Improved Dual-Luciferase Reporter Assays for Nuclear Receptors

PubMed Central

Paguio, Aileen; Stecha, Pete; Wood, Keith V; Fan, Frank

2010-01-01

Nuclear receptors play important roles in many cellular functions through control of gene transcription. It is also a large target class for drug discovery. Luciferase reporter assays are frequently used to study nuclear receptor function because of their wide dynamic range, low endogenous activity, and ease of use. Recent improvements of luciferase genes and vectors have further enhanced their utilities. Here we applied these improvements to two reporter formats for studying nuclear receptors. The first assay contains a Murine Mammary Tumor Virus promoter upstream of a destabilized luciferase. The presence of response elements for nuclear hormone receptor in this promoter allows the studies of endogenous and/or exogenous full length receptors. The second assay contains a ligand binding domain (LBD) of a nuclear receptor fused to the GAL4 DNA binding domain (DBD) on one vector and multiple Gal4 Upstream Activator Sequences (UAS) upstream of luciferase reporter on another vector. We showed that codon optimization of luciferase reporter genes increased expression levels in conjunction with the incorporation of protein destabilizing sequences into luciferase led to a larger assay dynamic range in both formats. The optimum number of UAS to generate the best response was determined. The expression vector for nuclear receptor LBD/GAL4 DBD fusion also constitutively expresses a Renilla luciferase-neoR fusion protein, which provides selection capability (G418 resistance, neoR) as well as an internal control (Renilla luciferase). This dual-luciferase format allowed detecting compound cytotoxicity or off-target change in expression during drug screening, therefore improved data quality. These luciferase reporter assays provided better research and drug discovery tools for studying the functions of full length nuclear receptors and ligand binding domains. PMID:21687560

An experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation

PubMed Central

Ryu, Byoung Y.; Evans-Galea, Marguerite V.; Gray, John T.; Bodine, David M.; Persons, Derek A.

2008-01-01

Pathogenic activation of the LMO2 proto-oncogene by an oncoretroviral vector insertion in a clinical trial for X-linked severe combined immunodeficiency (X-SCID) has prompted safety concerns. We used an adeno-associated virus vector to achieve targeted insertion of a γ-retroviral long terminal repeat (LTR) driving a GFP expression cassette with flanking loxP sites in a human T-cell line at the precise location of vector integration in one of the patients with X-SCID. The LTR-GFP cassette was inserted into the first intron of the LMO2 gene, resulting in strong activation of LMO2. Cre-mediated cassette exchange was used to replace the original LTR-GFP cassette with one flanked by insulator elements leading to a several fold reduction in LMO2 expression. The LTR-GFP cassette was also replaced with a globin gene regulatory cassette that failed to activate the LMO2 gene in lymphoid cells. A γ-retroviral vector with 2 intact LTRs resulted in activation of the LMO2 gene when inserted into the first intron, but a self-inactivating lentiviral vector with an internal cellular promoter and flanking insulator elements did not activate the LMO2 gene. Thus, this system is useful for comparing the safety profiles of vector cassettes with various regulatory elements for their potential for proto-oncogene activation. PMID:17991809

An oncolytic adenovirus vector combining enhanced cell-to-cell spreading, mediated by the ADP cytolytic protein, with selective replication in cancer cells with deregulated wnt signaling.

PubMed

Toth, Karoly; Djeha, Hakim; Ying, Baoling; Tollefson, Ann E; Kuppuswamy, Mohan; Doronin, Konstantin; Krajcsi, Peter; Lipinski, Kai; Wrighton, Christopher J; Wold, William S M

2004-05-15

We have constructed a novel oncolytic adenovirus (Ad) vector named VRX-009 that combines enhanced cell spread with tumor-specific replication. Enhanced spread, which could significantly increase antitumor efficacy, is mediated by overexpression of the Ad cytolytic protein named ADP (also known as E3-11.6K). Replication of VRX-009 is restricted to cells with a deregulated wnt signal transduction pathway by replacement of the wild-type Ad E4 promoter with a synthetic promoter consisting of five consensus binding sites for the T-cell factor transcription factor. Tumor-selective replication is indicated by several lines of evidence. VRX-009 expresses E4ORF3, a representative Ad E4 protein, only in colon cancer cell lines. Furthermore, VRX-009 replicates preferentially in colon cancer cell lines as evidenced by virus productivity 2 orders of magnitude higher in SW480 colon cancer cells than in A549 lung cancer cells. Replication in primary human bronchial epithelial cells and human umbilical vein endothelial cells was also significantly lower than in SW480 cells. When tested in human tumor xenografts in nude mice, VRX-009 effectively suppressed the growth of SW480 colon tumors but not of A549 lung tumors. VRX-009 may provide greater level of antitumor efficacy than standard oncolytic Ad vectors in tumors in which a defect in wnt signaling increases the level of nuclear beta-catenin.

Genetic Targeting of an Adenovirus Vector via Replacement of the Fiber Protein with the Phage T4 Fibritin

PubMed Central

Krasnykh, Victor; Belousova, Natalya; Korokhov, Nikolay; Mikheeva, Galina; Curiel, David T.

2001-01-01

The utility of adenovirus (Ad) vectors for gene therapy is restricted by their inability to selectively transduce disease-affected tissues. This limitation may be overcome by the derivation of vectors capable of interacting with receptors specifically expressed in the target tissue. Previous attempts to alter Ad tropism by genetic modification of the Ad fiber have had limited success due to structural conflicts between the fiber and the targeting ligand. Here we present a strategy to derive an Ad vector with enhanced targeting potential by a radical replacement of the fiber protein in the Ad capsid with a chimeric molecule containing a heterologous trimerization motif and a receptor-binding ligand. Our approach, which capitalized upon the overall structural similarity between the human Ad type 5 (Ad5) fiber and bacteriophage T4 fibritin proteins, has resulted in the generation of a genetically modified Ad5 incorporating chimeric fiber-fibritin proteins targeted to artificial receptor molecules. Gene transfer studies employing this novel viral vector have demonstrated its capacity to efficiently deliver a transgene payload to the target cells in a receptor-specific manner. PMID:11287567

Intron Retention Identifies a Malaria Vector within the Anopheles (Nyssorhynchus) Albitaris Complex (Diptera: Culicidae)

DTIC Science & Technology

2005-03-09

variation in local environments including changes driven by human activity . For example, Anopheles (Nyssorhynchus) marajoara Galvao, and Damasceno...Linthicum, 1988) is the principal malaria vector in northeastern Amazonia, replacing An. darling Root, perhaps as a result of changes in human activity (Conn

A vector based on the SV40 origin of replication and chromosomal S/MARs replicates episomally in CHO cells.

PubMed Central

Piechaczek, C; Fetzer, C; Baiker, A; Bode, J; Lipps, H J

1999-01-01

We have developed an episomal replicating expression vector in which the SV40 gene coding for the large T-antigen was replaced by chromosomal scaffold/matrix attached regions. Southern analysis as well as vector rescue experiments in CHO cells and in Escherichia coli demonstrate that the vector replicates episomally in CHO cells. It occurs in a very low copy number in the cells and is stably maintained over more than 100 generations without selection pressure. PMID:9862961

Nuclear targeting of viral and non-viral DNA.

PubMed

Chowdhury, E H

2009-07-01

The nuclear envelope presents a major barrier to transgene delivery and expression using a non-viral vector. Virus is capable of overcoming the barrier to deliver their genetic materials efficiently into the nucleus by virtue of the specialized protein components with the unique amino acid sequences recognizing cellular nuclear transport machinery. However, considering the safety issues in the clinical gene therapy for treating critical human diseases, non-viral systems are highly promising compared with their viral counterparts. This review summarizes the progress on exploring the nuclear traffic mechanisms for the prominent viral vectors and the technological innovations for the nuclear delivery of non-viral DNA by mimicking those natural processes evolved for the viruses as well as for many cellular proteins.

Assessment of hypoxia and TNF-alpha response by a vector with HRE and NF-kappaB response elements.

PubMed

Chen, Zhilin; Eadie, Ashley L; Hall, Sean R; Ballantyne, Laurel; Ademidun, David; Tse, M Yat; Pang, Stephen C; Melo, Luis G; Ward, Christopher A; Brunt, Keith R

2017-01-01

Hypoxia and inflammatory cytokine activation (H&I) are common processes in many acute and chronic diseases. Thus, a single vector that responds to both hypoxia and inflammatory cytokines, such as TNF-alpha, is useful for assesing the severity of such diseases. Adaptation to hypoxia is regulated primarily by hypoxia inducible transcription factor (HIF alpha) nuclear proteins that engage genes containing a hypoxia response element (HRE). Inflammation activates a multitude of cytokines, including TNF-alpha, that invariably modulate activation of the nuclear factor kappa B (NF-kB) transcription factor. We constructed a vector that encompassed both a hypoxia response element (HRE), and a NF-kappaB responsive element. We show that this vector was functionally responsive to both hypoxia and TNF-alpha, in vitro and in vivo . Thus, this vector might be suitable for the detection and assessment of hypoxia or TNF-alpha.

Identification of Human Semiochemicals Attractive to the Major Vectors of Onchocerciasis

PubMed Central

Young, Ryan M.; Burkett-Cadena, Nathan D.; McGaha, Tommy W.; Rodriguez-Perez, Mario A.; Toé, Laurent D.; Adeleke, Monsuru A.; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R.; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L.; Salinas-Carmona, Mario C.; Baker, Bill; Unnasch, Thomas R.; Cupp, Eddie W.

2015-01-01

Background Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Methodology/Principal Findings Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. Conclusions/Significance The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa. PMID:25569240

Identification of human semiochemicals attractive to the major vectors of onchocerciasis.

PubMed

Young, Ryan M; Burkett-Cadena, Nathan D; McGaha, Tommy W; Rodriguez-Perez, Mario A; Toé, Laurent D; Adeleke, Monsuru A; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L; Salinas-Carmona, Mario C; Baker, Bill; Unnasch, Thomas R; Cupp, Eddie W

2015-01-01

Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa.

Development of a NEW Vector Magnetograph at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

West, Edward; Hagyard, Mona; Gary, Allen; Smith, James; Adams, Mitzi; Rose, M. Franklin (Technical Monitor)

2001-01-01

This paper will describe the Experimental Vector Magnetograph that has been developed at the Marshall Space Flight Center (MSFC). This instrument was designed to improve linear polarization measurements by replacing electro-optic and rotating waveplate modulators with a rotating linear analyzer. Our paper will describe the motivation for developing this magnetograph, compare this instrument with traditional magnetograph designs, and present a comparison of the data acquired by this instrument and original MSFC vector magnetograph.

Antipathogen genes and the replacement of disease-vectoring mosquito populations: a model-based evaluation

PubMed Central

Robert, Michael A; Okamoto, Kenichi W; Gould, Fred; Lloyd, Alun L

2014-01-01

Recently, genetic strategies aimed at controlling populations of disease-vectoring mosquitoes have received considerable attention as alternatives to traditional measures. Theoretical studies have shown that female-killing (FK), antipathogen (AP), and reduce and replace (R&R) strategies can each decrease the number competent vectors. In this study, we utilize a mathematical model to evaluate impacts on competent Aedes aegypti populations of FK, AP, and R&R releases as well as hybrid strategies that result from combinations of these three approaches. We show that while the ordering of efficacy of these strategies depends upon population life history parameters, sex ratio of releases, and switch time in combination strategies, AP-only and R&R/AP releases typically lead to the greatest long-term reduction in competent vectors. R&R-only releases are often less effective at long-term reduction of competent vectors than AP-only releases or R&R/AP releases. Furthermore, the reduction in competent vectors caused by AP-only releases is easier to maintain than that caused by FK-only or R&R-only releases even when the AP gene confers a fitness cost. We discuss the roles that density dependence and inclusion of females play in the order of efficacy of the strategies. We anticipate that our results will provide added impetus to continue developing AP strategies. PMID:25558284

Program for life extension and preserving existing resources for motor control center components [nuclear plants

NASA Astrophysics Data System (ADS)

Sanwarwalla, M. H.; Alsammarae, A. J.

1995-08-01

Many nuclear power plants have motor control centers (MCCs) installed in a harsh, radiation only, environment. Procurement of safety-related replacement devices for these MCCs is an economic burden for the stations if these MCCs have become obsolete. Identical replacement components for many MCCs installed in older plants (ITE Gould, Allis-Chalmers, Klockner-Moeller, Cutler-Hammer, etc.) are no longer available. Plants are left with the option of either retrofitting these MCCs or finding ways to extend the qualified lives of the safety-related components to minimize replacement costs. ComEd nuclear station has embarked on a program to minimize the economic burden for the replacement of Klockner-Moeller (K-M) MCC components. This paper discusses the program adopted by this station and its economic benefits to ComEd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Durrer, Ruth; Tansella, Vittorio, E-mail: ruth.durrer@unige.ch, E-mail: vittorio.tansella@unige.ch

We derive the contribution to relativistic galaxy number count fluctuations from vector and tensor perturbations within linear perturbation theory. Our result is consistent with the the relativistic corrections to number counts due to scalar perturbation, where the Bardeen potentials are replaced with line-of-sight projection of vector and tensor quantities. Since vector and tensor perturbations do not lead to density fluctuations the standard density term in the number counts is absent. We apply our results to vector perturbations which are induced from scalar perturbations at second order and give numerical estimates of their contributions to the power spectrum of relativistic galaxymore » number counts.« less

Photoproduction of light vector mesons in Xe-Xe ultraperipheral collisions at the LHC and the nuclear density of Xe-129

NASA Astrophysics Data System (ADS)

Guzey, V.; Kryshen, E.; Zhalov, M.

2018-07-01

We make predictions for cross sections of ρ and ϕ vector meson photoproduction in ultraperipheral Xe-Xe collisions at √{sNN } = 5.44TeV. Analyzing the momentum transfer distribution of ρ mesons in this process, we explore the feasibility of extracting the nuclear density of 129Xe, which is needed in searches for dark matter with Xenon-based detectors.

Experimental investigation of vector static magnetic field detection using an NV center with a single first-shell 13C nuclear spin in diamond

NASA Astrophysics Data System (ADS)

Jiang, Feng-Jian; Ye, Jian-Feng; Jiao, Zheng; Jiang, Jun; Ma, Kun; Yan, Xin-Hu; Lv, Hai-Jiang

2018-05-01

We perform a proof-of-principle experiment that uses a single negatively charged nitrogen–vacancy (NV) color center with a nearest neighbor 13C nuclear spin in diamond to detect the strength and direction (including both polar and azimuth angles) of a static vector magnetic field by optical detection magnetic resonance (ODMR) technique. With the known hyperfine coupling tensor between an NV center and a nearest neighbor 13C nuclear spin, we show that the information of static vector magnetic field could be extracted by observing the pulsed continuous wave (CW) spectrum. Project supported by the National Natural Science Foundation of China (Grant Nos. 11305074, 11135002, and 11275083), the Key Program of the Education Department Outstanding Youth Foundation of Anhui Province, China (Grant No. gxyqZD2017080), and the Education Department Natural Science Foundation of Anhui Province, China (Grant No. KJHS2015B09).

Coanda-Assisted Spray Manipulation Collar for a Commercial Plasma Spray Gun

NASA Astrophysics Data System (ADS)

Mabey, K.; Smith, B. L.; Whichard, G.; McKechnie, T.

2011-06-01

A Coanda-assisted Spray Manipulation (CSM) collar was retrofitted to a Praxair SG-100 plasma spray gun. The CSM device makes it possible to change the direction of (vector) the plasma jet and powder without moving the gun. The two-piece retrofit device replaces the standard faceplate. Two separate collars were tested: one designed for small vector angles and one for larger vector angles. It was demonstrated that the small-angle device could modify the trajectory of zirconia powder up to several degrees. Doing so could realign the plasma with the powder resulting in increased powder temperature and velocity. The large-angle device was capable of vectoring the plasma jet up to 45°. However, the powder did not vector as much. Under large-angle vectoring, the powder velocity and temperature decreased steadily with vector angle. Both devices were tested using a supersonic configuration to demonstrate that CSM is capable of vectoring supersonic plasmas.

"Analytical" vector-functions I

NASA Astrophysics Data System (ADS)

Todorov, Vladimir Todorov

2017-12-01

In this note we try to give a new (or different) approach to the investigation of analytical vector functions. More precisely a notion of a power xn; n ∈ ℕ+ of a vector x ∈ ℝ3 is introduced which allows to define an "analytical" function f : ℝ3 → ℝ3. Let furthermore f (ξ )= ∑n =0 ∞ anξn be an analytical function of the real variable ξ. Here we replace the power ξn of the number ξ with the power of a vector x ∈ ℝ3 to obtain a vector "power series" f (x )= ∑n =0 ∞ anxn . We research some properties of the vector series as well as some applications of this idea. Note that an "analytical" vector function does not depend of any basis, which may be used in research into some problems in physics.

"Life without nuclear power": A nuclear plant retirement formulation model and guide based on economics. San Onofre Nuclear Generating Station case: Economic impacts and reliability considerations leading to plant retirement

NASA Astrophysics Data System (ADS)

Wasko, Frank

Traditionally, electric utilities have been slow to change and very bureaucratic in nature. This culture, in and of itself, has now contributed to a high percentage of United States electric utilities operating uneconomical nuclear plants (Crooks, 2014). The economic picture behind owning and operating United States nuclear plants is less than favorable for many reasons including rising fuel, capital and operating costs (EUCG, 2012). This doctoral dissertation is specifically focused on life without nuclear power. The purpose of this dissertation is to create a model and guide that will provide electric utilities who currently operate or will operate uneconomical nuclear plants the opportunity to economically assess whether or not their nuclear plant should be retired. This economic assessment and stakeholder analysis will provide local government, academia and communities the opportunity to understand how Southern California Edison (SCE) embraced system upgrade import and "voltage support" opportunities to replace "base load" generation from San Onofre Nuclear Generating Station (SONGS) versus building new replacement generation facilities. This model and guide will help eliminate the need to build large replacement generation units as demonstrated in the SONGS case analysis. The application of The Nuclear Power Retirement Model and Guide will provide electric utilities with economic assessment parameters and an evaluation assessment progression needed to better evaluate when an uneconomical nuclear plant should be retired. It will provide electric utilities the opportunity to utilize sound policy, planning and development skill sets when making this difficult decision. There are currently 62 nuclear power plants (with 100 nuclear reactors) operating in the United States (EIA, 2014). From this group, 38 are at risk of early retirement based on the work of Cooper (2013). As demonstrated in my model, 35 of the 38 nuclear power plants qualify to move to the economic assessment review and then on to the stakeholder cost benefit analysis (if model qualifications are met) leading to a final plant retirement decision. This application via the model and guide, in turn, will lead electric utilities to explore system upgrade import opportunities and mitigation measures versus building new replacement generation facilities. United States nuclear reactors are licensed for 40 years with a 20 year extension available prior to the expiration date (EIA, 2013). Since late 2012, electric power companies have announced the early retirement of four uneconomical nuclear power plants while other studies have indicated that as many as 70 percent of United States nuclear power plants are potentially at risk for early retirement (Crooks, 2014 and Cooper, 2013). A high percentage of these aforementioned nuclear plants have operating licenses that will not expire until 2030 and beyond. Thus, for the most part, replacement power contingency planning has not been initiated for these plants or is still in preliminary stages. The recent nuclear plant retirements are the first since 1998 (EIA, 2013). Decisions to retire the plants involved concerns over maintenance and repair costs as well as declining profitability (EIA, 2013). In addition, the Energy Information Administration (2010-2012) released data that demonstrated that the worst 25 percent of United States nuclear plants are far more expensive to operate and generate electricity than new gas plants. It is equally important to understand and explain the economic and power replacement implications to both ratepayers and end-users. A SONGS case study analysis will review the economic, operational and political challenges that SCE faced leading to the retirement decision of SONGS. As preface to the case study, replacement steam generators (RSGs) were installed in Unit 2 in 2009 and in Unit 3 in 2010. In January 2012, while Unit 2 was down for routine maintenance, a small leak was discovered inside a steam generator in Unit 3. Because of the situation, both units remained shut down to evaluate the cause of the leakage and to make repairs. SCE submitted plans to the Nuclear Regulatory Commission (NRC) to re-start Unit 2 at reduced power. However, concerns over the length of the review process and the high costs associated with steam generator repairs led SCE to retire both reactors (SCE SONGS Fact Sheets, 2012-2013). Finally, collaborative resource power replacement planning is needed more than ever as nuclear facilities in the United States are now being retired for economic related reasons (Crooks, 2014). This collaborative power replacement process and implementation must encompass all relevant stakeholders including state grid operators, ratepayers, shareholders and the electric utility company.

Cancelable biometrics realization with multispace random projections.

PubMed

Teoh, Andrew Beng Jin; Yuang, Chong Tze

2007-10-01

Biometric characteristics cannot be changed; therefore, the loss of privacy is permanent if they are ever compromised. This paper presents a two-factor cancelable formulation, where the biometric data are distorted in a revocable but non-reversible manner by first transforming the raw biometric data into a fixed-length feature vector and then projecting the feature vector onto a sequence of random subspaces that were derived from a user-specific pseudorandom number (PRN). This process is revocable and makes replacing biometrics as easy as replacing PRNs. The formulation has been verified under a number of scenarios (normal, stolen PRN, and compromised biometrics scenarios) using 2400 Facial Recognition Technology face images. The diversity property is also examined.

Vertical nuclear proliferation.

PubMed

Sidel, Victor W

2007-01-01

All the nuclear-weapon states are working to develop new nuclear-weapon systems and upgrade their existing ones. Although the US Congress has recently blocked further development of small nuclear weapons and earth-penetrating nuclear weapons, the United States is planning a range of new warheads under the Reliable Replacement Warhead programme, and renewing its nuclear weapons infrastructure. The United Kingdom is spending 1 billion pounds sterling on updating the Atomic Weapons Establishment at Aldermaston, and about 20 billion pounds sterling on replacing its Vanguard submarines and maintaining its Trident warhead stockpile. The US has withdrawn from the Anti-Ballistic Missile Treaty and plans to install missile defence systems in Poland and the Czech Republic; Russia threatens to upgrade its nuclear countermeasures. The nuclear-weapon states should comply with their obligations under Article VI of the Non-Proliferation Treaty, as summarised in the 13-point plan agreed at the 2000 NPT Review Conference, and they should negotiate a Nuclear Weapons Convention.

Development of replication-deficient adenovirus malaria vaccines.

PubMed

Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

2017-03-01

Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

Systematics of strong nuclear amplification of gluon saturation from exclusive vector meson production in high energy electron-nucleus collisions

NASA Astrophysics Data System (ADS)

Mäntysaari, Heikki; Venugopalan, Raju

2018-06-01

We show that gluon saturation gives rise to a strong modification of the scaling in both the nuclear mass number A and the virtuality Q2 of the vector meson production cross-section in exclusive deep-inelastic scattering off nuclei. We present qualitative analytic expressions for how the scaling exponents are modified as well as quantitative predictions that can be tested at an Electron-Ion Collider.

Molecular phylogeny of the Anopheles gambiae complex suggests genetic introgression between principal malaria vectors.

PubMed Central

Besansky, N J; Powell, J R; Caccone, A; Hamm, D M; Scott, J A; Collins, F H

1994-01-01

The six Afrotropical species of mosquitoes comprising the Anopheles gambiae complex include the most efficient vectors of malaria in the world as well as a nonvector species. The accepted interpretation of evolutionary relationships among these species is based on chromosomal inversions and suggests that the two principal vectors, A. gambiae and Anopheles arabiensis, are on distant branches of the phylogenetic tree. However, DNA sequence data indicate that these two species are sister taxa and suggest gene flow between them. These results have important implications for malaria control strategies involving the replacement of vector with nonvector populations. Images PMID:8041714

Nuclear routing networks span between nuclear pore complexes and genomic DNA to guide nucleoplasmic trafficking of biomolecules

PubMed Central

Malecki, Marek; Malecki, Bianca

2012-01-01

In health and disease, biomolecules, which are involved in gene expression, recombination, or reprogramming have to traffic through the nucleoplasm, between nuclear pore complexes (NPCs) and genomic DNA (gDNA). This trafficking is guided by the recently revealed nuclear routing networks (NRNs). In this study, we aimed to investigate, if the NRNs have established associations with the genomic DNA in situ and if the NRNs have capabilities to bind the DNA de novo. Moreover, we aimed to study further, if nucleoplasmic trafficking of the histones, rRNA, and transgenes’ vectors, between the NPCs and gDNA, is guided by the NRNs. We used Xenopus laevis oocytes as the model system. We engineered the transgenes’ DNA vectors equipped with the SV40 LTA nuclear localization signals (NLS) and/or HIV Rev nuclear export signals (NES). We purified histones, 5S rRNA, and gDNA. We rendered all these molecules superparamagnetic and fluorescent for detection with nuclear magnetic resonance (NMR), total reflection x-ray fluorescence (TXRF), energy dispersive x-ray spectroscopy (EDXS), and electron energy loss spectroscopy (EELS). The NRNs span between the NPCs and genomic DNA. They form firm bonds with the gDNA in situ. After complete digestion of the nucleic acids with the RNases and DNases, the newly added DNA - modified with the dNTP analogs, bonds firmly to the NRNs. Moreover, the NRNs guide the trafficking of the DNA transgenes’ vectors - modified with the SV40 LTA NLS, following their import into the nuclei through the NPCs. The pathway is identical to that of histones. The NRNs also guide the trafficking of the DNA transgenes’ vectors, modified with the HIV Rev NES, to the NPCs, followed by their export out of the nuclei. Ribosomal RNAs follow the same pathway. To summarize, the NRNs are the structures connecting the NPCs and the gDNA. They guide the trafficking of the biomolecules between the NPCs and the gDNA. PMID:23275893

A median filter approach for correcting errors in a vector field

NASA Technical Reports Server (NTRS)

Schultz, H.

1985-01-01

Techniques are presented for detecting and correcting errors in a vector field. These methods employ median filters which are frequently used in image processing to enhance edges and remove noise. A detailed example is given for wind field maps produced by a spaceborne scatterometer. The error detection and replacement algorithm was tested with simulation data from the NASA Scatterometer (NSCAT) project.

Light vector mesons in the nuclear medium

NASA Astrophysics Data System (ADS)

Wood, M. H.; Nasseripour, R.; Weygand, D. P.; Djalali, C.; Tur, C.; Mosel, U.; Muehlich, P.; Adams, G.; Amaryan, M. J.; Ambrozewicz, P.; Anghinolfi, M.; Asryan, G.; Avakian, H.; Bagdasaryan, H.; Baillie, N.; Ball, J. P.; Baltzell, N. A.; Barrow, S.; Battaglieri, M.; Bedlinskiy, I.; Bektasoglu, M.; Bellis, M.; Benmouna, N.; Berman, B. L.; Biselli, A. S.; Blaszczyk, L.; Bouchigny, S.; Boiarinov, S.; Bradford, R.; Branford, D.; Briscoe, W. J.; Brooks, W. K.; Burkert, V. D.; Butuceanu, C.; Calarco, J. R.; Careccia, S. L.; Carman, D. S.; Carnahan, B.; Casey, L.; Chen, S.; Cheng, L.; Cole, P. L.; Collins, P.; Coltharp, P.; Crabb, D.; Crannell, H.; Crede, V.; Cummings, J. P.; Dashyan, N.; de Vita, R.; de Sanctis, E.; Degtyarenko, P. V.; Denizli, H.; Dennis, L.; Deur, A.; Dharmawardane, K. V.; Dickson, R.; Dodge, G. E.; Doughty, D.; Dugger, M.; Dytman, S.; Dzyubak, O. P.; Egiyan, H.; Egiyan, K. S.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fedotov, G.; Feldman, G.; Feuerbach, R. J.; Fradi, A.; Funsten, H.; Garçon, M.; Gavalian, G.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Goetz, J. T.; Gordon, C. I. O.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guler, N.; Guo, L.; Gyurjyan, V.; Hadjidakis, C.; Hafidi, K.; Hakobyan, H.; Hakobyan, R. S.; Hanretty, C.; Hardie, J.; Hassall, N.; Hersman, F. W.; Hicks, K.; Hleiqawi, I.; Holtrop, M.; Hyde-Wright, C. E.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Ito, M. M.; Jenkins, D.; Jo, H. S.; Johnstone, J. R.; Joo, K.; Juengst, H. G.; Kalantarians, N.; Kellie, J. D.; Khandaker, M.; Khetarpal, P.; Kim, W.; Klein, A.; Klein, F. J.; Klimenko, A. V.; Kossov, M.; Krahn, Z.; Kramer, L. H.; Kubarovsky, V.; Kuhn, J.; Kuhn, S. E.; Kuleshov, S. V.; Lachniet, J.; Laget, J. M.; Langheinrich, J.; Lawrence, D.; Li, Ji; Livingston, K.; Lu, H. Y.; MacCormick, M.; Markov, N.; Mattione, P.; McAleer, S.; McKinnon, B.; McNabb, J. W. C.; Mecking, B. A.; Mehrabyan, S.; Melone, J. J.; Mestayer, M. D.; Meyer, C. A.; Mibe, T.; Mikhailov, K.; Minehart, R.; Mirazita, M.; Miskimen, R.; Mokeev, V.; Moriya, K.; Morrow, S. A.; Moteabbed, M.; Mueller, J.; Munevar, E.; Mutchler, G. S.; Nadel-Turonski, P.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Niczyporuk, B. B.; Niroula, M. R.; Niyazov, R. A.; Nozar, M.; Osipenko, M.; Ostrovidov, A. I.; Park, K.; Pasyuk, E.; Paterson, C.; Pereira, S. Anefalos; Pierce, J.; Pivnyuk, N.; Pocanic, D.; Pogorelko, O.; Pozdniakov, S.; Preedom, B. M.; Price, J. W.; Prok, Y.; Protopopescu, D.; Raue, B. A.; Riccardi, G.; Ricco, G.; Ripani, M.; Ritchie, B. G.; Ronchetti, F.; Rosner, G.; Rossi, P.; Sabatié, F.; Salamanca, J.; Salgado, C.; Santoro, J. P.; Sapunenko, V.; Schumacher, R. A.; Serov, V. S.; Sharabian, Y. G.; Sharov, D.; Shvedunov, N. V.; Smith, E. S.; Smith, L. C.; Sober, D. I.; Sokhan, D.; Stavinsky, A.; Stepanyan, S.; Stepanyan, S. S.; Stokes, B. E.; Stoler, P.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tedeschi, D. J.; Tkabladze, A.; Tkachenko, S.; Todor, L.; Ungaro, M.; Vineyard, M. F.; Vlassov, A. V.; Watts, D. P.; Weinstein, L. B.; Williams, M.; Wolin, E.; Yegneswaran, A.; Zana, L.; Zhang, B.; Zhang, J.; Zhao, B.; Zhao, Z. W.

2008-07-01

The light vector mesons (ρ,ω, and ϕ) were produced in deuterium, carbon, titanium, and iron targets in a search for possible in-medium modifications to the properties of the ρ meson at normal nuclear densities and zero temperature. The vector mesons were detected with the CEBAF Large Acceptance Spectrometer (CLAS) via their decays to e+e-. The rare leptonic decay was chosen to reduce final-state interactions. A combinatorial background was subtracted from the invariant mass spectra using a well-established event-mixing technique. The ρ-meson mass spectrum was extracted after the ω and ϕ signals were removed in a nearly model-independent way. Comparisons were made between the ρ mass spectra from the heavy targets (A>2) with the mass spectrum extracted from the deuterium target. With respect to the ρ-meson mass, we obtain a small shift compatible with zero. Also, we measure widths consistent with standard nuclear many-body effects such as collisional broadening and Fermi motion.

Hyperspectral recognition of processing tomato early blight based on GA and SVM

NASA Astrophysics Data System (ADS)

Yin, Xiaojun; Zhao, SiFeng

2013-03-01

Processing tomato early blight seriously affect the yield and quality of its.Determine the leaves spectrum of different disease severity level of processing tomato early blight.We take the sensitive bands of processing tomato early blight as support vector machine input vector.Through the genetic algorithm(GA) to optimize the parameters of SVM, We could recognize different disease severity level of processing tomato early blight.The result show:the sensitive bands of different disease severity levels of processing tomato early blight is 628-643nm and 689-692nm.The sensitive bands are as the GA and SVM input vector.We get the best penalty parameters is 0.129 and kernel function parameters is 3.479.We make classification training and testing by polynomial nuclear,radial basis function nuclear,Sigmoid nuclear.The best classification model is the radial basis function nuclear of SVM. Training accuracy is 84.615%,Testing accuracy is 80.681%.It is combined GA and SVM to achieve multi-classification of processing tomato early blight.It is provided the technical support of prediction processing tomato early blight occurrence, development and diffusion rule in large areas.

Tissue-specific expression of silkmoth chorion genes in vivo using Bombyx mori nuclear polyhedrosis virus as a transducing vector.

PubMed Central

Iatrou, K; Meidinger, R G

1990-01-01

A pair of silkmoth chorion chromosomal genes, HcA.12-HcB.12, was inserted into a baculovirus transfer vector, pBmp2, derived from the nuclear polyhedrosis virus of Bombyx mori. This vector, which permits the insertion of foreign genetic material in the vicinity of a mutationally inactivated polyhedrin gene, was used to acquire the corresponding recombinant virus. Injection of mutant silkmoth pupae that lack all Hc chorion genes with the recombinant virus resulted in the infection of all internal organs including follicular tissue. Analysis of RNA from infected tissues has demonstrated that the two chorion genes present in the viral genome are correctly transcribed under the control of their own promoter in follicular cells, the tissue in which chorion genes are normally expressed. The chorion primary transcripts are also correctly processed in the infected follicular cells and yield mature mRNAs indistinguishable from authentic chorion mRNAs present in wild-type follicles. These results demonstrate that recombinant nuclear polyhedrosis viruses can be used as transducing vectors for introducing genetic material of host origin into the cells of the organism and that the transduced genes are transiently expressed in a tissue-specific manner under the control of their resident regulatory sequences. Thus we show the in vivo expression of cloned genes under cellular promoter control in an insect other than Drosophila melanogaster. The approach should be applicable to all insect systems that are subject to nuclear polyhedrosis virus infection. Images PMID:2187186

Epidemiological Implications of Host Biodiversity and Vector Biology: Key Insights from Simple Models.

PubMed

Dobson, Andrew D M; Auld, Stuart K J R

2016-04-01

Models used to investigate the relationship between biodiversity change and vector-borne disease risk often do not explicitly include the vector; they instead rely on a frequency-dependent transmission function to represent vector dynamics. However, differences between classes of vector (e.g., ticks and insects) can cause discrepancies in epidemiological responses to environmental change. Using a pair of disease models (mosquito- and tick-borne), we simulated substitutive and additive biodiversity change (where noncompetent hosts replaced or were added to competent hosts, respectively), while considering different relationships between vector and host densities. We found important differences between classes of vector, including an increased likelihood of amplified disease risk under additive biodiversity change in mosquito models, driven by higher vector biting rates. We also draw attention to more general phenomena, such as a negative relationship between initial infection prevalence in vectors and likelihood of dilution, and the potential for a rise in density of infected vectors to occur simultaneously with a decline in proportion of infected hosts. This has important implications; the density of infected vectors is the most valid metric for primarily zoonotic infections, while the proportion of infected hosts is more relevant for infections where humans are a primary host.

Stokes vector based interpolation method to improve the efficiency of bio-inspired polarization-difference imaging in turbid media

NASA Astrophysics Data System (ADS)

Guan, Jinge; Ren, Wei; Cheng, Yaoyu

2018-04-01

We demonstrate an efficient polarization-difference imaging system in turbid conditions by using the Stokes vector of light. The interaction of scattered light with the polarizer is analyzed by the Stokes-Mueller formalism. An interpolation method is proposed to replace the mechanical rotation of the polarization axis of the analyzer theoretically, and its performance is verified by the experiment at different turbidity levels. We show that compared with direct imaging, the Stokes vector based imaging method can effectively reduce the effect of light scattering and enhance the image contrast.

Hypercluster - Parallel processing for computational mechanics

NASA Technical Reports Server (NTRS)

Blech, Richard A.

1988-01-01

An account is given of the development status, performance capabilities and implications for further development of NASA-Lewis' testbed 'hypercluster' parallel computer network, in which multiple processors communicate through a shared memory. Processors have local as well as shared memory; the hypercluster is expanded in the same manner as the hypercube, with processor clusters replacing the normal single processor node. The NASA-Lewis machine has three nodes with a vector personality and one node with a scalar personality. Each of the vector nodes uses four board-level vector processors, while the scalar node uses four general-purpose microcomputer boards.

Transfection of mitochondria: strategy towards a gene therapy of mitochondrial DNA diseases.

PubMed Central

Seibel, P; Trappe, J; Villani, G; Klopstock, T; Papa, S; Reichmann, H

1995-01-01

Successes in classical gene therapies have been achieved by placing a corrected copy of a defective nuclear gene in cells. A similar gene replacement approach for a mutant mitochondrial genome is invariably linked to the use of a yet unavailable mitochondrial transfection vector. Here we show that DNA coupled covalently to a short mitochondrial leader peptide (chimera) can enter mitochondria via the protein import pathway, opening a new way for gene-, antisense-RNA- or antisense-DNA-delivery in molecular therapies. The import behavior of the purified chimera, composed of the amino-terminal leader peptide of the rat ornithine transcarbamylase (OTC) and a double stranded DNA molecule (17 bp or 322 bp), was tested by incubating with coupled and 'energized' rat liver mitochondria in the presence of reticulocyte lysate. The chimera was translocated with a high efficiency into the matrix of mitochondria utilizing the protein import pathway, independent from the size of its passenger DNA. Images PMID:7870573

Vector Mesons in Cold Nuclear Matter

NASA Astrophysics Data System (ADS)

Rodrigues, Tulio E.; Dias de Toledo Arruda-Neto, Joāo

2013-03-01

The attenuation of vector mesons in cold nuclear matter is studied through the mechanism of incoherent photoproduction off complex nuclei. The latter is described via the time-dependent multi-collisional Monte Carlo (MCMC) intranuclear cascade model. The results for the transparency ratios of ω mesons reproduce previous measurements of CB-ELSA/TAPS with an inelastic ωN cross section around 40 mb for ρω ~ 1.1 GeV/c. The corresponding in-medium width (nuclear rest frame) is extracted dinamically from the algorithm and depends on the average nuclear density pN and target nucleus: ~ 49.2 MeV/c2 for carbon (pN 0.114 far-3) and ~ 77.3 MeV/c2 for lead (pN 0.137 far--3). The calculations fail to reproduce the huge absorption observed at JLab assuming the same inelastic cross section and the discrepancy between the two experiments remains a challenge.

The harmonic oscillator and nuclear physics

NASA Technical Reports Server (NTRS)

Rowe, D. J.

1993-01-01

The three-dimensional harmonic oscillator plays a central role in nuclear physics. It provides the underlying structure of the independent-particle shell model and gives rise to the dynamical group structures on which models of nuclear collective motion are based. It is shown that the three-dimensional harmonic oscillator features a rich variety of coherent states, including vibrations of the monopole, dipole, and quadrupole types, and rotations of the rigid flow, vortex flow, and irrotational flow types. Nuclear collective states exhibit all of these flows. It is also shown that the coherent state representations, which have their origins in applications to the dynamical groups of the simple harmonic oscillator, can be extended to vector coherent state representations with a much wider range of applicability. As a result, coherent state theory and vector coherent state theory become powerful tools in the application of algebraic methods in physics.

Maintaining a highly-qualified nuclear industry workforce.

PubMed

McAndrew-Benavides, Elizabeth

2011-01-01

Since 2001, the nuclear industry has conducted a series of staffing assessments to better understand workforce demographics and predict future workforce demands. The industry's 2007 workforce survey indicated that in the next 5 y, up to 35% of the current nuclear workforce could retire and would need to be replaced. Thousands of individuals will need to be hired to replace the retirees, especially in engineering, maintenance and operations. Because of the challenges at hand, NEI convened the Workforce Working Group to make recommendations to address recruitment, retention and education needs. Their recommendations are now being implemented. Copyright © 2010 Health Physics Society

Mineral Replacement Reactions as a Precursor to Strain Localisation: an (HR-)EBSD approach

NASA Astrophysics Data System (ADS)

Gardner, J.; Wheeler, J.; Wallis, D.; Hansen, L. N.; Mariani, E.

2017-12-01

Much remains to be learned about the links between metamorphism and deformation. Our work investigates the behaviour of fluid-mediated mineral replacement reaction products when exposed to subsequent shear stresses. We focus on albite from a metagabbro that has experienced metamorphism and subsequent deformation at greenschist facies, resulting in a reduction in grain size and associated strain localisation. EBSD maps show that prior to grain size reduction, product grains are highly distorted, yet they formed, and subsequently deformed, at temperatures at which extensive dislocation creep is unlikely. The Weighted Burgers Vector can be used to quantitatively describe the types of Burgers vectors present in geometrically necessary dislocation (GND) populations derived from 2-D EBSD map data. Application of this technique to the distorted product grains reveals the prominence of, among others, dislocations with apparent [010] Burgers vectors. This supports (with some caveats) the idea that dislocation creep is not responsible for the observed lattice distortion, as there are no known slip systems in plagioclase with a [010] Burgers vector. Distortion in a replacement microstructure has also been attributed to the presence of nanoscale product grains, which share very similar, but not identical, orientations due to topotactic nucleation from adjacent sites on the same substrate. As a precipitate, the product grains should be expected to be largely free of elastic strain. However, high angular resolution EBSD results demonstrate that product grains contain both elastic strains (> 10-3) and residual stresses (several hundred MPa), as well as GND densities on the order of 1014-1015 m-2. Thus we suggest the observed distortion (elastic strain plus rotations) in the lattice is produced during the mineral replacement reaction by a lattice mismatch and volume change between parent and product. Stored strain energy then provides a driving force for recovery and recrystallization. Recrystallization produces smaller grains with high angle boundaries, reducing the strength of, and allowing deformation to localise in, the albite phase. Grain size reduction in turn facilitates shear deformation to high strains by a grain size sensitive mechanism (fluid-assisted diffusion creep).

Influence of 5'-flanking sequence on 4.5SI RNA gene transcription by RNA polymerase III.

PubMed

Gogolevskaya, Irina K; Stasenko, Danil V; Tatosyan, Karina A; Kramerov, Dmitri A

2018-05-01

Short nuclear 4.5SI RNA can be found in three related rodent families. Its function remains unknown. The genes of 4.5SI RNA contain an internal promoter of RNA polymerase III composed of the boxes A and B. Here, the effect of the sequence immediately upstream of the mouse 4.5SI RNA gene on its transcription was studied. The gene with deletions and substitutions in the 5'-flanking sequence was used to transfect HeLa cells and its transcriptional activity was evaluated from the cellular level of 4.5SI RNA. Single-nucleotide substitutions in the region adjacent to the transcription start site (positions -2 to -8) decreased the expression activity of the gene down to 40%-60% of the control. The substitution of the conserved pentanucleotide AGAAT (positions -14 to -18) could either decrease (43%-56%) or increase (134%) the gene expression. A TATA-like box (TACATGA) was found at positions -24 to -30 of the 4.5SI RNA gene. Its replacement with a polylinker fragment of the vector did not decrease the transcription level, while its replacement with a GC-rich sequence almost completely (down to 2%-5%) suppressed the transcription of the 4.5SI RNA gene. The effect of plasmid sequences bordering the gene on its transcription by RNA polymerase III is discussed.

Intra-Operative Vector Flow Imaging Using Ultrasound of the Ascending Aorta among 40 Patients with Normal, Stenotic and Replaced Aortic Valves.

PubMed

Hansen, Kristoffer Lindskov; Møller-Sørensen, Hasse; Kjaergaard, Jesper; Jensen, Maiken Brit; Lund, Jens Teglgaard; Pedersen, Mads Møller; Lange, Theis; Jensen, Jørgen Arendt; Nielsen, Michael Bachmann

2016-10-01

Stenosis of the aortic valve gives rise to more complex blood flows with increased velocities. The angle-independent vector flow ultrasound technique transverse oscillation was employed intra-operatively on the ascending aorta of (I) 20 patients with a healthy aortic valve and 20 patients with aortic stenosis before (IIa) and after (IIb) valve replacement. The results indicate that aortic stenosis increased flow complexity (p < 0.0001), induced systolic backflow (p < 0.003) and reduced systolic jet width (p < 0.0001). After valve replacement, the systolic backflow and jet width were normalized (p < 0.52 and p < 0.22), but flow complexity was not (p < 0.0001). Flow complexity (p < 0.0001), systolic jet width (p < 0.0001) and systolic backflow (p < 0.001) were associated with peak systolic velocity. The study found that aortic stenosis changes blood flow in the ascending aorta and valve replacement corrects some of these changes. Transverse oscillation may be useful for assessment of aortic stenosis and optimization of valve surgery. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Design and test of a high power electromechanical actuator for thrust vector control

NASA Technical Reports Server (NTRS)

Cowan, J. R.; Myers, W. N.

1992-01-01

NASA-Marshall is involved in the development of electromechanical actuators (EMA) for thrust-vector control (TVC) system testing and implementation in spacecraft control/gimballing systems, with a view to the replacement of hydraulic hardware. TVC system control is furnished by solid state controllers and power supplies; a pair of resolvers supply position feedback to the controller for precise positioning. Performance comparisons between EMA and hydraulic TVC systems are performed.

Design and test of a high power electromechanical actuator for thrust vector control

NASA Astrophysics Data System (ADS)

Cowan, J. R.; Myers, W. N.

1992-07-01

NASA-Marshall is involved in the development of electromechanical actuators (EMA) for thrust-vector control (TVC) system testing and implementation in spacecraft control/gimballing systems, with a view to the replacement of hydraulic hardware. TVC system control is furnished by solid state controllers and power supplies; a pair of resolvers supply position feedback to the controller for precise positioning. Performance comparisons between EMA and hydraulic TVC systems are performed.

The Future of the U.S. Nuclear Weapons Program

NASA Astrophysics Data System (ADS)

Brooks, Linton F.

2007-03-01

This paper will examine our plans for the future of the U.S. nuclear weapons program including efforts to ``transform'' the stockpile and supporting infrastructure. We proceed from the premise that the United States will need a safe, secure, and reliable nuclear deterrent for the foreseeable future. Moreover, the Stockpile Stewardship Program is working. Today's stockpile---comprised of legacy warheads left over from the Cold War---is safe and reliable. That said, we see increased risk, absent nuclear testing, in assuring the long-term safety and reliability of our current stockpile. Nor is today's nuclear weapons complex sufficiently ``responsive'' to fixing technical problems in the stockpile, or to potential adverse geopolitical change. Our task is to work to ensure that the U.S. nuclear weapons enterprise, including the stockpile and supporting infrastructure, meets long-term national security needs. Our approach is to develop and field replacement warheads for the legacy stockpile---so-called Reliable Replacement Warheads (RRW)---as a means to transform both the nuclear stockpile and supporting infrastructure.

Microprocessor-based control systems application in nuclear power plant critical systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shah, M.R.; Nowak, J.B.

Microprocessor-based control systems have been used in fossil power plants and are receiving greater acceptance for application in nuclear plants. This technology is not new but it does require unique considerations when applied to nuclear power plants. Sargent and Lundy (S and L) has used a microprocessor-based component logic control system (interposing Logic System) for safety- and non-safety-related components in nuclear power plants under construction overseas. Currently, S and L is in the design stage to replace an existing analog control system with a microprocessor-based control system in the U.S. The trend in the industry is to replace systems inmore » existing plants or design new power plants with microprocessor-based control systems.« less

10 CFR 34.27 - Leak testing and replacement of sealed sources.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Leak testing and replacement of sealed sources. 34.27 Section 34.27 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Equipment § 34.27 Leak testing and replacement...

10 CFR 34.27 - Leak testing and replacement of sealed sources.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Leak testing and replacement of sealed sources. 34.27 Section 34.27 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Equipment § 34.27 Leak testing and replacement...

10 CFR 34.27 - Leak testing and replacement of sealed sources.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Leak testing and replacement of sealed sources. 34.27 Section 34.27 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Equipment § 34.27 Leak testing and replacement...

10 CFR 34.27 - Leak testing and replacement of sealed sources.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Leak testing and replacement of sealed sources. 34.27 Section 34.27 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Equipment § 34.27 Leak testing and replacement...

10 CFR 34.27 - Leak testing and replacement of sealed sources.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Leak testing and replacement of sealed sources. 34.27 Section 34.27 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Equipment § 34.27 Leak testing and replacement...

Deterrence with China: Avoiding Nuclear Miscalculation

DTIC Science & Technology

2014-01-01

When each nation can manage these three elements in the correct way, the cost -benefit calculations of each side should favor deterrence of a...under pressure to justify the cost of its plans to replace its SSBN fleet. After a recent 2-year delay in the planned SSBN replacement program, any...of CPGS may prove advantageous in some scenarios,31 but those advantages do not come with- out a cost to nuclear deterrence stability with China—a

[Lymphoscintigrams with anatomical landmarks obtained with vector graphics].

PubMed

Rubini, Giuseppe; Antonica, Filippo; Renna, Maria Antonia; Ferrari, Cristina; Iuele, Francesca; Stabile Ianora, Antonio Amato; Losco, Matteo; Niccoli Asabella, Artor

2012-11-01

Nuclear medicine images are difficult to interpret because they do not include anatomical details. The aim of this study was to obtain lymphoscintigrams with anatomical landmarks that could be easily interpreted by General Physicians. Traditional lymphoscintigrams were processed with Adobe© Photoshop® CS6 and converted into vector images created by Illustrator®. The combination with a silhouette vector improved image interpretation, without resulting in longer radiation exposure or acquisition times.

The new MSFC Solar vector magnetograph. Center director's discretionary fund

NASA Technical Reports Server (NTRS)

Hagyard, M. J.; West, E. A.; Cumings, N. P.

1984-01-01

The unique MSFC solar vector magnetograph allows measurements of all three components of the Sun's photospheric magnetic field over a wide field-of-view with spatial resolution determined by a 2.7 x 2.7 arc second pixel size. This system underwent extensive modifications to improve its sensitivity and temporal response. The modifications included replacing an SEC vidicon detector with a solid-state CCD camera; replacing the original digital logic circuitry with an electronic controller and a computer to provide complete, programmable control over the entire operation of the magnetograph; and installing a new polarimeter which consists of a single electro-optical modulator coupled with interchangeable waveplates mounted on a rotating assembly. The system is described and results of calibrations and tests are presented. Initial observations of solar magnetic fields with the new magnetograph are presented.

Substitution of blood coagulation factor X-binding to Ad5 by position-specific PEGylation: Preventing vector clearance and preserving infectivity.

PubMed

Krutzke, L; Prill, J M; Engler, T; Schmidt, C Q; Xu, Z; Byrnes, A P; Simmet, T; Kreppel, F

2016-08-10

The biodistribution of adenovirus type 5 (Ad5) vector particles is heavily influenced by interaction of the particles with plasma proteins, including coagulation factor X (FX), which binds specifically to the major Ad5 capsid protein hexon. FX mediates hepatocyte transduction by intravenously-injected Ad5 vectors and shields vector particles from neutralization by natural antibodies and complement. In mice, mutant Ad5 vectors that are ablated for FX-binding become detargeted from hepatocytes, which is desirable for certain applications, but unfortunately such FX-nonbinding vectors also become sensitive to neutralization by mouse plasma proteins. To improve the properties of Ad5 vectors for systemic delivery, we developed a strategy to replace the natural FX shield by a site-specific chemical polyethylene glycol shield. Coupling of polyethylene glycol to a specific site in hexon hypervariable region 1 yielded vector particles that were protected from neutralization by natural antibodies and complement although they were unable to bind FX. These vector particles evaded macrophages in vitro and showed significantly improved pharmacokinetics and hepatocyte transduction in vivo. Thus, site-specific shielding of Ad5 vectors with polyethylene glycol rendered vectors FX-independent and greatly improved their properties for systemic gene therapy. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

T-vector and in vivo recombination as tools to construct a large antibody library of breast cancer.

PubMed

Lv, Yong-Gang; Wang, Ting; Yuan, Shi-Fang; Li, Nan-Lin; Chen, Jiang-Hao; Zhao, Ai-Zhi; Ling, Rui; Wang, Ling

2010-06-01

The emergence of phage antibody libraries is an important advance in the field of antibody engineering. It provides a useful methodology to produce human antibodies and has the potential to replace traditional hybridoma technology. In our research, we used T-vector and in vivo recombination to construct a large antibody library from breast cancer patients. The use of T-vector considerably increased the cloning efficiency, and the diversity of the library could be increased easily using in vivo recombination. Taken together, a combination of these two techniques might be valuable in constructing a large antibody library.

