutrons. V. Nuclear fission: Otto Hahn and the german school. VI. Conclusions and two appendixes. (Author)

Catástrofe y no catastrofismo en las poéticas de Benedetti, Gelman, Hahn y Romero

Directory of Open Access Journals (Sweden)

Silvana Serrani

2013-06-01

Full Text Available Which significant expressive singularities can be pointed out in the poetic expression of apocalyptic issues in Southern Cone Spanish American poetry? This paper focuses on the poetics of four authors who produced part of their work in exile, as a result of apocalyptic XXth Century dictatorships in the Latin-American Southern Cone: Mario Benedetti (Uruguay, Juan Gelman (Argentina,Oscar Hahn (Chile and Elvio Romero (Paraguay. Our thematic approach does not concentrate on the Biblical Apocalypse or St John´s myths in literature, but, rather, on the poetic expressions of historical ruptures or extraordinary disasters. The paper takes into account the notion of (poetic constellation (Monteleone, 2003 & 2010 to explain the non-exhaustivity of the group of poetics and the relevance of considering these four formally dissimilar poetics together. A synthetic characterization of each of the poetics is presented, based on well-known critical studies, discussing and exemplifying: neo-manierism and elements of fantasy literature in Hahn´s poetry; torrential wordiness and symbolism in Gelman´s poetry; “realism” and songs of heroic deeds in Romero´s poetry and “humorous” colloquialism in Benedetti´s poetry. Finally, using Discourse Studies, mainly, the interdiscourse concept (Foucault, [1969]2012; Pêcheux, [1990]2009, we show that, despite the underlying differences between the four poetics, two points of convergence can be pointed out: non-catastrophism and the universal approach of (even local issues pervading the constellation composed by those four poetic expressions.

The Otto-Atkinson engine. A study of fluid flow and combustion with early and late inlet valve closing

Energy Technology Data Exchange (ETDEWEB)

Haakansson, Henrik

1999-10-01

This report contains results of measurements on an Otto engine. The purpose for this work has been to do measurements of the flow in the cylinder but also measurements of the cylinder pressure have been performed. The flow measurements are made with the method Laser Doppler Velocimetry, LDV. The reason why these measurements are made at all are the pump losses that implies a lower efficiency for the Otto engine at part load. In this work two alternative ways that highly reduces the pump losses are examined. These are early inlet valve closing and late inlet valve closing. To further increase the efficiency at part load an increased compression ratio has been used together with the different valve strategies. With these two ways of operation, at a part load of about 4 - 5 IMEP{sub net}, increases of about 20% of the net indicated efficiency has been obtained. Additionally this report contains a chapter about the possible use of a variable valve actuation or timing system, VVA or VVT. Many conditions for the Otto cycle can be improved by the use of a variable valve actuation and in this chapter it is dealt with the most important ones.

Performance of a cycle Otto engine using biogas; Desempenho de um motor ciclo Otto utilizando biogas como combustivel

Energy Technology Data Exchange (ETDEWEB)

Souza, Juliano de [Universidade Estadual do Oeste do Parana (UNIOESTE), Cascavel, PR (Brazil). Centro de Ciencias Exatas e Tecnologicas], e-mail: jsouza@unioeste.br; Souza, Samuel N. Melegari de, [Universidade Estadual do Oeste do Parana (UNIOESTE), Cascavel, PR (Brazil); Machado, Paulo Romeu M [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Dept. de Engenharia Mecanica

2004-07-01

The rising of the oil prices is increasing the search for alternative fuels. Brazil has a great availability of biogas from anaerobic digestion in the rural area, urban waste in the landfills and treatment of the municipal sewer. In this work were evaluated in dynamometer a cycle Otto engine using biogas, and were obtained the characteristics curves of torque and power. First was done the evidence test with gasoline, biogas and natural gas, using commercial systems for this fuels, using as comparison for other tests. After has been done tests for some combinations of ignition point, mixer of gas and compression tax. By the analysis of the results has been concluded that the better results for power and torque using biogas as fuel were with a tax compression of 12,5:1, gas mixer long and ignition point advanced in 45 deg. (author)

V strane piramid : zhizn i trudõ Otto Friedricha von Richtera / Sergei Stadnikov ; tõlk. Veronika Einberg

Index Scriptorium Estoniae

Stadnikov, Sergei, 1956-

2003-01-01

Vastse-Kuustest pärit egüptoloogist Otto Friedrich von Richter'ist (1791-1816). Richteri ja Lindmani Egiptuse-Nuubia ekspeditsioonist, Tartu Ülikooli Muinasteaduse muuseumile annetatud kollektsioonist

OTTO-PAP: An alternative option to the PBMR fuelling philosophy

International Nuclear Information System (INIS)

Mulder, E.; Teuchert, E.

1997-01-01

Once Through Then Out, Power Adjusted by Poison (OTTO-PAP) fuelling of a high temperature pebble-bed reactor offers a simple alternative to the MEDUL (Mehrfachdurchlauf = German for multi-pass) fuelling regime followed in pebble bed reactor designs to date. The prerequisite for a modular reactor unit of maximum power output, subject to observing passive safety characteristics is a sufficiently flat axial neutron flux profile. This is achieved by introducing B 4 C coated particles of pre-calculated size and packing density within the fuel spheres. In accordance with AVR operating practise the temperature profile is radially equalised by introducing a 2-zone core loading. Adding pure graphite spheres loosely into the centre column area of the core effectively reduced the maximum power in the middle. Increasing the reactor diameter is enabled by the introduction of noses. A 3-D geometric modeller developed in cylindrical co-ordinates enables a given flow description of the pebbles adjacent to the nose boundaries and in the vicinity of the shut down/control rods. After translation of the geometric data the neutronic behaviour of the reactor is followed in 3-D by the CITATION code. This study is aimed towards achieving an optimal core layout with a LEU (Low Enriched Uranium) fuel cycle. Physical properties of the OTTO-PAP, 150 MWt reference design is reported, while computations performed observe results obtained by the reference HTR-MODUL design. (author)

1981 research programme and budget of Hahn-Meitner-Institut fuer Kernforschung Berlin

International Nuclear Information System (INIS)

Anon.

1981-01-01

Hahn-Meitner-Institut fuer Kernforschung Berlin (HMI) is one of the twelve large research centers of the Federal Republic of Germany; like the other centers, it has to present a combined research programme and budget (programme budget) every year. In these programme budgets, as in the medium-term financial planning in the federal budget, planning for the current year is combined with a medium-term plan for the three next years. For the year 1981, the budget of HMI includes a total expenditure of about DM 85 million, DM 71.2 million of which are direct R + D expenditures. This R + D programme is carried by 396 of the total staff of 705. Research is done in the following fields (approximate figures): Heavy ion physics DM 23.0 million. Radiation- and photochemistry DM 11.4 million. Solid state research DM 20.9 million. Nuclear chemistry DM 8.9 million. Data processing/electronics DM 7.0 million. (orig./UA) [de

Practice of the Education for the Principle of Otto Cycle by the E-Learning CG-Content

Science.gov (United States)

Sato, Tomoaki; Nagaoka, Keizo; Oguchi, Kosei

A CG-animation content which supports the learning of the Otto cycle was developed. This content has a piston assembly and the diagrams of PV, VS, TP and TS. The each diagram has a pointer which moves along the line of the graph and they are synchronized with the movement of the piston. The learners can operate this content directly on the e-learning system. While watching the movements of the piston assembly, the learners can confirm the state of the engine about temperature, pressure, volume, and entropy by the synchronized pointer on the diagrams. This content was used for the class of the machining practice exercise. The learning effect of the content was examined by the score of the short test. As the result of this examination, the CG-animation content was effective in the learning of the Otto cycle.

Introduction to Network Simulator NS2

CERN Document Server

Issariyakul, Teerawat

2012-01-01

"Introduction to Network Simulator NS2" is a primer providing materials for NS2 beginners, whether students, professors, or researchers for understanding the architecture of Network Simulator 2 (NS2) and for incorporating simulation modules into NS2. The authors discuss the simulation architecture and the key components of NS2 including simulation-related objects, network objects, packet-related objects, and helper objects. The NS2 modules included within are nodes, links, SimpleLink objects, packets, agents, and applications. Further, the book covers three helper modules: timers, ra

Molecular dynamic simulation of complex NS2B-NS3 DENV2 ...

African Journals Online (AJOL)

Several vaccines have been developed against the disease, but they only ... a two component NS2B-NS3 protease that cleaves viral precursor proteins, and ... The results provide conformational changes of enzyme-inhibitor complex that is ...

Belated recognition: Lise Meitner's role in the discovery of fission

International Nuclear Information System (INIS)

Sime, R.L.

1990-01-01

Although physicist Lise Meitner is known for the first theoretical explanation of nuclear fission, the discovery itself is generally attributed only to her co-workers Otto Hahn and Fritz Strassmann. In fact, however, Meitner was essential to the discovery at every phase: she brought the uranium investigation to Berlin, led the Berlin group for four years, and, even after fleeing Germany, provided the critical direction which culminated in the identification of barium in December 1983. Recognition of Lise Meitner's contributions remedies a significant historical omission, and places the discovery itself in its proper scientific context. (author) 48 refs

Notes on the Wess-Zumino-Witten-like structure: L{sub ∞} triplet and NS-NS superstring field theory

Energy Technology Data Exchange (ETDEWEB)

Matsunaga, Hiroaki [Institute of Physics, the Czech Academy of Sciences,Na Slovance 2, Prague 8 (Czech Republic); Yukawa Institute for Theoretical Physics, Kyoto University,Kyoto 606-8502 (Japan)

2017-05-17

In the NS-NS sector of superstring field theory, there potentially exist three nilpotent generators of gauge transformations and two constraint equations: it makes the gauge algebra of type II theory somewhat complicated. In this paper, we show that every NS-NS actions have their WZW-like forms, and that a triplet of mutually commutative L{sub ∞} products completely determines the gauge structure of NS-NS superstring field theory via its WZW-like structure. We give detailed analysis about it and present its characteristic properties by focusing on two NS-NS actions proposed by https://www.doi.org/10.1007/JHEP01(2017)022 and https://www.doi.org/10.1007/JHEP08(2014)158.

Revista Espinhaço entrevistaDra. Bette Otto Bliesner(NCAR Boulder

Directory of Open Access Journals (Sweden)

Kourosh Behzadian

2016-12-01

Full Text Available Dra. Bette Otto Bliesner foi entrevistada pela Revista Espinhaço durante o BIARI 2016, que ocorreu em Providence (EUA na Brown University. Para este volume especial da Revista Espihaço, a Dra. Bette, pesquisadora do National Center for Atmospheric Research (NCAR e especialista em modelagem climática e paleo-climatologia, traz reflexões sobre seu recente trabalho no IPCC.Esta entrevista foi conduzida por Kourosh Behzadian (University of West London, Douglas Sathler (FIH/Cegeo/UFVJM and Lorena Fleury (UFRGS.

Briefe aus dem Morgenland - Otto Friedrich von Richters Forschungsreise in den Jahren 1814-1816 / Vladimir Sazonov

Index Scriptorium Estoniae

Sazonov, Vladimir, 1979-

2013-01-01

Arvustus: Briefe aus dem Morgenland - Otto Friedrich von Richters Forschungsreise in den Jahren 1814-1816, hrsg. von Indrek Jürjo, Sergei Stadnikov, Hamburger Beiträge zur Geschichte des östlichen Europa, Bd. 20. Hamburg: Verlag Dr. Kovač 2013, 313 lk.

THE PSYCHOLOGY OF THINKING BEFORE THE COGNITIVE REVOLUTION : Otto Selz on Problems, Schemas, and Creativity

NARCIS (Netherlands)

ter Hark, Michel

Otto Selz has been hailed as one of the most important precursors of the cognitive revolution, yet surprisingly few studies of his work exist. He is often mentioned in the context of the Wurzburg School of the psychology of thinking and sometimes in the context of Gestalt psychology. In this paper,

NMR analysis of the dynamic exchange of the NS2B cofactor between open and closed conformations of the West Nile virus NS2B-NS3 protease.

Directory of Open Access Journals (Sweden)

Xun-Cheng Su

Full Text Available BACKGROUND: The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation in the absence of inhibitor and lining the substrate binding site (closed conformation in the presence of an inhibitor. METHODS: In this work, nuclear magnetic resonance (NMR spectroscopy of isotope and spin-labeled samples of the West Nile virus protease was used to investigate the occurrence of equilibria between open and closed conformations in solution. FINDINGS: In solution, the closed form of the West Nile virus protease is the predominant conformation irrespective of the presence or absence of inhibitors. Nonetheless, dissociation of the C-terminal part of the NS2B cofactor from the NS3 protease (open conformation occurs in both the presence and the absence of inhibitors. Low-molecular-weight inhibitors can shift the conformational exchange equilibria so that over 90% of the West Nile virus protease molecules assume the closed conformation. The West Nile virus protease differs from the dengue virus protease, where the open conformation is the predominant form in the absence of inhibitors. CONCLUSION: Partial dissociation of NS2B from NS3 has implications for the way in which the NS3 protease can be positioned with respect to the host cell membrane when NS2B is membrane associated via N- and C-terminal segments present in the polyprotein. In the case of the West Nile virus protease, discovery of low-molecular-weight inhibitors that act by breaking the association of the NS2B cofactor with the NS3 protease is impeded by the natural affinity of the cofactor to the NS3 protease. The same strategy can be more successful in the case of the dengue virus NS2B-NS3 protease.

Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen

Directory of Open Access Journals (Sweden)

Canard Bruno

2011-10-01

Full Text Available Abstract Background The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4. Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle. Results We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation. Conclusions We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy.

Putini sõprade käes on Riia ja peagi võibolla ka Seim / Otto Ozols ; intervjueerinud Taavi Minnik

Index Scriptorium Estoniae

Ozols, Otto

2016-01-01

Intervjuu Läti kirjaniku ja publitsisti Otto Ozolsiga lõunanaabrite juures toimuvast ning sellest, kuidas on viimaste aastate arengud Euroopas ja Venemaal puudutanud Läti poliitikat ning ühiskonda

Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7

DEFF Research Database (Denmark)

Galli, Andrea; Scheel, Troels K H; Prentoe, Jannick C

2013-01-01

Hepatitis C virus (HCV) is an important human pathogen infecting hepatocytes. With the advent of infectious cell culture systems, the HCV particle assembly and release processes are finally being uncovered. The HCV core and NS5A proteins co-localize on cytoplasmic lipid droplets (c......LDs) or on the endoplasmic reticulum (ER) at different stages of particle assembly. Current knowledge on assembly and release is primarily based on studies in genotype 2a cell culture systems; however, given the high genetic heterogeneity of HCV, variations might exist among genotypes. Here, we developed novel HCV strain...... JFH1-based recombinants expressing core-NS2 and NS5A from genotypes 1-7, and analysed core and NS5A co-localization in infected cells. Huh7.5 cells were transfected with RNA of core-NS2/NS5A recombinants and putative adaptive mutations were analysed by reverse genetics. Adapted core-NS2/NS5A...

Otto Mennicke (1876-) and the first description of skull base anomalies causing cerebellar tonsillar ectopia: one of the first mentions of the Chiari I malformation.

Science.gov (United States)

Fries, Fabian N; Hendrix, Philipp; Brinker, Titus J; Loukas, Marios; Tubbs, R Shane

2017-05-01

Although Hans Chiari made significant and meaningful contributions to our understanding and classification of hindbrain herniations, others have also contributed to this knowledge. One figure who has been lost to history is Otto Mennicke. Herein, we discuss his role in our understanding of tonsillar ectopia and his life and connection to Hans Chiari. Our knowledge of what is now known as the Chiari malformations has been shaped by several clinicians including Otto Mennicke.

Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease.

Science.gov (United States)

Qamar, Tahir Ul; Mumtaz, Arooj; Ashfaq, Usman Ali; Azhar, Samia; Fatima, Tabeer; Hassan, Muhammad; Hussain, Syed Sajid; Akram, Waheed; Idrees, Sobia

2014-01-01

Dengue virus NS2/NS3 protease because of its ability to cleave viral proteins is considered as an attractive target to screen antiviral agents. Medicinal plants contain a variety of phytochemicals that can be used as drug against different diseases and infections. Therefore, this study was designed to uncover possible phytochemical of different classes (Aromatic, Carbohydrates, Lignin, Saponins, Steroids, Tannins, Terpenoids, Xanthones) that could be used as inhibitors against the NS2B/NS3 protease of DENV. With the help of molecular docking, Garcinia phytochemicals found to be bound deeply inside the active site of DENV NS2B/NS3 protease among all tested phytochemicals and had interactions with catalytic triad (His51, Asp75, Ser135). Thus, it can be concluded from the study that these Gracinia phytochemicals could serve as important inhibitors to inhibit the viral replication inside the host cell. Further in-vitro investigations require confirming their efficacy.

Otto Peters on Distance Education: The Industrialization of Teaching and Learning. Routledge Studies in Distance Education.

Science.gov (United States)

Keegan, Desmond, Ed.

This book contains new and previously published translations of 11 essays and articles about the industrialization of teaching and learning in distance education that were originally published in German by Otto Peters between 1965 and 1993. A "Preface" (Desmond Keegan) and an introduction placing Peters' writings in their historical…

A quantum Otto engine with finite heat baths

DEFF Research Database (Denmark)

Pozas-Kerstjens, Alejandro; Brown, Eric G.; Hovhannisyan, Karen V.

2018-01-01

We study a driven harmonic oscillator operating an Otto cycle by strongly interacting with two thermal baths of finite size. Using the tools of Gaussian quantum mechanics, we directly simulate the dynamics of the engine as a whole, without the need to make any approximations. This allows us...... to understand the non-equilibrium thermodynamics of the engine not only from the perspective of the working medium, but also as it is seen from the thermal baths' standpoint. For sufficiently large baths, our engine is capable of running a number of perfect cycles, delivering finite power while operating very...... close to maximal efficiency. Thereafter, having traversed the baths, the perturbations created by the interaction abruptly deteriorate the engine's performance. Weadditionally study the correlations generated in the system, and, in particular, we find a direct connection between the build up of bath...

NS simulator for beginners

CERN Document Server

Altman, Eitan

2012-01-01

NS-2 is an open-source discrete event network simulator which is widely used by both the research community as well as by the people involved in the standardization protocols of IETF. The goal of this book is twofold: on one hand to learn how to use the NS-2 simulator, and on the other hand, to become acquainted with and to understand the operation of some of the simulated objects using NS-2 simulations. The book is intended to help students, engineers or researchers who need not have much background in programming or who want to learn through simple examples how to analyse some simulated obje

75 FR 70237 - California State Motor Vehicle Pollution Control Standards; California Heavy-Duty On-Highway Otto...

Science.gov (United States)

2010-11-17

... for the current CARB categories of heavy-duty vehicles are within-the-scope of the previously granted...) (Diesel) and 53 FR 7022 (March 4, 1988) (Otto-cycle). \\3\\ 69 FR 59920 (October 6, 2004). CARB's current... threshold test of materiality and * * * thereafter assess such material evidence against a standard of proof...

Mutagenesis of Dengue Virus Protein NS2A Revealed a Novel Domain Responsible for Virus-Induced Cytopathic Effect and Interactions between NS2A and NS2B Transmembrane Segments.

Science.gov (United States)

Wu, Ren-Huang; Tsai, Ming-Han; Tsai, Kuen-Nan; Tian, Jia Ni; Wu, Jian-Sung; Wu, Su-Ying; Chern, Jyh-Haur; Chen, Chun-Hong; Yueh, Andrew

2017-06-15

The NS2A protein of dengue virus (DENV) has eight predicted transmembrane segments (pTMS1 to -8) and participates in RNA replication, virion assembly, and host antiviral response. However, the roles of specific amino acid residues within the pTMS regions of NS2A during the viral life cycle are not clear. Here, we explore the function of DENV NS2A by introducing a series of alanine substitutions into the N-terminal half (pTMS1 to -4) of the protein in the context of a DENV infectious clone or subgenomic replicon. Six NS2A mutants (NM5, -7, -9, and -17 to -19) around pTMS1 and -2 displayed a novel phenotype showing a >1,000-fold reduction in virus yield, an absence of plaque formation despite wild-type-like replicon activity, and infectious-virus-like particle yields. HEK-293 cells infected with the six NS2A mutant viruses failed to cause a virus-induced cytopathic effect (CPE) by MitoCapture staining, cell proliferation, and lactate dehydrogenase release assays. Sequencing analyses of pseudorevertant viruses derived from lethal-mutant viruses revealed two consensus reversion mutations, leucine to phenylalanine at codon 181 (L181F) within pTMS7 of NS2A and isoleucine to threonine at codon 114 (I114T) within NS2B. The introduction of an NS2A-L181F mutation into the lethal (NM15, -16, -25, and -33) and CPE-defective (NM7, -9, and -19) mutants substantially rescued virus infectivity and virus-induced CPE, respectively, whereas the NS2B-L114T mutation rescued the NM16, -25, and -33 mutants. In conclusion, the results revealed the essential roles of the N-terminal half of NS2A in RNA replication and virus-induced CPE. Intramolecular interactions between pTMSs of NS2A and intermolecular interactions between the NS2A and NS2B proteins were also implicated. IMPORTANCE The characterization of the N-terminal (current study) and C-terminal halves of DENV NS2A is the most comprehensive mutagenesis study to date to investigate the function of NS2A during the flaviviral life cycle

Perspective on Models in Theoretical and Practical Traditions of Knowledge: The Example of Otto Engine Animations

Science.gov (United States)

Haglund, Jesper; Stromdahl, Helge

2012-01-01

Nineteen informants (n = 19) were asked to study and comment two computer animations of the Otto combustion engine. One animation was non-interactive and realistic in the sense of depicting a physical engine. The other animation was more idealised, interactive and synchronised with a dynamic PV-graph. The informants represented practical and…

In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4

Directory of Open Access Journals (Sweden)

Thi Thanh Hanh Nguyen

2013-12-01

Full Text Available The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3pro of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3pro. Thirty-six compounds were selected for in vitro assay against NS2B-NS3pro expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC50 values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3pro inhibitors were further confirmed as competitive inhibitors with Ki values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3pro active site with inhibition compounds were also identified.

Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

Energy Technology Data Exchange (ETDEWEB)

Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore; Rice, Amy J.; Ojeda, Isabel; Light, Samuel; Minasov, George; Vargas, Jason; Nagarathnam, Dhanapalan; Anderson, Wayne F.; Johnson, Michael E. (UIC); (NWU); (Novalex); (DNSK)

2016-12-26

Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activity (IC50) and binding affinity (KD) of ~5–10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a Ki value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

Energy Technology Data Exchange (ETDEWEB)

Miyazaki, Masaya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Hasegawa, Hideki [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Tashiro, Masato [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Wang, Lei [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Tanaka, Shinya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)

2013-11-29

Highlights: •NS1 induced excessive phosphorylation of ERK and elevated cell viability. •NS1-BP expression and CRKL knockdown abolished survival effect of NS1. •NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

Energy Technology Data Exchange (ETDEWEB)

Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

2014-01-20

The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

Atomic Pioneers Book 2 From the Mid-19th to the Early 20th Century

Energy Technology Data Exchange (ETDEWEB)

Hiebert, Ray [University of Maryland; Hiebert, Roselyn

1971-01-01

This book gives a brief account of the lives and work of 26 men and women who contributed to the great surge of knowledge vital to atomic science from the 1800s to the mid-1900s. The 26 are: William Prout, Michael Faraday, Eilhardt Mitscherlich, Joseph Henry, Thomas Graham, Stanislao Cannizzaro, James Clerk Maxwell, Dmitri I. Mendeleev, Joseph Norman Lockyer, John William Strutt, Wilhelm Konrad Roentgen, Antione Henri Becquerel, Hendrik A. Lorentz, J.J. Thomson, Max Planck, Svante A. Arrhenius, Pierre Curie, Marie Curie, Pieter Zeeman, Theodore W. Richards, C.T.R. Wilson, Ernest Rutherford, Francis W. Aston, Frederick Soddy, Lise Meitner, and Otto Hahn.

Assessment of Drug Binding Potential of Pockets in the NS2B/NS3 Dengue Virus Protein

Science.gov (United States)

Amelia, F.; Iryani; Sari, P. Y.; Parikesit, A. A.; Bakri, R.; Toepak, E. P.; Tambunan, U. S. F.

2018-04-01

Every year an endemic dengue fever estimated to affect over 390 million cases in over 128 countries occurs. However, the antigen types which stimulate the human immune response are variable, as a result, neither effective vaccines nor antiviral treatments have been successfully developed for this disease. The NS2B/NS3 protease of the dengue virus (DENV) responsible for viral replication is a potential drug target. The ligand-enzyme binding site determination is a key role in the success of virtual screening of new inhibitors. The NS2B/NS3 protease of DENV (PDB ID: 2FOM) has two pockets consisting of 37 (Pocket 1) and 27 (Pocket 2) amino acid residues in each pocket. In this research, we characterized the amino acid residues for binding sites in NS3/NS2B based on the hydrophobicity, the percentage of charged residues, volume, depth, ΔGbinding, hydrogen bonding and bond length. The hydrophobic percentages of both pockets are high, 59 % (Pocket 1) and 41% (Pocket 2) and the percentage of charged residues in Pocket 1 and 2 are 22% and 48%, and the pocket volume is less than 700 Å3. An interaction analysis using molecular docking showed that interaction between the ligand complex and protein in Pocket 1 is more negative than Pocket 2. As a result, Pocket 1 is the better potential target for a ligand to inhibit the action of NS2B/NS3 DENV.

Boron tolerance in NS wheat lines

Directory of Open Access Journals (Sweden)

Brdar Milka

2006-01-01

Full Text Available Boron is an essential micronutrient for higher plants. Present in excessive amounts boron becomes toxic and can limit plant growth and yield. Suppression of root growth is one of the symptoms of boron toxicity in wheat. This study was undertaken to investigate the response of 10 perspective NS lines of wheat to high concentrations of boron. Analysis of root growth was done on young plants, germinated and grown in the presence of different concentrations of boric acid (0, 50,100 and 150 mg/1. Significant differences occurred between analyzed genotypes and treatments regarding root length. Average suppression of root growth was between 11,6 and 34,2%, for line NS 252/02 are even noted 61,4% longer roots at treatments in relation to the control. Lines with mean suppression of root growth less than 20% (NS 101/02, NS 138/01, NS 53/03 and NS 73/02 may be considered as boron tolerant. Spearmans coefficients showed high level of agreement regarding rang of root length for genotypes treated with 100 and 150 mg H3BO3/l.

75 years ago. The discovery of nuclear fission during the neutron irradiation of uranium on 17 December 1938 in Berlin

International Nuclear Information System (INIS)

Kuczera, Bernhard

2013-01-01

A ground-breaking, scientific discovery made in the Berlin experiments of the year 1938 on neutron irradiation of uranium, was that atom nuclei can be fissured and, during the fission energy, so-called nuclear energy, is released. If further U-235 atoms are in the immediate vicinity, the released neutrons can trigger a chain reaction of the nuclear fission. The story of this ground-breaking discovery that led to the worldwide civil utilisation of nuclear energy is outlined here. The discovery of neutrons and their implementation in radiation experiments occurred in the 1930s. The research work followed the model of the Stockholm citizen Niels Bohr on the configuration of an atom. In 1930, Walther Bothe reported on the occurrence of a high-energy radiation when beryllium was irradiated with alpha-particles. James Chadwick could prove experimentally in 1932 that this is a current of high-energy, electrically neutral particles. He called these particles neutrons. In Berlin, the radio-chemist Otto Hahn is the Director at the Kaiser-Wilhelm-Institute for Chemistry and head of the chemical-radioactive department. In the years 1935 to 1938, the radiation experiments of uranium with neutrons were at the centre of the research in Berlin. In October 1938, Hahn and Strassmann responded with their own experiments to the scientific challenge of Irene Curie and Paul Savitch of 3.5-hours of activity when uranium was radiated with neutrons. The decisive discovery for the neutron radiation of uranium was made by Hahn and Strassmann on 17 December 1938. From the results of different experiments, they conclude: 'Our radium isotopes have the properties of barium.' On 19 December, Hahn informs Lise Meitner and speaking on the issue of 'Where does the barium come from?' addresses a possible 'bursting' of the uranium nucleus. That is Hahn's 'Heureka.' moment: He recognises that the neutron radiation does not only effect radiochemical transformations, but can also cause the uranium

Docking, synthesis and bioassay studies of imine derivatives as potential inhibitors for dengue NS2B/ NS3 serine protease

Directory of Open Access Journals (Sweden)

Neni Frimayanti

2017-11-01

Full Text Available Objective: To search imine derivatives as new active agents against dengue type 2 NS2B/NS3 using molecular docking, since there is no effective vaccine against flaviviral infections. Methods: In this research, molecular docking was performed for a series of imine derivatives and the information obtained from the docking studies was used to explore the binding modes of these imine derivatives with dengue type 2 NS2B/NS3 serine protease. A set of imine were synthesized and bioassay study of the inhibitory activities of these compounds was then performed. Results: The results indicated that MY8 and MY4 have the ability to inhibit DEN2 NS2B/NS3 proteolytic activity. Conclusions: These two compounds were chosen as the reference for the next stage in drug design as new inhibitor agents against NS2B/NS3.

Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical Studies of Deleobuvir and Faldaprevir.

Directory of Open Access Journals (Sweden)

Kristi L Berger

Full Text Available The resistance profile of anti-hepatitis C virus (HCV agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor, deleobuvir (HCV polymerase non-nucleoside inhibitor, and ribavirin in multiple clinical studies.HCV NS3/4A and NS5B population sequencing (Sanger method was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b. Persistence and time to loss of resistance-associated variants (RAVs was estimated using Kaplan-Meier analysis.Faldaprevir RAVs (NS3 R155 and D168 and deleobuvir RAVs (NS5B 495 and 496 were rare (90%. Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b; some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b. Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months was less than that of GT-1b NS3 D168 (8.5 months and GT-1a R155 RAVs (11.5 months.Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b may reduce response to this deleobuvir-based regimen.

L'insegnamento dell'evoluzione nei manuali scolastici di otto paesi costieri del Mediterraneo

OpenAIRE

Quessada, Marie-Pierre; Clément, Pierre; Valente, Adriana; Selmaoui, Sabah

2012-01-01

I manuali scolastici di biologia di otto paesi mediterranei affrontano il tema dell'evoluzione in modi molto differenti. In Algeria e in Libano, l'argomento non viene trattato o non più. In Tunisia, il tema è trattato nella classe terminale (ovvero nell'ultima classe del Liceo n.d.R.), ma senza un capitolo specifico sull'evoluzione umana. In Maroccco, l'evoluzione è stata appena reintrodotta in classe terminale ma senza l'evoluzione umana. Il tema è più ampiamente coperto a Cipro e a Malta, e...

Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

Energy Technology Data Exchange (ETDEWEB)

D’Arcy, Allan, E-mail: allan.darcy@novartis.com; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Lim, Siew Pheng [Novartis Institutes of Tropical Diseases (Singapore); Lefeuvre, Peggy [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Erbel, Paul [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Novartis Institutes of Tropical Diseases (Singapore)

2006-02-01

Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.

Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

International Nuclear Information System (INIS)

D’Arcy, Allan; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic; Lim, Siew Pheng; Lefeuvre, Peggy; Erbel, Paul

2006-01-01

Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained

Centro Multiusos en Mannheim. Frei Otto. Doblando la malla hasta hacer una concha

Directory of Open Access Journals (Sweden)

Fernando G. Pino

2016-04-01

Full Text Available En 2015 Frei Otto recibió el Premio Pritzker. Como homenaje a este importante arquitecto del siglo XX este escrito busca profundizar en el Centro Polivalente de Mannheim como uno de los principales ejemplos de la arquitectura resuelta con la técnica Grid Shell, que consiste en una manera de doblar una superficie plana hecha con una malla de madera lo suficientemente flexible como para transformarse en una superficie ondulada que podría ofrecer un espacio complejo y rico, listo para ser usado. En clara oposición a los proyectos conocidos del estadio Olímpico de Munich o el Pabellón en la Exposición Universal de Montreal, con este edificio Frei Otto explora una estructura de compresión que sigue la geometría y la organización de las estructuras de la naturaleza. Este campo de experimentación e investigación acerca de las estructuras naturales es el centro en torno al que giró su trabajo durante toda su vida en el Instituto de Estructuras Ligeras en Stuttgart. La experimentación con maquetas y con técnicas de fotogrametría para extraer datos fidedignos relativos al estudio con las superficies de pompas de jabón, así como los estudios con pesos colgados de finas cadenas para obtener las formas finales de sus proyectos, caracterizan su trabajo.

Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of dengue viruses obtained during surveillance in Indonesia.

Science.gov (United States)

Aryati, Aryati; Trimarsanto, Hidayat; Yohan, Benediktus; Wardhani, Puspa; Fahri, Sukmal; Sasmono, R Tedjo

2013-12-29

Early diagnosis of dengue infection is crucial for better management of the disease. Diagnostic tests based on the detection of dengue virus (DENV) Non Structural Protein 1 (NS1) antigen are commercially available with different sensitivities and specificities observed in various settings. Dengue is endemic in Indonesia and clinicians are increasingly using the NS1 detection for dengue confirmation. This study described the performance of Panbio Dengue Early NS1 and IgM Capture ELISA assays for dengue detection during our surveillance in eight cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its relationship with the NS1 detection. The NS1 and IgM/IgG ELISA assays were used for screening and confirmation of dengue infection during surveillance in 2010-2012. Collected serum samples (n = 440) were subjected to RT-PCR and virus isolation, in which 188 samples were confirmed for dengue infection. The positivity of the ELISA assays were correlated with the RT-PCR results to obtain the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were sequenced and their genetic characteristics were studied. Using molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied when correlated with city/geographical origins and DENV serotype, in which the lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1 assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48 isolates revealed the presence of polymorphisms of the NS1 genes which apparently did not influence the NS1 sensitivity. We observed a relatively low sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples. The detection rate increased significantly

Performance Evaluation on Otto Engine Generator Using Gasoline and Biogas from Palm Oil Mill Effluent

Science.gov (United States)

Irvan; Trisakti, B.; Husaini, T.; Sitio, A.; Sitorus, TB

2017-06-01

Biogas is a flammable gas produced from the fermentation of organic materials by anaerobic bacteria originating from household waste manure and organic waste including palm oil mill effluent (POME). POME is mainly discharged from the sterilization unit of palm oil processing into crude palm oil. This study utilized biogas produced from liquid waste palm oil for use as fuel in the Otto engine generator 4 - stroke, type STARKE GFH1900LX with a peak power of 1.3 kW, 1.0 kW average power, bore 55 mm, stroke 40 mm, Vd 95 × 10-6 m3, Vc 10 × 10-6 m3, compression ratio of 10.5 : 1, and the number of cylinders = 1. The objective of this study is to evaluate the performance of Otto engine generator fueled with biogas that generated from POME, then comparing its performance fueled by gasoline. The performance included power, torque, specific fuel consumption, thermal efficiency, and the air-fuel ratio. Experiment was conducted by using a variation of the lamp load of 100, 200, 300, 400, and 500 W. The results revealed that the use of biogas as fuel decreased in power, torque, brake thermal efficiency, and air fuel ratio (AFR), while there is an increasing of value specific fuel consumption (SFC).

New technology on Otto engines for reducing the exhaust emission toxicity

International Nuclear Information System (INIS)

Mikarovska, Vesna; Stojanovski, Vasko

2003-01-01

The exhaust emission from the Otto engines with internal combustion contains a lot of toxicant components for human being as well as for the surrounding. There are a lot of possibilities to realize the engine work with minimum emission of toxicant components. However, all solutions could not be racial, especially if the engine should work with minimum fuel consumption. The engineers look for the solutions where the reducing of the exhaust emission toxicity could be done with the total fuel utilization in the engine's cylinder, without additionally combustion in catalytic or thermal reactors. The paper describes the new technologies for detail investigation of the combustion processes and optimization of all influence parameters on exhaust gases emission. (Original)

Rationalizing meat consumption. The 4Ns.

Science.gov (United States)

Piazza, Jared; Ruby, Matthew B; Loughnan, Steve; Luong, Mischel; Kulik, Juliana; Watkins, Hanne M; Seigerman, Mirra

2015-08-01

Recent theorizing suggests that the 4Ns - that is, the belief that eating meat is natural, normal, necessary, and nice - are common rationalizations people use to defend their choice of eating meat. However, such theorizing has yet to be subjected to empirical testing. Six studies were conducted on the 4Ns. Studies 1a and 1b demonstrated that the 4N classification captures the vast majority (83%-91%) of justifications people naturally offer in defense of eating meat. In Study 2, individuals who endorsed the 4Ns tended also to objectify (dementalize) animals and included fewer animals in their circle of moral concern, and this was true independent of social dominance orientation. Subsequent studies (Studies 3-5) showed that individuals who endorsed the 4Ns tend not to be motivated by ethical concerns when making food choices, are less involved in animal-welfare advocacy, less driven to restrict animal products from their diet, less proud of their animal-product decisions, tend to endorse Speciesist attitudes, tend to consume meat and animal products more frequently, and are highly committed to eating meat. Furthermore, omnivores who strongly endorsed the 4Ns tended to experience less guilt about their animal-product decisions, highlighting the guilt-alleviating function of the 4Ns. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nuclear fission discovered fifty years ago

International Nuclear Information System (INIS)

Weis, M.

1988-01-01

Fifty years ago, Otto Hahn, Lise Meitner and Fritz Strassmann discovered the process of nuclear fission which, more than other scientific discoveries to date, profoundly has changed the world and continues to influence our life significantly: This discovery made the up to then incontestable physicists' view of the atom as an inseparable whole suddenly shatter to pieces. It has brought about the invaluable advantages of a peaceful utilization of nuclear energy, and at the same time put scientists in the position to build the most terrible weapon ever, threatening mankind and earth with complete destruction. All this certainly is reason enough to recall the scientists, their work and the spirit of the time. (orig.) [de

Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

Science.gov (United States)

Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

2017-01-01

Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4 + and CD8 + T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

[The Swiss archaeologist Otto Hauser. His skeletal findings and hypothesis on the evolution of man and his extensive activities in the development of prehistorical research and evolution].

Science.gov (United States)

Drössler, Rudolf; Drössler, Sigrid; Freyberg, Manuela

2006-03-01

New investigations on Otto Hauser's skeleton findings and the excavations of this Swiss citizen in Southwest France from 1906 until 1914 placed the activities of this archaeologist again in the focus of scientific and public interest. This paper describes life and oeuvre of Otto Hauser and discusses the importance of the skeletons found by him and Hermann Klaatsch as well as the consequences of their discovery. The efforts of Otto Hauser to publish his discoveries, to present and spread his view concerning the evolution of man were remarkably manifold as well as the parallels between ancient man and contemporary ethnic groups living on a low technological level drawn by him and to wake and to promote the interest in prehistory. Many books, brochures, articles and public lectures contributed to this intention as well as co-operation with local historians and scientists of other disciplines, and also many films, teaching and illustrative materials. The scientific collection of the authors of this article comprises more than 6,500 written documents and photos.

Performance of an Otto cycle motor with natural gas direct injection; Desempenho de um motor ciclo Otto com injecao direta de gas natural

Energy Technology Data Exchange (ETDEWEB)

Barbosa, Cleiton Rubens Formiga

1997-07-01

A Otto cycle engine with natural gas direct injection, during the inlet stroke, was submitted to runs with full power in a Foucaut dynamometer. The results obtained show a increase in the volumetric efficiency of the engine with natural gas direct injection when compared with natural gas injection applied in the inlet manifold, upstream of the throttle butterfly. In the conversion to natural gas direct injection, the technical characteristics were not changed. A kit for natural gas direct injection, with electronic management was located on the cylinder head of the test engine. Maintaining the pressure constant in the natural gas fuel line, using a reduction valve, the mass of fuel injected into the cylinder was regulated, varying the opening time of the solenoid valve fuel injector. Engine performance data is compared, emphasizing the factors that contribute to this increase in relative volumetric efficiency. Modifications are made to maximize the power of the engine with natural gas direct injection. (author)

DESEMPENHO DE MOTOR-GERADOR DE CICLO OTTO OPERADO COM GASOLINA E BIOGÁS PROVENIENTE DE SUINOCULTURA / PERFORMANCE MOTOR-GENERATOR OPERATED WITH OTTO CYCLE GASOLINE AND BIOGAS FROM THE PIG.

Directory of Open Access Journals (Sweden)

C. Rossetto

2014-12-01

Full Text Available A busca por novas fontes energéticas que não poluam o meio ambiente, bem como a mitigação dos impactos ambientais gerados pelo aumento da população, abre uma nova perspectiva no campo da pesquisa do biogás provenientes do resultado de tratamento de efluentes. O processo de transformação de energia gerada pela combustão do biogás para energia em motores no ciclo Otto e posterior transformação em energia elétrica é de fácil realização sendo necessárias algumas adaptações no motor, neste trabalho foi realizada apenas a substituição do carburador por um misturador de ar/combustível tipo Venturi. O objetivo deste trabalho foi avaliar o desempenho de motor-gerador ciclo Otto alimentado com biogás proveniente de suinocultura. Como testemunha foram utilizados ensaios com gasolina, simulando diferentes condições de trabalho, com cargas de 0; 0,250 kW (10 % da carga; 0,500 kW (20 % da carga; 0,750 kW (30 % da carga; 1 kW (40 % da carga; 1,250 kW (50 % da carga; 1,500 kW (60 % da carga; 1,750 kW (70 % da carga; 2 kW (80 % da carga; 2,250 kW (90 % da carga e 2,500 kW (100 % da carga. Onde foram avaliadas as emissões de dióxido de carbono (CO2, monóxido de carbono (CO e oxido de nitrogênio (NOx, e analisado o rendimento do motor-gerador que foi baixo em torno de 76 % menor quando comparado com gasolina, sendo necessários ajustes para o melhor desempenho. 

Localisation system in wireless sensor networks using ns-2

CSIR Research Space (South Africa)

Abu-Mahfouz, Adnan M

2012-04-01

Full Text Available -1 /************************************************************************** ********** * * File: readme.asn * * Author: Adnan Abu-Mahfouz * * Date: March 2012 * * Description: Localisation system in wireless sensor networks using ns-2... *************************************************************************** *********/ /************************************************************************** *************************************************************************** *****/ 1. Introduction: ns-2 contains several flexible features that encourage researchers to use ns-2 to investigate the characteristics of wireless sensor networks (WSNs). However, to implement and evaluate localisation algorithms, the current ns- 2...

Quantitative Hahn-Banach Theorems and Isometric Extensions forWavelet and Other Banach Spaces

Directory of Open Access Journals (Sweden)

Sergey Ajiev

2013-05-01

Full Text Available We introduce and study Clarkson, Dol’nikov-Pichugov, Jacobi and mutual diameter constants reflecting the geometry of a Banach space and Clarkson, Jacobi and Pichugov classes of Banach spaces and their relations with James, self-Jung, Kottman and Schäffer constants in order to establish quantitative versions of Hahn-Banach separability theorem and to characterise the isometric extendability of Hölder-Lipschitz mappings. Abstract results are further applied to the spaces and pairs from the wide classes IG and IG+ and non-commutative Lp-spaces. The intimate relation between the subspaces and quotients of the IG-spaces on one side and various types of anisotropic Besov, Lizorkin-Triebel and Sobolev spaces of functions on open subsets of an Euclidean space defined in terms of differences, local polynomial approximations, wavelet decompositions and other means (as well as the duals and the lp-sums of all these spaces on the other side, allows us to present the algorithm of extending the main results of the article to the latter spaces and pairs. Special attention is paid to the matter of sharpness. Our approach is quasi-Euclidean in its nature because it relies on the extrapolation of properties of Hilbert spaces and the study of 1-complemented subspaces of the spaces under consideration.

Functional investigation of grass carp reovirus nonstructural protein NS80

Directory of Open Access Journals (Sweden)

Shao Ling

2011-04-01

Full Text Available Abstract Background Grass Carp Reovirus (GCRV, a highly virulent agent of aquatic animals, has an eleven segmented dsRNA genome encased in a multilayered capsid shell, which encodes twelve proteins including seven structural proteins (VP1-VP7, and five nonstructural proteins (NS80, NS38, NS31, NS26, and NS16. It has been suggested that the protein NS80 plays an important role in the viral replication cycle that is similar to that of its homologous protein μNS in the genus of Orthoreovirus. Results As a step to understanding the basis of the part played by NS80 in GCRV replication and particle assembly, we used the yeast two-hybrid (Y2H system to identify NS80 interactions with proteins NS38, VP4, and VP6 as well as NS80 and NS38 self-interactions, while no interactions appeared in the four protein pairs NS38-VP4, NS38-VP6, VP4-VP4, and VP4-VP6. Bioinformatic analyses of NS80 with its corresponding proteins were performed with all currently available homologous protein sequences in ARVs (avian reoviruses and MRVs (mammalian reoviruses to predict further potential functional domains of NS80 that are related to VFLS (viral factory-like structures formation and other roles in viral replication. Two conserved regions spanning from aa (amino acid residues of 388 to 433, and 562 to 580 were discovered in this study. The second conserved region with corresponding conserved residues Tyr565, His569, Cys571, Asn573, and Glu576 located between the two coiled-coils regions (aa ~513-550 and aa ~615-690 in carboxyl-proximal terminus were supposed to be essential to form VFLS, so that aa residues ranging from 513 to 742 of NS80 was inferred to be the smallest region that is necessary for forming VFLS. The function of the first conserved region including Ala395, Gly419, Asp421, Pro422, Leu438, and Leu443 residues is unclear, but one-third of the amino-terminal region might be species specific, dominating interactions with other viral components. Conclusions Our

Válka jako stav provizoria (Na příkladu Čechů ve Francii 1914-1918: František Kupka, Otto Gutfreund)

Czech Academy of Sciences Publication Activity Database

Brouček, Stanislav

33 /75/, č. 1 (2016), s. 15-31 ISSN 1211-8117 Institutional support: RVO:68378076 Keywords : emigration * Czechs in France * František Kupka * Otto Gutfreund * resistance movement abroad Subject RIV: AC - Archeology, Anthropology, Ethnology

Low-threshold optical bistability with multilayer graphene-covering Otto configuration

International Nuclear Information System (INIS)

Wang, Hengliang; Wu, Jipeng; Xiang, Yuanjiang; Wen, Shuangchun; Guo, Jun; Jiang, Leyong

2016-01-01

In this paper, we propose a modified Otto configuration to realize tunable and low-threshold optical bistability at terahertz frequencies by attaching multilayer graphene sheets to a nonlinear substrate interface. Our work demonstrates that the threshold of optical bistability can be markedly reduced (three orders of magnitude) by covering the nonlinear substrate with multilayer graphene sheets, due to strong local field enhancement with the excitation of surface plasmons. We present the influences of the Fermi energy of graphene, the incident angle, the thickness of air gap and the relaxation time of graphene on the hysteresis phenomenon and give a way to optimize the surface plasmon resonance, which will enable us to further lower the minimal power requirements for realizing optical bistability due to the strong interaction of light with graphene sheets. These results are promising for realization of terahertz optical switches, optical modulators and logical devices. (paper)

40 CFR 86.005-10 - Emission standards for 2005 and later model year Otto-cycle heavy-duty engines and vehicles.

Science.gov (United States)

2010-07-01

... model year Otto-cycle heavy-duty engines and vehicles. 86.005-10 Section 86.005-10 Protection of... AND IN-USE HIGHWAY VEHICLES AND ENGINES General Provisions for Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles, Light-Duty Trucks and Heavy-Duty Engines, and for 1985 and Later...

Lyso-myristoyl phosphatidylcholine micelles sustain the activity of Dengue non-structural (NS) protein 3 protease domain fused with the full-length NS2B.

Science.gov (United States)

Huang, Qiwei; Li, Qingxin; Joy, Joma; Chen, Angela Shuyi; Ruiz-Carrillo, David; Hill, Jeffrey; Lescar, Julien; Kang, Congbao

2013-12-01

Dengue virus (DENV), a member of the flavivirus genus, affects 50-100 million people in tropical and sub-tropical regions. The DENV protease domain is located at the N-terminus of the NS3 protease and requires for its enzymatic activity a hydrophilic segment of the NS2B that acts as a cofactor. The protease is an important antiviral drug target because it plays a crucial role in virus replication by cleaving the genome-coded polypeptide into mature functional proteins. Currently, there are no drugs to inhibit DENV protease activity. Most structural and functional studies have been conducted using protein constructs containing the NS3 protease domain connected to a soluble segment of the NS2B membrane protein via a nine-residue linker. For in vitro structural and functional studies, it would be useful to produce a natural form of the DENV protease containing the NS3 protease domain and the full-length NS2B protein. Herein, we describe the expression and purification of a natural form of DENV protease (NS2BFL-NS3pro) containing the full-length NS2B protein and the protease domain of NS3 (NS3pro). The protease was expressed and purified in detergent micelles necessary for its folding. Our results show that this purified protein was active in detergent micelles such as lyso-myristoyl phosphatidylcholine (LMPC). These findings should facilitate further structural and functional studies of the protease and will facilitate drug discovery targeting DENV. Copyright © 2013 Elsevier Inc. All rights reserved.

Multi-stage-flash desalination plants of relative small performance with integrated pressurized water reactors as a nuclear heat source

International Nuclear Information System (INIS)

Petersen, G.; Peltzer, M.

1977-01-01

In the Krupp-GKSS joint study MINIPLEX the requirements for seawater-desalination plants with a performance in the range of 10 000 to 80 000 m 3 distillate per day heated by a nuclear reactor are investigated. The reactor concept is similar to the Integrated Pressurized Water Reactor (IPWR) of the nuclear ship OTTO HAHN. The design study shows that IPWR systems have specific advantages up to 200 MWth compared to other reactor types at least being adapted for single- and dual-purpose desalination plants. The calculated costs of the desalinated water show that due to fuel cost advantages of reactors small and medium nuclear desalination plants are economically competetive with oil-fired plants since the steep rise of oil price in autumn 1973. (author)

Farm Hall and the German atomic project of World War II a dramatic history

CERN Document Server

Cassidy, David C

2017-01-01

This gripping book brings back to life the events surrounding the internment of ten German Nuclear Scientists immediately after World War II. It is also an "eye-witness" account of the dawning of the nuclear age, with the dialogue and narrative spanning the period before, during and after atomic bombs were dropped on Japan at the end of the war. This pivotal historical episode is conveyed, along with the emotions as well as the facts, through drama, historical narrative, and photographs of the captive German nuclear scientists - who included Werner Heisenberg, Otto Hahn, and Max von Laue. The unique story that unfolds in the play is based on secretly recorded transcripts of the scientists’ actual conversations at Farm Hall, together with related documents and photographs.

Gas chromatographic measurement in water-steam circuits

International Nuclear Information System (INIS)

Zschetke, J.; Nieder, R.

1984-01-01

A gas chromatographic technique for measurements in water-steam circuits, which has been well known for many years, has been improved by design modifications. A new type of equipment developed for special measuring tasks on nuclear engineering plant also has a general application. To date measurements have been carried out on the ''Otto Hahn'' nuclear powered ship, on the KNK and AVR experimental nuclear power plants at Karlsruhe and Juelich respectively and on experimental boiler circuits. The measurements at the power plants were carried out under different operating conditions. In addition measurements during the alkali operating mode and during combined cycle operation were carried out on the AVR reactor. It has been possible to draw new conclusion from the many measurements undertaken. (orig.) [de

Einstein, Ethics and the Atomic Bomb

Science.gov (United States)

Rife, Patricia

2005-03-01

Einstein voiced his ethical views against war as well as fascism via venues and alliances with a variety of organizations still debated today. In 1939, he signed a letter to President Roosevelt (drafted by younger colleagues Szilard, Wigner and others) warning the U.S.government about the danger of Nazi Germany gaining control of uranium in the Belgian-controlled Congo in order to develop atomic weapons, based on the discovery of fission by Otto Hahn and Lise Meitner. In 1945, he became a member of the Princeton-based ``Emergency Committee for Atomic Scientists'' organized by Bethe, Condon, Bacher, Urey, Szilard and Weisskopf. Rare Einstein slides will illustrate Dr.Rife's presentation on Albert Einstein's philosophic and ethical convictions about peace, and public stance against war (1914-1950).

Development of small and medium reactors for power and heat production

International Nuclear Information System (INIS)

Becka, J.

1978-01-01

Data are given on the current state of development of small and medium-power reactors designed mainly for electric power production in small power grids, for heat production for small- and medium-power desalination plants with possible electric power generation, for process steam production and heat development for district heating systems, again combined with electric power generation, and for propelling big and fast passenger ships. A diagram is shown of the primary system of an integrated PWR derived from the Otto Hahn reactor. The family is listed of the standard sizes of the integral INTERATOM company pressurized water reactors. Also listed are the specifications and design of CAS 2CG and AS 3G type reactors used mainly for long-distance heating systems. (J.B.)

Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

International Nuclear Information System (INIS)

Fang, Puxian; Fang, Liurong; Liu, Xiaorong; Hong, Yingying; Wang, Yongle; Dong, Nan; Ma, Panpan; Bi, Jing; Wang, Dang; Xiao, Shaobo

2016-01-01

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.

Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

Energy Technology Data Exchange (ETDEWEB)

Fang, Puxian; Fang, Liurong; Liu, Xiaorong; Hong, Yingying; Wang, Yongle; Dong, Nan; Ma, Panpan [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Bi, Jing [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); Department of Immunology and Aetology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan 430065 (China); Wang, Dang [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Xiao, Shaobo, E-mail: vet@mail.hzau.edu.cn [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China)

2016-12-15

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells. -- Highlights: •The leader-body fusion site of NS6 sgRNA is identified. •NS6 sgRNA uses a non-canonical transcription regulatory sequence (TRS). •NS6 can be expressed in PDCoV-infected cell. •NS6 predominantly localize to the ER complex and ER-Golgi intermediate compartment.

Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses.

Directory of Open Access Journals (Sweden)

Hung-Yu Sun

Full Text Available Molecular covariation of highly polymorphic viruses is thought to have crucial effects on viral replication and fitness. This study employs association rule data mining of hepatitis C virus (HCV sequences to search for specific evolutionary covariation and then tests functional relevance on HCV replication. Data mining is performed between nucleotides in the untranslated regions 5' and 3'UTR, and the amino acid residues in the non-structural proteins NS2, NS3 and NS5B. Results indicate covariance of the 243(rd nucleotide of the 5'UTR with the 14(th, 41(st, 76(th, 110(th, 211(th and 212(th residues of NS2 and with the 71(st, 175(th and 621(st residues of NS3. Real-time experiments using an HCV subgenomic system to quantify viral replication confirm replication regulation for each covariant pair between 5'UTR₂₄₃ and NS2-41, -76, -110, -211, and NS3-71, -175. The HCV subgenomic system with/without the NS2 region shows that regulatory effects vanish without NS2, so replicative modulation mediated by HCV 5'UTR₂₄₃ depends on NS2. Strong binding of the NS2 variants to HCV RNA correlates with reduced HCV replication whereas weak binding correlates with restoration of HCV replication efficiency, as determined by RNA-protein immunoprecipitation assay band intensity. The dominant haplotype 5'UTR₂₄₃-NS2-41-76-110-211-NS3-71-175 differs according to the HCV genotype: G-Ile-Ile-Ile-Gly-Ile-Met for genotype 1b and A-Leu-Val-Leu-Ser-Val-Leu for genotypes 1a, 2a and 2b. In conclusion, 5'UTR₂₄₃ co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication. This unreported mechanism involving HCV replication possibly can be exploited in the development of advanced anti-HCV medication.

Rab5 Enhances Classical Swine Fever Virus Proliferation and Interacts with Viral NS4B Protein to Facilitate Formation of NS4B Related Complex

Directory of Open Access Journals (Sweden)

Jihui Lin

2017-08-01

Full Text Available Classical swine fever virus (CSFV is a fatal pig pestivirus and causes serious financial losses to the pig industry. CSFV NS4B protein is one of the most important viral replicase proteins. Rab5, a member of the small Rab GTPase family, is involved in infection and replication of numerous viruses including hepatitis C virus and dengue virus. Until now, the effects of Rab5 on the proliferation of CSFV are poorly defined. In the present study, we showed that Rab5 could enhance CSFV proliferation by utilizing lentivirus-mediated constitutive overexpression and eukaryotic plasmid transient overexpression approaches. On the other hand, lentivirus-mediated short hairpin RNA knockdown of Rab5 dramatically inhibited virus production. Co-immunoprecipitation, glutathione S-transferase pulldown and laser confocal microscopy assays further confirmed the interaction between Rab5 and CSFV NS4B protein. In addition, intracellular distribution of NS4B-Red presented many granular fluorescent signals (GFS in CSFV infected PK-15 cells. Inhibition of basal Rab5 function with Rab5 dominant negative mutant Rab5S34N resulted in disruption of the GFS. These results indicate that Rab5 plays a critical role in facilitating the formation of the NS4B related complexes. Furthermore, it was observed that NS4B co-localized with viral NS3 and NS5A proteins in the cytoplasm, suggesting that NS3 and NS5A might be components of the NS4B related complex. Taken together, these results demonstrate that Rab5 positively modulates CSFV propagation and interacts with NS4B protein to facilitate the NS4B related complexes formation.

Multilevel quantum Otto heat engines with identical particles

Science.gov (United States)

Huang, X. L.; Guo, D. Y.; Wu, S. L.; Yi, X. X.

2018-02-01

A quantum Otto heat engine is studied with multilevel identical particles trapped in one-dimensional box potential as working substance. The symmetrical wave function for Bosons and the anti-symmetrical wave function for Fermions are considered. In two-particle case, we focus on the ratios of W^i (i=B,F) to W_s, where W^B and W^F are the work done by two Bosons and Fermions, respectively, and W_s is the work output of a single particle under the same conditions. Due to the symmetrical of the wave functions, the ratios are not equal to 2. Three different regimes, low-temperature regime, high-temperature regime, and intermediate-temperature regime, are analyzed, and the effects of energy level number and the differences between the two baths are calculated. In the multiparticle case, we calculate the ratios of W^i_M/M to W_s, where W^i_M/M can be seen as the average work done by a single particle in multiparticle heat engine. For other working substances whose energy spectrum has the form of E_n˜ n^2, the results are similar. For the case E_n˜ n, two different conclusions are obtained.

A través de la lente: Otto Moll González

Directory of Open Access Journals (Sweden)

Tatiana Urrea Uyabán

2012-06-01

Full Text Available La fotografía arquitectónica de Otto Moll se encanta con las propuestas de las firmas que despuntan en el decenio de 1950 y que conformarán ese Cali de verdad moderno. Un aire estadounidense que no necesariamente se integra al entorno natural. Resaltan los proyectos sobre ese terreno que antaño fue un bosque seco. La arquitectura es el objeto; más allá del juego de luces y sombras y de la técnica. Moll como ningún otro para entonces, saca a la luz la propuesta que despunta con estos proyectos. Serán la representación del "Movimiento Moderno" y quienes encargan los trabajos al fotógrafo van también a la vanguardia.

NS Pudarka: A new winter wheat cultivar

Directory of Open Access Journals (Sweden)

Hristov Nikola

2014-01-01

Full Text Available The high-yielding, medium late winter wheat cultivar NS Pudarka was developed by crossing genetic divergent parents: line NMNH-07 and cv. NS 40S and Simonida. In cultivar NS Pudarka genes responsible for high yield potential, very good technological quality, resistance to lodging, low temperature and diseases, were successfully combined. It was registered by Ministry of agriculture, forestry and water management of Serbia Republic in 2013. This cultivar has wide adaptability and stability of yield that enable growing in different environments with optimal agricultural practice. On the base of technological quality this cultivar belongs to the second quality class, A2 farinograph subgroup and second technological group.

The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

Science.gov (United States)

de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

2013-01-01

Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

Directory of Open Access Journals (Sweden)

Benoît de Chassey

Full Text Available Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1 appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

Silencing by H-NS potentiated the evolution of Salmonella.

Directory of Open Access Journals (Sweden)

Sabrina S Ali

2014-11-01

Full Text Available The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer the fitness consequences associated with foreign gene acquisition. Loss of H-NS results in severe growth defects in Salmonella, but the underlying reasons were unclear. An experimental evolution approach was employed to determine which secondary mutations could compensate for the loss of H-NS in Salmonella. Six independently derived S. Typhimurium hns mutant strains were serially passaged for 300 generations prior to whole genome sequencing. Growth rates of all lineages dramatically improved during the course of the experiment. Each of the hns mutant lineages acquired missense mutations in the gene encoding the H-NS paralog StpA encoding a poorly understood H-NS paralog, while 5 of the mutant lineages acquired deletions in the genes encoding the Salmonella Pathogenicity Island-1 (SPI-1 Type 3 secretion system critical to invoke inflammation. We further demonstrate that SPI-1 misregulation is a primary contributor to the decreased fitness in Salmonella hns mutants. Three of the lineages acquired additional loss of function mutations in the PhoPQ virulence regulatory system. Similarly passaged wild type Salmonella lineages did not acquire these mutations. The stpA missense mutations arose in the oligomerization domain and generated proteins that could compensate for the loss of H-NS to varying degrees. StpA variants most able to functionally substitute for H-NS displayed altered DNA binding and oligomerization properties that resembled those of H-NS. These findings indicate that H-NS was central to the evolution of the Salmonellae by buffering the negative fitness consequences caused by the secretion system that is the defining characteristic of the species.

Revision of Sternaspis Otto, 1821 (Polychaeta, Sternaspidae

Directory of Open Access Journals (Sweden)

Kelly Sendall

2013-04-01

Full Text Available Sternaspid polychaetes are common and often abundant in soft bottoms in the world oceans. Some authors suggest that only one species should be recognized, whereas others regard a few species as widely distributed in many seas and variable depths from the low intertidal to about 4400 m. There are some problems with species delineation and the distinctive ventro-caudal shield has been disregarded or barely used for identifying species. In order to clarify these issues, the ventral shield is evaluated in specimens from the same locality and its diagnostic potential is confirmed. On this basis, a revision of Sternaspis Otto, 1821 (Polychaeta: Sternaspidae is presented based upon type materials, or material collected from type localities. The sternaspid body, introvert hooks and shield show three distinct patterns, two genera have seven abdominal segments and tapered introvert hooks, and one genus has eight abdominal segments and spatulate introvert hooks. The ventro-caudal shield has three different patterns: stiff with ribs, and sometimes concentric lines, stiff with feebly-defined ribs but no concentric lines, and soft with firmly adhered sediment particles. Sternaspis is restricted to include species with seven abdominal segments, falcate introvert hooks, and stiff shields, often exhibiting radial ribs, concentric lines or both. Sternaspis includes, besides the type species, S. thalassemoides Otto, 1821 from the Mediterranean Sea, S. affinis Stimpson, 1864 from the Northeastern Pacific, S. africana Augener, 1918, stat. n. from Western Africa, S. andamanensis sp. n. from the Andaman Sea, S. costata von Marenzeller, 1879 from Japan, S. fossor Stimpson, 1853 from the Northwestern Atlantic, S. islandica Malmgren, 1867 from Iceland, S. maior Chamberlin, 1919 from the Gulf of California, S. princeps Selenka, 1885 from New Zealand, S. rietschi Caullery, 1944 from abyssal depths around Indonesia, S. scutata (Ranzani, 1817 from the Mediterranean Sea, S

Revision of sternaspis otto, 1821 (polychaeta, sternaspidae).

Science.gov (United States)

Sendall, Kelly; Salazar-Vallejo, Sergio I

2013-01-01

To the memory of William Ronald Sendall Sternaspid polychaetes are common and often abundant in soft bottoms in the world oceans. Some authors suggest that only one species should be recognized, whereas others regard a few species as widely distributed in many seas and variable depths from the low intertidal to about 4400 m. There are some problems with species delineation and the distinctive ventro-caudal shield has been disregarded or barely used for identifying species. In order to clarify these issues, the ventral shield is evaluated in specimens from the same locality and its diagnostic potential is confirmed. On this basis, a revision of Sternaspis Otto, 1821 (Polychaeta: Sternaspidae) is presented based upon type materials, or material collected from type localities. The sternaspid body, introvert hooks and shield show three distinct patterns, two genera have seven abdominal segments and tapered introvert hooks, and one genus has eight abdominal segments and spatulate introvert hooks. The ventro-caudal shield has three different patterns: stiff with ribs, and sometimes concentric lines, stiff with feebly-defined ribs but no concentric lines, and soft with firmly adhered sediment particles. Sternaspis is restricted to include species with seven abdominal segments, falcate introvert hooks, and stiff shields, often exhibiting radial ribs, concentric lines or both. Sternaspis includes, besides the type species, Sternaspis thalassemoides Otto, 1821 from the Mediterranean Sea, Sternaspis affinis Stimpson, 1864 from the Northeastern Pacific, Sternaspis africana Augener, 1918, stat. n. from Western Africa, Sternaspis andamanensis sp. n. from the Andaman Sea, Sternaspis costata von Marenzeller, 1879 from Japan, Sternaspis fossor Stimpson, 1853 from the Northwestern Atlantic, Sternaspis islandica Malmgren, 1867 from Iceland, Sternaspis maior Chamberlin, 1919 from the Gulf of California, Sternaspis princeps Selenka, 1885 from New Zealand, Sternaspis rietschi Caullery

Revision of Sternaspis Otto, 1821 (Polychaeta, Sternaspidae)

Science.gov (United States)

Sendall, Kelly; Salazar-Vallejo, Sergio I.

2013-01-01

Abstract To the memory of William Ronald Sendall Sternaspid polychaetes are common and often abundant in soft bottoms in the world oceans. Some authors suggest that only one species should be recognized, whereas others regard a few species as widely distributed in many seas and variable depths from the low intertidal to about 4400 m. There are some problems with species delineation and the distinctive ventro-caudal shield has been disregarded or barely used for identifying species. In order to clarify these issues, the ventral shield is evaluated in specimens from the same locality and its diagnostic potential is confirmed. On this basis, a revision of Sternaspis Otto, 1821 (Polychaeta: Sternaspidae) is presented based upon type materials, or material collected from type localities. The sternaspid body, introvert hooks and shield show three distinct patterns, two genera have seven abdominal segments and tapered introvert hooks, and one genus has eight abdominal segments and spatulate introvert hooks. The ventro-caudal shield has three different patterns: stiff with ribs, and sometimes concentric lines, stiff with feebly-defined ribs but no concentric lines, and soft with firmly adhered sediment particles. Sternaspis is restricted to include species with seven abdominal segments, falcate introvert hooks, and stiff shields, often exhibiting radial ribs, concentric lines or both. Sternaspis includes, besides the type species, Sternaspis thalassemoides Otto, 1821 from the Mediterranean Sea, Sternaspis affinis Stimpson, 1864 from the Northeastern Pacific, Sternaspis africana Augener, 1918, stat. n. from Western Africa, Sternaspis andamanensis sp. n. from the Andaman Sea, Sternaspis costata von Marenzeller, 1879 from Japan, Sternaspis fossor Stimpson, 1853 from the Northwestern Atlantic, Sternaspis islandica Malmgren, 1867 from Iceland, Sternaspis maior Chamberlin, 1919 from the Gulf of California, Sternaspis princeps Selenka, 1885 from New Zealand, Sternaspis rietschi

Person-Environment Mergence and Separation: Otto Rank's Psychology of Emotion, Personality, and Culture.

Science.gov (United States)

Sullivan, Daniel

2016-12-01

Between 1924 and 1939 Otto Rank put forward three major elements of a comprehensive theoretical edifice that has yet to be fully articulated. These are conceptually linked by the fundamental importance of person-environment mergence and separation. Rank's theory of emotions highlights anxiety as the affect of separation, and guilt as the feeling that binds the individual to others. His personality theory distinguishes between the partialist, who responds to life fear with identification, and the totalist, who responds to death fear with projection. His cultural psychology contrasts primal collectivism with contemporary individualism, which orients the person toward individual immortality striving. Individualism has produced problematic self-consciousness and neuroticism, in the face of which Rank struggled to find a new psychology.

Cleavage preference distinguishes the two-component NS2B-NS3 serine proteinases of Dengue and West Nile viruses.

Science.gov (United States)

Shiryaev, Sergey A; Kozlov, Igor A; Ratnikov, Boris I; Smith, Jeffrey W; Lebl, Michal; Strongin, Alex Y

2007-02-01

Regulated proteolysis of the polyprotein precursor by the NS2B-NS3 protease is required for the propagation of infectious virions. Unless the structural and functional parameters of NS2B-NS3 are precisely determined, an understanding of its functional role and the design of flaviviral inhibitors will be exceedingly difficult. Our objectives were to define the substrate recognition pattern of the NS2B-NS3 protease of West Nile and Dengue virises (WNV and DV respectively). To accomplish our goals, we used an efficient, 96-well plate format, method for the synthesis of 9-mer peptide substrates with the general P4-P3-P2-P1-P1'-P2'-P3'-P4'-Gly structure. The N-terminus and the constant C-terminal Gly of the peptides were tagged with a fluorescent tag and with a biotin tag respectively. The synthesis was followed by the proteolytic cleavage of the synthesized, tagged peptides. Because of the strict requirement for the presence of basic amino acid residues at the P1 and the P2 substrate positions, the analysis of approx. 300 peptide sequences was sufficient for an adequate representation of the cleavage preferences of the WNV and DV proteinases. Our results disclosed the strict substrate specificity of the WNV protease for which the (K/R)(K/R)R/GG amino acid motifs was optimal. The DV protease was less selective and it tolerated well the presence of a number of amino acid residue types at either the P1' or the P2' site, as long as the other position was occupied by a glycine residue. We believe that our data represent a valuable biochemical resource and a solid foundation to support the design of selective substrates and synthetic inhibitors of flaviviral proteinases.

NS&T Management Observations

Energy Technology Data Exchange (ETDEWEB)

Gianotto, David [Idaho National Laboratory (INL), Idaho Falls, ID (United States)

2014-09-01

The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

Recombinant HCV variants with NS5A from genotypes 1-7 have different sensitivities to an NS5A inhibitor but not interferon-a

DEFF Research Database (Denmark)

Scheel, Troels K H; Gottwein, Judith M; Mikkelsen, Lotte S

2011-01-01

Heterogeneity in the hepatitis C virus (HCV) protein NS5A influences its sensitivity to interferon-based therapy. Furthermore, NS5A is an important target for development of HCV-specific inhibitors. We aimed to develop recombinant infectious cell culture systems that express NS5A from isolates...

Preliminary neutronic study on Pu-based OTTO cycle pebble bed reactor

Energy Technology Data Exchange (ETDEWEB)

Setiadipura, Topan; Zuhair [National Nuclear Energy Agency of Indonesia (BATAN), Selatan (Indonesia). Center for Nuclear Reactor Technology and Safety; Irwanto, Dwi [Bandung Institute of Technology (ITB), Bandung (Indonesia). Nuclear Physics and Biophysics Research Group

2017-12-15

The neutron physics characteristic of Pebble Bed Reactor (PBR) allows a better incineration of plutonium (Pu). An optimized design of simple PBR might give a symbiotic solution of providing a safe energy source, effective fuel utilization shown by a higher burnup value, and incineration of Pu stockpiles. This study perform a preliminary neutronic design study of a 200 MWt Once Through Then Out (OTTO) cycle PBR with Pu-based fuel. The safety criteria of the design were represented by the per-fuel-pebble maximum power generation of 4.5 kW/pebble. In this preliminary phase, the parametric survey is limited to the heavy metal (HM) loading per pebble and the average axial speed of the fuel. An optimum high burnup of 419.7 MWd/kg-HM was achieved in this study. This optimum design uses a HM loading of 2.5 g/pebble with average axial fuel velocity 0.5 cm/day.

Role of nonstructural protein NS2A in flavivirus assembly

NARCIS (Netherlands)

Leung, J.Y.; Pijlman, G.P.; Kondratieva, N.; Hyde, J.; Mackenzie, J.M.; Khromykh, A.A.

2008-01-01

Flavivirus nonstructural (NS) proteins are involved in RNA replication and modulation of the host antiviral response; however, evidence is mounting that some NS proteins also have essential roles in virus assembly. Kunjin virus (KUN) NS2A is a small, hydrophobic, transmembrane protein that is part

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

Science.gov (United States)

Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

2017-05-15

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors

Otto Rank, the Rankian circle in Philadelphia, and the origins of Carl Rogers' person-centered psychotherapy.

Science.gov (United States)

deCarvalho, R J

1999-05-01

Otto Rank's will therapy helped shape the ideas and techniques of relationship therapy developed by the Philadelphia social workers Jessie Taft, Virginia Robinson, and Frederick Allen in the 1930s. Rank's work and these ideas and techniques in turn strongly influenced the formulation of Carl Rogers' person-centered psychotherapy. This article compares and contrasts will, relationship, and person-centered approaches to psychotherapy and discusses the social factors--primarily the professional conflicts between a male-dominated psychiatry and female social workers over the independent practice of psychotherapy--that were crucial in the dissemination of Rank's psychological thought and the early popularity of Rogers.

A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease.

Directory of Open Access Journals (Sweden)

Matthew Brecher

2017-05-01

Full Text Available The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors. Binding of an active-site inhibitor to the protease resulted in a conformational change of NS2B and led to significant SLC enhancement. Mutagenesis of key residues at an allosteric site abolished this induced conformational change and SLC enhancement. We also performed a virtual screen of NCI library compounds to identify allosteric inhibitors, followed by in vitro biochemical screening of the resultant candidates. Only three of these compounds, NSC135618, 260594, and 146771, significantly inhibited the protease of Dengue virus 2 (DENV2 in vitro, with IC50 values of 1.8 μM, 11.4 μM, and 4.8 μM, respectively. Among the three compounds, only NSC135618 significantly suppressed the SLC enhancement triggered by binding of active-site inhibitor in a dose-dependent manner, indicating that it inhibits the conformational change of NS2B. Results from virus titer reduction assays revealed that NSC135618 is a broad spectrum flavivirus protease inhibitor, and can significantly reduce titers of DENV2, Zika virus (ZIKV, West Nile virus (WNV, and Yellow fever virus (YFV on A549 cells in vivo, with EC50 values in low micromolar range. In contrast, the cytotoxicity of NSC135618 is only moderate with CC50 of 48.8 μM on A549 cells. Moreover, NSC135618 inhibited ZIKV in human placental and neural progenitor cells relevant to ZIKV pathogenesis. Results from binding, kinetics, Western blot, mass spectrometry and

Modifying Cement Hydration with NS@PCE Core-Shell Nanoparticles

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Yue Gu

2017-01-01

Full Text Available It is generally accepted that fine particles could accelerate cement hydration process, or, more specifically, this accelerating effect can be attributed to additional surface area introduced by fine particles. In addition to this view, the surface state of fine particles is also an important factor, especially for nanoparticles. In the previous study, a series of nano-SiO2-polycarboxylate superplasticizer core-shell nanoparticles (NS@PCE were synthesized, which have a similar particle size distribution but different surface properties. In this study, the impact of NS@PCE on cement hydration was investigated by heat flow calorimetry, mechanical property measurement, XRD, and SEM. Results show that, among a series of NS@PCE, NS@PCE-2 with a moderate shell-core ratio appeared to be more effective in accelerating cement hydration. As dosage increases, the efficiency of NS@PCE-2 would reach a plateau which is quantified by various characteristic values. Compressive strength results indicate that strength has a linear correlation with cumulative heat release. A hypothesis was proposed to explain the modification effect of NS@PCE, which highlights a balance between initial dispersion and pozzolanic reactivity. This paper provides a new understanding for the surface modification of supplementary cementitious materials and their application and also sheds a new light on nano-SiO2 for optimizing cement-based materials.

Effects of heat loss as percentage of fuel's energy, friction and variable specific heats of working fluid on performance of air standard Otto cycle

International Nuclear Information System (INIS)

Lin, J.-C.; Hou, S.-S.

2008-01-01

The objective of this study is to analyze the effects of heat loss characterized by a percentage of the fuel's energy, friction and variable specific heats of working fluid on the performance of an air standard Otto cycle with a restriction of maximum cycle temperature. A more realistic and precise relationship between the fuel's chemical energy and the heat leakage that is based on a pair of inequalities is derived through the resulting temperature. The variations in power output and thermal efficiency with compression ratio, and the relations between the power output and the thermal efficiency of the cycle are presented. The results show that the power output as well as the efficiency where maximum power output occurs will increase with increase of the maximum cycle temperature. The temperature dependent specific heats of the working fluid have a significant influence on the performance. The power output and the working range of the cycle increase with the increase of specific heats of the working fluid, while the efficiency decreases with the increase of specific heats of the working fluid. The friction loss has a negative effect on the performance. Therefore, the power output and efficiency of the cycle decrease with increasing friction loss. It is noteworthy that the effects of heat loss characterized by a percentage of the fuel's energy, friction and variable specific heats of the working fluid on the performance of an Otto cycle engine are significant and should be considered in practical cycle analysis. The results obtained in the present study are of importance to provide good guidance for performance evaluation and improvement of practical Otto engines

Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus.

Science.gov (United States)

Zhu, Shaomei; Li, Tingting; Liu, Bochao; Xu, Yuxia; Sun, Yachun; Wang, Yilin; Wang, Yuanzhan; Shuai, Lifang; Chen, Zixuan; Allain, Jean-Pierre; Li, Chengyao

2016-09-15

A lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis C virus (HCV) vaccines and affordable antiviral drugs. In this study, HCV/GB virus B (GBV-B) chimeric virus carrying the major nonstructural proteins NS2 to NS4A (HCV NS2 to -4A chimera) was produced and used to infect common marmosets, since HCV NS2 to NS4A proteins are critical proteases and major antigens. Seven marmosets were inoculated intrahepatically with HCV NS2 to -4A chimera RNA for primary infection or intravenously injected with chimera-containing serum for passage infection. Three animals used as controls were injected with phosphate-buffered saline (PBS) or GBV-B, respectively. Six of seven HCV NS2 to -4A chimera-infected marmosets exhibited consistent viremia and one showed transient viremia during the course of follow-up detection. All six infected animals with persistent circulating viremia presented characteristics typical of viral hepatitis, including viral RNA and proteins in hepatocytes and histopathological changes in liver tissue. Viremia was consistently detected for 5 to 54 weeks of follow-up. FK506 immunosuppression facilitated the establishment of persistent chimera infection in marmosets. An animal with chimera infection spontaneously cleared the virus in blood 7 weeks following the first inoculation, but viral-RNA persistence, low-level viral protein, and mild necroinflammation remained in liver tissue. The specific antibody and T-cell response to HCV NS3 in this viremia-resolved marmoset was boosted by rechallenging, but no viremia was detected during 57 weeks of follow-up. The chimera-infected marmosets described can be used as a suitable small-primate animal model for studying novel antiviral drugs and T-cell-based vaccines against HCV infection. HCV infection causes approximately 70% of chronic hepatitis and is frequently associated with primary liver cancer globally. Chimpanzees have been used as a reliable primate model for HCV infection

Dengue NS1 Antigen - for Early Detection of Dengue Virus Infection

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Amol Hartalkar

2015-08-01

Full Text Available Objectives: To evaluate the efficacy of NS1 antigen assay for early diagnosis of dengue virus infection in a tertiary care hospital. Methods: This cross sectional study was carried out in department of Medicine from August to December 2013. Total 100 patients with dengue fever were included. Complete blood count, alanine aminotransferase (ALT, aspartate aminotransferase (AST, Dengue NS1 antigen and IgM and IgG antibodies of dengue virus were done in all cases. Results: Of the 100 sera tested, 75% were positive for dengue virus infection based on dengue NS1 antigen, IgM antibody and IgG antibody. Dengue NS1 antigen and IgM, IgG antibody were able to detect dengue virus infection between day 1 to day 8 in 92% of samples, 86.7% of samples and 82.6% of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were IgM positive and 62% were IgG positive. Based on the dengue NS1 antigen and IgM antibody combination, 74% were positive for dengue virus infections. Sensitivity of Dengue NS1 antigen was 92.3% and specificity of 74.28% in comparison to IgM antibody. Detection rate increased to 75%, based on the antigen and IgG antibody combination. Sensitivity of dengue NS1 antigen was 90.3% and specificity of 65.8% in comparison to IgG antibody. Conclusion: Dengue NS1 antigen is a useful, sensitive and specific test for early diagnosis of dengue virus infection and it improves diagnostic efficiency in combination with antibody test. Key words: Dengue fever, NS1 antigen. Introduction: Dengue fever (DF is the most common arboviral illness in humans. Each year, an estimated 50-100 million cases of dengue fever and 500,000 cases of dengue hemorrhagic fever occur worldwide, with 30000 deaths (mainly in children. Globally 2.5-3 billion people in approximately 112 tropical and subtropical countries are at risk of dengue.of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were Ig

Efficient hepatitis c virus genotype 1b core-NS5A recombinants permit efficacy testing of protease and NS5A inhibitors

DEFF Research Database (Denmark)

Pham, Long V.; Ramirez Almeida, Santseharay; Carlsen, Thomas H R

2017-01-01

Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants......, permitted by the high replication capacity of strain JFH1 (genotype 2a), has advanced efficacy and resistance testing of antivirals. However, efficient infectious JFH1-based cell cultures of subtype 1b are limited and comprise only the 5= untranslated region (5=UTR)-NS2, NS4A, or NS5A regions. Importantly...

Geological and environmental observations in the Sunchales Creek and Tonco River , Don Otto uranium mine, Salta Province

International Nuclear Information System (INIS)

Gorustovich, S.; Guidi, F.; Bárbaro, N.; Nievas, H.; Tomellini, G.

2013-01-01

Results of geological and environmental observations made by professionals of the Comisión Nacional de Energía Atómica (CNEA) down streams Don Otto uranium mine on the Sunchales creek, from Los Guanacos strait down to the Tonco river mouth, and from river mouth down to narrow pass named Salto Grande, are presented in this report. La Yesera, Las Curtiembres and Los Blanquitos Formations of the Pirgua Subgroup, and Lecho and Yacoraite Formations of the Balbuena Subgroup crops out in that area (Salta Group, Cretaceous- Middle Eocene). Water stream analyses have given uranium contents between 890 μg/L and 1,100 μg/L, and uranium in stream sediments between 4 μg/g and 14 μg/g; radimetric anomalias up to 1,500 c/s in discoloured facies of the Las Curtiembres Formation, and 2,000 c/s in dark pelitic sediments of the Yacoraite Formation. A new zone with uranium traces in Curtiembres Formation belonging to the Pirgua Subgroup has been identified in the Alemanía cretaceous basin, which is stratigraphically similar to Cajoncillo, Las Abritas and El Fraile deposits. Those traces in addition to the other ones localized in the upper third of the Yacoraite Formation would have been originated by the geochemical uranium anomalies in waters and stream sediments by uranium leaching of rocks. The geochemical uranium anomalies in water and sediments are not a consequence of the antropic activity of the uranium mining carried out in Don Otto mine (1961-1982). (authors) [es

Evolutionary dynamics of hepatitis C virus NS3 protease domain during and following treatment with narlaprevir, a potent NS3 protease inhibitor

NARCIS (Netherlands)

de Bruijne, J.; Thomas, X. V.; Rebers, S. P.; Weegink, C. J.; Treitel, M. A.; Hughes, E.; Bergmann, J. F.; de Knegt, R. J.; Janssen, H. L. A.; Reesink, H. W.; Molenkamp, R.; Schinkel, J.

2013-01-01

Narlaprevir, a hepatitis C virus (HCV) NS3/4A serine protease inhibitor, has demonstrated robust antiviral activity in a placebo-controlled phase 1 study. To study evolutionary dynamics of resistant variants, the NS3 protease sequence was clonally analysed in thirty-two HCV genotype 1-infected

Review article Assessment of personality according to Otto Kernberg’s conception

Directory of Open Access Journals (Sweden)

Agnieszka Izdebska

2015-06-01

Full Text Available The subject matter of this paper is the model of personality developed by Otto Kernberg and the research tools designed on the basis of that conception. The paper presents the spectrum of diagnostic methods differing in terms of the level of structuralizing and the form in which they are applied. The first one constructed, the Structural Interview, due to the high requirements within psychoanalytical knowledge and clinical abilities for the individuals who apply it, initiated the development of subsequent methods. They include: the Structured Interview of Personality Organization (STIPO, inventory methods, and a clinician-rated instrument referred to as the Personality Organization Diagnostic Form (PODF. Within the scope of inventory methods, two principal tools for which Polish adaptations have been developed are presented, namely: the Inventory of Personality Organization of Kernberg and collaborators, and the Borderline Personality Inventory of Leichsenring. The existence of a broad spectrum of assessment methods of the personality structure makes it possible to take advantage of the conception of Kernberg in the realms of clinical diagnosis, scientific research, and recently also forensic psychology.

Angle-dependent quantum Otto heat engine based on coherent dipole-dipole coupling

Science.gov (United States)

Su, Shan-He; Luo, Xiao-Qing; Chen, Jin-Can; Sun, Chang-Pu

2016-08-01

Electromagnetic interactions between molecules or within a molecule have been widely observed in biological systems and exhibit broad application for molecular structural studies. Quantum delocalization of molecular dipole moments has inspired researchers to explore new avenues to utilize this physical effect for energy harvesting devices. Herein, we propose a simple model of the angle-dependent quantum Otto heat engine which seeks to facilitate the conversion of heat to work. Unlike previous studies, the adiabatic processes are accomplished by varying only the directions of the magnetic field. We show that the heat engine continues to generate power when the angle relative to the vector r joining the centres of coupled dipoles departs from the magic angle θm where the static coupling vanishes. A significant improvement in the device performance has to be attributed to the presence of the quantum delocalized levels associated with the coherent dipole-dipole coupling. These results obtained may provide a promising model for the biomimetic design and fabrication of quantum energy generators.

Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

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Kazi Abdus Salam

2013-01-01

Full Text Available Currently, hepatitis C virus (HCV infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin. The new therapy has significantly improved sustained virologic response (SVR; however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors.

CIAE 600 kV ns pulse neutron generator

International Nuclear Information System (INIS)

Shen Guanren; Guan Xialing; Chen Hongtao

2001-01-01

The overall composition of CIAE 600 kV ns Pulse Neutron Generator (CPNG) are introduced, and its characteristic, main technological performance and application were also given. CPNG consists of high voltage power supply with highest output voltage 600 kV, direct current 15 mA, stability and ripple ≤0.1%, 2214 mm x 1604 mm x 1504 mm stainless steel high voltage electrode, built in head equipment uniform field accelerating tube, ns pulsed installation, turbomolecular vacuum pump system and drift pipes at 0 degree and 45 degree. Its characteristics are: (1) high current beam; (2) high current beam ns pulsed installation made use of low energy for chopper and high energy for buncher; (3) compactly laid out and simple in structure

[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

DEFF Research Database (Denmark)

Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

2014-01-01

-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

Úloha a význam Otto von Bismarcka v mezinárodních vztazích

OpenAIRE

Bucifalová, Karolína

2015-01-01

In this bachelors thesis is analyzed a personality of Otto von Bismarck and his role and importance in international relations. The thesis is focused on the period from the German unification by iron and blood in 1871 to the beginning of the World War One. It includes the process of the unification of the German empire, international relations in the 19th century and the change of German foreign policy from the Realpolitik to Weltpolitik after Bismarcks abdication.

Homogeneous charge compression ignition compared with Otto-Atkinson in a passenger car size engine

Energy Technology Data Exchange (ETDEWEB)

Nagel, Andreas

2000-07-01

The use of Homogeneous Charge Compression Ignition (HCCI) was investigated in an ordinary SI (spark ignition) engine, in this case a modified Volvo 850, working on one cylinder only, the others towed. The major purpose of this study was to examine whether there were the same kind of throttle losses in this engine as in a Diesel engine (Volvo TD 100). One reason for throttling is that HCCI causes very cold exhaust gases. The Diesel engine has a larger cylinder volume (1.6 compared to 0.5 litre), working at low engine speed (1000 rpm) and only two valves with comparably small area. The smaller Volvo 850 engine has four valves and was in this examination working at up to 3500 rpm. To make the engine run by HCCI following modifications were made. The compression was set to 20:1 by changing the piston. To affect the ignition an electrical heater was installed near the air inlet. Mixing iso-octane (ON 100) and N-heptane (ON 0) set the octane number. A couple of camshafts with different cam-profiles were used to achieve the right valve opening duration depending on which kind of combustion that was studied. There could then also be a comparison between Otto and HCCI combustion both working with wide-open throttle. To obtain comparable indicated mean effective pressure (IMEP) the engine was working with late (LIVC) or early inlet valve closing (EIVC) at SI combustion. Measurements were taken involving in-cylinder pressure, temperature, speed, fuel-consumption, emissions etc. Regarding emissions there were special consideration taken to hydrocarbon and NO{sub x}, which are known to be extremely high respectively low with HCCI combustion. Important questions that should be answered were: * How does higher engine speed affect the combustion ?, * How does the engine size affect emissions ?, * How much is the valve area affecting gas exchange losses ?, and * How high is the efficiency with HCCI compared with Otto (LIVC/EIVC) ?. The best results are achieved at an indicated mean

Nuclear fission - the unexpected discovery seventy years ago

International Nuclear Information System (INIS)

Weis, Michael

2008-01-01

Seventy years ago, on December 17, 1938, Otto Hahn, Lise Meitner, and Fritz Strassmann discovered nuclear fission. It was a serendipitous discovery resulting from the consistent pursuit, for many years, of occasionally unexpected radiochemical experimental findings. Hardly any other scientific discovery has had such direct bearing on our life, changing our view of the world. It over-threw the tenet of physics, believed to be incontestable, that the atom was indivisible. The use of nuclear power it has made possible has given rise to immense benefits, but it has also allowed mankind's most dreadful weapon so far to be developed. All this is ample reason seventy years later to recall the discovery, the discoverers and their times. It will also be shown what later generations have made of this discovery, and what economic and ecological prospects it continues to hold. (orig.)