QuickMap: a public tool for large-scale gene therapy vector insertion site mapping and analysis.

PubMed

Appelt, J-U; Giordano, F A; Ecker, M; Roeder, I; Grund, N; Hotz-Wagenblatt, A; Opelz, G; Zeller, W J; Allgayer, H; Fruehauf, S; Laufs, S

2009-07-01

Several events of insertional mutagenesis in pre-clinical and clinical gene therapy studies have created intense interest in assessing the genomic insertion profiles of gene therapy vectors. For the construction of such profiles, vector-flanking sequences detected by inverse PCR, linear amplification-mediated-PCR or ligation-mediated-PCR need to be mapped to the host cell's genome and compared to a reference set. Although remarkable progress has been achieved in mapping gene therapy vector insertion sites, public reference sets are lacking, as are the possibilities to quickly detect non-random patterns in experimental data. We developed a tool termed QuickMap, which uniformly maps and analyzes human and murine vector-flanking sequences within seconds (available at www.gtsg.org). Besides information about hits in chromosomes and fragile sites, QuickMap automatically determines insertion frequencies in +/- 250 kb adjacency to genes, cancer genes, pseudogenes, transcription factor and (post-transcriptional) miRNA binding sites, CpG islands and repetitive elements (short interspersed nuclear elements (SINE), long interspersed nuclear elements (LINE), Type II elements and LTR elements). Additionally, all experimental frequencies are compared with the data obtained from a reference set, containing 1 000 000 random integrations ('random set'). Thus, for the first time a tool allowing high-throughput profiling of gene therapy vector insertion sites is available. It provides a basis for large-scale insertion site analyses, which is now urgently needed to discover novel gene therapy vectors with 'safe' insertion profiles.

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

PubMed

Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

2012-11-01

Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

Mouse mammary tumor virus-based vector transduces non-dividing cells, enters the nucleus via a TNPO3-independent pathway and integrates in a less biased fashion than other retroviruses.

PubMed

Konstantoulas, Constantine James; Indik, Stanislav

2014-04-30

Mouse mammary tumor virus (MMTV) is a complex, milk-born betaretrovirus, which preferentially infects dendritic cells (DC) in the gastrointestinal tract and then spreads to T and B lymphocytes and finally to the mammary gland. It is not clear how the prototypic betaretrovirus infects mucosal DCs and naïve lymphocytes as these cells are considered to be non-proliferative. Studies of MMTV biology have been hampered by the difficulty of obtaining sufficient virus/vector titers after transfection of a molecular clone in cultured cells. To surmount this barrier we developed a novel MMTV-based vector system with a split genome design containing potent posttranscriptional regulatory functions. Using this system, vector particles were produced to markedly greater titers (>1000-fold) than those obtained previously. The titers (>106 transduction units /ml) were comparable to those achieved with lentiviral or gammaretroviral vectors. Importantly, the vector transduced the enhanced green fluorescence protein gene into the chromosomes of non-dividing cells, such as cells arrested at the G2/M phase of the cell cycle and unstimulated hematopoietic progenitor cells, at an efficiency similar to that obtained with the HIV-1-based vector. In contrast to HIV-1, MMTV transductions were not affected by knocking down the expression of a factor involved in nuclear import of the HIV-1 pre-integration complexes, TNPO3. In contrast to HIV-1, the MMTV-based vector did not preferentially integrate in transcription units. Additionally, no preference for integration near transcription start sites, the regions preferentially targeted by gammaretroviral vectors, was observed. The vector derived from MMTV exhibits a random integration pattern. Overall, the betaretroviral vector system should facilitate molecular virology studies of the prototypic betaretrovirus as well as studies attempting to elucidate fundamental cellular processes such as nuclear import pathways. Random integration in cycling and non-cycling cells may be applicable in unbiased gene delivery.

Long-term systemic therapy of Fabry disease in a knockout mouse by adeno-associated virus-mediated muscle-directed gene transfer

PubMed Central

Takahashi, Hiroshi; Hirai, Yukihiko; Migita, Makoto; Seino, Yoshihiko; Fukuda, Yuh; Sakuraba, Hitoshi; Kase, Ryoichi; Kobayashi, Toshihide; Hashimoto, Yasuhiro; Shimada, Takashi

2002-01-01

Fabry disease is a systemic disease caused by genetic deficiency of a lysosomal enzyme, α-galactosidase A (α-gal A), and is thought to be an important target for enzyme replacement therapy. We studied the feasibility of gene-mediated enzyme replacement for Fabry disease. The adeno-associated virus (AAV) vector containing the α-gal A gene was injected into the right quadriceps muscles of Fabry knockout mice. A time course study showed that α-gal A activity in plasma was increased to ≈25% of normal mice and that this elevated activity persisted for up to at least 30 weeks without development of anti-α-gal A antibodies. The α-gal A activity in various organs of treated Fabry mice remained 5–20% of those observed in normal mice. Accumulated globotriaosylceramide in these organs was completely cleared by 25 weeks after vector injection. Reduction of globotriaosylceramide levels was also confirmed by immunohistochemical and electronmicroscopic analyses. Echocardiographic examination of treated mice demonstrated structural improvement of cardiac hypertrophy 25 weeks after the treatment. AAV vector-mediated muscle-directed gene transfer provides an efficient and practical therapeutic approach for Fabry disease. PMID:12370426

Vector processing efficiency of plasma MHD codes by use of the FACOM 230-75 APU

NASA Astrophysics Data System (ADS)

Matsuura, T.; Tanaka, Y.; Naraoka, K.; Takizuka, T.; Tsunematsu, T.; Tokuda, S.; Azumi, M.; Kurita, G.; Takeda, T.

1982-06-01

In the framework of pipelined vector architecture, the efficiency of vector processing is assessed with respect to plasma MHD codes in nuclear fusion research. By using a vector processor, the FACOM 230-75 APU, the limit of the enhancement factor due to parallelism of current vector machines is examined for three numerical codes based on a fluid model. Reasonable speed-up factors of approximately 6,6 and 4 times faster than the highly optimized scalar version are obtained for ERATO (linear stability code), AEOLUS-R1 (nonlinear stability code) and APOLLO (1-1/2D transport code), respectively. Problems of the pipelined vector processors are discussed from the viewpoint of restructuring, optimization and choice of algorithms. In conclusion, the important concept of "concurrency within pipelined parallelism" is emphasized.

Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells.

PubMed

Byrne, Susan M; Ortiz, Luis; Mali, Prashant; Aach, John; Church, George M

2015-02-18

Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient 'knock-in' targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Near-Wall Velocity Field Measurements of a Very Low Momentum Flux Transverse Jet

DTIC Science & Technology

2014-06-01

nozzle was used to generate olive oil droplets approximately 1 μm in diameter with approximately 20 particles per 32 x 32 px interrogation region...pair, two for each window size, 64 x 64 px and 32 x 32 px. Vectors with cross-correlation peak ratios Q < 1.7 were eliminated and replaced with a... vector whose value was interpolated by using values of its nearest neighbors. III. Results and Discussion A total of five momentum flux ratios were

Transgene expression of green fluorescent protein and germ line transmission in cloned pigs derived from in vitro transfected adult fibroblasts.

PubMed

Brunetti, Dario; Perota, Andrea; Lagutina, Irina; Colleoni, Silvia; Duchi, Roberto; Calabrese, Fiorella; Seveso, Michela; Cozzi, Emanuele; Lazzari, Giovanna; Lucchini, Franco; Galli, Cesare

2008-12-01

The pig represents the xenogeneic donor of choice for future organ transplantation in humans for anatomical and physiological reasons. However, to bypass several immunological barriers, strong and stable human genes expression must occur in the pig's organs. In this study we created transgenic pigs using in vitro transfection of cultured cells combined with somatic cell nuclear transfer (SCNT) to evaluate the ubiquitous transgene expression driven by pCAGGS vector in presence of different selectors. pCAGGS confirmed to be a very effective vector for ubiquitous transgene expression, irrespective of the selector that was used. Green fluorescent protein (GFP) expression observed in transfected fibroblasts was also maintained after nuclear transfer, through pre- and postimplantation development, at birth and during adulthood. Germ line transmission without silencing of the transgene was demonstrated. The ubiquitous expression of GFP was clearly confirmed in several tissues including endothelial cells, thus making it a suitable vector for the expression of multiple genes relevant to xenotransplantation where tissue specificity is not required. Finally cotransfection of green and red fluorescence protein transgenes was performed in fibroblasts and after nuclear transfer blastocysts expressing both fluorescent proteins were obtained.

Study on a hypothetical replacement of nuclear electricity by wind power in Sweden

NASA Astrophysics Data System (ADS)

Wagner, F.; Rachlew, E.

2016-05-01

The Swedish electricity supply system benefits strongly from the natural conditions which allow a high share of hydroelectricity. A complete supply is, however, not possible. Up to now, nuclear power is the other workhorse to serve the country with electricity. Thus, electricity production of Sweden is basically CO2 -free and Sweden has reached an environmental status which others in Europe plan to reach in 2050. Furthermore, there is an efficient exchange within the Nordic countries, Nordpol, which can ease possible capacity problems during dry cold years. In this study we investigate to what extent and with what consequences the base load supply of nuclear power can be replaced by intermittent wind power. Such a scenario leads unavoidably to high wind power installations. It is shown that hydroelectricity cannot completely smooth out the fluctuations of wind power and an additional back-up system using fossil fuel is necessary. From the operational dynamics, this system has to be based on gas. The back-up system cannot be replaced by a storage using surplus electricity from wind power. The surplus is too little. To overcome this, further strong extension of wind power is necessary which leads, however, to a reduction of the use of hydroelectricity if the annual consumption is kept constant. In this case one fossil-free energy form is replaced by another, however, more complex one. A mix of wind power at 22.3GW plus a gas based back-up system with 8.6GW producing together 64.8TWh would replace the present infrastructure with 9GW nuclear power producing 63.8TWh electricity. The specific CO2 -emission increases to the double in this case. Pumped storage for the exclusive supply of Sweden does not seem to be a meaningful investment.-1

Impact of the Central Polypurine Tract on the Kinetics of Human Immunodeficiency Virus Type 1 Vector Transduction

PubMed Central

Van Maele, Bénédicte; De Rijck, Jan; De Clercq, Erik; Debyser, Zeger

2003-01-01

Lentiviral vectors derived from human immunodeficiency virus type 1 (HIV-1) show great promise as gene carriers for future gene therapy. Insertion of a fragment containing the central polypurine tract (cPPT) in HIV-1 vector constructs is known to enhance transduction efficiency drastically, reportedly by facilitating the nuclear import of HIV-1 cDNA through a central DNA flap. We have studied the impact of the cPPT on the kinetics of HIV-1 vector transduction by real-time PCR. The kinetics of total HIV-1 DNA, two-long-terminal-repeat (2-LTR) circles, and, by an Alu-PCR, integrated proviral DNA were monitored. About 6 to 12 h after transduction, the total HIV-1 DNA reached a maximum level, followed by a steep decrease. The 2-LTR circles peaked after 24 to 48 h and were diluted upon cell division. Integration of HIV-1 DNA was first detected at 12 h postinfection. When HIV-1 vectors that contained the cPPT were used, DNA synthesis was similar but a threefold higher amount of 2-LTR circles was detected, confirming the impact on nuclear import. Moreover, a 10-fold increase in the amount of integrated DNA was observed in the presence of the cPPT. Only in the absence of the cPPT was a saturation in 2-LTR circle formation seen at a high multiplicity of infection, suggesting a role for the cPPT in overcoming a barrier to the nuclear import of HIV-1 DNA. A major effect of the central DNA flap on the juxtaposition of both LTRs is unlikely, since transduction with HIV-1 vectors containing ectopic cPPT fragments resulted in increased amounts of 2-LTR circles as well as integrated DNA. Inhibitors of transduction by cPPT-containing HIV vectors were also studied by real-time PCR. The reverse transcriptase inhibitor azidothymidine (AZT) and the nonnucleoside reverse transcriptase inhibitor α-APA clearly inhibited viral DNA synthesis, whereas integrase inhibitors such as the diketo acid L-708,906 and the pyranodipyrimidine V-165 specifically inhibited integration. PMID:12663775

Validation of a recombinant human bactericidal/permeability-increasing protein (hBPI) expression vector using murine mammary gland tumor cells and the early development of hBPI transgenic goat embryos.

PubMed

Gui, Tao; Liu, Xing; Tao, Jia; Chen, Jianwen; Li, Yunsheng; Zhang, Meiling; Wu, Ronghua; Zhang, Yuanliang; Peng, Kaisong; Liu, Ya; Zhang, Xiaorong; Zhang, Yunhai

2013-12-01

Human bactericidal/permeability-increasing protein (hBPI) is the only antibacterial peptide which acts against both gram-negative bacteria and neutralizes endotoxins in human polymorphonuclear neutrophils; therefore, hBPI is of great value in clinical applications. In the study, we constructed a hBPI expression vector (pBC1-Loxp-Neo-Loxp-hBPI) containing the full-length hBPI coding sequence which could be specifically expressed in the mammary gland. To validate the function of the vector, in vitro cultured C127 (mouse mammary Carcinoma Cells) were transfected with the vector, and the transgenic cell clones were selected to express hBPI by hormone induction. The mRNA and protein expression of hBPI showed that the constructed vector was effective and suitable for future application in producing mammary gland bioreactor. Then, female and male goat fibroblasts were transfected with the vector, and two male and two female transgenic clonal cell lines were obtained. Using the transgenic cell lines as nuclear donors for somatic cell nuclear transfer, the reconstructed goat embryos produced from all four clones could develop to blastocysts in vitro. In conclusion, we constructed and validated an efficient mammary gland-specific hBPI expression vector, pBC1-Loxp-Neo-Loxp-hBPI, and transgenic hBPI goat embryos were successfully produced, laying foundations for future production of recombinant hBPI in goat mammary gland. Copyright © 2013 Elsevier B.V. All rights reserved.

Modeling Musical Context With Word2Vec

NASA Astrophysics Data System (ADS)

Herremans, Dorien; Chuan, Ching-Hua

2017-05-01

We present a semantic vector space model for capturing complex polyphonic musical context. A word2vec model based on a skip-gram representation with negative sampling was used to model slices of music from a dataset of Beethoven's piano sonatas. A visualization of the reduced vector space using t-distributed stochastic neighbor embedding shows that the resulting embedded vector space captures tonal relationships, even without any explicit information about the musical contents of the slices. Secondly, an excerpt of the Moonlight Sonata from Beethoven was altered by replacing slices based on context similarity. The resulting music shows that the selected slice based on similar word2vec context also has a relatively short tonal distance from the original slice.

A Simple And Rapid Minicircle DNA Vector Manufacturing System

PubMed Central

Kay, Mark A; He, Cheng-Yi; Chen, Zhi-Ying

2010-01-01

Minicircle DNA vectors consisting of a circular expression cassette devoid of the bacterial plasmid DNA backbone provides several advantages including sustained transgene expression in quiescent cells/tissues. Their use has been limited by labor-intensive production. We report on a strategy for making multiple genetic modifications in E.coli to construct a producer strain that stably expresses a set of inducible minicircle-assembly enzymes, the øC31-integrase and I-SceI homing-endonuclease. This bacterial strain is capable of producing highly purified minicircle yields in the same time frame as routine plasmid DNA. It is now feasible for minicircle DNA vectors to replace routine plasmids in mammalian transgene expression studies. PMID:21102455

An efficient system for the generation of marked genetic mutants in members of the genus Burkholderia.

PubMed

Shastri, Sravanthi; Spiewak, Helena L; Sofoluwe, Aderonke; Eidsvaag, Vigdis A; Asghar, Atif H; Pereira, Tyrone; Bull, Edward H; Butt, Aaron T; Thomas, Mark S

2017-01-01

To elucidate the function of a gene in bacteria it is vital that targeted gene inactivation (allelic replacement) can be achieved. Allelic replacement is often carried out by disruption of the gene of interest by insertion of an antibiotic-resistance marker followed by subsequent transfer of the mutant allele to the genome of the host organism in place of the wild-type gene. However, due to their intrinsic resistance to many antibiotics only selected antibiotic-resistance markers can be used in members of the genus Burkholderia, including the Burkholderia cepacia complex (Bcc). Here we describe the construction of improved antibiotic-resistance cassettes that specify resistance to kanamycin, chloramphenicol or trimethoprim effectively in the Bcc and related species. These were then used in combination with and/or to construct a series enhanced suicide vectors, pSHAFT2, pSHAFT3 and pSHAFT-GFP to facilitate effective allelic replacement in the Bcc. Validation of these improved suicide vectors was demonstrated by the genetic inactivation of selected genes in the Bcc species Burkholderia cenocepacia and B. lata, and in the non-Bcc species, B. thailandensis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

MANCOVA for one way classification with homogeneity of regression coefficient vectors

NASA Astrophysics Data System (ADS)

Mokesh Rayalu, G.; Ravisankar, J.; Mythili, G. Y.

2017-11-01

The MANOVA and MANCOVA are the extensions of the univariate ANOVA and ANCOVA techniques to multidimensional or vector valued observations. The assumption of a Gaussian distribution has been replaced with the Multivariate Gaussian distribution for the vectors data and residual term variables in the statistical models of these techniques. The objective of MANCOVA is to determine if there are statistically reliable mean differences that can be demonstrated between groups later modifying the newly created variable. When randomization assignment of samples or subjects to groups is not possible, multivariate analysis of covariance (MANCOVA) provides statistical matching of groups by adjusting dependent variables as if all subjects scored the same on the covariates. In this research article, an extension has been made to the MANCOVA technique with more number of covariates and homogeneity of regression coefficient vectors is also tested.

75 FR 60745 - Notice of Intent To Prepare a Supplemental Environmental Impact Statement for the Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-01

... Supplemental Environmental Impact Statement for the Nuclear Facility Portion of the Chemistry and Metallurgy... construction and operation of the nuclear facility portion of the Chemistry and Metallurgy Research Building... Chemistry and Metallurgy Research Building Replacement Project at Los Alamos National Laboratory, Los Alamos...

Potential for worldwide displacement of fossil-fuel electricity by nuclear energy in three decades based on extrapolation of regional deployment data.

PubMed

Qvist, Staffan A; Brook, Barry W

2015-01-01

There is an ongoing debate about the deployment rates and composition of alternative energy plans that could feasibly displace fossil fuels globally by mid-century, as required to avoid the more extreme impacts of climate change. Here we demonstrate the potential for a large-scale expansion of global nuclear power to replace fossil-fuel electricity production, based on empirical data from the Swedish and French light water reactor programs of the 1960s to 1990s. Analysis of these historical deployments show that if the world built nuclear power at no more than the per capita rate of these exemplar nations during their national expansion, then coal- and gas-fired electricity could be replaced worldwide in less than a decade. Under more conservative projections that take into account probable constraints and uncertainties such as differing relative economic output across regions, current and past unit construction time and costs, future electricity demand growth forecasts and the retiring of existing aging nuclear plants, our modelling estimates that the global share of fossil-fuel-derived electricity could be replaced within 25-34 years. This would allow the world to meet the most stringent greenhouse-gas mitigation targets.

Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years.

PubMed

Mwangangi, Joseph M; Mbogo, Charles M; Orindi, Benedict O; Muturi, Ephantus J; Midega, Janet T; Nzovu, Joseph; Gatakaa, Hellen; Githure, John; Borgemeister, Christian; Keating, Joseph; Beier, John C

2013-01-08

Over the past 20 years, numerous studies have investigated the ecology and behaviour of malaria vectors and Plasmodium falciparum malaria transmission on the coast of Kenya. Substantial progress has been made to control vector populations and reduce high malaria prevalence and severe disease. The goal of this paper was to examine trends over the past 20 years in Anopheles species composition, density, blood-feeding behaviour, and P. falciparum sporozoite transmission along the coast of Kenya. Using data collected from 1990 to 2010, vector density, species composition, blood-feeding patterns, and malaria transmission intensity was examined along the Kenyan coast. Mosquitoes were identified to species, based on morphological characteristics and DNA extracted from Anopheles gambiae for amplification. Using negative binomial generalized estimating equations, mosquito abundance over the period were modelled while adjusting for season. A multiple logistic regression model was used to analyse the sporozoite rates. Results show that in some areas along the Kenyan coast, Anopheles arabiensis and Anopheles merus have replaced An. gambiae sensu stricto (s.s.) and Anopheles funestus as the major mosquito species. Further, there has been a shift from human to animal feeding for both An. gambiae sensu lato (s.l.) (99% to 16%) and An. funestus (100% to 3%), and P. falciparum sporozoite rates have significantly declined over the last 20 years, with the lowest sporozoite rates being observed in 2007 (0.19%) and 2008 (0.34%). There has been, on average, a significant reduction in the abundance of An. gambiae s.l. over the years (IRR = 0.94, 95% CI 0.90-0.98), with the density standing at low levels of an average 0.006 mosquitoes/house in the year 2010. Reductions in the densities of the major malaria vectors and a shift from human to animal feeding have contributed to the decreased burden of malaria along the Kenyan coast. Vector species composition remains heterogeneous but in many areas An. arabiensis has replaced An. gambiae as the major malaria vector. This has important implications for malaria epidemiology and control given that this vector predominately rests and feeds on humans outdoors. Strategies for vector control need to continue focusing on tools for protecting residents inside houses but additionally employ outdoor control tools because these are essential for further reducing the levels of malaria transmission.

Digital I and C system upgrade integration technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, H. W.; Shih, C.; Wang, J. R.

2012-07-01

This work developed an integration technique for digital I and C system upgrade, the utility can replace the I and C systems step by step systematically by this method. Inst. of Nuclear Energy Research (INER) developed a digital Instrumentation and Control (I and C) replacement integration technique on the basis of requirement of the three existing nuclear power plants (NPPs), which are Chin-Shan (CS) NPP, Kuo-Sheng (KS) NPP, and Maanshan (MS) NPP, in Taiwan, and also developed the related Critical Digital Review (CDR) Procedure. The digital I and C replacement integration technique includes: (I) Establishment of Nuclear Power Plant Digitalmore » Replacement Integration Guideline, (2) Preliminary Investigation on I and C System Digitalization, (3) Evaluation on I and C System Digitalization, and (4) Establishment of I and C System Digitalization Architectures. These works can be a reference for performing I and C system digital replacement integration of the three existing NPPs of Taiwan Power Company (TPC). A CDR is the review for a critical system digital I and C replacement. The major reference of this procedure is EPRI TR- 1011710 (2005) 'Handbook for Evaluating Critical Digital Equipment and Systems' which was published by the Electric Power Research Inst. (EPRI). With this document, INER developed a TPC-specific CDR procedure. Currently, CDR becomes one of the policies for digital I and C replacement in TPC. The contents of this CDR procedure include: Scope, Responsibility, Operation Procedure, Operation Flow Chart, CDR review items. The CDR review items include the comparison of the design change, Software Verification and Validation (SVandV), Failure Mode and Effects Analysis (FMEA), Evaluation of Diversity and Defense-in-depth (D3), Evaluation of Watchdog Timer, Evaluation of Electromagnetic Compatibility (EMC), Evaluation of Grounding for System/Component, Seismic Evaluation, Witness and Inspection, Lessons Learnt from the Digital I and C Failure Events. A solid review can assure the quality of the digital I and C system replacement. (authors)« less

Vectoring gypsy moth nuclear polyhedrosis virus by Apanteles melanoscelus (Hym.:Braconidae)

Treesearch

B. Raimo; R.C. Reardon; J.D. Podgwaite

1977-01-01

Gypsy moth Lymantria dispar L. larvae were exposed to Apanteles melanoscelus (Ratzeburg) females contaminated with nuclear polyhedrosis virus. Three methods of contamination (ovipositor, total body surface, and exposure to infected hosts) and two exposure periods (2 and 24 hours) were tested. A significantly greater incidence of...

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction

PubMed Central

Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L.; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R.; Kohn, Donald B.

2012-01-01

Gene therapy (GT) for adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada−/−). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist. PMID:22833548

A novel chimeric Newcastle disease virus vectored vaccine against highly pathogenic avian influenza virus.

PubMed

Kim, Shin-Hee; Paldurai, Anandan; Samal, Siba K

2017-03-01

Avian influenza (AI) is an economically-important disease of poultry worldwide. The use of vaccines to control AI has increased because of frequent outbreaks of the disease in endemic countries. Newcastle disease virus (NDV) vectored vaccine has shown to be effective in protecting chickens against a highly pathogenic avian influenza virus (HPAIV) infection. However, preexisting antibodies to NDV vector might affect protective efficacy of the vaccine in the field. As an alternative strategy, we evaluated vaccine efficacy of a chimeric NDV vectored vaccine in which the ectodomains of F and HN proteins were replaced by those of avian paramyxovirus serotype-2. The chimeric NDV vector stably expressed the HA protein in vivo, did not cross-react with NDV, was attenuated to be used as a safe vaccine, and provided a partial protection of 1-day-old immunized chickens against HPAIV subtype H5N1challenge, indicating its potential use for early protection of chickens. Copyright © 2017 Elsevier Inc. All rights reserved.

A Nuclear Energy Renaissance: Challenges to Nuclear Weapon Nonproliferation

DTIC Science & Technology

2009-03-30

carbon dioxide every second.12 Nuclear energy is currently the only energy source capable of significant expansion to replace the many terawatts of...environmental lobby, which for decades opposed nuclear power, has now to a significant part come to support it as an important answer to reduce carbon ...power produced by burning fossil fuels. The 4 likely addition of carbon emission taxes and tax credits will only make nuclear power more economically

Strategic nuclear deterrence in the 90's and beyond: Where do we go from here. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knowles, S.V.

With the end of the Cold War, the defense landscape has been substantially changed. But it has not been so dramatically altered as to eliminate the Russian need for a nuclear deterrent or to justify completely ignoring them as potential competitors on the world stage. The nuclear stalemate which characterized relations with the former Soviet Union has been replaced with an unpredictability which presents both danger and promise, prompting the question, 'where do we go from here.' The alternatives of defense dominance, U.S. nuclear superiority, or nuclear disarmament/near-disarmament have all been suggested as possible replacements to the strategy of deterrencemore » through assured destruction. A closer examination of these proposed strategies finds that all have the potential to leave us less secure than we might have otherwise believed. Before we try to escape from the mutual balance of terror which has dominated most of the nuclear age, we should have a firm idea of where the strategy will lead. This includes taking into consideration the legitimate security concerns of Russia and the other commonwealth states.« less

Intranuclear DNA release is a determinant of transfection activity for a non-viral vector: biocleavable polyrotaxane as a supramolecularly dissociative condenser for efficient intranuclear DNA release.

PubMed

Yamada, Yuma; Nomura, Taku; Harashima, Hideyoshi; Yamashita, Atsushi; Katoono, Ryo; Yui, Nobuhiko

2010-01-01

It has been believed that nuclear gene delivery is the most important process for gene expression, and various non-viral vectors are currently being developed with this assumption. However, some of our earlier studies revealed a surprising difference in transfection activity between viral and non-viral vectors: this difference is largely due to the result of the intranuclear disposition of DNA rather than its delivery to the nucleus (Hama S. et al. (2006), Quantitative comparison of intracellular trafficking and nuclear transcription between adenoviral and lipoplex systems. Mol. Ther., 13, 786-794). Here, we report on some direct evidence that demonstrates the importance of the release of intranuclear DNA on transfection activity. The data show that transfection activity can be substantially enhanced by integrating a multifunctional envelope-type nano device (MEND) and a biocleavable polyrotaxane (DMAE-SS-PRX) as an artificial condenser. Our integration system showed significantly higher transfection activity compared to conventional gene delivery system. Moreover, this system provides a strong support for our hypothesis that intranuclear DNA disposition plays a critical role in gene expression for non-viral vectors.

Hard QCD processes in the nuclear medium

NASA Astrophysics Data System (ADS)

Freese, Adam

The environment inside the atomic nucleus is one of the most fascinating arenas for the study of quantum chromodynamics (QCD). The strongly-interacting nature of the nuclear medium a?ects the nature of both QCD processes and the quark-gluon structure of hadrons, allowing several unique aspects of the strong nuclear force to be investigated in reactions involving nuclear targets. The research presented in this dissertation explores two aspects of nuclear QCD: firstly, the partonic structure of the nucleus itself; and secondly, the use of the nucleus as a micro-laboratory in which QCD processes can be studied. The partonic structure of the nucleus is calculated in this work by deriving and utilizing a convolution formula. The hadronic structure of the nucleus and the quark-gluon structure of its constituent nucleons are taken together to determine the nuclear partonic structure. Light cone descriptions of short range correlations, in terms of both hadronic and partonic structure, are derived and taken into account. Medium modifications of the bound nucleons are accounted for using the color screening model, and QCD evolution is used to connect nuclear partonic structure at vastly di?erent energy scales. The formalism developed for calculating nuclear partonic structure is applied to inclusive dijet production from proton-nucleus collisions at LHC kinematics, and novel predictions are calculated and presented for the dijet cross section. The nucleus is investigated as a micro-laboratory in vector meson photoproduction reactions. In particular, the deuteron is studied in the break-up reaction gammad → Vpn, for both the φ(1020) and J/v vector mesons. The generalized eikonal approximation is utilized, allowing unambiguous separation of the impulse approximation and final state interactions (FSIs). Two peaks or valleys are seen in the angular distribution of the reaction cross section, each of which is due to an FSI between either the proton and neutron, or the produced vector meson and the spectator nucleon. The presence and size of the latter FSI valley/peak contains information about the meson-nucleon interaction, and it is shown that several models of this interaction can be distinguished by measuring the angular distribution for the deuteron breakup reaction.

Aortic Valve Stenosis Increases Helical Flow and Flow Complexity: A Study of Intra-Operative Cardiac Vector Flow Imaging.

PubMed

Hansen, Kristoffer Lindskov; Møller-Sørensen, Hasse; Kjaergaard, Jesper; Jensen, Maiken Brit; Jensen, Jørgen Arendt; Nielsen, Michael Bachmann

2017-08-01

Aortic valve stenosis alters blood flow in the ascending aorta. Using intra-operative vector flow imaging on the ascending aorta, secondary helical flow during peak systole and diastole, as well as flow complexity of primary flow during systole, were investigated in patients with normal, stenotic and replaced aortic valves. Peak systolic helical flow, diastolic helical flow and flow complexity during systole differed between the groups (p < 0.0001), and correlated to peak systolic velocity (R = 0.94, 0.87 and 0.88, respectively). The study indicates that aortic valve stenosis increases helical flow and flow complexity, which are measurable with vector flow imaging. For assessment of aortic stenosis and optimization of valve surgery, vector flow imaging may be useful. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Interruption of vector transmission by native vectors and “the art of the possible”

PubMed Central

Salvatella, Roberto; Irabedra, Pilar; Castellanos, Luis G

2013-01-01

In a recent article in the Reader’s Opinion, advantages and disadvantages of the certification processes of interrupted Chagas disease transmission (American trypanosomiasis) by native vector were discussed. Such concept, accepted by those authors for the case of endemic situations with introduced vectors, has been built on a long and laborious process by endemic countries and Subregional Initiatives for Prevention, Control and Treatment of Chagas, with Technical Secretariat of the Pan American Health Organization/World Health Organization, to create a horizon target and goal to concentrate priorities and resource allocation and actions. With varying degrees of sucess, which are not replaceable for a certificate of good practice, has allowed during 23 years to safeguard the effective control of transmission of Trypanosoma cruzi not to hundreds of thousands, but millions of people at risk conditions, truly “the art of the possible.” PMID:24626310

Technology Roadmap Instrumentation, Control, and Human-Machine Interface to Support DOE Advanced Nuclear Energy Programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donald D Dudenhoeffer; Burce P Hallbert

Instrumentation, Controls, and Human-Machine Interface (ICHMI) technologies are essential to ensuring delivery and effective operation of optimized advanced Generation IV (Gen IV) nuclear energy systems. In 1996, the Watts Bar I nuclear power plant in Tennessee was the last U.S. nuclear power plant to go on line. It was, in fact, built based on pre-1990 technology. Since this last U.S. nuclear power plant was designed, there have been major advances in the field of ICHMI systems. Computer technology employed in other industries has advanced dramatically, and computing systems are now replaced every few years as they become functionally obsolete. Functionalmore » obsolescence occurs when newer, more functional technology replaces or supersedes an existing technology, even though an existing technology may well be in working order.Although ICHMI architectures are comprised of much of the same technology, they have not been updated nearly as often in the nuclear power industry. For example, some newer Personal Digital Assistants (PDAs) or handheld computers may, in fact, have more functionality than the 1996 computer control system at the Watts Bar I plant. This illustrates the need to transition and upgrade current nuclear power plant ICHMI technologies.« less

3G vector-primer plasmid for constructing full-length-enriched cDNA libraries.

PubMed

Zheng, Dong; Zhou, Yanna; Zhang, Zidong; Li, Zaiyu; Liu, Xuedong

2008-09-01

We designed a 3G vector-primer plasmid for the generation of full-length-enriched complementary DNA (cDNA) libraries. By employing the terminal transferase activity of reverse transcriptase and the modified strand replacement method, this plasmid (assembled with a polydT end and a deoxyguanosine [dG] end) combines priming full-length cDNA strand synthesis and directional cDNA cloning. As a result, the number of steps involved in cDNA library preparation is decreased while simplifying downstream gene manipulation, sequencing, and subcloning. The 3G vector-primer plasmid method yields fully represented plasmid primed libraries that are equivalent to those made by the SMART (switching mechanism at 5' end of RNA transcript) approach.

Modeling the Effects of Augmentation Strategies on the Control of Dengue Fever With an Impulsive Differential Equation.

PubMed

Zhang, Xianghong; Tang, Sanyi; Cheke, Robert A; Zhu, Huaiping

2016-10-01

Dengue fever has rapidly become the world's most common vector-borne viral disease. Use of endosymbiotic Wolbachia is an innovative technology to prevent vector mosquitoes from reproducing and so break the cycle of dengue transmission. However, strategies such as population eradication and replacement will only succeed if appropriate augmentations with Wolbachia-infected mosquitoes that take account of a variety of factors are carried out. Here, we describe the spread of Wolbachia in mosquito populations using an impulsive differential system with four state variables, incorporating the effects of cytoplasmic incompatibility and the augmentation of Wolbachia-infected mosquitoes with different sex ratios. We then evaluated (a) how each parameter value contributes to the success of population replacement; (b) how different release quantities of infected mosquitoes with different sex ratios affect the success of population suppression or replacement; and (c) how the success of these two strategies can be realized to block the transmission of dengue fever. Analysis of the system's stability, bifurcations and sensitivity reveals the existence of forward and backward bifurcations, multiple attractors and the contribution of each parameter to the success of the strategies. The results indicate that the initial density of mosquitoes, the quantities of mosquitoes released in augmentations and their sex ratios have impacts on whether or not the strategies of population suppression or replacement can be achieved. Therefore, successful strategies rely on selecting suitable strains of Wolbachia and carefully designing the mosquito augmentation program.

Nuclear Warheads: The Reliable Replacement Warhead program and the Life Extension Program

DTIC Science & Technology

2007-12-03

eliminate the need for ESD controls.”67 CRS-22 68 The Defense Nuclear Facilities Safety Board was created by Congress 1988 “as an independent oversight...public health and safety’ at DOE’s defense nuclear facilities .” U.S. Defense Nuclear Facilities Safety Board. “Who We Are,” at [http://www.dnfsb.gov...about/index.html]. 69 Personal communication, Kent Fortenberry, Technical Director, Defense Nuclear Facilities Safety Board, September 14, 2006. 70

Nuclear Warheads: The Reliable Replacement Warhead Program and the Life Extension Program

DTIC Science & Technology

2006-12-13

Defense Nuclear Facilities Safety Board was created by Congress 1988 "as an independent oversight organization within the Executive Branch charged... nuclear facilities ." U.S. Defense Nuclear Facilities Safety Board. “Who We Are,” at [http://www.dnfsb.gov/about/index.html]. involving CHE and plutonium...approach, if successful, would “reduce or eliminate the need for ESD controls.”42 Kent Fortenberry, Technical Director of the Defense Nuclear Facilities

Nuclear Warheads: The Reliable Replacement Warhead Program and the Life Extension Program

DTIC Science & Technology

2007-04-04

Information provided by Pantex Plant, Sept. 19, 2006. 50 The Defense Nuclear Facilities Safety Board was created by Congress 1988 “as an independent...protection of public health and safety’ at DOE’s defense nuclear facilities .” U.S. Defense Nuclear Facilities Safety Board. “Who We Are,” at [http...www.dnfsb.gov/about/index.html]. 51 Personal communication, Kent Fortenberry, Technical Director, Defense Nuclear Facilities Safety Board, Sept. 14, 2006

Nuclear Warheads: The Reliable Replacement Warhead Program and the Life Extension Program

DTIC Science & Technology

2007-07-16

The Defense Nuclear Facilities Safety Board was created by Congress 1988 “as an independent oversight organization within the Executive Branch charged... nuclear facilities .” U.S. Defense Nuclear Facilities Safety Board. “Who We Are,” at [http://www.dnfsb.gov/about/index.html]. beginning, addressed safety...approach, if successful, would “reduce or eliminate the need for ESD controls.”55 Kent Fortenberry, Technical Director of the Defense Nuclear Facilities Safety

The Future Nuclear Arms Control Agenda and Its Potential Implications for the Air Force

DTIC Science & Technology

2015-08-01

triad of delivery systems will need to be replaced. Nuclear warhead life-cycle extension also will need to continue, assuming it remains too difficult...U.S. and Russian strategic nuclear forces. Thus, formal U.S.-Russian arms control negotiations for strategic nuclear systems will almost certainly...reductions in numbers of deployed systems to a more far-reaching agreement that would begin a process of verified elimination of nuclear warheads. The

Insulated Foamy Viral Vectors

PubMed Central

Browning, Diana L.; Collins, Casey P.; Hocum, Jonah D.; Leap, David J.; Rae, Dustin T.; Trobridge, Grant D.

2016-01-01

Retroviral vector-mediated gene therapy is promising, but genotoxicity has limited its use in the clinic. Genotoxicity is highly dependent on the retroviral vector used, and foamy viral (FV) vectors appear relatively safe. However, internal promoters may still potentially activate nearby genes. We developed insulated FV vectors, using four previously described insulators: a version of the well-studied chicken hypersensitivity site 4 insulator (650cHS4), two synthetic CCCTC-binding factor (CTCF)-based insulators, and an insulator based on the CCAAT box-binding transcription factor/nuclear factor I (7xCTF/NF1). We directly compared these insulators for enhancer-blocking activity, effect on FV vector titer, and fidelity of transfer to both proviral long terminal repeats. The synthetic CTCF-based insulators had the strongest insulating activity, but reduced titers significantly. The 7xCTF/NF1 insulator did not reduce titers but had weak insulating activity. The 650cHS4-insulated FV vector was identified as the overall most promising vector. Uninsulated and 650cHS4-insulated FV vectors were both significantly less genotoxic than gammaretroviral vectors. Integration sites were evaluated in cord blood CD34+ cells and the 650cHS4-insulated FV vector had fewer hotspots compared with an uninsulated FV vector. These data suggest that insulated FV vectors are promising for hematopoietic stem cell gene therapy. PMID:26715244

Development of a Novel Trap for the Collection of Black Flies of the Simulium ochraceum Complex

PubMed Central

Rodríguez-Pérez, Mario A.; Adeleke, Monsuru A.; Burkett-Cadena, Nathan D.; Garza-Hernández, Javier A.; Reyes-Villanueva, Filiberto; Cupp, Eddie W.; Toé, Laurent; Salinas-Carmona, Mario C.; Rodríguez-Ramírez, Américo D.; Katholi, Charles R.; Unnasch, Thomas R.

2013-01-01

Background Human landing collections are currently the standard method for collecting onchocerciasis vectors in Africa and Latin America. As part of the efforts to develop a trap to replace human landing collections for the monitoring and surveillance of onchocerciasis transmission, comprehensive evaluations of several trap types were conducted to assess their ability to collect Simulium ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in Latin America. Methodology/Principal Findings Diverse trap designs with numerous modifications and bait variations were evaluated for their abilities to collect S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A novel trap dubbed the “Esperanza window trap” showed particular promise over other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor components) a pair of Esperanza window traps collected numbers of S. Ochraceum s.l. females similar to those collected by a team of vector collectors. Conclusions/Significance The Esperanza window trap, when baited with chemical lures and CO2 can be used to collect epidemiologically significant numbers of Simulium ochraceum s.l., potentially serving as a replacement for human landing collections for evaluation of the transmission of O. volvulus. PMID:24116169

Identification of an Internal Ribosome Entry Segment in the 5′ Region of the Mouse VL30 Retrotransposon and Its Use in the Development of Retroviral Vectors

PubMed Central

López-Lastra, Marcelo; Ulrici, Sandrine; Gabus, Caroline; Darlix, Jean-Luc

1999-01-01

Mouse virus-like 30S RNAs (VL30m) constitute a family of retrotransposons, present at 100 to 200 copies, dispersed in the mouse genome. They display little sequence homology to Moloney murine leukemia virus (MoMLV), do not encode virus-like proteins, and have not been implicated in retroviral carcinogenesis. However, VL30 RNAs are efficiently packaged into MLV particles that are propagated in cell culture. In this study, we addressed whether the 5′ region of VL30m could replace the 5′ leader of MoMLV functionally in a recombinant vector construct. Our data confirm that the putative packaging sequence of VL30 is located within the 5′ region (nucleotides 362 to 1149 with respect to the cap structure) and that it can replace the packaging sequence of MoMLV. We also show that VL30m contains an internal ribosome entry segment (IRES) in the 5′ region, as do MoMLV, Friend murine leukemia virus, Harvey murine sarcoma virus, and avian reticuloendotheliosis virus type A. Our data show that both the packaging and IRES functions of the 5′ region of VL30m RNA can be efficiently used to develop retrotransposon-based vectors. PMID:10482590

Identification of an internal ribosome entry segment in the 5' region of the mouse VL30 retrotransposon and its use in the development of retroviral vectors.

PubMed

López-Lastra, M; Ulrici, S; Gabus, C; Darlix, J L

1999-10-01

Mouse virus-like 30S RNAs (VL30m) constitute a family of retrotransposons, present at 100 to 200 copies, dispersed in the mouse genome. They display little sequence homology to Moloney murine leukemia virus (MoMLV), do not encode virus-like proteins, and have not been implicated in retroviral carcinogenesis. However, VL30 RNAs are efficiently packaged into MLV particles that are propagated in cell culture. In this study, we addressed whether the 5' region of VL30m could replace the 5' leader of MoMLV functionally in a recombinant vector construct. Our data confirm that the putative packaging sequence of VL30 is located within the 5' region (nucleotides 362 to 1149 with respect to the cap structure) and that it can replace the packaging sequence of MoMLV. We also show that VL30m contains an internal ribosome entry segment (IRES) in the 5' region, as do MoMLV, Friend murine leukemia virus, Harvey murine sarcoma virus, and avian reticuloendotheliosis virus type A. Our data show that both the packaging and IRES functions of the 5' region of VL30m RNA can be efficiently used to develop retrotransposon-based vectors.

Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.

PubMed

Abes, Saïd; Moulton, Hong M; Clair, Philippe; Prevot, Paul; Youngblood, Derek S; Wu, Rebecca P; Iversen, Patrick L; Lebleu, Bernard

2006-12-01

The efficient and non-toxic nuclear delivery of steric-block oligonucleotides (ON) is a prerequisite for therapeutic strategies involving splice correction or exon skipping. Cationic cell penetrating peptides (CPPs) have given rise to much interest for the intracellular delivery of biomolecules, but their efficiency in promoting cytoplasmic or nuclear delivery of oligonucleotides has been hampered by endocytic sequestration and subsequent degradation of most internalized material in endocytic compartments. In the present study, we compared the splice correction activity of three different CPPs conjugated to PMO(705), a steric-block ON targeted against the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc705 splice correction model. In contrast to Tat48-60 (Tat) and oligoarginine (R(9)F(2)) PMO(705) conjugates, the 6-aminohexanoic-spaced oligoarginine (R-Ahx-R)(4)-PMO(705) conjugate was able to promote an efficient splice correction in the absence of endosomolytic agents. Our mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. This vector, which has displays an extremely low cytotoxicity, the ability to function without chloroquine adjunction and in the presence of serum proteins. It thus offers a promising lead for the development of vectors able to enhance the delivery of therapeutic steric-block ON in clinically relevant models.

Mitochondrial replacement techniques: egg donation, genealogy and eugenics.

PubMed

Palacios-González, César

2016-03-01

Several objections against the morality of researching or employing mitochondrial replacement techniques have been advanced recently. In this paper, I examine three of these objections and show that they are found wanting. First I examine whether mitochondrial replacement techniques, research and clinical practice, should not be carried out because of possible harms to egg donors. Next I assess whether mitochondrial replacement techniques should be banned because they could affect the study of genealogical ancestry. Finally, I examine the claim that mitochondrial replacement techniques are not transferring mitochondrial DNA but nuclear DNA, and that this should be prohibited on ethical grounds.

Potential for Worldwide Displacement of Fossil-Fuel Electricity by Nuclear Energy in Three Decades Based on Extrapolation of Regional Deployment Data

PubMed Central

Qvist, Staffan A.; Brook, Barry W.

2015-01-01

There is an ongoing debate about the deployment rates and composition of alternative energy plans that could feasibly displace fossil fuels globally by mid-century, as required to avoid the more extreme impacts of climate change. Here we demonstrate the potential for a large-scale expansion of global nuclear power to replace fossil-fuel electricity production, based on empirical data from the Swedish and French light water reactor programs of the 1960s to 1990s. Analysis of these historical deployments show that if the world built nuclear power at no more than the per capita rate of these exemplar nations during their national expansion, then coal- and gas-fired electricity could be replaced worldwide in less than a decade. Under more conservative projections that take into account probable constraints and uncertainties such as differing relative economic output across regions, current and past unit construction time and costs, future electricity demand growth forecasts and the retiring of existing aging nuclear plants, our modelling estimates that the global share of fossil-fuel-derived electricity could be replaced within 25–34 years. This would allow the world to meet the most stringent greenhouse-gas mitigation targets. PMID:25970621

Pushing Memory Bandwidth Limitations Through Efficient Implementations of Block-Krylov Space Solvers on GPUs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, M. A.; Strelchenko, Alexei; Vaquero, Alejandro

Lattice quantum chromodynamics simulations in nuclear physics have benefited from a tremendous number of algorithmic advances such as multigrid and eigenvector deflation. These improve the time to solution but do not alleviate the intrinsic memory-bandwidth constraints of the matrix-vector operation dominating iterative solvers. Batching this operation for multiple vectors and exploiting cache and register blocking can yield a super-linear speed up. Block-Krylov solvers can naturally take advantage of such batched matrix-vector operations, further reducing the iterations to solution by sharing the Krylov space between solves. However, practical implementations typically suffer from the quadratic scaling in the number of vector-vector operations.more » Using the QUDA library, we present an implementation of a block-CG solver on NVIDIA GPUs which reduces the memory-bandwidth complexity of vector-vector operations from quadratic to linear. We present results for the HISQ discretization, showing a 5x speedup compared to highly-optimized independent Krylov solves on NVIDIA's SaturnV cluster.« less

First measurement of the vector analyzing power in muon capture by polarized muonic {sup 3}He

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cummings, W.J.; Behr, J.; Bogorad, P.

1995-09-01

This paper describes the first measurement of spin observables in nuclear muon capture by {sup 3}He. The sensitivity of spin observables to the pseudoscalar coupling is described. The triton asymmetry presented has to be corrected for small systematic effects in order to extract the vector analyzing power. The analysis of these effects is currently underway.

Relating hybrid advantage and genome replacement in unisexual salamanders.

PubMed

Charney, Noah D

2012-05-01

Unisexual vertebrates are model systems for understanding the evolution of sex. Many predominantly clonal lineages allow occasional genetic recombination, which may be sufficient to avoid the accumulation of deleterious mutations and parasites. Introgression of paternal DNA into an all-female lineage represents a one-way flow of genetic material. Over many generations, this could result in complete replacement of the unisexual genomes by those of the donor species. The process of genome replacement may be counteracted by contemporary dispersal or by positive selection on hybrid nuclear genomes in ecotones. I present a conceptual model that relates nuclear genome replacement, positive selection on hybrids and biogeography in unisexual systems. I execute an individual-based simulation of the fate of hybrid genotypes in contact with a single host species. I parameterize these models for unisexual salamanders in the Ambystoma genus, for which the frequency of genome replacement has been a source of ongoing debate. I find that, if genome replacement occurs at a rate greater than 1/10,000 in Ambystoma, then there must be compensating positive selection in order to maintain observed levels of hybrid nuclei. Future researchers studying unisexual systems may use this framework as a guide to evaluating the hybrid superiority hypothesis. © 2011 The Author. Evolution© 2011 The Society for the Study of Evolution.

Caspase Inhibition with XIAP as an Adjunct to AAV Vector Gene-Replacement Therapy: Improving Efficacy and Prolonging the Treatment Window

PubMed Central

Yao, Jingyu; Jia, Lin; Khan, Naheed; Zheng, Qiong-Duan; Moncrief, Ashley; Hauswirth, William W.; Thompson, Debra A.; Zacks, David N.

2012-01-01

Purpose AAV-mediated gene therapy in the rd10 mouse, with retinal degeneration caused by mutation in the rod cyclic guanosine monophosphate phosphodiesterase β-subunit (PDEβ) gene, produces significant, but transient, rescue of photoreceptor structure and function. This study evaluates the ability of AAV-mediated delivery of X-linked inhibitor of apoptosis (XIAP) to enhance and prolong the efficacy of PDEβ gene-replacement therapy. Methods Rd10 mice were bred and housed in darkness. Two groups of animals were generated: Group 1 received sub-retinal AAV5-XIAP or AAV5-GFP at postnatal age (P) 4 or 21 days; Group 2 received sub-retinal AAV5-XIAP plus AAV5- PDEβ, AAV5-GFP plus AAV5- PDEβ, or AAV- PDEβ alone at age P4 or P21. Animals were maintained for an additional 4 weeks in darkness before being moved to a cyclic-light environment. A subset of animals from Group 1 received a second sub-retinal injection of AAV8-733-PDEβ two weeks after being moved to the light. Histology, immunohistochemistry, Western blots, and electroretinograms were performed at different times after moving to the light. Results Injection of AAV5-XIAP alone at P4 and 21 resulted in significant slowing of light-induced retinal degeneration, as measured by outer nuclear thickness and cell counts, but did not result in improved outer segment structure and rhodopsin localization. In contrast, co-injection of AAV5-XIAP and AAV5-PDEβ resulted in increased levels of rescue and decreased rates of retinal degeneration compared to treatment with AAV5-PDEβ alone. Mice treated with AAV5-XIAP at P4, but not P21, remained responsive to subsequent rescue by AAV8-733-PDEβ when injected two weeks after moving to a light-cycling environment. Conclusions Adjunctive treatment with the anti-apoptotic gene XIAP confers additive protective effect to gene-replacement therapy with AAV5-PDEβ in the rd10 mouse. In addition, AAV5-XIAP, when given early, can increase the age at which gene-replacement therapy remains effective, thus effectively prolonging the window of opportunity for therapeutic intervention. PMID:22615940

Vector boson production in pPb and PbPb collisions at the LHC and its impact on nCTEQ15 PDFs

NASA Astrophysics Data System (ADS)

Kusina, A.; Lyonnet, F.; Clark, D. B.; Godat, E.; Ježo, T.; Kovařík, K.; Olness, F. I.; Schienbein, I.; Yu, J. Y.

2017-07-01

We provide a comprehensive comparison of W^± / Z vector boson production data in pPb and PbPb collisions at the LHC with predictions obtained using the nCTEQ15 PDFs. We identify the measurements which have the largest potential impact on the PDFs, and estimate the effect of including these data using a Bayesian reweighting method. We find this data set can provide information as regards both the nuclear corrections and the heavy flavor (strange quark) PDF components. As for the proton, the parton flavor determination/separation is dependent on nuclear corrections (from heavy target DIS, for example), this information can also help improve the proton PDFs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flavin, C.; Lenssen, N.

When the sad history of nuclear power is written, April 26, 1986, will be recorded as the day the dream died. The explosion at the Chernobyl plant was a terrible human tragedy- and it delivered a stark verdict on the hope that nuclear power will one day replace fossil fuel-based energy systems. Nuclear advocates may soldier on, but a decade after Chernobyl it is clear that nuclear power is no longer a viable energy option for the twenty-first century.