Mosquito densonucleosis virus non-structural protein NS2 is necessary for a productive infection

International Nuclear Information System (INIS)

Azarkh, Eugene; Robinson, Erin; Hirunkanokpun, Supanee; Afanasiev, Boris; Kittayapong, Pattamaporn; Carlson, Jonathan; Corsini, Joe

2008-01-01

Mosquito densonucleosis viruses synthesize two non-structural proteins, NS1 and NS2. While NS1 has been studied relatively well, little is known about NS2. Antiserum was raised against a peptide near the N-terminus of NS2, and used to conduct Western blot analysis and immuno-fluorescence assays. Western blots revealed a prominent band near the expected size (41 kDa). Immuno-fluorescence studies of mosquito cells transfected with AeDNV indicate that NS2 has a wider distribution pattern than does NS1, and the distribution pattern appears to be a function of time post-infection. Nuclear localization of NS2 requires intact C-terminus but does not require additional viral proteins. Mutations ranging from complete NS2 knock-out to a single missense amino acid substitution in NS2 can significantly reduce viral replication and production of viable progeny

Josef Ježek a Otto Bláha – cesta dvou četnických generálů před Národní soud

Czech Academy of Sciences Publication Activity Database

Klečacký, Martin

2014-01-01

Roč. 22, č. 2 (2014), s. 155-187 ISSN 1210-6860 R&D Projects: GA ČR(CZ) GAP410/12/0468 Institutional support: RVO:67985921 Keywords : gendarmerie * National court * Josef Ježek * Otto Bláha Subject RIV: AB - History

AGILE Observations of the Gravitational-wave Source GW170817: Constraining Gamma-Ray Emission from an NS-NS Coalescence

Science.gov (United States)

Verrecchia, F.; Tavani, M.; Donnarumma, I.; Bulgarelli, A.; Evangelista, Y.; Pacciani, L.; Ursi, A.; Piano, G.; Pilia, M.; Cardillo, M.; Parmiggiani, N.; Giuliani, A.; Pittori, C.; Longo, F.; Lucarelli, F.; Minervini, G.; Feroci, M.; Argan, A.; Fuschino, F.; Labanti, C.; Marisaldi, M.; Fioretti, V.; Trois, A.; Del Monte, E.; Antonelli, L. A.; Barbiellini, G.; Caraveo, P.; Cattaneo, P. W.; Colafrancesco, S.; Costa, E.; D'Amico, F.; Ferrari, A.; Giommi, P.; Morselli, A.; Paoletti, F.; Pellizzoni, A.; Picozza, P.; Rappoldi, A.; Soffitta, P.; Vercellone, S.; Baroncelli, L.; Zollino, G.

2017-12-01

The LIGO-Virgo Collaboration (LVC) detected, on 2017 August 17, an exceptional gravitational-wave (GW) event temporally consistent within ˜ 1.7 {{s}} with the GRB 1708117A observed by Fermi-GBM and INTEGRAL. The event turns out to be compatible with a neutron star-neutron star (NS-NS) coalescence that subsequently produced a radio/optical/X-ray transient detected at later times. We report the main results of the observations by the AGILE satellite of the GW170817 localization region (LR) and its electromagnetic (EM) counterpart. At the LVC detection time T 0, the GW170817 LR was occulted by the Earth. The AGILE instrument collected useful data before and after the GW/GRB event because in its spinning observation mode it can scan a given source many times per hour. The earliest exposure of the GW170817 LR by the gamma-ray imaging detector started about 935 s after T 0. No significant X-ray or gamma-ray emission was detected from the LR that was repeatedly exposed over timescales of minutes, hours, and days before and after GW170817, also considering Mini-calorimeter and Super-AGILE data. Our measurements are among the earliest ones obtained by space satellites on GW170817 and provide useful constraints on the precursor and delayed emission properties of the NS-NS coalescence event. We can exclude with high confidence the existence of an X-ray/gamma-ray emitting magnetar-like object with a large magnetic field of {10}15 {{G}}. Our data are particularly significant during the early stage of evolution of the EM remnant.

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.

Science.gov (United States)

Turkington, Hannah L; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin; Hale, Benjamin G

2018-03-01

Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The

Rediscovery of Otto Frank's contribution to science.

Science.gov (United States)

Kuhtz-Buschbeck, Johann P; Drake-Holland, Angela; Noble, Mark I M; Lohff, Brigitte; Schaefer, Jochen

2018-06-01

In the late 19th century, German physiologist Otto Frank (1865-1944) embarked on a near life-long research program of laying down the mathematical, methodological, and theoretical foundations in order to understand and define the performance of the heart and circulatory system in all their complexity. The existence of the "Frank-Starling law" testifies to this. Two of his seminal publications have been translated into English previously, introducing Frank's research on the dynamics of the heart and the arterial pulse to a wider audience. It is likely that there are a host of other comparable achievements and publications of Frank that are still unknown to the international scientific (cardiological and physiological) community. However, their influence can still be felt and seen in modern cardiology and cardio-physiology, such as in the development of modern interactive simulating and teaching programs. We have translated and commented on ten of these papers, which can be read in parallel with the German originals. These publications show a wealth of theoretical assumptions and projections regarding the importance of the sarcomere, the development of models of contraction, thermo-dynamical considerations for muscular activity, differences between cardiac and skeletal muscles, problems related to methodology and measurement, and the first pressure-volume diagram (published 120 years ago). These topics were envisioned by Frank long before they became a focus of subsequent modern research. Nowadays, frequent measurements of pressure-volume relationships are made in research using the pressure-volume conductance catheter technique. In commenting Frank's scientific topics, we try to show how interconnected his thinking was, and thus how it enabled him to cover such a wide range of subjects. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Patrimonio fotográfico del Valle del Cauca: el archivo de Otto Moll González

Directory of Open Access Journals (Sweden)

Olga Cecilia Eusse González

2012-06-01

Full Text Available El Departamento Red de Bibliotecas, a través del Área Cultural de Cali, adquirió en 2009 el archivo fotográfico de Otto Moll González (Cúcuta, 1904-Cali, 1988. Este archivo, conformado por alrededor de 30.000 documentos entre negativos blanco y negro (en película y vidrio y fotografías blanco y negro en papel de diferentes formatos, constituye una de las colecciones de imágenes más valiosas que tiene el Valle del Cauca para los decenios de 1950 a 1980 y es un aporte importante a las colecciones documentales de la Red de Bibliotecas sobre el suroccidente y otras regiones del país.

[Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

Science.gov (United States)

Ren, K; Qian, D; Wang, Y W; Pang, Q S; Zhang, W C; Yuan, Z Y; Wang, P

2018-01-23

Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference ( P =0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results ( P =0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients( P <0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast

The discovery of the neutron and its consequences (1930-1940)

Science.gov (United States)

Nesvizhevsky, Valery; Villain, Jacques

2017-11-01

In 1930, Walther Bothe and Herbert Becker performed an experiment, which was further improved by Irène and Frédéric Joliot-Curie. These authors, however, misinterpreted their results and believed to have observed γ-rays while they had seen neutrons. After additional experimental verifications, James Chadwick gave the correct interpretation of these experiments in 1932. Immediately, the new particle, the neutron, became an essential actor of nuclear and elementary particle physics, and completely changed the whole research landscape. Enrico Fermi and his group applied it to artificial radioactivity, substituting neutrons to α-rays initially used by Joliot-Curies. They also discovered that slow neutrons were more efficient than fast ones in certain nuclear reactions. A crucial discovery of Otto Hahn, Fritz Straßmann, Lise Meitner, and Otto Frisch, after several misinterpretations of complicated experimental results, was nuclear fission. When Joliot, Halban, and Kowarski demonstrated the possibility of a chain reaction by neutron multiplication due to fission, nuclear physics became a military science, at the very moment when the Second World War was beginning. Later it led to nuclear power applications and use of neutrons as an important tool and object of scientific research at large-scale neutron facilities. The Comptes rendus de l'Académie des sciences were partner of a vivid international debate involving several other journals.

Structure-based discovery of clinically approved drugs as Zika virus NS2B-NS3 protease inhibitors that potently inhibit Zika virus infection in vitro and in vivo.

Science.gov (United States)

Yuan, Shuofeng; Chan, Jasper Fuk-Woo; den-Haan, Helena; Chik, Kenn Ka-Heng; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Zheng; Zou, Zijiao; Tee, Kah-Meng; Cai, Jian-Piao; Chan, Kwok-Hung; de la Peña, Jorge; Pérez-Sánchez, Horacio; Cerón-Carrasco, José Pedro; Yuen, Kwok-Yung

2017-09-01

Zika virus (ZIKV) infection may be associated with severe complications in fetuses and adults, but treatment options are limited. We performed an in silico structure-based screening of a large chemical library to identify potential ZIKV NS2B-NS3 protease inhibitors. Clinically approved drugs belonging to different drug classes were selected among the 100 primary hit compounds with the highest predicted binding affinities to ZIKV NS2B-NS3-protease for validation studies. ZIKV NS2B-NS3 protease inhibitory activity was validated in most of the selected drugs and in vitro anti-ZIKV activity was identified in two of them (novobiocin and lopinavir-ritonavir). Molecular docking and molecular dynamics simulations predicted that novobiocin bound to ZIKV NS2B-NS3-protease with high stability. Dexamethasone-immunosuppressed mice with disseminated ZIKV infection and novobiocin treatment had significantly (P < 0.05) higher survival rate (100% vs 0%), lower mean blood and tissue viral loads, and less severe histopathological changes than untreated controls. This structure-based drug discovery platform should facilitate the identification of additional enzyme inhibitors of ZIKV. Copyright © 2017 Elsevier B.V. All rights reserved.

Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

Science.gov (United States)

Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

2017-07-01

Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC 50 ) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC 50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC 50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC 50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir

Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies

Directory of Open Access Journals (Sweden)

Leticia Barboza Rocha

2017-10-01

Full Text Available Dengue nonstructural protein 1 (NS1 is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2, which were used to map three NS1 epitopes. The sequence 193AVHADMGYWIESALNDT209 was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV protein. On the other hand, the sequence 25VHTWTEQYKFQPES38 was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence 127ELHNQTFLIDGPETAEC143, is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections.

The effect of glycosylation on cytotoxicity of Ibaraki virus nonstructural protein NS3

Science.gov (United States)

URATA, Maho; WATANABE, Rie; IWATA, Hiroyuki

2015-01-01

The cytotoxicity of Ibaraki virus nonstructural protein NS3 was confirmed, and the contribution of glycosylation to this activity was examined by using glycosylation mutants of NS3 generated by site-directed mutagenesis. The expression of NS3 resulted in leakage of lactate dehydrogenase to the culture supernatant, suggesting the cytotoxicity of this protein. The lack of glycosylation impaired the transport of NS3 to the plasma membrane and resulted in reduced cytotoxicity. Combined with the previous observation that NS3 glycosylation was specifically observed in mammalian cells (Urata et al., Virus Research 2014), it was suggested that the alteration of NS3 cytotoxicity through modulating glycosylation is one of the strategies to achieve host specific pathogenisity of Ibaraki virus between mammals and vector arthropods. PMID:26178820

Sigmund Freud and Otto Rank: debates and confrontations about anxiety and birth.

Science.gov (United States)

Pizarro Obaid, Francisco

2012-06-01

The publication of Otto Rank's The Trauma of Birth (1924) gave rise to an intense debate within the secret Committee and confronted Freud with one of his most beloved disciples. After analyzing the letters that the Professor exchanged with his closest collaborators and reviewing the works he published during this period, it is clear that anxiety was a crucial element among the topics in dispute. His reflections linked to the signal anxiety concept allowed Freud to refute Rank's thesis that defined birth trauma as the paradigmatic key to understanding neurosis, and, in turn, was a way of confirming the validity of the concepts of Oedipus complex, repression and castration in the conceptualization of anxiety. The reasons for the modifications of anxiety theory in the mid-1920s cannot be reduced, as Freud would affirm officially in his work of 1926, to the detection of internal contradictions in his theory or to the desire to establish a metapsychological version of the problem, for they gain their essential impulse from the debate with Rank. Copyright © 2012 Institute of Psychoanalysis.

The Future of HCV Therapy: NS4B as an Antiviral Target

Directory of Open Access Journals (Sweden)

Hadas Dvory-Sobol

2010-11-01

Full Text Available Chronic hepatitis C virus (HCV infection is a major worldwide cause of liver disease, including cirrhosis and hepatocellular carcinoma. It is estimated that more than 170 million individuals are infected with HCV, with three to four million new cases each year. The current standard of care, combination treatment with interferon and ribavirin, eradicates the virus in only about 50% of chronically infected patients. Notably, neither of these drugs directly target HCV. Many new antiviral therapies that specifically target hepatitis C (e.g. NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant number having advanced into clinical trials. The nonstructural 4B (NS4B protein, is among the least characterized of the HCV structural and nonstructural proteins and has been subjected to few pharmacological studies. NS4B is an integral membrane protein with at least four predicted transmembrane (TM domains. A variety of functions have been postulated for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. This review summarizes potential targets within the nonstructural protein NS4B, with a focus on novel classes of NS4B inhibitors.

Uncoupling of Protease trans-Cleavage and Helicase Activities in Pestivirus NS3.

Science.gov (United States)

Zheng, Fengwei; Lu, Guoliang; Li, Ling; Gong, Peng; Pan, Zishu

2017-11-01

The nonstructural protein NS3 from the Flaviviridae family is a multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å 2 intramolecular protease-helicase interface comprising three clusters of interactions, representing a "closed" global conformation related to the NS3-NS4A cis -cleavage event. Although this conformation is incompatible with protease trans -cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities in vitro and virus production in vivo Our work reveals important features of protease-helicase coordination in pestivirus NS3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein. IMPORTANCE Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the Flaviviridae family viruses are unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease cis -cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through different

The effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on protein-protein interactions.

Science.gov (United States)

Yates, Christopher M; Sternberg, Michael J E

2013-11-01

Non-synonymous single nucleotide polymorphisms (nsSNPs) are single base changes leading to a change to the amino acid sequence of the encoded protein. Many of these variants are associated with disease, so nsSNPs have been well studied, with studies looking at the effects of nsSNPs on individual proteins, for example, on stability and enzyme active sites. In recent years, the impact of nsSNPs upon protein-protein interactions has also been investigated, giving a greater insight into the mechanisms by which nsSNPs can lead to disease. In this review, we summarize these studies, looking at the various mechanisms by which nsSNPs can affect protein-protein interactions. We focus on structural changes that can impair interaction, changes to disorder, gain of interaction, and post-translational modifications before looking at some examples of nsSNPs at human-pathogen protein-protein interfaces and the analysis of nsSNPs from a network perspective. © 2013.

Nodding syndrome (NS) and Onchocerca Volvulus (OV) in Northern Uganda.

Science.gov (United States)

Lagoro, David Kitara; Arony, Denis Anywar

2017-01-01

Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus ( OV ). These findings suggest a neuro-inflammatory cause of NS and they are important findings in the search for the cause of Nodding Syndrome. These observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus . Many clinical and epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease, Onchocerciasis , some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with ( OV infection (using positive skin snips), we observe that ( OV is generally endemic in many parts of Sub Saharan Africa and Latin America and that to date, no NS cases have been recorded in those regions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda.

Genetic Defects Underlie the Non-syndromic Autosomal Recessive Intellectual Disability (NS-ARID

Directory of Open Access Journals (Sweden)

Saleha Shamim

2017-05-01

Full Text Available Intellectual disability (ID is a neurodevelopmental disorder which appears frequently as the result of genetic mutations and may be syndromic (S-ID or non-syndromic (NS-ID. ID causes an important economic burden, for patient's family, health systems, and society. Identifying genes that cause S-ID can easily be evaluated due to the clinical symptoms or physical anomalies. However, in the case of NS-ID due to the absence of co-morbid features, the latest molecular genetic techniques can be used to understand the genetic defects that underlie it. Recent studies have shown that non-syndromic autosomal recessive (NS-ARID is extremely heterogeneous and contributes much more than X-linked ID. However, very little is known about the genes and loci involved in NS-ARID relative to X-linked ID, and whose complete genetic etiology remains obscure. In this review article, the known genetic etiology of NS-ARID and possible relationships between genes and the associated molecular pathways of their encoded proteins has been reviewed which will enhance our understanding about the underlying genes and mechanisms in NS-ARID.

Production of recombinant dengue non-structural 1 (NS1) proteins from clinical virus isolates.

Science.gov (United States)

Yohan, Benediktus; Wardhani, Puspa; Aryati; Trimarsanto, Hidayat; Sasmono, R Tedjo

2017-01-01

Dengue is a febrile disease caused by infection of dengue virus (DENV). Early diagnosis of dengue infection is important for better management of the disease. The DENV Non-Structural Protein 1 (NS1) antigen has been routinely used for the early dengue detection. In dengue epidemic countries such as Indonesia, clinicians are increasingly relying on the NS1 detection for confirmation of dengue infection. Various NS1 diagnostic tests are commercially available, however different sensitivities and specificities were observed in various settings. This study was aimed to generate dengue NS1 recombinant protein for the development of dengue diagnostic tests. Four Indonesian DENV isolates were used as the source of the NS1 gene cloning, expression, and purification in bacterial expression system. Recombinant NS1 proteins were successfully purified and their antigenicities were assessed. Immunization of mice with recombinant proteins observed the immunogenicity of the NS1 protein. The generated recombinant proteins can be potentially used in the development of NS1 diagnostic test. With minimal modifications, this method can be used for producing NS1 recombinant proteins from isolates obtained from other geographical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene.

Science.gov (United States)

Sabet, Salwa; George, Marina A; El-Shorbagy, Haidan M; Bassiony, Heba; Farroh, Khaled Y; Youssef, Tareq; Salaheldin, Taher A

2017-01-01

Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system. Gel.NPs were synthesized and characterized (size: 150±2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the recombinant NS2 protein was confirmed by Western blotting to verify the efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin nanoparticles and a successful conjugation was confirmed by labeling and imaging using Confocal Laser Scanning Microscope (CLSM). Interestingly, the transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-α was 50% more efficient than transformation with the gene alone. In addition, conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation efficiency into E. coli DH5-α than the other ratios (1:50 and 2:50). Gel.NPs effectively enhanced the gene delivery in bacterial cells without affecting the structure of NS2 gene and could be used as a safe, easy, rapid, cost-effective and non-viral vaccine delivery system for HCV.

D-Branes in the Background of NS Fivebranes

CERN Document Server

Elitzur, Shmuel; Rabinovici, Eliezer; Sarkisian, G; Kutasov, D; Elitzur, Shmuel; Giveon, Amit; Kutasov, David; Rabinovici, Eliezer; Sarkissian, Gor

2000-01-01

We study the dynamics of $D$-branes in the near-horizon geometry of $NS$ fivebranes. This leads to a holographically dual description of the physics of $D$-branes ending on and/or intersecting $NS5$-branes. We use it to verify some properties of such $D$-branes which were deduced indirectly in the past, and discuss some instabilities of non-supersymmetric brane configurations. Our construction also describes vacua of Little String Theory which are dual to open plus closed string theory in asymptotically linear dilaton spacetimes.

Chain reaction. History of the atomic bomb

International Nuclear Information System (INIS)

Mania, Hubert

2010-01-01

Henri becquerel tracked down in 1896 a strange radiation, which was called radioactivity by Marie Curie. In the following centuries German scientists Max Planck, Albert Einstein and Werner Heisenberg presented fundamental contributions to understand processes in the atomic nucleus. At Goettingen, center of the international nuclear physics community, the American student J. Robert Oppenheimer admit to this physical research. In the beginning of 1939 the message of Otto Hahns' nuclear fission electrified researchers. The first step, unleashing atomic energy, was done. A half year later the Second World War begun. And suddenly being friend with and busily communicating physicians were devided into hostile power blocs as bearers of official secrets. The author tells in this exciting book the story of the first atomic bomb as a chain reaction of ideas, discoveries and visions, of friendships, jealousy and intrigues of scientists, adventurers and genius. (orig./GL)

An overview of the teaching of nuclear chemistry

International Nuclear Information System (INIS)

Seaborg, G.I.

1990-01-01

Otto Hahn's book, Applied Radiochemistry, published in 1936, marked the author's entry into this field. Notes concerning a lecture course, An Introduction to Nuclear Chemistry, given during the summer of 1942 at the University of Chicago, as an introduction to the Plutonium Project of the Manhattan District, were widely distributed for use by participants in the Project. Nuclear chemistry courses, undergraduate and graduate, instigated at Berkeley in 1946, were taken by large numbers of students many of who became pioneers in the field. Noteworthy is Friedlander's and Kennedy's 1949 textbook, Introduction to Radiochemistry (and subsequent revisions). These courses and this book serve as typical examples, many other such courses were taught and books published during the intervening years. More recently the Department of Energy Summer School in Nuclear Chemistry (for high school students) at San Jose State University has helped to revive student interest in nuclear chemistry

Chain reaction. History of the atomic bomb; Kettenreaktion. Die Geschichte der Atombombe

Energy Technology Data Exchange (ETDEWEB)

Mania, Hubert

2010-07-01

Henri becquerel tracked down in 1896 a strange radiation, which was called radioactivity by Marie Curie. In the following centuries German scientists Max Planck, Albert Einstein and Werner Heisenberg presented fundamental contributions to understand processes in the atomic nucleus. At Goettingen, center of the international nuclear physics community, the American student J. Robert Oppenheimer admit to this physical research. In the beginning of 1939 the message of Otto Hahns' nuclear fission electrified researchers. The first step, unleashing atomic energy, was done. A half year later the Second World War begun. And suddenly being friend with and busily communicating physicians were devided into hostile power blocs as bearers of official secrets. The author tells in this exciting book the story of the first atomic bomb as a chain reaction of ideas, discoveries and visions, of friendships, jealousy and intrigues of scientists, adventurers and genius. (orig./GL)

60 years controlled nuclear fission: CP-1

International Nuclear Information System (INIS)

Anon.

2002-01-01

On December 2, 1942, the Chicago Pile 1 (CP-1) went critical for the first time. In this way, the scientists and engineers involved in the project under the leadership of Enrico Fermi succeeded in demonstrating that a self-sustaining nuclear reaction with nuclear fission processes was technically feasible. Only four years after the discovery and proof of nuclear fission by Otto Hahn, Fritz Strassmann, and Lise Meitner, the experiment consisting of graphite blocks as the moderator and uranium dioxide pellets as the fuel, as well as instrumentation and control devices, had been set up in the former squash court of the field and track stadium of the University of Chicago. Precisely at 3.36 a.m. Chicago time, after control rods had been withdrawn, the instruments showed the chain reaction by the neutron flux they indicated. An important cornerstone in the use of nuclear power had thus been laid. (orig.)

Predicting deleterious nsSNPs: an analysis of sequence and structural attributes

Directory of Open Access Journals (Sweden)

Saqi Mansoor AS

2006-04-01

Full Text Available Abstract Background There has been an explosion in the number of single nucleotide polymorphisms (SNPs within public databases. In this study we focused on non-synonymous protein coding single nucleotide polymorphisms (nsSNPs, some associated with disease and others which are thought to be neutral. We describe the distribution of both types of nsSNPs using structural and sequence based features and assess the relative value of these attributes as predictors of function using machine learning methods. We also address the common problem of balance within machine learning methods and show the effect of imbalance on nsSNP function prediction. We show that nsSNP function prediction can be significantly improved by 100% undersampling of the majority class. The learnt rules were then applied to make predictions of function on all nsSNPs within Ensembl. Results The measure of prediction success is greatly affected by the level of imbalance in the training dataset. We found the balanced dataset that included all attributes produced the best prediction. The performance as measured by the Matthews correlation coefficient (MCC varied between 0.49 and 0.25 depending on the imbalance. As previously observed, the degree of sequence conservation at the nsSNP position is the single most useful attribute. In addition to conservation, structural predictions made using a balanced dataset can be of value. Conclusion The predictions for all nsSNPs within Ensembl, based on a balanced dataset using all attributes, are available as a DAS annotation. Instructions for adding the track to Ensembl are at http://www.brightstudy.ac.uk/das_help.html

Oncolytic effects of a novel influenza A virus expressing interleukin-15 from the NS reading frame.

Directory of Open Access Journals (Sweden)

Marijke van Rikxoort

Full Text Available Oncolytic influenza A viruses with deleted NS1 gene (delNS1 replicate selectively in tumour cells with defective interferon response and/or activated Ras/Raf/MEK/ERK signalling pathway. To develop a delNS1 virus with specific immunostimulatory properties, we used an optimised technology to insert the interleukin-15 (IL-15 coding sequence into the viral NS gene segment (delNS1-IL-15. DelNS1 and delNS1-IL-15 exerted similar oncolytic effects. Both viruses replicated and caused caspase-dependent apoptosis in interferon-defective melanoma cells. Virus replication was required for their oncolytic activity. Cisplatin enhanced the oncolytic activity of delNS1 viruses. The cytotoxic drug increased delNS1 replication and delNS1-induced caspase-dependent apoptosis. Interference with MEK/ERK signalling by RNAi-mediated depletion or the MEK inhibitor U0126 did not affect the oncolytic effects of the delNS1 viruses. In oncolysis sensitive melanoma cells, delNS1-IL-15 (but not delNS1 infection resulted in the production of IL-15 levels ranging from 70 to 1140 pg/mL in the cell culture supernatants. The supernatants of delNS1-IL-15-infected (but not of delNS1-infected melanoma cells induced primary human natural killer cell-mediated lysis of non-infected tumour cells. In conclusion, we constructed a novel oncolytic influenza virus that combines the oncolytic activity of delNS1 viruses with immunostimulatory properties through production of functional IL-15. Moreover, we showed that the oncolytic activity of delNS1 viruses can be enhanced in combination with cytotoxic anti-cancer drugs.

Otto Dix, Pablo Picasso y la pintura de guerra

Directory of Open Access Journals (Sweden)

Ángel Llorente Hernández

2012-01-01

Full Text Available La Primera Guerra Mundial provocó desde su desencadenamiento cambios importantes en los países implicados que afectaron a todos los ámbitos de la vida de sus poblaciones. Algunos artistas sintieron especialmente la repercusión moral y la convulsión causadas por la guerra mecanizada en la que un número cada vez mayor de soldados morían en el frente, a la vez que se producían masacres en zonas de la retaguardia. El pintor expresionista alemán Otto Dix recogió en sus dibujos, hechos en primera línea de combate, la dureza de los enfrentamientos y de la vida de los combatientes en las trincheras del frente occidental y reflejó en grabados y pinturas posteriores a la Gran Guerra las penalidades y los horrores sufridas por aquellos. Sus obras son, además de testimonios de las atrocidades de los combates, condena y denuncia de todas las guerras. En el año 1937 el español Pablo Picasso pintó el mural Guernica, cuyo título alude al bombardeo de la localidad vasca del mismo nombre, ocurrido poco tiempo antes de que su autor lo comenzase. Ya desde su creación, el cuadro se convirtió en una de las obras artísticas principales del pasado siglo y en icono de la lucha por la paz. Ambos artistas emplearon lenguajes vanguardistas para crear formas nuevas, alejadas de las maneras tradicionales de representar la guerra en la cultura occidental. Dix se sirvió del expresionismo para mostrar en sus composiciones escenas verosímiles de una dureza difícil de soportar para quienes las contemplan. Picasso se apoyó sobre todo en el cubismo y el surrealismo para aludir a los efectos de la guerra moderna sobre la población indefensa.Countries involved in The Great War experienced dramatic changes in every aspect of their day to day life. Some artists were especially sensitive towards the moral convulsion caused by a mechanized war where an increasing number of soldiers were dying in the frontline and massacres were taking place in the rear. Through

Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production.

Science.gov (United States)

Gouklani, H; Beyer, C; Drummer, H; Gowans, E J; Netter, H J; Haqshenas, G

2013-04-01

The p7 protein of hepatitis C virus (HCV) is a small, integral membrane protein that plays a critical role in virus replication. Recently, we reported two intergenotypic JFH1 chimeric viruses encoding the partial or full-length p7 protein of the HCV-A strain of genotype 1b (GT1b; Virology; 2007; 360:134). In this study, we determined the consensus sequences of the entire polyprotein coding regions of the wild-type JFH1 and the revertant chimeric viruses and identified predominant amino acid substitutions in core (K74M), NS2 (T23N, H99P) and NS5A (D251G). Forward genetic analysis demonstrated that all single mutations restored the infectivity of the defective chimeric genomes suggesting that the infectious virus production involves the association of p7 with specific regions in core, NS2 and NS5A. In addition, it was demonstrated that the NS2 T23N facilitated the generation of infectious intergenotypic chimeric virus encoding p7 from GT6 of HCV. © 2012 Blackwell Publishing Ltd.

A Model of H-NS Mediated Compaction of Bacterial DNA

NARCIS (Netherlands)

Joyeux, M.; Vreede, J.

2013-01-01

The histone-like nucleoid structuring protein (H-NS) is a nucleoid-associated protein, which is involved in both gene regulation and DNA compaction. H-NS can bind to DNA in two different ways: in trans, by binding to two separate DNA duplexes, or in cis, by binding to different sites on the same

Supersymmetric non-singular fractional D2-branes and NS-NS 2-branes

International Nuclear Information System (INIS)

Cvetic, M.; Gibbons, G.W.; Lue, H.; Pope, C.N.

2001-01-01

We obtain regular deformed D2-brane solutions with fractional D2-branes arising as wrapped D4-branes. The space transverse to the D2-brane is a complete Ricci-flat 7-manifold of G 2 holonomy, which is asymptotically conical with principal orbits that are topologically CP 3 or the flag manifold SU(3)/(U(1)xU(1)). We obtain the solution by first constructing an L 2 normalisable harmonic 3-form. We also review a previously-obtained regular deformed D2-brane whose transverse space is a different 7-manifold of G 2 holonomy, with principal orbits that are topologically S 3 xS 3 . This describes D2-branes with fractional NS-NS 2-branes coming from the wrapping of 5-branes, which is supported by a non-normalisable harmonic 3-form on the 7-manifold. We prove that both types of solutions are supersymmetric, preserving 1/16 of the maximal supersymmetry and hence that they are dual to N=1 three-dimensional gauge theories. In each case, the spectrum for minimally-coupled scalars is discrete, indicating confinement in the infrared region of the dual gauge theories. We examine resolutions of other branes, and obtain necessary conditions for their regularity. The resolution of many of these seems to lie beyond supergravity. In the process of studying these questions, we construct new explicit examples of complete Ricci-flat metrics

Measuring energy conservation on Nova Scotia (NS) farms: A 2004 to 2011 comparison

International Nuclear Information System (INIS)

Bailey, J.A.; Duinker, P.; Amyotte, P.; Adams, M.; Khan, F.

2016-01-01

Many jurisdictions, including Nova Scotia (NS), have implemented policies and programs around energy. The NS government has targeted energy efficiency and more renewable energy as two main policy areas. The NS Department of Agriculture has taken initiative to provide support to implement energy conservation, energy efficiency and renewable energy opportunities in recent years but have these programs and policies been effective? A baseline energy use survey was conducted in 2005 and responses from mail surveys in 2012 (n = 273, 11.4% response rate) were used to measure the change in NS farm energy use data reported for 2004 and 2011. There have been significant reductions in energy use on NS farms. On average, NS farmers spent $8790 on energy expenses in 2011 compared to $11,228 in 2004. Adjusting for inflation, this is a 32% decrease, despite energy commodity pricing increases beyond the inflation rate. This is likely due to a decrease in energy use and a shift from gasoline use to diesel use. By the end of 2012, 36.0% of NS farmers (more than 860) had received some level of support to evaluate their energy options. This includes 410 energy audits compared to only 36 by the end of 2005. - Highlights: • Nova Scotia farmers decreased their energy costs by 32% between 2004 and 2011. • Energy reductions were likely due to decreased energy use and a shift in fuel use. • An estimated 374 NS farms had an energy audit between 2005 and 2012.

Expression of NS1 of PPV in E.coli%猪细小病毒NS1基因的原核表达

Institute of Scientific and Technical Information of China (English)

冉旭华; 闻晓波; 孟凡; 周恩民

2007-01-01

根据GenBank发表的猪细小病毒(porcine parvovirus, PPV)中国株基因序列设计引物,通过PCR方法扩增到了PPV LJL12株NS1全长基因,将其克隆到原核表达载pET30a(+)上,成功构建原核表达载体pET30a-NS1,将其转化到大肠杆菌BL21(DE3)感受态细胞.经IPTG诱导表达后,进行SDS-PAGE和Western blot分析.SDS-PAGE电泳显示NS1在大肠杆菌中得到成功表达,重组蛋白大小约为86 ku,与预期大小相符;Western blot分析表明,该蛋白能与PPV阳性血清发生特异性反应,证明该蛋白具有良好生物学活性.NS1在大肠杆菌中成功表达,具有免疫原性,可作为鉴别诊断抗原用于PPV的临床检测.

Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB).

Science.gov (United States)

Wang, Nai-Jyuan; Lee, Chi-Ching; Cheng, Chao-Sheng; Lo, Wei-Cheng; Yang, Ya-Fen; Chen, Ming-Nan; Lyu, Ping-Chiang

2012-01-01

Plant non-specific lipid transfer proteins (nsLTPs) are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database--nsLTPDB--which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs http://nsltpdb.life.nthu.edu.tw/. Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined.

Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB

Directory of Open Access Journals (Sweden)

Wang Nai-Jyuan

2012-01-01

Full Text Available Abstract Background Plant non-specific lipid transfer proteins (nsLTPs are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. Methods In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database -- nsLTPDB -- which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs http://nsltpdb.life.nthu.edu.tw/. Results Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. Conclusions Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined.

LHC experience with different bunch spacings in 2011 (25, 50 and 75 ns)

International Nuclear Information System (INIS)

Rumolo, G.; Iadarola, G.; Dominguez, O.; Arduini, G.; Bartosik, H.; Claudet, S.; Esteban-Mueller, J.; Roncarolo, F.; Shaposhnikova, E.; Tavian, L.

2012-01-01

LHC operation in 2011 had a smooth start in March with 75 ns beams and only one month later moved to 50 ns beam, after a successful dedicated scrubbing run. Several observables, such as pressure rise, heat load in the arcs, beam instability, emittance growth and synchronous phase shift, clearly pointed to the presence of an electron cloud inside the machine during the first days of operation with 50 ns beams. The gradual reduction of all these effects, and their eventual disappearance, over the days of the scrubbing run, indicated electron cloud mitigation and allowed physics production to shift to 50 ns beams. Up to the end of the run the quality of the 50 ns beams was increased by regular stages (first lower transverse emittances, then higher intensities), so that these beams could provide steadily improving peak luminosities. Furthermore, five MD sessions with 25 ns beams took place in the period June-October, but the quality of these beams was always deteriorated by severe electron cloud effects. However, a clear improvement was noticed also with the 25 ns runs. An estimation of the present state of conditioning of the machine and the required scrubbing time can be inferred from electron cloud simulations compared with measured data. (authors)

Utility of dengue NS1 antigen rapid diagnostic test for use in difficult to reach areas and its comparison with dengue NS1 ELISA and qRT-PCR.

Science.gov (United States)

Shukla, Mohan K; Singh, Neeru; Sharma, Ravendra K; Barde, Pradip V

2017-07-01

The objective of this study was to demonstrate the utility of dengue virus (DENV) non structural protein 1 (NS1) based rapid diagnostic test (RDT) for use in tribal and difficult to reach areas for early dengue (DEN) diagnosis in acute phase patients and evaluate its sensitivity and specificity against DENV NS1 enzyme linked immune sorbent assay (ELISA) and real time reverse transcriptase polymerase chain reaction (qRT-PCR). The DENV NS1 RDT was used for preliminary diagnosis during outbreaks in difficult to reach rural and tribal areas. The diagnosis was confirmed by DENV NS1 ELISA in the laboratory. The samples were also tested and serotyped by qRT-PCR. The results were evaluated using statistical tests. The DENV NS1 RDT showed 99.2% sensitivity and 96.0% specificity when analyzed using DENV NS1 ELISA as standard. The specificity and sensitivity of the RDT when compared with qRT-PCR was 93.6% and 91.1%, respectively. The serotype specific evaluation showed more than 90% sensitivity and specificity for DENV-1, 2, and 3. The RDT proved a good diagnostic tool in difficult to reach rural and tribal areas. Further evaluation studies with different commercially available RDTs in different field conditions are essential, that will help clinicians and patients for treatment and programme managers for timely intervention. © 2017 Wiley Periodicals, Inc.

H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

Directory of Open Access Journals (Sweden)

Koichi Higashi

2016-01-01

Full Text Available Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches.

H-NS Facilitates Sequence Diversification of Horizontally Transferred DNAs during Their Integration in Host Chromosomes.

Science.gov (United States)

Higashi, Koichi; Tobe, Toru; Kanai, Akinori; Uyar, Ebru; Ishikawa, Shu; Suzuki, Yutaka; Ogasawara, Naotake; Kurokawa, Ken; Oshima, Taku

2016-01-01

Bacteria can acquire new traits through horizontal gene transfer. Inappropriate expression of transferred genes, however, can disrupt the physiology of the host bacteria. To reduce this risk, Escherichia coli expresses the nucleoid-associated protein, H-NS, which preferentially binds to horizontally transferred genes to control their expression. Once expression is optimized, the horizontally transferred genes may actually contribute to E. coli survival in new habitats. Therefore, we investigated whether and how H-NS contributes to this optimization process. A comparison of H-NS binding profiles on common chromosomal segments of three E. coli strains belonging to different phylogenetic groups indicated that the positions of H-NS-bound regions have been conserved in E. coli strains. The sequences of the H-NS-bound regions appear to have diverged more so than H-NS-unbound regions only when H-NS-bound regions are located upstream or in coding regions of genes. Because these regions generally contain regulatory elements for gene expression, sequence divergence in these regions may be associated with alteration of gene expression. Indeed, nucleotide substitutions in H-NS-bound regions of the ybdO promoter and coding regions have diversified the potential for H-NS-independent negative regulation among E. coli strains. The ybdO expression in these strains was still negatively regulated by H-NS, which reduced the effect of H-NS-independent regulation under normal growth conditions. Hence, we propose that, during E. coli evolution, the conservation of H-NS binding sites resulted in the diversification of the regulation of horizontally transferred genes, which may have facilitated E. coli adaptation to new ecological niches.

ns-2 extension to simulate localization system in wireless sensor networks

CSIR Research Space (South Africa)

Abu-Mahfouz, Adnan M

2011-09-01

Full Text Available The ns-2 network simulator is one of the most widely used tools by researchers to investigate the characteristics of wireless sensor networks. Academic papers focus on results and rarely include details of how ns-2 simulations are implemented...

No consensus for consensus's sake. Interview with DAtF-President Dr. Otto Majewski

International Nuclear Information System (INIS)

Anon.

1999-01-01

The German power industry is not prepared to make special sacrifices at the expense of its shareholders, staff and customers merely to cure the apparent internal problems of the German government coalition and help the Greens to regain lost votes. Unless the Federal Minister for the Environment rescinds his current cascade of conditions and requirements impeding the efforts on the part of operators to resume fuel transports, everything 'boils down to a court case'. That the French government, contrary to general expectations, had not given the green light this year for the construction of a first EPR plant was due primarily to internal political reasons, which had to be respected. It did not really matter whether that decision was taken in 2000 or 2001. The important thing was that the EPR was built at all, which was beyond any doubt. This is the gist of the statements by Dr. Otto Majewski, President of the German Atomic Forum and Chief Executive Officer of Bayernwerk AG, in the interview granted atw Editor-in-Chief Gerhard Kuebler and printed in this issue of 'Atomwirtschaft'. (orig.) [de

Spiky strings on AdS3 x S3 with NS-NS flux

CERN Document Server

Banerjee, Aritra; Pradhan, Pabitra M.

2014-01-01

We study rigidly rotating strings in the background of AdS3 x S3 with Neveu-Schwarz (NS) fluxes. We find two interesting limiting cases corresponding to the known giant magnon and the new single spike solution of strings in the above background and write down the dispersion relations among various conserved charges. We use proper regularization to find the correct relations among them. We further study the circular and infinite spiky strings on AdS and study their properties.

Adapted J6/JFH1-based Hepatitis C virus recombinants with genotype-specific NS4A show similar efficacies against lead protease inhibitors, alpha interferon, and a putative NS4A inhibitor

DEFF Research Database (Denmark)

Gottwein, Judith M; Jensen, Sanne B; Serre, Stéphanie B N

2013-01-01

To facilitate studies of hepatitis C virus (HCV) NS4A, we aimed at developing J6/JFH1-based recombinants with genotype 1- to 7-specific NS4A proteins. We developed efficient culture systems expressing NS4A proteins of genotypes (isolates) 1a (H77 and TN), 1b (J4), 2a (J6), 4a (ED43), 5a (SA13), 6a...... (HK6a), and 7a (QC69), with peak infectivity titers of ∼3.5 to 4.5 log10 focus-forming units per ml. Except for genotype 2a (J6), growth depended on adaptive mutations identified in long-term culture. Genotype 1a, 1b, and 4a recombinants were adapted by amino acid substitutions F772S (p7) and V1663A...... (NS4A), while 5a, 6a, and 7a recombinants required additional substitutions in the NS3 protease and/or NS4A. We demonstrated applicability of the developed recombinants for study of antivirals. Genotype 1 to 7 NS4A recombinants showed similar responses to the protease inhibitors telaprevir (VX-950...

Electron paramagnetic resonance of the ns1 centers in crystals

International Nuclear Information System (INIS)

Nistor, S.V.; Ursu, I.

1993-05-01

The results of the EPR studies concerning the paramagnetic centers with ns 1 (N=n>2) outer electronic configuration contained in crystals are reviewed. Such centers, with 2 S 1/2 ground state, are produced by electron trapping at impurities of the IB and IIB group or by hole trapping at impurities of the IIIB and IV group of elements. The production and structural properties of such centers consisting of ns 1 ions (atoms) at various sites in the crystal lattice with different configurations of neighbouring defects are discussed in connection with their EPR characteristics. Tables containing the spin Hamiltonian parameters of all ns 1 centers reported in the literature until the end of year 1992 are given. (author). 146 refs, 14 tabs

Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

Science.gov (United States)

Furuta, Atsushi; Tsubuki, Masayoshi; Endoh, Miduki; Miyamoto, Tatsuki; Tanaka, Junichi; Abdus Salam, Kazi; Akimitsu, Nobuyoshi; Tani, Hidenori; Yamashita, Atsuya; Moriishi, Kohji; Nakakoshi, Masamichi; Sekiguchi, Yuji; Tsuneda, Satoshi; Noda, Naohiro

2015-01-01

Hepatitis C virus (HCV) is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3) helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure–activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 µM. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 µM, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition. PMID:26262613

Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase

Directory of Open Access Journals (Sweden)

Atsushi Furuta

2015-08-01

Full Text Available Hepatitis C virus (HCV is an important etiological agent of severe liver diseases, including cirrhosis and hepatocellular carcinoma. The HCV genome encodes nonstructural protein 3 (NS3 helicase, which is a potential anti-HCV drug target because its enzymatic activity is essential for viral replication. Some anthracyclines are known to be NS3 helicase inhibitors and have a hydroxyanthraquinone moiety in their structures; mitoxantrone, a hydroxyanthraquinone analogue, is also known to inhibit NS3 helicase. Therefore, we hypothesized that the hydroxyanthraquinone moiety alone could also inhibit NS3 helicase. Here, we performed a structure–activity relationship study on a series of hydroxyanthraquinones by using a fluorescence-based helicase assay. Hydroxyanthraquinones inhibited NS3 helicase with IC50 values in the micromolar range. The inhibitory activity varied depending on the number and position of the phenolic hydroxyl groups, and among different hydroxyanthraquinones examined, 1,4,5,8-tetrahydroxyanthraquinone strongly inhibited NS3 helicase with an IC50 value of 6 µM. Furthermore, hypericin and sennidin A, which both have two hydroxyanthraquinone-like moieties, were found to exert even stronger inhibition with IC50 values of 3 and 0.8 µM, respectively. These results indicate that the hydroxyanthraquinone moiety can inhibit NS3 helicase and suggest that several key chemical structures are important for the inhibition.

Decreasing the infusion rate reduces the proarrhythmic risk of NS-7

DEFF Research Database (Denmark)

Detre, Elke; Thomsen, Morten Bækgaard; Beekman, Jet D

2005-01-01

1 The rate of infusion has been suggested to be important for drug-induced torsades de pointes (TdP) arrhythmias. We investigated the repolarisation-prolonging effects and proarrhythmic properties of NS-7, a neuroprotective drug in development, using two different infusion rates. 2 A fast (5 min...... intravenously (i.v.)) escalating dosing regimen (0.3 and 3.0 mg kg(-1), n=4) of NS-7 was investigated in anaesthetised control dogs in sinus rhythm (SR). This was compared to a slow infusion (60 min i.v.) of one dose (3.0 mg kg(-1), n=4) NS-7. The similar dosing regimens were investigated in anaesthetised dogs...... with chronic, complete AV block (CAVB), an animal model of TdP (n=6). 3 No electrophysiological effects were seen after 0.3 mg kg(-1) NS-7. Fast infusion of 3.0 mg kg(-1) caused prolongation of repolarisation, for example, heart rate corrected QT interval (QT(c)): in SR: 6+/-1%; in CAVB: 10+/-7%, which...

Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain

Directory of Open Access Journals (Sweden)

Spaan Willy JM

2009-05-01

Full Text Available Abstract Background Hepatitis C virus (HCV induces membrane rearrangements during replication. All HCV proteins are associated to membranes, pointing out the importance of membranes for HCV. Non structural protein 4B (NS4B has been reported to induce cellular membrane alterations like the membranous web. Four transmembrane segments in the middle of the protein anchor NS4B to membranes. An amphipatic helix at the amino-terminus attaches to membranes as well. The carboxy-terminal domain (CTD of NS4B is highly conserved in Hepaciviruses, though its function remains unknown. Results A cytosolic localization is predicted for the NS4B-CTD. However, using membrane floatation assays and immunofluorescence, we now show targeting of the NS4B-CTD to membranes. Furthermore, a profile-profile search, with an HCV NS4B-CTD multiple sequence alignment, indicates sequence similarity to the membrane binding domain of prokaryotic D-lactate dehydrogenase (d-LDH. The crystal structure of E. coli d-LDH suggests that the region similar to NS4B-CTD is located in the membrane binding domain (MBD of d-LDH, implying analogy in membrane association. Targeting of d-LDH to membranes occurs via electrostatic interactions of positive residues on the outside of the protein with negative head groups of lipids. To verify that anchorage of d-LDH MBD and NS4B-CTD is analogous, NS4B-CTD mutants were designed to disrupt these electrostatic interactions. Membrane association was confirmed by swopping the membrane contacting helix of d-LDH with the corresponding domain of the 4B-CTD. Furthermore, the functionality of these residues was tested in the HCV replicon system. Conclusion Together these data show that NS4B-CTD is associated to membranes, similar to the prokaryotic d-LDH MBD, and is important for replication.

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

Science.gov (United States)

Roth, Caleb C.; Barnes Jr., Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Christopher Mimun, L.; Maswadi, Saher M.; Shadaram, Mehdi; Glickman, Randolph D.

2015-01-01

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane. PMID:26450165

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure.

Science.gov (United States)

Roth, Caleb C; Barnes, Ronald A; Ibey, Bennett L; Beier, Hope T; Christopher Mimun, L; Maswadi, Saher M; Shadaram, Mehdi; Glickman, Randolph D

2015-10-09

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane.

Discovery of Dengue Virus NS4B Inhibitors

Science.gov (United States)

Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

2015-01-01

ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

Improved Bunch Splitting for the 75ns LHC Beam

CERN Document Server

Damerau, H

2011-01-01

The 75ns variant was added to the PS arsenal of LHC-type beams by adapting the 20MHz cavity used to produce the 25 and 50ns variants to operate at a switchable 13MHz. This permitted splitting from harmonic 14 to 28, but at a cost in adiabaticity compared with the h=2142 splitting of the other two cases. Consequently, a delicate empirical optimization was necessary to bring the 75ns beam inside specification. More recently the speed at which the bunches, once fully distinct, are moved apart has been revisited and further optimization achieved. As a by-product, deliberately degrading the splitting by moving the bunches apart too quickly led to sufficient coherent motion in the resultant bunch pair to permit a voltage calibration of the 13MHz cavity by means of the influence on convergence of the rf voltage input into the iterative algorithm of the Tomoscope [1,2].

Experimental voyages of N.S. Mutsu

International Nuclear Information System (INIS)

Ochiai, Masaaki

1993-01-01

The first Japanese nuclear ship, N.S. MUTSU was commissioned by the Government on February 14 1991, after power up test and official sea trial with much success. Four experimental voyages of the ship were taken in the Pacific Ocean from March to December 1991 to study the performance of the nuclear power plant when it was influenced by marine conditions. In such an environment, incessant ship motion and load changes due to wave, wind, maneuvering, etc. are experienced. The ship sailed for a total of 110 days, a total distance of 64,180 km and for a total reactor operating time of 2,321 hours. Integrated reactor power was about 2,250 efph (effective full power hour) including that during the power up test. Zero power experiments were done again in Jan. 1992 to measure the core characteristics after finishing all the N.S. MUTSU plant operation program. Thus the most essential parts in the R ampersand D program on N.S. MUTSU was completed. The voyages demonstrated that the nuclear power plant worked well in any case and that the plant system had excellent capability as a marine engine. The data acquired through the experiments will contribute to the research and development program of the advanced marine reactor in Japan Atomic Energy Research Institute. This paper describes the technical informations obtained through the experimental voyages, such as load following abilities, system performances during the high sea sailing and the tropical sea sailing and behavior of system parameters accompanied with steering. The latest technical results yielded by the program are also summarized here

New NS varieties of six-rowed winter barley

Directory of Open Access Journals (Sweden)

Pržulj Novo

2009-01-01

Full Text Available The paper describes the characteristics of several new NS varieties of winter six-rowed barley released in Serbia between 2004 and 2007. These are Somborac, Ozren, Javor, Novosadski 773, Sremac and Leotar. In the official variety trials in the country, all six of these varieties outyielded the check variety, and the margins were as follows: Somborac - 3.4%, Ozren - 5.0%, Javor - 7.3%, Novosadski 773 - 3.4%, Sremac - 7.4%, and Leotar - 7.2%. Yield levels in absolute terms depended on the variety as well as year. All six-rowed NS varieties headed earlier than the check and had better resistance to lodging than the check has. The test weight of the new varieties was 70.2-73.8 kg/hl and the 1000-grain weight 33.4-50.2 g. The cellulose content was 4.4-4.8%, the fat content 1.4%, and the protein content 13.3-14.6%. The high variability of the new NS varieties of winter six-rowed barley makes it possible to choose the most suitable genotype for each barley-growing area in the country. .

Direct binding of ledipasvir to HCV NS5A: mechanism of resistance to an HCV antiviral agent.

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Hyock Joo Kwon

Full Text Available Ledipasvir, a direct acting antiviral agent (DAA targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants.

Designing cyclopentapeptide inhibitor as potential antiviral drug for dengue virus ns5 methyltransferase.

Science.gov (United States)

Idrus, Syarifuddin; Tambunan, Usman Sumo Friend; Zubaidi, Ahmad Ardilla

2012-01-01

NS5 methyltransferase (Mtase) has a crucial role in the replication of dengue virus. There are two active sites on NS5 Mtase i.e., SAM and RNA-cap binding sites. Inhibition of the NS5 Mtase activity is expected to prevent the propagation of dengue virus. This study was conducted to design cyclic peptide ligands as enzyme inhibitors of dengue virus NS5 Mtase through computational approach. Cyclopentapeptides were designed as ligand of SAM binding site as much as 1635 and 736 cyclopentpeptides were designed as ligand of RNA-cap binding site. Interaction between ligand and NS5 Mtase has been conducted on the Docking simulation. The result shows that cyclopentapeptide CTWYC was the best peptide candidate on SAM binding site, with estimated free binding energy -30.72 kca/mol. Cyclopentapeptide CYEFC was the best peptide on RNA-cap binding site with estimated free binding energy -22.89 kcal/mol. Both peptides did not have tendency toward toxicity properties. So it is expected that both CTWYC and CYEFC ligands could be used as a potential antiviral drug candidates, which can inhibit the SAM and RNA-cap binding sites of dengue virus NS5 Mtase.

Electron Cloud Observations during LHC Operation with 25 ns Beams

CERN Document Server

Li, Kevin; Iadarola, Giovanni; Mether, Lotta; Romano, Annalisa; Rumolo, Giovanni; Schenk, Michael

2016-01-01

While during the Run 1 (2010-2012) of the Large Hadron Collider (LHC) most of the integrated luminosity was produced with 50 ns bunch spacing, for the Run 2 start-up (2015) it was decided to move to the nominal bunch spacing of 25 ns. As expected, with this beam configuration strong electron cloud effects were observed in the machine, which had to be mitigated with dedicated 'scrubbing' periods at injection energy. This enabled to start the operation with 25 ns beams at 6.5 TeV, but e-cloud effects continued to pose challenges while gradually increasing the number of circulating bunch trains. This contribution will review the encountered limitations and the mitigation measures that where put in place and will discuss possible strategies for further performance gain.

Nuclear merchant ship propulsion

International Nuclear Information System (INIS)

Schroeder, E.; Jager, W.; Schafstall, H.G.

1977-01-01

The operation of about 300 nuclear naval vessels has proven the feasibility of nuclear ship propulsion. Until now six non military ships have been built or are under construction. In the Soviet Union two nuclear icebreakers are in operation, and a third one is under construction. In the western world three prototype merchant ships have been built. Of these ships only the NS OTTO HAHN is in operation and provides valuable experience for future large scale use of nuclear merchant ship propulsion. In many countries studies and plans are made for future nuclear merchant ships. Types of vessels investigated are large containerships, tankers and specialized ships like icebreakers or ice-breaking ships. The future of nuclear merchant ship propulsion depends on three interrelated items: (1) nuclear ship technology; (2) economy of nuclear ship propulsion; (3) legal questions. Nuclear merchant ship technology is based until now on standard ship technology and light water reactor technology. Except for special questions due to the non-stationary type of the plant entirely new problems do not arise. This has been proven by the recent conceptual licensing procedure for a large nuclear containership in Germany. The economics of nuclear propulsion will be under discussion until they are proven by the operation of privately owned lead ships. Unsolved legal questions e.g. in connection with port entry permissions are at present another problem for nuclear shipping. Efforts are made to solve these questions on an international basis. The future development of nuclear energy electricity production in large land based plants will stimulate the employment of smaller units. Any future development of long distance sea transport will have to take this opportunity of a reliable and economic energy supply into account

Naturally occurring mutations associated with resistance to HCV NS5B polymerase and NS3 protease inhibitors in treatment-naïve patients with chronic hepatitis C.

Science.gov (United States)

Costantino, Angela; Spada, Enea; Equestre, Michele; Bruni, Roberto; Tritarelli, Elena; Coppola, Nicola; Sagnelli, Caterina; Sagnelli, Evangelista; Ciccaglione, Anna Rita

2015-11-14

The detection of baseline resistance mutations to new direct-acting antivirals (DAAs) in HCV chronically infected treatment-naïve patients could be important for their management and outcome prevision. In this study, we investigated the presence of mutations, which have been previously reported to be associated with resistance to DAAs in HCV polymerase (NS5B) and HCV protease (NS3) regions, in sera of treatment-naïve patients. HCV RNA from 152 naïve patients (84 % Italian and 16 % immigrants from various countries) infected with different HCV genotypes (21,1a; 21, 1b; 2, 2a; 60, 2c; 22, 3a; 25, 4d and 1, 4k) was evaluated for sequence analysis. Amplification and sequencing of fragments in the NS5B (nt 8256-8640) and NS3 (nt 3420-3960) regions of HCV genome were carried out for 152 and 28 patients, respectively. The polymorphism C316N/H in NS5B region, associated with resistance to sofosbuvir, was detected in 9 of the 21 (43 %) analysed sequences from genotype 1b-infected patients. Naturally occurring mutations V36L, and M175L in the NS3 protease region were observed in 100 % of patients infected with subtype 2c and 4. A relevant proportion of treatment naïve genotype 1b infected patients evaluated in this study harboured N316 polymorphism and might poorly respond to sofosbuvir treatment. As sofosbuvir has been approved for treatment of HCV chronic infection in USA and Europe including Italy, pre-treatment testing for N316 polymorphism on genotype 1b naïve patients should be considered for this drug.

X-ray structure of the pestivirus NS3 helicase and its conformation in solution.

Science.gov (United States)

Tortorici, M Alejandra; Duquerroy, Stéphane; Kwok, Jane; Vonrhein, Clemens; Perez, Javier; Lamp, Benjamin; Bricogne, Gerard; Rümenapf, Till; Vachette, Patrice; Rey, Félix A

2015-04-01

Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of nonstructural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-Å resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as it contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses from which the core protein is deleted map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with the findings of small-angle X-ray-scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a nonhydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication. Although pestivirus infections impose an important toll on the livestock industry worldwide, little information is available about the nonstructural proteins essential for viral replication, such as the NS3 helicase. We provide here a comparative structural and functional analysis of pNS3h with respect to its orthologs in other viruses of the same family, the flaviviruses and hepatitis C virus. Our studies reveal differences in the nucleic acid binding groove that could have implications for understanding the

Effects of NS lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet

Science.gov (United States)

2013-01-01

Background Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression

Simultaneous removal of chlorothalonil and nitrate by Bacillus cereus strain NS1

International Nuclear Information System (INIS)

Zhang Yiqiang; Lu Jianhang; Wu Laosheng; Chang, Andrew; Frankenberger, William T.

2007-01-01

Elevated NO 3 - and chlorothalonil (CTN) have been found in production nursery recycling ponds. Bacillus cereus strain NS1 isolated from nursery recycling pond sediment was assessed for its ability to reduce NO 3 - and degrade CTN in a mineral medium. The results showed that the efficiency of NO 3 - reduction and CTN degradation by B. cereus strain NS1 were related to the nature of organic carbon sources added to the medium. In the medium amended with 100 mg/L yeast extract, 86% of NO 3 - (100 mg/L) and 99% of CTN (78 μg/L) were simultaneously removed by B. cereus strain NS1 during the first day of the experiment. It took 6 days for the removal of 82-93% of NO 3 - and 87-91% of CTN in the media containing glucose and acetate. B. cereus strain NS1 needed organic carbon as energy sources and electron donors to respire NO 3 - , and simultaneously degrade CTN. These results suggest that B. cereus strain NS1 may have great potential to remediate NO 3 - and CTN contaminated water in nursery recycling ponds

The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

Directory of Open Access Journals (Sweden)

Jie Zhang

Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

NS&T Management Observations - 3rd Quarter

Energy Technology Data Exchange (ETDEWEB)

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

2014-07-01

The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

NS&T Management Observations: Quarterly Performance Analysis

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-01

The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY-14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

NS&T Managment Observations - 1st Quarter

Energy Technology Data Exchange (ETDEWEB)

David Gianotto

2014-06-01

The INL Management Observation Program (MOP) is designed to improve managers and supervisors understanding of work being performed by employees and the barriers impacting their success. The MOP also increases workers understanding of managements’ expectations as they relate to safety, security, quality, and work performance. Management observations (observations) are designed to improve the relationship and trust between employees and managers through increased engagement and interactions between managers and researchers in the field. As part of continuous improvement, NS&T management took initiative to focus on the participation and quality of observations in FY 14. This quarterly report is intended to (a) summarize the participation and quality of management’s observations, (b) assess observations for commonalities or trends related to facility or process barriers impacting research, and (c) provide feedback and make recommendations for improvements NS&T’s MOP.

Hepatitis C virus NS3/4A protease inhibits complement activation by cleaving complement component 4.

Directory of Open Access Journals (Sweden)

Seiichi Mawatari

Full Text Available BACKGROUND: It has been hypothesized that persistent hepatitis C virus (HCV infection is mediated in part by viral proteins that abrogate the host immune response, including the complement system, but the precise mechanisms are not well understood. We investigated whether HCV proteins are involved in the fragmentation of complement component 4 (C4, composed of subunits C4α, C4β, and C4γ, and the role of HCV proteins in complement activation. METHODS: Human C4 was incubated with HCV nonstructural (NS 3/4A protease, core, or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then subjected to peptide sequencing. The activity of the classical complement pathway was examined using an erythrocyte hemolysis assay. The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells, respectively, was also examined. RESULTS: HCV NS3/4A protease cleaved C4γ in a concentration-dependent manner, but viral core and NS5 did not. A specific inhibitor of NS3/4A protease reduced C4γ cleavage. NS3/4A protease-mediated cleavage of C4 inhibited classical pathway activation, which was abrogated by a NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild-type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4γ fragments. Such C4 processing, with a concomitant reduction in levels of full-length C4γ, was also observed in HCV-infected cells expressing C4. CONCLUSIONS: C4 is a novel cellular substrate of the HCV NS3/4A protease. Understanding disturbances in the complement system mediated by NS3/4A protease may provide new insights into the mechanisms underlying persistent HCV infection.

Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5

Energy Technology Data Exchange (ETDEWEB)

Upadhyay, Anup K.; Cyr, Matthew; Longenecker, Kenton; Tripathi, Rakesh; Sun, Chaohong; Kempf, Dale J. (AbbVie)

2017-02-21

The rapid spread of the recentZika virus(ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 ofZika virus(ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space groupP2₁2₁2 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein fromJapanese encephalitis virusand suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.

The Pyramid and the Mosaic. Otto Neurath’s encyclopedism as a critical model

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Andrea Alberto Dutto

2017-07-01

Full Text Available Otto Neurath, one of the founding members of the Vienna Circle, took up a firm opposition in relation to his colleagues. Instead of searching for an ideal language, he asserted the possibility of a ‘universal empiricist slang’, including both everyday and scientific language. Particularly, Neurath conceives of a comprehensive theory of a unified science that postulates the necessity of orchestration within the discursive procedures in science, inspired by the model of encyclopedism.In the field of architecture, a similar encyclopedic endeavor was undertaken in Italy by Mario Ridolfi who, together with other leading exponents of architectural culture, conceived the Manuale dell’Architetto at the end of World War II. This construction handbook provided  support to engineers  during the intense period of post-war reconstruction. Unlike any previous attempt to document building culture, this collective work aspired to create a shared language able to cross the boundaries among the various fields of building science.Finally, encyclopedism is considered as a possible ‘foundation’ for building design as a shared practice, with a specific focus on Ridolfi’s late research on the relation between traditional construction methods and housing design, in the countryside around Umbria.

Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types.

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Gianulis, Elena C; Labib, Chantelle; Saulis, Gintautas; Novickij, Vitalij; Pakhomova, Olga N; Pakhomov, Andrei G

2017-05-01

Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0-2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD 50 spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.

Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro

International Nuclear Information System (INIS)

Rubach, Jon K.; Wasik, Brian R.; Rupp, Jonathan C.; Kuhn, Richard J.; Hardy, Richard W.; Smith, Janet L.

2009-01-01

The Sindbis virus RNA-dependent RNA polymerase (nsP4) is responsible for the replication of the viral RNA genome. In infected cells, nsP4 is localized in a replication complex along with the other viral non-structural proteins. nsP4 has been difficult to homogenously purify from infected cells due to its interactions with the other replication proteins and the fact that its N-terminal residue, a tyrosine, causes the protein to be rapidly turned over in cells. We report the successful expression and purification of Sindbis nsP4 in a bacterial system, in which nsP4 is expressed as an N-terminal SUMO fusion protein. After purification the SUMO tag is removed, resulting in the isolation of full-length nsP4 possessing the authentic N-terminal tyrosine. This purified enzyme is able to produce minus-strand RNA de novo from plus-strand templates, as well as terminally add adenosine residues to the 3' end of an RNA substrate. In the presence of the partially processed viral replicase polyprotein, P123, purified nsP4 is able to synthesize discrete template length minus-strand RNA products. Mutations in the 3' CSE or poly(A) tail of viral template RNA prevent RNA synthesis by the replicase complex containing purified nsP4, consistent with previously reported template requirements for minus-strand RNA synthesis. Optimal reaction conditions were determined by investigating the effects of time, pH, and the concentrations of nsP4, P123 and magnesium on the synthesis of RNA

A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

International Nuclear Information System (INIS)

Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F.

2016-01-01

The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease

Energy Technology Data Exchange (ETDEWEB)

Campos-Gomez, Javier; Ahmad, Fahim; Rodriguez, Efrain; Saeed, Mohammad F., E-mail: saeed@southernresearch.org

2016-09-15

The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. - Highlights: • A novel cell-based assay to measure VEEV nsP2 protease activity was developed. • Assay utility was demonstrated for antiviral screening. • .The assay also proved to be useful in basic mechanistic studies of nsP2 protease.

Analysis of the PDZ binding specificities of Influenza A Virus NS1 proteins

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Nagasaka Kazunori

2011-01-01

Full Text Available Abstract The Influenza A virus non-structural protein 1 (NS1 is a multifunctional virulence factor with several protein-protein interaction domains, involved in preventing apoptosis of the infected cell and in evading the interferon response. In addition, the majority of influenza A virus NS1 proteins have a class I PDZ-binding motif at the C-terminus, and this itself has been shown to be a virulence determinant. In the majority of human influenza NS1 proteins the consensus motif is RSxV: in avian NS1 it is ESxV. Of the few human strains that have the avian motif, all were from very high mortality outbreaks of the disease. Previous work has shown that minor differences in PDZ-binding motifs can have major effects on the spectrum of cellular proteins targeted. In this study we analyse the effect of these differences upon the binding of Influenza A virus NS1 protein to a range of cellular proteins involved in polarity and signal transduction.

A new approach to dengue fatal cases diagnosis: NS1 antigen capture in tissues.

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Monique da Rocha Queiroz Lima

Full Text Available UNLABELLED: / BACKGROUND: Dengue is the most important arthropod borne viral disease worldwide in terms of morbidity and mortality and is caused by any of the four serotypes of dengue virus (DENV-1 to 4. Brazil is responsible for approximately 80% of dengue cases in the Americas, and since the introduction of dengue in 1986, a total of 5,944,270 cases have been reported including 21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many cell types and cause diverse clinical and pathological effects. The goal of the study was to investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from previously confirmed dengue fatal cases (n = 23 that occurred in 2002 in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: A total of 74 tissue specimens were available: liver (n = 23, lung (n = 14, kidney (n = 04, brain (n = 10, heart (n = 02, skin (n = 01, spleen (n = 15, thymus (n = 03 and lymph nodes (n = 02. We evaluated three tests for NS1 antigen capture: first generation Dengue Early ELISA (PanBio Diagnostics, Platelia NS1 (BioRad Laboratories and the rapid test NS1 Ag Strip (BioRad Laboratories. The overall dengue fatal case diagnosis based on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag Strip was 34.7% (08/23, 60.8% (14/23 and 91.3% (21/23, respectively. The Dengue Early ELISA detected NS1 in 22.9% (17/74 of the specimens analyzed and the Platelia NS1 in 45.9% (34/74. The highest sensitivity (78.3%; 58/74 was achieved by the NS1 Ag Strip, and the differences in the sensitivities were statistically significant (p<0.05. The NS1 Ag Strip was the most sensitive in liver (91.3%; 21/23, lung (71.4%; 10/14, kidney (100%; 4/4, brain (80%; 8/10, spleen (66.6%, 10/15 and thymus (100%, 3/3 when compared to the other two ELISA assays. CONCLUSIONS/SIGNIFICANCE: This study shows the DENV NS1 capture assay as a rapid and valuable approach to postmortem dengue confirmation. With an

Broadband Fan Noise Prediction System for Turbofan Engines. Volume 2; BFaNS User's Manual and Developer's Guide

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Morin, Bruce L.

2010-01-01

Pratt & Whitney has developed a Broadband Fan Noise Prediction System (BFaNS) for turbofan engines. This system computes the noise generated by turbulence impinging on the leading edges of the fan and fan exit guide vane, and noise generated by boundary-layer turbulence passing over the fan trailing edge. BFaNS has been validated on three fan rigs that were tested during the NASA Advanced Subsonic Technology Program (AST). The predicted noise spectra agreed well with measured data. The predicted effects of fan speed, vane count, and vane sweep also agreed well with measurements. The noise prediction system consists of two computer programs: Setup_BFaNS and BFaNS. Setup_BFaNS converts user-specified geometry and flow-field information into a BFaNS input file. From this input file, BFaNS computes the inlet and aft broadband sound power spectra generated by the fan and FEGV. The output file from BFaNS contains the inlet, aft and total sound power spectra from each noise source. This report is the second volume of a three-volume set documenting the Broadband Fan Noise Prediction System: Volume 1: Setup_BFaNS User s Manual and Developer s Guide; Volume 2: BFaNS User s Manual and Developer s Guide; and Volume 3: Validation and Test Cases. The present volume begins with an overview of the Broadband Fan Noise Prediction System, followed by step-by-step instructions for installing and running BFaNS. It concludes with technical documentation of the BFaNS computer program.

Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

DEFF Research Database (Denmark)

Antunes, Paula Soares Martins; Watterson, Daniel; Parmvi, Mattias

2015-01-01

Dengue is a tropical vector-borne disease without cure or vaccine that progressively spreads into regions with temperate climates. Diagnostic tools amenable to resource-limited settings would be highly valuable for epidemiologic control and containment during outbreaks. Here, we present a novel low......-cost automated biosensing platform for detection of dengue fever biomarker NS1 and demonstrate it on NS1 spiked in human serum. Magnetic nanoparticles (MNPs) are coated with high-affinity monoclonal antibodies against NS1 via bio-orthogonal Cu-free 'click' chemistry on an anti-fouling surface molecular...... method. The resulting automated dengue fever assay takes just 8 minutes, requires 6 μL of serum sample and shows a limit of detection of 25 ng/mL with an upper detection range of 20000 ng/mL. The technology holds a great potential to be applied to NS1 detection in patient samples. As the assay...

The CENNS-10 liquid argon detector to measure CEvNS at the Spallation Neutron Source

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Tayloe, R.

2018-04-01

The COHERENT collaboration is deploying a suite of low-energy detectors in a low-background corridor of the ORNL Spallation Neutron Source (SNS) to measure coherent elastic neutrino-nucleus scattering (CEvNS) on an array of nuclear targets employing different detector technologies. A measurement of CEvNS on different nuclei will test the N2-dependence of the CEvNS cross section and further the physics reach of the COHERENT effort. The first step of this program has been realized recently with the observation of CEvNS in a 14.6 kg CsI detector. Operation and deployment of Ge and NaI detectors are also underway. A 22 kg, single-phase, liquid argon detector (CENNS-10) started data-taking in Dec. 2016 and will provide results on CEvNS from a lighter nucleus. Initial results indicate that light output, pulse-shape discrimination, and background suppression are sufficient for a measurement of CEvNS on argon.

Nucleolar localization of influenza A NS1: striking differences between mammalian and avian cells

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Mazel-Sanchez Beryl

2010-03-01

Full Text Available Abstract In mammalian cells, nucleolar localization of influenza A NS1 requires the presence of a C-terminal nucleolar localization signal. This nucleolar localization signal is present only in certain strains of influenza A viruses. Therefore, only certain NS1 accumulate in the nucleolus of mammalian cells. In contrast, we show that all NS1 tested in this study accumulated in the nucleolus of avian cells even in the absence of the above described C-terminal nucleolar localization signal. Thus, nucleolar localization of NS1 in avian cells appears to rely on a different nucleolar localization signal that is more conserved among influenza virus strains.

Pomegranate ( Punica granatum L.) expresses several nsLTP isoforms characterized by different immunoglobulin E-binding properties.

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Bolla, Michela; Zenoni, Sara; Scheurer, Stephan; Vieths, Stefan; San Miguel Moncin, Maria Del Mar; Olivieri, Mario; Antico, Andrea; Ferrer, Marta; Berroa, Felicia; Enrique, Ernesto; Avesani, Linda; Marsano, Francesco; Zoccatelli, Gianni

2014-01-01

Pomegranate allergy is associated with sensitization to non-specific lipid transfer proteins (nsLTPs). Our aim was to identify and characterize the non-specific nsLTPs expressed in pomegranate at the molecular level and to study their allergenic properties in terms of immunoglobulin E (IgE)-binding and cross-reactivity with peach nsLTP (Pru p 3). A non-equilibrium two-dimensional (2-D) electrophoretic approach based on acid-urea PAGE and sodium dodecyl sulfate PAGE was set up to separate pomegranate nsLTPs. Their immunoreactivity was tested by immunoblotting carried out with anti-Pru p 3 polyclonal antibodies and sera from pomegranate-allergic patients. For final identification, pomegranate nsLTPs were purified by chromatography and subjected to trypsin digestion and mass spectrometry (MS) analysis. For this purpose, the sequences obtained by cDNA cloning of three pomegranate nsLTPs were integrated in the database that was subsequently searched for MS data interpretation. Four nsLTPs were identified by 2-D immunoblotting. The detected proteins showed different IgE-binding capacity and partial cross-reactivity with Pru p 3. cDNA cloning and MS analyses led to the identification of three nsLTP isoforms with 66-68% amino acid sequence identity named Pun g 1.0101, Pun g 1.0201 and Pun g 1.0301. By 2-D electrophoresis, we could separate different nsLTP isoforms possessing different IgE-binding properties, which might reflect peculiar allergenic potencies. The contribution of Pru p 3 to prime sensitization is not central as in other plant nsLTPs. © 2014 S. Karger AG, Basel.

Detergent-resistant membrane association of NS2 and E2 during hepatitis C virus replication.

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Shanmugam, Saravanabalaji; Saravanabalaji, Dhanaranjani; Yi, MinKyung

2015-04-01

Previously, we demonstrated that the efficiency of hepatitis C virus (HCV) E2-p7 processing regulates p7-dependent NS2 localization to putative virus assembly sites near lipid droplets (LD). In this study, we have employed subcellular fractionations and membrane flotation assays to demonstrate that NS2 associates with detergent-resistant membranes (DRM) in a p7-dependent manner. However, p7 likely plays an indirect role in this process, since only the background level of p7 was detectable in the DRM fractions. Our data also suggest that the p7-NS2 precursor is not involved in NS2 recruitment to the DRM, despite its apparent targeting to this location. Deletion of NS2 specifically inhibited E2 localization to the DRM, indicating that NS2 regulates this process. Treatment of cells with methyl-β-cyclodextrin (MβCD) significantly reduced the DRM association of Core, NS2, and E2 and reduced infectious HCV production. Since disruption of the DRM localization of NS2 and E2, either due to p7 and NS2 defects, respectively, or by MβCD treatment, inhibited infectious HCV production, these proteins' associations with the DRM likely play an important role during HCV assembly. Interestingly, we detected the HCV replication-dependent accumulation of ApoE in the DRM fractions. Taking into consideration the facts that ApoE was shown to be a major determinant for infectious HCV particle production at the postenvelopment step and that the HCV Core protein strongly associates with the DRM, recruitment of E2 and ApoE to the DRM may allow the efficient coordination of Core particle envelopment and postenvelopment events at the DRM to generate infectious HCV production. The biochemical nature of HCV assembly sites is currently unknown. In this study, we investigated the correlation between NS2 and E2 localization to the detergent-resistant membranes (DRM) and HCV particle assembly. We determined that although NS2's DRM localization is dependent on p7, p7 was not targeted to these

On the meaning of NS comparisons in Israel-critical discourse

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Wilhelm Kempf

2017-04-01

Full Text Available Apart from Holocaust denial, probably nothing outrages Israelis and Jews around the world more than comparisons of Israeli Palestinian policy with National Socialist Jewish policy. Particularly, if Germans make such comparisons, the obvious suspicion is that they are an expression of secondary anti-Semitism. On the other hand, in Western democracies it is virtually part of political culture to fall back on NS comparisons whenever one wants to dramatize precarious human rights situations and justify the need for action to change them. Based on new analyses of survey data published in Kempf (2015a,b, this study shows that NS comparisons can constitute not only anti-Semitic demonization of Jews but also anti-Zionist dramatization of the Palestinian human rights situation. People who work consequently and without reservation for human rights, however, indeed see a strong need for action to change Israeli policy, but strictly refuse to equate it with NS policy.

Evolution of Bacterial Global Modulators: Role of a Novel H-NS Paralogue in the Enteroaggregative Escherichia coli Strain 042.

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Prieto, A; Bernabeu, M; Aznar, S; Ruiz-Cruz, S; Bravo, A; Queiroz, M H; Juárez, A

2018-01-01

Bacterial genomes sometimes contain genes that code for homologues of global regulators, the function of which is unclear. In members of the family Enterobacteriaceae , cells express the global regulator H-NS and its paralogue StpA. In Escherichia coli , out of providing a molecular backup for H-NS, the role of StpA is poorly characterized. The enteroaggregative E. coli strain 042 carries, in addition to the hns and stpA genes, a third gene encoding an hns paralogue ( hns2 ). We present in this paper information about its biological function. Transcriptomic analysis has shown that the H-NS2 protein targets a subset of the genes targeted by H-NS. Genes targeted by H-NS2 correspond mainly with horizontally transferred (HGT) genes and are also targeted by the Hha protein, a fine-tuner of H-NS activity. Compared with H-NS, H-NS2 expression levels are lower. In addition, H-NS2 expression exhibits specific features: it is sensitive to the growth temperature and to the nature of the culture medium. This novel H-NS paralogue is widespread within the Enterobacteriaceae . IMPORTANCE Global regulators such as H-NS play key relevant roles enabling bacterial cells to adapt to a changing environment. H-NS modulates both core and horizontally transferred (HGT) genes, but the mechanism by which H-NS can differentially regulate these genes remains to be elucidated. There are several instances of bacterial cells carrying genes that encode homologues of the global regulators. The question is what the roles of these proteins are. We noticed that the enteroaggregative E. coli strain 042 carries a new hitherto uncharacterized copy of the hns gene. We decided to investigate why this pathogenic E. coli strain requires an extra H-NS paralogue, termed H-NS2. In our work, we show that H-NS2 displays specific expression and regulatory properties. H-NS2 targets a subset of H-NS-specific genes and may help to differentially modulate core and HGT genes by the H-NS cellular pool.

Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

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Jiang, Wei; Sheng, Chunjie; Gu, Xiuling; Liu, Dong; Yao, Chen; Gao, Shijuan; Chen, Shuai; Huang, Yinghui; Huang, Wenlin; Fang, Min

2016-01-01

Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets. PMID:27869202

NS maize hybrids in production regions of Serbia

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Stojaković Milisav

2010-01-01

Full Text Available Fifteen NS maize hybrids of FAO 300-700 maturity groups were evaluated in strip trials (plot size 1,120 m2 at 30 locations in Serbia. In all locations including all production regions, the most yielding hybrid was NS 6030 with average yield of 10.9 t ha-1. The additive Main Effects and Multiplicative Interaction (AMMI and the sites regression (SREG models were used to study basic structure of G x E interactions and the possible existence of different mega-environments in Serbian maize growing regions in 2009. The results of the 15 hybrids x 10 locations for grain yield in maize showed by biplot technique indicate several specific location-hybrid deviations (the AMMI biplot, and possible existence of at least one mega-environment (the GGE biplot. .

StpA and Hha stimulate pausing by RNA polymerase by promoting DNA-DNA bridging of H-NS filaments.

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Boudreau, Beth A; Hron, Daniel R; Qin, Liang; van der Valk, Ramon A; Kotlajich, Matthew V; Dame, Remus T; Landick, Robert

2018-06-20

In enterobacteria, AT-rich horizontally acquired genes, including virulence genes, are silenced through the actions of at least three nucleoid-associated proteins (NAPs): H-NS, StpA and Hha. These proteins form gene-silencing nucleoprotein filaments through direct DNA binding by H-NS and StpA homodimers or heterodimers. Both linear and bridged filaments, in which NAPs bind one or two DNA segments, respectively, have been observed. Hha can interact with H-NS or StpA filaments, but itself lacks a DNA-binding domain. Filaments composed of H-NS alone can inhibit transcription initiation and, in the bridged conformation, slow elongating RNA polymerase (RNAP) by promoting backtracking at pause sites. How the other NAPs modulate these effects of H-NS is unknown, despite evidence that they help regulate subsets of silenced genes in vivo (e.g. in pathogenicity islands). Here we report that Hha and StpA greatly enhance H-NS-stimulated pausing by RNAP at 20°C. StpA:H-NS or StpA-only filaments also stimulate pausing at 37°C, a temperature at which Hha:H-NS or H-NS-only filaments have much less effect. In addition, we report that both Hha and StpA greatly stimulate DNA-DNA bridging by H-NS filaments. Together, these observations indicate that Hha and StpA can affect H-NS-mediated gene regulation by stimulating bridging of H-NS/DNA filaments.

Potential of plant alkaloids as dengue ns3 protease inhibitors: Molecular docking and simulation approach

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Muhammad Tahir ul Qamar

2014-08-01

Full Text Available Dengue infection has become a worldwide health problem and infection rate is increasing each year. Alkaloids are important phytochemicals of medicinal plant and can be used as vaccine candidates for viruses. Therefore, present study was designed to find potential alkaloids inhibitors against the Dengue virus NS2B/NS3 protease which can inhibit the viral replication inside the host cell. Through molecular docking it was investigated that most of the alkaloids bound deeply in the binding pocket of Dengue virus NS2B/NS3 protease and had potential interactions with catalytic triad. Five alkaloids (6’-desmethylthalifaboramin; 3,5-dihydroxythalifaboramine; Betanin; Reserpic acid and Tubulosine successfully blocked the catalytic triad of NS2B/NS3 protease and these alkaloids can serve as a potential drug candidate to stop viral replication. It can be concluded from this study that these alkaloids could serve as important inhibitors to inhibit the replication of DENV and need further in-vitro investigations to confirm their efficacy and drug ability.

Comparative Analysis of Disruption Tolerant Network Routing Simulations in the One and NS-3

Science.gov (United States)

2017-12-01

The added levels of simulation increase the processing required by a simulation . ns-3’s simulation of other layers of the network stack permits...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3...Thesis 03-23-2016 to 12-15-2017 4. TITLE AND SUBTITLE COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3 5

Structure and influence factors of fuel cycle costs of pebble bed HTRs with OTTO-fuel management

Energy Technology Data Exchange (ETDEWEB)

Jacke, S.

1975-06-15

The study in this paper can be divided into two parts. The first part deals with the analysis of the structure of the fuel cycle costs of today in 1974. A comparison is made between two pebble bed HTRs with OTTO-refueling-management (once-through) and a LWR of the type Biblis A. The two HTRs use different fuels: The one low-enriched Uranium (LOTTO), the other high-enriched Uranium and Thorium (TOTTO). The analysis of the structure of the fuel cycle costs consists of a discussion of the most important input parameters, and a comparison of each cost item. This study was made without adjustment of the core design to the changing market conditions. It is quite natural that an adaptation of the moderation ratio, of the conversion ratio, of the enrichment level, and of the burn-up may lower the fuel cycle costs. But the differences cannot be very important, and the results of this examination may remain valid, even on best adjustment conditions.

[Advances in Parvovirus Non-structural Protein NS1 Induced Apoptosis].

Science.gov (United States)

Tu, Mengyu; Liu, Fei; Chen, Shun; Wang, Mingshu; Cheng, Anchun

2015-11-01

Until now, more than seventeen parvovirus have been reported which can infect mammals and poultries. The infected cells appeared different properties of apoptosis and death, present a typical cytopathic effect. NS1 is a major nonstructural protein of parvovirus, with a conservative structure and function, which plays an important role in the viral life cycle. In addition to the influence on viral replication, the NS1 also participates in apoptosis induced by viruses. Parvovirus induced apoptosis which is mainly mediated by mitochondrial pathway, this review summarized the latest research progresses of parvovirus induced apoptosis.

Molecular models of NS3 protease variants of the Hepatitis C virus

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Mello Isabel MVGC

2005-01-01

Full Text Available Abstract Background Hepatitis C virus (HCV currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed. Results The atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures. Conclusions This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure

Raising the avermectins production in Streptomyces avermitilis by utilizing nanosecond pulsed electric fields (nsPEFs)

Science.gov (United States)

Guo, Jinsong; Ma, Ruonan; Su, Bo; Li, Yinglong; Zhang, Jue; Fang, Jing

2016-05-01

Avermectins, a group of anthelmintic and insecticidal agents produced from Streptomyces avermitilis, are widely used in agricultural, veterinary, and medical fields. This study presents the first report on the potential of using nanosecond pulsed electric fields (nsPEFs) to improve avermectin production in S. avermitilis. The results of colony forming units showed that 20 pulses of nsPEFs at 10 kV/cm and 20 kV/cm had a significant effect on proliferation, while 100 pulses of nsPEFs at 30 kV/cm exhibited an obvious effect on inhibition of agents. Ultraviolet spectrophotometry assay revealed that 20 pulses of nsPEFs at 15 kV/cm increased avermectin production by 42% and reduced the time for reaching a plateau in fermentation process from 7 days to 5 days. In addition, the decreased oxidation reduction potential (ORP) and increased temperature of nsPEFs-treated liquid were evidenced to be closely associated with the improved cell growth and fermentation efficiency of avermectins in S. avermitilis. More importantly, the real-time RT-PCR analysis showed that nsPEFs could remarkably enhance the expression of aveR and malE in S. avermitilis during fermentation, which are positive regulator for avermectin biosynthesis. Therefore, the nsPEFs technology presents an alternative strategy to be developed to increase avermectin output in fermentation industry.

Broadband Fan Noise Prediction System for Turbofan Engines. Volume 1; Setup_BFaNS User's Manual and Developer's Guide

Science.gov (United States)

Morin, Bruce L.

2010-01-01

Pratt & Whitney has developed a Broadband Fan Noise Prediction System (BFaNS) for turbofan engines. This system computes the noise generated by turbulence impinging on the leading edges of the fan and fan exit guide vane, and noise generated by boundary-layer turbulence passing over the fan trailing edge. BFaNS has been validated on three fan rigs that were tested during the NASA Advanced Subsonic Technology Program (AST). The predicted noise spectra agreed well with measured data. The predicted effects of fan speed, vane count, and vane sweep also agreed well with measurements. The noise prediction system consists of two computer programs: Setup_BFaNS and BFaNS. Setup_BFaNS converts user-specified geometry and flow-field information into a BFaNS input file. From this input file, BFaNS computes the inlet and aft broadband sound power spectra generated by the fan and FEGV. The output file from BFaNS contains the inlet, aft and total sound power spectra from each noise source. This report is the first volume of a three-volume set documenting the Broadband Fan Noise Prediction System: Volume 1: Setup_BFaNS User s Manual and Developer s Guide; Volume 2: BFaNS User's Manual and Developer s Guide; and Volume 3: Validation and Test Cases. The present volume begins with an overview of the Broadband Fan Noise Prediction System, followed by step-by-step instructions for installing and running Setup_BFaNS. It concludes with technical documentation of the Setup_BFaNS computer program.

H-NS represses transcription of the flagellin gene lafA of lateral flagella in Vibrio parahaemolyticus.

Science.gov (United States)

Wang, Yan; Zhang, Yiquan; Yin, Zhe; Wang, Jie; Zhu, Yongzhe; Peng, Haoran; Zhou, Dongsheng; Qi, Zhongtian; Yang, Wenhui

2018-01-01

Swarming motility is ultimately mediated by the proton-powered lateral flagellar (laf) system in Vibrio parahaemolyticus. Expression of laf genes is tightly regulated by a number of environmental conditions and regulatory factors. The nucleoid-associated DNA-binding protein H-NS is a small and abundant protein that is widely distributed in bacteria, and H-NS-like protein-dependent expression of laf genes has been identified in Vibrio cholerae and V. parahaemolyticus. The data presented here show that H-NS acts as a repressor of the swarming motility in V. parahaemolyticus. A single σ 28 -dependent promoter was detected for lafA encoding the flagellin of the lateral flagella, and its activity was directly repressed by H-NS. Thus, H-NS represses swarming motility by directly acting on lafA. Briefly, this work revealed a novel function for H-NS as a repressor of the expression of lafA and swarming motility in V. parahaemolyticus.

Mosquito Rasputin interacts with chikungunya virus nsP3 and determines the infection rate in Aedes albopictus.

Science.gov (United States)

Fros, Jelke J; Geertsema, Corinne; Zouache, Karima; Baggen, Jim; Domeradzka, Natalia; van Leeuwen, Daniël M; Flipse, Jacky; Vlak, Just M; Failloux, Anna-Bella; Pijlman, Gorben P

2015-09-17

Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes. CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding epidemic. While alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsP3 remain elusive. CHIKV nsP3 modulates the mammalian stress response by preventing stress granule formation through sequestration of G3BP. In mosquitoes, nsP3 is a determinant of vector specificity, but its functional interaction with mosquito proteins is unclear. In this research we studied the domains required for localization of CHIKV nsP3 in insect cells and demonstrated its molecular interaction with Rasputin (Rin), the mosquito homologue of G3BP. The biological involvement of Rin in CHIKV infection was investigated in live Ae. albopictus mosquitoes. In insect cells, nsP3 localized as cytoplasmic granules, which was dependent on the central domain and the C-terminal variable region but independent of the N-terminal macrodomain. Ae. albopictus Rin displayed a diffuse, cytoplasmic localization, but was effectively sequestered into nsP3-granules upon nsP3 co-expression. Site-directed mutagenesis showed that the Rin-nsP3 interaction involved the NTF2-like domain of Rin and two conserved TFGD repeats in the C-terminal variable domain of nsP3. Although in vitro silencing of Rin did not impact nsP3 localization or CHIKV replication in cell culture, Rin depletion in vivo significantly decreased the CHIKV infection rate and transmissibility in Ae.albopictus. We identified the nsP3 hypervariable C-terminal domain as a critical factor for granular localization and sequestration of mosquito Rin. Our study offers novel insight into a conserved virus-mosquito interaction at the molecular level, and reveals a strong proviral role for G3BP homologue Rin in live mosquitoes

In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig

DEFF Research Database (Denmark)

Hansen, Rie Schultz; Olesen, Søren-Peter; Rønn, Lars Christian B

2008-01-01

to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a h......ERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically...... induced QT prolongation in both anaesthetized and conscious guinea pigs....