Compute Server Performance Results

NASA Technical Reports Server (NTRS)

Stockdale, I. E.; Barton, John; Woodrow, Thomas (Technical Monitor)

1994-01-01

Parallel-vector supercomputers have been the workhorses of high performance computing. As expectations of future computing needs have risen faster than projected vector supercomputer performance, much work has been done investigating the feasibility of using Massively Parallel Processor systems as supercomputers. An even more recent development is the availability of high performance workstations which have the potential, when clustered together, to replace parallel-vector systems. We present a systematic comparison of floating point performance and price-performance for various compute server systems. A suite of highly vectorized programs was run on systems including traditional vector systems such as the Cray C90, and RISC workstations such as the IBM RS/6000 590 and the SGI R8000. The C90 system delivers 460 million floating point operations per second (FLOPS), the highest single processor rate of any vendor. However, if the price-performance ration (PPR) is considered to be most important, then the IBM and SGI processors are superior to the C90 processors. Even without code tuning, the IBM and SGI PPR's of 260 and 220 FLOPS per dollar exceed the C90 PPR of 160 FLOPS per dollar when running our highly vectorized suite,

77 FR 41814 - Entergy Operations, Inc.; Grand Gulf Nuclear Station, Unit 1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-16

... Unit 1 result primarily from periodic testing of diesel generators and fire water pump diesel engines... rural. GGNS Unit 1 is a General Electric Mark 3 boiling-water reactor. Identification of the Proposed... following: replacing the reactor feed pump turbine rotors; replacing the main generator current transformers...

76 FR 28222 - Extension of the Public Review and Comment Period and Announcement of an Additional Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-16

... Impact Statement for the Nuclear Facility Portion of the Chemistry and Metallurgy Research Building... Chemistry and Metallurgy Research Building Replacement Project at Los Alamos National Laboratory, Los Alamos... Chemistry and Metallurgy Research Building Replacement Project (CMRR-NF) at Los Alamos National Laboratory...

An Improved Single-Step Cloning Strategy Simplifies the Agrobacterium tumefaciens-Mediated Transformation (ATMT)-Based Gene-Disruption Method for Verticillium dahliae.

PubMed

Wang, Sheng; Xing, Haiying; Hua, Chenlei; Guo, Hui-Shan; Zhang, Jie

2016-06-01

The soilborne fungal pathogen Verticillium dahliae infects a broad range of plant species to cause severe diseases. The availability of Verticillium genome sequences has provided opportunities for large-scale investigations of individual gene function in Verticillium strains using Agrobacterium tumefaciens-mediated transformation (ATMT)-based gene-disruption strategies. Traditional ATMT vectors require multiple cloning steps and elaborate characterization procedures to achieve successful gene replacement; thus, these vectors are not suitable for high-throughput ATMT-based gene deletion. Several advancements have been made that either involve simplification of the steps required for gene-deletion vector construction or increase the efficiency of the technique for rapid recombinant characterization. However, an ATMT binary vector that is both simple and efficient is still lacking. Here, we generated a USER-ATMT dual-selection (DS) binary vector, which combines both the advantages of the USER single-step cloning technique and the efficiency of the herpes simplex virus thymidine kinase negative-selection marker. Highly efficient deletion of three different genes in V. dahliae using the USER-ATMT-DS vector enabled verification that this newly-generated vector not only facilitates the cloning process but also simplifies the subsequent identification of fungal homologous recombinants. The results suggest that the USER-ATMT-DS vector is applicable for efficient gene deletion and suitable for large-scale gene deletion in V. dahliae.

Widespread plant specialization in the polyphagous planthopper Hyalesthes obsoletus (Cixiidae), a major vector of stolbur phytoplasma: Evidence of cryptic speciation

PubMed Central

Kosovac, Andrea; Johannesen, Jes; Krstić, Oliver; Cvrković, Tatjana; Toševski, Ivo

2018-01-01

The stolbur phytoplasma vector Hyalesthes obsoletus is generally considered as a polyphagous species associated with numerous wild and cultivated plants. However, recent research in southeastern Europe, the distribution centre of H. obsoletus and the area of most stolbur-inflicted crop diseases, points toward specific host-plant associations of the vector, indicating specific vector-based transmission routes. Here, we study the specificity of populations associated with four host-plants using mitochondrial and nuclear genetic markers, and we evaluate the evolution of host-shifts in H. obsoletus. Host-plant use was confirmed for Convolvulus arvensis, Urtica dioica, Vitex agnus-castus and Crepis foetida. Mitochondrial genetic analysis showed sympatric occurrence of three phylogenetic lineages that were ecologically delineated by host-plant preference, but were morphologically inseparable. Nuclear data supported the existence of three genetic groups (Evanno’s ΔK(3) = 803.72) with average genetic membership probabilities > 90%. While populations associated with C. arvensis and U. dioica form a homogenous group, populations affiliated with V. agnus-castus and C. foetida constitute two independent plant-associated lineages. The geographical signal permeating the surveyed populations indicated complex diversification processes associated with host-plant selection and likely derived from post-glacial refugia in the eastern Mediterranean. This study provides evidence for cryptic species diversification within H. obsoletus sensu lato: i) consistent mitochondrial differentiation (1.1–1.5%) among host-associated populations in syntopy and in geographically distant areas, ii) nuclear genetic variance supporting mitochondrial data, and iii) average mitochondrial genetic distances among host-associated meta-populations are comparable to the most closely related, morphologically distinguishable species, i.e., Hyalesthes thracicus (2.1–3.3%). PMID:29738577

Widespread plant specialization in the polyphagous planthopper Hyalesthes obsoletus (Cixiidae), a major vector of stolbur phytoplasma: Evidence of cryptic speciation.

PubMed

Kosovac, Andrea; Johannesen, Jes; Krstić, Oliver; Mitrović, Milana; Cvrković, Tatjana; Toševski, Ivo; Jović, Jelena

2018-01-01

The stolbur phytoplasma vector Hyalesthes obsoletus is generally considered as a polyphagous species associated with numerous wild and cultivated plants. However, recent research in southeastern Europe, the distribution centre of H. obsoletus and the area of most stolbur-inflicted crop diseases, points toward specific host-plant associations of the vector, indicating specific vector-based transmission routes. Here, we study the specificity of populations associated with four host-plants using mitochondrial and nuclear genetic markers, and we evaluate the evolution of host-shifts in H. obsoletus. Host-plant use was confirmed for Convolvulus arvensis, Urtica dioica, Vitex agnus-castus and Crepis foetida. Mitochondrial genetic analysis showed sympatric occurrence of three phylogenetic lineages that were ecologically delineated by host-plant preference, but were morphologically inseparable. Nuclear data supported the existence of three genetic groups (Evanno's ΔK(3) = 803.72) with average genetic membership probabilities > 90%. While populations associated with C. arvensis and U. dioica form a homogenous group, populations affiliated with V. agnus-castus and C. foetida constitute two independent plant-associated lineages. The geographical signal permeating the surveyed populations indicated complex diversification processes associated with host-plant selection and likely derived from post-glacial refugia in the eastern Mediterranean. This study provides evidence for cryptic species diversification within H. obsoletus sensu lato: i) consistent mitochondrial differentiation (1.1-1.5%) among host-associated populations in syntopy and in geographically distant areas, ii) nuclear genetic variance supporting mitochondrial data, and iii) average mitochondrial genetic distances among host-associated meta-populations are comparable to the most closely related, morphologically distinguishable species, i.e., Hyalesthes thracicus (2.1-3.3%).

Contributions Regarding the Aircraft Nuclear Propulsion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitrica, Bogdan; Petre, Marian; Dima, Mihai Octavian

2010-01-21

The possibility to use a nuclear reactor for airplanes propulsion was investigated taking in to account 2 possible solutions: the direct cycle (where the fluid pass through the reactor's core) and the indirect cycle (where the fluid is passing through a heat exchanger). Taking in to account the radioprotection problems, the only realistic solution seems to be the indirect cycle, where the energy transfer should be performed by a heat exchanger that must work at very high speed of the fluid. The heat exchanger will replace the classical burning room. We had performed a more precise theoretical study for themore » nuclear jet engine regarding the performances of the nuclear reactor, of the heat exchanger and of the jet engine. It was taken in to account that in the moment when the burning room is replaced by a heat exchanger, a new model for gasodynamic process from the engine must be performed. Studies regarding the high flow speed heat transfer were performed.« less

Commercial grade item (CGI) dedication of generators for nuclear safety related applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, R.K.; Hajos, L.G.

1993-03-01

The number of nuclear safety related equipment suppliers and the availability of spare and replacement parts designed specifically for nuclear safety related application are shrinking rapidly. These have made it necessary for utilities to apply commercial grade spare and replacement parts in nuclear safety related applications after implementing proper acceptance and dedication process to verify that such items conform with the requirements of their use in nuclear safety related application. The general guidelines for the commercial grade item (CGI) acceptance and dedication are provided in US Nuclear Regulatory Commission (NRC) Generic Letters and Electric Power Research Institute (EPRI) Report NP-5652,more » Guideline for the Utilization of Commercial Grade Items in Nuclear Safety Related Applications. This paper presents an application of these generic guidelines for procurement, acceptance, and dedication of a commercial grade generator for use as a standby generator at Salem Generating Station Units 1 and 2. The paper identifies the critical characteristics of the generator which once verified, will provide reasonable assurance that the generator will perform its intended safety function. The paper also delineates the method of verification of the critical characteristics through tests and provide acceptance criteria for the test results. The methodology presented in this paper may be used as specific guidelines for reliable and cost effective procurement and dedication of commercial grade generators for use as standby generators at nuclear power plants.« less

Intrinsic operators for the electromagnetic nuclear current

DOE Office of Scientific and Technical Information (OSTI.GOV)

J. Adam, Jr.; H. Arenhovel

1996-09-01

The intrinsic electromagnetic nuclear meson exchange charge and current operators arising from a separation of the center-of-mass motion are derived for a one-boson-exchange model for the nuclear interaction with scalar, pseudoscalar and vector meson exchange including leading order relativistic terms. Explicit expressions for the meson exchange operators corresponding to the different meson types are given in detail for a two-nucleon system. These intrinsic operators are to be evaluated between intrinsic wave functions in their center-of-mass frame.

A Comparative Verification of Forecasts from Two Operational Solar Wind Models (Postprint)

DTIC Science & Technology

2012-02-08

much confidence to place on predicted parameters. Cost /benefit information is provided to administrators who decide to sustain or replace existing...magnetic field magnitude and three components of the magnetic field vector in the geocentric solar magnetospheric (GSM) coordinate system at each hour of

Tissue-specific, tumor-selective, replication-competent adenovirus vector for cancer gene therapy.

PubMed

Doronin, K; Kuppuswamy, M; Toth, K; Tollefson, A E; Krajcsi, P; Krougliak, V; Wold, W S

2001-04-01

We have previously described two replication-competent adenovirus vectors, named KD1 and KD3, for potential use in cancer gene therapy. KD1 and KD3 have two small deletions in the E1A gene that restrict efficient replication of these vectors to human cancer cell lines. These vectors also have increased capacity to lyse cells and spread from cell to cell because they overexpress the adenovirus death protein, an adenovirus protein required for efficient cell lysis and release of adenovirus from the cell. We now describe a new vector, named KD1-SPB, which is the KD1 vector with the E4 promoter replaced by the promoter for surfactant protein B (SPB). SPB promoter activity is restricted in the adult to type II alveolar epithelial cells and bronchial epithelial cells. Because KD1-SPB has the E1A mutations, it should replicate within and destroy only alveolar and bronchial cancer cells. We show that KD1-SPB replicates, lyses cells, and spreads from cell to cell as well as does KD1 in H441 cells, a human cancer cell line where the SPB promoter is active. KD1-SPB replicates, lyses cells, and spreads only poorly in Hep3B liver cancer cells. Replication was determined by expression of the E4ORF3 protein, viral DNA accumulation, fiber synthesis, and virus yield. Cell lysis and vector spread were measured by lactate dehydrogenase release and a "vector spread" assay. In addition to Hep3B cells, KD1-SPB also did not express E4ORF3 in HT29.14S (colon), HeLa (cervix), KB (nasopharynx), or LNCaP (prostate) cancer cell lines, in which the SPB promoter is not expected to be active. Following injection into H441 or Hep3B tumors growing in nude mice, KD1-SPB caused a three- to fourfold suppression of growth of H441 tumors, similar to that seen with KD1. KD1-SPB had only a minimal effect on the growth of Hep3B tumors, whereas KD1 again caused a three- to fourfold suppression. These results establish that the adenovirus E4 promoter can be replaced by a tissue-specific promoter in a replication-competent vector. The vector has three engineered safety features: the tissue-specific promoter, the mutations in E1A that preclude efficient replication in nondividing cells, and a deletion of the E3 genes which shield the virus from attack by the immune system. KD1-SPB may have use in treating human lung cancers in which the SPB promoter is active.

Arginine-rich cross-linking peptides with different SV40 nuclear localization signal content as vectors for intranuclear DNA delivery.

PubMed

Bogacheva, Mariia; Egorova, Anna; Slita, Anna; Maretina, Marianna; Baranov, Vladislav; Kiselev, Anton

2017-11-01

The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively. We investigated three polyplexes with different NLS content (10 mol%, 50 mol% and 90 mol% of SV40 NLS) as vectors for intranuclear DNA delivery. All carriers tested were able to condense DNA, to protect it from DNAase I and were not toxic to the cells. We observed that cell cycle arrest by hydroxyurea did not affect transfection efficacy of NLS-modified carriers which we confirmed using quantitative confocal microscopy analysis. Overall, peptide carrier modified with 90 mol% of SV40 NLS provided efficient transfection and nuclear uptake in non-dividing cells. Thus, incorporation of NLS into arginine-rich cross-linking peptides is an adequate approach to the development of efficient intranuclear gene delivery vehicles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Converting point-wise nuclear cross sections to pole representation using regularized vector fitting

NASA Astrophysics Data System (ADS)

Peng, Xingjie; Ducru, Pablo; Liu, Shichang; Forget, Benoit; Liang, Jingang; Smith, Kord

2018-03-01

Direct Doppler broadening of nuclear cross sections in Monte Carlo codes has been widely sought for coupled reactor simulations. One recent approach proposed analytical broadening using a pole representation of the commonly used resonance models and the introduction of a local windowing scheme to improve performance (Hwang, 1987; Forget et al., 2014; Josey et al., 2015, 2016). This pole representation has been achieved in the past by converting resonance parameters in the evaluation nuclear data library into poles and residues. However, cross sections of some isotopes are only provided as point-wise data in ENDF/B-VII.1 library. To convert these isotopes to pole representation, a recent approach has been proposed using the relaxed vector fitting (RVF) algorithm (Gustavsen and Semlyen, 1999; Gustavsen, 2006; Liu et al., 2018). This approach however needs to specify ahead of time the number of poles. This article addresses this issue by adding a poles and residues filtering step to the RVF procedure. This regularized VF (ReV-Fit) algorithm is shown to efficiently converge the poles close to the physical ones, eliminating most of the superfluous poles, and thus enabling the conversion of point-wise nuclear cross sections.

Presence of a predator image in potential breeding sites and oviposition responses of a dengue vector.

PubMed

Dieng, Hamady; Satho, Tomomitsu; Suradi, Nur Farrahana Binti; Hakim, Hafijah; Abang, Fatimah; Aliasan, Nur Ezzati; Miake, Fumio; Zuharah, Wan Fatma; Kassim, Nur Faeza A; Majid, Abdul Hafiz A; Fadzly, Nik; Vargas, Ronald E Morales; Morales, Noppawan P; Noweg, Gabriel Tonga

2017-12-01

In dengue vector control, attempts to minimize or replace the use of pesticides have mostly involved use of predators, but success has been severely impeded by difficulties associated with financial and environmental costs, predator mass production, and persistence in target habitats. Visual deterrents have been used successfully to control animal pests, in some cases in an effort to replace pesticide use. Despite evidence that visual signals are crucial in site choice for egg deposition by dengue vectors, and that female mosquitoes respond to artificial predation, the role of predator intimidation as it affects the oviposition behavior of dengue vectors remains largely unexplored. Here, we examined the oviposition responses of Aedes aegypti exposed to various mosquito predator pictures. Gravid females were presented with equal opportunities to oviposit in two cups with predator images [Toxorhynchites splendens-TXI, Goldfish (Carassius auratus)-small (SFI) and large (LFI) and Tx. splendens+Goldfish-TXFI] and two others without pictures. Differences in egg deposition were examined between sites with and without these images. When given a chance to oviposit in cups with and without TXI, Ae. aegypti females were similarly attracted to both sites. When provided an opportunity to oviposit in cups displaying pictures of fish (SFI or LFI) and blank cups, egg deposition rates were much lower in the fish picture sites. Females showed a preference for blank cups over TXFI for egg deposition. They also equally avoided cups with pictures of fish, regardless of the size of the picture. Our results indicate that the presence of images of goldfish and their association with Tx. larvae significantly reduced egg deposition by Ae. aegypti, and this was not the case with the predatory larvae alone. The observations that the images of natural predators can repel gravid females of a dengue vector provide novel possibilities to develop effective and inexpensive alternative tools to harmful insecticides. Copyright © 2017 Elsevier B.V. All rights reserved.

Electro-gravity via geometric chrononfield

NASA Astrophysics Data System (ADS)

Suchard, Eytan H.

2017-05-01

In De Sitter / Anti De Sitter space-time and in other geometries, reference sub-manifolds from which proper time is measured along integral curves, are described as events. We introduce here a foliation with the help of a scalar field. The scalar field need not be unique but from the gradient of the scalar field, an intrinsic Reeb vector of the foliations perpendicular to the gradient vector is calculated. The Reeb vector describes the acceleration of a physical particle that moves along the integral curves that are formed by the gradient of the scalar field. The Reeb vector appears as a component of an anti-symmetric matrix which is a part of a rank-2, 2-Form. The 2-form is extended into a non-degenerate 4-form and into rank-4 matrix of a 2-form, which when multiplied by a velocity of a particle, becomes the acceleration of the particle. The matrix has one U(1) degree of freedom and an additional SU(2) degrees of freedom in two vectors that span the plane perpendicular to the gradient of the scalar field and to the Reeb vector. In total, there are U(1) x SU(2) degrees of freedom. SU(3) degrees of freedom arise from three dimensional foliations but require an additional symmetry to exist in order to have a valid covariant meaning. Matter in the Einstein Grossmann equation is replaced by the action of the acceleration field, i.e. by a geometric action which is not anticipated by the metric alone. This idea leads to a new formalism that replaces the conventional stress-energy-momentum-tensor. The formalism will be mainly developed for classical physics but will also be discussed for quantized physics based on events instead of particles. The result is that a positive charge manifests small attracting gravity and a stronger but small repelling acceleration field that repels even uncharged particles that have a rest mass. Negative charge manifests a repelling anti-gravity but also a stronger acceleration field that attracts even uncharged particles that have rest mass. Preliminary version: http://sciencedomain.org/abstract/9858

Effects of Circular DNA Length on Transfection Efficiency by Electroporation into HeLa Cells.

PubMed

Hornstein, Benjamin D; Roman, Dany; Arévalo-Soliz, Lirio M; Engevik, Melinda A; Zechiedrich, Lynn

2016-01-01

The ability to produce extremely small and circular supercoiled vectors has opened new territory for improving non-viral gene therapy vectors. In this work, we compared transfection of supercoiled DNA vectors ranging from 383 to 4,548 bp, each encoding shRNA against GFP under control of the H1 promoter. We assessed knockdown of GFP by electroporation into HeLa cells. All of our vectors entered cells in comparable numbers when electroporated with equal moles of DNA. Despite similar cell entry, we found length-dependent differences in how efficiently the vectors knocked down GFP. As vector length increased up to 1,869 bp, GFP knockdown efficiency per mole of transfected DNA increased. From 1,869 to 4,257 bp, GFP knockdown efficiency per mole was steady, then decreased with increasing vector length. In comparing GFP knockdown with equal masses of vectors, we found that the shorter vectors transfect more efficiently per nanogram of DNA transfected. Our results rule out cell entry and DNA mass as determining factors for gene knockdown efficiency via electroporation. The length-dependent effects we have uncovered are likely explained by differences in nuclear translocation or transcription. These data add an important step towards clinical applications of non-viral vector delivery.

Effects of Circular DNA Length on Transfection Efficiency by Electroporation into HeLa Cells

PubMed Central

Hornstein, Benjamin D.; Roman, Dany; Arévalo-Soliz, Lirio M.; Engevik, Melinda A.

2016-01-01

The ability to produce extremely small and circular supercoiled vectors has opened new territory for improving non-viral gene therapy vectors. In this work, we compared transfection of supercoiled DNA vectors ranging from 383 to 4,548 bp, each encoding shRNA against GFP under control of the H1 promoter. We assessed knockdown of GFP by electroporation into HeLa cells. All of our vectors entered cells in comparable numbers when electroporated with equal moles of DNA. Despite similar cell entry, we found length-dependent differences in how efficiently the vectors knocked down GFP. As vector length increased up to 1,869 bp, GFP knockdown efficiency per mole of transfected DNA increased. From 1,869 to 4,257 bp, GFP knockdown efficiency per mole was steady, then decreased with increasing vector length. In comparing GFP knockdown with equal masses of vectors, we found that the shorter vectors transfect more efficiently per nanogram of DNA transfected. Our results rule out cell entry and DNA mass as determining factors for gene knockdown efficiency via electroporation. The length-dependent effects we have uncovered are likely explained by differences in nuclear translocation or transcription. These data add an important step towards clinical applications of non-viral vector delivery. PMID:27918590

Tombusvirus-based vector systems to permit over-expression of genes or that serve as sensors of antiviral RNA silencing in plants.

PubMed

Shamekova, Malika; Mendoza, Maria R; Hsieh, Yi-Cheng; Lindbo, John; Omarov, Rustem T; Scholthof, Herman B

2014-03-01

A next generation Tomato bushy stunt virus (TBSV) coat protein gene replacement vector system is described that can be applied by either RNA inoculation or through agroinfiltration. A vector expressing GFP rapidly yields high levels of transient gene expression in inoculated leaves of various plant species, as illustrated for Nicotiana benthamiana, cowpea, tomato, pepper, and lettuce. A start-codon mutation to down-regulate the dose of the P19 silencing suppressor reduces GFP accumulation, whereas mutations that result in undetectable levels of P19 trigger rapid silencing of GFP. Compared to existing virus vectors the TBSV system has a unique combination of a very broad host range, rapid and high levels of replication and gene expression, and the ability to regulate its suppressor. These features are attractive for quick transient assays in numerous plant species for over-expression of genes of interest, or as a sensor to monitor the efficacy of antiviral RNA silencing. Copyright © 2014. Published by Elsevier Inc.

Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy

PubMed Central

Bengtsson, Niclas E.; Hall, John K.; Odom, Guy L.; Phelps, Michael P.; Andrus, Colin R.; Hawkins, R. David; Hauschka, Stephen D.; Chamberlain, Joel R.; Chamberlain, Jeffrey S.

2017-01-01

Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx4cv mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. Muscle-restricted Cas9 expression enables direct editing of the mutation, multi-exon deletion or complete gene correction via homologous recombination in myogenic cells. Treated muscles express dystrophin in up to 70% of the myogenic area and increased force generation following intramuscular delivery. Furthermore, systemic administration of the vectors results in widespread expression of dystrophin in both skeletal and cardiac muscles. Our results demonstrate that AAV-mediated muscle-specific gene editing has significant potential for therapy of neuromuscular disorders. PMID:28195574

Heterologous Protein Secretion in Lactobacilli with Modified pSIP Vectors

PubMed Central

Karlskås, Ingrid Lea; Maudal, Kristina; Axelsson, Lars; Rud, Ida; Eijsink, Vincent G. H.; Mathiesen, Geir

2014-01-01

We describe new variants of the modular pSIP-vectors for inducible gene expression and protein secretion in lactobacilli. The basic functionality of the pSIP system was tested in Lactobacillus strains representing 14 species using pSIP411, which harbors the broad-host-range Lactococcus lactis SH71rep replicon and a β-glucuronidase encoding reporter gene. In 10 species, the inducible gene expression system was functional. Based on these results, three pSIP vectors with different signal peptides were modified by replacing their narrow-host-range L. plantarum 256rep replicon with SH71rep and transformed into strains of five different species of Lactobacillus. All recombinant strains secreted the target protein NucA, albeit with varying production levels and secretion efficiencies. The Lp_3050 derived signal peptide generally resulted in the highest levels of secreted NucA. These modified pSIP vectors are useful tools for engineering a wide variety of Lactobacillus species. PMID:24614815

Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Xiao; Gang, Yi; Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi Province

2015-02-06

Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself.more » The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity.« less

Effects of duration of electric pulse on in vitro development of cloned cat embryos with human artificial chromosome vector.

PubMed

Do, Ltk; Wittayarat, M; Terazono, T; Sato, Y; Taniguchi, M; Tanihara, F; Takemoto, T; Kazuki, Y; Kazuki, K; Oshimura, M; Otoi, T

2016-12-01

The current applications for cat cloning include production of models for the study of human and animal diseases. This study was conducted to investigate the optimal fusion protocol on in vitro development of transgenic cloned cat embryos by comparing duration of electric pulse. Cat fibroblast cells containing a human artificial chromosome (HAC) vector were used as genetically modified nuclear donor cells. Couplets were fused and activated simultaneously with a single DC pulse of 3.0 kV/cm for either 30 or 60 μs. Low rates of fusion and embryo development to the blastocyst stage were observed in the reconstructed HAC-transchromosomic embryos, when the duration of fusion was prolonged to 60 μs. In contrast, the prolongation of electric pulse duration improved the embryo development and quality in the reconstructed control embryos without HAC vector. Our results suggested that the optimal parameters of electric pulses for fusion in cat somatic cell nuclear transfer vary among the types used for donor cells. © 2016 Blackwell Verlag GmbH.

Polyploidization without mitosis improves in vivo liver transduction with lentiviral vectors.

PubMed

Pichard, Virginie; Couton, Dominique; Desdouets, Chantal; Ferry, Nicolas

2013-02-01

Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vectors. However, the precise relationship between hepatocyte division and transduction efficiency has not been determined yet. Here we compared gene transfer efficiency in the liver after in vivo injection of recombinant lentiviral or Moloney murine leukemia viral (MoMuLV) vectors in hepatectomized rats treated or not with retrorsine, an alkaloid that blocks hepatocyte division and induces megalocytosis. Partial hepatectomy alone resulted in a similar increase in hepatocyte transduction using either vector. In retrorsine-treated and partially hepatectomized rats, transduction with MoMuLV vectors dropped dramatically. In contrast, we observed that retrorsine treatment combined with partial hepatectomy increased lentiviral transduction to higher levels than hepatectomy alone. Analysis of nuclear ploidy in single cells showed that a high level of transduction was associated with polyploidization. In conclusion, endoreplication could be exploited to improve the efficiency of liver-directed lentiviral gene therapy.

Polyploidization Without Mitosis Improves In Vivo Liver Transduction With Lentiviral Vectors

PubMed Central

Couton, Dominique; Desdouets, Chantal; Ferry, Nicolas

2013-01-01

Abstract Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vectors. However, the precise relationship between hepatocyte division and transduction efficiency has not been determined yet. Here we compared gene transfer efficiency in the liver after in vivo injection of recombinant lentiviral or Moloney murine leukemia viral (MoMuLV) vectors in hepatectomized rats treated or not with retrorsine, an alkaloid that blocks hepatocyte division and induces megalocytosis. Partial hepatectomy alone resulted in a similar increase in hepatocyte transduction using either vector. In retrorsine-treated and partially hepatectomized rats, transduction with MoMuLV vectors dropped dramatically. In contrast, we observed that retrorsine treatment combined with partial hepatectomy increased lentiviral transduction to higher levels than hepatectomy alone. Analysis of nuclear ploidy in single cells showed that a high level of transduction was associated with polyploidization. In conclusion, endoreplication could be exploited to improve the efficiency of liver-directed lentiviral gene therapy. PMID:23249390

Vector boson production in pPb and PbPb collisions at the LHC and its impact on nCTEQ15 PDFs

DOE PAGES

Kusina, A.; Lyonnet, F.; Clark, D. B.; ...

2017-07-21

Here, we provide a comprehensive comparison of W ±/Z vector boson production data in pPb and PbPb collisions at the LHC with predictions obtained using the nCTEQ15 PDFs. We also identify the measurements which have the largest potential impact on the PDFs, and estimate the effect of including these data using a Bayesian reweighting method. We find this data set can provide information as regards both the nuclear corrections and the heavy flavor (strange quark) PDF components. As for the proton, the parton flavor determination/separation is dependent on nuclear corrections (from heavy target DIS, for example), this information can alsomore » help improve the proton PDFs.« less

Vector boson production in pPb and PbPb collisions at the LHC and its impact on nCTEQ15 PDFs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kusina, A.; Lyonnet, F.; Clark, D. B.

Here, we provide a comprehensive comparison of W ±/Z vector boson production data in pPb and PbPb collisions at the LHC with predictions obtained using the nCTEQ15 PDFs. We also identify the measurements which have the largest potential impact on the PDFs, and estimate the effect of including these data using a Bayesian reweighting method. We find this data set can provide information as regards both the nuclear corrections and the heavy flavor (strange quark) PDF components. As for the proton, the parton flavor determination/separation is dependent on nuclear corrections (from heavy target DIS, for example), this information can alsomore » help improve the proton PDFs.« less

First non-OEM steam-generator replacement in US a success

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendsbee, P.M.; Lees, M.D.; Smith, J.C.

1994-04-01

In selecting replacements for major powerplant components, a fresh approach can be advantageous--even when complex nuclear components are involved. This was the experience at Unit 2 of Millstone nuclear station, which features an 870-MW pressurized-water reactor (PWR) with two nuclear recirculating steam generators. The unit began operation in 1975. In the early 1980s, pitting problems surfaced in the steam generator tubing; by the mid eighties, tube corrosion had reached an unacceptable level. Virtually all of the 17,000 tubes in the two units were deteriorating, with 2500 plugged and 5000 sleeved. Several new problems also were identified, including secondary-side circumferential crackingmore » of the Alloy 600 tubing near the tubesheet face, and deterioration of the carbon steel egg-crate tube supports. Despite improvements to primary and secondary steam-generator water chemistry, including almost complete copper removal from the condensate and feedwater loops, Northeast Utilities (NU) was unable to completely control degradation of the tube bundles. The utility decided in 1987 that full replacement was the most viable alternative. NU made a bold move, selecting a supplier other than the original equipment manufacturer (OEM).« less

U.S. Nuclear Power Plants: Continued Life or Replacement After 60? (released in AEO2010)

EIA Publications

2010-01-01

Nuclear power plants generate approximately 20% of U.S. electricity, and the plants in operation today are often seen as attractive assets in the current environment of uncertainty about future fossil fuel prices, high construction costs for new power plants (particularly nuclear plants), and the potential enactment of greenhouse gas regulations. Existing nuclear power plants have low fuel costs and relatively high power output. However, there is uncertainty about how long they will be allowed to continue operating.

Navy Ohio Replacement (SSBN[X]) Ballistic Missile Submarine Program: Background and Issues for Congress

DTIC Science & Technology

2012-12-10

nuclear powered submarines, which are powered by energy sources such as diesel engines. A submarine’s use of nuclear or non-nuclear power as its energy ...WA, in Puget Sound; the other six are homeported at Kings Bay, GA, close to the Florida border. Unlike most Navy ships, which are operated by...countries on nuclear-related issues that is carried out under the 1958 Agreement for Cooperation on the Uses of Atomic Energy for Mutual Defense

Introduction of a point mutation into the mouse genome by homologous recombination in embryonic stem cells using a replacement type vector with a selectable marker.

PubMed

Rubinstein, M; Japón, M A; Low, M J

1993-06-11

The introduction of small mutations instead of null alleles into the mouse genome has broad applications to the study of protein structure-function relationships and the creation of animal models of human genetic diseases. To test a simple mutational strategy we designed a targeting vector for the mouse proopiomelanocortin (POMC) gene containing a single nucleotide insertion that converts the initial tyrosine codon of beta-endorphin 1-31 to a premature translational termination codon and introduces a unique Hpal endonuclease restriction site. The targeting vector also contains a neo cassette immediately 3' to the last POMC exon and a herpes simplex virus thymidine kinase cassette to allow positive and negative selection. Homologous recombination occurred at a frequency of 1/30 clones of electroporated embryonic stem cells selected in G418 and gancyclovir. 10/11 clones identified initially by a polymerase chain reaction (PCR) strategy had the predicted structure without evidence of concatemer formation by Southern blot analysis. We used a combination of Hpa I digestion of PCR amplified fragments and direct nucleotide sequencing to further confirm that the point mutation was retained in 9/10 clones. The POMC gene was transcriptionally silent in embryonic stem cells and the targeted allele was not activated by the downstream phosphoglycerate kinase-1 promoter that transcribed the neo gene. Under the electroporation conditions used, we have demonstrated that a point mutation can be introduced with high efficiency and precision into the POMC gene using a replacement type vector containing a retained selectable marker without affecting expression of the allele in the embryonic stem cells. A similar strategy may be useful for a wide range of genes.

Introduction of a point mutation into the mouse genome by homologous recombination in embryonic stem cells using a replacement type vector with a selectable marker.

PubMed Central

Rubinstein, M; Japón, M A; Low, M J

1993-01-01

The introduction of small mutations instead of null alleles into the mouse genome has broad applications to the study of protein structure-function relationships and the creation of animal models of human genetic diseases. To test a simple mutational strategy we designed a targeting vector for the mouse proopiomelanocortin (POMC) gene containing a single nucleotide insertion that converts the initial tyrosine codon of beta-endorphin 1-31 to a premature translational termination codon and introduces a unique Hpal endonuclease restriction site. The targeting vector also contains a neo cassette immediately 3' to the last POMC exon and a herpes simplex virus thymidine kinase cassette to allow positive and negative selection. Homologous recombination occurred at a frequency of 1/30 clones of electroporated embryonic stem cells selected in G418 and gancyclovir. 10/11 clones identified initially by a polymerase chain reaction (PCR) strategy had the predicted structure without evidence of concatemer formation by Southern blot analysis. We used a combination of Hpa I digestion of PCR amplified fragments and direct nucleotide sequencing to further confirm that the point mutation was retained in 9/10 clones. The POMC gene was transcriptionally silent in embryonic stem cells and the targeted allele was not activated by the downstream phosphoglycerate kinase-1 promoter that transcribed the neo gene. Under the electroporation conditions used, we have demonstrated that a point mutation can be introduced with high efficiency and precision into the POMC gene using a replacement type vector containing a retained selectable marker without affecting expression of the allele in the embryonic stem cells. A similar strategy may be useful for a wide range of genes. Images PMID:8392702

Thailand Momentum on Policy and Practice in Local Legislation on Dengue Vector Control

PubMed Central

Bhumiratana, Adisak; Intarapuk, Apiradee; Chujun, Suriyo; Kaewwaen, Wuthichai; Sorosjinda-Nunthawarasilp, Prapa; Koyadun, Surachart

2014-01-01

Over a past decade, an administrative decentralization model, adopted for local administration development in Thailand, is replacing the prior centralized (top-down) command system. The change offers challenges to local governmental agencies and other public health agencies at all the ministerial, regional, and provincial levels. A public health regulatory and legislative framework for dengue vector control by local governmental agencies is a national topic of interest because dengue control program has been integrated into healthcare services at the provincial level and also has been given priority in health plans of local governmental agencies. The enabling environments of local administrations are unique, so this critical review focuses on the authority of local governmental agencies responsible for disease prevention and control and on the functioning of local legislation with respect to dengue vector control and practices. PMID:24799896

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Brien, K H

Nuclear weapons play an essential role in United States (U.S.) National Security Policy and a succession of official reviews has concluded that nuclear weapons will continue to have a role for the foreseeable future. Under the evolving U.S. government policy, it is clear that role will be quite different from what it was during the Cold War. The nuclear-weapons stockpile as well as the nuclear-weapons enterprise needs to continue to change to reflect this evolving role. Stockpile reductions in the early 1990s and the Stockpile Stewardship Program (SSP), established after the cessation of nuclear testing in 1992, began this processmore » of change. Further evolution is needed to address changing security environments, to enable further reductions in the number of stockpiled weapons, and to create a nuclear enterprise that is cost effective and sustainable for the long term. The SSP has successfully maintained the U.S. nuclear stockpile for more than a decade, since the end of nuclear testing. Current plans foresee maintaining warheads produced in the 1980s until about 2040. These warheads continue to age and they are expensive to refurbish. The current Life Extension Program plans for these legacy warheads are straining both the nuclear-weapons production and certification infrastructure making it difficult to respond rapidly to problems or changes in requirements. Furthermore, refurbishing and preserving Cold-War-era nuclear weapons requires refurbishing and preserving an infrastructure geared to support old technology. Stockpile Stewardship could continue this refurbishment approach, but an alternative approach could be considered that is more focused on sustainable technologies, and developing a more responsive nuclear weapons infrastructure. Guided by what we have learned from SSP during the last decade, the stewardship program can be evolved to address this increasing challenge using its computational and experimental tools and capabilities. This approach must start with an improved vision of the future stockpile and enterprise, and find a path that moves us toward that future. The goal of this approach is to achieve a more affordable, sustainable, and responsive enterprise. In order to transform the enterprise in this way, the SSP warhead designs that drive the enterprise must change. Designs that emphasize manufacturability, certifiability, and increased safety and security can enable enterprise transformation. It is anticipated that such warheads can be certified and sustained with high confidence without nuclear testing. The SSP provides the tools to provide such designs, and can develop replacement designs and produce them for the stockpile. The Cold War currency of optimizing warhead yield-to-weight can be replaced by SSP designs optimizing margin-to-uncertainty. The immediate challenge facing the nuclear weapons enterprise is to find a credible path that leads to this vision of the future stockpile and enterprise. Reliable warheads within a sustainable enterprise can best be achieved by shifting from a program of legacy-warhead refurbishment to one of warhead replacement. The nuclear weapons stockpile and the nuclear weapons enterprise must transform together to achieve this vision. The current Reliable Replacement Warhead (RRW) program represents an approach that can begin this process of transformation. If the RRW program succeeds, the designs, manufacturing complex, and certification strategy can evolve together and in so doing come up with a more cost-efficient solution that meets today's and tomorrow's national security requirements.« less

Detailed requirements for a next generation nuclear data structure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, D.

2016-07-05

This document attempts to compile the requirements for the top-levels of a hierarchical arrangement of nuclear data such as found in the ENDF format. This set of requirements will be used to guide the development of a new data structure to replace the legacy ENDF format.

Adeno-associated virus vectors can be efficiently produced without helper virus.

PubMed

Matsushita, T; Elliger, S; Elliger, C; Podsakoff, G; Villarreal, L; Kurtzman, G J; Iwaki, Y; Colosi, P

1998-07-01

The purpose of this work was to develop an efficient method for the production of adeno-associated virus (AAV) vectors in the absence of helper virus. The adenovirus regions that mediate AAV vector replication were identified and assembled into a helper plasmid. These included the VA, E2A and E4 regions. When this helper plasmid was cotransfected into 293 cells, along with plasmids encoding the AAV vector, and rep and cap genes, AAV vector was produced as efficiently as when using adenovirus infection as a source of help. CMV-driven constructs expressing the E4orf6 and the 72-M(r), E2A proteins were able to functionally replace the E4 and E2A regions, respectively. Therefore the minimum set of genes required to produce AAV helper activity equivalent to that provided by adenovirus infection consists of, or is a subset of, the following genes: the E4orf6 gene, the 72-M(r), E2A protein gene, the VA RNA genes and the E1 region. AAV vector preparations made with adenovirus and by the helper virus-free method were essentially indistinguishable with respect to particle density, particle to infectivity ratio, capsimer ratio and efficiency of muscle transduction in vivo. Only AAV vector preparations made by the helper virus-free method were not reactive with anti-adenovirus sera.

Correction of Murine Sickle Cell Disease Using γ-Globin Lentiviral Vectors to Mediate High-level Expression of Fetal Hemoglobin

PubMed Central

Pestina, Tamara I; Hargrove, Phillip W; Jay, Dennis; Gray, John T; Boyd, Kelli M; Persons, Derek A

2008-01-01

Increased levels of red cell fetal hemogloblin, whether due to hereditary persistence of expression or from induction with hydroxyurea therapy, effectively ameliorate sickle cell disease (SCD). Therefore, we developed erythroid-specific, γ-globin lentiviral vectors for hematopoietic stem cell (HSC)-targeted gene therapy with the goal of permanently increasing fetal hemoglobin (HbF) production in sickle red cells. We evaluated two different γ-globin lentiviral vectors for therapeutic efficacy in the BERK sickle cell mouse model. The first vector, V5, contained the γ-globin gene driven by 3.1 kb of β-globin regulatory sequences and a 130-bp β-globin promoter. The second vector, V5m3, was identical except that the γ-globin 3′-untranslated region (3′-UTR) was replaced with the β-globin 3′-UTR. Adult erythroid cells have β-globin mRNA 3′-UTR-binding proteins that enhance β-globin mRNA stability and we postulated this design might enhance γ-globin expression. Stem cell gene transfer was efficient and nearly all red cells in transplanted mice expressed human γ-globin. Both vectors demonstrated efficacy in disease correction, with the V5m3 vector producing a higher level of γ-globin mRNA which was associated with high-level correction of anemia and secondary organ pathology. These data support the rationale for a gene therapy approach to SCD by permanently enhancing HbF using a γ-globin lentiviral vector. PMID:19050697

A Model Framework to Estimate Impact and Cost of Genetics-Based Sterile Insect Methods for Dengue Vector Control

PubMed Central

Alphey, Nina; Alphey, Luke; Bonsall, Michael B.

2011-01-01

Vector-borne diseases impose enormous health and economic burdens and additional methods to control vector populations are clearly needed. The Sterile Insect Technique (SIT) has been successful against agricultural pests, but is not in large-scale use for suppressing or eliminating mosquito populations. Genetic RIDL technology (Release of Insects carrying a Dominant Lethal) is a proposed modification that involves releasing insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation, and could potentially overcome some technical difficulties with the conventional SIT technology. Using the arboviral disease dengue as an example, we combine vector population dynamics and epidemiological models to explore the effect of a program of RIDL releases on disease transmission. We use these to derive a preliminary estimate of the potential cost-effectiveness of vector control by applying estimates of the costs of SIT. We predict that this genetic control strategy could eliminate dengue rapidly from a human community, and at lower expense (approximately US$ 2∼30 per case averted) than the direct and indirect costs of disease (mean US$ 86–190 per case of dengue). The theoretical framework has wider potential use; by appropriately adapting or replacing each component of the framework (entomological, epidemiological, vector control bio-economics and health economics), it could be applied to other vector-borne diseases or vector control strategies and extended to include other health interventions. PMID:21998654

Impaired expression of importin/karyopherin {beta}1 leads to post-implantation lethality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miura, Katsutaka; Yoshinobu, Kumiko; Imaizumi, Takashi

2006-03-03

Importin {beta}1 (Imp{beta})/karyopherin {beta}1 (Kpnb1) mediates the nuclear import of a large variety of substrates. This study aimed to investigate the requirement for the Kpnb1 gene in mouse development, using a gene trap line, B6-CB-Ayu8108 {sup GtgeoIMEG} (Ayu8108 {sup geo}), in which the trap vector was inserted into the promoter region of the Kpnb1 gene, but in reverse orientation of the Kpnb1 gene. Ayu8108 {sup geo/geo} homozygous embryos could develop to the blastocyst stage, but died before embryonic day 5.5, and expression of the Kpnb1 gene in homozygous blastocysts was undetectable. We also replaced the {beta}geo gene with Imp{beta} cDNAmore » through Cre-mediated recombination to rescue Imp{beta} expression. Homozygous mice for the rescued allele Ayu8108 {sup Imp{beta}}{sup /Imp{beta}} were born and developed normally. These results demonstrated that the cause of post-implantation lethality of Ayu8108 {sup geo/geo} homozygous embryos was impaired expression of the Kpnb1 gene, indicating indispensable roles of Imp{beta}1 in early development of mice.« less

A lentiviral vector with expression controlled by E2F-1: A potential tool for the study and treatment of proliferative diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strauss, Bryan E.; Patricio, Juliana Rotelli; Program in Biotechnology, University of Sao Paulo

2006-10-06

We have constructed a lentiviral vector with expression limited to cells presenting active E2F-1 protein, a potential advantage for gene therapy of proliferative diseases. For the FE2FLW vector, the promoter region of the human E2F-1 gene was utilized to drive expression of luciferase cDNA, included as a reporter of viral expression. Primary, immortalized, and transformed cells were transduced with the FE2FLW vector and cell cycle alterations were induced with serum starvation/replacement, contact inhibition or drug treatment, revealing cell cycle-dependent changes in reporter activity. Forced E2F-1 expression, but not E2F-2 or E2F-3, increased reporter activity, indicating a major role for thismore » factor in controlling expression from the FE2FLW virus. We show the utility of this vector as a reporter of E2F-1 and proliferation-dependent cellular alterations upon cytotoxic/cytostatic treatment, such as the introduction of tumor suppressor genes. We propose that the FE2FLW vector may be a starting point for the development of gene therapy strategies for proliferative diseases, such as cancer or restinosis.« less

Laboratory instrumentation modernization at the WPI Nuclear Reactor Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1995-01-01

With partial funding from the Department of Energy (DOE) University Reactor Instrumentation Program several laboratory instruments utilized by students and researchers at the WPI Nuclear Reactor Facility have been upgraded or replaced. Designed and built by General Electric in 1959, the open pool nuclear training reactor at WPI was one of the first such facilities in the nation located on a university campus. Devoted to undergraduate use, the reactor and its related facilities have been since used to train two generations of nuclear engineers and scientists for the nuclear industry. The low power output of the reactor and an ergonomicmore » facility design make it an ideal tool for undergraduate nuclear engineering education and other training. The reactor, its control system, and the associate laboratory equipment are all located in the same room. Over the years, several important milestones have taken place at the WPI reactor. In 1969, the reactor power level was upgraded from 1 kW to 10 kW. The reactor`s Nuclear Regulatory Commission operating license was renewed for 20 years in 1983. In 1988, under DOE Grant No. DE-FG07-86ER75271, the reactor was converted to low-enriched uranium fuel. In 1992, again with partial funding from DOE (Grant No. DE-FG02-90ER12982), the original control console was replaced.« less

Support vector machines for nuclear reactor state estimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zavaljevski, N.; Gross, K. C.

2000-02-14

Validation of nuclear power reactor signals is often performed by comparing signal prototypes with the actual reactor signals. The signal prototypes are often computed based on empirical data. The implementation of an estimation algorithm which can make predictions on limited data is an important issue. A new machine learning algorithm called support vector machines (SVMS) recently developed by Vladimir Vapnik and his coworkers enables a high level of generalization with finite high-dimensional data. The improved generalization in comparison with standard methods like neural networks is due mainly to the following characteristics of the method. The input data space is transformedmore » into a high-dimensional feature space using a kernel function, and the learning problem is formulated as a convex quadratic programming problem with a unique solution. In this paper the authors have applied the SVM method for data-based state estimation in nuclear power reactors. In particular, they implemented and tested kernels developed at Argonne National Laboratory for the Multivariate State Estimation Technique (MSET), a nonlinear, nonparametric estimation technique with a wide range of applications in nuclear reactors. The methodology has been applied to three data sets from experimental and commercial nuclear power reactor applications. The results are promising. The combination of MSET kernels with the SVM method has better noise reduction and generalization properties than the standard MSET algorithm.« less

Scalar pseudo-Nambu-Goldstone boson in nuclei and dense nuclear matter

NASA Astrophysics Data System (ADS)

Lee, Hyun Kyu; Paeng, Won-Gi; Rho, Mannque

2015-12-01

The notion that the scalar listed as f0(500 ) in the particle data booklet is a pseudo-Nambu-Goldstone (NG) boson of spontaneously broken scale symmetry, explicitly broken by a small departure from an infrared fixed point, is explored in nuclear dynamics. This notion—which puts the scalar (which we shall identify as the "dilaton") on the same footing as the pseudoscalar pseudo-NG bosons, i.e., octet π , while providing a simple explanation for the Δ I =1 /2 rule for kaon decay—generalizes the standard chiral perturbation theory (χ PT ) to "scale chiral perturbation theory," denoted χPT σ , with one infrared mass scale for both symmetries, with the σ figuring as a chiral singlet NG mode in the nonstrange sector. Applied to nuclear dynamics, it is seen to provide answers to various hitherto unclarified nuclear phenomena, such as the success of one-boson-exchange potentials, the large cancellation of a strongly attractive scalar potential by a strongly repulsive vector potential in relativistic mean-field theory of nuclear systems and in-medium QCD sum rules, the interplay of the dilaton and the vector meson ω in dense Skyrmion matter, the Bogomol'nyi-Prasad-Sommerfeld Skyrmion structure of nuclei accounting for small binding energies of medium-heavy nuclei, and the suppression of hyperon degrees of freedom in compact-star matter.

A Technical and Economic Review of Solar Hydrogen Production Technologies

ERIC Educational Resources Information Center

Wilhelm, Erik; Fowler, Michael

2006-01-01

Hydrogen energy systems are being developed to replace fossil fuels-based systems for transportation and stationary application. One of the challenges facing the widespread adoption of hydrogen as an energy vector is the lack of an efficient, economical, and sustainable method of hydrogen production. In the short term, hydrogen produced from…

An asymptotical machine

NASA Astrophysics Data System (ADS)

Cristallini, Achille

2016-07-01

A new and intriguing machine may be obtained replacing the moving pulley of a gun tackle with a fixed point in the rope. Its most important feature is the asymptotic efficiency. Here we obtain a satisfactory description of this machine by means of vector calculus and elementary trigonometry. The mathematical model has been compared with experimental data and briefly discussed.

Divergence Boundary Conditions for Vector Helmholtz Equations with Divergence Constraints

NASA Technical Reports Server (NTRS)

Kangro, Urve; Nicolaides, Roy

1997-01-01

The idea of replacing a divergence constraint by a divergence boundary condition is investigated. The connections between the formulations are considered in detail. It is shown that the most common methods of using divergence boundary conditions do not always work properly. Necessary and sufficient conditions for the equivalence of the formulations are given.

75 FR 13320 - Florida Power Corporation, et al., Crystal River Unit 3 Nuclear Generating Plant; Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

... replacement outage that is currently underway at CR-3. In addition to steam generators, other large components (e.g., moisture separators and large heat exchangers) are being replaced during this outage... on the Internet at the NRC Web site: http://www.nrc.gov/reading-rm/adams.html . Persons who do not...

Memory efficient solution of the primitive equations for numerical weather prediction on the CYBER 205

NASA Technical Reports Server (NTRS)

Tuccillo, J. J.

1984-01-01

Numerical Weather Prediction (NWP), for both operational and research purposes, requires only fast computational speed but also large memory. A technique for solving the Primitive Equations for atmospheric motion on the CYBER 205, as implemented in the Mesoscale Atmospheric Simulation System, which is fully vectorized and requires substantially less memory than other techniques such as the Leapfrog or Adams-Bashforth Schemes is discussed. The technique presented uses the Euler-Backard time marching scheme. Also discussed are several techniques for reducing computational time of the model by replacing slow intrinsic routines by faster algorithms which use only hardware vector instructions.

Applications of Support Vector Machines In Chemo And Bioinformatics

NASA Astrophysics Data System (ADS)

Jayaraman, V. K.; Sundararajan, V.

2010-10-01

Conventional linear & nonlinear tools for classification, regression & data driven modeling are being replaced on a rapid scale by newer techniques & tools based on artificial intelligence and machine learning. While the linear techniques are not applicable for inherently nonlinear problems, newer methods serve as attractive alternatives for solving real life problems. Support Vector Machine (SVM) classifiers are a set of universal feed-forward network based classification algorithms that have been formulated from statistical learning theory and structural risk minimization principle. SVM regression closely follows the classification methodology. In this work recent applications of SVM in Chemo & Bioinformatics will be described with suitable illustrative examples.

A genetically adjuvanted influenza B virus vector increases immunogenicity and protective efficacy in mice.

PubMed

Kittel, Christian; Wressnigg, Nina; Shurygina, Anna Polina; Wolschek, Markus; Stukova, Marina; Romanovskaya-Romanko, Ekatherina; Romanova, Julia; Kiselev, Oleg; Muster, Thomas; Egorov, Andrej

2015-10-01

The existence of multiple antigenically distinct types and subtypes of influenza viruses allows the construction of a multivalent vector system for the mucosal delivery of foreign sequences. Influenza A viruses have been exploited successfully for the expression of extraneous antigens as well as immunostimulatory molecules. In this study, we describe the development of an influenza B virus vector whose functional part of the interferon antagonist NS1 was replaced by human interleukin 2 (IL2) as a genetic adjuvant. We demonstrate that IL2 expressed by this viral vector displays immune adjuvant activity in immunized mice. Animals vaccinated with the IL2 viral vector showed an increased hemagglutination inhibition antibody response and higher protective efficacy after challenge with a wild-type influenza B virus when compared to mice vaccinated with a control virus. Our results demonstrate that it is feasible to construct influenza B vaccine strains expressing immune-potentiating foreign sequences from the NS genomic segment. Based on these data, it is now hypothetically possible to create a trivalent (or quadrivalent) live attenuated influenza vaccine in which each component expresses a selected genetic adjuvant with tailored expression levels.

Flufenoxuron, an insect growth regulator, promotes peroral infection by nucleopolyhedrovirus (BmNPV) budded particles in the silkworm, Bombyx mori L.

PubMed

Arakawa, Toru; Furuta, Yoji; Miyazawa, Mitsuhiro; Kato, Masao

2002-02-01

A novel method was developed to infect perorally the silkworm Bombyx mori L. with budded particles of nucleopolyhedrovirus (BmNPV) using flufenoxuron, an insect growth regulator. NPV vectors are used to obtain proteins that occur naturally in minute amounts. NPV vectors are constructed conventionally by replacing the polyhedrin gene with the foreign gene of interest. These vectors thus do not produce polyhedra. The budded virus particle suspension of these vectors is produced in a cell culture and used as the stock inoculum. Budded NPV particles do not infect their host perorally. The inoculum is injected manually into the individual host using a syringe. It was found that B. mori L. fed on the insect growth regulator flufenoxuron were sensitive to BmNPV budded particles given perorally. Over 90% of B. mori L. ingesting BmNPV budded particles (1.3 x 10(6) TCID(50) units per larva) after consuming an artificial diet for 24 h, containing 0.1% (w/w) flufenoxuron died of the viral infection. The peroral inoculation of BmNPV budded particles by flufenoxuron may thus lead to industrial pharmaceutical production using a baculovirus vector for large numbers of insect hosts.

Characterization of a 3rd Generation Lentiviral Vector Pseudotyped With Nipah Virus Envelope Proteins For Endothelial Cell Transduction

PubMed Central

Witting, Scott R.; Vallanda, Priya; Gamble, Aisha L.

2013-01-01

Lentiviruses are becoming progressively more popular as gene therapy vectors due to their ability to integrate into quiescent cells and recent clinical trial successes. Directing these vectors to specific cell types and limiting off-target transduction in vivo remains a challenge. Replacing the viral envelope proteins responsible for cellular binding, or pseudotyping, remains a common method to improve lentiviral targeting. Here, we describe the development of a high titer, 3rd generation lentiviral vector pseudotyped with Nipah virus fusion protein (NiV-F) and attachment protein (NiV-G). Critical to high titers was truncation of the cytoplasmic domains of both NiV-F and NiV-G. As known targets of wild-type Nipah virus, primary endothelial cells are shown to be effectively transduced by the Nipah pseudotype. In contrast, human CD34+ hematopoietic progenitors were not significantly transduced. Additionally, the Nipah pseudotype has increased stability in human serum compared to VSV pseudotyped lentivirus. These findings suggest that the use of Nipah virus envelope proteins in 3rd generation lentiviral vectors would be a valuable tool for gene delivery targeted to endothelial cells. PMID:23698741

Characterization of a third generation lentiviral vector pseudotyped with Nipah virus envelope proteins for endothelial cell transduction.

PubMed

Witting, S R; Vallanda, P; Gamble, A L

2013-10-01

Lentiviruses are becoming progressively more popular as gene therapy vectors due to their ability to integrate into quiescent cells and recent clinical trial successes. Directing these vectors to specific cell types and limiting off-target transduction in vivo remains a challenge. Replacing the viral envelope proteins responsible for cellular binding, or pseudotyping, remains a common method to improve lentiviral targeting. Here, we describe the development of a high titer, third generation lentiviral vector pseudotyped with Nipah virus fusion protein (NiV-F) and attachment protein (NiV-G). Critical to high titers was truncation of the cytoplasmic domains of both NiV-F and NiV-G. As known targets of wild-type Nipah virus, primary endothelial cells are shown to be effectively transduced by the Nipah pseudotype. In contrast, human CD34+ hematopoietic progenitors were not significantly transduced. Additionally, the Nipah pseudotype has increased stability in human serum compared with vesicular stomatitis virus pseudotyped lentivirus. These findings suggest that the use of Nipah virus envelope proteins in third generation lentiviral vectors would be a valuable tool for gene delivery targeted to endothelial cells.

A new implementation of the CMRH method for solving dense linear systems

NASA Astrophysics Data System (ADS)

Heyouni, M.; Sadok, H.

2008-04-01

The CMRH method [H. Sadok, Methodes de projections pour les systemes lineaires et non lineaires, Habilitation thesis, University of Lille1, Lille, France, 1994; H. Sadok, CMRH: A new method for solving nonsymmetric linear systems based on the Hessenberg reduction algorithm, Numer. Algorithms 20 (1999) 303-321] is an algorithm for solving nonsymmetric linear systems in which the Arnoldi component of GMRES is replaced by the Hessenberg process, which generates Krylov basis vectors which are orthogonal to standard unit basis vectors rather than mutually orthogonal. The iterate is formed from these vectors by solving a small least squares problem involving a Hessenberg matrix. Like GMRES, this method requires one matrix-vector product per iteration. However, it can be implemented to require half as much arithmetic work and less storage. Moreover, numerical experiments show that this method performs accurately and reduces the residual about as fast as GMRES. With this new implementation, we show that the CMRH method is the only method with long-term recurrence which requires not storing at the same time the entire Krylov vectors basis and the original matrix as in the GMRES algorithmE A comparison with Gaussian elimination is provided.

Vectors expressing chimeric Japanese encephalitis dengue 2 viruses.

PubMed

Wei, Y; Wang, S; Wang, X

2014-01-01

Vectors based on self-replicating RNAs (replicons) of flaviviruses are becoming powerful tool for expression of heterologous genes in mammalian cells and development of novel antiviral and anticancer vaccines. We constructed two vectors expressing chimeric viruses consisting of attenuated SA14-14-2 strain of Japanese encephalitis virus (JEV) in which the PrM/M-E genes were replaced fully or partially with those of dengue 2 virus (DENV-2). These vectors, named pJED2 and pJED2-1770 were transfected to BHK-21 cells and produced chimeric viruses JED2V and JED2-1770V, respectively. The chimeric viruses could be passaged in C6/36 but not BHK-21 cells. The chimeric viruses produced in C6/36 cells CPE 4-5 days after infection and RT-PCR, sequencing, immunofluorescence assay (IFA) and Western blot analysis confirmed the chimeric nature of produced viruses. The immunogenicity of chimeric viruses in mice was proved by detecting DENV-2 E protein-specific serum IgG antibodies with neutralization titer of 10. Successful preparation of infectious clones of chimeric JEV-DENV-2 viruses showed that JEV-based expression vectors are fully functional.

Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients.

PubMed

Poyau, A; Buchet, K; Bouzidi, M F; Zabot, M T; Echenne, B; Yao, J; Shoubridge, E A; Godinot, C

2000-02-01

We have studied the fibroblasts of three patients suffering from Leigh syndrome associated with cytochrome c oxidase deficiency (LS-COX-). Their mitochondrial DNA was functional and all nuclear COX subunits had a normal sequence. The expression of transcripts encoding mitochondrial and nuclear COX subunits was normal or slightly increased. Similarly, the OXA1 transcript coding for a protein involved in COX assembly was increased. However, several COX-protein subunits were severely depressed, indicating deficient COX assembly. Surf1, a factor involved in COX biogenesis, was recently reported as mutated in LS-COX- patients, all mutations predicting a truncated protein. Sequence analysis of SURF1 gene in our three patients revealed seven heterozygous mutations, six of which were new : an insertion, a nonsense mutation, a splicing mutation of intron 7 in addition to three missense mutations. The mutation G385 A (Gly124-->Glu) changes a Gly that is strictly conserved in Surfl homologs of 12 species. The substitution G618 C (Asp202-->His), changing an Asp that is conserved only in mammals, appears to be a polymorphism. The mutation T751 C changes Ile246 to Thr, a position at which a hydrophobic amino acid is conserved in all eukaryotic and some bacterial species. Replacing Ile246 by Thr disrupts a predicted beta sheet structure present in all higher eukaryotes. COX activity could be restored in fibroblasts of the three patients by complementation with a retroviral vector containing normal SURF1 cDNA. These mutations identify domains essential to Surf1 protein structure and/or function.

Massive neutral gauge boson production as a probe of nuclear modifications of parton distributions at the LHC

NASA Astrophysics Data System (ADS)

Guzey, Vadim; Guzzi, Marco; Nadolsky, Pavel M.; Strikman, Mark; Wang, Bowen

2013-03-01

We analyze the role of nuclear modifications of parton distributions, notably, the nuclear shadowing and antishadowing corrections, in the production of lepton pairs from decays of neutral Z and γ∗ gauge bosons in proton-lead and lead-lead collisions at the LHC. Using the Collins-Soper-Sterman resummation formalism that we extended to the case of nuclear parton distributions, we observed a direct correlation between the predicted behavior of the transverse momentum and rapidity distributions of the produced vector bosons and the pattern of quark and gluon nuclear modifications. This makes the production of Z/γ∗ in pA and AA collisions at the LHC a useful tool for constraining nuclear PDFs in the small- x shadowing and moderate- x antishadowing regions.

Vendor advertorial issue, 2004

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnihotri, Newal

The focus of the July-August issue is on vendor advertorials. Major articles/reports in this issue include: A fascinating technology, by Andy White, GE Energy; Exciting times for the nuclear industry, by John Polcyn, AECL Technologies; SG replacement oversight program, by Ram Prabhakar, Palo Verde Nuclear Generating Station; Modifications for improvement, by Herbert Deutschmann, Swiss Federal Nuclear Safety Inspectorate, HSK, Switzerland; and, Human factor approach in engineering, by Laure Quentin, EDF and Didier Niger, UNIPE, France.

NUCLEAR CONVERSION APPARATUS

DOEpatents

Seaborg, G.T.

1960-09-13

A nuclear conversion apparatus is described which comprises a body of neutron moderator, tubes extending therethrough, uranium in the tubes, a fluid- circulating system associated with the tubes, a thorium-containing fluid coolant in the system and tubes, and means for withdrawing the fluid from the system and replacing it in the system whereby thorium conversion products may be recovered.

Control console replacement at the WPI Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-01-01

With partial funding from the Department of Energy (DOE) University Reactor Instrumentation Upgrade Program (DOE Grant No. DE-FG02-90ER12982), the original control console at the Worcester Polytechnic Institute (WPI) Reactor has been replaced with a modern system. The new console maintains the original design bases and functionality while utilizing current technology. An advanced remote monitoring system has been added to augment the educational capabilities of the reactor. Designed and built by General Electric in 1959, the open pool nuclear training reactor at WPI was one of the first such facilities in the nation located on a university campus. Devoted to undergraduatemore » use, the reactor and its related facilities have been since used to train two generations of nuclear engineers and scientists for the nuclear industry. The reactor power level was upgraded from 1 to 10 kill in 1969, and its operating license was renewed for 20 years in 1983. In 1988, the reactor was converted to low enriched uranium. The low power output of the reactor and ergonomic facility design make it an ideal tool for undergraduate nuclear engineering education and other training.« less

Contrasting genetic structure between mitochondrial and nuclear markers in the dengue fever mosquito from Rio de Janeiro: implications for vector control

PubMed Central

Rašić, Gordana; Schama, Renata; Powell, Rosanna; Maciel-de Freitas, Rafael; Endersby-Harshman, Nancy M; Filipović, Igor; Sylvestre, Gabriel; Máspero, Renato C; Hoffmann, Ary A

2015-01-01

Dengue is the most prevalent global arboviral disease that affects over 300 million people every year. Brazil has the highest number of dengue cases in the world, with the most severe epidemics in the city of Rio de Janeiro (Rio). The effective control of dengue is critically dependent on the knowledge of population genetic structuring in the primary dengue vector, the mosquito Aedes aegypti. We analyzed mitochondrial and nuclear genomewide single nucleotide polymorphism markers generated via Restriction-site Associated DNA sequencing, as well as traditional microsatellite markers in Ae. aegypti from Rio. We found four divergent mitochondrial lineages and a strong spatial structuring of mitochondrial variation, in contrast to the overall nuclear homogeneity across Rio. Despite a low overall differentiation in the nuclear genome, we detected strong spatial structure for variation in over 20 genes that have a significantly altered expression in response to insecticides, xenobiotics, and pathogens, including the novel biocontrol agent Wolbachia. Our results indicate that high genetic diversity, spatially unconstrained admixing likely mediated by male dispersal, along with locally heterogeneous genetic variation that could affect insecticide resistance and mosquito vectorial capacity, set limits to the effectiveness of measures to control dengue fever in Rio. PMID:26495042

Nuclear modification factor RCP for φ meson production in d+Au collisions at √SNN=200 GeV measured by the PHENIX experiment at RHIC

NASA Astrophysics Data System (ADS)

Guo, Lei

2009-10-01

In d+Au collisions, vector mesons produced in hard scattering are sensitive to various nuclear effects such as parton shadowing/saturation in the small x region (forward rapidity) leading to suppression, and antishadowing (large x region, backward rapidity) or the Cronin effect which both can produce enhancement. Since approaches such as the Color Glass Condensate (CGC) and pQCD-based Glauber-Eikonal models do not agree on the nature of these nuclear effects on particle production at large rapidity, it is essential that they be tested with experimental data in this kinematic regime. Knowledge of the difference between the forward and backward rapidity regions, in d+Au collisions, could also be used to separate the initial-state nuclear wave function modifications and final state in-medium effects in Au+Au collisions. In addition, the relative ratio for the production of ρ, φ and φ can provide information on the production mechanisms of light vector mesons. The PHENIX collaboration at RHIC has recently collected data in d+Au collisions at √s=200 GeV during the 2008 run. The latest work on the RCP measurements of φ, through the di-muon decays at forward and backward rapidities (1.2<η<2.2), will be discussed.

Nuclear Data Sheets for A = 152

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, M.J.

2013-11-15

Detailed level schemes, decay schemes, and the experimental data on which they are based are presented for all nuclei with mass number A=152. The experimental data are evaluated; inconsistencies and discrepancies are noted; and adopted values for level and γ–ray energies, γ intensities, as well as for other nuclear properties are given. This evaluation replaces the A=152 evaluation published by Agda Artna–Cohen in Nuclear Data Sheets 79, 1 (1996) and the evaluation for 152Dy prepared by Balraj Singh and published in Nuclear Data Sheets 95, 995 (2002)

Vector-averaged gravity alters myocyte and neuron properties in cell culture

NASA Technical Reports Server (NTRS)

Gruener, Raphael; Hoeger, Glenn

1991-01-01

The effect of changes in the gravitational field of developing neurons and myocytes on the development of these cells was investigated using observations of rotated cultures of embryonic spinal neurons and myocytes in a horizontal clinostat, in which rotation produces, from the cells' perspective, a 'vector-free' gravity environment by continous averaging of the vector, thus simulating the microgravity of space. It was found that, at rotation rates between 1 and 50 rpm, cellular and nuclear areas of myocytes become significantly enlarged and the number of presumptive nucleoli increase; in neurons, frequent and large swellings appeared along neuritic shafts. Some of these changes were reversible after the cessation of rotation.

Fault tolerant vector control of induction motor drive

NASA Astrophysics Data System (ADS)

Odnokopylov, G.; Bragin, A.

2014-10-01

For electric composed of technical objects hazardous industries, such as nuclear, military, chemical, etc. an urgent task is to increase their resiliency and survivability. The construction principle of vector control system fault-tolerant asynchronous electric. Displaying recovery efficiency three-phase induction motor drive in emergency mode using two-phase vector control system. The process of formation of a simulation model of the asynchronous electric unbalance in emergency mode. When modeling used coordinate transformation, providing emergency operation electric unbalance work. The results of modeling transient phase loss motor stator. During a power failure phase induction motor cannot save circular rotating field in the air gap of the motor and ensure the restoration of its efficiency at rated torque and speed.

Implementation of the block-Krylov boundary flexibility method of component synthesis

NASA Technical Reports Server (NTRS)

Carney, Kelly S.; Abdallah, Ayman A.; Hucklebridge, Arthur A.

1993-01-01

A method of dynamic substructuring is presented which utilizes a set of static Ritz vectors as a replacement for normal eigenvectors in component mode synthesis. This set of Ritz vectors is generated in a recurrence relationship, which has the form of a block-Krylov subspace. The initial seed to the recurrence algorithm is based on the boundary flexibility vectors of the component. This algorithm is not load-dependent, is applicable to both fixed and free-interface boundary components, and results in a general component model appropriate for any type of dynamic analysis. This methodology was implemented in the MSC/NASTRAN normal modes solution sequence using DMAP. The accuracy is found to be comparable to that of component synthesis based upon normal modes. The block-Krylov recurrence algorithm is a series of static solutions and so requires significantly less computation than solving the normal eigenspace problem.

Laplace-Runge-Lenz vector in quantum mechanics in noncommutative space

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gáliková, Veronika; Kováčik, Samuel; Prešnajder, Peter

2013-12-15

The main point of this paper is to examine a “hidden” dynamical symmetry connected with the conservation of Laplace-Runge-Lenz vector (LRL) in the hydrogen atom problem solved by means of non-commutative quantum mechanics (NCQM). The basic features of NCQM will be introduced to the reader, the key one being the fact that the notion of a point, or a zero distance in the considered configuration space, is abandoned and replaced with a “fuzzy” structure in such a way that the rotational invariance is preserved. The main facts about the conservation of LRL vector in both classical and quantum theory willmore » be reviewed. Finally, we will search for an analogy in the NCQM, provide our results and their comparison with the QM predictions. The key notions we are going to deal with are non-commutative space, Coulomb-Kepler problem, and symmetry.« less

Pseudo-Linear Attitude Determination of Spinning Spacecraft

NASA Technical Reports Server (NTRS)

Bar-Itzhack, Itzhack Y.; Harman, Richard R.

2004-01-01

This paper presents the overall mathematical model and results from pseudo linear recursive estimators of attitude and rate for a spinning spacecraft. The measurements considered are vector measurements obtained by sun-sensors, fixed head star trackers, horizon sensors, and three axis magnetometers. Two filters are proposed for estimating the attitude as well as the angular rate vector. One filter, called the q-Filter, yields the attitude estimate as a quaternion estimate, and the other filter, called the D-Filter, yields the estimated direction cosine matrix. Because the spacecraft is gyro-less, Euler s equation of angular motion of rigid bodies is used to enable the estimation of the angular velocity. A simpler Markov model is suggested as a replacement for Euler's equation in the case where the vector measurements are obtained at high rates relative to the spacecraft angular rate. The performance of the two filters is examined using simulated data.

Longitudinal vector form factors in weak decays of nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Šimkovic, F.; Department of Nuclear Physics and Biophysics, Comenius University, Mlynská dolina F1 SK–842 48 Bratislava; Kovalenko, S.

2015-10-28

The longitudinal form factors of the weak vector current of particles with spin J = 1/2 and isospin I = 1/2 are determined by the mass difference and the charge radii of members of the isotopic doublets. The most promising reactions to measure these form factors are the reactions with large momentum transfers involving the spin-1/2 isotopic doublets with a maximum mass splitting. Numerical estimates of longitudinal form factors are given for nucleons and eight nuclear spin-1/2 isotopic doublets.

Conserved quantities in non-Abelian monopole fields

NASA Astrophysics Data System (ADS)

Horváthy, P. A.; Ngome, J.-P.

2009-06-01

Van Holten’s covariant Hamiltonian framework is used to find conserved quantities for an isospin-carrying particle in a non-Abelian monopolelike field. For a Wu-Yang monopole we find the most general scalar potential such that the combined system admits a conserved Runge-Lenz vector. In the effective non-Abelian field for nuclear motion in a diatomic molecule due to Moody, Shapere, and Wilczek, a conserved angular momentum is constructed, despite the nonconservation of the electric charge. No Runge-Lenz vector has been found.

Development of Sendai Virus Vectors and their Potential Applications in Gene Therapy and Regenerative Medicine

PubMed Central

Nakanishi, Mahito; Otsu, Makoto

2012-01-01

Gene delivery/expression vectors have been used as fundamental technologies in gene therapy since the 1980s. These technologies are also being applied in regenerative medicine as tools to reprogram cell genomes to a pluripotent state and to other cell lineages. Rapid progress in these new research areas and expectations for their translation into clinical applications have facilitated the development of more sophisticated gene delivery/expression technologies. Since its isolation in 1953 in Japan, Sendai virus (SeV) has been widely used as a research tool in cell biology and in industry, but the application of SeV as a recombinant viral vector has been investigated only recently. Recombinant SeV vectors have various unique characteristics, such as low pathogenicity, powerful capacity for gene expression and a wide host range. In addition, the cytoplasmic gene expression mediated by this vector is advantageous for applications, in that chromosomal integration of exogenous genes can be undesirable. In this review, we introduce a brief historical background on the development of recombinant SeV vectors and describe their current applications in gene therapy. We also describe the application of SeV vectors in advanced nuclear reprogramming and introduce a defective and persistent SeV vector (SeVdp) optimized for such reprogramming. PMID:22920683

Gene therapy decreases seizures in a model of Incontinentia pigmenti.

PubMed

Dogbevia, Godwin K; Töllner, Kathrin; Körbelin, Jakob; Bröer, Sonja; Ridder, Dirk A; Grasshoff, Hanna; Brandt, Claudia; Wenzel, Jan; Straub, Beate K; Trepel, Martin; Löscher, Wolfgang; Schwaninger, Markus

2017-07-01

Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. In a mouse model of IP, we administered a single intravenous dose of the adeno-associated virus (AAV) vector, AAV-BR1-CAG-NEMO, delivering the Nemo gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood-brain barrier (BBB) were monitored. The endothelium-targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV-BR1-CAG-NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile. The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in IP. Ann Neurol 2017;82:93-104. © 2017 American Neurological Association.

Output-only modal parameter estimator of linear time-varying structural systems based on vector TAR model and least squares support vector machine

NASA Astrophysics Data System (ADS)

Zhou, Si-Da; Ma, Yuan-Chen; Liu, Li; Kang, Jie; Ma, Zhi-Sai; Yu, Lei

2018-01-01

Identification of time-varying modal parameters contributes to the structural health monitoring, fault detection, vibration control, etc. of the operational time-varying structural systems. However, it is a challenging task because there is not more information for the identification of the time-varying systems than that of the time-invariant systems. This paper presents a vector time-dependent autoregressive model and least squares support vector machine based modal parameter estimator for linear time-varying structural systems in case of output-only measurements. To reduce the computational cost, a Wendland's compactly supported radial basis function is used to achieve the sparsity of the Gram matrix. A Gamma-test-based non-parametric approach of selecting the regularization factor is adapted for the proposed estimator to replace the time-consuming n-fold cross validation. A series of numerical examples have illustrated the advantages of the proposed modal parameter estimator on the suppression of the overestimate and the short data. A laboratory experiment has further validated the proposed estimator.

Absorptive corrections for vector mesons: matching to complex mass scheme and longitudinal corrections

NASA Astrophysics Data System (ADS)

Jiménez Pérez, L. A.; Toledo Sánchez, G.

2017-12-01

Unstable spin-1 particles are properly described by including absorptive corrections to the electromagnetic vertex and propagator, without breaking the electromagnetic gauge invariance. We show that the modified propagator can be set in a complex mass form, provided the mass and width parameters, which are properly defined at the pole, are replaced by energy dependent functions fulfilling the same requirements at the pole. We exemplify the case for the {K}* (892) vector meson, and find that the mass function deviates around 2 MeV from the Kπ threshold to the pole, and that the width function exhibits a different behavior compared to the uncorrected energy dependent width. Considering the {τ }-\\to {K}{{S}}{π }-{ν }τ decay as dominated by the {K}* (892) and {K}{\\prime * }(1410) vectors and one scalar particle, we exhibit the role of the transversal and longitudinal corrections to the vector propagator by obtaining the modified vector and scalar form factors. The modified vector form factor is found to be the same as in the complex mass form, while the scalar form factor receives a modification from the longitudinal correction to the vector propagator. A fit to the experimental Kπ spectrum shows that the phase induced by the presence of this new contribution in the scalar sector improves the description of the experimental data in the troublesome region around 0.7 GeV. Besides that, the correction to the scalar form factor is found to be negligible.

Potent and reversible lentiviral vector restriction in murine induced pluripotent stem cells.

PubMed

Geis, Franziska K; Galla, Melanie; Hoffmann, Dirk; Kuehle, Johannes; Zychlinski, Daniela; Maetzig, Tobias; Schott, Juliane W; Schwarzer, Adrian; Goffinet, Christine; Goff, Stephen P; Schambach, Axel

2017-05-31

Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers. Much remains to be elucidated in the field of anti-viral immunity in stem cells, especially in PSC. In this study, we report that transduction with HIV-1-based, lentiviral vectors (LV) is impaired in murine PSC. Analyses of early retroviral events in induced pluripotent stem cells (iPSC) revealed that the restriction is independent of envelope choice and does not affect reverse transcription, but perturbs nuclear entry and proviral integration. Proteasomal inhibition by MG132 could not circumvent the restriction. However, prevention of cyclophilin A (CypA) binding to the HIV-1 capsid via use of either a CypA inhibitor (cyclosporine A) or CypA-independent capsid mutants improved transduction. In addition, application of higher vector doses also increased transduction. Our data revealed a CypA mediated restriction in iPSC, which was acquired during reprogramming, associated with pluripotency and relieved upon subsequent differentiation. We showed that murine PSC and iPSC are less susceptible to LV. The block observed in iPSC was CypA-dependent and resulted in reduced nuclear entry of viral DNA and proviral integration. Our study helps to improve transduction of murine pluripotent cells with HIV-1-based vectors and contributes to our understanding of retrovirus-host interactions in PSC.

Solid lipid nanoparticle-based vectors intended for the treatment of X-linked juvenile retinoschisis by gene therapy: In vivo approaches in Rs1h-deficient mouse model.

PubMed

Apaolaza, P S; Del Pozo-Rodríguez, A; Torrecilla, J; Rodríguez-Gascón, A; Rodríguez, J M; Friedrich, U; Weber, B H F; Solinís, M A

2015-11-10

X-linked juvenile retinoschisis (XLRS), which results from mutations in the gene RS1 that encodes the protein retinoschisin, is a retinal degenerative disease affecting between 1/5000 and 1/25,000 people worldwide. Currently, there is no cure for this disease and the treatment is based on the application of low-vision aids. The aim of the present work was the in vitro and in vivo evaluation of two different non-viral vectors based on solid lipid nanoparticles (SLNs), protamine and two anionic polysaccharides, hyaluronic acid (HA) or dextran (DX), for the treatment of XLRS. First, the vectors containing a plasmid which encodes both the reporter green fluorescent protein (GFP) and the therapeutic protein retinoschisin, under the control of CMV promoters, were characterized in vitro. Then, the vectors were subretinally or intravitreally administrated to C57BL/6 wild type mice. One week later, GFP was detected in all treated mice and in all retinal layers except in the Outer Nuclear Layer (ONL) and the Inner Nuclear Layer (INL), regardless of the administration route and the vector employed. Finally, two weeks after subretinal or intravitreal injection to Rs1h-deficient mice, GFP and retinoschisin expression was detected in all retinal layers, except in the ONL, which was maintained for at least two months after subretinal administration. The structural analysis of the treated Rs1h-deficient eyes showed a partial recovery of the retina related to the production of retinoschisin. This work shows for the first time a successful RS1 gene transfer to Rs1h-deficient animals using non-viral nanocarriers, with promising results that point to non-viral gene therapy as a feasible future therapeutic tool for retinal disorders.

Knockdown of Progesterone Receptor (PGR) in Macaque Granulosa Cells Disrupts Ovulation and Progesterone Production.

PubMed

Bishop, Cecily V; Hennebold, Jon D; Kahl, Christoph A; Stouffer, Richard L

2016-05-01

Adenoviral vectors (vectors) expressing short-hairpin RNAs complementary to macaque nuclear progesterone (P) receptor PGR mRNA (shPGR) or a nontargeting scrambled control (shScram) were used to determine the role PGR plays in ovulation/luteinization in rhesus monkeys. Nonluteinized granulosa cells collected from monkeys (n = 4) undergoing controlled ovarian stimulation protocols were exposed to either shPGR, shScram, or no virus for 24 h; human chorionic gonadotropin (hCG) was then added to half of the wells to induce luteinization (luteinized granulosa cells [LGCs]; n = 4-6 wells/treatment/monkey). Cells/media were collected 48, 72, and 120 h postvector for evaluation of PGR mRNA and P levels. Addition of hCG increased (P < 0.05) PGR mRNA and medium P levels in controls. However, a time-dependent decline (P < 0.05) in PGR mRNA and P occurred in shPGR vector groups. Injection of shPGR, but not shScram, vector into the preovulatory follicle 20 h before hCG administration during controlled ovulation protocols prevented follicle rupture in five of six monkeys as determined by laparoscopic evaluation, with a trapped oocyte confirmed in three of four follicles of excised ovaries. Injection of shPGR also prevented the rise in serum P levels following the hCG bolus compared to shScram (P < 0.05). Nuclear PGR immunostaining was undetectable in granulosa cells from shPGR-injected follicles, compared to intense staining in shScram controls. Thus, the nuclear PGR appears to mediate P action in the dominant follicle promoting ovulation in primates. In vitro and in vivo effects of PGR knockdown in LGCs also support the hypothesis that P enhances its own synthesis in the primate corpus luteum by promoting luteinization. © 2016 by the Society for the Study of Reproduction, Inc.

78 FR 15753 - Maintenance, Testing, and Replacement of Vented Lead-Acid Storage Batteries for Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-12

.... Although a time limit is given, comments and suggestions in connection with items for inclusion in guides currently being developed or improvements in all published guides are encouraged at any time. ADDRESSES: You...: 301-251-7455, or by email: [email protected] . Both of the Office of Nuclear Regulatory Research...

Receptor-mediated gene transfer vectors: progress towards genetic pharmaceuticals.

PubMed

Molas, M; Gómez-Valadés, A G; Vidal-Alabró, A; Miguel-Turu, M; Bermudez, J; Bartrons, R; Perales, J C

2003-10-01

Although specific delivery to tissues and unique cell types in vivo has been demonstrated for many non-viral vectors, current methods are still inadequate for human applications, mainly because of limitations on their efficiencies. All the steps required for an efficient receptor-mediated gene transfer process may in principle be exploited to enhance targeted gene delivery. These steps are: DNA/vector binding, internalization, subcellular trafficking, vesicular escape, nuclear import, and unpacking either for transcription or other functions (i.e., antisense, RNA interference, etc.). The large variety of vector designs that are currently available, usually aimed at improving the efficiency of these steps, has complicated the evaluation of data obtained from specific derivatives of such vectors. The importance of the structure of the final vector and the consequences of design decisions at specific steps on the overall efficiency of the vector will be discussed in detail. We emphasize in this review that stability in serum and thus, proper bioavailability of vectors to their specific receptors may be the single greatest limiting factor on the overall gene transfer efficiency in vivo. We discuss current approaches to overcome the intrinsic instability of synthetic vectors in the blood. In this regard, a summary of the structural features of the vectors obtained from current protocols will be presented and their functional characteristics evaluated. Dissecting information on molecular conjugates obtained by such methodologies, when carefully evaluated, should provide important guidelines for the creation of effective, targeted and safe DNA therapeutics.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Igarashi, Aki; Yamagata, Kousuke; Sugai, Tomokazu

Apple latent spherical virus (ALSV) vectors were evaluated for virus-induced gene silencing (VIGS) of endogenous genes among a broad range of plant species. ALSV vectors carrying partial sequences of a subunit of magnesium chelatase (SU) and phytoene desaturase (PDS) genes induced highly uniform knockout phenotypes typical of SU and PDS inhibition on model plants such as tobacco and Arabidopsis thaliana, and economically important crops such as tomato, legume, and cucurbit species. The silencing phenotypes persisted throughout plant growth in these plants. In addition, ALSV vectors could be successfully used to silence a meristem gene, proliferating cell nuclear antigen and diseasemore » resistant N gene in tobacco and RCY1 gene in A. thaliana. As ALSV infects most host plants symptomlessly and effectively induces stable VIGS for long periods, the ALSV vector is a valuable tool to determine the functions of interested genes among a broad range of plant species.« less

Coherent vector meson photoproduction from deuterium at intermediate energies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rogers, T.C.; Strikman, M.I.; Sargsian, M.M.

2006-04-15

We analyze the cross section for vector meson photoproduction off a deuteron for the intermediate range of photon energies starting at a few giga-electron-volts above the threshold and higher. We reproduce the steps in the derivation of the conventional nonrelativistic Glauber expression based on an effective diagrammatic method while making corrections for Fermi motion and intermediate-energy kinematic effects. We show that, for intermediate-energy vector meson production, the usual Glauber factorization breaks down, and we derive corrections to the usual Glauber method to linear order in longitudinal nucleon momentum. The purpose of our analysis is to establish methods for probing interestingmore » physics in the production mechanism for {phi} mesons and heavier vector mesons. We demonstrate how neglecting the breakdown of Glauber factorization can lead to errors in measurements of basic cross sections extracted from nuclear data.« less

Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases.

PubMed

Okamoto, Kenichi W; Gould, Fred; Lloyd, Alun L

2016-03-01

Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication) can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted). We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences-consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even modest perturbations induced by weak interventions can exhibit strong, albeit transient, epidemiological effects. This, together with our finding that under some conditions combining strategies could have transient adverse epidemiological effects suggests that a relatively long time horizon may be necessary to discern the efficacy of alternative intervention strategies.

Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases

PubMed Central

Okamoto, Kenichi W.; Gould, Fred; Lloyd, Alun L.

2016-01-01

Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication) can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted). We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences—consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even modest perturbations induced by weak interventions can exhibit strong, albeit transient, epidemiological effects. This, together with our finding that under some conditions combining strategies could have transient adverse epidemiological effects suggests that a relatively long time horizon may be necessary to discern the efficacy of alternative intervention strategies. PMID:26962871

Dynamic Isovector Reorientation of Deuteron as a Probe to Nuclear Symmetry Energy.

PubMed

Ou, Li; Xiao, Zhigang; Yi, Han; Wang, Ning; Liu, Min; Tian, Junlong

2015-11-20

We present the calculations on a novel reorientation effect of deuteron attributed to isovector interaction in the nuclear field of heavy target nuclei. The correlation angle determined by the relative momentum vector of the proton and the neutron originating from the breakup deuteron, which is experimentally detectable, exhibits significant dependence on the isovector nuclear potential but is robust against the variation of the isoscaler sector. In terms of sensitivity and cleanness, the breakup reactions induced by the polarized deuteron beam at about 100 MeV/u provide a more stringent constraint to the symmetry energy at subsaturation densities.

Construction of improved temperature-sensitive and mobilizable vectors and their use for constructing mutations in the adhesin-encoding acm gene of poorly transformable clinical Enterococcus faecium strains.

PubMed

Nallapareddy, Sreedhar R; Singh, Kavindra V; Murray, Barbara E

2006-01-01

Inactivation by allelic exchange in clinical isolates of the emerging nosocomial pathogen Enterococcus faecium has been hindered by lack of efficient tools, and, in this study, transformation of clinical isolates was found to be particularly problematic. For this reason, a vector for allelic replacement (pTEX5500ts) was constructed that includes (i) the pWV01-based gram-positive repAts replication region, which is known to confer a high degree of temperature intolerance, (ii) Escherichia coli oriR from pUC18, (iii) two extended multiple-cloning sites located upstream and downstream of one of the marker genes for efficient cloning of flanking regions for double-crossover mutagenesis, (iv) transcriptional terminator sites to terminate undesired readthrough, and (v) a synthetic extended promoter region containing the cat gene for allelic exchange and a high-level gentamicin resistance gene, aph(2'')-Id, to distinguish double-crossover recombination, both of which are functional in gram-positive and gram-negative backgrounds. To demonstrate the functionality of this vector, the vector was used to construct an acm (encoding an adhesin to collagen from E. faecium) deletion mutant of a poorly transformable multidrug-resistant E. faecium endocarditis isolate, TX0082. The acm-deleted strain, TX6051 (TX0082Deltaacm), was shown to lack Acm on its surface, which resulted in the abolishment of the collagen adherence phenotype observed in TX0082. A mobilizable derivative (pTEX5501ts) that contains oriT of Tn916 to facilitate conjugative transfer from the transformable E. faecalis strain JH2Sm::Tn916 to E. faecium was also constructed. Using this vector, the acm gene of a nonelectroporable E. faecium wound isolate was successfully interrupted. Thus, pTEX5500ts and its mobilizable derivative demonstrated their roles as important tools by helping to create the first reported allelic replacement in E. faecium; the constructed this acm deletion mutant will be useful for assessing the role of acm in E. faecium pathogenesis using animal models.

A T Matrix Method Based upon Scalar Basis Functions

NASA Technical Reports Server (NTRS)

Mackowski, D.W.; Kahnert, F. M.; Mishchenko, Michael I.

2013-01-01

A surface integral formulation is developed for the T matrix of a homogenous and isotropic particle of arbitrary shape, which employs scalar basis functions represented by the translation matrix elements of the vector spherical wave functions. The formulation begins with the volume integral equation for scattering by the particle, which is transformed so that the vector and dyadic components in the equation are replaced with associated dipole and multipole level scalar harmonic wave functions. The approach leads to a volume integral formulation for the T matrix, which can be extended, by use of Green's identities, to the surface integral formulation. The result is shown to be equivalent to the traditional surface integral formulas based on the VSWF basis.

The quest for the next information processing technology

NASA Astrophysics Data System (ADS)

Welser, Jeffrey J.; Bourianoff, George I.; Zhirnov, Victor V.; Cavin, Ralph Keary

2008-01-01

Fundamental physical considerations indicate that the scaling of devices that use electron charge as the information carrier will limit within the next one to two decades. The Nanoelectronics Research Initiative (NRI), a joint industry-government program, has been developed to fund university research seeking devices that utilize alternative physical information carriers or non-equilibrium switching mechanisms to continue the historical cost and performance trends of information technology. Three research centers have been established to pursue five research vectors that have been identified as critical to the effort to replace the electronic switch. A brief history and rationale for NRI is given and the projects currently underway are described in the context of the five research vectors.

Pipeline synthetic aperture radar data compression utilizing systolic binary tree-searched architecture for vector quantization

NASA Technical Reports Server (NTRS)

Chang, Chi-Yung (Inventor); Fang, Wai-Chi (Inventor); Curlander, John C. (Inventor)

1995-01-01

A system for data compression utilizing systolic array architecture for Vector Quantization (VQ) is disclosed for both full-searched and tree-searched. For a tree-searched VQ, the special case of a Binary Tree-Search VQ (BTSVQ) is disclosed with identical Processing Elements (PE) in the array for both a Raw-Codebook VQ (RCVQ) and a Difference-Codebook VQ (DCVQ) algorithm. A fault tolerant system is disclosed which allows a PE that has developed a fault to be bypassed in the array and replaced by a spare at the end of the array, with codebook memory assignment shifted one PE past the faulty PE of the array.

Head ballistocardiogram based on wireless multi-location sensors.

PubMed

Onizuka, Kohei; Sodini, Charles G

2015-08-01

Recently a wearable BCG monitoring technique based on an accelerometer worn at the ear was demonstrated to replace a conventional bulky BCG acquisition system. In this work, a multi-location wireless vital signs monitor was developed, and at least two common acceleration vectors correlating to sitting-BCG were found in the supine position by using head PPG signal as a reference for eight healthy human subjects. The head side amplitude in the supine position is roughly proportional to the sitting amplitude that is in turn proportional to the stroke volume. Signal processing techniques to identify J-waves in a subject having small amplitude was also developed based on the two common vectors at the head side and top.

Role of cellular FKBP52 protein in intracellular trafficking of recombinant adeno-associated virus 2 vectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao Weihong; Wu Jianqing; Zhong Li

2006-09-30

We have reported that tyrosine-phosphorylated forms of a cellular protein, FKBP52, inhibit the second-strand DNA synthesis of adeno-associated virus 2 (AAV), leading to inefficient transgene expression from recombinant AAV vectors. To further explore the role of FKBP52 in AAV-mediated transduction, we established murine embryo fibroblasts (MEFs) cultures from FKBP52 wild-type (WT), heterozygous (HE), and knockout (KO) mice. Conventional AAV vectors failed to transduce WT MEFs efficiently, and the transduction efficiency was not significantly increased in HE or KO MEFs. AAV vectors failed to traffic efficiently to the nucleus in these cells. Treatment with hydroxyurea (HU) increased the transduction efficiency ofmore » conventional AAV vectors by {approx}25-fold in WT MEFs, but only by {approx}4-fold in KO MEFs. The use of self-complementary AAV (scAAV) vectors, which bypass the requirement of viral second-strand DNA synthesis, revealed that HU treatment increased the transduction efficiency {approx}23-fold in WT MEFs, but only {approx}4-fold in KO MEFs, indicating that the lack of HU treatment-mediated increase in KO MEFs was not due to failure of AAV to undergo viral second-strand DNA synthesis. Following HU treatment, {approx}59% of AAV genomes were present in the nuclear fraction from WT MEFs, but only {approx}28% in KO MEFs, indicating that the pathway by which HU treatment mediates nuclear transport of AAV was impaired in KO MEFs. When KO MEFs were stably transfected with an FKBP52 expression plasmid, HU treatment-mediated increase in the transduction efficiency was restored in these cells, which correlated directly with improved intracellular trafficking. Intact AAV particles were also shown to interact with FKBP52 as well as with dynein, a known cellular protein involved in AAV trafficking. These studies suggest that FKBP52, being a cellular chaperone protein, facilitates intracellular trafficking of AAV, which has implications in the optimal use of recombinant AAV vectors in human gene therapy.« less

Human somatic cell nuclear transfer and cloning.

PubMed

2012-10-01

This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer (cloning)," last published in Fertil Steril 2000;74:873-6. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Implementation of a new fuzzy vector control of induction motor.

PubMed

Rafa, Souad; Larabi, Abdelkader; Barazane, Linda; Manceur, Malik; Essounbouli, Najib; Hamzaoui, Abdelaziz

2014-05-01

The aim of this paper is to present a new approach to control an induction motor using type-1 fuzzy logic. The induction motor has a nonlinear model, uncertain and strongly coupled. The vector control technique, which is based on the inverse model of the induction motors, solves the coupling problem. Unfortunately, in practice this is not checked because of model uncertainties. Indeed, the presence of the uncertainties led us to use human expertise such as the fuzzy logic techniques. In order to maintain the decoupling and to overcome the problem of the sensitivity to the parametric variations, the field-oriented control is replaced by a new block control. The simulation results show that the both control schemes provide in their basic configuration, comparable performances regarding the decoupling. However, the fuzzy vector control provides the insensitivity to the parametric variations compared to the classical one. The fuzzy vector control scheme is successfully implemented in real-time using a digital signal processor board dSPACE 1104. The efficiency of this technique is verified as well as experimentally at different dynamic operating conditions such as sudden loads change, parameter variations, speed changes, etc. The fuzzy vector control is found to be a best control for application in an induction motor. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Employing the Components of the Human Development Index to Drive Resources to Educational Policies

ERIC Educational Resources Information Center

Sant'Anna, Annibal Parracho; de Araujo Ribeiro, Rodrigo Otavio; Dutt-Ross, Steven

2011-01-01

A new form of composition of the indicators employed to generate the United Nations Human Development Index (HDI) is presented here. This form of composition is based on the assumption that random errors affect the measurement of each indicator. This assumption allows for replacing the vector of evaluations according to each indicator by vectors…

75 FR 17970 - Nine Mile Point Nuclear Station, LLC; Nine Mile Point Nuclear Station, Unit No. 2; Draft...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-08

... industrial use. Potable water in the area is supplied to residents either through the Scriba Water District... and drift losses from the cooling tower. NMP2 has its own cooling water intake and discharge... service water system and makeup to the circulating water system to replace evaporation and drift losses...

78 FR 58574 - Maintenance, Testing, and Replacement of Vented Lead-Acid Storage Batteries for Nuclear Power Plants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... time that a document is referenced. Revision 3 of Regulatory Guide 1.129 is available in ADAMS under...-251-7455; email: [email protected] . Both of the Office of Nuclear Regulatory Research, U.S... NRC is issuing a revision to an existing guide in the NRC's ``Regulatory Guide'' series. This series...

Control console replacement at the WPI Reactor. [Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-12-31

With partial funding from the Department of Energy (DOE) University Reactor Instrumentation Upgrade Program (DOE Grant No. DE-FG02-90ER12982), the original control console at the Worcester Polytechnic Institute (WPI) Reactor has been replaced with a modern system. The new console maintains the original design bases and functionality while utilizing current technology. An advanced remote monitoring system has been added to augment the educational capabilities of the reactor. Designed and built by General Electric in 1959, the open pool nuclear training reactor at WPI was one of the first such facilities in the nation located on a university campus. Devoted to undergraduatemore » use, the reactor and its related facilities have been since used to train two generations of nuclear engineers and scientists for the nuclear industry. The reactor power level was upgraded from 1 to 10 kill in 1969, and its operating license was renewed for 20 years in 1983. In 1988, the reactor was converted to low enriched uranium. The low power output of the reactor and ergonomic facility design make it an ideal tool for undergraduate nuclear engineering education and other training.« less

Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors.

PubMed Central

Podsakoff, G; Wong, K K; Chatterjee, S

1994-01-01

Gene transfer vectors based on adeno-associated virus (AAV) are emerging as highly promising for use in human gene therapy by virtue of their characteristics of wide host range, high transduction efficiencies, and lack of cytopathogenicity. To better define the biology of AAV-mediated gene transfer, we tested the ability of an AAV vector to efficiently introduce transgenes into nonproliferating cell populations. Cells were induced into a nonproliferative state by treatment with the DNA synthesis inhibitors fluorodeoxyuridine and aphidicolin or by contact inhibition induced by confluence and serum starvation. Cells in logarithmic growth or DNA synthesis arrest were transduced with vCWR:beta gal, an AAV-based vector encoding beta-galactosidase under Rous sarcoma virus long terminal repeat promoter control. Under each condition tested, vCWR:beta Gal expression in nondividing cells was at least equivalent to that in actively proliferating cells, suggesting that mechanisms for virus attachment, nuclear transport, virion uncoating, and perhaps some limited second-strand synthesis of AAV vectors were present in nondividing cells. Southern hybridization analysis of vector sequences from cells transduced while in DNA synthetic arrest and expanded after release of the block confirmed ultimate integration of the vector genome into cellular chromosomal DNA. These findings may provide the basis for the use of AAV-based vectors for gene transfer into quiescent cell populations such as totipotent hematopoietic stem cells. Images PMID:8057446

Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors.

PubMed

Podsakoff, G; Wong, K K; Chatterjee, S

1994-09-01

Gene transfer vectors based on adeno-associated virus (AAV) are emerging as highly promising for use in human gene therapy by virtue of their characteristics of wide host range, high transduction efficiencies, and lack of cytopathogenicity. To better define the biology of AAV-mediated gene transfer, we tested the ability of an AAV vector to efficiently introduce transgenes into nonproliferating cell populations. Cells were induced into a nonproliferative state by treatment with the DNA synthesis inhibitors fluorodeoxyuridine and aphidicolin or by contact inhibition induced by confluence and serum starvation. Cells in logarithmic growth or DNA synthesis arrest were transduced with vCWR:beta gal, an AAV-based vector encoding beta-galactosidase under Rous sarcoma virus long terminal repeat promoter control. Under each condition tested, vCWR:beta Gal expression in nondividing cells was at least equivalent to that in actively proliferating cells, suggesting that mechanisms for virus attachment, nuclear transport, virion uncoating, and perhaps some limited second-strand synthesis of AAV vectors were present in nondividing cells. Southern hybridization analysis of vector sequences from cells transduced while in DNA synthetic arrest and expanded after release of the block confirmed ultimate integration of the vector genome into cellular chromosomal DNA. These findings may provide the basis for the use of AAV-based vectors for gene transfer into quiescent cell populations such as totipotent hematopoietic stem cells.

Defense Threat Reduction Agency Radiochemical Needs

NASA Astrophysics Data System (ADS)

Walsh, Michael A. R.; Velazquez, Daniel L.

2009-08-01

The United States Government (USG) first developed nuclear forensics-related capabilities to analyze radiological and nuclear materials, including underground nuclear test debris and interdicted materials. Nuclear forensics is not a new mission for Department of Defense (DoD). The department's existing nuclear forensics capability is the result of programs that span six (6) decades and includes activities to assess foreign nuclear weapons testing activities, monitor and verify nuclear arms control treaties, and to support intelligence and law enforcement activities. Today, nuclear forensics must support not only weapons programs and nuclear smuggling incidents, but also the scientific analysis and subsequent attribution of terrorists' use of radiological or nuclear materials/devices. Nuclear forensics can help divulge the source of origin of nuclear materials, the type of design for an interdicted or detonated device, as well as the pathway of the materials or device to the incident. To accomplish this mission, the USG will need trained radiochemists and nuclear scientists to fill new positions and replace the retiring staff.

Cell-surface glycosaminoglycans inhibit intranuclear uptake but promote post-nuclear processes of polyamidoamine dendrimer-pDNA transfection.

PubMed

Ziraksaz, Zarrintaj; Nomani, Alireza; Ruponen, Marika; Soleimani, Masoud; Tabbakhian, Majid; Haririan, Ismaeil

2013-01-23

Interaction of cell-surface glycosaminoglycans (GAGs) with non-viral vectors seems to be an important factor which modifies the intracellular destination of the gene complexes. Intracellular kinetics of polyamidoamine (PAMAM) dendrimer as a non-viral vector in cellular uptake, intranuclear delivery and transgene expression of plasmid DNA with regard to the cell-surface GAGs has not been investigated until now. The physicochemical properties of the PAMAM-pDNA complexes were characterized by photon correlation spectroscopy, atomic force microscopy, zeta measurement and agarose gel electrophoresis. The transfection efficiency and toxicity of the complexes at different nitrogen to phosphate (N:P) ratios were determined using various in vitro cell models such as human embryonic kidney cells, chinese hamster ovary cells and its mutants lacking cell-surface GAGs or heparan sulphate proteoglycans (HSPGs). Cellular uptake, nuclear uptake and transfection efficiency of the complexes were determined using flow cytometry and optimized cell-nuclei isolation with quantitative real-time PCR and luciferase assay. Physicochemical studies showed that PAMAM dendrimer binds pDNA efficiently, forms small complexes with high positive zeta potential and transfects cells properly at N:P ratios around 5 and higher. The cytotoxicity could be a problem at N:Ps higher than 10. GAGs elimination caused nearly one order of magnitude higher pDNA nuclear uptake and more than 2.6-fold higher transfection efficiency than CHO parent cells. However, neither AUC of nuclear uptake, nor AUC of transfection affected significantly by only cell-surface HSPGs elimination and interesting data related to the effect of GAGs on intranuclear pDNA using PAMAM as delivery vector have been reported in this study. Presented data shows that the rate-limiting step of PAMAM-pDNA complexes transfection is located after delivery to the cell nucleus and GAGs are regarded as an inhibitor of the intranuclear delivery step, while slightly promotes transgene expression. Copyright © 2012 Elsevier B.V. All rights reserved.

Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.

PubMed

Shaw, Kit L; Garabedian, Elizabeth; Mishra, Suparna; Barman, Provaboti; Davila, Alejandra; Carbonaro, Denise; Shupien, Sally; Silvin, Christopher; Geiger, Sabine; Nowicki, Barbara; Smogorzewska, E Monika; Brown, Berkley; Wang, Xiaoyan; de Oliveira, Satiro; Choi, Yeong; Ikeda, Alan; Terrazas, Dayna; Fu, Pei-Yu; Yu, Allen; Fernandez, Beatriz Campo; Cooper, Aaron R; Engel, Barbara; Podsakoff, Greg; Balamurugan, Arumugam; Anderson, Stacie; Muul, Linda; Jagadeesh, G Jayashree; Kapoor, Neena; Tse, John; Moore, Theodore B; Purdy, Ken; Rishi, Radha; Mohan, Kathey; Skoda-Smith, Suzanne; Buchbinder, David; Abraham, Roshini S; Scharenberg, Andrew; Yang, Otto O; Cornetta, Kenneth; Gjertson, David; Hershfield, Michael; Sokolic, Rob; Candotti, Fabio; Kohn, Donald B

2017-05-01

Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1-2.6) and granulocytes (VCN = 0.01-0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. ClinicalTrials.gov NCT00794508. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA Clinical and Translational Science Institute awards, UL1RR033176 and UL1TR000124.

Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency

PubMed Central

Shaw, Kit L.; Garabedian, Elizabeth; Mishra, Suparna; Barman, Provaboti; Davila, Alejandra; Carbonaro, Denise; Shupien, Sally; Silvin, Christopher; Geiger, Sabine; Nowicki, Barbara; Smogorzewska, E. Monika; Brown, Berkley; Wang, Xiaoyan; de Oliveira, Satiro; Choi, Yeong; Ikeda, Alan; Terrazas, Dayna; Fu, Pei-Yu; Yu, Allen; Fernandez, Beatriz Campo; Cooper, Aaron R.; Engel, Barbara; Podsakoff, Greg; Balamurugan, Arumugam; Anderson, Stacie; Muul, Linda; Jagadeesh, G. Jayashree; Kapoor, Neena; Tse, John; Moore, Theodore B.; Purdy, Ken; Rishi, Radha; Mohan, Kathey; Skoda-Smith, Suzanne; Buchbinder, David; Abraham, Roshini S.; Scharenberg, Andrew; Yang, Otto O.; Cornetta, Kenneth; Gjertson, David; Hershfield, Michael; Sokolic, Rob; Candotti, Fabio

2017-01-01

BACKGROUND. Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase–deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. RESULTS. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1–2.6) and granulocytes (VCN = 0.01–0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. CONCLUSION. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. TRIAL REGISTRATION. ClinicalTrials.gov NCT00794508. FUNDING. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA Clinical and Translational Science Institute awards, UL1RR033176 and UL1TR000124. PMID:28346229

A recombinant chimeric Ad5/3 vector expressing a multi-stage Plasmodium antigen induces protective immunity in mice using heterologous prime-boost immunization regimens1

PubMed Central

Cabrera-Mora, Monica; Fonseca, Jairo Andres; Singh, Balwan; Zhao, Chunxia; Makarova, Natalia; Dmitriev, Igor; Curiel, David T.; Blackwell, Jerry; Moreno, Alberto

2016-01-01

An ideal malaria vaccine should target several stages of the parasite life cycle and induce anti-parasite and anti-disease immunity. We have reported a Plasmodium yoelii chimeric multi-stage recombinant protein (PyLPC/RMC), engineered to express several autologous T cell epitopes and sequences derived from the circumsporozoite protein (CSP) and the merozoite surface protein 1 (MSP-1). This chimeric protein elicits protective immunity, mediated by CD4+ T cells and neutralizing antibodies. However, experimental evidence from pre-erythrocytic vaccine candidates and irradiated sporozoites has shown that CD8+ T cells play a significant role in protection. Recombinant viral vectors have been used as a vaccine platform to elicit effective CD8+ T cell responses. The human adenovirus serotype 5 (Ad5) has been tested in malaria vaccine clinical trials with excellent safety profile. Nevertheless, a major concern for the use of Ad5 is the high prevalence of anti-vector neutralizing antibodies in humans, hampering its immunogenicity. To minimize the impact of anti-vector pre-existing immunity we developed a chimeric Ad5/3 vector in which the knob region of Ad5 was replaced with that of Ad3, conferring partial resistance to anti-Ad5 neutralizing antibodies. Furthermore, we implemented heterologous adenovirus/protein immunization regimens which include a single immunization with recombinant Ad vectors. Our data show that immunization with the recombinant Ad5/3 vector induces protective efficacy indistinguishable from that elicited by Ad5. Our study also demonstrate that the dose of the Ad vectors has an impact on the memory profile and protective efficacy. The results support further studies with Ad5/3 for malaria vaccine development. PMID:27574299

Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens

PubMed Central

Kim, Shin-Hee; Paldurai, Anandan; Xiao, Sa; Collins, Peter L.; Samal, Siba K.

2016-01-01

Naturally-occurring attenuated strains of Newcastle disease virus (NDV) are being developed as vaccine vectors for use in poultry and humans. However, some NDV strains, such as Beaudette C (BC), may retain too much virulence in poultry for safe use, and more highly attenuated strains may be suboptimally immunogenic. We therefore modified the BC strain by changing the multibasic cleavage site sequence of the F protein to the dibasic sequence of avirulent strain LaSota. Additionally, the BC, F, and HN proteins were modified in several ways to enhance virus replication. These modified BC-derived vectors and the LaSota strain were engineered to express the hemagglutin (HA) protein of H5N1 highly pathogenic influenza virus (HPAIV). In general, the modified BC-based vectors expressing HA replicated better than LaSota/HA, and expressed higher levels of HA protein. Pathogenicity tests indicated that all the modified viruses were highly attenuated in chickens. Based on in vitro characterization, two of the modified BC vectors were chosen for evaluation in chickens as vaccine vectors against H5N1 HPAIV A/Vietnam/1203/04. Immunization of chickens with rNDV vector vaccines followed by challenge with HPAIV demonstrated high levels of protection against clinical disease and mortality. However, only those chickens immunized with modified BC/HA in which residues 271–330 from the F protein had been replaced with the corresponding sequence from the NDV AKO strain conferred complete protection against challenge virus shedding. Our findings suggest that this modified rNDV can be used safely as a vaccine vector with enhanced replication, expression, and protective efficacy in avian species, and potentially in humans. PMID:24968158

Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

PubMed

Ono, Motoharu; Yamada, Kayo; Avolio, Fabio; Afzal, Vackar; Bensaddek, Dalila; Lamond, Angus I

2015-01-01

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

Semiautomated skeletonization of the pulmonary arterial tree in micro-CT images

NASA Astrophysics Data System (ADS)

Hanger, Christopher C.; Haworth, Steven T.; Molthen, Robert C.; Dawson, Christopher A.

2001-05-01

We present a simple and robust approach that utilizes planar images at different angular rotations combined with unfiltered back-projection to locate the central axes of the pulmonary arterial tree. Three-dimensional points are selected interactively by the user. The computer calculates a sub- volume unfiltered back-projection orthogonal to the vector connecting the two points and centered on the first point. Because more x-rays are absorbed at the thickest portion of the vessel, in the unfiltered back-projection, the darkest pixel is assumed to be the center of the vessel. The computer replaces this point with the newly computer-calculated point. A second back-projection is calculated around the original point orthogonal to a vector connecting the newly-calculated first point and user-determined second point. The darkest pixel within the reconstruction is determined. The computer then replaces the second point with the XYZ coordinates of the darkest pixel within this second reconstruction. Following a vector based on a moving average of previously determined 3- dimensional points along the vessel's axis, the computer continues this skeletonization process until stopped by the user. The computer estimates the vessel diameter along the set of previously determined points using a method similar to the full width-half max algorithm. On all subsequent vessels, the process works the same way except that at each point, distances between the current point and all previously determined points along different vessels are determined. If the difference is less than the previously estimated diameter, the vessels are assumed to branch. This user/computer interaction continues until the vascular tree has been skeletonized.

76 FR 61346 - Sunshine Act Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... defense nuclear facilities, including the Chemistry and Metallurgy Research Building, Area G in Technical... the integration of safety-in-design for the Chemistry and Metallurgy Research Replacement project, the...

Comparison of deterministic and stochastic approaches for isotopic concentration and decay heat uncertainty quantification on elementary fission pulse

NASA Astrophysics Data System (ADS)

Lahaye, S.; Huynh, T. D.; Tsilanizara, A.

2016-03-01

Uncertainty quantification of interest outputs in nuclear fuel cycle is an important issue for nuclear safety, from nuclear facilities to long term deposits. Most of those outputs are functions of the isotopic vector density which is estimated by fuel cycle codes, such as DARWIN/PEPIN2, MENDEL, ORIGEN or FISPACT. CEA code systems DARWIN/PEPIN2 and MENDEL propagate by two different methods the uncertainty from nuclear data inputs to isotopic concentrations and decay heat. This paper shows comparisons between those two codes on a Uranium-235 thermal fission pulse. Effects of nuclear data evaluation's choice (ENDF/B-VII.1, JEFF-3.1.1 and JENDL-2011) is inspected in this paper. All results show good agreement between both codes and methods, ensuring the reliability of both approaches for a given evaluation.

Photons in dense nuclear matter: Random-phase approximation

NASA Astrophysics Data System (ADS)

Stetina, Stephan; Rrapaj, Ermal; Reddy, Sanjay

2018-04-01

We present a comprehensive and pedagogic discussion of the properties of photons in cold and dense nuclear matter based on the resummed one-loop photon self-energy. Correlations among electrons, muons, protons, and neutrons in β equilibrium that arise as a result of electromagnetic and strong interactions are consistently taken into account within the random phase approximation. Screening effects, damping, and collective excitations are systematically studied in a fully relativistic setup. Our study is relevant to the linear response theory of dense nuclear matter, calculations of transport properties of cold dense matter, and investigations of the production and propagation of hypothetical vector bosons such as the dark photons.

Selection against Heteroplasmy Explains the Evolution of Uniparental Inheritance of Mitochondria

PubMed Central

Christie, Joshua R.; Schaerf, Timothy M.; Beekman, Madeleine

2015-01-01

Why are mitochondria almost always inherited from one parent during sexual reproduction? Current explanations for this evolutionary mystery include conflict avoidance between the nuclear and mitochondrial genomes, clearing of deleterious mutations, and optimization of mitochondrial-nuclear coadaptation. Mathematical models, however, fail to show that uniparental inheritance can replace biparental inheritance under any existing hypothesis. Recent empirical evidence indicates that mixing two different but normal mitochondrial haplotypes within a cell (heteroplasmy) can cause cell and organism dysfunction. Using a mathematical model, we test if selection against heteroplasmy can lead to the evolution of uniparental inheritance. When we assume selection against heteroplasmy and mutations are neither advantageous nor deleterious (neutral mutations), uniparental inheritance replaces biparental inheritance for all tested parameter values. When heteroplasmy involves mutations that are advantageous or deleterious (non-neutral mutations), uniparental inheritance can still replace biparental inheritance. We show that uniparental inheritance can evolve with or without pre-existing mating types. Finally, we show that selection against heteroplasmy can explain why some organisms deviate from strict uniparental inheritance. Thus, we suggest that selection against heteroplasmy explains the evolution of uniparental inheritance. PMID:25880558

Towards more accurate and reliable predictions for nuclear applications

NASA Astrophysics Data System (ADS)

Goriely, Stephane; Hilaire, Stephane; Dubray, Noel; Lemaître, Jean-François

2017-09-01

The need for nuclear data far from the valley of stability, for applications such as nuclear astrophysics or future nuclear facilities, challenges the robustness as well as the predictive power of present nuclear models. Most of the nuclear data evaluation and prediction are still performed on the basis of phenomenological nuclear models. For the last decades, important progress has been achieved in fundamental nuclear physics, making it now feasible to use more reliable, but also more complex microscopic or semi-microscopic models in the evaluation and prediction of nuclear data for practical applications. Nowadays mean-field models can be tuned at the same level of accuracy as the phenomenological models, renormalized on experimental data if needed, and therefore can replace the phenomenological inputs in the evaluation of nuclear data. The latest achievements to determine nuclear masses within the non-relativistic HFB approach, including the related uncertainties in the model predictions, are discussed. Similarly, recent efforts to determine fission observables within the mean-field approach are described and compared with more traditional existing models.

General Relativity Exactly Described by Use of Newton's Laws within a Curved Geometry

NASA Astrophysics Data System (ADS)

Savickas, David

2014-03-01

The connection between general relativity and Newtonian mechanics is shown to be much closer than generally recognized. When Newton's second law is written in a curved geometry by using the physical components of a vector as defined in tensor calculus, and by replacing distance within the momentum's velocity by the vector metric ds in a curved geometry, the second law can then be easily shown to be exactly identical to the geodesic equation of motion occurring in general relativity. By using a time whose vector direction is constant, as similarly occurs in Newtonian mechanics, this equation can be separated into two equations one of which is a curved three-dimensional equation of motion and the other is an equation for energy. For the gravitational field of an isolated particle, they yield the Schwarzschild equations. They can be used to describe gravitation for any array of masses for which the Newtonian gravitational potential is known, and is applied here to describe motion in the gravitational field of a thin mass-rod.

Vaccines against Botulism.

PubMed

Sundeen, Grace; Barbieri, Joseph T

2017-09-02

Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin.

Vaccines against Botulism

PubMed Central

Sundeen, Grace; Barbieri, Joseph T.

2017-01-01

Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin. PMID:28869493

Biological Gene Delivery Vehicles: Beyond Viral Vectors

PubMed Central

Seow, Yiqi; Wood, Matthew J

2009-01-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Biological gene delivery vehicles: beyond viral vectors.

PubMed

Seow, Yiqi; Wood, Matthew J

2009-05-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.

The quantitative structure-insecticidal activity relationships from plant derived compounds against chikungunya and zika Aedes aegypti (Diptera:Culicidae) vector.

PubMed

Saavedra, Laura M; Romanelli, Gustavo P; Rozo, Ciro E; Duchowicz, Pablo R

2018-01-01

The insecticidal activity of a series of 62 plant derived molecules against the chikungunya, dengue and zika vector, the Aedes aegypti (Diptera:Culicidae) mosquito, is subjected to a Quantitative Structure-Activity Relationships (QSAR) analysis. The Replacement Method (RM) variable subset selection technique based on Multivariable Linear Regression (MLR) proves to be successful for exploring 4885 molecular descriptors calculated with Dragon 6. The predictive capability of the obtained models is confirmed through an external test set of compounds, Leave-One-Out (LOO) cross-validation and Y-Randomization. The present study constitutes a first necessary computational step for designing less toxic insecticides. Copyright © 2017 Elsevier B.V. All rights reserved.

Short-Range Action, Focusing, and Saturation of Nuclear Forces in a Gravitational-Electrodynamic Model of GRT

NASA Astrophysics Data System (ADS)

Sukhanova, L. A.; Khlestkov, Yu. A.

2015-12-01

An equation for a massive vector field that explains the short-range action of nuclear forces has been obtained via a consistent solution of the Einstein-Maxwell-Lorentz equations in curved spacetime. The nucleus is identified with the throat, whose radius of curvature is adopted as the radius of the nucleus. In this gravitational model the experimentally observed proportionality of the radius of the nucleus to the cubic root of the mass number is obtained.

Monitoring the invasion of an exotic tree (Ligustrum lucidum) from 1983 to 2006 with Landsat TM/ETM+ satellite data and support vector machines in Cordoba, Argentina

Treesearch

Gregorio I. Gavier-Pizarro; Tobias Kuemmerle; Laura E. Hoyos; Susan I. Stewart; Cynthia D. Huebner; Nicholas S. Keuler; Volker C. Radeloff

2012-01-01

In central Argentina, the Chinese tree glossy privet (Ligustrum lucidum) is an aggressive invasive species replacing native forests, forming dense stands, and is thus a major conservation concern. Mapping the spread of biological invasions is a necessary first step toward understanding the factors determining invasion patterns. Urban areas may...

Inducible Transgenic Models of BRCA1 Function

DTIC Science & Technology

1999-10-01

inducible expression vectors were created to conditionally express four different hammerhead ribozymes designed to specifically cleave the Brca...transcript. Hammerhead ribozymes are catalytic RNAs that efficiently cleave RNA and thereby down- regulate gene expression. Hammerhead ribozymes can cleave...any RNA containing its 5’-UH-3’ consensus sequence where U can be replaced by a C, and H=C, U or A. Hammerhead ribozymes effectively and selectively

A new image representation for compact and secure communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prasad, Lakshman; Skourikhine, A. N.

In many areas of nuclear materials management there is a need for communication, archival, and retrieval of annotated image data between heterogeneous platforms and devices to effectively implement safety, security, and safeguards of nuclear materials. Current image formats such as JPEG are not ideally suited in such scenarios as they are not scalable to different viewing formats, and do not provide a high-level representation of images that facilitate automatic object/change detection or annotation. The new Scalable Vector Graphics (SVG) open standard for representing graphical information, recommended by the World Wide Web Consortium (W3C) is designed to address issues of imagemore » scalability, portability, and annotation. However, until now there has been no viable technology to efficiently field images of high visual quality under this standard. Recently, LANL has developed a vectorized image representation that is compatible with the SVG standard and preserves visual quality. This is based on a new geometric framework for characterizing complex features in real-world imagery that incorporates perceptual principles of processing visual information known from cognitive psychology and vision science, to obtain a polygonal image representation of high fidelity. This representation can take advantage of all textual compression and encryption routines unavailable to other image formats. Moreover, this vectorized image representation can be exploited to facilitate automated object recognition that can reduce time required for data review. The objects/features of interest in these vectorized images can be annotated via animated graphics to facilitate quick and easy display and comprehension of processed image content.« less

Covariant kaon dynamics and kaon flow in heavy ion collisions

NASA Astrophysics Data System (ADS)

Zheng, Yu-Ming; Fuchs, C.; Faessler, Amand; Shekhter, K.; Yan, Yu-Peng; Kobdaj, Chinorat

2004-03-01

The influence of the chiral mean field on the K+ transverse flow in heavy ion collisions at SIS energy is investigated within covariant kaon dynamics. For the kaon mesons inside the nuclear medium a quasiparticle picture including scalar and vector fields is adopted and compared to the standard treatment with a static potential. It is confirmed that a Lorentz force from spatial component of the vector field provides an important contribution to the in-medium kaon dynamics and strongly counterbalances the influence of the vector potential on the K+ in-plane flow. The FOPI data can be reasonably described using in-medium kaon potentials based on effective chiral models. The information on the in-medium K+ potential extracted from kaon flow is consistent with the knowledge from other sources.

Cytosol-dependent membrane fusion in ER, nuclear envelope and nuclear pore assembly: biological implications.

PubMed

Rafikova, Elvira R; Melikov, Kamran; Chernomordik, Leonid V

2010-01-01

Endoplasmic reticulum and nuclear envelope rearrangements after mitosis are often studied in the reconstitution system based on Xenopus egg extract. In our recent work we partially replaced the membrane vesicles in the reconstitution mix with protein-free liposomes to explore the relative contributions of cytosolic and transmembrane proteins. Here we discuss our finding that cytosolic proteins mediate fusion between membranes lacking functional transmembrane proteins and the role of membrane fusion in endoplasmic reticulum and nuclear envelope reorganization. Cytosol-dependent liposome fusion has allowed us to restore, without adding transmembrane nucleoporins, functionality of nuclear pores, their spatial distribution and chromatin decondensation in nuclei formed at insufficient amounts of membrane material and characterized by only partial decondensation of chromatin and lack of nuclear transport. Both the mechanisms and the biological implications of the discovered coupling between spatial distribution of nuclear pores, chromatin decondensation and nuclear transport are discussed.

Dangers associated with civil nuclear power programmes: weaponization and nuclear waste.

PubMed

Boulton, Frank

2015-07-24

The number of nuclear power plants in the world rose exponentially to 420 by 1990 and peaked at 438 in 2002; but by 2014, as closed plants were not replaced, there were just 388. In spite of using more renewable energy, the world still relies on fossil fuels, but some countries plan to develop new nuclear programmes. Spent nuclear fuel, one of the most dangerous and toxic materials known, can be reprocessed into fresh fuel or into weapons-grade materials, and generates large amounts of highly active waste. This article reviews available literature on government and industry websites and from independent analysts on world energy production, the aspirations of the 'new nuclear build' programmes in China and the UK, and the difficulties in keeping the environment safe over an immense timescale while minimizing adverse health impacts and production of greenhouse gases, and preventing weaponization by non-nuclear-weapons states acquiring civil nuclear technology.

Pro-Nuclear Environmentalism: Should We Learn to Stop Worrying and Love Nuclear Energy?

PubMed

van Munster, Rens; Sylvest, Casper

2015-10-01

In light of repeated failures to reach political agreement on effective policies to combat climate change, pro-nuclear environmentalists have set out to reverse the traditionally anti-nuclear inclinations of environmentalists. This essay examines the ideological commitments and assumptions of pro-nuclear environmentalism by performing a critical, historical analysis of the nuclear-environment nexus through the prism of documentary film. We focus on the work and career of documentary filmmaker Rob Stone, whose most recent production, Pandora's Promise (PP) (2013), has emerged as a central statement of this creed. PP actively forges a new political imaginary that replaces the apocalyptic image of nuclear fallout with that of catastrophic climate change. In terms of its rhetorical and visual strategies, however, PP also reveals that pro-nuclear environmentalist arguments have a long lineage. A close study of such continuities reveals a number of political implications that call for reflection as well as caution.

Navy Ohio Replacement (SSBN[X]) Ballistic Missile Submarine Program: Background and Issues for Congress

DTIC Science & Technology

2015-12-17

requirement. Given the time needed for at-sea training operations, restocking SSBNs with food and other consumables, performing maintenance and repair...affect U.S. military capabilities and funding requirements, and the U.S. shipbuilding industrial base. This report focuses on the Ohio replacement...strategic nuclear arms reduction treaty that included 14 Ohio-class SSBNs, all armed with D- 5s . This recommendation prompted interest in the idea of

Patriarchal Hierarchies of Power and the Subordination of Women: Real Doll as a Replacement of Woman Figure

ERIC Educational Resources Information Center

Shokri, Natasha; Asl, Moussa Pourya

2015-01-01

The social structure of the family has always been in the state of transformation. In the past centuries, the nuclear family was replaced with a Patriarchal Family which lasted for only two centuries from 16th to the beginning of 18th century. In this new structure of the family, men were privileged to play the role of the master and the women…

U.S. Strategic Nuclear Forces: Background, Developments, and Issues

DTIC Science & Technology

2016-09-27

meet the terms of the New START Treaty. The Air Force is also modernizing the Minuteman missiles, replacing and upgrading their rocket motors...began in 1998 and has been replacing the propellant, the solid rocket fuel, in the Minuteman motors to extend the life of the rocket motors. A...complete the program. It has not requested additional funding in subsequent years. Propulsion System Rocket Engine Program (PSRE) According to the Air

Open release of male mosquitoes infected with a wolbachia biopesticide: field performance and infection containment.

PubMed

O'Connor, Linda; Plichart, Catherine; Sang, Ayo Cheong; Brelsfoard, Corey L; Bossin, Hervé C; Dobson, Stephen L

2012-01-01

Lymphatic filariasis (LF) is a globally significant disease, with 1.3 billion persons in 83 countries at risk. A coordinated effort of administering annual macrofilaricidal prophylactics to the entire at-risk population has succeeded in impacting and eliminating LF transmission in multiple regions. However, some areas in the South Pacific are predicted to persist as transmission sites, due in part to the biology of the mosquito vector, which has led to a call for additional tools to augment drug treatments. Autocidal strategies against mosquitoes are resurging in the effort against invasive mosquitoes and vector borne disease, with examples that include field trials of genetically modified mosquitoes and Wolbachia population replacement. However, critical questions must be addressed in anticipation of full field trials, including assessments of field competitiveness of transfected males and the risk of unintended population replacement. We report the outcome of field experiments testing a strategy that employs Wolbachia as a biopesticide. The strategy is based upon Wolbachia-induced conditional sterility, known as cytoplasmic incompatibility, and the repeated release of incompatible males to suppress a population. A criticism of the Wolbachia biopesticide approach is that unintended female release or horizontal Wolbachia transmission can result in population replacement instead of suppression. We present the outcome of laboratory and field experiments assessing the competitiveness of transfected males and their ability to transmit Wolbachia via horizontal transmission. The results demonstrate that Wolbachia-transfected Aedes polynesiensis males are competitive under field conditions during a thirty-week open release period, as indicated by mark, release, recapture and brood-hatch failure among females at the release site. Experiments demonstrate the males to be 'dead end hosts' for Wolbachia and that methods were adequate to prevent population replacement at the field site. The findings encourage the continued development and extension of a Wolbachia autocidal approach to additional medically important mosquito species.

Testing of electrical equipment for a commercial grade dedication program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, J.L.; Srinivas, N.

1995-10-01

The availability of qualified safety related replacement parts for use in nuclear power plants has decreased over time. This has caused many nuclear power plants to purchase commercial grade items (CGI) and utilize the commercial grade dedication process to qualify the items for use in nuclear safety related applications. The laboratories of Technical and Engineering Services (the testing facility of Detroit Edison) have been providing testing services for verification of critical characteristics of these items. This paper presents an overview of the experience in testing electrical equipment with an emphasis on fuses.

Human somatic cell nuclear transfer and reproductive cloning: an Ethics Committee opinion.

PubMed

2016-04-01

This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer and cloning," last published in Fertil Steril 2012;98:804-7. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Navy Ohio Replacement (SSBN[X]) Ballistic Missile Submarine Program: Background and Issues for Congress

DTIC Science & Technology

2013-03-14

submarines, which are powered by energy sources such as diesel engines. A submarine’s use of nuclear or non-nuclear power as its energy source is not an...current force of 14 Ohio-class SSBNs, all of which are armed with D-5 SLBMs. Eight of the 14 Ohio-class SSBNs are homeported at Bangor, WA, in Puget ...nuclear-related issues that is carried out under the 1958 Agreement for Cooperation on the Uses of Atomic Energy for Mutual Defense Purposes (also known as

Short- and long-term responses to molybdenum-99 shortages in nuclear medicine.

PubMed

Ballinger, J R

2010-11-01

Most nuclear medicine studies use (99)Tc(m), which is the decay product of (99)Mo. The world supply of (99)Mo comes from only five nuclear research reactors and availability has been much reduced in recent times owing to problems at the largest reactors. In the short-term there are limited actions that can be taken owing to capacity issues on alternative imaging modalities. In the long-term, stability of (99)Mo supply will rely on a combination of replacing conventional reactors and developing new technologies.

Short- and long-term responses to molybdenum-99 shortages in nuclear medicine

PubMed Central

Ballinger, J R

2010-01-01

Most nuclear medicine studies use 99Tcm, which is the decay product of 99Mo. The world supply of 99Mo comes from only five nuclear research reactors and availability has been much reduced in recent times owing to problems at the largest reactors. In the short-term there are limited actions that can be taken owing to capacity issues on alternative imaging modalities. In the long-term, stability of 99Mo supply will rely on a combination of replacing conventional reactors and developing new technologies. PMID:20965898

Neutrino Processes in Neutron Stars

NASA Astrophysics Data System (ADS)

Kolomeitsev, E. E.; Voskresensky, D. N.

2010-10-01

The aim of these lectures is to introduce basic processes responsible for cooling of neutron stars and to show how to calculate the neutrino production rate in dense strongly interacting nuclear medium. The formalism is presented that treats on equal footing one-nucleon and multiple-nucleon processes and reactions with virtual bosonic modes and condensates. We demonstrate that neutrino emission from dense hadronic component in neutron stars is subject of strong modifications due to collective effects in the nuclear matter. With the most important in-medium processes incorporated in the cooling code an overall agreement with available soft X ray data can be easily achieved. With these findings the so-called “standard” and “non-standard” cooling scenarios are replaced by one general “nuclear medium cooling scenario” which relates slow and rapid neutron star coolings to the star masses (interior densities). The lectures are split in four parts. Part I: After short introduction to the neutron star cooling problem we show how to calculate neutrino reaction rates of the most efficient one-nucleon and two-nucleon processes. No medium effects are taken into account in this instance. The effects of a possible nucleon pairing are discussed. We demonstrate that the data on neutron star cooling cannot be described without inclusion of medium effects. It motivates an assumption that masses of the neutron stars are different and that neutrino reaction rates should be strongly density dependent. Part II: We introduce the Green’s function diagram technique for systems in and out of equilibrium and the optical theorem formalism. The latter allows to perform calculations of production rates with full Green’s functions including all off-mass-shell effects. We demonstrate how this formalism works within the quasiparticle approximation. Part III: The basic concepts of the nuclear Fermi liquid approach are introduced. We show how strong interaction effects can be included within the Green’s function formalism. Softening of the pion mode with an baryon density increase is explicitly incorporated. We show examples of inconsistencies in calculations without inclusion of medium effects. Then we demonstrate calculations of different reaction rates in non-superfluid nuclear matter with taking into account medium effects. Many new reaction channels are open up in the medium and should be analyzed. Part IV: We discuss the neutrino production reactions in superfluid nuclear systems. The reaction rates of processes associated with the pair breaking and formation are calculated. Special attention is focused on the gauge invariance and the exact fulfillment of the Ward identities for the vector current. Finally we present comparison of calculations of neutron star cooling performed within nuclear medium cooling scenario with the available data.

Image Coding Based on Address Vector Quantization.

NASA Astrophysics Data System (ADS)

Feng, Yushu

Image coding is finding increased application in teleconferencing, archiving, and remote sensing. This thesis investigates the potential of Vector Quantization (VQ), a relatively new source coding technique, for compression of monochromatic and color images. Extensions of the Vector Quantization technique to the Address Vector Quantization method have been investigated. In Vector Quantization, the image data to be encoded are first processed to yield a set of vectors. A codeword from the codebook which best matches the input image vector is then selected. Compression is achieved by replacing the image vector with the index of the code-word which produced the best match, the index is sent to the channel. Reconstruction of the image is done by using a table lookup technique, where the label is simply used as an address for a table containing the representative vectors. A code-book of representative vectors (codewords) is generated using an iterative clustering algorithm such as K-means, or the generalized Lloyd algorithm. A review of different Vector Quantization techniques are given in chapter 1. Chapter 2 gives an overview of codebook design methods including the Kohonen neural network to design codebook. During the encoding process, the correlation of the address is considered and Address Vector Quantization is developed for color image and monochrome image coding. Address VQ which includes static and dynamic processes is introduced in chapter 3. In order to overcome the problems in Hierarchical VQ, Multi-layer Address Vector Quantization is proposed in chapter 4. This approach gives the same performance as that of the normal VQ scheme but the bit rate is about 1/2 to 1/3 as that of the normal VQ method. In chapter 5, a Dynamic Finite State VQ based on a probability transition matrix to select the best subcodebook to encode the image is developed. In chapter 6, a new adaptive vector quantization scheme, suitable for color video coding, called "A Self -Organizing Adaptive VQ Technique" is presented. In addition to chapters 2 through 6 which report on new work, this dissertation includes one chapter (chapter 1) and part of chapter 2 which review previous work on VQ and image coding, respectively. Finally, a short discussion of directions for further research is presented in conclusion.

Population Genetics of Two Key Mosquito Vectors of Rift Valley Fever Virus Reveals New Insights into the Changing Disease Outbreak Patterns in Kenya

PubMed Central

Tchouassi, David P.; Bastos, Armanda D. S.; Sole, Catherine L.; Diallo, Mawlouth; Lutomiah, Joel; Mutisya, James; Mulwa, Francis; Borgemeister, Christian; Sang, Rosemary; Torto, Baldwyn

2014-01-01

Rift Valley fever (RVF) outbreaks in Kenya have increased in frequency and range to include northeastern Kenya where viruses are increasingly being isolated from known (Aedes mcintoshi) and newly-associated (Ae. ochraceus) vectors. The factors contributing to these changing outbreak patterns are unclear and the population genetic structure of key vectors and/or specific virus-vector associations, in particular, are under-studied. By conducting mitochondrial and nuclear DNA analyses on >220 Kenyan specimens of Ae. mcintoshi and Ae. ochraceus, we uncovered high levels of vector complexity which may partly explain the disease outbreak pattern. Results indicate that Ae. mcintoshi consists of a species complex with one of the member species being unique to the newly-established RVF outbreak-prone northeastern region of Kenya, whereas Ae. ochraceus is a homogeneous population that appears to be undergoing expansion. Characterization of specimens from a RVF-prone site in Senegal, where Ae. ochraceus is a primary vector, revealed direct genetic links between the two Ae. ochraceus populations from both countries. Our data strongly suggest that unlike Ae. mcintoshi, Ae. ochraceus appears to be a relatively recent, single 'introduction' into Kenya. These results, together with increasing isolations from this vector, indicate that Ae. ochraceus will likely be of greater epidemiological importance in future RVF outbreaks in Kenya. Furthermore, the overall vector complexity calls into question the feasibility of mosquito population control approaches reliant on genetic modification. PMID:25474018

Improving semi-text-independent method of writer verification using difference vector

NASA Astrophysics Data System (ADS)

Li, Xin; Ding, Xiaoqing

2009-01-01

The semi-text-independent method of writer verification based on the linear framework is a method that can use all characters of two handwritings to discriminate the writers in the condition of knowing the text contents. The handwritings are allowed to just have small numbers of even totally different characters. This fills the vacancy of the classical text-dependent methods and the text-independent methods of writer verification. Moreover, the information, what every character is, is used for the semi-text-independent method in this paper. Two types of standard templates, generated from many writer-unknown handwritten samples and printed samples of each character, are introduced to represent the content information of each character. The difference vectors of the character samples are gotten by subtracting the standard templates from the original feature vectors and used to replace the original vectors in the process of writer verification. By removing a large amount of content information and remaining the style information, the verification accuracy of the semi-text-independent method is improved. On a handwriting database involving 30 writers, when the query handwriting and the reference handwriting are composed of 30 distinct characters respectively, the average equal error rate (EER) of writer verification reaches 9.96%. And when the handwritings contain 50 characters, the average EER falls to 6.34%, which is 23.9% lower than the EER of not using the difference vectors.

Quasiperiodicity in time evolution of the Bloch vector under the thermal Jaynes-Cummings model

NASA Astrophysics Data System (ADS)

Azuma, Hiroo; Ban, Masashi

2014-07-01

We study a quasiperiodic structure in the time evolution of the Bloch vector, whose dynamics is governed by the thermal Jaynes-Cummings model (JCM). Putting the two-level atom into a certain pure state and the cavity field into a mixed state in thermal equilibrium at initial time, we let the whole system evolve according to the JCM Hamiltonian. During this time evolution, motion of the Bloch vector seems to be in disorder. Because of the thermal photon distribution, both a norm and a direction of the Bloch vector change hard at random. In this paper, taking a different viewpoint compared with ones that we have been used to, we investigate quasiperiodicity of the Bloch vector’s trajectories. Introducing the concept of the quasiperiodic motion, we can explain the confused behaviour of the system as an intermediate state between periodic and chaotic motions. More specifically, we discuss the following two facts: (1) If we adjust the time interval Δt properly, figures consisting of plotted dots at the constant time interval acquire scale invariance under replacement of Δt by sΔt, where s(>1) is an arbitrary real but not transcendental number. (2) We can compute values of the time variable t, which let |Sz(t)| (the absolute value of the z-component of the Bloch vector) be very small, with the Diophantine approximation (a rational approximation of an irrational number).

Limit on Tensor Currents from Li 8 β Decay

NASA Astrophysics Data System (ADS)

Sternberg, M. G.; Segel, R.; Scielzo, N. D.; Savard, G.; Clark, J. A.; Bertone, P. F.; Buchinger, F.; Burkey, M.; Caldwell, S.; Chaudhuri, A.; Crawford, J. E.; Deibel, C. M.; Greene, J.; Gulick, S.; Lascar, D.; Levand, A. F.; Li, G.; Pérez Galván, A.; Sharma, K. S.; Van Schelt, J.; Yee, R. M.; Zabransky, B. J.

2015-10-01

In the standard model, the weak interaction is formulated with a purely vector-axial-vector (V -A ) structure. Without restriction on the chirality of the neutrino, the most general limits on tensor currents from nuclear β decay are dominated by a single measurement of the β -ν ¯ correlation in He 6 β decay dating back over a half century. In the present work, the β -ν ¯ -α correlation in the β decay of Li 8 and subsequent α -particle breakup of the Be8 * daughter was measured. The results are consistent with a purely V -A interaction and in the case of couplings to right-handed neutrinos (CT=-CT' ) limits the tensor fraction to |CT/CA|2<0.011 (95.5% C.L.). The measurement confirms the He 6 result using a different nuclear system and employing modern ion-trapping techniques subject to different systematic uncertainties.

Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomono, Takumi; Kajita, Masahiro; Yano, Kentaro

P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNAmore » expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment. -- Highlights: •Adenovirus vector infection induced P-gp mRNA expression in three NSCLC cell lines. •Adenovirus vector infection enhanced P-gp-mediated doxorubicin efflux from the cells. •The increase of P-gp was not mediated by nuclear receptors (PXR, CAR) or COX-2.« less

Experimental study on cesium immobilization in struvite structures.

PubMed

Wagh, Arun S; Sayenko, S Y; Shkuropatenko, V A; Tarasov, R V; Dykiy, M P; Svitlychniy, Y O; Virych, V D; Ulybkina, Е А

2016-01-25

Ceramicrete, a chemically bonded phosphate ceramic, was developed for nuclear waste immobilization and nuclear radiation shielding. Ceramicrete products are fabricated by an acid-base reaction between magnesium oxide and mono potassium phosphate that has a struvite-K mineral structure. In this study, we demonstrate that this crystalline structure is ideal for incorporating radioactive Cs into a Ceramicrete matrix. This is accomplished by partially replacing K by Cs in the struvite-K structure, thus forming struvite-(K, Cs) mineral. X-ray diffraction and thermo-gravimetric analyses are used to confirm such a replacement. The resulting product is non-leachable and stable at high temperatures, and hence it is an ideal matrix for immobilizing Cs found in high-activity nuclear waste streams. The product can also be used for immobilizing secondary waste streams generated during glass vitrification of spent fuel, or the method described in this article can be used as a pretreatment method during glass vitrification of high level radioactive waste streams. Furthermore, it suggests a method of producing safe commercial radioactive Cs sources. Copyright © 2015 Elsevier B.V. All rights reserved.

Minimization of the energy loss of nuclear power plants in case of partial in-core monitoring system failure

NASA Astrophysics Data System (ADS)

Zagrebaev, A. M.; Ramazanov, R. N.; Lunegova, E. A.

2017-01-01

In this paper we consider the optimization problem minimize of the energy loss of nuclear power plants in case of partial in-core monitoring system failure. It is possible to continuation of reactor operation at reduced power or total replacement of the channel neutron measurements, requiring shutdown of the reactor and the stock of detectors. This article examines the reconstruction of the energy release in the core of a nuclear reactor on the basis of the indications of height sensors. The missing measurement information can be reconstructed by mathematical methods, and replacement of the failed sensors can be avoided. It is suggested that a set of ‘natural’ functions determined by means of statistical estimates obtained from archival data be constructed. The procedure proposed makes it possible to reconstruct the field even with a significant loss of measurement information. Improving the accuracy of the restoration of the neutron flux density in partial loss of measurement information to minimize the stock of necessary components and the associated losses.

Laser Induced Nuclear Fusion, LINF, In Muonic Molecules With Ultrashort Super Intense Laser Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bandrauk, Andre D.; Paramonov, Gennady K.

2010-02-02

Muonium molecules where muons replace electrons increase the stability of molecules to ionization at superhigh intensities, I>10{sup 20} W/cm{sup 2}. We show furthermore from numerical simulations that in the nonsymmetric series, pdu, dtu, ptu, the permanent dipole moments can be used to enhance LINF, Laser Induced Nuclear Fusion by laser induced recollision of the light nucleus with the heavier nucleus.

JPRS Report, Science & Technology, China.

DTIC Science & Technology

1992-08-20

nature of the nuclear medium. QCD [quantum chromodynamic] lattice gauge calculations have predicted the existence of a new phase of the nuclear medium...and A106 octahedra; the atoms Nb and Al are located at the vacants of the octahedra, but a fraction of Al in the lattice is replaced by Nb atoms, and...superlattice and quantum-well lattice dynamics and electron structure, transport processes in superlattice low-dimensionality systems, semiconductor

Passive cooling system for liquid metal cooled nuclear reactors with backup coolant flow path

DOEpatents

Hunsbedt, Anstein; Boardman, Charles E.

1993-01-01

A liquid metal cooled nuclear fission reactor plant having a passive auxiliary safety cooling system for removing residual heat resulting from fuel decay during reactor shutdown, or heat produced during a mishap. This reactor plant is enhanced by a backup or secondary passive safety cooling system which augments the primary passive auxiliary cooling system when in operation, and replaces the primary system when rendered inoperable.

Nuclear Weapons: The Reliable Replacement Warhead Program

DTIC Science & Technology

2005-07-20

time to age. The United States introduced generation after generation of new nuclear “delivery vehicles ” — bombers, missile submarines, and land...less constrained in weight because bombers carry heavier loads than missiles. 26 Ballistic missiles carry warheads inside reentry vehicles (RVs). An...RV is a streamlined shell that protects its warhead from the intense heat and other stresses of reentering the atmosphere at high speed. RVs are

Nuclear Data Sheets for A=150

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, S.K.; Sonzogni, A.A.

The experimental results from the various reaction and decay studies leading to nuclides in the A=150 mass chain have been reviewed. These data are summarized and presented, together with the adopted level schemes and properties, for the nuclides from Cs(Z=55) through Lu(Z=71). This evaluation replaces the previous evaluation by E. der Mateosian and J. K. Tuli (1995De28), which appeared in Nuclear Data Sheets 75, 827 (1995)

Nuclear Data Sheets for A=150

NASA Astrophysics Data System (ADS)

Basu, S. K.; Sonzogni, A. A.

2013-04-01

The experimental results from the various reaction and decay studies leading to nuclides in the A=150 mass chain have been reviewed. These data are summarized and presented, together with the adopted level schemes and properties, for the nuclides from Cs(Z=55) through Lu(Z=71). This evaluation replaces the previous evaluation by E. der Mateosian and J. K. Tuli (1995De28), which appeared in Nuclear Data Sheets 75, 827 (1995).

Cost Differences in Public and Private Shipyards

DTIC Science & Technology

1981-01-01

block number) coefficients, costs, maintenance, naval shore facilities, naval vessels, nuclear powered ships, regression analysis, repair, salaries...of overhauls of nucler submarines, we mnight exp.,_t to find both production costs and the price of labor to be higher in naval shipyardi than in...about 18 months; in addition to the type of work done during regular overhauls, they include replacement of the nuclear core which powers the submarine

Theater-Level Gaming and Analysis Workshop for Force Planning. Volume II. Summary, Discussion of Issues and Requirements for Research. September 27- 29, 1977, Held at Xerox International Center for Training and Management Development, Leesburg, Virginia

DTIC Science & Technology

1981-05-01

be allocated to targets on the battlefield and in the rear area. The speaker describes the VECTOR I/NUCLEAR model, a combination of the UNICORN target...outlined. UNICORN is compatible with VECTOR 1 in level of detail. It is an expected value damage model and uses linear programming to optimize the...and a growing appreciation for the power of simulation in addressing large, complex problems, it was only a few short years before these games had

Improvements in Block-Krylov Ritz Vectors and the Boundary Flexibility Method of Component Synthesis

NASA Technical Reports Server (NTRS)

Carney, Kelly Scott

1997-01-01

A method of dynamic substructuring is presented which utilizes a set of static Ritz vectors as a replacement for normal eigenvectors in component mode synthesis. This set of Ritz vectors is generated in a recurrence relationship, proposed by Wilson, which has the form of a block-Krylov subspace. The initial seed to the recurrence algorithm is based upon the boundary flexibility vectors of the component. Improvements have been made in the formulation of the initial seed to the Krylov sequence, through the use of block-filtering. A method to shift the Krylov sequence to create Ritz vectors that will represent the dynamic behavior of the component at target frequencies, the target frequency being determined by the applied forcing functions, has been developed. A method to terminate the Krylov sequence has also been developed. Various orthonormalization schemes have been developed and evaluated, including the Cholesky/QR method. Several auxiliary theorems and proofs which illustrate issues in component mode synthesis and loss of orthogonality in the Krylov sequence have also been presented. The resulting methodology is applicable to both fixed and free- interface boundary components, and results in a general component model appropriate for any type of dynamic analysis. The accuracy is found to be comparable to that of component synthesis based upon normal modes, using fewer generalized coordinates. In addition, the block-Krylov recurrence algorithm is a series of static solutions and so requires significantly less computation than solving the normal eigenspace problem. The requirement for less vectors to form the component, coupled with the lower computational expense of calculating these Ritz vectors, combine to create a method more efficient than traditional component mode synthesis.

Construction of Various γ34.5 Deleted Fluorescent-Expressing Oncolytic herpes Simplex type 1 (oHSV) for Generation and Isolation of HSV-Based Vectors

PubMed

Abdoli, Shahriyar; Roohvand, Farzin; Teimoori-Toolabi, Ladan; Shokrgozar, Mohammad Ali; Bahrololoumi, Mina; Azadmanesh, Kayhan

2017-07-01

Oncolytic herpes simplex virus (oHSV)-based vectors lacking γ34.5 gene, are considered as ideal templates to construct efficient vectors for (targeted) cancer gene therapy. Herein, we reported the construction of three single/dually-flourescence labeled and γ34.5-deleted, recombinant HSV-1 vectors for rapid generation and easy selection/isolation of different HSV-Based vectors. Generation of recombinant viruses was performed with conventional homologous recombination methods using green fluorescent protein (GFP) and BleCherry harboring shuttle vectors. Viruses were isolated by direct fluorescence observation and standard plaque purifying methods and confirmed by PCR and sequencing and flow cytometry. XTT and plaque assay titration were performed on Vero, U87MG, and T98 GBM cell lines. We generated three recombinant viruses, HSV-GFP, HSV-GR (Green-Red), and HSV-Red. The HSV-GFP showed two log higher titer (1010 PFU) than wild type (108 PFU). In contrast, HSV-GR and HSV-Red showed one log lower titer (107 PFU) than parental HSV. Cytotoxicity analysis showed that HSV-GR and HSV-Red can lyse target tumor cells at multiplicity of infection of 10 and 1 (P<0.001). Moreover, HSV-GFP showed higher infection potency (98%) in comparison with HSV-GR (82%). Our oHSVs provide a simple and an efficient platform for construction and rapid isolation of 2nd and 3rd generation oHSVs by replacing the inserted dyes with transgenes and also for rapid identification via fluorescence activated cell sorting. These vectors can also be used for tracing the efficacy of therapeutic agents on target cells, imaging of neural or tumoral cells in vitro/in vivo and as oncolytic agents in cancer therapy.

A Systematic Approach for Model-Based Aircraft Engine Performance Estimation

NASA Technical Reports Server (NTRS)

Simon, Donald L.; Garg, Sanjay

2010-01-01

A requirement for effective aircraft engine performance estimation is the ability to account for engine degradation, generally described in terms of unmeasurable health parameters such as efficiencies and flow capacities related to each major engine module. This paper presents a linear point design methodology for minimizing the degradation-induced error in model-based aircraft engine performance estimation applications. The technique specifically focuses on the underdetermined estimation problem, where there are more unknown health parameters than available sensor measurements. A condition for Kalman filter-based estimation is that the number of health parameters estimated cannot exceed the number of sensed measurements. In this paper, the estimated health parameter vector will be replaced by a reduced order tuner vector whose dimension is equivalent to the sensed measurement vector. The reduced order tuner vector is systematically selected to minimize the theoretical mean squared estimation error of a maximum a posteriori estimator formulation. This paper derives theoretical estimation errors at steady-state operating conditions, and presents the tuner selection routine applied to minimize these values. Results from the application of the technique to an aircraft engine simulation are presented and compared to the estimation accuracy achieved through conventional maximum a posteriori and Kalman filter estimation approaches. Maximum a posteriori estimation results demonstrate that reduced order tuning parameter vectors can be found that approximate the accuracy of estimating all health parameters directly. Kalman filter estimation results based on the same reduced order tuning parameter vectors demonstrate that significantly improved estimation accuracy can be achieved over the conventional approach of selecting a subset of health parameters to serve as the tuner vector. However, additional development is necessary to fully extend the methodology to Kalman filter-based estimation applications.

Current density tensors

NASA Astrophysics Data System (ADS)

Lazzeretti, Paolo

2018-04-01

It is shown that nonsymmetric second-rank current density tensors, related to the current densities induced by magnetic fields and nuclear magnetic dipole moments, are fundamental properties of a molecule. Together with magnetizability, nuclear magnetic shielding, and nuclear spin-spin coupling, they completely characterize its response to magnetic perturbations. Gauge invariance, resolution into isotropic, deviatoric, and antisymmetric parts, and contributions of current density tensors to magnetic properties are discussed. The components of the second-rank tensor properties are rationalized via relationships explicitly connecting them to the direction of the induced current density vectors and to the components of the current density tensors. The contribution of the deviatoric part to the average value of magnetizability, nuclear shielding, and nuclear spin-spin coupling, uniquely determined by the antisymmetric part of current density tensors, vanishes identically. The physical meaning of isotropic and anisotropic invariants of current density tensors has been investigated, and the connection between anisotropy magnitude and electron delocalization has been discussed.

β-Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells.

PubMed

Sui, Lina; Danzl, Nichole; Campbell, Sean R; Viola, Ryan; Williams, Damian; Xing, Yuan; Wang, Yong; Phillips, Neil; Poffenberger, Greg; Johannesson, Bjarki; Oberholzer, Jose; Powers, Alvin C; Leibel, Rudolph L; Chen, Xiaojuan; Sykes, Megan; Egli, Dieter

2018-01-01

β-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into β-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature β-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These β-cells adapt insulin secretion to ambient metabolite status and show normal insulin processing. Importantly, NT-ES-β-cells maintain normal blood glucose levels after ablation of the mouse endogenous β-cells. Cystic structures, but no teratomas, were observed in NT-ES-β-cell grafts. Isogenic induced pluripotent stem cell lines showed greater variability in β-cell differentiation. Even though different methods of somatic cell reprogramming result in stem cell lines that are molecularly indistinguishable, full differentiation competence is more common in ES cell lines than in induced pluripotent stem cell lines. These results demonstrate the suitability of NT-ES-β-cells for cell replacement for type 1 diabetes and provide proof of principle for therapeutic cloning combined with cell therapy. © 2017 by the American Diabetes Association.

Finite element based electric motor design optimization

NASA Technical Reports Server (NTRS)

Campbell, C. Warren

1993-01-01

The purpose of this effort was to develop a finite element code for the analysis and design of permanent magnet electric motors. These motors would drive electromechanical actuators in advanced rocket engines. The actuators would control fuel valves and thrust vector control systems. Refurbishing the hydraulic systems of the Space Shuttle after each flight is costly and time consuming. Electromechanical actuators could replace hydraulics, improve system reliability, and reduce down time.

TVC actuator model. [for the space shuttle main engine

NASA Technical Reports Server (NTRS)

Baslock, R. W.

1977-01-01

A prototype Space Shuttle Main Engine (SSME) Thrust Vector Control (TVC) Actuator analog model was successfully completed. The prototype, mounted on five printed circuit (PC) boards, was delivered to NASA, checked out and tested using a modular replacement technique on an analog computer. In all cases, the prototype model performed within the recording techniques of the analog computer which is well within the tolerances of the specifications.

Computational identification of post-translational modification-based nuclear import regulations by characterizing nuclear localization signal-import receptor interaction.

PubMed

Lin, Jhih-Rong; Liu, Zhonghao; Hu, Jianjun

2014-10-01

The binding affinity between a nuclear localization signal (NLS) and its import receptor is closely related to corresponding nuclear import activity. PTM-based modulation of the NLS binding affinity to the import receptor is one of the most understood mechanisms to regulate nuclear import of proteins. However, identification of such regulation mechanisms is challenging due to the difficulty of assessing the impact of PTM on corresponding nuclear import activities. In this study we proposed NIpredict, an effective algorithm to predict nuclear import activity given its NLS, in which molecular interaction energy components (MIECs) were used to characterize the NLS-import receptor interaction, and the support vector regression machine (SVR) was used to learn the relationship between the characterized NLS-import receptor interaction and the corresponding nuclear import activity. Our experiments showed that nuclear import activity change due to NLS change could be accurately predicted by the NIpredict algorithm. Based on NIpredict, we developed a systematic framework to identify potential PTM-based nuclear import regulations for human and yeast nuclear proteins. Application of this approach has identified the potential nuclear import regulation mechanisms by phosphorylation of two nuclear proteins including SF1 and ORC6. © 2014 Wiley Periodicals, Inc.

Vector potential of houseflies (Musca domestica) for Helicobacter pylori.