Hepatitis C virus expressing reporter tagged NS5A protein

DEFF Research Database (Denmark)

2014-01-01

Hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A were developed. A deletion upstream of the inserted reporter gene sequence conferred favorable...... growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. JFH1-based intergenotypic recombinants with genotype specific homotypic 5'UTR, or heterotypic 5'UTR (either of genotype 1a (strain H...

The μs and ns mode modulation system for grid controlled gun of the HESYRL linac

International Nuclear Information System (INIS)

Wang, Guicheng; Hong, Jun; Pei, Yuanji

1988-01-01

A μs and ns mode modulation system has been developed for the grid-controlled gun in the HESYRL. The gun drived by this system generated 1A and 500 MA pulse current for μs and ns mode respectively. In the ns mode modulation pulse formulation system, the sharper was built up using one transistor 3DA87D as avalanche switch and a shortcircuit coaxal cable as waveform sharp element. Outline of the μs mode system and details of the ns mode system are presented. (author)

76 FR 59174 - Environmental Assessment and Finding of No Significant Impact for the N.S. Savannah; License NS-1...

Science.gov (United States)

2011-09-23

... of Federal Regulations (10 CFR) part 73 and 10 CFR 50.54(p) for the N.S. Savannah (NSS). This... security requirements from the 10 CFR Part 50 licensed site because the NSS spent fuel elements were... Carolina. There is no longer any special nuclear material (SNM) located within the NSS other than that...

Comics Journalism and Fine Art: War, Massacre, and The Individual, in works of Pieter Bruegel, Joe Sacco and Otto Dix

Directory of Open Access Journals (Sweden)

Sara Owj

2017-02-01

Full Text Available As a pioneer of Comics Journalism, Joe Sacco’s works have been linked to conflict studies, migration, education, and so on. But despite references that Sacco makes to 16th Century master painter, Pieter Bruegel, and 20th century New Objectivity painter Otto Dix in his interviews, there have been few studies on the potential link between comics of Sacco and works of these masters of fine art. In this study I explore this connection by examining the questions of war, individuality and portrayal of massacre in paintings of Bruegel and Dix and journalistic comics of Sacco. My greater aim is to demonstrate the potential of further comparative studies between arts and comics journalism, especially between Renaissance and modern artists.

Process Performances of 2 ns Pulsed Discharge Plasma

Science.gov (United States)

Matsumoto, Takao; Wang, Douyan; Namihira, Takao; Akiyama, Hidenori

2011-08-01

Pulsed discharge plasmas have been used to treat exhaust gases. Since pulse duration and the rise time of applied voltage to the discharge electrode has a strong influence on the energy efficiency of pollutant removal, the development of a short-pulse generator is of paramount importance for practical applications. In this work, it is demonstrated that the non thermal plasma produced by the 2 ns pulsed discharge has a higher energy efficiency than the 5 ns pulsed discharge plasma for NO removal and ozone generation. Typically, the NO removal efficiency was 1.0 mol kW-1 h-1 for 70% NO removal (initial NO concentration = 200 ppm, gas flow = 10 L/min). Meanwhile, the ozone yield was 500 g kW-1 h-1 for 20 g/m3 ozone concentration in the case of oxygen feeding. These energy efficiencies are the highest in the literature.

Data center network performance evaluation in ns3

DEFF Research Database (Denmark)

Andrus, Bogdan-Mihai; Vegas Olmos, Juan José

2015-01-01

In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3 and subjec......In the following paper we present the analysis of highly interconnected topologies like hypercube and torus and how they can be implemented in data centers in order to cope with the rapid increase and demands for performance of the internal traffic. By replicating the topologies in NS3...... and subjecting them to uniformly distributed traffic routed by shortest path algorithms we are able to extract statistics related to average throughput, latency and loss rate that show the decrease in the average throughput per connection is only about 5% for the hypercube compared to 16% for the 3D torus when...

Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples.

Directory of Open Access Journals (Sweden)

Subhamoy Pal

Full Text Available Early diagnosis of dengue virus (DENV infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. Non-structural glycoprotein-1 (NS1 has proven to be a useful biomarker for early diagnosis of dengue. A number of rapid diagnostic tests (RDTs and enzyme-linked immunosorbent assays (ELISAs targeting NS1 antigen (Ag are now commercially available. Here we evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis.Retrospective samples from South America were used to evaluate the following tests: (i "Dengue NS1 Ag STRIP" and (ii "Platelia Dengue NS1 Ag ELISA" (Bio-Rad, France, (iii "Dengue NS1 Detect Rapid Test (1st Generation" and (iv "DENV Detect NS1 ELISA" (InBios International, United States, (v "Panbio Dengue Early Rapid (1st generation" (vi "Panbio Dengue Early ELISA (2nd generation" and (vii "SD Bioline Dengue NS1 Ag Rapid Test" (Alere, United States. Overall, the sensitivity of the RDTs ranged from 71.9%-79.1% while the sensitivity of the ELISAs varied between 85.6-95.9%, using virus isolation as the reference method. Most tests had lower sensitivity for DENV-4 relative to the other three serotypes, were less sensitive in detecting secondary infections, and appeared to be most sensitive on Day 3-4 post symptom onset. The specificity of all evaluated tests ranged from 95%-100%.ELISAs had greater overall sensitivity than RDTs. In conjunction with other parameters, the performance data can help determine which dengue diagnostics should be used during the first few days of illness, when the patients are most likely to present to a clinic seeking care.

Burnup performance of OTTO cycle pebble bed reactors with ROX fuel

International Nuclear Information System (INIS)

Ho, Hai Quan; Obara, Toru

2015-01-01

Highlights: • A 300 MW t Small Pebble Bed Reactor with Rock-like oxide fuel is proposed. • Using ROX fuel can achieve high discharged burnup of spent fuel. • High geological stability can be expected in direct disposal of the spent ROX fuel. • The Pebble Bed Reactor with ROX fuel can be critical at steady state operation. • All the reactor designs have a negative temperature coefficient. - Abstract: A pebble bed high-temperature gas-cooled reactor (PBR) with rock-like oxide (ROX) fuel was designed to achieve high discharged burnup and improve the integrity of the spent fuel in geological disposal. The MCPBR code with a JENDL-4.0 library, which developed the analysis of the Once-Through-Then-Out (OTTO) cycle in PBR, was used to perform the criticality and burnup analysis. Burnup calculations for eight cases were carried out for both ROX fuel and a UO 2 fuel reactor with different heavy-metal loading conditions. The effective multiplication factor of all cases approximately equalled unity in the equilibrium condition. The ROX fuel reactor showed lower FIFA than the UO 2 fuel reactor at the same heavy-metal loading, about 5–15%. However, the power peaking factor and maximum power per fuel ball in the ROX fuel core were lower than that of UO 2 fuel core. This effect makes it possible to compensate for the lower-FIFA disadvantage in a ROX fuel core. All reactor designs had a negative temperature coefficient that is needed for the passive safety features of a pebble bed reactor

Resistance Patterns Associated with HCV NS5A Inhibitors Provide Limited Insight into Drug Binding

Directory of Open Access Journals (Sweden)

Moheshwarnath Issur

2014-11-01

Full Text Available Direct-acting antivirals (DAAs have significantly improved the treatment of infection with the hepatitis C virus. A promising class of novel antiviral agents targets the HCV NS5A protein. The high potency and broad genotypic coverage are favorable properties. NS5A inhibitors are currently assessed in advanced clinical trials in combination with viral polymerase inhibitors and/or viral protease inhibitors. However, the clinical use of NS5A inhibitors is also associated with new challenges. HCV variants with decreased susceptibility to these drugs can emerge and compromise therapy. In this review, we discuss resistance patterns in NS5A with focus prevalence and implications for inhibitor binding.

In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene.

Directory of Open Access Journals (Sweden)

Sayed AbdulAzeez

Full Text Available α-Thalassemia (α-thal is a genetic disorder caused by the substitution of single amino acid or large deletions in the HBA1 and/or HBA2 genes.Using modern bioinformatics tools as a systematic in-silico approach to predict the deleterious SNPs in the HBA1 gene and its significant pathogenic impact on the functions and structure of HBA1 protein was predicted.A total of 389 SNPs in HBA1 were retrieved from dbSNP database, which includes: 201 non-coding synonymous (nsSNPs, 43 human active SNPs, 16 intronic SNPs, 11 mRNA 3' UTR SNPs, 9 coding synonymous SNPs, 9 5' UTR SNPs and other types. Structural homology-based method (PolyPhen and sequence homology-based tool (SIFT, SNPs&Go, PROVEAN and PANTHER revealed that 2.4% of the nsSNPs are pathogenic.A total of 5 nsSNPs (G60V, K17M, K17T, L92F and W15R were predicted to be responsible for the structural and functional modifications of HBA1 protein. It is evident from the deep comprehensive in-silico analysis that, two nsSNPs such as G60V and W15R in HBA1 are highly deleterious. These "2 pathogenic nsSNPs" can be considered for wet-lab confirmatory analysis.

Activation of ERG2 potassium channels by the diphenylurea NS1643

DEFF Research Database (Denmark)

Elmedyb, Pernille; Olesen, Søren-Peter; Grunnet, Morten

2007-01-01

Three members of the ERG potassium channel family have been described (ERG1-3 or Kv 11.1-3). ERG1 is by far the best characterized subtype and it constitutes the molecular component of the cardiac I(Kr) current. All three channel subtypes are expressed in neurons but their function remains unclear....... The lack of functional information is at least partly due to the lack of specific pharmacological tools. The compound NS1643 has earlier been reported as an ERG1 channel activator. We found that NS1643 also activates the ERG2 channel; however, the molecular mechanism of the activation differs between...... the ERG1 and ERG2 channels. This is surprising since ERG1 and ERG2 channels have very similar biophysical and structural characteristics. For ERG2, NS1643 causes a left-ward shift of the activation curve, a faster time-constant of activation and a slower time-constant of inactivation as well...

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

Directory of Open Access Journals (Sweden)

Markus M. Knodel

2018-01-01

Full Text Available Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

Science.gov (United States)

Knodel, Markus M; Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; Targett-Adams, Paul; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-08

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

Science.gov (United States)

Nägel, Arne; Reiter, Sebastian; Vogel, Andreas; McLauchlan, John; Herrmann, Eva; Wittum, Gabriel

2018-01-01

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles. PMID:29316722

Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface

KAUST Repository

Knodel, Markus

2018-01-08

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Achievements in NS rapeseed hybrids breeding

Directory of Open Access Journals (Sweden)

Marjanović-Jeromela Ana

2016-01-01

Full Text Available The increased production of oilseed rape (Brassica napus L. is evident on a global scale, but also in Serbia in the last decade. Rapeseed is used primarily for vegetable oil and processing industry, but also as a source of protein for animal feed and green manure. Following the cultivation of varieties, breeding and cultivation of hybrid rapeseed started in the 1990's, to take advantage of heterosis in F1 generation, while protecting the breeder's rights during seed commercialization. The breeding of hybrid oilseed rape requires high quality starting material (lines with good combining abilities for introduction of male sterility. Ogura sterility system is primarily used at the Institute of Field and Vegetable Crops, Novi Sad, Serbia. To use this system, separate lines are modified with genes for cytoplasmic male sterility (cms female line - mother line and restoration of fertility (Rf male lines - father line. In order to maintain the sterility of the mother line it is necessary to produce a maintainer line of cytoplasmic male sterility. Creation of these lines and hybrids at the Institute of Field and Vegetable Crops was successfully monitored with intense use of cytogenetic laboratory methods. The structure and vitality of pollen, including different phases during meiosis were checked so that cms stability was confirmed during the introduction of these genes into different lines. Rapeseed breeding program in Serbia resulted in numerous varieties through collaboration of researchers engaged in breeding and genetics of this plant species. So far, in addition to 12 varieties of winter rapeseed and two varieties of spring rapeseed, a new hybrid of winter rapeseed NS Ras was registered in Serbia. NS Ras is an early-maturing hybrid characterized by high seed yield and oil content. Average yield of NS Ras for two seasons and three sites was 4256 kg ha-1 of seed and 1704 kg ha-1 of oil. Three promising winter rapeseed hybrids are in the process of

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

OpenAIRE

Caleb C. Roth; Ronald A. Barnes Jr.; Bennett L. Ibey; Hope T. Beier; L. Christopher Mimun; Saher M. Maswadi; Mehdi Shadaram; Randolph D. Glickman

2015-01-01

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, el...

Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore

KAUST Repository

Jumat, Muhammad; Sugrue, Richard J.; Tan, Boon Huan; Maurer-Stroh, Sebastian; Lee, Raphael Tze Chuen; Wong, Puisan

2016-01-01

In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92–93), and that p23 contained the first 92 amino acids of the NS1 protein. Sequence analysis of the Singapore strains indicated the presence of either DP92–93 or NP92–93 in the NS1 protein, but protein expression analysis showed that p23 was only detected in NS1 proteins with DP92–93.. An additional adjacent proline residue at position 94 (P94) was present in some strains and correlated with increased p23 levels, suggesting that P94 has a synergistic effect on the cleavage of the NS1 protein. The first 145 amino acids of the NS1 protein are required for inhibition of ISG15-mediated ubiquitination, and our analysis showed that Influenza B viruses circulating in Singapore with DP92–93 expressed truncated NS1 proteins and may differ in their capacity to inhibit ISG15 activity. Thus, DP92–93 in the NS1 protein may confer a disadvantage to Influenza B viruses circulating in the human population and interestingly the low frequency of DP92–93detection in the NS1 protein since 2004 is consistent with this suggestion.

Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore

KAUST Repository

Jumat, Muhammad Raihan

2016-08-04

In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92–93), and that p23 contained the first 92 amino acids of the NS1 protein. Sequence analysis of the Singapore strains indicated the presence of either DP92–93 or NP92–93 in the NS1 protein, but protein expression analysis showed that p23 was only detected in NS1 proteins with DP92–93.. An additional adjacent proline residue at position 94 (P94) was present in some strains and correlated with increased p23 levels, suggesting that P94 has a synergistic effect on the cleavage of the NS1 protein. The first 145 amino acids of the NS1 protein are required for inhibition of ISG15-mediated ubiquitination, and our analysis showed that Influenza B viruses circulating in Singapore with DP92–93 expressed truncated NS1 proteins and may differ in their capacity to inhibit ISG15 activity. Thus, DP92–93 in the NS1 protein may confer a disadvantage to Influenza B viruses circulating in the human population and interestingly the low frequency of DP92–93detection in the NS1 protein since 2004 is consistent with this suggestion.

Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors—A Computational Approach

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Noorsaadah Abd. Rahman

2011-02-01

Full Text Available Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA. The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA with various substituents.

Multiplex Outputs ns Grade High-voltage Fast Pulse Generator Study

International Nuclear Information System (INIS)

Wang Xin; Chen Kenan

2009-01-01

Using a double-grid hydrogen thyratron, a fast pulse generator with four outputs, high-voltage, low jitter, was made to use at special occasion.In this paper, the basic structure of pulser, switching theory and double-grid driving of hydrogen thyratron was introduced, and also, the effects of grids driving pulses characteristics, the delay between too grids driving, the reservoir heater voltage and cathode heater voltage on the output are carefully examined in experiments. The pulse generator with four outputs was made to producing pulses with amplitude up to 4 kV, rise-time less than 15 ns and jitter less than 3 ns. (authors)

Characterization of the expression and immunogenicity of the ns4b protein of human coronavirus 229E

DEFF Research Database (Denmark)

Chagnon, F; Lamarre, A; Lachance, C

1998-01-01

to demonstrate the expression of ns4b in HCV-229E-infected cells using flow cytometry. Given a previously reported contiguous five amino acid shared region between ns4b and myelin basic protein, a purified recombinant histidine-tagged ns4b protein and (or) human myelin basic protein were injected into mice......Sequencing of complementary DNAs prepared from various coronaviruses has revealed open reading frames encoding putative proteins that are yet to be characterized and are so far only described as nonstructural (ns). As a first step in the elucidation of its function, we characterized the expression...... and immunogenicity of the ns4b gene product from strain 229E of human coronavirus (HCV-229E), a respiratory virus with a neurotropic potential. The gene was cloned and expressed in bacteria. A fusion protein of ns4b with maltose-binding protein was injected into rabbits to generate specific antibodies that were used...

Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

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Arne Bilet

Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

Influenza A virus NS1 gene mutations F103L and M106I increase replication and virulence

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Ping Jihui

2011-01-01

Full Text Available Abstract Background To understand the evolutionary steps required for a virus to become virulent in a new host, a human influenza A virus (IAV, A/Hong Kong/1/68(H3N2 (HK-wt, was adapted to increased virulence in the mouse. Among eleven mutations selected in the NS1 gene, two mutations F103L and M106I had been previously detected in the highly virulent human H5N1 isolate, A/HK/156/97, suggesting a role for these mutations in virulence in mice and humans. Results To determine the selective advantage of these mutations, reverse genetics was used to rescue viruses containing each of the NS1 mouse adapted mutations into viruses possessing the HK-wt NS1 gene on the A/PR/8/34 genetic backbone. Both F103L and M106I NS1 mutations significantly enhanced growth in vitro (mouse and canine cells and in vivo (BALB/c mouse lungs as well as enhanced virulence in the mouse. Only the M106I NS1 mutation enhanced growth in human cells. Furthermore, these NS1 mutations enhanced early viral protein synthesis in MDCK cells and showed an increased ability to replicate in mouse interferon β (IFN-β pre-treated mouse cells relative to rPR8-HK-NS-wt NS1. The double mutant, rPR8-HK-NS-F103L + M106I, demonstrated growth attenuation late in infection due to increased IFN-β induction in mouse cells. We then generated a rPR8 virus possessing the A/HK/156/97 NS gene that possesses 103L + 106I, and then rescued the L103F + I106M mutant. The 103L + 106I mutations increased virulence by >10 fold in BALB/c mice. We also inserted the avian A/Ck/Beijing/1/95 NS1 gene (the source lineage of the A/HK/156/97 NS1 gene that possesses 103L + 106I, onto the A/WSN/33 backbone and then generated the L103F + I106M mutant. None of the H5N1 and H9N2 NS containing viruses resulted in increased IFN-β induction. The rWSN-A/Ck/Beijing/1/95-NS1 gene possessing 103L and 106I demonstrated 100 fold enhanced growth and >10 fold enhanced virulence that was associated with increased tropism for lung

New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

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Hugo de Almeida

Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

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Yu-Fu Hung

2015-07-01

Full Text Available Dengue virus (DENV is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A is a vital component of the viral replication complex (RC and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48 is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48 to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48 to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.

A Review of Staphylococcal Cassette Chromosome mec (SCCmec) Types in Coagulase-Negative Staphylococci (CoNS) Species.

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Saber, Huda; Jasni, Azmiza Syawani; Jamaluddin, Tengku Zetty Maztura Tengku; Ibrahim, Rosni

2017-10-01

Coagulase-negative staphylococci (CoNS) are considered low pathogenic organisms. However, they are progressively causing more serious infections with time because they have adapted well to various antibiotics owing to their ability to form biofilms. Few studies have been conducted on CoNS in both, hospital and community-acquired settings, especially in Malaysia. Thus, it is important to study their species and gene distributions. A mobile genetic element, staphylococcal cassette chromosome mec (SCC mec ), plays an important role in staphylococci pathogenesis. Among CoNS, SCC mec has been studied less frequently than Staphylococcus aureus (coagulase-positive staphylococci). A recent study (8) conducted in Malaysia successfully detected SCC mec type I to VIII as well as several new combination patterns in CoNS species, particularly Staphylococcus epidermidis . However, data are still limited, and further research is warranted. This paper provides a review on SCC mec types among CoNS species.

NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo

DEFF Research Database (Denmark)

Dagø, Lone; Bonde, Christian; Peters, Dan

2002-01-01

reduced NMDA-induced excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of transient global ischaemia, treatment with NS 1231 reduced the delayed loss of neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in a 43% reduction in total infarct volume...

The Influenza NS1 Protein: What Do We Know in Equine Influenza Virus Pathogenesis?

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Marta Barba

2016-08-01

Full Text Available Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1 has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translation of host antiviral response genes such as type I interferon. Details are provided regarding what it is known about NS1 in equine influenza, especially concerning C-terminal truncation. Further research is needed to determine the role of NS1 in equine influenza infection, which will help to understand the pathophysiology of complicated cases related to cytokine imbalance and secondary bacterial infection, and to investigate new therapeutic and vaccination strategies.

An NS5A single optimized method to determine genotype, subtype and resistance profiles of Hepatitis C strains.

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Elisabeth Andre-Garnier

Full Text Available The objective was to develop a method of HCV genome sequencing that allowed simultaneous genotyping and NS5A inhibitor resistance profiling. In order to validate the use of a unique RT-PCR for genotypes 1-5, 142 plasma samples from patients infected with HCV were analysed. The NS4B-NS5A partial region was successfully amplified and sequenced in all samples. In parallel, partial NS3 sequences were analyzed obtained for genotyping. Phylogenetic analysis showed concordance of genotypes and subtypes with a bootstrap >95% for each type cluster. NS5A resistance mutations were analyzed using the Geno2pheno [hcv] v0.92 tool and compared to the list of known Resistant Associated Substitutions recently published. In conclusion, this tool allows determination of HCV genotypes, subtypes and identification of NS5A resistance mutations. This single method can be used to detect pre-existing resistance mutations in NS5A before treatment and to check the emergence of resistant viruses while undergoing treatment in major HCV genotypes (G1-5 in the EU and the US.

The NS1 Protein from Influenza Virus Stimulates Translation Initiation by Enhancing Ribosome Recruitment to mRNAs.

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Panthu, Baptiste; Terrier, Olivier; Carron, Coralie; Traversier, Aurélien; Corbin, Antoine; Balvay, Laurent; Lina, Bruno; Rosa-Calatrava, Manuel; Ohlmann, Théophile

2017-10-27

The non-structural protein NS1 of influenza A viruses exerts pleiotropic functions during infection. Among these functions, NS1 was shown to be involved in the control of both viral and cellular translation; however, the mechanism by which this occurs remains to be determined. Thus, we have revisited the role of NS1 in translation by using a combination of influenza infection, mRNA reporter transfection, and in vitro functional and biochemical assays. Our data show that the NS1 protein is able to enhance the translation of virtually all tested mRNAs with the exception of constructs bearing the Dicistroviruses Internal ribosome entry segment (IRESes) (DCV and CrPV), suggesting a role at the level of translation initiation. The domain of NS1 required for translation stimulation was mapped to the RNA binding amino-terminal motif of the protein with residues R38 and K41 being critical for activity. Although we show that NS1 can bind directly to mRNAs, it does not correlate with its ability to stimulate translation. This activity rather relies on the property of NS1 to associate with ribosomes and to recruit them to target mRNAs. Copyright © 2017 Elsevier Ltd. All rights reserved.

The psychology of thinking before the cognitive revolution: Otto Selz on problems, schemas, and creativity.

Science.gov (United States)

ter Hark, Michel

2010-02-01

Otto Selz has been hailed as one of the most important precursors of the cognitive revolution, yet surprisingly few studies of his work exist. He is often mentioned in the context of the Würzburg School of the psychology of thinking and sometimes in the context of Gestalt psychology. In this paper, it is argued that Selz's emphasis on the role of problems and schemas in the direction of thought processes and creativity sets him apart from the program of the Würzburg School. On the other hand, by developing a theory of thinking that is exclusively at the intentional level, Selz also differs from psychologists that take physics as a model for psychology, such as the Gestalt psychology of Wolfgang Kihler. Special emphasis is given in this paper to Selz's use of the concept of problem or task and the concept of the schema. It is further argued that the concept of the schema is the result of Selz's adaptation of the theory of relations as developed by the philosopher Meinong. The paper begins with a sketch of Selz's life that ended so tragically.

Radiating matter

International Nuclear Information System (INIS)

Zimen, K.E.

1987-01-01

The author describes the history and uses of radioactivity. The narration is completed by bibliographic notes on Otto Hahn with a number of so far unpublished letters and documents and on Leo Szilard, the most far-sighted among the nuclear researchers actively engaged during the war. The first part deals with the discovery of radioactivity and the discovery of uranium fission in 1938 with its military consequences, up to the short-lived euphoria on the 'atomic age' (Geneva conference 1955). This is followed by an account of natural radioactivity in our environment, a brief of useful information on radiation effects and radiation protection, and of typical applications of radioactive beams in science, engineering, and medicine. The final part is concerned with the most important instances of insight into nature triggered by the discovery of radioactivity: From cosmological to chemical evolution, from Democrit's atom theory to modern nuclear physics' particle zoo, from the contest of ideas between acausalists and determinists on what is commonly termed 'coincidence' to the limits of graphic views on nature. (orig./HP) [de

Radiating matter

International Nuclear Information System (INIS)

Zimen, K.E.

1990-01-01

The author describes the history and uses of radioactivity. The narration is completed by bibliographic notes on Otto Hahn with a number of so far unpublished letters and documents and on Leo Szilard, the most far-sighted among the nuclear researchers actively engaged during the war. The first part deals with the discovery of radioactivity and the discovery of uranium fission in 1938 with its military consequences, up to the short-lived euphoria on the 'atomic age' (Geneva conference 1955). This is followed by an account of natural radioactivity in our environment, a brief of useful information on radiation effects and radiation protection, and of typical applications of radioactive beams in science, engineering, and medicine. The final part is concerned with the most important instances of insight into nature triggered by the discovery of radioactivity: From cosmological to chemical evolution, from Democrit's atom theory to modern nuclear physics' particle zoo, from the contest of ideas between acausalists and determinists on what is commonly termed 'coincidence' to the limits of graphic views on nature. (orig.) With 40 figs [de

Fritz Haber: December 9, 1868-January 29, 1934.

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Witschi, H

2000-08-14

Fritz Haber (1868-1934) was a German physical chemist. Nobel laureate and foreign member of the US National Academy of Sciences. His greatest accomplishment in science was the development of a practical method to prepare nitrogen from air (nitrogen fixation or Haber-Bosch process). While working on the toxicity of war gases. he formulated 'Haber's rule', also known as C x T= constant in order to characterize the toxicity of an inhalant. Between 1919 and 1933. he was one of the leading figures in revitalizing science in Germany. At his institute in Berlin worked such luminaries as Albert Einstein, Lise Meitner and Otto Hahn. His last paper described what became known as the Haber-Weiss reaction. After his death he was for a long time forgotten by the Nazis because he was Jewish and after World War II by the Allies because of his work on war gases in World War I. And yet he was one of the truly great modern scientists. not only because of his science, but also because of the role he played in science politics and policies.

Effects of nanosecond pulsed electric fields (nsPEFs) on the human fungal pathogen Candida albicans: an in vitro study

Science.gov (United States)

Guo, Jinsong; Dang, Jie; Wang, Kaile; Zhang, Jue; Fang, Jing

2018-05-01

Candida albicans is the leading human fungal pathogen that causes many life-threatening infections. Notably, the current clinical trial data indicate that Candida species shows the emerging resistance to anti-fungal drugs. The aim of this study was to evaluate the antifungal effects of nanosecond pulsed electric fields (nsPEFs) as a novel drug-free strategy in vitro. In this study, we investigated the inactivation and permeabilization effects of C. albicans under different nsPEFs exposure conditions (100 pulses, 100 ns in duration, intensities of 20, 40 kV cm‑1). Cell death was studied by annexin-V and propidium iodide staining. The changes of intracellular Ca2+ concentration after nsPEFs treatment were observed using Fluo-4 AM. Results show that C. albicans cells and biofilms were both obviously inhibited and destroyed after nsPEFs treatment. Furthermore, C. albicans cells were significantly permeabilized after nsPEFs treatment. Additionally, nsPEFs exposure led to a large amount of DNA and protein leakage. Importantly, nsPEFs induced a field strength-dependent apoptosis in C. albicans cells. Further experiments revealed that Ca2+ involved in nsPEFs induced C. albicans apoptosis. In conclusion, this proof-of-concept study provides a potential alternative drug-free strategy for killing pathogenic Candida species.

Symposium on CIAE 600 kV ns pulse neutron generator

International Nuclear Information System (INIS)

Shen Guanren

2001-01-01

CIAE 600 kV ns Pulse Neutron Generator was built by China National Nuclear Corporation, which is an important facility mainly used for experimental researches of nuclear reactions induced by 14 MeV neutrons, experimental measurements of energy spectra of secondary neutrons and charged particles and macro-checking experiments of evaluated neutron database and dosimetry researches of neutrons and γ rays. It is the first home made one, but the fourth similar facility in the world. Six articles are included in this symposium. The articles details the general structure, radio frequency ion source, high current beam ns pulsed system, etc. The main technical problems resolved during development are discussed. And attentions and experiences in the generator adjustments are introduced

Meissner effect in clean proximity-contact N-S double layer

International Nuclear Information System (INIS)

Higashitani, S.; Nagai, K.

1994-01-01

The Meissner effect in proximity-contact normal-superconducting (N-S) double layers is discussed in the clean limit. We obtain the quasi-classical Green's function linear in the vector potential such that satisfies the boundary conditions at the layer ends and also at the N-S interface with a finite reflection coefficient R. We find that, when there is no pairing interaction in the normal layer, the diamagnetic current in the normal layer is constant in space, consequently the magnetic field decreases linearly in the normal layer. To compare our theory with experiments, we calculate the screening length and find a good agreement in the temperature dependence with the experiments in the Au-Nb system. (orig.)

Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells.

Science.gov (United States)

Gao, Yunfeng; Foo, Yong Hwee; Winardhi, Ricksen S; Tang, Qingnan; Yan, Jie; Kenney, Linda J

2017-11-21

Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in single cells. We discovered a role for the unstructured linker region connecting the N-terminal oligomerization and C-terminal DNA binding domains. In the present work we demonstrate that linker amino acids promote engagement with DNA. In the absence of linker contacts, H-NS binding is significantly reduced, although no change in chromosome compaction is observed. H-NS is not localized to two distinct foci; rather, it is scattered all around the nucleoid. The linker makes DNA contacts that are required for gene silencing, while chromosome compaction does not appear to be an important H-NS function.

Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways

International Nuclear Information System (INIS)

Kim, Kyoung Mi; Kwon, Shi-Nae; Kang, Ju-Il; Lee, Song Hee; Jang, Sung Key; Ahn, Byung-Yoon; Kim, Yoon Ki

2007-01-01

Chronic infection of the hepatitis C virus (HCV) leads to liver cirrhosis and cancer. The mechanism leading to viral persistence and hepatocellular carcinoma, however, has not been fully understood. In this study, we show that the HCV infection activates cellular cAMP-dependent pathways. Expression of a luciferase reporter gene controlled by a basic promoter with the cAMP response element (CRE) was significantly elevated in human hepatoma Huh-7 cells infected with the HCV JFH1. Analysis with viral subgenomic replicons indicated that the HCV NS2 protein is responsible for the effect. Furthermore, the level of cellular transcripts whose stability is known to be regulated by cAMP was specifically reduced in cells harboring NS2-expressing replicons. These results allude to the HCV NS2 protein having a novel function of regulating cellular gene expression and proliferation through the cAMP-dependent pathway

"Os quatro cavaleiros de um íntimo apocalipse" e suas biografias vicárias: Fernando Sabino, Otto Lara Resende, Hélio Pellegrino e Paulo Mendes Campos na escrita de perfis

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Gabriela Kvacek Betella

2007-08-01

Full Text Available Fernando Sabino, Otto Lara Resende, Hélio Pellegrino e Paulo Mendes Campos traçaram retratos de pessoas com as quais conviveram ao longo de suas vidas por meio de perfis concisos, seja na forma de elegias seja mesmo de necrológios. Embora esses textos sejam imprescindíveis para fundamentar o estilo de cada um dos escritores mineiros, eles também carregam a síntese de cada experiência pessoal, que é fundamental para a análise da crônica, gênero que o quarteto praticou e no qual podem ser enquadrados os perfis examinados neste ensaio.Fernando Sabino, Otto Lara Resende, Hélio Pellegrino and Paulo Mendes Campos wrote portraits of people with whom they were intimate along their lives by means of short profiles, either in the form of elegies or even of necrologies. Although these texts are necessary in order to set up the style of each one of these writers from Minas Gerais, they also carry the synthesis of each personal experience, which is fundamental for the analysis of the chronicle, a literary genre that the quartet of writers practiced and within which the profiles examined in this essay can be classified.

Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel

Science.gov (United States)

Chatel-Chaix, Laurent; Baril, Martin; Lamarre, Daniel

2010-01-01

Hepatitis C virus (HCV) infection is a serious and growing threat to human health. The current treatment provides limited efficacy and is poorly tolerated, highlighting the urgent medical need for novel therapeutics. The membrane-targeted NS3 protein in complex with the NS4A comprises a serine protease domain (NS3/4A protease) that is essential for viral polyprotein maturation and contributes to the evasion of the host innate antiviral immunity by HCV. Therefore, the NS3/4A protease represents an attractive target for drug discovery, which is tied in with the challenge to develop selective small-molecule inhibitors. A rational drug design approach, based on the discovery of N-terminus product inhibition, led to the identification of potent and orally bioavailable NS3 inhibitors that target the highly conserved protease active site. This review summarizes the NS3 protease inhibitors currently challenged in clinical trials as one of the most promising antiviral drug class, and possibly among the first anti-HCV agents to be approved for the treatment of HCV infection. PMID:21994705

Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel

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Laurent Chatel-Chaix

2010-08-01

Full Text Available Hepatitis C virus (HCV infection is a serious and growing threat to human health. The current treatment provides limited efficacy and is poorly tolerated, highlighting the urgent medical need for novel therapeutics. The membrane-targeted NS3 protein in complex with the NS4A comprises a serine protease domain (NS3/4A protease that is essential for viral polyprotein maturation and contributes to the evasion of the host innate antiviral immunity by HCV. Therefore, the NS3/4A protease represents an attractive target for drug discovery, which is tied in with the challenge to develop selective small-molecule inhibitors. A rational drug design approach, based on the discovery of N-terminus product inhibition, led to the identification of potent and orally bioavailable NS3 inhibitors that target the highly conserved protease active site. This review summarizes the NS3 protease inhibitors currently challenged in clinical trials as one of the most promising antiviral drug class, and possibly among the first anti-HCV agents to be approved for the treatment of HCV infection.

Identification of human hnRNP C1/C2 as a dengue virus NS1-interacting protein

International Nuclear Information System (INIS)

Noisakran, Sansanee; Sengsai, Suchada; Thongboonkerd, Visith; Kanlaya, Rattiyaporn; Sinchaikul, Supachok; Chen, Shui-Tein; Puttikhunt, Chunya

2008-01-01

Dengue virus nonstructural protein 1 (NS1) is a key glycoprotein involved in the production of infectious virus and the pathogenesis of dengue diseases. Very little is known how NS1 interacts with host cellular proteins and functions in dengue virus-infected cells. This study aimed at identifying NS1-interacting host cellular proteins in dengue virus-infected cells by employing co-immunoprecipitation, two-dimensional gel electrophoresis, and mass spectrometry. Using lysates of dengue virus-infected human embryonic kidney cells (HEK 293T), immunoprecipitation with an anti-NS1 monoclonal antibody revealed eight isoforms of dengue virus NS1 and a 40-kDa protein, which was subsequently identified by quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS) as human heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. Further investigation by co-immunoprecipitation and co-localization confirmed the association of hnRNP C1/C2 and dengue virus NS1 proteins in dengue virus-infected cells. Their interaction may have implications in virus replication and/or cellular responses favorable to survival of the virus in host cells

PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase

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Kazi Abdus Salam

2014-04-01

Full Text Available The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3 is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1 on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1 against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency.

HCV RNA traffic and association with NS5A in living cells

Energy Technology Data Exchange (ETDEWEB)

Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.; Van Der Hoek, Kylie [Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, University of Adelaide, Adelaide and Centre for Cancer Biology, SA Pathology, Adelaide, SA (Australia); Betz-Stablein, Brigit; Luciani, Fabio [Systems Immunology, School of Medical Sciences, University of New South Wales, Sydney, NSW (Australia); Chopra, Abha [Institute for Immunology and infectious diseases (IIID), Murdoch University, Perth, WA (Australia); Beard, Michael R., E-mail: michael.beard@adelaide.edu.au [Department of Molecular and Cellular Biology, Research Centre for Infectious Diseases, University of Adelaide, Adelaide and Centre for Cancer Biology, SA Pathology, Adelaide, SA (Australia)

2016-06-15

The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3′-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly. - Highlights: • HCV can tolerate can bacteriophage MS2 stem-loop insertions within the 3′ UTR. • MS2 stem-loop containing HCV genomes allow for real-time imaging of HCV RNA. • HCV RNA is both static and motile and associates with NS5A and lipid droplets.

HCV RNA traffic and association with NS5A in living cells

International Nuclear Information System (INIS)

Fiches, Guillaume N.; Eyre, Nicholas S.; Aloia, Amanda L.; Van Der Hoek, Kylie; Betz-Stablein, Brigit; Luciani, Fabio; Chopra, Abha; Beard, Michael R.

2016-01-01

The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3′-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly. - Highlights: • HCV can tolerate can bacteriophage MS2 stem-loop insertions within the 3′ UTR. • MS2 stem-loop containing HCV genomes allow for real-time imaging of HCV RNA. • HCV RNA is both static and motile and associates with NS5A and lipid droplets.

Comparative study and grouping of nonstructural (NS1)proteins of influenza A viruses by the method of oligopeptide mapping

International Nuclear Information System (INIS)

Sokolov, B.P.; Rudneva, I.A.; Zhdanov, V.M.

1983-01-01

Oligopeptide mapping of 35 S-methionine labeled non-stuctural (NS1) proteins of 23 influenza A virus strains showed the presence of both common and variable oligopeptides. Analysis of the oligopeptide maps revealed at least four groups of NS1 proteins. The first group includes NS1 proteins of several human H1N1 influenza viruses (that were designated as H0N1 according to the old classification). The second group is composed of NS1 proteins of H1N1 and H2N2 viruses. The third group includes NS1 proteins of H3N2 human influenza viruses. The fourth group is composed of NS1 proteins of five avian influenza viruses and an equine (H3N8) influenza virus. Two animal influenza viruses A/equi/Prague/56 (H7N7) and A/duck/England/56 (H11N6) contain NS1 proteins that belong to the second group. (Author)

Identification of one B-cell epitope from NS1 protein of duck Tembusu virus with monoclonal antibodies.

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Jinfeng Ti

Full Text Available This study describes the identification of one linear B-cell epitope on TMUV NS1 protein with monoclonal antibody (mAb 3G2 by indirect enzyme-linked immunosorbent assay (ELISA. In this study, NS1 protein was expressed in prokaryotic expression system and purified. One mAb against NS1 protein was generated from Balb/c mice immunized with recombinant protein NS1. A set of 35 partially-overlapping polypeptides covering the entire NS1 protein was expressed with PGEX-6P-1 vector and screened with mAb 3G2. One polypeptide against the mAb was acquired and identified by indirect ELISA and western-blot. To map the epitope accurately, one or two amino acid residues were removed from the carboxy and amino terminal of polypeptide sequentially. A series of truncated oligopeptides were expressed and purified. The minimal determinant of the linear B cell epitope was recognized and identified with mAb 3G2. The accurate linear B-cell epitope was 269DEKEIV274 located in NS1 protein. Furthermore, sequence alignment showed that the epitope was highly conserved and specific among TMUV strains and other flavivirus respectively. The linear B-cell epitope of TMUV NS1 protein could benefit the development of new vaccines and diagnostic assays.

Experiencing memory museums in Berlin. The Otto Weidt Workshop for the Blind Museum and the Jewish Museum Berlin

Directory of Open Access Journals (Sweden)

Ana Souto

2018-03-01

Full Text Available This article explores memory studies from the audience’s perspective, focusing on the perception of Holocaust narratives in two museums in Berlin. This research builds on and contributes to a number of emerging issues on memory studies, tourism perception and museum design: the debate on experiential authenticity, Dark Tourism, as well as the analysis of memory studies from the perspective of the user. The main data facilitating the analysis is based on responses shared on TripAdvisor; the case studies being the Otto Weidt Workshop for the Blind Museum and the Jewish Museum Berlin. The analysis of these museums, focusing on their narratives, design features and comments from visitors, will highlight a potential shift from the traditional object-focused museum, to a phenomenological subject-focused one. It will be argued, then, that the understanding and consumption of authenticity encompasses a very flexible definition, not only based on the nature of the objects exhibited, but on the production of authentic experiences.

Structural Basis for dsRNA Recognition by NS1 Protein of Influenza A Virus

Energy Technology Data Exchange (ETDEWEB)

Cheng, A.; Wong, S; Yuan, Y

2009-01-01

Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the crystal structure of NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a length-independent mode by its conserved concave surface formed by dimeric anti-parallel alpha-helices. dsRNA is anchored by a pair of invariable arginines (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the structural observation, isothermal titration calorimetry assay shows that the unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding, and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co-infiltration assay further supports that the unique Arg38 pair plays important roles in dsRNA binding in vivo.

A search for RNA insertions and NS3 gene duplication in the genome of cytopathic isolates of bovine viral diarrhea virus

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V.L. Quadros

2006-07-01

Full Text Available Calves born persistently infected with non-cytopathic bovine viral diarrhea virus (ncpBVDV frequently develop a fatal gastroenteric illness called mucosal disease. Both the original virus (ncpBVDV and an antigenically identical but cytopathic virus (cpBVDV can be isolated from animals affected by mucosal disease. Cytopathic BVDVs originate from their ncp counterparts by diverse genetic mechanisms, all leading to the expression of the non-structural polypeptide NS3 as a discrete protein. In contrast, ncpBVDVs express only the large precursor polypeptide, NS2-3, which contains the NS3 sequence within its carboxy-terminal half. We report here the investigation of the mechanism leading to NS3 expression in 41 cpBVDV isolates. An RT-PCR strategy was employed to detect RNA insertions within the NS2-3 gene and/or duplication of the NS3 gene, two common mechanisms of NS3 expression. RT-PCR amplification revealed insertions in the NS2-3 gene of three cp isolates, with the inserts being similar in size to that present in the cpBVDV NADL strain. Sequencing of one such insert revealed a 296-nucleotide sequence with a central core of 270 nucleotides coding for an amino acid sequence highly homologous (98% to the NADL insert, a sequence corresponding to part of the cellular J-Domain gene. One cpBVDV isolate contained a duplication of the NS3 gene downstream from the original locus. In contrast, no detectable NS2-3 insertions or NS3 gene duplications were observed in the genome of 37 cp isolates. These results demonstrate that processing of NS2-3 without bulk mRNA insertions or NS3 gene duplications seems to be a frequent mechanism leading to NS3 expression and BVDV cytopathology.

Positioning system in wireless sensor networks using NS-2

CSIR Research Space (South Africa)

Abu-Mahfouz, Adnan M

2012-10-01

Full Text Available The practical difficulties of setting up a wireless sensor network (WSN) and analysing its performance have made simulation essential for the study of WSNs. The ns-2 network simulator is one of the most widely used tools by researchers...

NS5A Sequence Heterogeneity and Mechanisms of Daclatasvir Resistance in Hepatitis C Virus Genotype 4 Infection.

Science.gov (United States)

Zhou, Nannan; Hernandez, Dennis; Ueland, Joseph; Yang, Xiaoyan; Yu, Fei; Sims, Karen; Yin, Philip D; McPhee, Fiona

2016-01-15

Daclatasvir is an NS5A inhibitor approved for treatment of infection due to hepatitis C virus (HCV) genotypes (GTs) 1-4. To support daclatasvir use in HCV genotype 4 infection, we examined a diverse genotype 4-infected population for HCV genotype 4 subtype prevalence, NS5A polymorphisms at residues associated with daclatasvir resistance (positions 28, 30, 31, or 93), and their effects on daclatasvir activity in vitro and clinically. We performed phylogenetic analysis of genotype 4 NS5A sequences from 186 clinical trial patients and 43 sequences from the European HCV database, and susceptibility analyses of NS5A polymorphisms and patient-derived NS5A sequences by using genotype 4 NS5A hybrid genotype 2a replicons. The clinical trial patients represented 14 genotype 4 subtypes; most prevalent were genotype 4a (55%) and genotype 4d (27%). Daclatasvir 50% effective concentrations for 10 patient-derived NS5A sequences representing diverse phylogenetic clusters were ≤0.080 nM. Most baseline sequences had ≥1 NS5A polymorphism at residues associated with daclatasvir resistance; however, only 3 patients (1.6%) had polymorphisms conferring ≥1000-fold daclatasvir resistance in vitro. Among 46 patients enrolled in daclatasvir trials, all 20 with baseline resistance polymorphisms achieved a sustained virologic response. Circulating genotype 4 subtypes are genetically diverse. Polymorphisms conferring high-level daclatasvir resistance in vitro are uncommon before therapy, and clinical data suggest that genotype 4 subtype and baseline polymorphisms have minimal impact on responses to daclatasvir-containing regimens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

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Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

2013-01-01

Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

Anticuerpos policlonales contra la proteína recombinante NS3 del virus del dengue

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Liliana Morales

2017-01-01

Resultados. Los anticuerpos producidos fueron útiles en ensayos de Western blot e inmunofluorescencia y se reportó por primera vez un anticuerpo policlonal anti-NS3 que permitió la inmunoprecipitación de la proteína viral y la detecta con Western blot sin necesidad de inducir sobreexpresión de NS3 o de usar extractos de células marcados metabólicamente con radioisótopos. Conclusión. Las proteínas recombinantes expresadas y los anticuerpos producidos constituyen herramientas valiosas para estudiar procesos infecciosos del DENV que involucren a la proteína NS3 y evaluar pruebas dirigidas a interferir las funciones de esta proteína.

Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening

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Halim, Sobia A.; Khan, Shanza; Khan, Ajmal; Wadood, Abdul; Mabood, Fazal; Hussain, Javid; Al-Harrasi, Ahmed

2017-10-01

Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, twenty five compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase in silico, and can be helpful in the treatment of Dengue.

Sensitive detection of novel Indian isolate of BTV 21 using ns1 gene based real-time PCR assay

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Gaya Prasad

2013-06-01

Full Text Available Aim: The study was conducted to develop ns1 gene based sensitive real-time RT-PCR assay for diagnosis of India isolates of bluetongue virus (BTV. Materials and Methods: The BTV serotype 21 isolate (KMNO7 was isolated from Andhra Pradesh and propagated in BHK-21 cell line in our laboratory. The Nucleic acid (dsRNA of virus was extracted using Trizol method and cDNA was prepared using a standard protocol. The cDNA was allowed to ns1 gene based group specific PCR to confirm the isolate as BTV. The viral RNA was diluted 10 folds and the detection limit of ns1 gene based RT-PCR was determined. Finally the tenfold diluted viral RNA was subjected to real-time RT-PCR using ns1 gene primer and Taq man probe to standardized the reaction and determine the detection limit. Results: The ns1 gene based group specific PCR showed a single 366bp amplicon in agarose gel electrophoresis confirmed the sample as BTV. The ns1 gene RT-PCR using tenfold diluted viral RNA showed the detection limit of 70.0 fg in 1%agarose gel electrophoresis. The ns1 gene based real time RT-PCR was successfully standardized and the detection limit was found to be 7.0 fg. Conclusion: The ns1 gene based real-time RT-PCR was successfully standardized and it was found to be 10 times more sensitive than conventional RT-PCR. Key words: bluetongue, BTV21, RT-PCR, Real time RT-PCR, ns1 gene [Vet World 2013; 6(8.000: 554-557

Hepatitis C Virus Particle Assembly Involves Phosphorylation of NS5A by the c-Abl Tyrosine Kinase.

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Yamauchi, Shota; Takeuchi, Kenji; Chihara, Kazuyasu; Sun, Xuedong; Honjoh, Chisato; Yoshiki, Hatsumi; Hotta, Hak; Sada, Kiyonao

2015-09-04

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is thought to regulate the replication of viral RNA and the assembly of virus particles in a serine/threonine phosphorylation-dependent manner. However, the host kinases that phosphorylate NS5A have not been fully identified. Here, we show that HCV particle assembly involves the phosphorylation of NS5A by the c-Abl tyrosine kinase. Pharmacological inhibition or knockdown of c-Abl reduces the production of infectious HCV (J6/JFH1) particles in Huh-7.5 cells without markedly affecting viral RNA translation and replication. NS5A is tyrosine-phosphorylated in HCV-infected cells, and this phosphorylation is also reduced by the knockdown of c-Abl. Mutational analysis reveals that NS5A tyrosine phosphorylation is dependent, at least in part, on Tyr(330) (Tyr(2306) in polyprotein numbering). Mutation of this residue to phenylalanine reduces the production of infectious HCV particles but does not affect the replication of the JFH1 subgenomic replicon. These findings suggest that c-Abl promotes HCV particle assembly by phosphorylating NS5A at Tyr(330). © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Detection of antibodies against porcine parvovirus nonstructural protein NS1 may distinguish between vaccinated and infected pigs

DEFF Research Database (Denmark)

Madsen, Eva Smedegaard; Madsen, Knud Gert; Nielsen, Jens

1997-01-01

The humoral antibody response against the nonstructural protein NS1 and the structural protein VP2 of porcine parvovirus (PPV) was evaluated by immuno-peroxidase test (IPT) and enzyme linked immune sorbent assay (ELISA) using recombinant PPV antigens. The coding sequence for NS1 and VP2...... was inserted into the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV) genome resulting in two recombinant baculoviruses AcNPV-NS1 and AcNPV-VP2, respectively. Sf9 cells (Spodoptora frugidiperda) inoculated with AcNPV-NS1 producing recombinant nonstructural protein (rNS1) and AcNPV-VP2...... producing recombinant virion protein (rVP2) were used in IPT and ELISA to analyse serum antibodies. Pigs vaccinated with an inactivated whole virus vaccine and experimentally infected pigs were studied. Significant titers against rVP2 were obtained in both vaccinated and infected pigs. Specific antibodies...

A Proline-Rich N-Terminal Region of the Dengue Virus NS3 Is Crucial for Infectious Particle Production.

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Gebhard, Leopoldo G; Iglesias, Néstor G; Byk, Laura A; Filomatori, Claudia V; De Maio, Federico A; Gamarnik, Andrea V

2016-06-01

Dengue virus is currently the most important insect-borne viral human pathogen. Viral nonstructural protein 3 (NS3) is a key component of the viral replication machinery that performs multiple functions during viral replication and participates in antiviral evasion. Using dengue virus infectious clones and reporter systems to dissect each step of the viral life cycle, we examined the requirements of different domains of NS3 on viral particle assembly. A thorough site-directed mutagenesis study based on solvent-accessible surface areas of NS3 revealed that, in addition to being essential for RNA replication, different domains of dengue virus NS3 are critically required for production of infectious viral particles. Unexpectedly, point mutations in the protease, interdomain linker, or helicase domain were sufficient to abolish infectious particle formation without affecting translation, polyprotein processing, or RNA replication. In particular, we identified a novel proline-rich N-terminal unstructured region of NS3 that contains several amino acid residues involved in infectious particle formation. We also showed a new role for the interdomain linker of NS3 in virion assembly. In conclusion, we present a comprehensive genetic map of novel NS3 determinants for viral particle assembly. Importantly, our results provide evidence of a central role of NS3 in the coordination of both dengue virus RNA replication and particle formation. Dengue virus is an important human pathogen, and its prominence is expanding globally; however, basic aspects of its biology are still unclear, hindering the development of effective therapeutic and prophylactic treatments. Little is known about the initial steps of dengue and other flavivirus particle assembly. This process involves a complex interplay between viral and cellular components, making it an attractive antiviral target. Unpredictably, we identified spatially separated regions of the large NS3 viral protein as determinants for

Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwide Isolates of Viral Genotypes 1 to 6.

Science.gov (United States)

Patiño-Galindo, Juan Ángel; Salvatierra, Karina; González-Candelas, Fernando; López-Labrador, F Xavier

2016-04-01

There is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. In addition, we found a low genetic barrier for the generation of new RAVs, irrespective of the viral genotype. Furthermore, in 1,126 HCV genomes, including sequences spanning the three genes, haplotype analysis revealed a remarkably high frequency of viruses carrying more than one natural RAV to DAAs (53% of HCV-1a, 28.5% of HCV-1b, 67.1% of HCV-6, and 100% of genotype 2, 3, 4, and 5 haplotypes). With the exception of HCV-1a, the most prevalent haplotypes showed RAVs in at least two different viral genes. Finally, evolutionary analyses revealed that, while most natural RAVs appeared recently, others have been efficiently transmitted over time and cluster in well-supported clades. In summary, and despite the observed high efficacy of DAA-based regimens, we show that naturally occurring RAVs are common in all HCV genotypes and that there is an overall low genetic barrier for the selection of resistance mutations. There is a need for natural DAA resistance profiling specific for each HCV genotype. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

In Silico Screening, Alanine Mutation, and DFT Approaches for Identification of NS2B/NS3 Protease Inhibitors

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R. Balajee

2016-01-01

Full Text Available To identify the ligand that binds to a target protein with high affinity is a nontrivial task in computer-assisted approaches. Antiviral drugs have been identified for NS2B/NS3 protease enzyme on the mechanism to cleave the viral protein using the computational tools. The consequence of the molecular docking, free energy calculations, and simulation protocols explores the better ligand. It provides in-depth structural insights with the catalytic triad of His51, Asp75, Ser135, and Gly133. The MD simulation was employed here to predict the stability of the complex. The alanine mutation has been performed and its stability was monitored by using the molecular dynamics simulation. The minimal RMSD value suggests that the derived complexes are close to equilibrium. The DFT outcome reveals that the HOMO-LUMO gap of Ligand19 is 2.86 kcal/mol. Among the considered ligands, Ligand19 shows the lowest gap and it is suggested that the HOMO of Ligand19 may transfer the electrons to the LUMO in the active regions. The calculated binding energy of Ligand19 using the DFT method is in good agreement with the docking studies. The pharmacological activity of ligand was performed and satisfies Lipinski rule of 5. Moreover, the computational results are compared with the available IC50 values of experimental results.

Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806.

Science.gov (United States)

Cheng, Hongwei; Cannell, Mark B; Hancox, Jules C

2017-03-01

Transient outward potassium current (I to ) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of I to may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine I to This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular I to Whole cell patch-clamp recordings of I to and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10  μ mol/L NS5806 increased ventricular I to with a leftward shift in I to activation and accelerated restitution. At higher concentrations, stimulation of I to was followed by inhibition. The EC 50 for stimulation was 1.6  μ mol/L and inhibition had an IC 50 of 40.7  μ mol/L. NS5806 only inhibited atrial I to (IC 50 of 18  μ mol/L) and produced a modest leftward shifts in I to activation and inactivation, without an effect on restitution. 10  μ mol/L NS5806 shortened ventricular action potential duration (APD) at APD 20 -APD 90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na + channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial I to NS5806 discriminates between rabbit ventricular and atrial I to, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac I to . © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Sensitive luminescent reporter viruses reveal appreciable release of hepatitis C virus NS5A protein into the extracellular environment.

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Eyre, Nicholas S; Aloia, Amanda L; Joyce, Michael A; Chulanetra, Monrat; Tyrrell, D Lorne; Beard, Michael R

2017-07-01

The HCV NS5A protein is essential for viral RNA replication and virus particle assembly. To study the viral replication cycle and NS5A biology we generated an infectious HCV construct with a NanoLuciferase (NLuc) insertion within NS5A. Surprisingly, beyond its utility as a sensitive reporter of cytoplasmic viral RNA replication, we also observed strong luminescence in cell culture fluids. Further analysis using assembly-defective viruses and subgenomic replicons revealed that infectious virus production was not required for extracellular NS5A-NLuc activity but was associated with enrichment of extracellular NS5A-NLuc in intermediate-density fractions similar to those of exosomes and virus particles. Additionally, BRET analysis indicated that intracellular and extracellular forms of NS5A may adopt differing conformations. Importantly, infection studies using a human liver chimeric mouse model confirmed robust infection in vivo and ready detection of NLuc activity in serum. We hypothesise that the presence of NS5A in extracellular fluids contributes to HCV pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Radioactivity in the twentieth century and some of its implications for the third millennium

International Nuclear Information System (INIS)

Paschoa, Anselmo S.

1997-01-01

Radioactivity has always been present in the Earth, as well in the Universe at large. However, the discovery of the phenomenon of radioactivity occurred just over 100 years ago. It is well known today that nuclear processes are directly related to the nucleosynthesis in starts. As a matter of fact, all types of nuclear reactions, like fission and captures, occur in stars at different stages of stellar evolution. The sequence of episodes that took place between 1896 and 1898, involving Henry Becquerel, and Marie and Pierre Curie, led to the discover of the phenomena that would greatly influence the twentieth century. It took, however, until 1939 for the phenomenon of fission to be explained by Otto Frish and Lise Meitner, based on experimental results obtained earlier by Otto Hahn and Fritz Strassman. Aware of the potential military implications of fission Leo Szilard exhorted Albert Einstein to write a letter to the President of the United States, Franklin Delano Roosevelt. Such letter is regarded as the initial step of the mammoth Manhattan Project to build the first nuclear weapons. The aftermath of nuclear attacks to Japan, at the end of the Second World War, created dramatic changes in the relations among the nations. The escalation of the nuclear arsenals throughout the world created peculiar and secretive that, by and large, produced wastes of many kinds and a variety of radioactive concentrations which were held by the governments and/or the military industries themselves. The paper will discuss some possible international cooperative efforts to reduce some of the deleterious implications for the third millennium of the inheritance left behind by the military nuclear programs. (author)

Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function ex vivo

DEFF Research Database (Denmark)

Bentzen, Bo Hjorth; Andersen, Rune Wederkinck; Olesen, Søren-Peter

2009-01-01

Pharmacological activation of the large-conductance Ca(2+)-activated K(+) channel (KCa1.1) in the cardiac inner mitochondrial membrane has been found to protect the heart against ischemia reperfusion injuries. However, there are concerns about the selectivity of the pharmacological tools used...... to modulate the channel. Here, we address this issue by synthesising a methylated analogue of the tool KCa1.1 channel activator NS11021. The compound (NS13558) is designed as a structurally closely related and biologically inactive analogue of NS11021. NS13558 did not elicit any significant opening of cloned...... human KCa1.1 channels, but maintained comparable biological activity towards other cardiac ion channels as compared to NS11021. In isolated perfused rat hearts subjected to ischemia-reperfusion, infarct size was reduced from 29% in control to 7% in NS11021 treated hearts. In comparison, the inactive...

Ebselen inhibits hepatitis C virus NS3 helicase binding to nucleic acid and prevents viral replication.

Science.gov (United States)

Mukherjee, Sourav; Weiner, Warren S; Schroeder, Chad E; Simpson, Denise S; Hanson, Alicia M; Sweeney, Noreena L; Marvin, Rachel K; Ndjomou, Jean; Kolli, Rajesh; Isailovic, Dragan; Schoenen, Frank J; Frick, David N

2014-10-17

The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is both a protease, which cleaves viral and host proteins, and a helicase that separates nucleic acid strands, using ATP hydrolysis to fuel the reaction. Many antiviral drugs, and compounds in clinical trials, target the NS3 protease, but few helicase inhibitors that function as antivirals have been reported. This study focuses on the analysis of the mechanism by which ebselen (2-phenyl-1,2-benzisoselenazol-3-one), a compound previously shown to be a HCV antiviral agent, inhibits the NS3 helicase. Ebselen inhibited the abilities of NS3 to unwind nucleic acids, to bind nucleic acids, and to hydrolyze ATP, and about 1 μM ebselen was sufficient to inhibit each of these activities by 50%. However, ebselen had no effect on the activity of the NS3 protease, even at 100 times higher ebselen concentrations. At concentrations below 10 μM, the ability of ebselen to inhibit HCV helicase was reversible, but prolonged incubation of HCV helicase with higher ebselen concentrations led to irreversible inhibition and the formation of covalent adducts between ebselen and all 14 cysteines present in HCV helicase. Ebselen analogues with sulfur replacing the selenium were just as potent HCV helicase inhibitors as ebselen, but the length of the linker between the phenyl and benzisoselenazol rings was critical. Modifications of the phenyl ring also affected compound potency over 30-fold, and ebselen was a far more potent helicase inhibitor than other, structurally unrelated, thiol-modifying agents. Ebselen analogues were also more effective antiviral agents, and they were less toxic to hepatocytes than ebselen. Although the above structure-activity relationship studies suggest that ebselen targets a specific site on NS3, we were unable to confirm binding to either the NS3 ATP binding site or nucleic acid binding cleft by examining the effects of ebselen on NS3 proteins lacking key cysteines.

2D non-separable linear canonical transform (2D-NS-LCT) based cryptography

Science.gov (United States)

Zhao, Liang; Muniraj, Inbarasan; Healy, John J.; Malallah, Ra'ed; Cui, Xiao-Guang; Ryle, James P.; Sheridan, John T.

2017-05-01

The 2D non-separable linear canonical transform (2D-NS-LCT) can describe a variety of paraxial optical systems. Digital algorithms to numerically evaluate the 2D-NS-LCTs are not only important in modeling the light field propagations but also of interest in various signal processing based applications, for instance optical encryption. Therefore, in this paper, for the first time, a 2D-NS-LCT based optical Double-random- Phase-Encryption (DRPE) system is proposed which offers encrypting information in multiple degrees of freedom. Compared with the traditional systems, i.e. (i) Fourier transform (FT); (ii) Fresnel transform (FST); (iii) Fractional Fourier transform (FRT); and (iv) Linear Canonical transform (LCT), based DRPE systems, the proposed system is more secure and robust as it encrypts the data with more degrees of freedom with an augmented key-space.

Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen.

Science.gov (United States)

Alves, Rúbens Prince Dos Santos; Pereira, Lennon Ramos; Fabris, Denicar Lina Nascimento; Salvador, Felipe Scassi; Santos, Robert Andreata; Zanotto, Paolo Marinho de Andrade; Romano, Camila Malta; Amorim, Jaime Henrique; Ferreira, Luís Carlos de Souza

2016-06-01

Dengue fever is caused by any of the four known dengue virus serotypes (DENV1 to DENV4) that affect millions of people worldwide, causing a significant number of deaths. There are vaccines based on chimeric viruses, but they still are not in clinical use. Anti-DENV vaccine strategies based on nonstructural proteins are promising alternatives to those based on whole virus or structural proteins. The DENV nonstructural protein 5 (NS5) is the main target of anti-DENV T cell-based immune responses in humans. In this study, we purified a soluble recombinant form of DENV2 NS5 expressed in Escherichia coli at large amounts and high purity after optimization of expression conditions and purification steps. The purified DENV2 NS5 was recognized by serum from DENV1-, DENV2-, DENV3-, or DENV4-infected patients in an epitope-conformation-dependent manner. In addition, immunization of BALB/c mice with NS5 induced high levels of NS5-specific antibodies and expansion of gamma interferon- and tumor necrosis factor alpha-producing T cells. Moreover, mice immunized with purified NS5 were partially protected from lethal challenges with the DENV2 NGC strain and with a clinical isolate (JHA1). These results indicate that the recombinant NS5 protein preserves immunological determinants of the native protein and is a promising vaccine antigen capable of inducing protective immune responses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Structural insight and flexible features of NS5 proteins from all four serotypes of Dengue virus in solution

Energy Technology Data Exchange (ETDEWEB)

Saw, Wuan Geok; Tria, Giancarlo; Grüber, Ardina; Subramanian Manimekalai, Malathy Sony; Zhao, Yongqian; Chandramohan, Arun; Srinivasan Anand, Ganesh; Matsui, Tsutomu; Weiss, Thomas M.; Vasudevan, Subhash G.; Grüber, Gerhard

2015-10-31

Infection by the four serotypes ofDengue virus(DENV-1 to DENV-4) causes an important arthropod-borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA-dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all fourDengue virusserotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full-length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV-1 to DENV-4 NS5 forms are elongated and flexible in solution, with DENV-4 NS5 being more compact relative to NS5 from DENV-1, DENV-2 and DENV-3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten-residue linker region to the flexibility of the entire NS5. Swapping the ten-residue linker between DENV-4 NS5FL and DENV-3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented.

Analyses of thermodynamic performance for the endoreversible Otto cycle with the concepts of entropy generation and entransy

Institute of Scientific and Technical Information of China (English)

WU; YanQiu

2017-01-01

In this paper,power the the and endoreversible the Otto cycle is analyzed with the entropy generation minimization objectives,and the the entransy theory.of The output power,the heat-work conversion efficiency are taken as the optimization rate,and relationships the output heat-work conversion efficiency,entransy the entropy generation and the entropy generation rate numbers,the work entransy are loss rate,The entransy loss of coefficient,the dissipation rate the entransy variation associated with discussed.applicability entropy the entropy generation minimization and the entransy theory while to the analyses is also analyzed.It is found do that smaller generation rate does not always lead to larger output our power,smaller entropy entransy generation loss numbers and not always lead to larger heat-work conversion efficiency,either.larger the In calculations,power,both larger larger rate larger entransy variation heat-work rate associated with work correspond also to that output while entransy is loss coefficient suitable results the in larger conversion developed efficiency.It is found concept of entransy dissipation not always for analyses because it was for heat transfer.

SPS Injection and Beam Quality for LHC Heavy Ions With 150 ns Kicker Rise Time

CERN Document Server

Goddard, Brennan; Ducimetière, Laurent; Kotzian, Gerd; Uythoven, Jan; Velotti, Francesco

2016-01-01

As part of the LHC Injectors Upgrade project for LHC heavy ions, the SPS injection kicker system rise time needs reduction below its present 225 ns. One technically challenging option under consideration is the addition of fast Pulse Forming Lines in parallel to the existing Pulse Forming Networks for the 12 kicker magnets MKP-S, targeting a system field rise time of 100 ns. An alternative option is to optimise the system to approach the existing individual magnet field rise time (2-98%) of 150 ns. This would still significantly increase the number of colliding bunches in LHC while minimising the cost and effort of the system upgrade. The observed characteristics of the present system are described, compared to the expected system rise time, together with results of simulations and measurements with 175 and 150 ns injection batch spacing. The expected beam quality at injection into LHC is quantified, with the emittance growth and simulated tail population taking into account expected jitter and synchronisatio...

A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

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Mohamed Lamine Hafirassou

2017-12-01

Full Text Available Dengue virus (DENV infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT and oligosaccharyltransferase (OST complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

Dynamic Nucleolar Targeting of Dengue Virus Polymerase NS5 in Response to Extracellular pH

Science.gov (United States)

Fraser, Johanna E.; Rawlinson, Stephen M.; Heaton, Steven M.

2016-01-01

ABSTRACT The nucleolar subcompartment of the nucleus is increasingly recognized as an important target of RNA viruses. Here we document for the first time the ability of dengue virus (DENV) polymerase, nonstructural protein 5 (NS5), to accumulate within the nucleolus of infected cells and to target green fluorescent protein (GFP) to the nucleolus of live transfected cells. Intriguingly, NS5 exchange between the nucleus and nucleolus is dynamically modulated by extracellular pH, responding rapidly and reversibly to pH change, in contrast to GFP alone or other nucleolar and non-nucleolar targeted protein controls. The minimal pH-sensitive nucleolar targeting region (pHNTR), sufficient to target GFP to the nucleolus in a pH-sensitive fashion, was mapped to NS5 residues 1 to 244, with mutation of key hydrophobic residues, Leu-165, Leu-167, and Val-168, abolishing pHNTR function in NS5-transfected cells, and severely attenuating DENV growth in infected cells. This is the first report of a viral protein whose nucleolar targeting ability is rapidly modulated by extracellular stimuli, suggesting that DENV has the ability to detect and respond dynamically to the extracellular environment. IMPORTANCE Infections by dengue virus (DENV) threaten 40% of the world's population yet there is no approved vaccine or antiviral therapeutic to treat infections. Understanding the molecular details that govern effective viral replication is key for the development of novel antiviral strategies. Here, we describe for the first time dynamic trafficking of DENV nonstructural protein 5 (NS5) to the subnuclear compartment, the nucleolus. We demonstrate that NS5's targeting to the nucleolus occurs in response to acidic pH, identify the key amino acid residues within NS5 that are responsible, and demonstrate that their mutation severely impairs production of infectious DENV. Overall, this study identifies a unique subcellular trafficking event and suggests that DENV is able to detect and respond

Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP.

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Caleb C Roth

Full Text Available Nanosecond electrical pulse (nsEP exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure. We hypothesized that by studying the genetic response of the cells following exposure, we would gain direct insight into the stresses experienced by the cell and in turn better understand the biophysical interaction taking place during the exposure. Using Ingenuity Systems software, we found genes associated with cell growth, movement and development to be significantly up-regulated in both cell types 4 h post exposure to nsEP. In agreement with our hypothesis, we also found that both cell lines exhibit significant biological changes consistent with mechanical stress induction. These results advance nsEP research by providing strong evidence that the interaction of nsEPs with cells involves mechanical stress.

Amino acids 16-275 of minute virus of mice NS1 include a domain that specifically binds (ACCA)2-3-containing DNA.

Science.gov (United States)

Mouw, M; Pintel, D J

1998-11-10

GST-NS1 purified from Escherichia coli and insect cells binds double-strand DNA in an (ACCA)2-3-dependent fashion under similar ionic conditions, independent of the presence of anti-NS1 antisera or exogenously supplied ATP and interacts with single-strand DNA and RNA in a sequence-independent manner. An amino-terminal domain (amino acids 1-275) of NS1 [GST-NS1(1-275)], representing 41% of the full-length NS1 molecule, includes a domain that binds double-strand DNA in a sequence-specific manner at levels comparable to full-length GST-NS1, as well as single-strand DNA and RNA in a sequence-independent manner. The deletion of 15 additional amino-terminal amino acids yielded a molecule [GST-NS1(1-275)] that maintained (ACCA)2-3-specific double-strand DNA binding; however, this molecule was more sensitive to increasing ionic conditions than full-length GST-NS1 and GST-NS1(1-275) and could not be demonstrated to bind single-strand nucleic acids. A quantitative filter binding assay showed that E. coli- and baculovirus-expressed GST-NS1 and E. coli GST-NS1(1-275) specifically bound double-strand DNA with similar equilibrium kinetics [as measured by their apparent equilibrium DNA binding constants (KD)], whereas GST-NS1(16-275) bound 4- to 8-fold less well. Copyright 1998 Academic Press.

HCV Core Residues Critical for Infectivity Are Also Involved in Core-NS5A Complex Formation

Science.gov (United States)

Gawlik, Katarzyna; Baugh, James; Chatterji, Udayan; Lim, Precious J.; Bobardt, Michael D.; Gallay, Philippe A.

2014-01-01

Hepatitis C virus (HCV) infection is a major cause of liver disease. The molecular machinery of HCV assembly and particle release remains obscure. A better understanding of the assembly events might reveal new potential antiviral strategies. It was suggested that the nonstructural protein 5A (NS5A), an attractive recent drug target, participates in the production of infectious particles as a result of its interaction with the HCV core protein. However, prior to the present study, the NS5A-binding site in the viral core remained unknown. We found that the D1 domain of core contains the NS5A-binding site with the strongest interacting capacity in the basic P38-K74 cluster. We also demonstrated that the N-terminal basic residues of core at positions 50, 51, 59 and 62 were required for NS5A binding. Analysis of all substitution combinations of R50A, K51A, R59A, and R62A, in the context of the HCVcc system, showed that single, double, triple, and quadruple mutants were fully competent for viral RNA replication, but deficient in secretion of viral particles. Furthermore, we found that the extracellular and intracellular infectivity of all the mutants was abolished, suggesting a defect in the formation of infectious particles. Importantly, we showed that the interaction between the single and quadruple core mutants and NS5A was impaired in cells expressing full-length HCV genome. Interestingly, mutations of the four basic residues of core did not alter the association of core or NS5A with lipid droplets. This study showed for the first time that basic residues in the D1 domain of core that are critical for the formation of infectious extracellular and intracellular particles also play a role in core-NS5A interactions. PMID:24533158

Human Parvovirus B19 NS1 Protein Aggravates Liver Injury in NZB/W F1 Mice

Science.gov (United States)

Tsai, Chun-Chou; Chiu, Chun-Ching; Hsu, Jeng-Dong; Hsu, Huai-Sheng; Tzang, Bor-Show; Hsu, Tsai-Ching

2013-01-01

Human parvovirus B19 (B19) has been associated with a variety of diseases. However, the influence of B19 viral proteins on hepatic injury in SLE is still obscure. To elucidate the effects of B19 viral proteins on livers in SLE, recombinant B19 NS1, VP1u or VP2 proteins were injected subcutaneously into NZB/W F1 mice, respectively. Significant expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected in NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Markedly hepatocyte disarray and lymphocyte infiltration were observed in livers from NZB/WF 1 mice receiving B19 NS1 as compared to those mice receiving PBS. Additionally, significant increases of Tumor Necrosis Factor –α (TNF-α), TNF-α receptor, IκB kinase –α (IKK-α), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB) and nuclear factor-kappa B (NF-κB) were detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Accordingly, significant increases of matrix metalloproteinase-9 (MMP9) and U-plasminogen activator (uPA) were also detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Contrarily, no significant variation on livers from NZB/W F1 mice receiving B19 VP1u or VP2 was observed as compared to those mice receiving PBS. These findings firstly demonstrated the aggravated effects of B19 NS1 but not VP1u or VP2 protein on hepatic injury and provide a clue in understanding the role of B19 NS1 on hepatic injury in SLE. PMID:23555760

Guía del investigador americanista: La Universidad de Tulane en Nueva Orleáns

OpenAIRE

Betancourt, Margarita Vargas

2009-01-01

Introducción La Universidad de Tulane se encuentra en una de las ciudades más interesantes de Estados Unidos, y probablemente, una de las ciudades norteamericanas que más se parece a las ciudades de Latino América: Nueva Orleáns. Copyright © (fotografías de Daniela Castillo y James Huck) Ejemplo de ello es que Nueva Orleáns tiene un centro histórico (el barrio francés) y una plaza o zócalo (Jackson Square). Antes de que Napoleón vendiera Luisiana a Thomas Jefferson en 1803, Nueva Orleáns fue...

Processing quality of NS soybean varieties

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Đorđević Vuk

2012-01-01

Full Text Available Current NS soybean varieties are of satisfactory technological quality, and also significant technological diversity. Varieties Triumf and Venera possess higher oil content. Variety Sava has a balanced oil and protein content, and can be used for obtaining different soy products. Variety Rubin has the highest protein content and is suitable for new high protein products. Estimated processing value is a good parameter to describe the processing quality of soybeans. Based on several years and spatial analysis, it is possible to separate the geographic regions with prevailing favourable conditions for obtaining higher protein or oil content.

A thiophene-modified screen printed electrode for detection of dengue virus NS1 protein.

Science.gov (United States)

Silva, M M S; Dias, A C M S; Cordeiro, M T; Marques, E; Goulart, M O F; Dutra, R F

2014-10-01

A thiophene-modified screen printed electrode (SPE) for detection of the Dengue virus non-structural protein 1 (NS1), an important marker for acute phase diagnosis, is described. A sulfur-containing heterocyclic compound, the thiophene was incorporated to a carbon ink to prepare reproducible screen printed electrodes. After cured, the thiophene SPE was coated by gold nanoparticles conjugated to Protein A to form a nanostrutured surface. The Anti-NS1 antibodies immobilized via their Fc portions via Protein A, leaving their antigen specific sites free circumventing the problem of a random antibodies immobilization. Amperometric responses to the NS1 protein of dengue virus were obtained by cyclic voltammetries performed in presence of ferrocyanide/ferricyanide as redox probe. The calibration curve of immunosensor showed a linear response from 0.04 µg mL(-1) to 0.6 µg mL(-1) of NS1 with a good linear correlation (r=0.991, pink enhanced the electroanalytical properties of the SPEs, increasing their reproducibility and sensitivity. This point-of-care testing represents a great potential for use in epidemic situations, facilitating the early diagnosis in acute phase of dengue virus. Copyright © 2014 Elsevier B.V. All rights reserved.

SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication.

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Maarit Neuvonen

2011-11-01

Full Text Available Among the four non-structural proteins of alphaviruses the function of nsP3 is the least well understood. NsP3 is a component of the viral replication complex, and composed of a conserved aminoterminal macro domain implicated in viral RNA synthesis, and a poorly conserved carboxyterminal region. Despite the lack of overall homology we noted a carboxyterminal proline-rich sequence motif shared by many alphaviral nsP3 proteins, and found it to serve as a preferred target site for the Src-homology 3 (SH3 domains of amphiphysin-1 and -2. Nsp3 proteins of Semliki Forest (SFV, Sindbis (SINV, and Chikungunya viruses all showed avid and SH3-dependent binding to amphiphysins. Upon alphavirus infection the intracellular distribution of amphiphysin was dramatically altered and colocalized with nsP3. Mutations in nsP3 disrupting the amphiphysin SH3 binding motif as well as RNAi-mediated silencing of amphiphysin-2 expression resulted in impaired viral RNA replication in HeLa cells infected with SINV or SFV. Infection of Balb/c mice with SFV carrying an SH3 binding-defective nsP3 was associated with significantly decreased mortality. These data establish SH3 domain-mediated binding of nsP3 with amphiphysin as an important host cell interaction promoting alphavirus replication.

Differential sensitivity of 5'UTR-NS5A recombinants of hepatitis C virus genotypes 1-6 to protease and NS5A inhibitors

DEFF Research Database (Denmark)

Li, Yi-Ping; Ramirez, Santseharay; Humes, Daryl

2014-01-01

BACKGROUND & AIMS: Hepatitis C virus (HCV) therapy will benefit from the preclinical evaluation of direct-acting antiviral (DAA) agents in infectious culture systems that test the effects on different virus genotypes. We developed HCV recombinants comprising the 5' untranslated region-NS5A (5-5A...... daclatasvir. The 1a(TN) 5-5A and JFH1-independent full-length viruses had similar levels of sensitivity to the DAA agents, validating the 5-5A recombinants as surrogates for full-length viruses in DAA testing. Compared with the 1a(TN) full-length virus, the 3a(S52) 5-5A recombinant was highly resistant to all...... protease inhibitors, and the 4a(ED43) recombinant was highly resistant to telaprevir and boceprevir, but most sensitive to other protease inhibitors. Compared with other protease inhibitors, MK-5172 had exceptional potency against all HCV genotypes. The NS5A inhibitor daclatasvir had the highest potency...

The Great Wall: Urca Cooling Layers in the Accreted NS Crust

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Meisel Zach

2018-01-01

Full Text Available Accreting neutron stars host a number of astronomical observables which can be used to infer the properties of the underlying dense matter. These observables are sensitive to the heating and cooling processes taking place in the accreted neutron star (NS crust. Within the past few years it has become apparent that electron-capture/beta-decay (urca cycles can operate within the NS crust at high temperatures. Layers of nuclei undergoing urca cycling can create a thermal barrier, or Great Wall, between heating occurring deep in the crust and the regions above the urca layers. This paper briefly reviews the urca process and the implications for observables from accreting neutron stars.

Multiple Sensing Application on Wireless Sensor Network Simulation using NS3

Science.gov (United States)

Kurniawan, I. F.; Bisma, R.

2018-01-01

Hardware enhancement provides opportunity to install various sensor device on single monitoring node which then enables users to acquire multiple data simultaneously. Constructing multiple sensing application in NS3 is a challenging task since numbers of aspects such as wireless communication, packet transmission pattern, and energy model must be taken into account. Despite of numerous types of monitoring data available, this study only considers two types such as periodic, and event-based data. Periodical data will generate monitoring data follows configured interval, while event-based transmit data when certain determined condition is met. Therefore, this study attempts to cover mentioned aspects in NS3. Several simulations are performed with different number of nodes on arbitrary communication scheme.

Structure-Based Mutational Analysis of the Hepatitis C Virus NS3 Helicase

Science.gov (United States)

Tai, Chun-Ling; Pan, Wen-Ching; Liaw, Shwu-Huey; Yang, Ueng-Cheng; Hwang, Lih-Hwa; Chen, Ding-Shinn

2001-01-01

The carboxyl terminus of the hepatitis C virus (HCV) nonstructural protein 3 (NS3) possesses ATP-dependent RNA helicase activity. Based on the conserved sequence motifs and the crystal structures of the helicase domain, 17 mutants of the HCV NS3 helicase were generated. The ATP hydrolysis, RNA binding, and RNA unwinding activities of the mutant proteins were examined in vitro to determine the functional role of the mutated residues. The data revealed that Lys-210 in the Walker A motif and Asp-290, Glu-291, and His-293 in the Walker B motif were crucial to ATPase activity and that Thr-322 and Thr-324 in motif III and Arg-461 in motif VI significantly influenced ATPase activity. When the pairing between His-293 and Gln-460, referred to as gatekeepers, was replaced with the Asp-293/His-460 pair, which makes the NS3 helicase more like the DEAD helicase subgroup, ATPase activity was not restored. It thus indicated that the whole microenvironment surrounding the gatekeepers, rather than the residues per se, was important to the enzymatic activities. Arg-461 and Trp-501 are important residues for RNA binding, while Val-432 may only play a coadjutant role. The data demonstrated that RNA helicase activity was possibly abolished by the loss of ATPase activity or by reduced RNA binding activity. Nevertheless, a low threshold level of ATPase activity was found sufficient for helicase activity. Results in this study provide a valuable reference for efforts under way to develop anti-HCV therapeutic drugs targeting NS3. PMID:11483774

MADE YOU LOOK: NIQABS, THE MUSLIM CANADIAN CONGRESS, AND R V NS

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Fathima Cader

2013-02-01

Full Text Available R v NS was the first Canadian case to involve a niqab-wearing sexual assault complainant. At the Supreme Court of Canada, the Muslim Canadian Congress [MCC] was especially vocal in arguing it would be un-Canadian to allow NS to testify while wearing a niqab. This paper sets out to investigate the MCC’s depictions of Muslim women, Muslim men, and the mainstream public, with specific attention paid to the details of the MCC’s “clash of civilisations” framing, its impact on the Court’s reasons, and its implications for women combatting sexual violence.   R c NS a été la première cause canadienne où une plaignante, victime d’une agression sexuelle, portait le niqab. Dans ses interventions devant la Cour suprême du Canada, le Congrès musulman canadien [CMC] a souligné avec beaucoup d’insistance qu’il serait anti-canadien de permettre à NS de témoigner en portant son niqab. Le présent article vise à briser les stéréotypes que le CMC a véhiculé dans ses arguments concernant les femmes musulmanes, les hommes musulmans et le grand public, et porte une attention spéciale aux particularités de la conception par le CMC du « choc des civilisations », leur impact sur les motifs de la Cour et leurs conséquences pour les femmes qui luttent contre la violence sexuelle.

Analysis of functional differences between hepatitis C virus NS5A of genotypes 1-7 in infectious cell culture systems

DEFF Research Database (Denmark)

Scheel, Troels K H; Prentoe, Jannick; Carlsen, Thomas H R

2012-01-01

, but ED43(4a) and SA13(5a) also displayed impaired particle assembly. Compared to the original H77C(1a) NS5A recombinant, the changes in LCSII and domain III reduced the amounts of NS5A present. For H77C(1a) and TN(1a) NS5A recombinants, we observed a genetic linkage between NS5A and p7, since introduced...

Lipid droplet-binding protein TIP47 regulates hepatitis C Virus RNA replication through interaction with the viral NS5A protein.

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Dorothee A Vogt

Full Text Available The nonstructural protein NS5A has emerged as a new drug target in antiviral therapies for Hepatitis C Virus (HCV infection. NS5A is critically involved in viral RNA replication that takes place at newly formed membranes within the endoplasmic reticulum (membranous web and assists viral assembly in the close vicinity of lipid droplets (LDs. To identify host proteins that interact with NS5A, we performed a yeast two-hybrid screen with the N-terminus of NS5A (amino acids 1-31, a well-studied α-helical domain important for the membrane tethering of NS5A. Our studies identified the LD-associated host protein, Tail-Interacting Protein 47 (TIP47 as a novel NS5A interaction partner. Coimmunoprecipitation experiments in Huh7 hepatoma cells confirmed the interaction of TIP47 with full-length NS5A. shRNA-mediated knockdown of TIP47 caused a more than 10-fold decrease in the propagation of full-length infectious HCV in Huh7.5 hepatoma cells. A similar reduction was observed when TIP47 was knocked down in cells harboring an autonomously replicating HCV RNA (subgenomic replicon, indicating that TIP47 is required for efficient HCV RNA replication. A single point mutation (W9A in NS5A that disrupts the interaction with TIP47 but preserves proper subcellular localization severely decreased HCV RNA replication. In biochemical membrane flotation assays, TIP47 cofractionated with HCV NS3, NS5A, NS5B proteins, and viral RNA, and together with nonstructural viral proteins was uniquely distributed to lower-density LD-rich membrane fractions in cells actively replicating HCV RNA. Collectively, our data support a model where TIP47--via its interaction with NS5A--serves as a novel cofactor for HCV infection possibly by integrating LD membranes into the membranous web.

Hagedorn Behavior of Little String Theories from string corrections to NS5-branes

DEFF Research Database (Denmark)

Harmark, Troels; Obers, N. A.

2000-01-01

We examine the Hagedorn behavior of little string theory using its conjectured duality with near-horizon NS5-branes. In particular, by studying the string-corrected NS5-brane supergravity solution, it is shown that tree-level corrections to the temperature vanish, while the leading one-loop string...... correction generates the correct temperature dependence of the entropy near the Hagedorn temperature. Finally, the Hagedorn behavior of ODp-brane theories, which are deformed versions of little string theory, is considered via their supergravity duals....

Role of N-S strike-slip faulting in structuring of north-eastern Tunisia; geodynamic implications

Science.gov (United States)

Arfaoui, Aymen; Soumaya, Abdelkader; Ben Ayed, Noureddine; Delvaux, Damien; Ghanmi, Mohamed; Kadri, Ali; Zargouni, Fouad

2017-05-01

Three major compressional events characterized by folding, thrusting and strike-slip faulting occurred in the Eocene, Late Miocene and Quaternary along the NE Tunisian domain between Bou Kornine-Ressas-Msella and Cap Bon Peninsula. During the Plio-Quaternary, the Grombalia and Mornag grabens show a maximum of collapse in parallelism with the NNW-SSE SHmax direction and developed as 3rd order distensives zones within a global compressional regime. Using existing tectonic and geophysical data supplemented by new fault-kinematic observations, we show that Cenozoic deformation of the Mesozoic sedimentary sequences is dominated by first order N-S faults reactivation, this sinistral wrench system is responsible for the formation of strike-slip duplexes, thrusts, folds and grabens. Following our new structural interpretation, the major faults of N-S Axis, Bou Kornine-Ressas-Messella (MRB) and Hammamet-Korbous (HK) form an N-S first order compressive relay within a left lateral strike-slip duplex. The N-S master MRB fault is dominated by contractional imbricate fans, while the parallel HK fault is characterized by a trailing of extensional imbricate fans. The Eocene and Miocene compression phases in the study area caused sinistral strike-slip reactivation of pre-existing N-S faults, reverse reactivation of NE-SW trending faults and normal-oblique reactivation of NW-SE faults, creating a NE-SW to N-S trending system of east-verging folds and overlaps. Existing seismic tomography images suggest a key role for the lithospheric subvertical tear or STEP fault (Slab Transfer Edge Propagator) evidenced below this region on the development of the MRB and the HK relay zone. The presence of extensive syntectonic Pliocene on top of this crustal scale fault may be the result of a recent lithospheric vertical kinematic of this STEP fault, due to the rollback and lateral migration of the Calabrian slab eastward.

Sistema de otto-codificação modificado para endereçamento de redes hidrográficas An improved stream network addressing system: the modified pfafstetter coding scheme

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Natanael dos Santos Silva

2008-10-01

Full Text Available Há, no âmbito do gerenciamento de recursos hídricos, uma carência por sistemas de aplicação global que referenciem, indiquem e identifiquem, de forma única e eficiente, a organização espacial das bacias hidrográficas e respectivas redes de drenagem. Neste trabalho, propôs-se uma modificação no sistema de endereçamento originalmente concebido por Otto Pfafstetter. A nova metodologia utiliza tão-somente as redes de drenagem no formato vetorial e considera, em vez da área das bacias, o comprimento dos seus cursos d'água para codificá-los. Essa estratégia elimina o elevado ônus associado à obtenção de dados de altimetria e à derivação dos respectivos modelos digitais de elevação, imprescindíveis à correta determinação das áreas de contribuição das bacias hidrográficas. Adicionalmente, elimina-se o esforço computacional das operações baseadas em localização espacial, uma vez que agora é possível realizá-las exclusivamente por atributos. Com base nessa metodologia, desenvolveu-se o aplicativo Otto-Sys, utilizando a linguagem de programação AML, nativa do sistema de informações geográficas Arc/INFO workstation. Para exemplificar os resultados da otto-codificação por comprimento dos cursos d'água, apresentou-se um estudo de caso utilizando a rede de drenagem do rio Caeté, afluente do rio Iaco, pertencente à bacia do rio Purus, no Estado do Amazonas. O detalhamento dessa hidrografia vetorial implicou cinco níveis de codificação. Tendo-se codificado toda a rede hidrográfica, qualquer sistema de informações geográficas, mesmo aqueles que não dispõem de recursos específicos para análises e navegação em redes, poderá oferecer serviços de navegação topológica, organização, estruturação, endereçamento e gerenciamento dessas bases de dados. Desse modo, o acesso em tempo real a tais procedimentos poderá ser perfeitamente estendido a qualquer dispositivo capaz de acessar os sistemas web

The 150 ns detector project: Prototype preamplifier results

Science.gov (United States)

Warburton, W. K.; Russell, S. R.; Kleinfelder, Stuart A.