PubMed

Grübel, P; Hoffman, J S; Chong, F K; Burstein, N A; Mepani, C; Cave, D R

1997-06-01

The mode of transmission of Helicobacter pylori is unknown. Since viable bacteria have been shown to be excreted in feces from infected individuals and houseflies habitually develop and feed on excrement, we hypothesized that flies ingest and harbor H. pylori and, in turn, contaminate the human environment. This study examined the possible vector potential of houseflies (Musca domestica) for H. pylori. Caged houseflies were exposed to freshly grown H. pylori on agar plates. After a 6-h feeding period, the plates were removed and were replaced with sterile petri dishes containing a droplet of sterile brucella broth. At regular intervals, small numbers of houseflies were removed for microbiological and histological analysis, and the petri dishes were replaced with fresh sterile plates with fresh drops of brucella broth. The flies' bodies, the flies' dissected alimentary tracts, and excreta on the petri dishes were cultured for H. pylori, whose identity was confirmed by the urease, catalase, and oxidase reactions and Gram staining. In contrast to control flies, viable H. pylori could be isolated from external surfaces for up to 12 h and from gut and excreta for as long as 30 h after the initial feeding period. After 30 h other gram-negative bacteria overgrew the cultures of samples from all locations tested, rendering the selective culture of H. pylori colonies impossible. Histological analysis revealed Helicobacter-like organisms in the gut lumen and attached to intestinal epithelial cells. We conclude that houseflies can harbor viable H. pylori on their bodies and in their intestinal tracts. They are also able to disseminate viable H. pylori in excreta, and they may therefore present a significant reservoir and be a vector in the transmission of H. pylori.

Vector potential of houseflies (Musca domestica) for Helicobacter pylori.

PubMed Central

Grübel, P; Hoffman, J S; Chong, F K; Burstein, N A; Mepani, C; Cave, D R

1997-01-01

The mode of transmission of Helicobacter pylori is unknown. Since viable bacteria have been shown to be excreted in feces from infected individuals and houseflies habitually develop and feed on excrement, we hypothesized that flies ingest and harbor H. pylori and, in turn, contaminate the human environment. This study examined the possible vector potential of houseflies (Musca domestica) for H. pylori. Caged houseflies were exposed to freshly grown H. pylori on agar plates. After a 6-h feeding period, the plates were removed and were replaced with sterile petri dishes containing a droplet of sterile brucella broth. At regular intervals, small numbers of houseflies were removed for microbiological and histological analysis, and the petri dishes were replaced with fresh sterile plates with fresh drops of brucella broth. The flies' bodies, the flies' dissected alimentary tracts, and excreta on the petri dishes were cultured for H. pylori, whose identity was confirmed by the urease, catalase, and oxidase reactions and Gram staining. In contrast to control flies, viable H. pylori could be isolated from external surfaces for up to 12 h and from gut and excreta for as long as 30 h after the initial feeding period. After 30 h other gram-negative bacteria overgrew the cultures of samples from all locations tested, rendering the selective culture of H. pylori colonies impossible. Histological analysis revealed Helicobacter-like organisms in the gut lumen and attached to intestinal epithelial cells. We conclude that houseflies can harbor viable H. pylori on their bodies and in their intestinal tracts. They are also able to disseminate viable H. pylori in excreta, and they may therefore present a significant reservoir and be a vector in the transmission of H. pylori. PMID:9163433

Elimination of secular terms from the differential equations for the elements of perturbed two-body motion

NASA Technical Reports Server (NTRS)

Bond, Victor R.; Fraietta, Michael F.

1991-01-01

In 1961, Sperling linearized and regularized the differential equations of motion of the two-body problem by changing the independent variable from time to fictitious time by Sundman's transformation (r = dt/ds) and by embedding the two-body energy integral and the Laplace vector. In 1968, Burdet developed a perturbation theory which was uniformly valid for all types of orbits using a variation of parameters approach on the elements which appeared in Sperling's equations for the two-body solution. In 1973, Bond and Hanssen improved Burdet's set of differential equations by embedding the total energy (which is a constant when the potential function is explicitly dependent upon time.) The Jacobian constant was used as an element to replace the total energy in a reformulation of the differential equations of motion. In the process, another element which is proportional to a component of the angular momentum was introduced. Recently trajectories computed during numerical studies of atmospheric entry from circular orbits and low thrust beginning in near-circular orbits exhibited numerical instability when solved by the method of Bond and Gottlieb (1989) for long time intervals. It was found that this instability was due to secular terms which appear on the righthand sides of the differential equations of some of the elements. In this paper, this instability is removed by the introduction of another vector integral called the delta integral (which replaces the Laplace Vector) and another scalar integral which removes the secular terms. The introduction of these integrals requires a new derivation of the differential equations for most of the elements. For this rederivation, the Lagrange method of variation of parameters is used, making the development more concise. Numerical examples of this improvement are presented.

Simultaneous neuron- and astrocyte-specific fluorescent marking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulze, Wiebke; Hayata-Takano, Atsuko; Kamo, Toshihiko

2015-03-27

Systematic and simultaneous analysis of multiple cell types in the brain is becoming important, but such tools have not yet been adequately developed. Here, we aimed to generate a method for the specific fluorescent labeling of neurons and astrocytes, two major cell types in the brain, and we have developed lentiviral vectors to express the red fluorescent protein tdTomato in neurons and the enhanced green fluorescent protein (EGFP) in astrocytes. Importantly, both fluorescent proteins are fused to histone 2B protein (H2B) to confer nuclear localization to distinguish between single cells. We also constructed several expression constructs, including a tandem alignmentmore » of the neuron- and astrocyte-expression cassettes for simultaneous labeling. Introducing these vectors and constructs in vitro and in vivo resulted in cell type-specific and nuclear-localized fluorescence signals enabling easy detection and distinguishability of neurons and astrocytes. This tool is expected to be utilized for the simultaneous analysis of changes in neurons and astrocytes in healthy and diseased brains. - Highlights: • We develop a method for the specific fluorescent labeling of neurons and astrocytes. • Neuron-specific labeling is achieved using Scg10 and synapsin promoters. • Astrocyte-specific labeling is generated using the minimal GFAP promoter. • Nuclear localization of fluorescent proteins is achieved with histone 2B protein.« less

Development of Defective and Persistent Sendai Virus Vector

PubMed Central

Nishimura, Ken; Sano, Masayuki; Ohtaka, Manami; Furuta, Birei; Umemura, Yoko; Nakajima, Yoshiro; Ikehara, Yuzuru; Kobayashi, Toshihiro; Segawa, Hiroaki; Takayasu, Satoko; Sato, Hideyuki; Motomura, Kaori; Uchida, Eriko; Kanayasu-Toyoda, Toshie; Asashima, Makoto; Nakauchi, Hiromitsu; Yamaguchi, Teruhide; Nakanishi, Mahito

2011-01-01

The ectopic expression of transcription factors can reprogram differentiated tissue cells into induced pluripotent stem cells. However, this is a slow and inefficient process, depending on the simultaneous delivery of multiple genes encoding essential reprogramming factors and on their sustained expression in target cells. Moreover, once cell reprogramming is accomplished, these exogenous reprogramming factors should be replaced with their endogenous counterparts for establishing autoregulated pluripotency. Complete and designed removal of the exogenous genes from the reprogrammed cells would be an ideal option for satisfying this latter requisite as well as for minimizing the risk of malignant cell transformation. However, no single gene delivery/expression system has ever been equipped with these contradictory characteristics. Here we report the development of a novel replication-defective and persistent Sendai virus (SeVdp) vector based on a noncytopathic variant virus, which fulfills all of these requirements for cell reprogramming. The SeVdp vector could accommodate up to four exogenous genes, deliver them efficiently into various mammalian cells (including primary tissue cells and human hematopoietic stem cells) and express them stably in the cytoplasm at a prefixed balance. Furthermore, interfering with viral transcription/replication using siRNA could erase the genomic RNA of SeVdp vector from the target cells quickly and thoroughly. A SeVdp vector installed with Oct4/Sox2/Klf4/c-Myc could reprogram mouse primary fibroblasts quite efficiently; ∼1% of the cells were reprogrammed to Nanog-positive induced pluripotent stem cells without chromosomal gene integration. Thus, this SeVdp vector has potential as a tool for advanced cell reprogramming and for stem cell research. PMID:21138846

Ares I Static Tests Design

NASA Technical Reports Server (NTRS)

Carson, William; Lindemuth, Kathleen; Mich, John; White, K. Preston; Parker, Peter A.

2009-01-01

Probabilistic engineering design enhances safety and reduces costs by incorporating risk assessment directly into the design process. In this paper, we assess the format of the quantitative metrics for the vehicle which will replace the Space Shuttle, the Ares I rocket. Specifically, we address the metrics for in-flight measurement error in the vector position of the motor nozzle, dictated by limits on guidance, navigation, and control systems. Analyses include the propagation of error from measured to derived parameters, the time-series of dwell points for the duty cycle during static tests, and commanded versus achieved yaw angle during tests. Based on these analyses, we recommend a probabilistic template for specifying the maximum error in angular displacement and radial offset for the nozzle-position vector. Criteria for evaluating individual tests and risky decisions also are developed.

[Gene therapy for the treatment of inborn errors of metabolism].

PubMed

Pérez-López, Jordi

2014-06-16

Due to the enzymatic defect in inborn errors of metabolism, there is a blockage in the metabolic pathways and an accumulation of toxic metabolites. Currently available therapies include dietary restriction, empowering of alternative metabolic pathways, and the replacement of the deficient enzyme by cell transplantation, liver transplantation or administration of the purified enzyme. Gene therapy, using the transfer in the body of the correct copy of the altered gene by a vector, is emerging as a promising treatment. However, the difficulty of vectors currently used to cross the blood brain barrier, the immune response, the cellular toxicity and potential oncogenesis are some limitations that could greatly limit its potential clinical application in human beings. Copyright © 2013 Elsevier España, S.L. All rights reserved.

A hybrid quantum eraser scheme for characterization of free-space and fiber communication channels

NASA Astrophysics Data System (ADS)

Nape, Isaac; Kyeremah, Charlotte; Vallés, Adam; Rosales-Guzmán, Carmelo; Buah-Bassuah, Paul K.; Forbes, Andrew

2018-02-01

We demonstrate a simple projective measurement based on the quantum eraser concept that can be used to characterize the disturbances of any communication channel. Quantum erasers are commonly implemented as spatially separated path interferometric schemes. Here we exploit the advantages of redefining the which-path information in terms of spatial modes, replacing physical paths with abstract paths of orbital angular momentum (OAM). Remarkably, vector modes (natural modes of free-space and fiber) have a non-separable feature of spin-orbit coupled states, equivalent to the description of two independently marked paths. We explore the effects of fiber perturbations by probing a step-index optical fiber channel with a vector mode, relevant to high-order spatial mode encoding of information for ultra-fast fiber communications.

Sharp comparison theorems for the Klein-Gordon equation in d dimensions

NASA Astrophysics Data System (ADS)

Hall, Richard L.; Zorin, Petr

2016-06-01

We establish sharp (or ’refined’) comparison theorems for the Klein-Gordon equation. We show that the condition Va ≤ Vb, which leads to Ea ≤ Eb, can be replaced by the weaker assumption Ua ≤ Ub which still implies the spectral ordering Ea ≤ Eb. In the simplest case, for d = 1, Ui(x) =∫0xV i(t)dt, i = a or b and for d > 1, Ui(r) =∫0rV i(t)td-1dt, i = a or b. We also consider sharp comparison theorems in the presence of a scalar potential S (a ‘variable mass’) in addition to the vector term V (the time component of a four-vector). The theorems are illustrated by a variety of explicit detailed examples.

Initial review of rapid moisture measurement for roadway base and subgrade.

DOT National Transportation Integrated Search

2013-05-01

This project searched available moisture-measurement technologies using gravimetric, dielectric, electrical conductivity, and suction-based methods, as potential replacements for the nuclear gauge to provide rapid moisture measurement on field constr...

Fault Tree Analysis for an Inspection Robot in a Nuclear Power Plant

NASA Astrophysics Data System (ADS)

Ferguson, Thomas A.; Lu, Lixuan

2017-09-01

The life extension of current nuclear reactors has led to an increasing demand on inspection and maintenance of critical reactor components that are too expensive to replace. To reduce the exposure dosage to workers, robotics have become an attractive alternative as a preventative safety tool in nuclear power plants. It is crucial to understand the reliability of these robots in order to increase the veracity and confidence of their results. This study presents the Fault Tree (FT) analysis to a coolant outlet piper snake-arm inspection robot in a nuclear power plant. Fault trees were constructed for a qualitative analysis to determine the reliability of the robot. Insight on the applicability of fault tree methods for inspection robotics in the nuclear industry is gained through this investigation.

Boom or Bust: Britain’s Nuclear Deterrent Beyond 2025

DTIC Science & Technology

2012-04-26

Labour government of the day, spelt out a commitment to replace Britain’s Submarine Launched Ballistic Missile (SLBM) nuclear deterrent with a similar...global and national economies; banks collapsed, markets went into turmoil and the extent of government debts and borrowing was laid bare. The fiscal...disarmament. In 2010 Nick Clegg stated that: "Neither Labour nor the Conservatives are prepared to question spending tens of billions of pounds on a like

Nuclear Weapons: The Reliable Replacement Warhead Program

DTIC Science & Technology

2006-03-09

time to age. The United States introduced generation after generation of new nuclear “delivery vehicles ” — bombers, missile submarines, and land-based...missile’s carrying capacity divided among fewer warheads, each CRS-13 29 Ballistic missiles carry warheads inside reentry vehicles (RVs). An RV is a...streamlined shell that protects its warhead from the intense heat and other stresses of reentering the atmosphere at high speed. RVs are designed to carry a

Nuclear Weapons: The Reliable Replacement Warhead Program

DTIC Science & Technology

2005-06-03

inside reentry vehicles (RVs). An RV is a streamlined shell that protects its warhead from the intense heat and other stresses of reentering the...generation after generation of new nuclear “delivery vehicles ” — bombers, missile submarines, and land-based missiles — each of which would typically...reentry vehicle and the missile’s guidance. The ability to conduct small strikes depends on command and control. There may be various ways to reduce

Integrating Chemical Biological, Radiologic, and Nuclear (CBRN) Protocols Into TCCC Introduction of a Conceptual Model - TCCC + CBRN = (MARCHE)2.

PubMed

DeFeo, Devin R; Givens, Melissa L

The authors would like to introduce TCCC [Tactical Combat Casualty Care] + CBRN [chemical, biological, radiological, and nuclear] = (MARCHE)2 as a conceptual model to frame the response to CBRN events. This model is not intended to replace existing and well-established literature on CBRNE events but rather to serve as a response tool that is an adjunct to agent specific resources. 2018.

Experimental assessment of precision and accuracy of radiostereometric analysis for the determination of polyethylene wear in a total hip replacement model.

PubMed

Bragdon, Charles R; Malchau, Henrik; Yuan, Xunhua; Perinchief, Rebecca; Kärrholm, Johan; Börlin, Niclas; Estok, Daniel M; Harris, William H

2002-07-01

The purpose of this study was to develop and test a phantom model based on actual total hip replacement (THR) components to simulate the true penetration of the femoral head resulting from polyethylene wear. This model was used to study both the accuracy and the precision of radiostereometric analysis, RSA, in measuring wear. We also used this model to evaluate optimum tantalum bead configuration for this particular cup design when used in a clinical setting. A physical model of a total hip replacement (a phantom) was constructed which could simulate progressive, three-dimensional (3-D) penetration of the femoral head into the polyethylene component of a THR. Using a coordinate measuring machine (CMM) the positioning of the femoral head using the phantom was measured to be accurate to within 7 microm. The accuracy and precision of an RSA analysis system was determined from five repeat examinations of the phantom using various experimental set-ups of the phantom. The accuracy of the radiostereometric analysis, in this optimal experimental set-up studied was 33 microm for the medial direction, 22 microm for the superior direction, 86 microm for the posterior direction and 55 microm for the resultant 3-D vector length. The corresponding precision at the 95% confidence interval of the test results for repositioning the phantom five times, measured 8.4 microm for the medial direction, 5.5 microm for the superior direction, 16.0 microm for the posterior direction, and 13.5 microm for the resultant 3-D vector length. This in vitro model is proposed as a useful tool for developing a standard for the evaluation of radiostereometric and other radiographic methods used to measure in vivo wear.

Rotating-frame gradient fields for magnetic resonance imaging and nuclear magnetic resonance in low fields

DOEpatents

Bouchard, Louis-Serge; Pines, Alexander; Demas, Vasiliki

2014-01-21

A system and method for Fourier encoding a nuclear magnetic resonance (NMR) signal is disclosed. A static magnetic field B.sub.0 is provided along a first direction. An NMR signal from the sample is Fourier encoded by applying a rotating-frame gradient field B.sub.G superimposed on the B.sub.0, where the B.sub.G comprises a vector component rotating in a plane perpendicular to the first direction at an angular frequency .omega.in a laboratory frame. The Fourier-encoded NMR signal is detected.

An Expert System for Automating Nuclear Strike Aircraft Replacement, Aircraft Beddown, and Logistics Movement for the Theater Warfare Exercise.

DTIC Science & Technology

1989-12-01

that can be easily understood. (9) Parallelism. Several system components may need to execute in parallel. For example, the processing of sensor data...knowledge base are not accessible for processing by the database. Also in the likely case that the expert system poses a series of related queries, the...hiharken nxpfilcs’Iog - Knowledge base for the automation of loCgistics rr-ovenet T’he Ii rectorY containing the strike aircraft replacement knowledge base

Physics and the New Games -- or Pretend You're an Atom.

ERIC Educational Resources Information Center

Edge, Ronald D.

1982-01-01

Describes several games in which physics principles are demonstrated using students. These include Pirates Treasure Game (vectors), Three-Meter Dash (kinematics), Knee-Bend Game (energy and power), Wave Game, Reaction Kinematics, Statics-People Pyramids, and games demonstrating nuclear reactions, collisions, electrons in a wire, close packing, and…

The Gpn3 Q279* cancer-associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting.

PubMed

Barbosa-Camacho, Angel A; Méndez-Hernández, Lucía E; Lara-Chacón, Bárbara; Peña-Gómez, Sonia G; Romero, Violeta; González-González, Rogelio; Guerra-Moreno, José A; Robledo-Rivera, Angélica Y; Sánchez-Olea, Roberto; Calera, Mónica R

2017-11-01

Gpn3 is required for RNA polymerase II (RNAPII) nuclear targeting. Here, we investigated the effect of a cancer-associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi-resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity were markedly decreased in cells expressing only Gpn3R Q279*. Wild-type Gpn3R localized to the cytoplasm but a fraction of Gpn3R Q279* entered the cell nucleus and inhibited Gpn1-EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*-expressing cells required a PDZ-binding motif generated by the Q279* mutation. We conclude that an acquired PDZ-binding motif in Gpn3 Q279* caused Gpn3 nuclear entry, and inhibited Gpn1 nuclear export and Gpn3-mediated RNAPII nuclear targeting. © 2017 Federation of European Biochemical Societies.

An Energy Scaled and Expanded Vector-Based Forwarding Scheme for Industrial Underwater Acoustic Sensor Networks with Sink Mobility.

PubMed

Wadud, Zahid; Hussain, Sajjad; Javaid, Nadeem; Bouk, Safdar Hussain; Alrajeh, Nabil; Alabed, Mohamad Souheil; Guizani, Nadra

2017-09-30

Industrial Underwater Acoustic Sensor Networks (IUASNs) come with intrinsic challenges like long propagation delay, small bandwidth, large energy consumption, three-dimensional deployment, and high deployment and battery replacement cost. Any routing strategy proposed for IUASN must take into account these constraints. The vector based forwarding schemes in literature forward data packets to sink using holding time and location information of the sender, forwarder, and sink nodes. Holding time suppresses data broadcasts; however, it fails to keep energy and delay fairness in the network. To achieve this, we propose an Energy Scaled and Expanded Vector-Based Forwarding (ESEVBF) scheme. ESEVBF uses the residual energy of the node to scale and vector pipeline distance ratio to expand the holding time. Resulting scaled and expanded holding time of all forwarding nodes has a significant difference to avoid multiple forwarding, which reduces energy consumption and energy balancing in the network. If a node has a minimum holding time among its neighbors, it shrinks the holding time and quickly forwards the data packets upstream. The performance of ESEVBF is analyzed through in network scenario with and without node mobility to ensure its effectiveness. Simulation results show that ESEVBF has low energy consumption, reduces forwarded data copies, and less end-to-end delay.

Tyrosine-phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong Li; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL; Genetics Institute, University of Florida College of Medicine, Gainesville, FL

2008-11-25

We have documented that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects intracellular trafficking and transduction efficiency of recombinant adeno-associated virus 2 (AAV2) vectors. Specifically, inhibition of EGFR-PTK signaling leads to decreased ubiquitination of AAV2 capsid proteins, which in turn, facilitates viral nuclear transport by limiting proteasome-mediated degradation of AAV2 vectors. In the present studies, we observed that AAV capsids can indeed be phosphorylated at tyrosine residues by EGFR-PTK in in vitro phosphorylation assays and that phosphorylated AAV capsids retain their structural integrity. However, although phosphorylated AAV vectors enter cells as efficiently as their unphosphorylated counterparts, theirmore » transduction efficiency is significantly reduced. This reduction is not due to impaired viral second-strand DNA synthesis since transduction efficiency of both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors is decreased by {approx} 68% and {approx} 74%, respectively. We also observed that intracellular trafficking of tyrosine-phosphorylated AAV vectors from cytoplasm to nucleus is significantly decreased, which results from ubiquitination of AAV capsids followed by proteasome-mediated degradation, although downstream consequences of capsid ubiquitination may also be affected by tyrosine-phosphorylation. These studies provide new insights into the role of tyrosine-phosphorylation of AAV capsids in various steps in the virus life cycle, which has implications in the optimal use of recombinant AAV vectors in human gene therapy.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tenney, Rebeca M.; Bell, Christie L.; Wilson, James M., E-mail: wilsonjm@mail.med.upenn.edu

Adeno-associated virus serotype 8 (AAV8) is a promising vector for liver-directed gene therapy. Although efficient uncoating of viral capsids has been implicated in AAV8's robust liver transduction, much about the biology of AAV8 hepatotropism remains unclear. Our study investigated the structural basis of AAV8 liver transduction efficiency by constructing chimeric vector capsids containing sequences derived from AAV8 and AAV2 – a highly homologous yet poorly hepatotropic serotype. Engineered vectors containing capsid variable regions (VR) VII and IX from AAV8 in an AAV2 backbone mediated near AAV8-like transduction in mouse liver, with higher numbers of chimeric genomes detected in whole livermore » cells and isolated nuclei. Interestingly, chimeric capsids within liver nuclei also uncoated similarly to AAV8 by 6 weeks after administration, in contrast with AAV2, of which a significantly smaller proportion were uncoated. This study links specific AAV capsid regions to the transduction ability of a clinically relevant AAV serotype. - Highlights: • We construct chimeric vectors to identify determinants of AAV8 liver transduction. • An AAV2-based vector with 17 AAV8 residues exhibited high liver transduction in mice. • This vector also surpassed AAV2 in cell entry, nuclear entry and onset of expression. • Most chimeric vector particles were uncoated at 6 weeks, like AAV8 and unlike AAV2. • Chimera retained heparin binding and was antigenically distinct from AAV2 and AAV8.« less

New limit on possible long-range parity-odd interactions of the neutron from neutron-spin rotation in liquid 4He.

PubMed

Yan, H; Snow, W M

2013-02-22

Various theories beyond the standard model predict new particles with masses in the sub-eV range with very weak couplings to ordinary matter. A parity-odd interaction between polarized nucleons and unpolarized matter proportional to g(V)g(A)s · p is one such possibility, where s[over →] and p[over →] are the spin and the momentum of the polarized nucleon, and g(V) and g(A) are the vector and axial vector couplings of an interaction induced by the exchange of a new light vector boson. We report a new experimental upper bound on such possible long-range parity-odd interactions of the neutron with nucleons and electrons from a recent search for parity violation in neutron spin rotation in liquid ^{4}He. Our constraint on the product of vector and axial vector couplings of a possible new light vector boson is g(V) g(A)(n) ≤ 10(-32) for an interaction range of 1 m. This upper bound is more than 7 orders of magnitude more stringent than the existing laboratory constraints for interaction ranges below 1 m, corresponding to a broad range of vector boson masses above 10(-6) eV. More sensitive searches for a g(V) g(A)(n) coupling could be performed using neutron spin rotation measurements in heavy nuclei or through analysis of experiments conducted to search for nucleon-nucleon weak interactions and nuclear anapole moments.

Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila; a theoretical exploration of Medea-dependent population suppression.

PubMed

Akbari, Omar S; Chen, Chun-Hong; Marshall, John M; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A

2014-12-19

Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.

PABPN1 gene therapy for oculopharyngeal muscular dystrophy

PubMed Central

Malerba, A.; Klein, P.; Bachtarzi, H.; Jarmin, S. A.; Cordova, G.; Ferry, A.; Strings, V.; Espinoza, M. Polay; Mamchaoui, K.; Blumen, S. C.; St Guily, J. Lacau; Mouly, V.; Graham, M.; Butler-Browne, G.; Suhy, D. A.; Trollet, C.; Dickson, G.

2017-01-01

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment. PMID:28361972

[Nuclear transfer and therapeutic cloning].

PubMed

Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

2005-03-01

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Fast Breeder Reactors in Sweden: Vision and Reality.

PubMed

Fjaestad, Maja

2015-01-01

The fast breeder is a type of nuclear reactor that aroused much attention in the 1950s and '60s. Its ability to produce more nuclear fuel than it consumes offered promises of cheap and reliable energy. Sweden had advanced plans for a nuclear breeder program, but canceled them in the middle of the 1970s with the rise of nuclear skepticism. The article investigates the nuclear breeder as a technological vision. The nuclear breeder reactor is an example of a technological future that did not meet its industrial expectations. But that does not change the fact that the breeder was an influential technology. Decisions about the contemporary reactors were taken with the idea that in a foreseeable future they would be replaced with the efficient breeder. The article argues that general themes in the history of the breeder reactor can deepen our understanding of the mechanisms behind technological change.

TEMPORARY REMOVAL: Non-viral vectors based on cationic niosomes as efficient gene delivery vehicles to central nervous system cells into the brain.

PubMed

Mashal, Mohamed; Attia, Noha; Soto-Sánchez, Cristina; Martínez-Navarrete, Gema; Fernández, Eduardo; Puras, Gustavo; Pedraz, José Luis

2018-05-23

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal. Copyright © 2018.

Balancing Chemical Reactions With Matrix Methods and Computer Assistance. Applications of Linear Algebra to Chemistry. Modules and Monographs in Undergraduate Mathematics and Its Applications Project. UMAP Unit 339.

ERIC Educational Resources Information Center

Grimaldi, Ralph P.

This material was developed to provide an application of matrix mathematics in chemistry, and to show the concepts of linear independence and dependence in vector spaces of dimensions greater than three in a concrete setting. The techniques presented are not intended to be considered as replacements for such chemical methods as oxidation-reduction…

Reversible Oxidation of a Conserved Methionine in the Nuclear Export Sequence Determines Subcellular Distribution and Activity of the Fungal Nitrate Regulator NirA.

PubMed

Gallmetzer, Andreas; Silvestrini, Lucia; Schinko, Thorsten; Gesslbauer, Bernd; Hortschansky, Peter; Dattenböck, Christoph; Muro-Pastor, María Isabel; Kungl, Andreas; Brakhage, Axel A; Scazzocchio, Claudio; Strauss, Joseph

2015-07-01

The assimilation of nitrate, a most important soil nitrogen source, is tightly regulated in microorganisms and plants. In Aspergillus nidulans, during the transcriptional activation process of nitrate assimilatory genes, the interaction between the pathway-specific transcription factor NirA and the exportin KapK/CRM1 is disrupted, and this leads to rapid nuclear accumulation and transcriptional activity of NirA. In this work by mass spectrometry, we found that in the absence of nitrate, when NirA is inactive and predominantly cytosolic, methionine 169 in the nuclear export sequence (NES) is oxidized to methionine sulfoxide (Metox169). This oxidation depends on FmoB, a flavin-containing monooxygenase which in vitro uses methionine and cysteine, but not glutathione, as oxidation substrates. The function of FmoB cannot be replaced by alternative Fmo proteins present in A. nidulans. Exposure of A. nidulans cells to nitrate led to rapid reduction of NirA-Metox169 to Met169; this reduction being independent from thioredoxin and classical methionine sulfoxide reductases. Replacement of Met169 by isoleucine, a sterically similar but not oxidizable residue, led to partial loss of NirA activity and insensitivity to FmoB-mediated nuclear export. In contrast, replacement of Met169 by alanine transformed the protein into a permanently nuclear and active transcription factor. Co-immunoprecipitation analysis of NirA-KapK interactions and subcellular localization studies of NirA mutants lacking different parts of the protein provided evidence that Met169 oxidation leads to a change in NirA conformation. Based on these results we propose that in the presence of nitrate the activation domain is exposed, but the NES is masked by a central portion of the protein (termed nitrate responsive domain, NiRD), thus restricting active NirA molecules to the nucleus. In the absence of nitrate, Met169 in the NES is oxidized by an FmoB-dependent process leading to loss of protection by the NiRD, NES exposure, and relocation of the inactive NirA to the cytosol.

Mechanisms of double-strand-break repair during gene targeting in mammalian cells.

PubMed Central

Ng, P; Baker, M D

1999-01-01

In the present study, the mechanism of double-strand-break (DSB) repair during gene targeting at the chromosomal immunoglobulin mu-locus in a murine hybridoma was examined. The gene-targeting assay utilized specially designed insertion vectors genetically marked in the region of homology to the chromosomal mu-locus by six diagnostic restriction enzyme site markers. The restriction enzyme markers permitted the contribution of vector-borne and chromosomal mu-sequences in the recombinant product to be determined. The use of the insertion vectors in conjunction with a plating procedure in which individual integrative homologous recombination events were retained for analysis revealed several important features about the mammalian DSB repair process:The presence of the markers within the region of shared homology did not affect the efficiency of gene targeting.In the majority of recombinants, the vector-borne marker proximal to the DSB was absent, being replaced with the corresponding chromosomal restriction enzyme site. This result is consistent with either formation and repair of a vector-borne gap or an "end" bias in mismatch repair of heteroduplex DNA (hDNA) that favored the chromosomal sequence. Formation of hDNA was frequently associated with gene targeting and, in most cases, began approximately 645 bp from the DSB and could encompass a distance of at least 1469 bp.The hDNA was efficiently repaired prior to DNA replication.The repair of adjacent mismatches in hDNA occurred predominantly on the same strand, suggesting the involvement of a long-patch repair mechanism. PMID:10049929

Conditions for success of engineered underdominance gene drive systems.

PubMed

Edgington, Matthew P; Alphey, Luke S

2017-10-07

Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually suppressing lethals. In such a system two genetic constructs are introduced, each possessing a lethal element and a suppressor of the lethal at the other locus. Specifically, we formulate and analyse a population genetics model of this system to assess when different combinations of release strategies (i.e. single or multiple releases of both sexes or males only) and genetic systems (i.e. bisex lethal or female-specific lethal elements and different strengths of suppressors) will give population replacement or fail to do so. We anticipate that results presented here will inform the future design of engineered underdominance gene drive systems as well as providing a point of reference regarding release strategies for those looking to test such a system. Our discussion is framed in the context of genetic control of insect vectors of disease. One of several serious threats in this context are Aedes aegypti mosquitoes as they are the primary vectors of dengue viruses. However, results are also applicable to Ae. aegypti as vectors of Zika, yellow fever and chikungunya viruses and also to the control of a number of other insect species and thereby of insect-vectored pathogens. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Using Phage Display to Create Recombinant Antibodies.

PubMed

Dasch, James R; Dasch, Amy L

2017-09-01

A variety of phage display technologies have been developed since the approach was first described for antibodies. The most widely used approaches incorporate antibody sequences into the minor coat protein pIII of the nonlytic filamentous phage fd or M13. Libraries of variable gene sequences, encoding either scFv or Fab fragments, are made by incorporating sequences into phagemid vectors. The phagemid is packaged into phage particles with the assistance of a helper phage to produce the antibody display phage. This protocol describes a method for creating a phagemid library. The multiple cloning site (MCS) of the pBluescript KS(-) phagemid vector is replaced by digestion with the restriction enzyme BssHII, followed by the insertion of four overlapping oligonucleotides to create a new MCS within the vector. Next, the 3' portion of gene III (from M13mp18) is amplified and combined with an antibody sequence using overlap extension PCR. This product is inserted into the phagemid vector to create pPDS. Two helper plasmids are also created from the modified pBluescript vector: pLINK provides the linker between the heavy and light chains, and pFABC provides the CH1 domain of the heavy chain. An antibody cDNA library is constructed from the RNA of interest and ligated into pPDS. The phagemid library is electroporated into Escherichia coli cells along with the VCS-M13 helper phage. © 2017 Cold Spring Harbor Laboratory Press.

Motility and infectivity of Plasmodium berghei sporozoites expressing avian Plasmodium gallinaceum circumsporozoite protein.

PubMed

Tewari, Rita; Rathore, Dharmendar; Crisanti, Andrea

2005-05-01

Avian and rodent malaria sporozoites selectively invade different vertebrate cell types, namely macrophages and hepatocytes, and develop in distantly related vector species. To investigate the role of the circumsporozoite (CS) protein in determining parasite survival in different vector species and vertebrate host cell types, we replaced the endogenous CS protein gene of the rodent malaria parasite Plasmodium berghei with that of the avian parasite P. gallinaceum and control rodent parasite P. yoelii. In anopheline mosquitoes, P. berghei parasites carrying P. gallinaceum and rodent parasite P. yoelii CS protein gene developed into oocysts and sporozoites. Plasmodium gallinaceum CS expressing transgenic sporozoites, although motile, failed to invade mosquito salivary glands and to infect mice, which suggests that motility alone is not sufficient for invasion. Notably, a percentage of infected Anopheles stephensi mosquitoes showed melanotic encapsulation of late stage oocysts. This was not observed in control infections or in A. gambiae infections. These findings shed new light on the role of the CS protein in the interaction of the parasite with both the mosquito vector and the rodent host.

Exact Descriptions of General Relativity Derived from Newtonian Mechanics within Curved Geometries

NASA Astrophysics Data System (ADS)

Savickas, David

2015-04-01

General relativity and Newtonian mechanics are shown to be exactly related when Newton's second law is written in a curved geometry by using the physical components of a vector as is defined in tensor calculus. By replacing length within the momentum's velocity by the vector metric in a curved geometry the second law can then be shown to be exactly identical to the geodesic equation of motion occurring in general relativity. When time's vector direction is constant, as similarly occurs in Newtonian mechanics, this equation can be reduced to a curved three-dimensional equation of motion that yields the the Schwarzschild equations of motion for an isolated particle. They can be used to describe gravitational behavior for any array of masses for which the Newtonian gravitational potential is known, and is shown to describe a mass particle's behavior in the gravitational field of a thin mass-rod. This use of Newton's laws allows relativistic behavior to be described in a physically comprehensible manner. D. Savickas, Int. J. Mod. Phys. D 23 1430018, (2014).

Reduced Stress Tensor and Dissipation and the Transport of Lamb Vector

NASA Technical Reports Server (NTRS)

Wu, Jie-Zhi; Zhou, Ye; Wu, Jian-Ming

1996-01-01

We develop a methodology to ensure that the stress tensor, regardless of its number of independent components, can be reduced to an exactly equivalent one which has the same number of independent components as the surface force. It is applicable to the momentum balance if the shear viscosity is constant. A direct application of this method to the energy balance also leads to a reduction of the dissipation rate of kinetic energy. Following this procedure, significant saving in analysis and computation may be achieved. For turbulent flows, this strategy immediately implies that a given Reynolds stress model can always be replaced by a reduced one before putting it into computation. Furthermore, we show how the modeling of Reynolds stress tensor can be reduced to that of the mean turbulent Lamb vector alone, which is much simpler. As a first step of this alternative modeling development, we derive the governing equations for the Lamb vector and its square. These equations form a basis of new second-order closure schemes and, we believe, should be favorably compared to that of traditional Reynolds stress transport equation.

Exclusive J / Ψ vector-meson production in high-energy nuclear collisions

NASA Astrophysics Data System (ADS)

Ramnath, A.; Weigert, H.; Hamilton, A.

2014-12-01

We illustrate the first steps in a cross-section determination for exclusive J / Ψ production in ultra-peripheral heavy ion collisions from two viewpoints. First, the setup for a theoretical calculation is done in the context of the Colour Glass Condensate effective field theory, using the Gaussian truncation to parametrise rapidity-averaged n-point correlators. Secondly, a feasibility study is carried out using STARlight Monte Carlo simulations to predict how many exclusive J / Ψ vector-mesons might be expected in ATLAS at the LHC. In a data set corresponding to 160 μb-1 of total integrated luminosity, about 150 candidate events are expected.

Consequences of covariant kaon dynamics in heavy ion collisions

NASA Astrophysics Data System (ADS)

Fuchs, C.; Kosov, D. S.; Faessler, Amand; Wang, Z. S.; Waindzoch, T.

1998-08-01

The influence of the chiral mean field on the kaon dynamics in heavy ion reactions is investigated. Inside the nuclear medium the kaons are described as dressed quasi-particles carrying effective masses and momenta. A momentum dependent part of the interaction which resembles a Lorentz force originates from spatial components of the vector field and provides an important contribution to the in-medium kaon dynamics. This contribution is found to counterbalance the influence of the vector potential on the K+ in-plane flow to a strong extent. Thus it appears to be difficult to restrict the in-medium potential from the analysis of the corresponding transverse flow.

A physics based method for combining multiple anatomy models with application to medical simulation.

PubMed

Zhu, Yanong; Magee, Derek; Ratnalingam, Rishya; Kessel, David

2009-01-01

We present a physics based approach to the construction of anatomy models by combining components from different sources; different image modalities, protocols, and patients. Given an initial anatomy, a mass-spring model is generated which mimics the physical properties of the solid anatomy components. This helps maintain valid spatial relationships between the components, as well as the validity of their shapes. Combination can be either replacing/modifying an existing component, or inserting a new component. The external forces that deform the model components to fit the new shape are estimated from Gradient Vector Flow and Distance Transform maps. We demonstrate the applicability and validity of the described approach in the area of medical simulation, by showing the processes of non-rigid surface alignment, component replacement, and component insertion.

Precomputed state dependent digital control of a nuclear rocket engine

NASA Technical Reports Server (NTRS)

Johnson, M. R.

1972-01-01

A control method applicable to multiple-input multiple-output nonlinear time-invariant systems in which desired behavior can be expressed explicitly as a trajectory in system state space is developed. The precomputed state dependent control method is basically a synthesis technique in which a suboptimal control law is developed off-line, prior to system operation. This law is obtained by conducting searches at a finite number of points in state space, in the vicinity of some desired trajectory, to obtain a set of constant control vectors which tend to return the system to the desired trajectory. These vectors are used to evaluate the unknown coefficients in a control law having an assumed hyperellipsoidal form. The resulting coefficients constitute the heart of the controller and are used in the on-line computation of control vectors. Two examples of PSDC are given prior to the more detailed description of the NERVA control system development.

Passive cooling system for top entry liquid metal cooled nuclear reactors

DOEpatents

Boardman, Charles E.; Hunsbedt, Anstein; Hui, Marvin M.

1992-01-01

A liquid metal cooled nuclear fission reactor plant having a top entry loop joined satellite assembly with a passive auxiliary safety cooling system for removing residual heat resulting from fuel decay during shutdown, or heat produced during a mishap. This satellite type reactor plant is enhanced by a backup or secondary passive safety cooling system which augments the primary passive auxiliary cooling system when in operation, and replaces the primary cooling system when rendered inoperative.

The New Triad. Diffusion, Illusion, and Confusion in the Nuclear Mission

DTIC Science & Technology

2016-09-01

The confusion engendered suggests that it was not sufficiently vetted in the “user community ” that would have to live with it, and that includes...capabilities. This New Triad, depicted in Figure  S-1, was meant to replace the traditional Triad of intercontinental ballistic missiles, submarine -launched...Figure S-1. The New Triad We find the New Triad to be an impediment to clear thinking, communication , and consensus regarding nuclear issues. Its fatal

Velocimetry Overview for visitors from the DOD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briggs, Matthew E.; Holtkamp, David Bruce

2016-08-19

We are in the midst of a transformative period in which technological advances are making fundamental changes in the measurement techniques that form the backbone of nuclear weapon certification. Optical velocimetry has replaced electrical shorting pins in “Hydrotests,” which measure the dynamic implosion process. This advance has revolutionized nuclear weapons certification during the last 5 years. We can now measure the implosion process that drives a nuclear detonation with many orders of magnitude more resolution in both space and time than was possible just 10 years ago. It has been compared to going from Morse Code to HDTV, resulting inmore » a dozen or more improvements in models of these weapons. These Hydrotests are carried out at LANL, LLNL and the NNSS, with the later holding the important role of allowing us to test with nuclear materials, in sub-critical configurations (i.e., no yield.) Each of these institutions has largely replaced pins with hundreds of channels of optical velocimetry. Velocimetry is non-contact and is used simultaneously with the X-ray capability of these facilities. The U1-a facility at NNSS pioneered this approach in the Gemini series in 2012, and continues to lead, both in channel count and technological advances. Close cooperation among LANL, LLNL and NSTec in these advances serves the complex by leveraging capabilities across sites and accelerating the pace of technical improvements.« less

78 FR 79643 - Energy Conservation Program for Consumer Products: Landmark Legal Foundation; Petition for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... Group'' or ``IWG'') was formed to allow agencies to incorporate the monetized social benefits of... that all fossil-fueled power plants should be replaced with nuclear power plants and DOE should be...

A Review of Selected Models.

DTIC Science & Technology

1982-02-01

evacuation, essential maintenance, transportation, decontamination, and field services (i.e., replacements, graves registration, finance , etc.). 2...such logic through the tactical decision rules input by the user. With such a device, the UNICORN nuclear weapons 78 -T -- : I-, -- r, Pow- allocation

Transformation of Chloroplast Ribosomal RNA Genes in Chlamydomonas: Molecular and Genetic Characterization of Integration Events

PubMed Central

Newman, S. M.; Boynton, J. E.; Gillham, N. W.; Randolph-Anderson, B. L.; Johnson, A. M.; Harris, E. H.

1990-01-01

Transformation of chloroplast ribosomal RNA (rRNA) genes in Chlamydomonas has been achieved by the biolistic process using cloned chloroplast DNA fragments carrying mutations that confer antibiotic resistance. The sites of exchange employed during the integration of the donor DNA into the recipient genome have been localized using a combination of antibiotic resistance mutations in the 16S and 23S rRNA genes and restriction fragment length polymorphisms that flank these genes. Complete or nearly complete replacement of a region of the chloroplast genome in the recipient cell by the corresponding sequence from the donor plasmid was the most common integration event. Exchange events between the homologous donor and recipient sequences occurred preferentially near the vector:insert junctions. Insertion of the donor rRNA genes and flanking sequences into one inverted repeat of the recipient genome was followed by intramolecular copy correction so that both copies of the inverted repeat acquired identical sequences. Increased frequencies of rRNA gene transformants were achieved by reducing the copy number of the chloroplast genome in the recipient cells and by decreasing the heterology between donor and recipient DNA sequences flanking the selectable markers. In addition to producing bona fide chloroplast rRNA transformants, the biolistic process induced mutants resistant to low levels of streptomycin, typical of nuclear mutations in Chlamydomonas. PMID:1981764

Methodology and issues of integral experiments selection for nuclear data validation

NASA Astrophysics Data System (ADS)

Tatiana, Ivanova; Ivanov, Evgeny; Hill, Ian

2017-09-01

Nuclear data validation involves a large suite of Integral Experiments (IEs) for criticality, reactor physics and dosimetry applications. [1] Often benchmarks are taken from international Handbooks. [2, 3] Depending on the application, IEs have different degrees of usefulness in validation, and usually the use of a single benchmark is not advised; indeed, it may lead to erroneous interpretation and results. [1] This work aims at quantifying the importance of benchmarks used in application dependent cross section validation. The approach is based on well-known General Linear Least Squared Method (GLLSM) extended to establish biases and uncertainties for given cross sections (within a given energy interval). The statistical treatment results in a vector of weighting factors for the integral benchmarks. These factors characterize the value added by a benchmark for nuclear data validation for the given application. The methodology is illustrated by one example, selecting benchmarks for 239Pu cross section validation. The studies were performed in the framework of Subgroup 39 (Methods and approaches to provide feedback from nuclear and covariance data adjustment for improvement of nuclear data files) established at the Working Party on International Nuclear Data Evaluation Cooperation (WPEC) of the Nuclear Science Committee under the Nuclear Energy Agency (NEA/OECD).

Improved efficacy of soluble human receptor activator of nuclear factor kappa B (RANK) fusion protein by site-directed mutagenesis.

PubMed

Son, Young Jun; Han, Jihye; Lee, Jae Yeon; Kim, HaHyung; Chun, Taehoon

2015-06-01

Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin (hRANK-Ig) has been considered as one of the therapeutic agents to treat osteoporosis or diseases associated with bone destruction by blocking the interaction between RANK and the receptor activator of nuclear factor kappa B ligand (RANKL). However, no scientific record showing critical amino acid residues within the structural interface between the human RANKL and RANK complex is yet available. In this study, we produced several mutants of hRANK-Ig by replacement of amino acid residue(s) and tested whether the mutants had increased binding affinity to human RANKL. Based on the results from flow cytometry and surface plasmon resonance analyses, the replacement of E(125) with D(125), or E(125) and C(127) with D(125) and F(127) within loop 3 of cysteine-rich domain 3 of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK-Ig. This result may provide the first example of improvement in the efficacy of hRANK-Ig by protein engineering and may give additional information to understand a more defined structural interface between hRANK and RANKL.

From nuclear power to coal power: Aerosol-induced health and radiative effects

NASA Astrophysics Data System (ADS)

Mielonen, Tero; Laakso, Anton; Karhunen, Anni; Kokkola, Harri; Partanen, Antti-Ilari; Korhonen, Hannele; Romakkaniemi, Sami; Lehtinen, Kari E. J.

2015-12-01

We have investigated what would be the climate and PM-induced air quality consequences if all nuclear reactors worldwide were closed down and replaced by coal combustion. In a way, this presents a "worst-case scenario" since less polluting energy sources are available. We studied simultaneously the radiative and health effects of coal power emissions using a global 3-D aerosol-climate model (ECHAM-HAMMOZ). This approach allowed us to estimate the effects of a major global energy production change from low carbon source to a high carbon one using detailed spatially resolved population density information. We included the radiative effects of both CO2 and PM2.5 but limited the study of health effects to PM2.5 only. Our results show that the replacement of nuclear power with coal power would have globally caused an average of 150,000 premature deaths per year during the period 2005-2009 with two thirds of them in Europe. For 37 years the aerosol emissions from the additional coal power plants would cool the climate but after that the accumulating CO2 emissions would accelerate the warming of the climate.

Status of nuclear Class 1 component requalification: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooper, W.E.

1986-12-01

Qualification relates to assurance of acceptability of the component with respect to structural integrity, operability and functional capability. Requalification is required if existing qualification is lost because of: expiration of the qualified service life (life extension); reactivation of a cancelled or suspended plant; failure to conform with certain requirements of the Technical Specifications, or revision to the applicable Regulatory requirements. The alternatives to requalification are replacement or removal from service. The choice between requalification, replacement and removal from service is governed by economics. The purpose of requalification standards is to ensure the acceptability of the requalification process. A previous EPRImore » Report prepared by Teledyne Engineering Services (TES) (NP-1921) developed a rationale for, and a draft of, a generic requalification standard for Class 1 Pressure Boundary Components presently considered by the Boiler and Pressure Vessel Code published by The American Society of Mechanical Engineers (ASME/BPVC). International Energy Associates Limited (IEA) prepared another report for EPRI shortly thereafter (NP-2418), which reviewed the economic and technologies factors of nuclear plant life extension, and concluded that NP-1921 makes a strong case that the nuclear industry will benefit from the development of the proposed standard.« less

Totipotency, Pluripotency and Nuclear Reprogramming

NASA Astrophysics Data System (ADS)

Mitalipov, Shoukhrat; Wolf, Don

Mammalian development commences with the totipotent zygote which is capable of developing into all the specialized cells that make up the adult animal. As development unfolds, cells of the early embryo proliferate and differentiate into the first two lineages, the pluripotent inner cell mass and the trophectoderm. Pluripotent cells can be isolated, adapted and propagated indefinitely in vitro in an undifferentiated state as embryonic stem cells (ESCs). ESCs retain their ability to differentiate into cells representing the three major germ layers: endoderm, mesoderm or ectoderm or any of the 200+ cell types present in the adult body. Since many human diseases result from defects in a single cell type, pluripotent human ESCs represent an unlimited source of any cell or tissue type for replacement therapy thus providing a possible cure for many devastating conditions. Pluripotent cells resembling ESCs can also be derived experimentally by the nuclear reprogramming of somatic cells. Reprogrammed somatic cells may have an even more important role in cell replacement therapies since the patient's own somatic cells can be used for reprogramming thereby eliminating immune based rejection of transplanted cells. In this review, we summarize two major approaches to reprogramming: (1) somatic cell nuclear transfer and (2) direct reprogramming using genetic manipulations.

Vector-Free and Transgene-Free Human iPS Cells Differentiate into Functional Neurons and Enhance Functional Recovery after Ischemic Stroke in Mice

PubMed Central

Mohamad, Osama; Faulkner, Ben; Chen, Dongdong; Yu, Shan Ping; Wei, Ling

2013-01-01

Stroke is a leading cause of human death and disability in the adult population in the United States and around the world. While stroke treatment is limited, stem cell transplantation has emerged as a promising regenerative therapy to replace or repair damaged tissues and enhance functional recovery after stroke. Recently, the creation of induced pluripotent stem (iPS) cells through reprogramming of somatic cells has revolutionized cell therapy by providing an unlimited source of autologous cells for transplantation. In addition, the creation of vector-free and transgene-free human iPS (hiPS) cells provides a new generation of stem cells with a reduced risk of tumor formation that was associated with the random integration of viral vectors seen with previous techniques. However, the potential use of these cells in the treatment of ischemic stroke has not been explored. In the present investigation, we examined the neuronal differentiation of vector-free and transgene-free hiPS cells and the transplantation of hiPS cell-derived neural progenitor cells (hiPS-NPCs) in an ischemic stroke model in mice. Vector-free hiPS cells were maintained in feeder-free and serum-free conditions and differentiated into functional neurons in vitro using a newly developed differentiation protocol. Twenty eight days after transplantation in stroke mice, hiPS-NPCs showed mature neuronal markers in vivo. No tumor formation was seen up to 12 months after transplantation. Transplantation of hiPS-NPCs restored neurovascular coupling, increased trophic support and promoted behavioral recovery after stroke. These data suggest that using vector-free and transgene-free hiPS cells in stem cell therapy are safe and efficacious in enhancing recovery after focal ischemic stroke in mice. PMID:23717557

Gene Therapy for Neurologic Manifestations of Mucopolysaccharidoses

PubMed Central

Wolf, Daniel A.; Banerjee, Sharbani; Hackett, Perry B.; Whitley, Chester B.; McIvor, R. Scott; Low, Walter C.

2015-01-01

Introduction Mucopolysaccharidoses are a family of lysosomal disorders caused by mutations in genes that encode enzymes involved in the catabolism of glycoaminoglycans. These mutations affect multiple organ systems and can be particularly deleterious to the nervous system. At the present time, enzyme replacement therapy and hematopoietic stem-cell therapy are used to treat patients with different forms of these disorders. However, to a great extent the nervous system is not adequately responsive to current therapeutic approaches. Areas Covered Recent advances in gene therapy show great promise for treating mucopolysaccharidoses. This article reviews the current state of the art for routes of delivery in developing genetic therapies for treating the neurologic manifestations of mucopolysaccharidoses. Expert Opinion Gene therapy for treating neurological manifestations of mucopolysaccharidoses can be achieved by intraventricular, intrathecal, intranasal, and systemic administration. The intraventricular route of administration appears to provide the most wide-spread distribution of gene therapy vectors to the brain. The intrathecal route of delivery results in predominant distribution to the caudal areas of the brain while the intranasal route of delivery results in good distribution to the rostral areas of brain. The systemic route of delivery via intravenous delivery can also achieve wide spread delivery to the CNS, however, the distribution to the brain is greatly dependent on the vector system. Intravenous delivery using lentiviral vectors appear to be less effective than adeno-associated viral (AAV) vectors. Moreover, some subtypes of AAV vectors are more effective than others in crossing the blood-brain-barrier. In summary, the recent advances in gene vector technology and routes of delivery to the CNS will facilitate the clinical translation of gene therapy for the treatment of the neurological manifestations of mucopolysaccharidoses. PMID:25510418

Neuronal differentiation modulates the dystrophin Dp71d binding to the nuclear matrix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Munoz, Rafael; Villarreal-Silva, Marcela; Gonzalez-Ramirez, Ricardo

The function of dystrophin Dp71 in neuronal cells remains unknown. To approach this issue, we have selected the PC12 neuronal cell line. These cells express both a Dp71f cytoplasmic variant and a Dp71d nuclear isoform. In this study, we demonstrated by electron and confocal microscopy analyses of in situ nuclear matrices and Western blotting evaluation of cell extracts that Dp71d associates with the nuclear matrix. Interestingly, this binding is modulated during NGF-induced neuronal differentiation of PC12 cells with a twofold increment in the differentiated cells, compared to control cells. Also, distribution of Dp71d along the periphery of the nuclear matrixmore » observed in the undifferentiated cells is replaced by intense fluorescent foci localized in Center of the nucleoskeletal structure. In summary, we revealed that Dp71d is a dynamic component of nuclear matrix that might participate in the nuclear modeling occurring during neuronal differentiation.« less

Observational Investigation of Solar Interior and Atmosphere

NASA Technical Reports Server (NTRS)

Kuhn, Jeffrey R.

2003-01-01

The Imaging Vector Magnetograph (IVM) has been modified to make it easier to observe at more than one spectral line. The cell holding the blocking filter has been replaced by a four-position filter wheel, so that changing to a different line is a matter of a few minutes rather than the several hours it used to take to disassemble the cell and install a new filter. Three new filters have been obtained, for Na 1589.6 nm, Fe 1630.25 nm, and H 1656.3 nm. The new filters have better bandpass profiles than the ones they replaced: somewhat wider, with flatter tops and steeper wings. This results in a reduction of parasitic light coming from adjacent Fabry-Perot orders, from seven percent to about two percent, and flattens the apparent continuum. The Mees CCD Imaging Spectrograph (MCCD) was upgraded under this grant, with a new control computer and data system. The camera was replaced with a faster, larger-format frame-transfer camera. Final integration of the upgrades is not yet complete, but tests indicate that the system cadence will be improved by a factor of five to ten, while increasing the spatial coverage by a factor of two (depending on observation options). Synoptic observations with the IVM and MCCD continue to be conducted daily, to the extent permitted by the fact that we have a single observer responsible for the observations. The older Haleakala Stokes Polarimeter is also used to make a daily vector magnetogram, normally of the region selected by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) duty scientists. This instrument, however, is showing its age to the extent that its maintenance is becoming something of a challenge. We also run a white light full-disk imager and a video H alpha prominence camera, continuously during times of observations. Of particular interest, we obtained rapid-cadence observations of the 2003 July 15 white light flare with both the IVM and MCCD. The vector magnetograms show no obvious difference between the preflare and postflare configurations. The photospheric magnetogram sequence and H alpha spectra we obtained can be combined with spacecraft observations to construct a rather detailed picture of the events of this flare. Several papers are in preparation.

Clinical Applications Involving CNS Gene Transfer

PubMed Central

Kantor, Boris; McCown, Thomas; Leone, Paola; Gray, Steven J.

2015-01-01

Diseases of the central nervous system (CNS) have traditionally been the most difficult to treat by traditional pharmacological methods, due mostly to the blood–brain barrier and the difficulties associated with repeated drug administration targeting the CNS. Viral vector gene transfer represents a way to permanently provide a therapeutic protein within the nervous system after a single administration, whether this be a gene replacement strategy for an inherited disorder or a disease-modifying protein for a disease such as Parkinson's. Gene therapy approaches for CNS disorders has evolved considerably over the last two decades. Although a breakthrough treatment has remained elusive, current strategies are now considerably safer and potentially much more effective. This chapter will explore the past, current, and future status of CNS gene therapy, focusing on clinical trials utilizing adeno-associated virus and lentiviral vectors. PMID:25311921

A Computer Simulation of the System-Wide Effects of Parallel-Offset Route Maneuvers

NASA Technical Reports Server (NTRS)

Lauderdale, Todd A.; Santiago, Confesor; Pankok, Carl

2010-01-01

Most aircraft managed by air-traffic controllers in the National Airspace System are capable of flying parallel-offset routes. This paper presents the results of two related studies on the effects of increased use of offset routes as a conflict resolution maneuver. The first study analyzes offset routes in the context of all standard resolution types which air-traffic controllers currently use. This study shows that by utilizing parallel-offset route maneuvers, significant system-wide savings in delay due to conflict resolution of up to 30% are possible. It also shows that most offset resolutions replace horizontal-vectoring resolutions. The second study builds on the results of the first and directly compares offset resolutions and standard horizontal-vectoring maneuvers to determine that in-trail conflicts are often more efficiently resolved by offset maneuvers.

Using mitogenomic and nuclear ribosomal sequence data to investigate the phylogeny of the Xiphinema americanum species complex

USDA-ARS?s Scientific Manuscript database

Nematodes within the Xiphinema americanum species complex are economically important because they vector nepoviruses which cause considerable damage to a variety of agricultural crops. The taxonomy of X. americanum is controversial, with the number of putative species being the subject of debate. Ac...

Legubicin a Tumor-activated Prodrug for Breast Cancer Therapy

DTIC Science & Technology

2008-04-01

slides were incubated with a cocktail of first primary antibodies for overnight (biotin-conjugeted rat anti-mouse CD68 at 1:100 dilution and sheep anti... sheep (green) (Vector Laboratories) for 40 minutes. Nuclear staining was performed DEPI (10ug/ml) for 10 minutes, then mount cover slip with anti-fade

Expression of exogenous human hepatic nuclear factor-1α by a lentiviral vector and its interactions with Plasmodium falciparum subtilisin-like protease 2.

PubMed

Liao, Shunyao; Liu, Yunqiang; Zheng, Bing; Cho, Pyo Yun; Song, Hyun Ok; Lee, Yun-Seok; Jung, Suk-Yul; Park, Hyun

2011-12-01

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-1α is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions. In this study, we analyzed the expression of host HNF-1α in relation to malaria infection and evaluated its interaction with the 5'-untranslated region of subtilisin-like protease 2 (subtilase, Sub2). Recombinant human HNF-1α expressed by a lentiviral vector (LV HNF-1α) was introduced into mice. Interestingly, differences in the activity of the 5'-untranslated region of the Pf-Sub2 promoter were detected in 293T cells, and LV HNF-1α was observed to influence promoter activity, suggesting that host HNF-1α interacts with the Sub2 gene.

A baculovirus dual expression vector derived from the Autographa californica nuclear polyhedrosis virus polyhedrin and p10 promoters: co-expression of two influenza virus genes in insect cells.

PubMed

Weyer, U; Possee, R D

1991-12-01

A baculovirus transfer vector, pAcUW3, was developed to facilitate the insertion of two influenza virus genes, those encoding the haemagglutinin (HA) and neuraminidase (NA) membrane glycoproteins, into the Autographa californica nuclear polyhedrosis virus genome in a single cotransfection experiment. The NA gene was inserted in place of the polyhedrin coding sequences under the control of the polyhedrin promoter, whereas the HA gene was placed under the control of a copy of the p10 promoter at a site upstream of and in opposite orientation to the polyhedrin promoter. After infection of Spodoptera frugiperda cells with the recombinant virus, AcUW3HANA, both HA and NA were expressed in the very late phase of infection and were shown to be functional in appropriate assays. Immunofluorescence assays demonstrated their localization at the surface of infected insect cells. The expression of both foreign genes in the recombinant virus was found to be stable for at least 12 passages in cell culture.

Many body effects in nuclear matter QCD sum rules

NASA Astrophysics Data System (ADS)

Drukarev, E. G.; Ryskin, M. G.; Sadovnikova, V. A.

2017-12-01

We calculate the single-particle nucleon characteristics in symmetric nuclear matter with inclusion of the 3N and 4N interactions. We calculated the contribution of the 3N interactions earlier, now we add that of the 4N ones. The contribution of the 4N forces to nucleon self energies is expressed in terms of the nonlocal scalar condensate (d = 3) and of the configurations of the vector-scalar and the scalar-scalar quark condensates (d = 6) in which two diquark operators act on two different nucleons of the matter.These four-quark condensates are obtained in the model-independent way. The density dependence of the nucleon effective mass, of the vector self energy and of the single-particle potential energy are obtained. We traced the dependence of the nucleon characteristics on the actual value of the pion-nucleon sigma term. We obtained also the nucleon characteristics in terms of the quasifree nucleons, with the noninteracting nucleons surrounded by their pion clouds as the starting point. This approach leads to strict hierarchy of the many body forces.

Studies of the Three-Nucleon System Dynamics in the Deuteron-Proton Breakup Reaction

NASA Astrophysics Data System (ADS)

Ciepał, I.; Kłos, B.; Stephan, E.; Kistryn, St.; Biegun, A.; Bodek, K.; Deltuva, A.; Epelbaum, E.; Eslami-Kalantari, M.; Fonseca, A. C.; Golak, J.; Jha, V.; Kalantar-Nayestanaki, N.; Kamada, H.; Khatri, G.; Kirillov, Da.; Kirillov, Di.; Kliczewski, St.; Kozela, A.; Kravcikova, M.; Machner, H.; Magiera, A.; Martinska, G.; Messchendorp, J.; Nogga, A.; Parol, W.; Ramazani-Moghaddam-Arani, A.; Roy, B. J.; Sakai, H.; Sekiguchi, K.; Sitnik, I.; Siudak, R.; Skibiński, R.; Sworst, R.; Urban, J.; Witała, H.; Zejma, J.

2014-03-01

One of the most important goals of modern nuclear physics is to contruct nuclear force model which properly describes the experimental data. To develop and test predictions of current models the breakup 1H(overrightarrow d, pp)n reaction was investigated experimentally at 100 and 130 MeV deuteron beam energies. Rich set of data for cross section, vector and tensor analyzing powers was obtained with the use of the SALAD and BINA detectors at KVI and Germanium Wall setup at FZ-Jülich. Results are compared with various theoretical approaches which describe the three-nucleon (3N) system dynamics. For correct description of the cross section data both, three-nucleon force (3NF) and Coulomb force, have to be included into calculations and influence of those ingredients is seizable at specific parts of the phase space. In case of the vector analyzing powers very low sensitivity to any effects beyond nucleon-nucleon interaction was found. At 130 MeV, the Axy data are not correctly described when 3NF models are included into calculations.

Muon, photon and nuclear CERs for ββ - ν response studies

NASA Astrophysics Data System (ADS)

Ejiri, H.

2015-10-01

Neutrino nuclear responses for neutrino-less double beta decays (0νββ DBD) are studied by muon, photon and nuclear charge exchange reactions (CER) and β-EC transitions. These experimental responses with low and medium momentum transfers are used to evaluate 0νββ nuclear matrix elements and the solar neutrino interactions with atoms and nuclei of DBD detectors. Gamma-ray measurements from residual RI nuclei produced by (µ, νµxn) reactions on 100Mo shows a giant resonance around 12-15 MeV for µ- capture strength. Single β Gamow-Teller (GT) and spin-dipole (SD) strengths are reduced with respect to pnQRPA calculations by gAe f f≈0.5 -0.6 gA , suggesting considerable reductions of the axial vector responses for DBD. Solar neutrino nuclear interactions with nuclei of the DBD isotopes and atoms of liquid scintillators used for DBD experiments are shown to be the serious backgrounds at the ROI (region of interest) of 0νββ.

[New strategy for RNA vectorization in mammalian cells. Use of a peptide vector].

PubMed

Vidal, P; Morris, M C; Chaloin, L; Heitz, F; Divita, G

1997-04-01

A major barrier for gene delivery is the low permeability of nucleic acids to cellular membranes. The development of antisenses and gene therapy has focused mainly on improving methods of oligonucleotide or gene delivery to the cell. In this report we described a new strategy for RNA cell delivery, based on a short single peptide. This peptide vector is derived from both the fusion domain of the gp41 protein of HIV and the nuclear localization sequence of the SV40 large T antigen. This peptide vector localizes rapidly to the cytoplasm then to the nucleus of human fibroblasts (HS-68) within a few minutes and exhibits a high affinity for a single-stranded mRNA encoding the p66 subunit of the HIV-1 reverse transcriptase (in a 100 nM range). The peptide/RNA complex formation involves mainly electrostatic interactions between the basic residues of the peptide and the charges on the phosphate group of the RNA. In the presence of the peptide-vector fluorescently-labelled mRNA is delivered into the cytoplasm of mammalian cells (HS68 human fibroblasts) in less than 1 h with a relatively high efficiency (80%). This new concept based on a peptide-derived vector offers several advantages compared to other compounds commonly used in gene delivery. This vector is highly soluble and exhibits no cytotoxicity at the concentrations used for optimal gene delivery. This result clearly supports the fact that this peptide vector is a powerful tool and that it can be used widely, as much for laboratory research as for new applications and development in gene and/or antisense therapy.

Toward DNA-based Security Circuitry: First Step - Random Number Generation.

PubMed

Bogard, Christy M; Arazi, Benjamin; Rouchka, Eric C

2008-08-10

DNA-based circuit design is an area of research in which traditional silicon-based technologies are replaced by naturally occurring phenomena taken from biochemistry and molecular biology. Our team investigates the implications of DNA-based circuit design in serving security applications. As an initial step we develop a random number generation circuitry. A novel prototype schema employs solid-phase synthesis of oligonucleotides for random construction of DNA sequences. Temporary storage and retrieval is achieved through plasmid vectors.

Large-N -approximated field theory for multipartite entanglement

NASA Astrophysics Data System (ADS)

Facchi, P.; Florio, G.; Parisi, G.; Pascazio, S.; Scardicchio, A.

2015-12-01

We try to characterize the statistics of multipartite entanglement of the random states of an n -qubit system. Unable to solve the problem exactly we generalize it, replacing complex numbers with real vectors with Nc components (the original problem is recovered for Nc=2 ). Studying the leading diagrams in the large-Nc approximation, we unearth the presence of a phase transition and, in an explicit example, show that the so-called entanglement frustration disappears in the large-Nc limit.

Ballistic Impact Resistance of Multi-Layer Textile Fabrics

DTIC Science & Technology

1981-10-01

REBOT (NNOLA, NVAR). the first array contains the vector of forces externally applied to the ’ top surface of the layer under consideration, while the...array REBOT (NNOLA, NVAR) contains the forces externally applied to the lower surface of the array. Initially all the elements of each of the two arrays...Qodes in a layer, the contents of array REBOT are now replaced with those of array RETOP in preparation for the repetition of the same calculations for

The Causal Mediation Formula - A Guide to the Assessment of Pathways and Mechanisms

DTIC Science & Technology

2011-10-01

for estimating CDE(z) in observational studies (in the presence of unobserved confounders) can be derived using do- calculus (Pearl, 2009, pp. 85–88...2011; Albert and Nelson , 2011). 7In the presence of measured and unmeasured confounders, the general conditions under which NDE is estimable from...achieve this independence (see footnote 7), that Z may represent a vector of variables, and that integrals should replace summations when dealing with

CURRENTLY AVAILABLE TECHNOLOGIES DEMONSTRATION FOR ALTERNATIVES TO RADIOLOGICAL SOURCES

EPA Science Inventory

EPA's Office of Radiation and Indoor Air awarded a contract to demonstrate that non-nuclear measurement using optical and magnetic technology can replace radioactive devices used to measure the thickness and density of various paper, film, and plastic sheets.

NMR studies of spin dynamics in cuprates

NASA Astrophysics Data System (ADS)

Takigawa, M.; Mitzi, D. B.

1994-04-01

We report recent NMR results in cuprates. The oxygen Knight shift and the Cu nuclear spin-lattice relaxation rate in Bi2.1Sr1.94Ca0.88Cu2.07O8+δ single crystals revealed a gapless superconducting state, which can be most naturally explained by a d-wave pairing state and the intrinsic disorder in this material. The Cu nuclear spin-spin relaxation rate in underdoped YBa2Cu3O6.63 shows distinct temperature dependence from the spin-lattice relaxation rate, providing direct evidence for a pseudo spin-gap near the antiferromagnetic wave vector.

A Ramsey’s Method With Pulsed Neutrons for a T-Violation Experiment

PubMed Central

Masuda, Y.; Ino, T.; Muto, S.; Skoy, V.

2005-01-01

A Ramsey’s method with pulsed neutrons is discussed for neutron spin manipulation in a time reversal (T) symmetry violation experiment. The neutron spin (sn) is aligned to the direction of a vector product of the nuclear spin (I) and the neutron momentum (kn) for the measurement of a T-odd correlation term, which is represented as sn · (kn × I), during propagation through a polarized nuclear target. The phase control and amplitude modulation of separated oscillatory fields are discussed for the measurement of the T-odd correlation term. PMID:27308171

A Ramsey's Method With Pulsed Neutrons for a T-Violation Experiment.

PubMed

Masuda, Y; Ino, T; Muto, S; Skoy, V

2005-01-01

A Ramsey's method with pulsed neutrons is discussed for neutron spin manipulation in a time reversal (T) symmetry violation experiment. The neutron spin (s n) is aligned to the direction of a vector product of the nuclear spin ( I ) and the neutron momentum ( k n) for the measurement of a T-odd correlation term, which is represented as s n · ( k n × I ), during propagation through a polarized nuclear target. The phase control and amplitude modulation of separated oscillatory fields are discussed for the measurement of the T-odd correlation term.

Navy Ohio Replacement (SSBN[X]) Ballistic Missile Submarine Program: Background and Issues for Congress

DTIC Science & Technology

2015-12-17

strategic nuclear arms reduction treaty that included 14 Ohio-class SSBNs, all armed with D- 5s . This recommendation prompted interest in the idea of...a program to extend the service life of the Trident II D-5 SLBM into the 2040s, and to have its next-generation SSBNs carry D- 5s . Following this...Navy states that 10 operational SSBNs—meaning boats not encumbered by lengthy maintenance actions—are needed to meet strategic nuclear deterrence

Design reuse experience of space and hazardous operations robots

NASA Technical Reports Server (NTRS)

Oneil, P. Graham

1994-01-01

A comparison of design drivers for space and hazardous nuclear waste operating robots details similarities and differences in operations, performance and environmental parameters for these critical environments. The similarities are exploited to provide low risk system components based on reuse principles and design knowledge. Risk reduction techniques are used for bridging areas of significant differences. As an example, risk reduction of a new sensor design for nuclear environment operations is employed to provide upgradeable replacement units in a reusable architecture for significantly higher levels of radiation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carruth, R.C.; Sotos, W.G.

As the nation`s nuclear power plants age, the need to consider upgrading of their electronic protection and control systems becomes more urgent. Hardware obsolescence and mechanical wear out resulting from frequent calibration and surveillance play a major role in defining their useful life. At Cook Nuclear Plant, a decision was made to replace a major portion of the plant`s protection and control systems with newer technology. This paper describes the engineering processes involved in this successful upgrade and explains the basis for many decisions made while performing the digital upgrade.

Novel Synthetic Medea selfish genetic elements drive population replacement in Drosophila, and a theoretical exploration of Medea-dependent population suppression

PubMed Central

Akbari, Omar S.; Chen, Chun-Hong; Marshall, John M.; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A.

2013-01-01

Insects act as vectors for diseases of plants, animals and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression. PMID:23654248

Robotics for Nuclear Material Handling at LANL:Capabilities and Needs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harden, Troy A; Lloyd, Jane A; Turner, Cameron J

Nuclear material processing operations present numerous challenges for effective automation. Confined spaces, hazardous materials and processes, particulate contamination, radiation sources, and corrosive chemical operations are but a few of the significant hazards. However, automated systems represent a significant safety advance when deployed in place of manual tasks performed by human workers. The replacement of manual operations with automated systems has been desirable for nearly 40 years, yet only recently are automated systems becoming increasingly common for nuclear materials handling applications. This paper reviews several automation systems which are deployed or about to be deployed at Los Alamos National Laboratory formore » nuclear material handling operations. Highlighted are the current social and technological challenges faced in deploying automated systems into hazardous material handling environments and the opportunities for future innovations.« less

Replacing zoledronic acid with denosumab is a risk factor for developing osteonecrosis of the jaw.

PubMed

Higuchi, Tomoko; Soga, Yoshihiko; Muro, Misato; Kajizono, Makoto; Kitamura, Yoshihisa; Sendo, Toshiaki; Sasaki, Akira

2018-06-01

Intravenous zoledronic acid (ZA) is often replaced with subcutaneous denosumab in patients with bone metastatic cancer. Despite their different pharmacologic mechanisms of action, both denosumab and ZA are effective in bone metastasis but cause osteonecrosis of the jaw (ONJ) as a side effect. ZA persists in the body almost indefinitely, whereas denosumab does not persist for long periods. This study evaluated the risks of developing ONJ when replacing ZA with denosumab. In total, 161 Japanese patients administered ZA for bone metastatic cancer were enrolled in this single-center, retrospective, observational study. The risk of developing ONJ was evaluated by logistic regression analysis using the following factors: age, gender, cancer type, angiogenesis inhibitors, steroids, and replacement of ZA with denosumab. Seventeen patients (10.6%) developed ONJ. Multiple regression analysis indicated a significant difference in rate of ONJ associated with replacement of ZA with denosumab (odds ratio = 3.81; 95% confidence interval 1.04-13.97; P = .043). Replacing ZA with denosumab is a risk factor for the development of ONJ. Both binding of bisphosphonate to bone and receptor activator of nuclear factor-κ B ligand inhibition could additively increase the risk of ONJ. We bring the replacement of ZA with denosumab to the attention of clinical oncologists. Copyright © 2018 Elsevier Inc. All rights reserved.

Ballistic protons in incoherent exclusive vector meson production as a measure of rare parton fluctuations at an electron-ion collider

DOE PAGES

Lappi, T.; Venugopalan, R.; Mantysaari, H.

2015-02-25

We argue that the proton multiplicities measured in Roman pot detectors at an electron ion collider can be used to determine centrality classes in incoherent diffractive scattering. Incoherent diffraction probes the fluctuations in the interaction strengths of multi-parton Fock states in the nuclear wavefunctions. In particular, the saturation scale that characterizes this multi-parton dynamics is significantly larger in central events relative to minimum bias events. As an application, we examine the centrality dependence of incoherent diffractive vector meson production. We identify an observable which is simultaneously very sensitive to centrality triggered parton fluctuations and insensitive to details of the model.

The Skyrme Model

NASA Astrophysics Data System (ADS)

Zahed, I.; Brown, G. E.

We review the recent developments on the Skyrme model in the context of OCD, and analyze their relevance to low-energy phenomenology. The fundamentals of chiral symmetry and PCAC are presented, and their importance in effective chiral models of the Skyrme type discussed. The nature and properties of skyrmions are thoroughly investigated, with particular stress on the basic role of the Wess-Zumino term. The conventional Skyrme model is extended to the low-lying vector meson resonances, and the rudiments of vector meson dominance are elucidated. A detailed account of the static and dynamical properties of nucleons and Δ-isobars is presented. The relevance of the Skyrme model to the nuclear many-body problem is outlined and its importance for boson exchange models stressed.

Towards a Safer, More Randomized Lentiviral Vector Integration Profile Exploring Artificial LEDGF Chimeras

PubMed Central

Vranckx, Lenard S.; Demeulemeester, Jonas; Debyser, Zeger

2016-01-01

The capacity to integrate transgenes into the host cell genome makes retroviral vectors an interesting tool for gene therapy. Although stable insertion resulted in successful correction of several monogenic disorders, it also accounts for insertional mutagenesis, a major setback in otherwise successful clinical gene therapy trials due to leukemia development in a subset of treated patients. Despite improvements in vector design, their use is still not risk-free. Lentiviral vector (LV) integration is directed into active transcription units by LEDGF/p75, a host-cell protein co-opted by the viral integrase. We engineered LEDGF/p75-based hybrid tethers in an effort to elicit a more random integration pattern to increase biosafety, and potentially reduce proto-oncogene activation. We therefore truncated LEDGF/p75 by deleting the N-terminal chromatin-reading PWWP-domain, and replaced this domain with alternative pan-chromatin binding peptides. Expression of these LEDGF-hybrids in LEDGF-depleted cells efficiently rescued LV transduction and resulted in LV integrations that distributed more randomly throughout the host-cell genome. In addition, when considering safe harbor criteria, LV integration sites for these LEDGF-hybrids distributed more safely compared to LEDGF/p75-mediated integration in wild-type cells. This approach should be broadly applicable to introduce therapeutic or suicide genes for cell therapy, such as patient-specific iPS cells. PMID:27788138

Crispr-mediated Gene Targeting of Human Induced Pluripotent Stem Cells.

PubMed

Byrne, Susan M; Church, George M

2015-01-01

CRISPR/Cas9 nuclease systems can create double-stranded DNA breaks at specific sequences to efficiently and precisely disrupt, excise, mutate, insert, or replace genes. However, human embryonic stem or induced pluripotent stem cells (iPSCs) are more difficult to transfect and less resilient to DNA damage than immortalized tumor cell lines. Here, we describe an optimized protocol for genome engineering of human iPSCs using a simple transient transfection of plasmids and/or single-stranded oligonucleotides. With this protocol, we achieve transfection efficiencies greater than 60%, with gene disruption efficiencies from 1-25% and gene insertion/replacement efficiencies from 0.5-10% without any further selection or enrichment steps. We also describe how to design and assess optimal sgRNA target sites and donor targeting vectors; cloning individual iPSC by single cell FACS sorting, and genotyping successfully edited cells.

Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

PubMed Central

Li, Fang; Ryu, Byoung Y.; Krueger, Robin L.; Heldt, Scott A.

2012-01-01

Here we report a novel viral glycoprotein created by replacing a natural receptor-binding sequence of the ecotropic Moloney murine leukemia virus envelope glycoprotein with the peptide ligand somatostatin. This new chimeric glycoprotein, which has been named the Sst receptor binding site (Sst-RBS), gives targeted transduction based on three criteria: (i) a gain of the use of a new entry receptor not used by any known virus; (ii) targeted entry at levels comparable to gene delivery by wild-type ecotropic Moloney murine leukemia virus and vesicular stomatitis virus (VSV) G glycoproteins; and (iii) a loss of the use of the natural ecotropic virus receptor. Retroviral vectors coated with Sst-RBS gained the ability to bind and transduce human 293 cells expressing somatostatin receptors. Their infection was specific to target somatostatin receptors, since a synthetic somatostatin peptide inhibited infection in a dose-dependent manner and the ability to transduce mouse cells bearing the natural ecotropic receptor was effectively lost. Importantly, vectors coated with the Sst-RBS glycoprotein gave targeted entry of up to 1 × 106 transducing U/ml, a level comparable to that seen with infection of vectors coated with the parental wild-type ecotropic Moloney murine leukemia virus glycoprotein through the ecotropic receptor and approaching that of infection of VSV G-coated vectors through the VSV receptor. To our knowledge, this is the first example of a glycoprotein that gives targeted entry of retroviral vectors at levels comparable to the natural capacity of viral envelope glycoproteins. PMID:22013043

THERANOSTICS—clinical aimshots in surgical warfare against well-differentiated neuroendocrine neoplasms

PubMed Central

Kulkarni, Harshad R.; Baum, Richard P.

2014-01-01

Targeted, personalized or molecular medicine all imply maximal treatment with minimal side effects and requires definition and detection of molecular targets prior to therapy. THERANOSTICS in nuclear medicine utilizes the same vector with distinct radionuclides for diagnosis and treatment and has become innovative standard for the treatment of somatostatin receptor expressing neuroendocrine neoplasms. PMID:25332977

Cryptic Diversity within the Major Trypanosomiasis Vector Glossina fuscipes Revealed by Molecular Markers

PubMed Central

Choi, Kwang-Shik; Darby, Alistair C.; Causse, Sandrine; Kapitano, Berisha; Hall, Martin J. R.; Steen, Keith; Lutumba, Pascal; Madinga, Joules; Torr, Steve J.; Okedi, Loyce M.; Lehane, Michael J.; Donnelly, Martin J.

2011-01-01

Background The tsetse fly Glossina fuscipes s.l. is responsible for the transmission of approximately 90% of cases of human African trypanosomiasis (HAT) or sleeping sickness. Three G. fuscipes subspecies have been described, primarily based upon subtle differences in the morphology of their genitalia. Here we describe a study conducted across the range of this important vector to determine whether molecular evidence generated from nuclear DNA (microsatellites and gene sequence information), mitochondrial DNA and symbiont DNA support the existence of these taxa as discrete taxonomic units. Principal Findings The nuclear ribosomal Internal transcribed spacer 1 (ITS1) provided support for the three subspecies. However nuclear and mitochondrial sequence data did not support the monophyly of the morphological subspecies G. f. fuscipes or G. f. quanzensis. Instead, the most strongly supported monophyletic group was comprised of flies sampled from Ethiopia. Maternally inherited loci (mtDNA and symbiont) also suggested monophyly of a group from Lake Victoria basin and Tanzania, but this group was not supported by nuclear loci, suggesting different histories of these markers. Microsatellite data confirmed strong structuring across the range of G. fuscipes s.l., and was useful for deriving the interrelationship of closely related populations. Conclusion/Significance We propose that the morphological classification alone is not used to classify populations of G. fuscipes for control purposes. The Ethiopian population, which is scheduled to be the target of a sterile insect release (SIT) programme, was notably discrete. From a programmatic perspective this may be both positive, given that it may reflect limited migration into the area or negative if the high levels of differentiation are also reflected in reproductive isolation between this population and the flies to be used in the release programme. PMID:21858237

Improving the selection efficiency of the counter-selection marker pheS* for the genetic engineering of Bacillus amyloliquefaciens.

PubMed

Kharchenko, Maria S; Teslya, Petr N; Babaeva, Maria N; Zakataeva, Natalia P

2018-05-01

Bacillus subtilis pheS was genetically modified to obtain a counter-selection marker with high selection efficiency in Bacillus amyloliquefaciens. The application of the new replication-thermosensitive integrative vector pNZTM1, containing this marker, pheS BsT255S/A309G , with a two-step replacement recombination procedure provides an effective tool for the genetic engineering of industrially important Bacillus species. Copyright © 2018. Published by Elsevier B.V.

A nuclear wind/solar oil-shale system for variable electricity and liquid fuels production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forsberg, C.

2012-07-01

The recoverable reserves of oil shale in the United States exceed the total quantity of oil produced to date worldwide. Oil shale contains no oil, rather it contains kerogen which when heated decomposes into oil, gases, and a carbon char. The energy required to heat the kerogen-containing rock to produce the oil is about a quarter of the energy value of the recovered products. If fossil fuels are burned to supply this energy, the greenhouse gas releases are large relative to producing gasoline and diesel from crude oil. The oil shale can be heated underground with steam from nuclear reactorsmore » leaving the carbon char underground - a form of carbon sequestration. Because the thermal conductivity of the oil shale is low, the heating process takes months to years. This process characteristic in a system where the reactor dominates the capital costs creates the option to operate the nuclear reactor at base load while providing variable electricity to meet peak electricity demand and heat for the shale oil at times of low electricity demand. This, in turn, may enable the large scale use of renewables such as wind and solar for electricity production because the base-load nuclear plants can provide lower-cost variable backup electricity. Nuclear shale oil may reduce the greenhouse gas releases from using gasoline and diesel in half relative to gasoline and diesel produced from conventional oil. The variable electricity replaces electricity that would have been produced by fossil plants. The carbon credits from replacing fossil fuels for variable electricity production, if assigned to shale oil production, results in a carbon footprint from burning gasoline or diesel from shale oil that may half that of conventional crude oil. The U.S. imports about 10 million barrels of oil per day at a cost of a billion dollars per day. It would require about 200 GW of high-temperature nuclear heat to recover this quantity of shale oil - about two-thirds the thermal output of existing nuclear reactors in the United States. With the added variable electricity production to enable renewables, additional nuclear capacity would be required. (authors)« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fathi, Nima; McDaniel, Patrick; Vorobieff, Peter

The aim of this paper is evaluating the efficiency of a novel combined solar-nuclear cycle. CFD-Thermal analysis is performed to apply the available surplus heat from the nuclear cycle and measure the available kinetic energy of air for the turbine of a solar chimney power plant system (SCPPS). The presented idea helps to decrease the thermal pollution and handle the water shortage supply for water plant by replacing the cooling tower by solar chimney power plant to get the surplus heat from the available warm air in the secondary loop of the reactor. By applying this idea to a typicalmore » 1000 MW nuclear power plant with a 0.33 thermal efficiency, we can increase it to 0.39.« less

[Reasons to recommend vaccination against dengue in Easter Island: Immunization Advisory Committee of Sociedad Chilena de Infectología].

PubMed

Fica, Alberto; Potin, Marcela; Moreno, Gabriela; Véliz, Liliana; Cerda, Jaime; Escobar, Carola; Wilhelm, Jan

2016-08-01

Dengue was first diagnosed on Easter Island on year 2002 and thereafter recurrent outbreaks have occurred involving different serotypes of dengue virus. Its vector, Aedes aegypti has not been eliminated despite the small size of the island. Conditions at the local hospital preclude adequate management of severe and hemorrhagic cases due to the absence of a Critical Care Unit as well as no availability of platelets, or plasma units for transfusion. Besides, transfer, of severely affected patients to continental Chile is cumbersome, slow and expensive. In this scenario, it is advisable to implement selective vaccination of Easter Island habitants with an available quadrivalent attenuated dengue vaccine with the aim to reduce hemorrhagic and severe dengue cases. This strategy should not replace permanent efforts to control waste disposal sites, water sources, maintain vector surveillance and increase education of the population.

Biological Control Strategies for Mosquito Vectors of Arboviruses.

PubMed

Huang, Yan-Jang S; Higgs, Stephen; Vanlandingham, Dana L

2017-02-10

Historically, biological control utilizes predatory species and pathogenic microorganisms to reduce the population of mosquitoes as disease vectors. This is particularly important for the control of mosquito-borne arboviruses, which normally do not have specific antiviral therapies available. Although development of resistance is likely, the advantages of biological control are that the resources used are typically biodegradable and ecologically friendly. Over the past decade, the advancement of molecular biology has enabled optimization by the manipulation of genetic materials associated with biological control agents. Two significant advancements are the discovery of cytoplasmic incompatibility induced by Wolbachia bacteria, which has enhanced replacement programs, and the introduction of dominant lethal genes into local mosquito populations through the release of genetically modified mosquitoes. As various arboviruses continue to be significant public health threats, biological control strategies have evolved to be more diverse and become critical tools to reduce the disease burden of arboviruses.

PIV-DCNN: cascaded deep convolutional neural networks for particle image velocimetry

NASA Astrophysics Data System (ADS)

Lee, Yong; Yang, Hua; Yin, Zhouping

2017-12-01

Velocity estimation (extracting the displacement vector information) from the particle image pairs is of critical importance for particle image velocimetry. This problem is mostly transformed into finding the sub-pixel peak in a correlation map. To address the original displacement extraction problem, we propose a different evaluation scheme (PIV-DCNN) with four-level regression deep convolutional neural networks. At each level, the networks are trained to predict a vector from two input image patches. The low-level network is skilled at large displacement estimation and the high- level networks are devoted to improving the accuracy. Outlier replacement and symmetric window offset operation glue the well- functioning networks in a cascaded manner. Through comparison with the standard PIV methods (one-pass cross-correlation method, three-pass window deformation), the practicability of the proposed PIV-DCNN is verified by the application to a diversity of synthetic and experimental PIV images.

Experiments with a Regional Vector-Vorticity Model, and Comparison with Other Models

NASA Astrophysics Data System (ADS)

Konor, C. S.; Dazlich, D. A.; Jung, J.; Randall, D. A.

2017-12-01

The Vector-Vorticity Model (VVM) is an anelastic model with a unique dynamical core that predicts the three-dimensional vorticity instead of the three-dimensional momentum. The VVM is used in the CRMs of the Global Quasi-3D Multiscale Modeling Framework, which is discussed by Joon-Hee Jung and collaborators elsewhere in this session. We are updating the physics package of the VVM, replacing it with the physics package of the System for Atmosphere Modeling (SAM). The new physics package includes a double-moment microphysics, Mellor-Yamada turbulence, Monin-Obukov surface fluxes, and the RRTMG radiation parameterization. We briefly describe the VVM and show results from standard test cases, including TWP-ICE. We compare the results with those obtained using the earlier physics. We also show results from experiments on convection aggregation in radiative-convective equilibrium, and compare with those obtained using both SAM and the Regional Atmospheric Modeling System (RAMS).

Identification of germline transcriptional regulatory elements in Aedes aegypti.

PubMed

Akbari, Omar S; Papathanos, Philippos A; Sandler, Jeremy E; Kennedy, Katie; Hay, Bruce A

2014-02-04

The mosquito Aedes aegypti is the principal vector for the yellow fever and dengue viruses, and is also responsible for recent outbreaks of the alphavirus chikungunya. Vector control strategies utilizing engineered gene drive systems are being developed as a means of replacing wild, pathogen transmitting mosquitoes with individuals refractory to disease transmission, or bringing about population suppression. Several of these systems, including Medea, UD(MEL), and site-specific nucleases, which can be used to drive genes into populations or bring about population suppression, utilize transcriptional regulatory elements that drive germline-specific expression. Here we report the identification of multiple regulatory elements able to drive gene expression specifically in the female germline, or in the male and female germline, in the mosquito Aedes aegypti. These elements can also be used as tools with which to probe the roles of specific genes in germline function and in the early embryo, through overexpression or RNA interference.

Identification of germline transcriptional regulatory elements in Aedes aegypti

NASA Astrophysics Data System (ADS)

Akbari, Omar S.; Papathanos, Philippos A.; Sandler, Jeremy E.; Kennedy, Katie; Hay, Bruce A.

2014-02-01

The mosquito Aedes aegypti is the principal vector for the yellow fever and dengue viruses, and is also responsible for recent outbreaks of the alphavirus chikungunya. Vector control strategies utilizing engineered gene drive systems are being developed as a means of replacing wild, pathogen transmitting mosquitoes with individuals refractory to disease transmission, or bringing about population suppression. Several of these systems, including Medea, UDMEL, and site-specific nucleases, which can be used to drive genes into populations or bring about population suppression, utilize transcriptional regulatory elements that drive germline-specific expression. Here we report the identification of multiple regulatory elements able to drive gene expression specifically in the female germline, or in the male and female germline, in the mosquito Aedes aegypti. These elements can also be used as tools with which to probe the roles of specific genes in germline function and in the early embryo, through overexpression or RNA interference.

Biological Control Strategies for Mosquito Vectors of Arboviruses

PubMed Central

Huang, Yan-Jang S.; Higgs, Stephen; Vanlandingham, Dana L.

2017-01-01

Historically, biological control utilizes predatory species and pathogenic microorganisms to reduce the population of mosquitoes as disease vectors. This is particularly important for the control of mosquito-borne arboviruses, which normally do not have specific antiviral therapies available. Although development of resistance is likely, the advantages of biological control are that the resources used are typically biodegradable and ecologically friendly. Over the past decade, the advancement of molecular biology has enabled optimization by the manipulation of genetic materials associated with biological control agents. Two significant advancements are the discovery of cytoplasmic incompatibility induced by Wolbachia bacteria, which has enhanced replacement programs, and the introduction of dominant lethal genes into local mosquito populations through the release of genetically modified mosquitoes. As various arboviruses continue to be significant public health threats, biological control strategies have evolved to be more diverse and become critical tools to reduce the disease burden of arboviruses. PMID:28208639

Possibilities and limits concerning the substitution of oil by nuclear energy and coal

NASA Astrophysics Data System (ADS)

Penczynski, P.

1981-05-01

The energy situation in West Germany is discussed. About 96% of the crude oil consumed has to be imported. It is pointed out that this situation together with general developments concerning the diminishing petroleum resources of the world will make it necessary to replace the oil with other energy carriers. Coal resources in West Germany are large enough to last for a few hundred years. However, the consumption of coal as energy carrier should not exceed certain limits in connection with ecological considerations. Uranium as raw material for nuclear energy must also be imported. However, the quantities involved are very small, in connection with the high-energy density of the material. Consequently, a storage of uranium corresponding to a large amount of energy does not present any problems. Various approaches for replacing oil are discussed, taking into account the heat pump, possibilities for storing electric energy generated during the night, automobiles operated with electric energy, energy carriers obtained from coal, and the direct use of coal.

Inactivation of retinoblastoma protein does not overcome the requirement for human cytomegalovirus UL97 in lamina disruption and nuclear egress.

PubMed

Reim, Natalia I; Kamil, Jeremy P; Wang, Depeng; Lin, Alison; Sharma, Mayuri; Ericsson, Maria; Pesola, Jean M; Golan, David E; Coen, Donald M

2013-05-01

Human cytomegalovirus (HCMV) encodes one conventional protein kinase, UL97. During infection, UL97 phosphorylates the retinoblastoma tumor suppressor protein (pRb) on sites ordinarily phosphorylated by cyclin-dependent kinases (CDK), inactivating the ability of pRb to repress host genes required for cell cycle progression to S phase. UL97 is important for viral DNA synthesis in quiescent cells, but this function can be replaced by human papillomavirus type 16 E7, which targets pRb for degradation. However, viruses in which E7 replaces UL97 are still defective for virus production. UL97 is also required for efficient nuclear egress of viral nucleocapsids, which is associated with disruption of the nuclear lamina during infection, and phosphorylation of lamin A/C on serine 22, which antagonizes lamin polymerization. We investigated whether inactivation of pRb might overcome the requirement of UL97 for these roles, as pRb inactivation induces CDK1, and CDK1 phosphorylates lamin A/C on serine 22. We found that lamin A/C serine 22 phosphorylation during HCMV infection correlated with expression of UL97 and was considerably delayed in UL97-null mutants, even when E7 was expressed. E7 failed to restore gaps in the nuclear lamina seen in wild-type but not UL97-null virus infections. In electron microscopy analyses, a UL97-null virus expressing E7 was as impaired as a UL97-null mutant in cytoplasmic accumulation of viral nucleocapsids. Our results demonstrate that pRb inactivation is insufficient to restore efficient viral nuclear egress of HCMV in the absence of UL97 and instead argue further for a direct role of UL97 in this stage of the infectious cycle.

Hybridization during altitudinal range shifts: nuclear introgression leads to extensive cyto-nuclear discordance in the fire salamander.

PubMed

Pereira, Ricardo J; Martínez-Solano, Iñigo; Buckley, David

2016-04-01

Ecological models predict that, in the face of climate change, taxa occupying steep altitudinal gradients will shift their distributions, leading to the contraction or extinction of the high-elevation (cold-adapted) taxa. However, hybridization between ecomorphologically divergent taxa commonly occurs in nature and may lead to alternative evolutionary outcomes, such as genetic merger or gene flow at specific genes. We evaluate this hypothesis by studying patterns of divergence and gene flow across three replicate contact zones between high- and low-elevation ecomorphs of the fire salamander (Salamandra salamandra) that have experienced altitudinal range shifts over the current postglacial period. Strong population structure with high genetic divergence in mitochondrial DNA suggests that vicariant evolution has occurred over several glacial-interglacial cycles and that it has led to cryptic differentiation within ecomorphs. In current parapatric boundaries, we do not find evidence for local extinction and replacement upon postglacial expansion. Instead, parapatric taxa recurrently show discordance between mitochondrial and nuclear markers, suggesting nuclear-mediated gene flow across contact zones. Isolation with migration models support this hypothesis by showing significant gene flow across all five parapatric boundaries. Together, our results suggest that, while some genomic regions, such as the mitochondria, may follow morphologic species traits and retreat to isolated mountain tops, other genomic regions, such as nuclear markers, may flow across parapatric boundaries, sometimes leading to a complete genetic merger. We show that despite high ecologic and morphologic divergence over prolonged periods of time, hybridization allows for evolutionary outcomes alternative to extinction and replacement of taxa in response to climate change. © 2016 John Wiley & Sons Ltd.

Isoscalar-vector interaction and hybrid quark core in massive neutron stars

NASA Astrophysics Data System (ADS)

Shao, G. Y.; Colonna, M.; Di Toro, M.; Liu, Y. X.; Liu, B.

2013-05-01

The hadron-quark phase transition in the core of massive neutron stars is studied with a newly constructed two-phase model. For nuclear matter, a nonlinear Walecka type model with general nucleon-meson and meson-meson couplings, recently calibrated by Steiner, Hemper and Fischer, is taken. For quark matter, a modified Polyakov-Nambu—Jona-Lasinio model, which gives consistent results with lattice QCD data, is used. Most importantly, we introduce an isoscalar-vector interaction in the description of quark matter, and we study its influence on the hadron-quark phase transition in the interior of massive neutron stars. With the constraints of neutron star observations, our calculation shows that the isoscalar-vector interaction between quarks is indispensable if massive hybrids star exist in the universe, and its strength determines the onset density of quark matter, as well as the mass-radius relations of hybrid stars. Furthermore, as a connection with heavy-ion-collision experiments we give some discussions about the strength of isoscalar-vector interaction and its effect on the signals of hadron-quark phase transition in heavy-ion collisions, in the energy range of the NICA at JINR-Dubna and FAIR at GSI-Darmstadt facilities.

Estimation of vector static magnetic field by a nitrogen-vacancy center with a single first-shell 13C nuclear (NV–13C) spin in diamond

NASA Astrophysics Data System (ADS)

Jiang, Feng-Jian; Ye, Jian-Feng; Jiao, Zheng; Huang, Zhi-Yong; Lv, Hai-Jiang

2018-05-01

We suggest an experimental scheme that a single nitrogen-vacancy (NV) center coupled to a nearest neighbor 13C nucleus as a sensor in diamond can be used to detect a static vector magnetic field. By means of optical detection magnetic resonance (ODMR) technique, both the strength and the direction of the vector field could be determined by relevant resonance frequencies of continuous wave (CW) and Ramsey spectrums. In addition, we give a method that determines the unique one of eight possible hyperfine tensors for an (NV–13C) system. Finally, we propose an unambiguous method to exclude the symmetrical solution from eight possible vector fields, which correspond to nearly identical resonance frequencies due to their mirror symmetry about 14N–Vacancy–13C (14N–V–13C) plane. Protect supported by the National Natural Science Foundation of China (Grant Nos. 11305074, 11135002, and 11275083), the Key Program of the Education Department Outstanding Youth Foundation of Anhui Province, China (Grant No. gxyqZD2017080), and the Natural Science Foundation of Anhui Province, China (Grant No. KJHS2015B09).

Bias and uncertainty in regression-calibrated models of groundwater flow in heterogeneous media

USGS Publications Warehouse

Cooley, R.L.; Christensen, S.

2006-01-01

Groundwater models need to account for detailed but generally unknown spatial variability (heterogeneity) of the hydrogeologic model inputs. To address this problem we replace the large, m-dimensional stochastic vector ?? that reflects both small and large scales of heterogeneity in the inputs by a lumped or smoothed m-dimensional approximation ????*, where ?? is an interpolation matrix and ??* is a stochastic vector of parameters. Vector ??* has small enough dimension to allow its estimation with the available data. The consequence of the replacement is that model function f(????*) written in terms of the approximate inputs is in error with respect to the same model function written in terms of ??, ??,f(??), which is assumed to be nearly exact. The difference f(??) - f(????*), termed model error, is spatially correlated, generates prediction biases, and causes standard confidence and prediction intervals to be too small. Model error is accounted for in the weighted nonlinear regression methodology developed to estimate ??* and assess model uncertainties by incorporating the second-moment matrix of the model errors into the weight matrix. Techniques developed by statisticians to analyze classical nonlinear regression methods are extended to analyze the revised method. The analysis develops analytical expressions for bias terms reflecting the interaction of model nonlinearity and model error, for correction factors needed to adjust the sizes of confidence and prediction intervals for this interaction, and for correction factors needed to adjust the sizes of confidence and prediction intervals for possible use of a diagonal weight matrix in place of the correct one. If terms expressing the degree of intrinsic nonlinearity for f(??) and f(????*) are small, then most of the biases are small and the correction factors are reduced in magnitude. Biases, correction factors, and confidence and prediction intervals were obtained for a test problem for which model error is large to test robustness of the methodology. Numerical results conform with the theoretical analysis. ?? 2005 Elsevier Ltd. All rights reserved.

Food-grade host/vector expression system for Lactobacillus casei based on complementation of plasmid-associated phospho-beta-galactosidase gene lacG.

PubMed

Takala, T M; Saris, P E J; Tynkkynen, S S H

2003-01-01

A new food-grade host/vector system for Lactobacillus casei based on lactose selection was constructed. The wild-type non-starter host Lb. casei strain E utilizes lactose via a plasmid-encoded phosphotransferase system. For food-grade cloning, a stable lactose-deficient mutant was constructed by deleting a 141-bp fragment from the phospho-beta-galactosidase gene lacG via gene replacement. The deletion resulted in an inactive phospho-beta-galactosidase enzyme with an internal in-frame deletion of 47 amino acids. A complementation plasmid was constructed containing a replicon from Lactococcus lactis, the lacG gene from Lb. casei, and the constitutive promoter of pepR for lacG expression from Lb. rhamnosus. The expression of the lacG gene from the resulting food-grade plasmid pLEB600 restored the ability of the lactose-negative mutant strain to grow on lactose to the wild-type level. The vector pLEB600 was used for expression of the proline iminopeptidase gene pepI from Lb. helveticus in Lb. casei. The results show that the food-grade expression system reported in this paper can be used for expression of foreign genes in Lb. casei.

β-Glucuronidase as a Sensitive and Versatile Reporter in Actinomycetes ▿

PubMed Central

Myronovskyi, Maksym; Welle, Elisabeth; Fedorenko, Viktor; Luzhetskyy, Andriy

2011-01-01

Here we describe a versatile and sensitive reporter system for actinomycetes that is based on gusA, which encodes the β-glucuronidase enzyme. A series of gusA-containing transcriptional and translational fusion vectors were constructed and utilized to study the regulatory cascade of the phenalinolactone biosynthetic gene cluster. Furthermore, these vectors were used to study the efficiency of translation initiation at the ATG, GTG, TTG, and CTG start codons. Surprisingly, constructs using a TTG start codon showed the best activity, whereas those using ATG or GTG were approximately one-half or one-third as active, respectively. The CTG fusion showed only 5% of the activity of the TTG fusion. A suicide vector, pKGLP2, carrying gusA in its backbone was used to visually detect merodiploid formation and resolution, making gene targeting in actinomycetes much faster and easier. Three regulatory genes, plaR1, plaR2, and plaR3, involved in phenalinolactone biosynthesis were efficiently replaced with an apramycin resistance marker using this system. Finally, we expanded the genetic code of actinomycetes by introducing the nonproteinogenic amino acid N-epsilon-cyclopentyloxycarbonyl-l-lysine with the GusA protein as a reporter. PMID:21685164

Human action recognition with group lasso regularized-support vector machine

NASA Astrophysics Data System (ADS)

Luo, Huiwu; Lu, Huanzhang; Wu, Yabei; Zhao, Fei

2016-05-01

The bag-of-visual-words (BOVW) and Fisher kernel are two popular models in human action recognition, and support vector machine (SVM) is the most commonly used classifier for the two models. We show two kinds of group structures in the feature representation constructed by BOVW and Fisher kernel, respectively, since the structural information of feature representation can be seen as a prior for the classifier and can improve the performance of the classifier, which has been verified in several areas. However, the standard SVM employs L2-norm regularization in its learning procedure, which penalizes each variable individually and cannot express the structural information of feature representation. We replace the L2-norm regularization with group lasso regularization in standard SVM, and a group lasso regularized-support vector machine (GLRSVM) is proposed. Then, we embed the group structural information of feature representation into GLRSVM. Finally, we introduce an algorithm to solve the optimization problem of GLRSVM by alternating directions method of multipliers. The experiments evaluated on KTH, YouTube, and Hollywood2 datasets show that our method achieves promising results and improves the state-of-the-art methods on KTH and YouTube datasets.

Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide

PubMed Central

2011-01-01

Background Insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex. Methods An adenoviral vector harboring the rat IGF-I gene and a control adenoviral vector harboring a hybrid gene encoding the herpes simplex virus type 1 thymidine kinase fused to Aequorea victoria enhanced green fluorescent protein were used in this study. Primary astrocytes from mice cerebral cortex were incubated for 24 h or 72 h with vehicle, IGF-I, the IGF-I adenoviral vector, or control vector; and exposed to bacterial lipopolysaccharide to induce an inflammatory response. IGF-I levels were measured by radioimmunoassay. Levels of interleukin 6, tumor necrosis factor-α, interleukin-1β and toll-like receptor 4 mRNA were assessed by quantitative real-time polymerase chain reaction. Levels of IGF-I receptor and IGF binding proteins 2 and 3 were assessed by western blotting. The subcellular distribution of nuclear factor κB (p65) was assessed by immunocytochemistry. Statistical significance was assessed by one way analysis of variance followed by the Bonferroni pot hoc test. Results IGF-I gene therapy increased IGF-I levels without affecting IGF-I receptors or IGF binding proteins. Exogenous IGF-I, and IGF-I gene therapy, decreased expression of toll-like receptor 4 and counteracted the lipopolysaccharide-induced inflammatory response of astrocytes. In addition, IGF-I gene therapy decreased lipopolysaccharide-induced translocation of nuclear factor κB (p65) to the cell nucleus. Conclusion These findings demonstrate efficacy of exogenous IGF-I and of IGF-I gene therapy in reducing the inflammatory response of astrocytes. IGF-I gene therapy may represent a new approach to reduce inflammatory reactions in glial cells. PMID:21371294

Prevented mortality and greenhouse gas emissions from historical and projected nuclear power.