1994-08-01

The long-term goal of the 150 ns detector project is to develop a pixel area detector capable of 6 MHz frame rates (150 ns/frame). Our milestones toward this goal are: a single pixel, 1×256 1D and 8×8 2D detectors, 256×256 2D detectors and, finally, 1024 × 1024 2D detectors. The design strategy is to supply a complete electronics chain (resetting preamp, selectable gain amplifier, analog-to-digital converter (ADC), and memory) for each pixel. In the final detectors these will all be custom integrated circuits. The front-end preamplifiers are integrated first, since their design and performance are the most unusual and also critical to the project's success. Similarly, our early work is concentrated on devising and perfecting detector structures. In this paper we demonstrate the performance of prototypes of our integrated preamplifiers. While the final design will have 64 preamps to a chip, including a switchable gain stage, the prototypes were integrated 8 channels to a "Tiny Chip" and tested in 4 configurations (feedback capacitor Cf equal 2.5 or 4.0 pF, output directly or through a source follower). These devices have been tested thoroughly for reset settling times, gain, linearity, and electronic noise. They generally work as designed, being fast enough to easily integrate detector charge, settle, and reset in 150 ns. Gain and linearity appear to be acceptable. Current values of electronic noise, in double-sampling mode, are about twice the design goal of {2}/{3} of a single photon at 6 keV. We expect this figure to improve with the addition of the onboard amplifier stage and improved packaging. Our next test chip will include these improvements and allow testing with our first detector samples, which will be 1×256 (50 μm wide pixels) and 8×8 (1 mm 2 pixels) element detector on 1 mm thick silicon.

Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors.

Science.gov (United States)

Saleh, Noha A; Elshemey, Wael M

2017-10-15

Hepatitis C Virus (HCV) represents a global health threat not only due to the large number of reported worldwide HCV infections, but also due to the absence of a reliable vaccine for its prevention. HCV NS3 protease is one of the most important targets for drug design aiming at the deactivation of HCV. In the present work, molecular docking simulations are carried out for suggested novel NS3 protease inhibitors applied to the Egyptian genotype 4. These inhibitors are modifications of dimer cellulose by adding a hexa-peptide to the cellulose at one of the positions 2, 3, 6, 2', 3' or 6'. Results show that the inhibitor compound with the hexa-peptide at position 6 shows significantly higher simulation docking score with HCV NS3 protease active site. This is supported by low total energy value of docking system, formation of two H-bonds with HCV NS3 protease active site residues, high binding affinity and increased stability in the interaction system. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of {alpha}7 nicotinic acetylcholine receptor availability in juvenile pig brain with [{sup 18}F]NS10743

Energy Technology Data Exchange (ETDEWEB)

Deuther-Conrad, Winnie; Fischer, Steffen; Hiller, Achim; Funke, Uta; Brust, Peter [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmacy, Leipzig (Germany); Becker, Georg; Sabri, Osama [Univ. of Leipzig, Dept. of Nuclear Medicine, Leipzig (Germany); Cumming, Paul; Xiong, Guoming [Univ. of Munich, Dept. of Nuclear Medicine, Munich (Germany); Peters, Dan [NeuroSearch A/S, Ballerup (Denmark)

2011-08-15

To conduct a quantitative PET assessment of the specific binding sites in the brain of juvenile pigs for [{sup 18}F]NS10743, a novel diazabicyclononane derivative targeting {alpha}7 nicotinic acetylcholine receptors ({alpha}7 nAChRs). Dynamic PET recordings were made in isoflurane-anaesthetized juvenile pigs during 120 min after administration of [{sup 18}F]NS10743 under baseline conditions (n = 3) and after blocking of the {alpha}7 nAChR with NS6740 (3 mg.kg{sup -1} bolus + 1 mg.kg{sup -1}.h{sup -1} continuous infusion; n = 3). Arterial plasma samples were collected for determining the input function of the unmetabolized tracer. Kinetic analysis of regional brain time-radioactivity curves was performed, and parametric maps were calculated relative to arterial input. Plasma [{sup 18}F]NS10743 passed readily into the brain, with peak uptake occurring in {alpha}7 nAChR-expressing brain regions such as the colliculi, thalamus, temporal lobe and hippocampus. The highest SUV{sub max} was approximately 2.3, whereas the lowest uptake was in the olfactory bulb (SUV{sub max} 1.53 {+-} 0.32). Administration of NS6740 significantly decreased [{sup 18}F]NS10743 binding late in the emission recording throughout the brain, except in the olfactory bulb, which was therefore chosen as reference region for calculation of BP{sub ND}. The baseline BP{sub ND} ranged from 0.39 {+-} 0.08 in the cerebellum to 0.76 {+-} 0.07 in the temporal lobe. Pretreatment and constant infusion with NS6740 significantly reduced the BP{sub ND} in regions with high [{sup 18}F]NS10743 binding (temporal lobe -29%, p = 0.01; midbrain: -35%, p = 0.02), without significantly altering the BP{sub ND} in low binding regions (cerebellum: -16%, p = 0.2). This study confirms the potential of [{sup 18}F]NS10743 as a target-specific radiotracer for the molecular imaging of central {alpha}7 nAChRs by PET. (orig.)

Growth behavior of laser-induced damage on fused silica optics under UV, ns laser irradiation.

Science.gov (United States)

Negres, Raluca A; Norton, Mary A; Cross, David A; Carr, Christopher W

2010-09-13

The growth behavior of laser-induced damage sites is affected by a large number of laser parameters as well as site morphology. Here we investigate the effects of pulse duration on the growth rate of damage sites located on the exit surface of fused silica optics. Results demonstrate a significant dependence of the growth parameters on laser pulse duration at 351 nm from 1 ns to 15 ns, including the observation of a dominant exponential versus linear, multiple-shot growth behavior for long and short pulses, respectively. These salient behaviors are tied to the damage morphology and suggest a shift in the fundamental growth mechanisms for pulses in the 1-5 ns range.

Synthesis and evaluation of racemic [11C]NS2456 and its enantiomers as selective serotonin reuptake radiotracers for PET

International Nuclear Information System (INIS)

Smith, D.F.; Bender, D.; Marthi, K.; Cumming, P.; Hansen, S.B.; Peters, D.; Oestergaard Nielsen, E.; Scheel-Krueger, J.; Gjedde, A.

2001-01-01

Positron emission tomography (PET) radiotracers are needed for quantifying serotonin uptake sites in the living brain. Therefore, we evaluated a new selective serotonin reuptake inhibitor, NS2456, to determine whether it is suited for use in PET. Racemic NS2456 [(1RS,5SR)-8-methyl-3-[4-trifluoromethoxyphenyl]-8-azabicyclo [3.2.1]oct-2-ene] and its N-demethylated analog, racemic NS2463, selectively inhibited serotonin uptake in rat brain synaptosomes; their IC 50 values were 3000-fold lower for [ 3 H]serotonin than for either [ 3 H]dopamine or [ 3 H]noradrenaline. The enantiomers of NS2463 were also potent inhibitors of serotonin uptake in vitro, but they failed to show stereoselectivity. Racemic NS2463 as well as its enantiomers were radiolabelled by N-methylation with C-11, yielding [ 11 C]NS2456 for use in PET of the living porcine brain. The compounds crossed the blood-brain barrier rapidly and accumulated preferentially in regions rich in serotonin uptake sites (e.g., brainstem, subthalamus and thalamus). However, their binding potentials were relatively low and no stereoselectivity was found. Thus, neither racemic [ 11 C]NS2456 nor its [ 11 C]-labelled enantiomers are ideal for PET neuroimaging of neuronal serotonin uptake sites

Robust translocation along a molecular monorail: the NS3 helicase from hepatitis C virus traverses unusually large disruptions in its track.

Science.gov (United States)

Beran, Rudolf K F; Bruno, Michael M; Bowers, Heath A; Jankowsky, Eckhard; Pyle, Anna Marie

2006-05-12

The NS3 helicase is essential for replication of the hepatitis C virus. This multifunctional Superfamily 2 helicase protein unwinds nucleic acid duplexes in a stepwise, ATP-dependent manner. Although kinetic features of its mechanism are beginning to emerge, little is known about the physical determinants for NS3 translocation along a strand of nucleic acid. For example, it is not known whether NS3 can traverse covalent or physical discontinuities on the tracking strand. Here we provide evidence that NS3 translocates with a mechanism that is different from its well-studied relative, the Vaccinia helicase NPH-II. Like NPH-II, NS3 translocates along the loading strand (the strand bearing the 3'-overhang) and it fails to unwind substrates that contain nicks, or covalent discontinuities in the loading strand. However, unlike NPH-II, NS3 readily unwinds RNA duplexes that contain long stretches of polyglycol, which are moieties that bear no resemblance to nucleic acid. Whether located on the tracking strand, the top strand, or both, long polyglycol regions fail to disrupt the function of NS3. This suggests that NS3 does not require the continuous formation of specific contacts with the ribose-phosphate backbone as it translocates along an RNA duplex, which is an observation consistent with the large NS3 kinetic step size (18 base-pairs). Rather, once NS3 loads onto a substrate, the helicase can translocate along the loading strand of an RNA duplex like a monorail train following a track. Bumps in the track do not significantly disturb NS3 unwinding, but a break in the track de-rails the helicase.

Conservation of a crystallographic interface suggests a role for β-sheet augmentation in influenza virus NS1 multifunctionality

International Nuclear Information System (INIS)

Kerry, Philip S.; Long, Elizabeth; Taylor, Margaret A.; Russell, Rupert J. M.

2011-01-01

The structure of a monomeric effector domain from influenza A virus NS1 is presented from diffraction data extending to 1.8 Å resolution. Comparison of this and other NS1 effector-domain structures shows conformational changes at a strand–strand packing interface, hinting at a role for β-strand augmentation in NS1 function. The effector domain (ED) of the influenza virus virulence factor NS1 is capable of interaction with a variety of cellular and viral targets, although regulation of these events is poorly understood. Introduction of a W187A mutation into the ED abolishes dimer formation; however, strand–strand interactions between mutant NS1 ED monomers have been observed in two previous crystal forms. A new condition for crystallization of this protein [0.1 M Bis-Tris pH 6.0, 0.2 M NaCl, 22%(w/v) PEG 3350, 20 mM xylitol] was discovered using the hanging-drop vapour-diffusion method. Diffraction data extending to 1.8 Å resolution were collected from a crystal grown in the presence of 40 mM thieno[2,3-b]pyridin-2-ylmethanol. It was observed that there is conservation of the strand–strand interface in crystals of this monomeric NS1 ED in three different space groups. This observation, coupled with conformational changes in the interface region, suggests a potential role for β-sheet augmentation in NS1 function

Estudio e implementación de un sistema Dual para optimizar la combustión de un motor Otto mediante el uso de gas de Brown (HHO)

OpenAIRE

Cujilema Cujilema, José Sebastián; Ramírez Gonzaga, Carlos Manuel

2011-01-01

La implementación de un sistema Dual para optimizar la combustión de un motor Otto surge debido a que existen millones de vehículos a gasolina circulando por el mundo y cada uno de ellos es una fuente de contaminación y consumo. En ciudades grandes la contaminación de estos vehículos presentan altos índices de gases nocivos para la salud y el medio ambiente. Los altos índices de emisiones contaminantes están determinados por algunos factores como la mala calidad del combustible, la falta d...

Rift Valley fever virus NS{sub S} gene expression correlates with a defect in nuclear mRNA export

Energy Technology Data Exchange (ETDEWEB)

Copeland, Anna Maria; Van Deusen, Nicole M.; Schmaljohn, Connie S., E-mail: Connie.s.schmaljohn.civ@mail.mil

2015-12-15

We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NS{sub S} gene, but not the N, G{sub N} or NS{sub M} genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NS{sub S}, confirming that expression of NS{sub S} is likely responsible for this phenomenon. - Highlights: • Rift Valley fever virus (RVFV) infection alters the localization of host mRNA. • mRNA accumulates in the nuclei of RVFV-infected but not mock-infected cells. • NS{sub S} is likely responsible for mRNA relocalization to the nucleus.

Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection.

Science.gov (United States)

Wan, Shu-Wen; Chen, Pei-Wei; Chen, Chin-Yu; Lai, Yen-Chung; Chu, Ya-Ting; Hung, Chia-Yi; Lee, Han; Wu, Hsuan Franziska; Chuang, Yung-Chun; Lin, Jessica; Chang, Chih-Peng; Wang, Shuying; Liu, Ching-Chuan; Ho, Tzong-Shiann; Lin, Chiou-Feng; Lee, Chien-Kuo; Wu-Hsieh, Betty A; Anderson, Robert; Yeh, Trai-Ming; Lin, Yee-Shin

2017-10-15

Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti-DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host-cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Ns-scaled time-gated fluorescence lifetime imaging for forensic document examination

Science.gov (United States)

Zhong, Xin; Wang, Xinwei; Zhou, Yan

2018-01-01

A method of ns-scaled time-gated fluorescence lifetime imaging (TFLI) is proposed to distinguish different fluorescent substances in forensic document examination. Compared with Video Spectral Comparator (VSC) which can examine fluorescence intensity images only, TFLI can detect questioned documents like falsification or alteration. TFLI system can enhance weak signal by accumulation method. The two fluorescence intensity images of the interval delay time tg are acquired by ICCD and fitted into fluorescence lifetime image. The lifetimes of fluorescence substances are represented by different colors, which make it easy to detect the fluorescent substances and the sequence of handwritings. It proves that TFLI is a powerful tool for forensic document examination. Furthermore, the advantages of TFLI system are ns-scaled precision preservation and powerful capture capability.

Thin film removal mechanisms in ns-laser processing of photovoltaic materials

International Nuclear Information System (INIS)

Bovatsek, J.; Tamhankar, A.; Patel, R.S.; Bulgakova, N.M.; Bonse, J.

2010-01-01

The removal of thin films widely used in photovoltaics (amorphous silicon, tin oxide, zinc oxide, aluminum, and molybdenum) is studied experimentally using multi-kHz Q-switched solid-state lasers at 532 nm and 1064 nm wavelengths. The processing ('scribing') is performed through the film-supporting glass plate at scribing speeds of the order of m/s. The dependence of the film removal threshold on the laser pulse duration (8 ns to 40 ns) is investigated and the results are complemented by a multi-layer thermal model used for numerical simulations of the laser-induced spatio-temporal temperature field within the samples. Possible film removal mechanisms are discussed upon consideration of optical, geometrical, thermal and mechanical properties of the layers.

Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E.

Directory of Open Access Journals (Sweden)

Panisadee Avirutnan

2007-11-01

Full Text Available Dengue virus (DENV nonstructural protein-1 (NS1 is a secreted glycoprotein that is absent from viral particles but accumulates in the supernatant and on the plasma membrane of cells during infection. Immune recognition of cell surface NS1 on endothelial cells has been hypothesized as a mechanism for the vascular leakage that occurs during severe DENV infection. However, it has remained unclear how NS1 becomes associated with the plasma membrane, as it contains no membrane-spanning sequence motif. Using flow cytometric and ELISA-based binding assays and mutant cell lines lacking selective glycosaminoglycans, we show that soluble NS1 binds back to the surface of uninfected cells primarily via interactions with heparan sulfate and chondroitin sulfate E. DENV NS1 binds directly to the surface of many types of epithelial and mesenchymal cells yet attaches poorly to most peripheral blood cells. Moreover, DENV NS1 preferentially binds to cultured human microvascular compared to aortic or umbilical cord vein endothelial cells. This binding specificity was confirmed in situ as DENV NS1 bound to lung and liver but not intestine or brain endothelium of mouse tissues. Differential binding of soluble NS1 by tissue endothelium and subsequent recognition by anti-NS1 antibodies could contribute to the selective vascular leakage syndrome that occurs during severe secondary DENV infection.

ns-ms excitation of alkali atoms in the Glauber approximation

International Nuclear Information System (INIS)

Barros, H.G. de P.L. de

1980-05-01

An expression for the scattering amplitude in the Glauber approximation for ns-ms electronic excitation of alkali atoms is obtained. The interaction potential between the incident electron, the core electrons and N-1 protons is approximated by an appropriate spherical potential. (Author) [pt

Folding Proteins at 500 ns/hour with Work Queue.

Science.gov (United States)

Abdul-Wahid, Badi'; Yu, Li; Rajan, Dinesh; Feng, Haoyun; Darve, Eric; Thain, Douglas; Izaguirre, Jesús A

2012-10-01

Molecular modeling is a field that traditionally has large computational costs. Until recently, most simulation techniques relied on long trajectories, which inherently have poor scalability. A new class of methods is proposed that requires only a large number of short calculations, and for which minimal communication between computer nodes is required. We considered one of the more accurate variants called Accelerated Weighted Ensemble Dynamics (AWE) and for which distributed computing can be made efficient. We implemented AWE using the Work Queue framework for task management and applied it to an all atom protein model (Fip35 WW domain). We can run with excellent scalability by simultaneously utilizing heterogeneous resources from multiple computing platforms such as clouds (Amazon EC2, Microsoft Azure), dedicated clusters, grids, on multiple architectures (CPU/GPU, 32/64bit), and in a dynamic environment in which processes are regularly added or removed from the pool. This has allowed us to achieve an aggregate sampling rate of over 500 ns/hour. As a comparison, a single process typically achieves 0.1 ns/hour.

Evaluation of the Tone Fan Noise Design/Prediction System (TFaNS) at the NASA Glenn Research Center

Science.gov (United States)

Koch, L. Danielle

1999-01-01

Version 1.4 of TFaNS, the Tone Fan Noise Design/Prediction System. has recently been evaluated at the NASA Glenn Research Center. Data from tests of the Allison Ultra High Bypass Fan (UHBF) were used to compare to predicted farfield directivities for the radial stator configuration. There was good agreement between measured and predicted directivities at low fan speeds when rotor effects were neglected in the TFaNS calculations. At higher fan speeds, TFaNS is shown to be useful in predicting overall trends rather than absolute sound pressure levels.

The NS1 polypeptide of the murine parvovirus minute virus of mice binds to DNA sequences containing the motif [ACCA]2-3.

Science.gov (United States)

Cotmore, S F; Christensen, J; Nüesch, J P; Tattersall, P

1995-03-01

A DNA fragment containing the minute virus of mice 3' replication origin was specifically coprecipitated in immune complexes containing the virally coded NS1, but not the NS2, polypeptide. Antibodies directed against the amino- or carboxy-terminal regions of NS1 precipitated the NS1-origin complexes, but antibodies directed against NS1 amino acids 284 to 459 blocked complex formation. Using affinity-purified histidine-tagged NS1 preparations, we have shown that the specific protein-DNA interaction is of moderate affinity, being stable in 0.1 M salt but rapidly lost at higher salt concentrations. In contrast, generalized (or nonspecific) DNA binding by NS1 could be demonstrated only in low salt. Addition of ATP or gamma S-ATP enhanced specific DNA binding by wild-type NS1 severalfold, but binding was lost under conditions which favored ATP hydrolysis. NS1 molecules with mutations in a critical lysine residue (amino acid 405) in the consensus ATP-binding site bound to the origin, but this binding could not be enhanced by ATP addition. DNase I protection assays carried out with wild-type NS1 in the presence of gamma S-ATP gave footprints which extended over 43 nucleotides on both DNA strands, from the middle of the origin bubble sequence to a position some 14 bp beyond the nick site. The DNA-binding site for NS1 was mapped to a 22-bp fragment from the middle of the 3' replication origin which contains the sequence ACCAACCA. This conforms to a reiterated motif (ACCA)2-3, which occurs, in more or less degenerate form, at many sites throughout the minute virus of mice genome (J. W. Bodner, Virus Genes 2:167-182, 1989). Insertion of a single copy of the sequence (ACCA)3 was shown to be sufficient to confer NS1 binding on an otherwise unrecognized plasmid fragment. The functions of NS1 in the viral life cycle are reevaluated in the light of this result.

A New Comptonization Model for Weakly Magnetized Accreting NS LMXBs

Science.gov (United States)

Paizis, A.; Farinelli, R.; Titarchuk, L.; Frontera, F.; Cocchi, M.; Ferrigno, C.

2009-05-01

We have developed a new Comptonization model to propose, for the first time, a self consistent physical interpretation of the complex spectral evolution seen in NS LMXBs. The model and its application to LMXBs are presented and compared to the Simbol-X expected capabilities.

Discrepancy between Hepatitis C Virus Genotypes and NS4-Based Serotypes: Association with Their Subgenomic Sequences

Directory of Open Access Journals (Sweden)

Nan Nwe Win

2017-01-01

Full Text Available Determination of hepatitis C virus (HCV genotypes plays an important role in the direct-acting agent era. Discrepancies between HCV genotyping and serotyping assays are occasionally observed. Eighteen samples with discrepant results between genotyping and serotyping methods were analyzed. HCV serotyping and genotyping were based on the HCV nonstructural 4 (NS4 region and 5′-untranslated region (5′-UTR, respectively. HCV core and NS4 regions were chosen to be sequenced and were compared with the genotyping and serotyping results. Deep sequencing was also performed for the corresponding HCV NS4 regions. Seventeen out of 18 discrepant samples could be sequenced by the Sanger method. Both HCV core and NS4 sequences were concordant with that of genotyping in the 5′-UTR in all 17 samples. In cloning analysis of the HCV NS4 region, there were several amino acid variations, but each sequence was much closer to the peptide with the same genotype. Deep sequencing revealed that minor clones with different subgenotypes existed in two of the 17 samples. Genotyping by genome amplification showed high consistency, while several false reactions were detected by serotyping. The deep sequencing method also provides accurate genotyping results and may be useful for analyzing discrepant cases. HCV genotyping should be correctly determined before antiviral treatment.

Development and characterization of serotype-specific monoclonal antibodies against the dengue virus-4 (DENV-4) non-structural protein (NS1).

Science.gov (United States)

Gelanew, Tesfaye; Hunsperger, Elizabeth

2018-02-06

Dengue, caused by one of the four serologically distinct dengue viruses (DENV-1 to - 4), is a mosquito-borne disease of serious global health significance. Reliable and cost-effective diagnostic tests, along with effective vaccines and vector-control strategies, are highly required to reduce dengue morbidity and mortality. Evaluation studies revealed that many commercially available NS1 antigen (Ag) tests have limited sensitivity to DENV-4 serotype compared to the other three serotypes. These studies indicated the need for development of new NS1 Ag detection test with improved sensitivity to DENV-4. An NS1 capture enzyme linked immunoassay (ELISA) specific to DENV-4 may improve the detection of DENV-4 cases worldwide. In addition, a serotype-specific NS1 Ag test identifies both DENV and the infecting serotype. In this study, we used a small-ubiquitin-like modifier (SUMO*) cloning vector to express a SUMO*-DENV-4 rNS1 fusion protein to develop NS1 DENV-4 specific monoclonal antibodies (MAbs). These newly developed MAbs were then optimized for use in an anti-NS1 DENV-4 capture ELISA. The serotype specificity and sensitivity of this ELISA was evaluated using (i) supernatants from DENV (1-4)-infected Vero cell cultures, (ii) rNS1s from all the four DENV (1-4) and, (iii) rNS1s of related flaviviruses (yellow fever virus; YFV and West Nile virus; WNV). From the evaluation studies of the newly developed MAbs, we identified three DENV-4 specific anti-NS1 MAbs: 3H7A9, 8A6F2 and 6D4B10. Two of these MAbs were optimal for use in a DENV-4 serotype-specific NS1 capture ELISA: MAb 8A6F2 as the capture antibody and 6D4B10 as a detection antibody. This ELISA was sensitive and specific to DENV-4 with no cross-reactivity to other three DENV (1-3) serotypes and other heterologous flaviviruses. Taken together these data indicated that our MAbs are useful reagents for the development of DENV-4 immunodiagnostic tests.

Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.

Science.gov (United States)

Mutso, Margit; Morro, Ainhoa Moliner; Smedberg, Cecilia; Kasvandik, Sergo; Aquilimeba, Muriel; Teppor, Mona; Tarve, Liisi; Lulla, Aleksei; Lulla, Valeria; Saul, Sirle; Thaa, Bastian; McInerney, Gerald M; Merits, Andres; Varjak, Margus

2018-04-27

Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir.

Science.gov (United States)

Ng, Teresa I; Krishnan, Preethi; Pilot-Matias, Tami; Kati, Warren; Schnell, Gretja; Beyer, Jill; Reisch, Thomas; Lu, Liangjun; Dekhtyar, Tatyana; Irvin, Michelle; Tripathi, Rakesh; Maring, Clarence; Randolph, John T; Wagner, Rolf; Collins, Christine

2017-05-01

Pibrentasvir (ABT-530) is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with 50% effective concentration (EC 50 ) values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir demonstrated similar activity against a panel of chimeric replicons containing HCV NS5A of genotypes 1 to 6 from clinical samples. Resistance selection studies were conducted using HCV replicon cells with NS5A from genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a, or 6a at a concentration of pibrentasvir that was 10- or 100-fold over its EC 50 for the respective replicon. With pibrentasvir at 10-fold over the respective EC 50 , only a small number of colonies (0.00015 to 0.0065% of input cells) with resistance-associated amino acid substitutions were selected in replicons containing genotype 1a, 2a, or 3a NS5A, and no viable colonies were selected in replicons containing NS5A from other genotypes. With pibrentasvir at 100-fold over the respective EC 50 , very few colonies (0.0002% of input cells) were selected by pibrentasvir in genotype 1a replicon cells while no colonies were selected in other replicons. Pibrentasvir is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that were identified for other NS5A inhibitors, including those at key amino acid positions 28, 30, 31, or 93. The combination of pibrentasvir with HCV inhibitors of other classes produced synergistic inhibition of HCV replication. In summary, pibrentasvir is a next-generation HCV NS5A inhibitor with potent and pan-genotypic activity, and it maintains activity against common amino acid substitutions of HCV genotypes 1 to 6 that are known to confer resistance to currently approved NS5A inhibitors. Copyright © 2017 Ng et al.

Engineered toxins "zymoxins" are activated by the HCV NS3 protease by removal of an inhibitory protein domain.

Directory of Open Access Journals (Sweden)

Assaf Shapira

Full Text Available The synthesis of inactive enzyme precursors, also known as "zymogens," serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV as a model, we designed two HCV NS3 protease-activated "zymogenized" chimeric toxins (which we denote "zymoxins". In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA and Ricin A chain (RTA, respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the "zymoxin" approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected.

Optical and EPR spectra of the thionitrosyl complex [Cr(OH2)5(NS)]2+

DEFF Research Database (Denmark)

Døssing, Anders Rørbæk; Dethlefsen, Johannes Wied

2008-01-01

. The optical data indicate that the NS ligand is a weaker p-acceptor than the NO ligand. The EPR parameters of [Cr(OH2)5(NS)]2+ were determined: giso, g¦ and g-: 1.96515, 1.92686(5) and 1.986860(8); Aiso(53Cr), A¦(53Cr) and A-(53Cr): 25.3´10-4, 38´10-4 and 18.5´10-4cm-1; Aiso(14N), A¦(14N) and A-(14N): 6...

Electronic structures and valence band splittings of transition metals doped GaNs

International Nuclear Information System (INIS)

Lee, Seung-Cheol; Lee, Kwang-Ryeol; Lee, Kyu-Hwan

2007-01-01

For a practical viewpoint, presence of spin splitting of valence band in host semiconductors by the doping of transition metal (TM) ions is an essential property when designing a diluted magnetic semiconductors (DMS) material. The first principle calculations were performed on the electronic and magnetic structure of 3d transition metal doped GaN. V, Cr, and Mn doped GaNs could not be candidates for DMS materials since most of their magnetic moments is concentrated on the TM ions and the splittings of valence band were negligible. In the cases of Fe, Co, Ni, and Cu doped GaNs, on the contrary, long-ranged spin splitting of valence band was found, which could be candidates for DMS materials

Computational study on the inhibitor binding mode and allosteric regulation mechanism in hepatitis C virus NS3/4A protein.

Directory of Open Access Journals (Sweden)

Weiwei Xue

Full Text Available HCV NS3/4A protein is an attractive therapeutic target responsible for harboring serine protease and RNA helicase activities during the viral replication. Small molecules binding at the interface between the protease and helicase domains can stabilize the closed conformation of the protein and thus block the catalytic function of HCV NS3/4A protein via an allosteric regulation mechanism. But the detailed mechanism remains elusive. Here, we aimed to provide some insight into the inhibitor binding mode and allosteric regulation mechanism of HCV NS3/4A protein by using computational methods. Four simulation systems were investigated. They include: apo state of HCV NS3/4A protein, HCV NS3/4A protein in complex with an allosteric inhibitor and the truncated form of the above two systems. The molecular dynamics simulation results indicate HCV NS3/4A protein in complex with the allosteric inhibitor 4VA adopts a closed conformation (inactive state, while the truncated apo protein adopts an open conformation (active state. Further residue interaction network analysis suggests the communication of the domain-domain interface play an important role in the transition from closed to open conformation of HCV NS3/4A protein. However, the inhibitor stabilizes the closed conformation through interaction with several key residues from both the protease and helicase domains, including His57, Asp79, Asp81, Asp168, Met485, Cys525 and Asp527, which blocks the information communication between the functional domains interface. Finally, a dynamic model about the allosteric regulation and conformational changes of HCV NS3/4A protein was proposed and could provide fundamental insights into the allosteric mechanism of HCV NS3/4A protein function regulation and design of new potent inhibitors.

NS5B RNA dependent RNA polymerase inhibitors: the promising approach to treat hepatitis C virus infections.

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Deore, R R; Chern, J-W

2010-01-01

Hepatitis C virus (HCV), a causative agent for non-A and non-B hepatitis, has infected approximately 3% of world's population. The current treatment option of ribavirin in combination with pegylated interferon possesses lower sustained virological response rates, and has serious disadvantages. Unfortunately, no prophylactic vaccine has been approved yet. Therefore, there is an unmet clinical need for more effective and safe anti-HCV drugs. HCV NS5B RNA dependent RNA polymerase is currently pursued as the most popular target to develop safe anti-HCV agents, as it is not expressed in uninfected cells. More than 25 pharmaceutical companies and some research groups have developed ≈50 structurally diverse scaffolds to inhibit NS5B. Here we provide comprehensive account of the drug development process of these scaffolds. NS5B polymerase inhibitors have been broadly classified in nucleoside and non nucleoside inhibitors and are sub classified according to their mechanism of action and structural diversities. With some additional considerations about the inhibitor bound NS5B enzyme X-ray crystal structure information and pharmacological aspects of the inhibitors, this review summarizes the lead identification, structure activity relationship (SAR) studies leading to the most potent NS5B inhibitors with subgenomic replicon activity.

Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus

Directory of Open Access Journals (Sweden)

Margit Mutso

2018-04-01

Full Text Available Infection by Chikungunya virus (CHIKV of the Old World alphaviruses (family Togaviridae in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP (nsP1, nsp2, nsP3 and nsP4 that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

Sn ion energy distributions of ns- and ps-laser produced plasmas

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Bayerle, A.; Deuzeman, M. J.; van der Heijden, S.; Kurilovich, D.; de Faria Pinto, T.; Stodolna, A.; Witte, S.; Eikema, K. S. E.; Ubachs, W.; Hoekstra, R.; Versolato, O. O.

2018-04-01

Ion energy distributions arising from laser-produced plasmas of Sn are measured over a wide laser parameter space. Planar-solid and liquid-droplet targets are exposed to infrared laser pulses with energy densities between 1 J cm‑2 and 4 kJ cm‑2 and durations spanning 0.5 ps to 6 ns. The measured ion energy distributions are compared to two self-similar solutions of a hydrodynamic approach assuming isothermal expansion of the plasma plume into vacuum. For planar and droplet targets exposed to ps-long pulses, we find good agreement between the experimental results and the self-similar solution of a semi-infinite simple planar plasma configuration with an exponential density profile. The ion energy distributions resulting from solid Sn exposed to ns-pulses agrees with solutions of a limited-mass model that assumes a Gaussian-shaped initial density profile.

Nanosecond pulsed electric field (nsPEF) disrupts the structure and metabolism of human Echinococcus granulosus protoscolex in vitro with a dose effect.

Science.gov (United States)

Zhang, Ruiqing; Aji, Tuerganaili; Shao, Yingmei; Jiang, Tiemin; Yang, Lei; Lv, Weimin; Chen, Yonggang; Chen, Xinhua; Wen, Hao

2017-04-01

The number of interventional treatments for hepatic cystic echinococcosis is increasing, but the chemicals or high temperatures used in these methodologies cause biliary complications, thus limiting their clinical applications. This experimental study aimed to apply a novel, non-thermal, non-chemical ablation method termed nanosecond pulsed electric field (nsPEF) for the treatment of human hepatic cystic echinococcosis. The nsPEF treatment parameters against protoscolices from human hepatic cystic echinococcosis were optimized in vitro. The efficacy and mechanism of nsPEF treatment were also investigated. Fresh protoscolices were isolated from human hepatic cystic echinococcosis and were exposed to 300 ns of nsPEF with different field strengths (0, 7, 14, 21, and 29 kV/cm) and pulse numbers (50 and 100 pulses). Then, the viability of the nsPEF-treated protoscolices was evaluated in vitro. Morphological and ultra-structural changes were visualized with H&E staining and scanning electron microscopy. The membrane enzyme activity of alkaline phosphatase (AP) and gamma-glutamyl-transpeptidase (GGT) was measured. nsPEF caused dose-dependent protoscolex death. One-hundred pulses of nsPEF at 21 kV/cm or higher caused a significant increase in the death rate of protoscolices. nsPEF induced significant lethal damage with 50 pulses at 21 or 29 kV/cm and with 100 pulses at 14, 21, or 29 kV/cm, accompanied by morphological destruction and increased levels of AP and GGT membrane enzymes. Thus, nsPEF induced dose-dependent protoscolex mortality and caused destruction of protoscolices and increased membrane enzymes. The mechanism may involve direct damage to the membrane structures of the protoscolices, promoting enzyme exhaustion and disruption of metabolism.

Radiometric calibration of the reflective bands of NS001-Thematic Mapper Simulator (TMS) and modular multispectral radiometers (MMR)

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Markham, Brian L.; Wood, Frank M., Jr.; Ahmad, Suraiya P.

1988-01-01

The NS001 Thematic Mapper Simulator scanner (TMS) and several modular multispectral radiometers (MMRs) are among the primary instruments used in the First ISLSCP (International Satellite Land Surface Climatology Project) Field Experiment (FIFE). The NS001 has a continuously variable gain setting. Calibration of the NS001 data is influenced by drift in the dark current level of up to six counts during a mirror scan at typical gain settings. The MMR instruments are being used in their 1 deg FOV configuration on the helicopter and 15 deg FOV on the ground.

Baseline NS5A resistance associated substitutions may impair DAA response in real-world hepatitis C patients.

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Carrasco, Itzíar; Arias, Ana; Benítez-Gutiérrez, Laura; Lledó, Gemma; Requena, Silvia; Cuesta, Miriam; Cuervas-Mons, Valentín; de Mendoza, Carmen

2018-03-01

Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance-associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real-life setting. All hepatitis C patients treated with DAA including NS5A inhibitors at our institution were retrospectively examined. The virus NS5A gene was analyzed using population sequencing at baseline and after 24 weeks of completing therapy in all patients that failed. All changes recorded at positions 28, 29, 30, 31, 32, 58, 62, 92, and 93 were considered. A total of 166 patients were analyzed. HCV genotypes were as follows: G1a (31.9%), G1b (48.2%), G3 (10.2%), and G4 (9.6%). Overall, 69 (41.6%) patients were coinfected with HIV and 46.7% had advanced liver fibrosis (Metavir F3-F4). Sixty (36.1%) patients had at least one RAS at baseline, including M28A/G/T (5), Q30X (12), L31I/F/M/V (6), T58P/S (25), Q/E62D (1), A92 K (7), and Y93C/H (15). Overall, 4.8% had two or more RAS, being more frequent in G4 (12.5%) followed by G1b (6.3%) and G1a (1.9%). Of 10 (6%) patients that failed DAA therapy, five had baseline NS5A RAS. No association was found for specific baseline RAS, although changes at position 30 were more frequent in failures than cures (22.2% vs 6.4%, P = 0.074). Moreover, the presence of two or more RAS at baseline was more frequent in failures (HR: 7.2; P = 0.029). Upon failure, six patients showed emerging RAS, including Q30C/H/R (3), L31M (1), and Y93C/H (2). Baseline NS5A RAS are frequently seen in DAA-naïve HCV patients. Two or more baseline NS5A RAS were found in nearly 5% and were significantly associated to DAA failure. Therefore, baseline NS5A testing should be considered when HCV treatment is planned with NS5A inhibitors. © 2017 Wiley Periodicals, Inc.

Evaluating vacquinol-1 in rats carrying glioblastoma models RG2 and NS1.

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Ahlstedt, Jonatan; Förnvik, Karolina; Zolfaghari, Shaian; Kwak, Dongoh; Hammarström, Lars G J; Ernfors, Patrik; Salford, Leif G; Redebrandt, Henrietta Nittby

2018-02-02

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells in vitro . Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival. No survival advantage or effect on tumor size was seen in animals carrying the NS1 models compared to untreated controls. Furthermore, immunological staining of FOXP3, CD4 and CD8 showed no marked difference in immune cell infiltrate in tumor environment following treatment. Taken together, a survival advantage of VQ-1 treatment alone could not be demonstrated here, even though some effect upon tumor size was seen. Staining for immune cell markers did not indicate that VQ-1 either reduced or increased host anti-tumor immune response.

Outbreak tracking of Aleutian mink disease virus (AMDV) using partial NS1 gene sequencing

DEFF Research Database (Denmark)

Ryt-Hansen, Pia; Hjulsager, Charlotte Kristiane; Hagberg, E. E.

2017-01-01

. However, in 2015, several outbreaks of AMDV occurred at mink farms throughout Denmark, and the sources of these outbreaks were not known. Partial NS1 gene sequencing, phylogenetic analyses data were utilized along with epidemiological to determine the origin of the outbreaks. The phylogenetic analyses...... not be excluded. This study confirmed that partial NS1 sequencing can be used in outbreak tracking to determine major viral clusters of AMDV. Using this method, two new distinct AMDV clusters with low intra-cluster sequence diversity were identified, and epidemiological data helped to reveal possible ways...

[Determination of drug resistance mutations of NS3 inhibitors in chronic hepatitis C patients infected with genotype 1].

Science.gov (United States)

Şanlıdağ, Tamer; Sayan, Murat; Akçalı, Sinem; Kasap, Elmas; Buran, Tahir; Arıkan, Ayşe

2017-04-01

Direct-acting antiviral agents (DAA) such as NS3 protease inhibitors is the first class of drugs used for chronic hepatitis C (CHC) treatment. NS3 inhibitors (PI) with low genetic barrier have been approved to be used in the CHC genotype 1 infections, and in the treatment of compensated liver disease including cirrhosis together with pegile interferon and ribavirin. Consequently, the development of drug resistance during DAA treatment of CHC is a major problem. NS3 resistant variants can be detected before treatment as they can occurnaturally. The aim of this study was to investigate new and old generation NS3 inhibitors resistance mutations before DAA treatment in hepatitis C virus (HCV) that were isolated from CHC. The present study was conducted in 2015 and included 97 naive DAA patients infected with HCV genotype 1, who were diagnosed in Manisa and Kocaeli cities of Turkey. Magnetic particle based HCV RNA extraction and than RNA detection and quantification were performed using commercial real-time PCR assay QIASypmhony + Rotorgene Q/ArtusHCV QS-RGQ and COBAS Ampliprep/COBAS TaqMan HCV Tests. HCV NS3 viral protease genome region was amplified with PCR and mutation analysis was performed by Sanger dideoxy sequencing technique of NS3 protease codons (codon 32-185). HCV NS3 protease inhibitors; asunaprevir, boceprevir, faldaprevir, grazoprevir, pariteprevir, simeprevir and telaprevir were analysed for resistant mutations by Geno2pheno-HCV resistance tool. HCV was genotyped in all patients and 88 patients (n= 88/97, 91%) had genotype 1. Eight (n= 8/97, 8.2%) and 80 (n= 80/97, 82.4%) HCC patients were subgenotyped as 1a and 1b, respectively. Many aminoacid substitutions and resistance mutations were determined in 39/88 (44%) patients in the study group. Q80L, S122C/N, S138W were defined as potential substitutions (6/88 patients; 7%); R109K, R117C, S122G, I132V, I170V, N174S were described as potential resistance (34/88 patients; 39%); V36L, T54S, V55A, Q80H were

Phosphorylation states of cell cycle and DNA repair proteins can be altered by the nsSNPs

International Nuclear Information System (INIS)

Savas, Sevtap; Ozcelik, Hilmi

2005-01-01

Phosphorylation is a reversible post-translational modification that affects the intrinsic properties of proteins, such as structure and function. Non-synonymous single nucleotide polymorphisms (nsSNPs) result in the substitution of the encoded amino acids and thus are likely to alter the phosphorylation motifs in the proteins. In this study, we used the web-based NetPhos tool to predict candidate nsSNPs that either introduce or remove putative phosphorylation sites in proteins that act in DNA repair and cell cycle pathways. Our results demonstrated that a total of 15 nsSNPs (16.9%) were likely to alter the putative phosphorylation patterns of 14 proteins. Three of these SNPs (CDKN1A-S31R, OGG1-S326C, and XRCC3-T241M) have already found to be associated with altered cancer risk. We believe that this set of nsSNPs constitutes an excellent resource for further molecular and genetic analyses. The novel systematic approach used in this study will accelerate the understanding of how naturally occurring human SNPs may alter protein function through the modification of phosphorylation mechanisms and contribute to disease susceptibility

Green fluorescent protein (GFP color reporter gene visualizes parvovirus B19 non-structural segment 1 (NS1 transfected endothelial modification.

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Thomas Wurster

Full Text Available BACKGROUND: Human Parvovirus B19 (PVB19 has been associated with myocarditis putative due to endothelial infection. Whether PVB19 infects endothelial cells and causes a modification of endothelial function and inflammation and, thus, disturbance of microcirculation has not been elucidated and could not be visualized so far. METHODS AND FINDINGS: To examine the PVB19-induced endothelial modification, we used green fluorescent protein (GFP color reporter gene in the non-structural segment 1 (NS1 of PVB19. NS1-GFP-PVB19 or GFP plasmid as control were transfected in an endothelial-like cell line (ECV304. The endothelial surface expression of intercellular-adhesion molecule-1 (CD54/ICAM-1 and extracellular matrix metalloproteinase inducer (EMMPRIN/CD147 were evaluated by flow cytometry after NS-1-GFP or control-GFP transfection. To evaluate platelet adhesion on NS-1 transfected ECs, we performed a dynamic adhesion assay (flow chamber. NS-1 transfection causes endothelial activation and enhanced expression of ICAM-1 (CD54: mean ± standard deviation: NS1-GFP vs. control-GFP: 85.3 ± 11.2 vs. 61.6 ± 8.1; P<0.05 and induces endothelial expression of EMMPRIN/CD147 (CD147: mean ± SEM: NS1-GFP vs. control-GFP: 114 ± 15.3 vs. 80 ± 0.91; P<0.05 compared to control-GFP transfected cells. Dynamic adhesion assays showed that adhesion of platelets is significantly enhanced on NS1 transfected ECs when compared to control-GFP (P<0.05. The transfection of ECs was verified simultaneously through flow cytometry, immunofluorescence microscopy and polymerase chain reaction (PCR analysis. CONCLUSIONS: GFP color reporter gene shows transfection of ECs and may help to visualize NS1-PVB19 induced endothelial activation and platelet adhesion as well as an enhanced monocyte adhesion directly, providing in vitro evidence of possible microcirculatory dysfunction in PVB19-induced myocarditis and, thus, myocardial tissue damage.

Molecular imaging of {alpha}7 nicotinic acetylcholine receptors: design and evaluation of the potent radioligand [{sup 18}F]NS10743

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Deuther-Conrad, Winnie; Fischer, Steffen; Hiller, Achim; Brust, Peter [Institute of Interdisciplinary Isotope Research, Leipzig (Germany); Oestergaard Nielsen, Elsebet; Brunicardi Timmermann, Daniel; Peters, Dan [NeuroSearch A/S, Ballerup (Denmark); Steinbach, Joerg [Institute of Interdisciplinary Isotope Research, Leipzig (Germany); Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, Dresden (Germany); Sabri, Osama [Universitaet Leipzig, Department of Nuclear Medicine, Leipzig (Germany)

2009-05-15

The outstanding diversity of cellular properties mediated by neuronal and nonneuronal {alpha}7 nicotinic acetylcholine receptors ({alpha}7 nAChR) points to the diagnostic potential of quantitative nuclear molecular imaging of {alpha}7 nAChR in neurology and oncology. It was our goal to radiolabel the {alpha}7 nAChR agonist 4-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane (NS10743) and to assess the selectivity of [{sup 18}F]NS10743 binding site occupancy in animal experiments. [{sup 18}F]NS10743 was synthesized by nucleophilic substitution of the nitro precursor. In vitro receptor affinity and selectivity were assessed by radioligand competition and autoradiography. The radiotracer properties were evaluated in female CD-1 mice by brain autoradiography and organ distribution. Target specificity was validated after treatment with SSR180711 (10 mg/kg, intraperitoneal), and metabolic stability was investigated using radio-HPLC. The specific activity of [{sup 18}F]NS10743 exceeded 150 GBq/{mu}mol at a radiochemical purity >99%. In vitro, NS10743 and [{sup 18}F]NS10743 showed high affinity and specificity towards {alpha}7 nAChR. The brain permeation of [{sup 18}F]NS10743 was fast and sufficient with values of 4.83 and 1.60% injected dose per gram and brain to plasma ratios of 3.83 and 2.05 at 5 and 60 min after radiotracer administration. Brain autoradiography and organ distribution showed target-specific accumulation of [{sup 18}F]NS10743 in brain substructures and various {alpha}7 nAChR-expressing organs. The radiotracer showed a high metabolic stability in vivo with a single polar radiometabolite, which did not cross the blood-brain barrier. The good in vitro and in vivo features of [{sup 18}F]NS10743 make this radioligand a promising candidate for quantitative in vivo imaging of {alpha}7 nAChR expression and encourage further investigations. (orig.)

Efficacy of NS5A Inhibitors Against Hepatitis C Virus Genotypes 1–7 and Escape Variants

DEFF Research Database (Denmark)

Gottwein, Judith M.; Pham, Long V.; Mikkelsen, Lotte S.

2018-01-01

, or that contained RAS previously reported from patients. Results: NS5A inhibitors had varying levels of efficacy against original and resistant viruses. Only velpatasvir and pibrentasvir had uniform high activity against all HCV genotypes tested. RAS hotspots in NS5A were found at amino acids 28, 30, 31, and 93...

Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation

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Eyre, Nicholas S., E-mail: nicholas.eyre@adelaide.edu.au [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Hampton-Smith, Rachel J.; Aloia, Amanda L. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Eddes, James S. [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Simpson, Kaylene J. [Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, East Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville (Australia); Hoffmann, Peter [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide (Australia); Beard, Michael R. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia)

2016-04-15

Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced membrane rearrangements while EM using ‘APEX2’-tagged viruses demonstrated S235D-mediated enrichment of NS5A in irregular membranous foci. Finally, using a customized siRNA screen of candidate NS5A kinases and subsequent analysis using a phospho-specific antibody, we show that phosphatidylinositol-4 kinase III alpha (PI4KIIIα) is important for Ser-235 phosphorylation. We conclude that Ser-235 phosphorylation of NS5A is essential for HCV RNA replication and normal replication complex formation and is regulated by PI4KIIIα. - Highlights: • NS5A residues Ser-222, Ser-235 and Thr-348 are phosphorylated during HCV infection. • Phosphorylation of Ser-235 is essential to HCV RNA replication. • Mutation of Ser-235 alters replication compartment localization and morphology. • Phosphatidylinositol-4 kinase III alpha is important for Ser-235 phosphorylation.

Dimerization site 2 of the bacterial DNA-binding protein H-NS is required for gene silencing and stiffened nucleoprotein filament formation.

Science.gov (United States)

Yamanaka, Yuki; Winardhi, Ricksen S; Yamauchi, Erika; Nishiyama, So-Ichiro; Sowa, Yoshiyuki; Yan, Jie; Kawagishi, Ikuro; Ishihama, Akira; Yamamoto, Kaneyoshi

2018-06-15

The bacterial nucleoid-associated protein H-NS is a DNA-binding protein, playing a major role in gene regulation. To regulate transcription, H-NS silences genes, including horizontally acquired foreign genes. Escherichia coli H-NS is 137 residues long and consists of two discrete and independent structural domains: an N-terminal oligomerization domain and a C-terminal DNA-binding domain, joined by a flexible linker. The N-terminal oligomerization domain is composed of two dimerization sites, dimerization sites 1 and 2, which are both required for H-NS oligomerization, but the exact role of dimerization site 2 in gene silencing is unclear. To this end, we constructed a whole set of single amino acid substitution variants spanning residues 2 to 137. Using a well-characterized H-NS target, the slp promoter of the glutamic acid-dependent acid resistance (GAD) cluster promoters, we screened for any variants defective in gene silencing. Focusing on the function of dimerization site 2, we analyzed four variants, I70C/I70A and L75C/L75A, which all could actively bind DNA but are defective in gene silencing. Atomic force microscopy analysis of DNA-H-NS complexes revealed that all of these four variants formed condensed complexes on DNA, whereas WT H-NS formed rigid and extended nucleoprotein filaments, a conformation required for gene silencing. Single-molecule stretching experiments confirmed that the four variants had lost the ability to form stiffened filaments. We conclude that dimerization site 2 of H-NS plays a key role in the formation of rigid H-NS nucleoprotein filament structures required for gene silencing. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

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Lalime, Erin N.; Pekosz, Andrew, E-mail: apekosz@jhsph.edu

2014-06-15

The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate that the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization. - Highlights: • Mutations were introduced into influenza NS1 NLS1. • NS1 R37A, R38A, K41A viruses had minimal changes in replication and NS1 localization. • Viruses from NS1 R35A rescue all contained additional mutations at D39. • NS1 R35A D39X mutations recover dimerization lost in NS1 R35A mutations. • These results reaffirm the importance of dimerization for NS1 protein function.

The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

International Nuclear Information System (INIS)

Lalime, Erin N.; Pekosz, Andrew

2014-01-01

The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate that the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization. - Highlights: • Mutations were introduced into influenza NS1 NLS1. • NS1 R37A, R38A, K41A viruses had minimal changes in replication and NS1 localization. • Viruses from NS1 R35A rescue all contained additional mutations at D39. • NS1 R35A D39X mutations recover dimerization lost in NS1 R35A mutations. • These results reaffirm the importance of dimerization for NS1 protein function

Engineered Toxins “Zymoxins” Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain

Science.gov (United States)

Shapira, Assaf; Gal-Tanamy, Meital; Nahary, Limor; Litvak-Greenfeld, Dana; Zemel, Romy; Tur-Kaspa, Ran; Benhar, Itai

2011-01-01

The synthesis of inactive enzyme precursors, also known as “zymogens,” serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated “zymogenized” chimeric toxins (which we denote “zymoxins”). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the “zymoxin” approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected. PMID:21264238

A crystal structure of the Dengue virus NS5 protein reveals a novel inter-domain interface essential for protein flexibility and virus replication.

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Yongqian Zhao

2015-03-01

Full Text Available Flavivirus RNA replication occurs within a replication complex (RC that assembles on ER membranes and comprises both non-structural (NS viral proteins and host cofactors. As the largest protein component within the flavivirus RC, NS5 plays key enzymatic roles through its N-terminal methyltransferase (MTase and C-terminal RNA-dependent-RNA polymerase (RdRp domains, and constitutes a major target for antivirals. We determined a crystal structure of the full-length NS5 protein from Dengue virus serotype 3 (DENV3 at a resolution of 2.3 Å in the presence of bound SAH and GTP. Although the overall molecular shape of NS5 from DENV3 resembles that of NS5 from Japanese Encephalitis Virus (JEV, the relative orientation between the MTase and RdRp domains differs between the two structures, providing direct evidence for the existence of a set of discrete stable molecular conformations that may be required for its function. While the inter-domain region is mostly disordered in NS5 from JEV, the NS5 structure from DENV3 reveals a well-ordered linker region comprising a short 310 helix that may act as a swivel. Solution Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS analysis reveals an increased mobility of the thumb subdomain of RdRp in the context of the full length NS5 protein which correlates well with the analysis of the crystallographic temperature factors. Site-directed mutagenesis targeting the mostly polar interface between the MTase and RdRp domains identified several evolutionarily conserved residues that are important for viral replication, suggesting that inter-domain cross-talk in NS5 regulates virus replication. Collectively, a picture for the molecular origin of NS5 flexibility is emerging with profound implications for flavivirus replication and for the development of therapeutics targeting NS5.

A system to measure isomeric state half-lives in the 10 ns to 10 μs range

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Toufen, D. L., E-mail: dennis@if.usp.br [Institute of Physics, University of São Paulo, C.P. 66318, 05315-970 São Paulo, São Paulo (Brazil); Federal Institute of Education, Science and Technology of São Paulo - IFSP, 07115-000 Guarulhos, São Paulo (Brazil); Allegro, P. R. P.; Medina, N. H.; Oliveira, J. R. B.; Cybulska, E. W.; Seale, W. A.; Ribas, R. V. [Institute of Physics, University of São Paulo, C.P. 66318, 05315-970 São Paulo, São Paulo (Brazil); Linares, R. [Fluminense Federal University, 24220-900 Niterói, Rio de Janeiro (Brazil); Silveira, M. A. G. [Universitary Center of FEI, 09850-901 São Bernardo do Campo, São Paulo (Brazil)

2014-07-15

The Isomeric State Measurement System (SISMEI) was developed to search for isomeric nuclear states produced by fusion-evaporation reactions. The SISMEI consists of 10 plastic phoswich telescopes, two lead shields, one NaI(Tl) scintillation detector, two Compton suppressed HPGe γ-ray detectors, and a cone with a recoil product catcher. The new system was tested at the 8 UD Pelletron tandem accelerator of the University of São Paulo with the measurement of two known isomeric states: {sup 54}Fe, 10{sup +} state (E = 6527.1 (11) keV, T{sub 1/2} = 364(7) ns) and the 5/2{sup +} state of {sup 19}F (E = 197.143 (4) keV, T{sub 1/2} = 89.3 (10) ns). The results indicate that the system is capable of identifying delayed transitions, of measuring isomeric state lifetimes, and of identifying the feeding transitions of the isomeric state through the delayed γ-γ coincidence method. The measured half-life for the 10{sup +} state was T{sub 1/2} = 365(14) ns and for the 5/2{sup +} state, 100(36) ns.

A system to measure isomeric state half-lives in the 10 ns to 10 μs range

Science.gov (United States)

Toufen, D. L.; Allegro, P. R. P.; Medina, N. H.; Oliveira, J. R. B.; Cybulska, E. W.; Seale, W. A.; Linares, R.; Silveira, M. A. G.; Ribas, R. V.

2014-07-01

The Isomeric State Measurement System (SISMEI) was developed to search for isomeric nuclear states produced by fusion-evaporation reactions. The SISMEI consists of 10 plastic phoswich telescopes, two lead shields, one NaI(Tl) scintillation detector, two Compton suppressed HPGe γ-ray detectors, and a cone with a recoil product catcher. The new system was tested at the 8 UD Pelletron tandem accelerator of the University of São Paulo with the measurement of two known isomeric states: 54Fe, 10+ state (E = 6527.1 (11) keV, T1/2 = 364(7) ns) and the 5/2+ state of 19F (E = 197.143 (4) keV, T1/2 = 89.3 (10) ns). The results indicate that the system is capable of identifying delayed transitions, of measuring isomeric state lifetimes, and of identifying the feeding transitions of the isomeric state through the delayed γ-γ coincidence method. The measured half-life for the 10+ state was T1/2 = 365(14) ns and for the 5/2+ state, 100(36) ns.

2′-O Methylation of Internal Adenosine by Flavivirus NS5 Methyltransferase

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Dong, Hongping; Chang, David C.; Hua, Maggie Ho Chia; Lim, Siew Pheng; Chionh, Yok Hian; Hia, Fabian; Lee, Yie Hou; Kukkaro, Petra; Lok, Shee-Mei; Dedon, Peter C.; Shi, Pei-Yong

2012-01-01

RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 2′-O methyltransferase activities that are required for the formation of 5′ type I cap (m7GpppAm) of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and Dengue virus (serotype 4; DENV-4) specifically methylates polyA, but not polyG, polyC, or polyU, indicating that the methylation occurs at adenosine residue. RNAs with internal adenosines substituted with 2′-O-methyladenosines are not active substrates for internal methylation, whereas RNAs with adenosines substituted with N6-methyladenosines can be efficiently methylated, suggesting that the internal methylation occurs at the 2′-OH position of adenosine. Mass spectroscopic analysis further demonstrated that the internal methylation product is 2′-O-methyladenosine. Importantly, genomic RNA purified from DENV virion contains 2′-O-methyladenosine. The 2′-O methylation of internal adenosine does not require specific RNA sequence since recombinant methyltransferase of DENV-4 can efficiently methylate RNAs spanning different regions of viral genome, host ribosomal RNAs, and polyA. Structure-based mutagenesis results indicate that K61-D146-K181-E217 tetrad of DENV-4 methyltransferase forms the active site of internal methylation activity; in addition, distinct residues within the methyl donor (S-adenosyl-L-methionine) pocket, GTP pocket, and RNA-binding site are critical for the internal methylation activity. Functional analysis using flavivirus replicon and genome-length RNAs showed that internal methylation attenuated viral RNA translation and replication. Polymerase assay revealed that internal 2′-O-methyladenosine reduces the efficiency of RNA elongation. Collectively, our results demonstrate that flavivirus NS5 performs 2′-O methylation of internal adenosine of

Polarization mechanism in a ns laser-induced plasma spectroscopy of Al alloy

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Aghababaei Nejad, Mahboobeh; Soltanolkotabi, Mahmood; Eslami Majd, Abdollah

2018-01-01

Polarization emission from aluminum alloy by ns laser-induced breakdown spectroscopy (LIBS) is carefully investigated in air using a non-gated CCD camera at integration time of 100 ms. First, the analysis reveals that the small polarization degree is the same for both continuum and discrete line emission spectra which also increases slowly with wavelength growth; second, laser fluence in the range of 347.81-550.10 J/cm2 has no significant changes in plasma polarization; and third, larger polarization in comparison with polarization introduced by preferential reflection of emission from the target surface (Fresnel reflectivity) is observed. The residual fluctuations of the anisotropic recombining plasma and the dynamic polarization of an ion's core are suggested as the possible main sources for observed polarized radiation in ns-LIBS.

Molecular Dynamics of the ZIKA Virus NS3 Helicase

Science.gov (United States)

Raubenolt, Bryan; Rick, Steven; The Rick Group Team

The recent outbreaks of the ZIKA virus (ZIKV) and its connection to microcephaly in newborns has raised its awareness as a global threat and many scientific research efforts are currently underway in attempt to create a vaccine. Molecular Dynamics is a powerful method of investigating the physical behavior of protein complexes. ZIKV is comprised of 3 structural and 7 nonstructural proteins. The NS3 helicase protein appears to play a significant role in the replication complex and its inhibition could be a crucial source of antiviral drug design. This research primarily focuses on studying the structural dynamics, over the course of few hundred nanoseconds, of NS3 helicase in the free state, as well as in complex form with human ssRNA, ATP, and an analogue of GTP. RMSD and RMSF plots of each simulation will provide details on the forces involved in the overall stability of the active and inactive states. Furthermore, free energy calculations on a per residue level will reveal the most interactive residues between states and ultimately the primary driving force behind these interactions. Together these analyses will provide highly relevant information on the binding surface chemistry and thus serve as the basis for potential drug design.

Identification and Biochemical Characterization of Halisulfate 3 and Suvanine as Novel Inhibitors of Hepatitis C Virus NS3 Helicase from a Marine Sponge

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Atsushi Furuta

2014-01-01

Full Text Available Hepatitis C virus (HCV is an important etiological agent that is responsible for the development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV nonstructural protein 3 (NS3 helicase is a possible target for novel drug development due to its essential role in viral replication. In this study, we identified halisulfate 3 (hal3 and suvanine as novel NS3 helicase inhibitors, with IC50 values of 4 and 3 µM, respectively, from a marine sponge by screening extracts of marine organisms. Both hal3 and suvanine inhibited the ATPase, RNA binding, and serine protease activities of NS3 helicase with IC50 values of 8, 8, and 14 µM, and 7, 3, and 34 µM, respectively. However, the dengue virus (DENV NS3 helicase, which shares a catalytic core (consisting mainly of ATPase and RNA binding sites with HCV NS3 helicase, was not inhibited by hal3 and suvanine, even at concentrations of 100 µM. Therefore, we conclude that hal3 and suvanine specifically inhibit HCV NS3 helicase via an interaction with an allosteric site in NS3 rather than binding to the catalytic core. This led to the inhibition of all NS3 activities, presumably by inducing conformational changes.

Location of the binding domains for the RNA polymerase L and the ribonucleocapsid template within different halves of the NS phosphoprotein of vesicular stomatitis virus

International Nuclear Information System (INIS)

Emerson, S.U.; Schubert, M.

1987-01-01

Recombinant DNA techniques were used to delete regions of a cDNA clone of the phosphoprotein NS gene of vesicular stomatitis virus. The complete NS gene and four mutant genes containing internal or terminal deletions were inserted into a modified pGem4 vector under the transcriptional control of the page T7 promoter. Run-off transcripts were synthesized and translated in vitro to provide [ 35 S]methionine-labeled complete NS or deletion mutant NS proteins. Immune coprecipitation assays involving these proteins were developed to map the regions of the NS protein responsible for binding to the structural viral nucleocapsid protein N and the catalytic RNA polymerase protein L. The data indicate the NS protein is a bivalent protein consisting of two discrete functional domains. Contrary to previous suggestions, the negatively charged amino-terminal half of NS protein binds to L protein, while the carboxyl-terminal half of NS protein binds to both soluble recombinant nucleocapsid protein N and viral ribonucleocapsid template

Conserved amino acids within the N-terminus of the West Nile virus NS4A protein contribute to virus replication, protein stability and membrane proliferation

International Nuclear Information System (INIS)

Ambrose, R.L.; Mackenzie, J.M.

2015-01-01

The West Nile virus strain Kunjin virus (WNV KUN ) NS4A protein is a multifunctional protein involved in many aspects of the virus life-cycle and is a major component of the WNV KUN replication complex (RC). Previously we identified a conserved region in the C-terminus of NS4A regulating proteolytic processing and RC assembly, and now investigate key conserved residues in the N-terminus of NS4A and their contribution to WNV KUN replication. Mutation of P13 completely ablated replication, whereas, mutation of P48 and D49, near the first transmembrane helix, and G66 within the helix, showed variable defects in replication, virion secretion and membrane proliferation. Intriguingly, the P48 and G66 NS4A mutants resulted in specific proteasome depletion of NS4A that could in part be rescued with a proteasome inhibitor. Our results suggest that the N-terminus of NS4A contributes to correct folding and stability, essential for facilitating the essential roles of NS4A during replication. - Highlights: • Mutation of Proline13 of the WNV NS4A protein is lethal to replication. • 1st TMB helix of NS4A contributes to protein stability and membrane remodelling. • Unstable mutants of NS4A can be rescued with a proteasome inhibitor. • This study (and of others) contributes to a functional mapping of the NS4A protein

Downregulation of viral RNA translation by hepatitis C virus non-structural protein NS5A requires the poly(U/UC) sequence in the 3' UTR.

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Hoffman, Brett; Li, Zhubing; Liu, Qiang

2015-08-01

Hepatitis C virus (HCV) non-structural protein 5A (NS5A) is essential for viral replication; however, its effect on HCV RNA translation remains controversial partially due to the use of reporters lacking the 3' UTR, where NS5A binds to the poly(U/UC) sequence. We investigated the role of NS5A in HCV translation using a monocistronic RNA containing a Renilla luciferase gene flanked by the HCV UTRs. We found that NS5A downregulated viral RNA translation in a dose-dependent manner. This downregulation required both the 5' and 3' UTRs of HCV because substitution of either sequence with the 5' and 3' UTRs of enterovirus 71 or a cap structure at the 5' end eliminated the effects of NS5A on translation. Translation of the HCV genomic RNA was also downregulated by NS5A. The inhibition of HCV translation by NS5A required the poly(U/UC) sequence in the 3' UTR as NS5A did not affect translation when it was deleted. In addition, we showed that, whilst the amphipathic α-helix of NS5A has no effect on viral translation, the three domains of NS5A can inhibit translation independently, also dependent on the presence of the poly(U/UC) sequence in the 3' UTR. These results suggested that NS5A downregulated HCV RNA translation through a mechanism involving the poly(U/UC) sequence in the 3' UTR.

Early diagnosis of dengue in travelers: comparison of a novel real-time RT-PCR, NS1 antigen detection and serology.

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Huhtamo, Eili; Hasu, Essi; Uzcátegui, Nathalie Y; Erra, Elina; Nikkari, Simo; Kantele, Anu; Vapalahti, Olli; Piiparinen, Heli

2010-01-01

The increased traveling to dengue endemic regions and the numerous epidemics have led to a rise in imported dengue. The laboratory diagnosis of acute dengue requires several types of tests and often paired samples are needed for obtaining reliable results. Although several diagnostic methods are available, proper comparative data on their performance are lacking. To compare the performance of novel methods including a novel pan-DENV real-time RT-PCR and a commercially available NS1 capture-EIA in regard to IgM detection for optimizing the early diagnosis of DENV in travelers. A panel of 99 selected early phase serum samples of dengue patients was studied by real-time RT-PCR, NS1 antigen ELISA, IgM-EIA, IgG-IFA and cell culture virus isolation. The novel real-time RT-PCR was shown specific and sensitive for detection of DENV-1-4 RNA and suitable for diagnostic use. The diagnostic rate using combination of RNA and IgM detection was 99% and using NS1 and IgM detection 95.9%. The results of RNA and NS1 antigen detection disagreed in 15.5% of samples that had only RNA or NS1 antigen detected. The diagnostic rates of early samples are higher when either RNA or NS1 antigen detection is combined with IgM detection. Besides the differences in the RNA and NS1 detection assays, the observed discrepancy of results could suggest individual variation or differences in timing of these markers in patient serum. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Pharmacologic inhibition of small-conductance calcium-activated potassium (SK) channels by NS8593 reveals atrial antiarrhythmic potential in horses

DEFF Research Database (Denmark)

Haugaard, Maria Mathilde; Hesselkilde, Eva Zander; Pehrson, Steen Michael

2015-01-01

and ventricular cardiomyocytes and contribute to atrial repolarization. Inhibition by NS8593 terminates pacing-induced AF of short duration and decreases AF duration and vulnerability without affecting ventricular conduction and repolarization. Thus, inhibition by NS8593 demonstrates clear atrial antiarrhythmic...

A comparison of 454 sequencing and clonal sequencing for the characterization of hepatitis C virus NS3 variants

NARCIS (Netherlands)

Ho, Cynthia K. Y.; Welkers, Matthijs R. A.; Thomas, Xiomara V.; Sullivan, James C.; Kieffer, Tara L.; Reesink, Henk W.; Rebers, Sjoerd P. H.; de Jong, Menno D.; Schinkel, Janke; Molenkamp, Richard

2015-01-01

We compared 454 amplicon sequencing with clonal sequencing for the characterization of intra-host hepatitis C virus (HCV) NS3 variants. Clonal and 454 sequences were obtained from 12 patients enrolled in a clinical phase I study for telaprevir, an NS3-4a protease inhibitor. Thirty-nine datasets were

Translation of the flavivirus kunjin NS3 gene in cis but not its RNA sequence or secondary structure is essential for efficient RNA packaging.

Science.gov (United States)

Pijlman, Gorben P; Kondratieva, Natasha; Khromykh, Alexander A

2006-11-01

Our previous studies using trans-complementation analysis of Kunjin virus (KUN) full-length cDNA clones harboring in-frame deletions in the NS3 gene demonstrated the inability of these defective complemented RNAs to be packaged into virus particles (W. J. Liu, P. L. Sedlak, N. Kondratieva, and A. A. Khromykh, J. Virol. 76:10766-10775). In this study we aimed to establish whether this requirement for NS3 in RNA packaging is determined by the secondary RNA structure of the NS3 gene or by the essential role of the translated NS3 gene product. Multiple silent mutations of three computer-predicted stable RNA structures in the NS3 coding region of KUN replicon RNA aimed at disrupting RNA secondary structure without affecting amino acid sequence did not affect RNA replication and packaging into virus-like particles in the packaging cell line, thus demonstrating that the predicted conserved RNA structures in the NS3 gene do not play a role in RNA replication and/or packaging. In contrast, double frameshift mutations in the NS3 coding region of full-length KUN RNA, producing scrambled NS3 protein but retaining secondary RNA structure, resulted in the loss of ability of these defective RNAs to be packaged into virus particles in complementation experiments in KUN replicon-expressing cells. Furthermore, the more robust complementation-packaging system based on established stable cell lines producing large amounts of complemented replicating NS3-deficient replicon RNAs and infection with KUN virus to provide structural proteins also failed to detect any secreted virus-like particles containing packaged NS3-deficient replicon RNAs. These results have now firmly established the requirement of KUN NS3 protein translated in cis for genome packaging into virus particles.

Exacerbating effects of human parvovirus B19 NS1 on liver fibrosis in NZB/W F1 mice.

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Tsai-Ching Hsu

Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19 is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-β/Smad fibrotic signaling by increasing the expressions of TGF-β, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and α-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling.

Exacerbating Effects of Human Parvovirus B19 NS1 on Liver Fibrosis in NZB/W F1 Mice

Science.gov (United States)

Hsu, Tsai-Ching; Tsai, Chun-Chou; Chiu, Chun-Ching; Hsu, Jeng-Dong; Tzang, Bor-Show

2013-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19) is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-β/Smad fibrotic signaling by increasing the expressions of TGF-β, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and α-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling. PMID:23840852

Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms

International Nuclear Information System (INIS)

Nakaya, Y; Shide, K; Niwa, T; Homan, J; Sugahara, S; Horio, T; Kuramoto, K; Kotera, T; Shibayama, H; Hori, K; Naito, H; Shimoda, K

2011-01-01

Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC 50 ) of <1 n, and had 30–50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL–JAK2 fusion gene; IC 50 =11–120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs

Naringenin and quercetin--potential anti-HCV agents for NS2 protease targets.

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Lulu, S Sajitha; Thabitha, A; Vino, S; Priya, A Mohana; Rout, Madhusmita

2016-01-01

Nonstructural proteins of hepatitis C virus had drawn much attention for the scientific fraternity in drug discovery due to its important role in the disease. 3D structure of the protein was predicted using molecular modelling protocol. Docking studies of 10 medicinal plant compounds and three drugs available in the market (control) with NS2 protease were employed by using rigid docking approach of AutoDock 4.2. Among the molecules tested for docking study, naringenin and quercetin revealed minimum binding energy of - 7.97 and - 7.95 kcal/mol with NS2 protease. All the ligands were docked deeply within the binding pocket region of the protein. The docking study results showed that these compounds are potential inhibitors of the target; and also all these docked compounds have good inhibition constant, vdW+Hbond+desolv energy with best RMSD value.

Neuronal excitation and permeabilization by 200-ns pulsed electric field: An optical membrane potential study with FluoVolt dye.

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Pakhomov, Andrei G; Semenov, Iurii; Casciola, Maura; Xiao, Shu

2017-07-01

Electric field pulses of nano- and picosecond duration are a novel modality for neurostimulation, activation of Ca 2+ signaling, and tissue ablation. However it is not known how such brief pulses activate voltage-gated ion channels. We studied excitation and electroporation of hippocampal neurons by 200-ns pulsed electric field (nsPEF), by means of time-lapse imaging of the optical membrane potential (OMP) with FluoVolt dye. Electroporation abruptly shifted OMP to a more depolarized level, which was reached within 10s), so cells remained above the resting OMP level for at least 20-30s. Activation of voltage-gated sodium channels (VGSC) enhanced the depolarizing effect of electroporation, resulting in an additional tetrodotoxin-sensitive OMP peak in 4-5ms after nsPEF. Omitting Ca 2+ in the extracellular solution did not reduce the depolarization, suggesting no contribution of voltage-gated calcium channels (VGCC). In 40% of neurons, nsPEF triggered a single action potential (AP), with the median threshold of 3kV/cm (range: 1.9-4kV/cm); no APs could be evoked by stimuli below the electroporation threshold (1.5-1.9kV/cm). VGSC opening could already be detected in 0.5ms after nsPEF, which is too fast to be mediated by the depolarizing effect of electroporation. The overlap of electroporation and AP thresholds does not necessarily reflect the causal relation, but suggests a low potency of nsPEF, as compared to conventional electrostimulation, for VGSC activation and AP induction. Copyright © 2017 Elsevier B.V. All rights reserved.

Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus NS5A Inhibitor.

Science.gov (United States)

Owens, Christopher M; Brasher, Bradley B; Polemeropoulos, Alex; Rhodin, Michael H J; McAllister, Nicole; Wong, Kelly A; Jones, Christopher T; Jiang, Lijuan; Lin, Kai; Or, Yat Sun

2016-10-01

EDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor developed for the treatment of HCV infection, has been investigated in vitro and in vivo This study sought to characterize genotypic changes in the HCV NS5A sequence of genotype 1 (GT1) replicons and to compare those changes to GT1 viral RNA mutations isolated from clinical trial patients. Resistance selection experiments in vitro using a subgenomic replicon identified resistance-associated mutations (RAMs) at GT1a NS5A amino acid positions 24, 28, 30, 31, and 93 that confer various degrees of resistance to EDP-239. Key RAMs were similarly identified in GT1b NS5A at amino acid positions 31 and 93. Mutations F36L in GT1a and A92V in GT1b do not confer resistance to EDP-239 individually but were found to enhance the resistance of GT1a K24R and GT1b Y93H. RAMs were identified in GT1 patients at baseline or after dosing with EDP-239 that were similar to those detected in vitro Baseline RAMs identified at NS5A position 93 in GT1, or positions 28 or 30 in GT1a only, correlated with a reduced treatment response. RAMs at additional positions were also detected and may have contributed to reduced EDP-239 efficacy. The most common GT1a and GT1b RAMs found to persist up to weeks 12, 24, or 48 were those at NS5A positions 28, 30, 31, 58 (GT1a only), and 93. Those RAMs persisting at the highest frequencies up to weeks 24 or 48 were L31M and Q30H/R for GT1a and L31M and Y93H for GT1b. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Engineering solutions for a reflector change concept in the high-temperature reactor with pebble bed core and OTTO-fueling

International Nuclear Information System (INIS)

Kasper, K.J.

1975-06-01

In the field of reactor engineering an increasing tendency is visible towards a 'repairable reactor'. In the construction of the HTR with spherical fuel elements this fact should already be taken into account at an early stage. Additionally it is possible that in connection with the OTTO-fueling load conditions for the graphite reflector could result which are locally not far away from limiting values. Therefore the removability of the reflector is included in the reactor construction as an accompanying technical step of the physical lay-out of the core. The core arrangements, realized for HTR until recently, are discussed as well as the properties of the graphites used and the operating conditions in the reactors are stated. At the example of the PR 3,000 proposals are offered for the construction of a removable side and top reflector for a pebble bed reactor. Hereby a solution was found which, on one hand allows the changing of the reflector and on the other hand requires no significant increase of the costs for the reactor assembly. Moreover the requirements of reactor operation and of repairability are satisfied in an optimal manner. (orig.) [de

A Crítica de Otto Klineberg aos testes de inteligência. O Brasil como laboratório racial

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Marcos Chor Maio

Full Text Available Resumo Otto Klineberg, professor de psicologia social na Universidade de Columbia, assegurou que os testes de inteligência eram uma ferramenta para legitimar hierarquias raciais. Ele conduziu numerosos estudos sobre as relações entre negros, brancos, índios e grupos de imigrantes nos Estados Unidos e na Europa na qual ressaltou que os aspectos ambientais superavam os fatores raciais. Klineberg concebia o Brasil como um ambiente privilegiado para demonstrar que os testes de inteligência não tinham qualquer base científica. O presente artigo tem um foco triplo: três estudos realizados por Klineberg entre 1927 e 1935; suas experiências no Brasil de 1945 a 1947 como professor da Universidade de São Paulo, quando ele tentou investigar a relação entre testes de inteligência e condições socioeconômicas em escolas do Rio de Janeiro; e sua atuação inicial na Unesco, após a 2a Guerra Mundial, quando muitos ainda estavam convencidos que os testes de inteligência eram uma forma adequada para medir as chamadas habilidades inatas.

NS3 from Hepatitis C Virus Strain JFH-1 Is an Unusually Robust Helicase That Is Primed To Bind and Unwind Viral RNA

Energy Technology Data Exchange (ETDEWEB)

Zhou, Ting; Ren, Xiaoming; Adams, Rebecca L.; Pyle, Anna Marie; Ou, J. -H. James

2017-10-25

Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral replication and assembly (nonstructural protein 3 [NS3]). This helicase has become the focus of extensive basic research on the general helicase mechanism, and it is also of interest as a novel drug target. Despite the importance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV strains that are used to study HCV genetics and mechanism in cell culture (such as JFH-1) is lacking. We therefore set out to determine whether NS3 from the replicatively efficient genotype 2a strain JFH-1 displays novel functional or structural properties. Using biochemical assays for RNA binding and duplex unwinding, we show that JFH-1 NS3 binds RNA much more rapidly than the previously studied NS3 variants from genotype 1b. Unlike NS3 variants from other genotypes, JFH-1 NS3 binds RNA with high affinity in a functionally active form that is capable of immediately unwinding RNA duplexes without undergoing rate-limiting conformational changes that precede activation. Unlike other superfamily 2 (SF2) helicases, JFH-1 NS3 does not require long 3' overhangs, and it unwinds duplexes that are flanked by only a few nucleotides, as in the folded HCV genome. To understand the physical basis for this, we solved the crystal structure of JFH-1 NS3, revealing a novel conformation that contains an open, positively charged RNA binding cleft that is primed for productive interaction with RNA targets, potentially explaining robust replication by HCV JFH-1.

IMPORTANCEGenotypes of HCV are as divergent as different types of flavivirus, and yet mechanistic features of HCV variants are presumed to be held in common. One of the most well-studied components of the HCV replication complex is a helicase known as nonstructural protein 3 (NS3). We set out to determine whether this important

Nanosecond pulsed electric field (nsPEF) enhance cytotoxicity of cisplatin to hepatocellular cells by microdomain disruption on plasma membrane.

Science.gov (United States)

Yin, Shengyong; Chen, Xinhua; Xie, Haiyang; Zhou, Lin; Guo, Danjing; Xu, Yuning; Wu, Liming; Zheng, Shusen

2016-08-15

Previous studies showed nanosecond pulsed electric field (nsPEF) can ablate solid tumors including hepatocellular carcinoma (HCC) but its effect on cell membrane is not fully understood. We hypothesized nsPEF disrupt the microdomains on outer-cellular membrane with direct mechanical force and as a result the plasma membrane permeability increases to facilitate the small molecule intake. Three HCC cells were pulsed one pulse per minute, an interval longer than nanopore resealing time. The cationized ferritin was used to mark up the electronegative microdomains, propidium iodide (PI) for membrane permeabilization, energy dispersive X-ray spectroscopy (EDS) for the negative cell surface charge and cisplatin for inner-cellular cytotoxicity. We demonstrated that the ferritin marked-microdomain and negative cell surface charge were disrupted by nsPEF caused-mechanical force. The cell uptake of propidium and cytotoxicity of DNA-targeted cisplatin increased with a dose effect. Cisplatin gains its maximum inner-cellular cytotoxicity when combining with nsPEF stimulation. We conclude that nsPEF disrupt the microdomains on the outer cellular membrane directly and increase the membrane permeabilization for PI and cisplatin. The microdomain disruption and membrane infiltration changes are caused by the mechanical force from the changes of negative cell surface charge. Copyright © 2016 Elsevier Inc. All rights reserved.

Nanosecond pulsed electric field (nsPEF) enhance cytotoxicity of cisplatin to hepatocellular cells by microdomain disruption on plasma membrane

International Nuclear Information System (INIS)

Yin, Shengyong; Chen, Xinhua; Xie, Haiyang; Zhou, Lin; Guo, Danjing; Xu, Yuning; Wu, Liming; Zheng, Shusen

2016-01-01

Previous studies showed nanosecond pulsed electric field (nsPEF) can ablate solid tumors including hepatocellular carcinoma (HCC) but its effect on cell membrane is not fully understood. We hypothesized nsPEF disrupt the microdomains on outer-cellular membrane with direct mechanical force and as a result the plasma membrane permeability increases to facilitate the small molecule intake. Three HCC cells were pulsed one pulse per minute, an interval longer than nanopore resealing time. The cationized ferritin was used to mark up the electronegative microdomains, propidium iodide (PI) for membrane permeabilization, energy dispersive X-ray spectroscopy (EDS) for the negative cell surface charge and cisplatin for inner-cellular cytotoxicity. We demonstrated that the ferritin marked-microdomain and negative cell surface charge were disrupted by nsPEF caused-mechanical force. The cell uptake of propidium and cytotoxicity of DNA-targeted cisplatin increased with a dose effect. Cisplatin gains its maximum inner-cellular cytotoxicity when combining with nsPEF stimulation. We conclude that nsPEF disrupt the microdomains on the outer cellular membrane directly and increase the membrane permeabilization for PI and cisplatin. The microdomain disruption and membrane infiltration changes are caused by the mechanical force from the changes of negative cell surface charge.

Nanosecond pulsed electric field (nsPEF) enhance cytotoxicity of cisplatin to hepatocellular cells by microdomain disruption on plasma membrane

Energy Technology Data Exchange (ETDEWEB)

Yin, Shengyong; Chen, Xinhua; Xie, Haiyang; Zhou, Lin [Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, The Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003 (China); Guo, Danjing; Xu, Yuning [Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, The Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003 (China); Wu, Liming, E-mail: wlm@zju.edu.cn [Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, The Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003 (China); Zheng, Shusen, E-mail: shusenzheng@zju.edu.cn [Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health and Key Laboratory of Organ Transplantation of Zhejiang Province, The Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003 (China)

2016-08-15

Previous studies showed nanosecond pulsed electric field (nsPEF) can ablate solid tumors including hepatocellular carcinoma (HCC) but its effect on cell membrane is not fully understood. We hypothesized nsPEF disrupt the microdomains on outer-cellular membrane with direct mechanical force and as a result the plasma membrane permeability increases to facilitate the small molecule intake. Three HCC cells were pulsed one pulse per minute, an interval longer than nanopore resealing time. The cationized ferritin was used to mark up the electronegative microdomains, propidium iodide (PI) for membrane permeabilization, energy dispersive X-ray spectroscopy (EDS) for the negative cell surface charge and cisplatin for inner-cellular cytotoxicity. We demonstrated that the ferritin marked-microdomain and negative cell surface charge were disrupted by nsPEF caused-mechanical force. The cell uptake of propidium and cytotoxicity of DNA-targeted cisplatin increased with a dose effect. Cisplatin gains its maximum inner-cellular cytotoxicity when combining with nsPEF stimulation. We conclude that nsPEF disrupt the microdomains on the outer cellular membrane directly and increase the membrane permeabilization for PI and cisplatin. The microdomain disruption and membrane infiltration changes are caused by the mechanical force from the changes of negative cell surface charge.

Oxacilin-resistant Coagulase-negative staphylococci (CoNS) bacteremia in a general hospital at São Paulo city, Brasil

Science.gov (United States)

d’Azevedo, P.A.; Secchi, C.; Antunes, A.L.S.; Sales, T.; Silva, F.M.; Tranchesi, R.; Pignatari, A.C.C.

2008-01-01

In the last decades, coagulase-negative staphylococci (CoNS), especially Staphylococcus epidermidis have become an important cause of bloodstream infections. In addition, rates of methicillin-resistance among CoNS have increased substantially, leading to the use of glicopeptides for therapy. The objective of this study was to evaluate eleven consecutives clinically relevant cases of oxacillin-resistant CoNS bacteremia in a general hospital localized in São Paulo city, Brazil. Five different species were identified by different phenotypic methods, including S. epidermidis (5), S. haemolyticus (3), S. hominis (1), S. warneri (1) and S. cohnii subsp urealyticus (1). A variety of Pulsed Field Gel Electrophoresis profiles was observed by macrorestriction DNA analysis in S. epidermidis isolates, but two of three S. haemolyticus isolates presented the same profile. These data indicated the heterogeneity of the CoNS isolates, suggesting that horizontal dissemination of these microorganisms in the investigated hospital was not frequent. One S. epidermidis and one S. haemolyticus isolates were resistant to teicoplanin and susceptible to vancomycin. The selective pressure due to the use of teicoplanin in this hospital is relevant. PMID:24031279

Development and application of hepatitis C reporter viruses with genotype 1 to 7 core-nonstructural protein 2 (NS2) expressing fluorescent proteins or luciferase in modified JFH1 NS5A

DEFF Research Database (Denmark)

Gottwein, Judith M; Jensen, Tanja B; Mathiesen, Christian K

2011-01-01

to 2a(J6) tagged with EGFP, DsRed-Express2, mCherry, or Renilla luciferase (RLuc), yielding peak supernatant infectivity titers of 4 to 5 log(10) focus-forming units (FFU)/ml. 2a(J6) with ¿40 or ¿25 was fully viable in Huh7.5 cells. In human liver chimeric mice, 2a(J6)-EGFP¿40 acquired various...... deletions in EGFP, while 2a(J6)¿40 did not show an impaired viability. We further developed panels of JFH1-based genotype 1 to 7 core-NS2 recombinants expressing EGFP- or RLuc-NS5A¿40 fusion proteins. In cell culture, the different EGFP recombinants showed growth characteristics comparable to those...

The eukaryotic translation initiation factor 3 subunit L protein interacts with Flavivirus NS5 and may modulate yellow fever virus replication.

Science.gov (United States)

Morais, Ana Ts; Terzian, Ana Cb; Duarte, Danilo Vb; Bronzoni, Roberta Vm; Madrid, Maria Cfs; Gavioli, Arieli F; Gil, Laura Hvg; Oliveira, Amanda G; Zanelli, Cleslei F; Valentini, Sandro R; Rahal, Paula; Nogueira, Mauricio L

2013-06-22

Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and the expansion of YFV-endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, which are essential for viral replication, and the interactions between NS5 and cellular proteins have been studied to better understand viral replication. The aim of this study was to characterize the interaction of the NS5 protein with eukaryotic translation initiation factor 3 subunit L (eIF3L) and to evaluate the role of eIF3L in yellow fever replication. To identify interactions of YFV NS5 with cellular proteins, we performed a two-hybrid screen using the YFV NS5 RdRp domain as bait with a human cDNA library, and RNApol deletion mutants were generated and analyzed using the two-hybrid system for mapping the interactions. The RNApol region involved was segmented into three fragments and analyzed using an eIF3L-expressing yeast strain. To map the NS5 residues that are critical for the interactions, we performed site-direct mutagenesis in segment 3 of the interaction domain (ID) and confirmed the interaction using in vitro assays and in vivo coimmunoprecipitation. The significance of eIF3L for YFV replication was investigated using eIF3L overexpression and RNA interference. In this work, we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed using in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs at a region (the interaction domain of the RNApol domain) that is conserved in several flaviviruses and that is, therefore, likely to be relevant to the genus. eIF3L overexpression and plaque reduction assays showed a slight effect on YFV replication, indicating that the interaction of eIF3L with YFV NS5 may play a role

A ns-Pulse Laser Microthruster

International Nuclear Information System (INIS)

Phipps, Claude R.; Luke, James R.; Helgeson, Wesley; Johnson, Richard

2006-01-01

We have developed a prototype device which demonstrates the feasibility of using ns-duration laser pulses in a laser microthruster. Relative to the ms-duration thrusters which we have demonstrated in the past, this change offers the use of any target material, the use of reflection-mode target illumination, and adjustable specific impulse. Specific impulse is adjusted by varying laser intensity on target. In this way, we were able to vary specific impulse from 200s to 3,200s on gold. We used a Concepts Research, Inc. microchip laser with 170mW average optical power, 8kHz repetition rate and 20μJ pulse energy for many of the measurements. Thrust was in the 100nN - 1μN range for all the work, requiring development of an extremely sensitive, low-noise thrust stand. We will discuss the design of metallic fuel delivery systems. Ablation efficiency near 100% was observed. Results obtained on metallic fuel systems agreed with simulations. We also report time-of-flight measurements on ejected metal ions, which gave velocities up to 80km/s

Exploration of structural stability in deleterious nsSNPs of the XPA gene: A molecular dynamics approach

Directory of Open Access Journals (Sweden)

N NagaSundaram

2011-01-01

Full Text Available Background: Distinguishing the deleterious from the massive number of non-functional nsSNPs that occur within a single genome is a considerable challenge in mutation research. In this approach, we have used the existing in silico methods to explore the mutation-structure-function relationship in the XPA gene. Materials and Methods: We used the Sorting Intolerant From Tolerant (SIFT, Polymorphism Phenotyping (PolyPhen, I-Mutant 2.0, and the Protein Analysis THrough Evolutionary Relationships methods to predict the effects of deleterious nsSNPs on protein function and evaluated the impact of mutation on protein stability by Molecular Dynamics simulations. Results: By comparing the scores of all the four in silico methods, nsSNP with an ID rs104894131 at position C108F was predicted to be highly deleterious. We extended our Molecular dynamics approach to gain insight into the impact of this non-synonymous polymorphism on structural changes that may affect the activity of the XPA gene. Conclusion: Based on the in silico methods score, potential energy, root-mean-square deviation, and root-mean-square fluctuation, we predict that deleterious nsSNP at position C108F would play a significant role in causing disease by the XPA gene. Our approach would present the application of in silico tools in understanding the functional variation from the perspective of structure, evolution, and phenotype.

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

Directory of Open Access Journals (Sweden)

Sujuan Chen

2017-06-01

Full Text Available H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128 were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.