PubMed

Kharecha, Pushker A; Hansen, James E

2013-05-07

In the aftermath of the March 2011 accident at Japan's Fukushima Daiichi nuclear power plant, the future contribution of nuclear power to the global energy supply has become somewhat uncertain. Because nuclear power is an abundant, low-carbon source of base-load power, it could make a large contribution to mitigation of global climate change and air pollution. Using historical production data, we calculate that global nuclear power has prevented an average of 1.84 million air pollution-related deaths and 64 gigatonnes of CO2-equivalent (GtCO2-eq) greenhouse gas (GHG) emissions that would have resulted from fossil fuel burning. On the basis of global projection data that take into account the effects of the Fukushima accident, we find that nuclear power could additionally prevent an average of 420,000-7.04 million deaths and 80-240 GtCO2-eq emissions due to fossil fuels by midcentury, depending on which fuel it replaces. By contrast, we assess that large-scale expansion of unconstrained natural gas use would not mitigate the climate problem and would cause far more deaths than expansion of nuclear power.

Prevented Mortality and Greenhouse Gas Emissions From Historical and Projected Nuclear Power

NASA Technical Reports Server (NTRS)

Kharecha, Pushker A.; Hansen, James E.

2013-01-01

In the aftermath of the March 2011 accident at Japan's Fukushima Daiichi nuclear power plant, the future contribution of nuclear power to the global energy supply has become somewhat uncertain. Because nuclear power is an abundant, low-carbon source of base-load power, it could make a large contribution to mitigation of global climate change and air pollution. Using historical production data, we calculate that global nuclear power has prevented an average of 1.84 million air pollution-related deaths and 64 gigatonnes of CO2-equivalent (GtCO2-eq) greenhouse gas (GHG) emissions that would have resulted from fossil fuel burning. On the basis of global projection data that take into account the effects of the Fukushima accident, we find that nuclear power could additionally prevent an average of 420 000-7.04 million deaths and 80-240 GtCO2-eq emissions due to fossil fuels by midcentury, depending on which fuel it replaces. By contrast, we assess that large-scale expansion of unconstrained natural gas use would not mitigate the climate problem and would cause far more deaths than expansion of nuclear power.

In vitro evaluation of a mammary gland specific expression vector encoding recombinant human lysozyme for development of transgenic dairy goat embryos.

PubMed

Gui, Tao; Zhang, Meiling; Chen, Jianwen; Zhang, Yuanliang; Zhou, Naru; Zhang, Yu; Tao, Jia; Sui, Liucai; Li, Yunsheng; Liu, Ya; Zhang, Xiaorong; Zhang, Yunhai

2012-08-01

A vector expressing human lysozyme (pBC1-hLYZ-GFP-Neo) was evaluated for gene and protein expression following liposome-mediated transformation of C-127 mouse mammary cancer cells. Cultures of G418-resistant clones were harvested 24-72 h after induction with prolactin, insulin and hydrocortisone. Target gene expression was analyzed by RT-PCR and Western blot and recombinant human lysozyme (rhLYZ) bacteriostatic activity was also evaluated. The hLYZ gene was correctly transcribed and translated in C-127 cells and hLYZ inhibited gram-positive bacterial growth, indicating the potential of this expression vector for development of a mammary gland bioreactor in goats. Guanzhong dairy goat skin fibroblasts transfected with pBC1-hLYZ-GFP-Neo were used to construct a goat embryo transgenically expressing rhLYZ by somatic nuclear transplantation with a blastocyst rate of 9.0 ± 2.8 %. These data establish the basis for cultivation of mastitis-resistant hLYZ transgenic goats.

Microgeographic Genetic Variation of the Malaria Vector Anopheles darlingi Root (Diptera: Culicidae) from Córdoba and Antioquia, Colombia

PubMed Central

Gutiérrez, Lina A.; Gómez, Giovan F.; González, John J.; Castro, Martha I.; Luckhart, Shirley; Conn, Jan E.; Correa, Margarita M.

2010-01-01

Anopheles darlingi is an important vector of Plasmodium spp. in several malaria-endemic regions of Colombia. This study was conducted to test genetic variation of An. darlingi at a microgeographic scale (approximately 100 km) from localities in Córdoba and Antioquia states, in western Colombia, to better understand the potential contribution of population genetics to local malaria control programs. Microsatellite loci: nuclear white and cytochrome oxidase subunit I (COI) gene sequences were analyzed. The northern white gene lineage was exclusively distributed in Córdoba and Antioquia and shared COI haplotypes were highly represented in mosquitoes from both states. COI analyses showed these An. darlingi are genetically closer to Central American populations than southern South American populations. Overall microsatellites and COI analysis showed low to moderate genetic differentiation among populations in northwestern Colombia. Given the existence of high gene flow between An. darlingi populations of Córdoba and Antioquia, integrated vector control strategies could be developed in this region of Colombia. PMID:20595475

Development of a Targeted anti-HER2 scFv Chimeric Peptide for Gene Delivery into HER2-Positive Breast Cancer Cells.

PubMed

Cheraghi, Roya; Nazari, Mahboobeh; Alipour, Mohsen; Majidi, Asia; Hosseinkhani, Saman

2016-12-30

Chimeric polymers are known as suitable carriers for gene delivery. Certain properties are critical for a polymer to be used as a gene delivery vector. A new polymer was designed for the targeted delivery of genes into breast cancer cell lines, based on MPG peptide. It is composed of different functional domains, including HIV gp41, nuclear localization sequence of SV40 T-antigen, two C-terminus repeats of histone H1, and the scFv of anti-HER2 antibody. The results demonstrated that the vector can effectively condense plasmid DNA into nanoparticles with an average size of 250nm. Moreover, fusion of the scFv portion to the carrier brought about the specific recognition of HER2. Overall, the transfection efficiency of the vector demonstrated that it could deliver the desired gene into BT-474 HER2-positive breast cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

A comparative study of history-based versus vectorized Monte Carlo methods in the GPU/CUDA environment for a simple neutron eigenvalue problem

NASA Astrophysics Data System (ADS)

Liu, Tianyu; Du, Xining; Ji, Wei; Xu, X. George; Brown, Forrest B.

2014-06-01

For nuclear reactor analysis such as the neutron eigenvalue calculations, the time consuming Monte Carlo (MC) simulations can be accelerated by using graphics processing units (GPUs). However, traditional MC methods are often history-based, and their performance on GPUs is affected significantly by the thread divergence problem. In this paper we describe the development of a newly designed event-based vectorized MC algorithm for solving the neutron eigenvalue problem. The code was implemented using NVIDIA's Compute Unified Device Architecture (CUDA), and tested on a NVIDIA Tesla M2090 GPU card. We found that although the vectorized MC algorithm greatly reduces the occurrence of thread divergence thus enhancing the warp execution efficiency, the overall simulation speed is roughly ten times slower than the history-based MC code on GPUs. Profiling results suggest that the slow speed is probably due to the memory access latency caused by the large amount of global memory transactions. Possible solutions to improve the code efficiency are discussed.

Gene expression promoted by the SV40 DNA targeting sequence and the hypoxia-responsive element under normoxia and hypoxia.

PubMed

Sacramento, C B; Moraes, J Z; Denapolis, P M A; Han, S W

2010-08-01

The main objective of the present study was to find suitable DNA-targeting sequences (DTS) for the construction of plasmid vectors to be used to treat ischemic diseases. The well-known Simian virus 40 nuclear DTS (SV40-DTS) and hypoxia-responsive element (HRE) sequences were used to construct plasmid vectors to express the human vascular endothelial growth factor gene (hVEGF). The rate of plasmid nuclear transport and consequent gene expression under normoxia (20% O2) and hypoxia (less than 5% O2) were determined. Plasmids containing the SV40-DTS or HRE sequences were constructed and used to transfect the A293T cell line (a human embryonic kidney cell line) in vitro and mouse skeletal muscle cells in vivo. Plasmid transport to the nucleus was monitored by real-time PCR, and the expression level of the hVEGF gene was measured by ELISA. The in vitro nuclear transport efficiency of the SV40-DTS plasmid was about 50% lower under hypoxia, while the HRE plasmid was about 50% higher under hypoxia. Quantitation of reporter gene expression in vitro and in vivo, under hypoxia and normoxia, confirmed that the SV40-DTS plasmid functioned better under normoxia, while the HRE plasmid was superior under hypoxia. These results indicate that the efficiency of gene expression by plasmids containing DNA binding sequences is affected by the concentration of oxygen in the medium.

Generalized Resistance to Thyroid Hormone Associated with a Mutation in the Ligand-Binding Domain of the Human Thyroid Hormone Receptor β

NASA Astrophysics Data System (ADS)

Sakurai, Akihiro; Takeda, Kyoko; Ain, Kenneth; Ceccarelli, Paola; Nakai, Akira; Seino, Susumu; Bell, Graeme I.; Refetoff, Samuel; Degroot, Leslie J.

1989-11-01

The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine --> cytosine replacement in the codon for amino acid 340 resulted in a glycine --> arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor β gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor β gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.

Theoretical nuclear physics

NASA Astrophysics Data System (ADS)

Rost, E.; Shephard, J. R.

1992-08-01

This report discusses the following topics: Exact 1-loop vacuum polarization effects in 1 + 1 dimensional QHD; exact 1-fermion loop contributions in 1 + 1 dimensional solitons; exact scalar 1-loop contributions in 1 + 3 dimensions; exact vacuum calculations in a hyper-spherical basis; relativistic nuclear matter with self-consistent correlation energy; consistent RHA-RPA for finite nuclei; transverse response functions in the (triangle)-resonance region; hadronic matter in a nontopological soliton model; scalar and vector contributions to (bar p)p yields (bar lambda)lambda reaction; 0+ and 2+ strengths in pion double-charge exchange to double giant-dipole resonances; and nucleons in a hybrid sigma model including a quantized pion field.

Sulfoximines as potent RORγ inverse agonists.

PubMed

Ouvry, Gilles; Bihl, Franck; Bouix-Peter, Claire; Christin, Olivier; Defoin-Platel, Claire; Deret, Sophie; Feret, Christophe; Froude, David; Hacini-Rachinel, Feriel; Harris, Craig S; Hervouet, Catherine; Lafitte, Guillaume; Luzy, Anne-Pascale; Musicki, Branislav; Orfila, Danielle; Parnet, Veronique; Pascau, Coralie; Pascau, Jonathan; Pierre, Romain; Raffin, Catherine; Rossio, Patricia; Spiesse, Delphine; Taquet, Nathalie; Thoreau, Etienne; Vatinel, Rodolphe; Vial, Emmanuel; Hennequin, Laurent F

2018-05-01

Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fuel subassembly leak test chamber for a nuclear reactor

DOEpatents

Divona, Charles J.

1978-04-04

A container with a valve at one end is inserted into a nuclear reactor coolant pool. Once in the pool, the valve is opened by a mechanical linkage. An individual fuel subassembly is lifted into the container by a gripper; the valve is then closed providing an isolated chamber for the subassembly. A vacuum is drawn on the chamber to encourage gaseous fission product leakage through any defects in the cladding of the fuel rods comprising the subassembly; this leakage may be detected by instrumentation, and the need for replacement of the assembly ascertained.

Design, Construction and Evaluation of 1a/JFH1 HCV Chimera by Replacing the Intergenotypic Variable Region

PubMed Central

Ghasemi, Faezeh; Ghayour-Mobarhan, Majid; Pasdar, Alireza; Pourianfar, Hamid; Reza Aghasadeghi, Mohammad; Gouklani, Hamed; Meshkat, Zahra

2016-01-01

Background The E2 glycoprotein is an important encoded hepatitis C virus (HCV) protein that contains three different variable regions. Objectives The aim of the present study was to construct an HCV 1a/JFH1 chimeric virus by replacing the intergenotypic variable region (igVR) fragment of the highly variable region of the E2 gene of the Japanese Fulminant hepatitis genotype 2a JFH1 virus with a similar region of HCV genotype 1a. This chimera was produced as a model virus with the ability to be cultured. We analyzed the adapted virus and the variations of nucleic acids within it. Methods Specific primers were designed for the igVR of HCV genotype 1a followed by the overlap-PCR method for the synthesis of the desired DNA fragment. The amplified igVR-1a chimera gene and pFL-J6/JFH were digested by KpnI and BsiWI restriction enzymes, and the fragment was ligated into pFL-J6/JFH. The recombinant vector was transformed into Escherichia coli JM109 strain competent cells. All clones were confirmed by colony PCR using specific primers, and the confirmed recombinant vector was sequenced. The recombinant vector was targeted for RNA synthesis by T7 RNA polymerase enzyme. RNA transfection was performed in the Huh7.5 cell line. Virus production in several passages and the evaluated viral load were studied using quantitative real-time PCR and ELISA methods. After 30 passages, the RNA virus was extracted and cloned in PCDNA3.1 vector, and was then sequenced Results Quantitative real-time PCR results showed 11,292,514 copies/mL of chimeric virus production in cell culture. The virus production was confirmed using ELISA, which showed a virus core production of 808.2 pg/mL. The results of cloning and sequencing showed that some of the nucleic acids in the chimera virus were changed, affecting the viral behavior in the cell culture. Conclusions Real-time PCR and ELISA showed high levels of production of 1a/JFH1 chimeric HCV in the Huh7.5 cell culture. The constructed virus can be used for future studies, including the development of new HCV drugs and vaccines. PMID:27882063

Protein Replacement Therapy and Gene Transfer in Canine Models of Hemophilia A, Hemophilia B, von Willebrand Disease, and Factor VII Deficiency

PubMed Central

Nichols, Timothy C.; Dillow, Aaron M.; Franck, Helen W.G.; Merricks, Elizabeth P.; Raymer, Robin A.; Bellinger, Dwight A.; Arruda, Valder R.; High, Katherine A.

2011-01-01

Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders. PMID:19293459

Synthesis of an Uncharged Tetra-cyclopeptide Acting as a Transmembrane Carrier: Enhanced Cellular and Nuclear Uptake.

PubMed

Francisco Hilário, Flaviane; Traoré, Mohamed Dit Mady; Zwick, Vincent; Berry, Laurence; Simões-Pires, Claudia A; Cuendet, Muriel; Fantozzi, Nicolas; Pereira de Freitas, Rossimiriam; Maynadier, Marjorie; Wein, Sharon; Vial, Henri; Wong, Yung-Sing

2017-02-03

A small uncharged cyclopeptide scaffold inspired by a natural product and designed to undergo postfunctionalizations was used as a new transmembrane vector. A bioactive and fluorescent triazole aminocoumarin was bound to this carrier to facilitate its moving across cell and subcellular membranes, and this led to an increase in its cell toxicity.

The reprogramming factor nuclear receptor subfamily 5, group A, member 2 cannot replace octamer-binding transcription factor 4 function in the self-renewal of embryonic stem cells.

PubMed

Choi, Kyeng-Won; Oh, Hye-Rim; Lee, Jaeyoung; Lim, Bobae; Han, Yong-Mahn; Oh, Junseo; Kim, Jungho

2014-02-01

Although octamer-binding transcription factor 4 (Oct-4) is one of the most intensively studied factors in mammalian development, no cellular genes capable of replacing Oct-4 function in embryonic stem (ES) cells have been found. Recent data show that nuclear receptor subfamily 5, group A, member 2 (Nr5a2) is able to replace Oct-4 function in the reprogramming process; however, it is unclear whether Nr5a2 can replace Oct-4 function in ES cells. In this study, the ability of Nr5a2 to maintain self-renewal and pluripotency in ES cells was investigated. Nr5a2 localized to the nucleus in ES cells, similarly to Oct-4. However, expression of Nr5a2 failed to rescue the stem cell phenotype or to maintain the self-renewal ability of ES cells. Furthermore, as compared with Oct-4-expressing ES cells, Nr5a2-expressing ES cells showed a reduced number of cells in S-phase, did not expand normally, and did not remain in an undifferentiated state. Ectopic expression of Nr5a2 in ES cells was not able to activate transcription of ES cell-specific genes, and gene expression profiling demonstrated differences between Nr5a2-expressing and Oct-4-expressing ES cells. In addition, Nr5a2-expressing ES cells were not able to form teratomas in nude mice. Taken together, these results strongly suggest that the gene regulation properties of Nr5a2 and Oct-4 and their abilities to confer self-renewal and pluripotency of ES cells differ. The present study provides strong evidence that Nr5a2 cannot replace Oct-4 function in ES cells. © 2013 FEBS.

Tβ4-overexpression based on the piggyBac transposon system in cashmere goats alters hair fiber characteristics.

PubMed

Shi, Bingbo; Ding, Qiang; He, Xiaolin; Zhu, Haijing; Niu, Yiyuan; Cai, Bei; Cai, Jiao; Lei, Anming; Kang, Danju; Yan, Hailong; Ma, Baohua; Wang, Xiaolong; Qu, Lei; Chen, Yulin

2017-02-01

Increasing cashmere yield is one of the vital aims of cashmere goats breeding. Compared to traditional breeding methods, transgenic technology is more efficient and the piggyBac (PB) transposon system has been widely applied to generate transgenic animals. For the present study, donor fibroblasts were stably transfected via a PB donor vector containing the coding sequence of cashmere goat thymosin beta-4 (Tβ4) and driven by a hair follicle-specific promoter, the keratin-associated protein 6.1 (KAP6.1) promoter. To obtain genetically modified cells as nuclear donors, we co-transfected donor vectors into fetal fibroblasts of cashmere goats. Five transgenic cashmere goats were generated following somatic cell nuclear transfer (SCNT). Via determination of the copy numbers and integration sites, the Tβ4 gene was successfully inserted into the goat genome. Histological examination of skin tissue revealed that Tβ4-overexpressing, transgenic goats had a higher secondary to primary hair follicle (S/P) ratio compared to wild type goats. This indicates that Tβ4-overexpressing goats possess increased numbers of secondary hair follicles (SHF). Our results indicate that Tβ4-overexpression in cashmere goats could be a feasible strategy to increase cashmere yield.

NMR studies of the helical antiferromagnetic compound EuCo2P2

NASA Astrophysics Data System (ADS)

Higa, N.; Ding, Q.-P.; Kubota, F.; Uehara, H.; Yogi, M.; Furukawa, Y.; Sangeetha, N. S.; Johnston, D. C.; Nakamura, A.; Hedo, M.; Nakama, T.; Ōnuki, Y.

2018-05-01

In EuCo2P2, 4f electron spins of Eu2+ ions order antiferromagnetically below a Néel temperature TN = 66.5 K . The magnetic structure below TN was reported to be helical with the helix axis along the c-axis from the neutron diffraction study. We report the results of 153Eu, 59Co and 31P nuclear magnetic resonance (NMR) measurements on EuCo2P2 using a single crystal and a powdered sample. In the antiferromagnetic (AFM) state, we succeeded in observing 153Eu, 59Co and 31P NMR spectra in zero magnetic field. The sharp 153Eu zero field NMR (ZF NMR) lines indicate homogeneous Eu ordered moment. The 59Co and 31P ZF NMR spectra showed an asymmetric spectral shape, indicating a distribution of the internal magnetic induction at each nuclear position. The AFM propagation vector k characterizing the helical AFM state can be determined from the internal magnetic induction at Co site. We have determined the model-independent value of the AFM propagation vector k distributed from (0, 0, 0.86)2π/c to (0, 0, 0.73)2π/c, where c is the lattice parameter.

Alkaline phosphatase activity in salivary gland cells of Rhodnius neglectus and R. prolixus (Hemiptera, Triatominae).

PubMed

Lima-Oliveira, A P M; Alevi, K C C; Anhê, A C B; Azeredo-Oliveira, M T V

2016-07-29

Alkaline phosphatase activity was detected in salivary gland cells of the Rhodnius neglectus Lent, 1954, and R. prolixus Stal, 1859, vectors of Trypanosoma cruzi Chagas, 1909 (etiological agent of Chagas disease) and T. rangeli Tejera, 1920 (pathogenic to insect). The Gomori technique was used to demonstrate alkaline phosphatase activity. Alkaline phosphatase activity was observed throughout the entire gland, with an increased activity in the posterior region of the principal gland. In particular, phosphatase activity was found in the nucleolar corpuscles, suggesting a relationship with the rRNA transcription and ribosomal biogenesis. Alkaline phosphatase was also detected in the nuclear membrane and nuclear matrix, suggesting an association with the nucleo-cytoplasmic transport of ribonucleoproteins and the mechanisms of cell cycle and DNA replication, respectively. This study highlights the importance of alkaline phosphatase in the salivary gland of R. prolixus and R. neglectus and emphasizes its importance in secretory activity. Secretory activity is directly involved in hematophagy and, consequently, in development during metamorphosis. The observed presence of alkaline phosphatase suggests its involvement in the production of saliva allowing feeding of these insects that are important vectors of Chagas disease.

Genetic engineering including superseding microinjection: new ways to make GM pigs.

PubMed

Galli, Cesare; Perota, Andrea; Brunetti, Dario; Lagutina, Irina; Lazzari, Giovanna; Lucchini, Franco

2010-01-01

Techniques for genetic engineering of swine are providing genetically modified animals of importance for the field of xenotransplantation, animal models for human diseases and for a variety of research applications. Many of these modifications have been directed toward avoiding naturally existing cellular and antibody responses to species-specific antigens. A number of techniques are today available to engineering the genome of mammals, these range from the well established less efficient method of DNA microinjection into the zygote, the use of viral vectors, to the more recent use of somatic cell nuclear transfer. The use of enzymatic engineering that are being developed now will refine the precision of the genetic modification combined with the use of new vectors like transposons. The use of somatic cell nuclear transfer is currently the most efficient way to generate genetically modified pigs. The development of enzymatic engineering with zinc-finger nucleases, recombinases and transposons will revolutionize the field. Nevertheless, genetic engineering in large domesticated animals will remain a challenging task. Recent improvements in several fields of cell and molecular biology offer new promises and opportunities toward an easier, cost-effective and efficient generation of transgenic pigs. © 2010 John Wiley & Sons A/S.

Coherent and incoherent J /ψ photonuclear production in an energy-dependent hot-spot model

NASA Astrophysics Data System (ADS)

Cepila, J.; Contreras, J. G.; Krelina, M.

2018-02-01

In a previous publication, we have presented a model for the photoproduction of J /ψ vector mesons off protons, where the proton structure in the impact-parameter plane is described by an energy-dependent hot-spot profile. Here we extend this model to study the photonuclear production of J /ψ vector mesons in coherent and incoherent interactions of heavy nuclei. We study two methods to extend the model to the nuclear case: using the standard Glauber-Gribov formalism and using geometric scaling to obtain the nuclear saturation scale. We find that the incoherent cross section changes sizably with the inclusion of subnucleonic hot spots and that this change is energy dependent. We propose to search for this behavior by measuring the ratio of the incoherent to coherent cross sections at different energies. We compare the results of our model to results from the Relativistic Heavy-Ion Collider (RHIC) and from run 1 at the Large Hadron Collider (LHC), finding satisfactory agreement. We also present predictions for the LHC at the new energies reached in run 2. The predictions include J /ψ production in ultraperipheral collisions, as well as the recently observed photonuclear production in peripheral collisions.

The HERMES Polarized Atomic Beam Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nass, A.

2003-07-30

The atomic beam source (ABS) provides nuclear polarized hydrogen or deuterium atoms for the HERMES target at flow rates of about 6.5 {center_dot} 1016H-vector/s (hydrogen in two hyperfine substates) and 6.0 {center_dot} 1016D-vector/s (deuterium in three hyperfine substates). The degree of dissociation of 93% for H (95% for D) at the entrance of the storage cell and the nuclear polarization of around 0.97 (H) and 0.92 (D) have been found to be constant within a a couple of percent over the whole running period of the HERMES experiment. A new dissociator (MWD) based on a microwave discharge at 2.45 GHzmore » has been developed and installed into the HERMES-ABS in 2000. Since the velocity distribution of the MWD differs from that of the RFD the intensity could be increased further with a modified sextupole magnet system. For this purpose the way for a new start generator for sextupole tracking calculations was opened. Monte-Carlo simulations were successfully used to describe the gas expansion between nozzle, skimmer and collimator. A new type of beam monitor was used to study the beam formation after the nozzle.« less

Changes in the Genetic Structure of Aedes aegypti (Diptera: Culicidae) Populations in Queensland, Australia, Across Two Seasons: Implications for Potential Mosquito Releases

PubMed Central

ENDERSBY, N. M.; HOFFMANN, A. A.; WHITE, V. L.; RITCHIE, S. A.; JOHNSON, P. H.; WEEKS, A. R.

2012-01-01

Diseases transmitted by mosquitoes could be controlled if vector populations were replaced with strains that have reduced vector competency. Such a strategy is being developed for control of dengue virus which is transmitted by Aedes aegypti (L.) (Diptera: Culicidae). Mosquitoes artificially infected with the bacterium, Wolbachia pipientis Hertig, are being assessed as candidates for release at the adult stage with the aim of replacement of the wild population. Wolbachia can reduce the capacity of Ae. aegypti to transmit dengue virus and has potential to be driven through the natural population via a system of cytoplasmic incompatibility. Deployment of benign mosquito strains will be influenced by population size and structure of wild-type Ae. aegypti in proposed release areas, as well as rates of gene flow among populations in the wet and dry tropical seasons. Mosquitoes from northern Queensland were screened with genetic markers to find an optimal locality for release of a benign strain of Ae. aegypti. The inland towns of Chillagoe and Charters Towers and the coastal town of Ingham had mosquito populations that were partly genetically isolated from mosquitoes in other areas across both seasons. These locations may be suitable release sites if it is important for the released strain to be restricted during initial phases of implementation. Smaller genetic differences were also evident among other regions and were consistent over two seasons (wet and dry). PMID:21936318

Nuclear energy: Where do we go from here?

NASA Astrophysics Data System (ADS)

Muslim, Dato'Noramly, Dr

2015-04-01

As Malaysia progresses towards 2020, the depleting resource of oil and gas has forced a re-look at alternatives to replace fossil fuels as energy sources. Among the viable options is nuclear energy, enabling us to meet energy needs and sustain national development in the twenty-first century. Three essential steps Malaysia must take to introduce nuclear power into its energy mix are: energy planning, infrastructure development, and deployment. Malaysia has to face a series of challenges, including public acceptance, waste management, minimizing proliferation risk, and ensuring the security of nuclear plants and materials. Timely development of qualified and competent manpower is a key limiting factor in the development and transfer of nuclear technologies — and education and training take time, effort and money. There is a need for political will. Within the Asian region, China, Korea and Japan are in the forefront in utilizing nuclear power to meet electricity demands. Countries such as UAE, Bangladesh, Vietnam and Turkey are moving ahead with the nuclear option for electricity generation and they have begun planning and construction of nuclear power plants. Against this backdrop, what are Malaysia's moves? This paper discusses various options and challenges, obstacles and repercussions in meeting future energy demands.

COHERENT constraints to conventional and exotic neutrino physics

NASA Astrophysics Data System (ADS)

Papoulias, D. K.; Kosmas, T. S.

2018-02-01

The process of neutral-current coherent elastic neutrino-nucleus scattering, consistent with the Standard Model (SM) expectation, has been recently measured by the COHERENT experiment at the Spallation Neutron Source. On the basis of the observed signal and our nuclear calculations for the relevant Cs and I isotopes, the extracted constraints on both conventional and exotic neutrino physics are updated. The present study concentrates on various SM extensions involving vector and tensor nonstandard interactions as well as neutrino electromagnetic properties, with an emphasis on the neutrino magnetic moment and the neutrino charge radius. Furthermore, models addressing a light sterile neutrino state and scenarios with new propagator fields—such as vector Z' and scalar bosons—are examined, and the corresponding regions excluded by the COHERENT experiment are presented.

A novel dynamic mechanical testing technique for reverse shoulder replacements.

PubMed

Dabirrahmani, Danè; Bokor, Desmond; Appleyard, Richard

2014-04-01

In vitro mechanical testing of orthopedic implants provides information regarding their mechanical performance under simulated biomechanical conditions. Current in vitro component stability testing methods for reverse shoulder implants are based on anatomical shoulder designs, which do not capture the dynamic nature of these loads. With glenoid component loosening as one of the most prevalent modes of failure in reverse shoulder replacements, it is important to establish a testing protocol with a more realistic loading regime. This paper introduces a novel method of mechanically testing reverse shoulder implants, using more realistic load magnitudes and vectors, than is currently practiced. Using a custom made jig setup within an Instron mechanical testing system, it is possible to simulate the change in magnitude and direction of the joint load during arm abduction. This method is a step towards a more realistic testing protocol for measuring reverse shoulder implant stability.

Tensor Fermi liquid parameters in nuclear matter from chiral effective field theory

NASA Astrophysics Data System (ADS)

Holt, J. W.; Kaiser, N.; Whitehead, T. R.

2018-05-01

We compute from chiral two- and three-body forces the complete quasiparticle interaction in symmetric nuclear matter up to twice nuclear matter saturation density. Second-order perturbative contributions that account for Pauli blocking and medium polarization are included, allowing for an exploration of the full set of central and noncentral operator structures permitted by symmetries and the long-wavelength limit. At the Hartree-Fock level, the next-to-next-to-leading order three-nucleon force contributes to all noncentral interactions, and their strengths grow approximately linearly with the nucleon density up to that of saturated nuclear matter. Three-body forces are shown to enhance the already strong proton-neutron effective tensor interaction, while the corresponding like-particle tensor force remains small. We also find a large isovector cross-vector interaction but small center-of-mass tensor interactions in the isoscalar and isovector channels. The convergence of the expansion of the noncentral quasiparticle interaction in Landau parameters and Legendre polynomials is studied in detail.

A computer-aided diagnosis system of nuclear cataract.

PubMed

Li, Huiqi; Lim, Joo Hwee; Liu, Jiang; Mitchell, Paul; Tan, Ava Grace; Wang, Jie Jin; Wong, Tien Yin

2010-07-01

Cataracts are the leading cause of blindness worldwide, and nuclear cataract is the most common form of cataract. An algorithm for automatic diagnosis of nuclear cataract is investigated in this paper. Nuclear cataract is graded according to the severity of opacity using slit lamp lens images. Anatomical structure in the lens image is detected using a modified active shape model. On the basis of the anatomical landmark, local features are extracted according to clinical grading protocol. Support vector machine regression is employed for grade prediction. This is the first time that the nucleus region can be detected automatically in slit lamp images. The system is validated using clinical images and clinical ground truth on >5000 images. The success rate of structure detection is 95% and the average grading difference is 0.36 on a 5.0 scale. The automatic diagnosis system can improve the grading objectivity and potentially be used in clinics and population studies to save the workload of ophthalmologists.

Malaysian public perception towards nuclear power energy-related issues

NASA Astrophysics Data System (ADS)

Misnon, Fauzan Amin; Hu, Yeoh Siong; Rahman, Irman Abd.; Yasir, Muhamad Samudi

2017-01-01

Malaysia had considered nuclear energy as an option for future electricity generation during the 9th Malaysia Development Plan. Since 2009, Malaysia had implemented a number of important preparatory steps towards this goal, including the establishment of Nuclear Power Corporation of Malaysia (MNPC) as first Nuclear Energy Programme Implementing Organization (NEPIO) in Malaysia. In light of the establishment of MNPC, the National Nuclear Policy was formulated in 2010 and a new comprehensive nuclear law to replace the existing Atomic Energy Licensing Act (Act 304) is currently in the pipeline. Internationally, public acceptance is generally used to gauge the acceptance of nuclear energy by the public whenever a government decides to engage in nuclear energy. A public survey was conducted in between 14 March 2016 to 10 May 2016 focusing on the Malaysian public acceptance and perception towards the implementation of nuclear energy in Malaysia. The methodology of this research was aim on finding an overview of the general knowledge, public-relation recommendation, perception and acceptance of Malaysian towards the nuclear power development program. The combination of information gathered from this study can be interpreted as an indication of the complexity surrounding the development of nuclear energy and its relationship with the unique background of Malaysian demography. This paper will focus mainly on energy-related section in the survey in comparison with nuclear energy.

The relationship between three-dimensional knee MRI bone shape and total knee replacement—a case control study: data from the Osteoarthritis Initiative

PubMed Central

Barr, Andrew J.; Dube, Bright; Hensor, Elizabeth M. A.; Kingsbury, Sarah R.; Peat, George; Bowes, Mike A.; Sharples, Linda D.

2016-01-01

Objective. There is growing understanding of the importance of bone in OA. Our aim was to determine the relationship between 3D MRI bone shape and total knee replacement (TKR). Methods. A nested case-control study within the Osteoarthritis Initiative cohort identified case knees with confirmed TKR for OA and controls that were matched using propensity scores. Active appearance modelling quantification of the bone shape of all knee bones identified vectors between knees having or not having OA. Vectors were scaled such that −1 and +1 represented the mean non-OA and mean OA shapes. Results. Compared to controls (n = 310), TKR cases (n = 310) had a more positive mean baseline 3D bone shape vector, indicating more advanced structural OA, for the femur [mean 0.98 vs −0.11; difference (95% CI) 1.10 (0.88, 1.31)], tibia [mean 0.86 vs −0.07; difference (95% CI) 0.94 (0.72, 1.16)] and patella [mean 0.95 vs 0.03; difference (95% CI) 0.92 (0.65, 1.20)]. Odds ratios (95% CI) for TKR per normalized unit of 3D bone shape vector for the femur, tibia and patella were: 1.85 (1.59, 2.16), 1.64 (1.42, 1.89) and 1.36 (1.22, 1.50), respectively, all P < 0.001. After including Kellgren–Lawrence grade in a multivariable analysis, only the femur 3D shape vector remained significantly associated with TKR [odds ratio 1.24 (1.02, 1.51)]. Conclusion. 3D bone shape was associated with the endpoint of this study, TKR, with femoral shape being most associated. This study contributes to the validation of quantitative MRI bone biomarkers for OA structure-modification trials. PMID:27185958

10 CFR Appendix H to Part 50 - Reactor Vessel Material Surveillance Program Requirements

Code of Federal Regulations, 2010 CFR

2010-01-01

... light water nuclear power reactors which result from exposure of these materials to neutron irradiation... the beltline region so that the specimen irradiation history duplicates, to the extent practicable... insertion of replacement capsules. Accelerated irradiation capsules may be used in addition to the required...

10 CFR Appendix H to Part 50 - Reactor Vessel Material Surveillance Program Requirements

Code of Federal Regulations, 2014 CFR

2014-01-01

... light water nuclear power reactors which result from exposure of these materials to neutron irradiation... the beltline region so that the specimen irradiation history duplicates, to the extent practicable... insertion of replacement capsules. Accelerated irradiation capsules may be used in addition to the required...

10 CFR Appendix H to Part 50 - Reactor Vessel Material Surveillance Program Requirements

Code of Federal Regulations, 2012 CFR

2012-01-01

... light water nuclear power reactors which result from exposure of these materials to neutron irradiation... the beltline region so that the specimen irradiation history duplicates, to the extent practicable... insertion of replacement capsules. Accelerated irradiation capsules may be used in addition to the required...

10 CFR Appendix H to Part 50 - Reactor Vessel Material Surveillance Program Requirements

Code of Federal Regulations, 2011 CFR

2011-01-01

... light water nuclear power reactors which result from exposure of these materials to neutron irradiation... the beltline region so that the specimen irradiation history duplicates, to the extent practicable... insertion of replacement capsules. Accelerated irradiation capsules may be used in addition to the required...

10 CFR Appendix H to Part 50 - Reactor Vessel Material Surveillance Program Requirements

Code of Federal Regulations, 2013 CFR

2013-01-01

... light water nuclear power reactors which result from exposure of these materials to neutron irradiation... the beltline region so that the specimen irradiation history duplicates, to the extent practicable... insertion of replacement capsules. Accelerated irradiation capsules may be used in addition to the required...

Minerals and design of new waste forms for conditioning nuclear waste

NASA Astrophysics Data System (ADS)

Montel, Jean-Marc

2011-02-01

Safe storage of radioactive waste is a major challenge for the nuclear industry. Mineralogy is a good basis for designing ceramics, which could eventually replace nuclear glasses. This requires a new storage concept: separation-conditioning. Basic rules of crystal chemistry allow one to select the most suitable structures and natural occurrences allow assessing the long-term performance of ceramics in a geological environment. Three criteria are of special interest: compatibility with geological environment, resistance to natural fluids, and effects of self-irradiation. If mineralogical information is efficient for predicting the behaviour of common, well-known minerals, such as zircon, monazite or apatite, more research is needed to rationalize the long-term behaviour of uncommon waste form analogs.

[Construction and Function Verification of a Novel Shuttle Vector Containing a Marker Gene Self-deletion System].

PubMed

Li, Lili; Wang, Zhan; Zhou, Yubai; Zhang, Fang; Shen, Sisi; Li, Zelin; Zeng, Yi

2015-09-01

For rapid and accurate screening of recombinant modified vaccinia virus Ankara (rMVA) that satisfied the quality standards of clinical trials, a novel shuttle vector that can delete the marker gene automatically during virus propagation was construted: pZL-EGFP. To construct the pZL-EGFP, the original shuttle vector pSC11 was modified by replacing the LacZ marker gene with enhanced green fluorescent protein (EGFP) and then inserting homologous sequences of TKL into the flank regions of EGFP. Baby hamster kidney (BHK)-21 cells were cotransfected with pZL-EGFP and MVA, and underwent ten passages and one plaque screening to obtain the EGFP-free rMVA carrying the exogenous gene. Resulting rMVA was tested by polymerase chain reaction and western blotting to verify pZL-EGFP function. A novel shuttle vector pZL-EGFP containing an EGFP marker gene which could be deleted automatically was constructed. This gene deletion had no effect on the activities of rMVA, and the exogenous gene could be expressed stably. These results suggest that rMVA can be packaged efficiently by homologous recombination between pZL-EGFP and MVA in BHK-21 cells, and that the carried EGFP gene can be removed automatically by intramolecular homologous recombination during virus passage. Meanwhile, the gene deletion had no influence on the activities of rMVA and the expression of exogenous target gene. This study lays a solid foundation for the future research.

Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key theory.

PubMed

Molina-Cruz, Alvaro; Canepa, Gaspar E; Kamath, Nitin; Pavlovic, Noelle V; Mu, Jianbing; Ramphul, Urvashi N; Ramirez, Jose Luis; Barillas-Mury, Carolina

2015-12-08

Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the "lock-and-key theory" of P. falciparum globalization, is proposed, and its implications are discussed.

Widespread Pyrethroid and DDT Resistance in the Major Malaria Vector Anopheles funestus in East Africa Is Driven by Metabolic Resistance Mechanisms

PubMed Central

Mulamba, Charles; Riveron, Jacob M.; Ibrahim, Sulaiman S.; Irving, Helen; Barnes, Kayla G.; Mukwaya, Louis G.; Birungi, Josephine; Wondji, Charles S.

2014-01-01

Background Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms. Methodology/Principal Findings Female An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin) and II (deltamethrin) pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance. Conclusion The extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management. PMID:25333491

A virus vector based on Canine Herpesvirus for vaccine applications in canids.

PubMed

Strive, T; Hardy, C M; Wright, J; Reubel, G H

2007-01-31

Canine Herpesvirus (CHV) is being developed as a virus vector for the vaccination of European red foxes. However, initial studies using recombinant CHV vaccines in foxes revealed viral attenuation and lack of antibody response to inserted foreign antigens. These findings were attributed both to inactivation of the thymidine kinase (TK) gene and excess foreign genetic material in the recombinant viral genome. In this study, we report an improved CHV-bacterial artificial chromosome (BAC) vector system designed to overcome attenuation in foxes. A non-essential region was identified in the CHV genome as an alternative insertion site for foreign genes. Replacement of a guanine/cytosine (GC)-rich intergenic region between UL21 and UL22 of CHV with a marker gene did not change growth behaviour in vitro, showing that this region is not essential for virus growth in cell culture. We subsequently produced a CHV-BAC vector with an intact TK gene in which the bacterial genes and the antigen expression cassette were inserted into this GC-rich locus. Unlike earlier constructs, the new CHV-BAC allowed self-excision of the bacterial genes via homologous recombination after transfection of BACs into cell culture. The BAC-CHV system was used to produce a recombinant virus that constitutively expressed porcine zona pellucida subunit C protein between the UL21 and UL22 genes of CHV. Complete self-excision of the bacterial genes from CHV was achieved within one round of replication whilst retaining antigen gene expression.

Progress and challenges in viral vector manufacturing

PubMed Central

van der Loo, Johannes C.M.; Wright, J. Fraser

2016-01-01

Promising results in several clinical studies have emphasized the potential of gene therapy to address important medical needs and initiated a surge of investments in drug development and commercialization. This enthusiasm is driven by positive data in clinical trials including gene replacement for Hemophilia B, X-linked Severe Combined Immunodeficiency, Leber's Congenital Amaurosis Type 2 and in cancer immunotherapy trials for hematological malignancies using chimeric antigen receptor T cells. These results build on the recent licensure of the European gene therapy product Glybera for the treatment of lipoprotein lipase deficiency. The progress from clinical development towards product licensure of several programs presents challenges to gene therapy product manufacturing. These include challenges in viral vector-manufacturing capacity, where an estimated 1–2 orders of magnitude increase will likely be needed to support eventual commercial supply requirements for many of the promising disease indications. In addition, the expanding potential commercial product pipeline and the continuously advancing development of recombinant viral vectors for gene therapy require that products are well characterized and consistently manufactured to rigorous tolerances of purity, potency and safety. Finally, there is an increase in regulatory scrutiny that affects manufacturers of investigational drugs for early-phase clinical trials engaged in industry partnerships. Along with the recent increase in biopharmaceutical funding in gene therapy, industry partners are requiring their academic counterparts to meet higher levels of GMP compliance at earlier stages of clinical development. This chapter provides a brief overview of current progress in the field and discusses challenges in vector manufacturing. PMID:26519140

Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function.

PubMed

Suzuki, Kunihiro; Olah, Gabor; Modis, Katalin; Coletta, Ciro; Kulp, Gabriella; Gerö, Domokos; Szoleczky, Petra; Chang, Tuanjie; Zhou, Zongmin; Wu, Lingyun; Wang, Rui; Papapetropoulos, Andreas; Szabo, Csaba

2011-08-16

The goal of the present studies was to investigate the role of changes in hydrogen sulfide (H(2)S) homeostasis in the pathogenesis of hyperglycemic endothelial dysfunction. Exposure of bEnd3 microvascular endothelial cells to elevated extracellular glucose (in vitro "hyperglycemia") induced the mitochondrial formation of reactive oxygen species (ROS), which resulted in an increased consumption of endogenous and exogenous H(2)S. Replacement of H(2)S or overexpression of the H(2)S-producing enzyme cystathionine-γ-lyase (CSE) attenuated the hyperglycemia-induced enhancement of ROS formation, attenuated nuclear DNA injury, reduced the activation of the nuclear enzyme poly(ADP-ribose) polymerase, and improved cellular viability. In vitro hyperglycemia resulted in a switch from oxidative phosphorylation to glycolysis, an effect that was partially corrected by H(2)S supplementation. Exposure of isolated vascular rings to high glucose in vitro induced an impairment of endothelium-dependent relaxations, which was prevented by CSE overexpression or H(2)S supplementation. siRNA silencing of CSE exacerbated ROS production in hyperglycemic endothelial cells. Vascular rings from CSE(-/-) mice exhibited an accelerated impairment of endothelium-dependent relaxations in response to in vitro hyperglycemia, compared with wild-type controls. Streptozotocin-induced diabetes in rats resulted in a decrease in the circulating level of H(2)S; replacement of H(2)S protected from the development of endothelial dysfunction ex vivo. In conclusion, endogenously produced H(2)S protects against the development of hyperglycemia-induced endothelial dysfunction. We hypothesize that, in hyperglycemic endothelial cells, mitochondrial ROS production and increased H(2)S catabolism form a positive feed-forward cycle. H(2)S replacement protects against these alterations, resulting in reduced ROS formation, improved endothelial metabolic state, and maintenance of normal endothelial function.

A Centrifugal Contactor Design to Facilitate Remote Replacement

DOE Office of Scientific and Technical Information (OSTI.GOV)

David H. Meikrantz; Jack. D. Law; Troy G. Garn

2011-03-01

Advanced designs of nuclear fuel recycling and radioactive waste treatment plants are expected to include more ambitious goals for solvent extraction based separations including; higher separations efficiency, high-level waste minimization, and a greater focus on continuous processes to minimize cost and footprint. Therefore, Annular Centrifugal Contactors (ACCs) are destined to play a more important role for such future processing schemes. This work continues the development of remote designs for ACCs that can process the large throughputs needed for future nuclear fuel recycling and radioactive waste treatment plants. A three stage, 12.5 cm diameter rotor module has been constructed and ismore » being evaluated for use in highly radioactive environments. This prototype assembly employs three standard CINC V-05 clean-in-place (CIP) units modified for remote service and replacement via new methods of connection for solution inlets, outlets, drain and CIP. Hydraulic testing and functional checks were successfully conducted and then the prototype was evaluated for remote handling and maintenance. Removal and replacement of the center position V-05R contactor in the three stage assembly was demonstrated using an overhead rail mounted PaR manipulator. Initial evaluation indicates a viable new design for interconnecting and cleaning individual stages while retaining the benefits of commercially reliable ACC equipment. Replacement of a single stage via remote manipulators and tools is estimated to take about 30 minutes, perhaps fast enough to support a contactor change without loss of process equilibrium. The design presented in this work is scalable to commercial ACC models from V-05 to V-20 with total throughput rates ranging from 20 to 650 liters per minute.« less

A dual selection based, targeted gene replacement tool for Magnaporthe grisea and Fusarium oxysporum.

PubMed

Khang, Chang Hyun; Park, Sook-Young; Lee, Yong-Hwan; Kang, Seogchan

2005-06-01

Rapid progress in fungal genome sequencing presents many new opportunities for functional genomic analysis of fungal biology through the systematic mutagenesis of the genes identified through sequencing. However, the lack of efficient tools for targeted gene replacement is a limiting factor for fungal functional genomics, as it often necessitates the screening of a large number of transformants to identify the desired mutant. We developed an efficient method of gene replacement and evaluated factors affecting the efficiency of this method using two plant pathogenic fungi, Magnaporthe grisea and Fusarium oxysporum. This method is based on Agrobacterium tumefaciens-mediated transformation with a mutant allele of the target gene flanked by the herpes simplex virus thymidine kinase (HSVtk) gene as a conditional negative selection marker against ectopic transformants. The HSVtk gene product converts 5-fluoro-2'-deoxyuridine to a compound toxic to diverse fungi. Because ectopic transformants express HSVtk, while gene replacement mutants lack HSVtk, growing transformants on a medium amended with 5-fluoro-2'-deoxyuridine facilitates the identification of targeted mutants by counter-selecting against ectopic transformants. In addition to M. grisea and F. oxysporum, the method and associated vectors are likely to be applicable to manipulating genes in a broad spectrum of fungi, thus potentially serving as an efficient, universal functional genomic tool for harnessing the growing body of fungal genome sequence data to study fungal biology.

Characterization of intronic uridine-rich sequence elements acting as possible targets for nuclear proteins during pre-mRNA splicing in Nicotiana plumbaginifolia.

PubMed

Gniadkowski, M; Hemmings-Mieszczak, M; Klahre, U; Liu, H X; Filipowicz, W

1996-02-15

Introns of nuclear pre-mRNAs in dicotyledonous plants, unlike introns in vertebrates or yeast, are distinctly rich in A+U nucleotides and this feature is essential for their processing. In order to define more precisely sequence elements important for intron recognition in plants, we investigated the effects of short insertions, either U-rich or A-rich, on splicing of synthetic introns in transfected protoplast of Nicotiana plumbaginifolia. It was found that insertions of U-rich (sequence UUUUUAU) but not A-rich (AUAAAAA) segments can activate splicing of a GC-rich synthetic infron, and that U-rich segments, or multimers thereof, can function irrespective of the site of insertion within the intron. Insertions of multiple U-rich segments, either at the same or different locations, generally had an additive, stimulatory effect on splicing. Mutational analysis showed that replacement of one or two U residues in the UUUUUAU sequence with A or C residues had only a small effect on splicing, but replacement with G residues was strongly inhibitory. Proteins that interact with fragments of natural and synthetic pre-mRNAs in vitro were identified in nuclear extracts of N.plumbaginifolia by UV cross- linking. The profile of cross-linked plant proteins was considerably less complex than that obtained with a HeLa cell nuclear extract. Two major cross-linkable plant proteins had apparent molecular mass of 50 and 54 kDa and showed affinity for oligouridilates present in synGC introns or for poly(U).

Characterization of intronic uridine-rich sequence elements acting as possible targets for nuclear proteins during pre-mRNA splicing in Nicotiana plumbaginifolia.

PubMed Central

Gniadkowski, M; Hemmings-Mieszczak, M; Klahre, U; Liu, H X; Filipowicz, W

1996-01-01

Introns of nuclear pre-mRNAs in dicotyledonous plants, unlike introns in vertebrates or yeast, are distinctly rich in A+U nucleotides and this feature is essential for their processing. In order to define more precisely sequence elements important for intron recognition in plants, we investigated the effects of short insertions, either U-rich or A-rich, on splicing of synthetic introns in transfected protoplast of Nicotiana plumbaginifolia. It was found that insertions of U-rich (sequence UUUUUAU) but not A-rich (AUAAAAA) segments can activate splicing of a GC-rich synthetic infron, and that U-rich segments, or multimers thereof, can function irrespective of the site of insertion within the intron. Insertions of multiple U-rich segments, either at the same or different locations, generally had an additive, stimulatory effect on splicing. Mutational analysis showed that replacement of one or two U residues in the UUUUUAU sequence with A or C residues had only a small effect on splicing, but replacement with G residues was strongly inhibitory. Proteins that interact with fragments of natural and synthetic pre-mRNAs in vitro were identified in nuclear extracts of N.plumbaginifolia by UV cross- linking. The profile of cross-linked plant proteins was considerably less complex than that obtained with a HeLa cell nuclear extract. Two major cross-linkable plant proteins had apparent molecular mass of 50 and 54 kDa and showed affinity for oligouridilates present in synGC introns or for poly(U). PMID:8604302

Nuclear design of a vapor core reactor for space nuclear propulsion

NASA Astrophysics Data System (ADS)

Dugan, Edward T.; Watanabe, Yoichi; Kuras, Stephen A.; Maya, Isaac; Diaz, Nils J.

1993-01-01

Neutronic analysis methodology and results are presented for the nuclear design of a vapor core reactor for space nuclear propulsion. The Nuclear Vapor Thermal Reactor (NVTR) Rocket Engine uses modified NERVA geometry and systems which the solid fuel replaced by uranium tetrafluoride vapor. The NVTR is an intermediate term gas core thermal rocket engine with specific impulse in the range of 1000-1200 seconds; a thrust of 75,000 lbs for a hydrogen flow rate of 30 kg/s; average core exit temperatures of 3100 K to 3400 K; and reactor thermal powers of 1400 to 1800 MW. Initial calculations were performed on epithermal NVTRs using ZrC fuel elements. Studies are now directed at thermal NVTRs that use fuel elements made of C-C composite. The large ZrC-moderated reactors resulted in thrust-to-weight ratios of only 1 to 2; the compact C-C composite systems yield thrust-to-weight ratios of 3 to 5.

Environmental security in the Czech Republic: Status and concerns in the post Communist era

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valley, P.J.

1998-10-01

The Czech Republic has made great strides toward reconciling its political and economic development with environmental protection and security issues since its recent democratization. Although new technological and legislative efforts continue to work at reducing emissions from automobiles, industries, power plants and coal mining, the Republic is committed to continuing its battle against air and water pollution, poor waste management, and needless destruction of nature. Shifting the structure of primary energy sources to qualitatively better fuels, along with the introduction of less energy-consuming technologies and the activation of new nuclear reactors, would eventually replace most of the output of coalmore » burning power plants. However, the use of nuclear power has been opposed by several political and environmental activists groups. At the international level, Austria`s opposition to the Temelin Nuclear Power plant is of great concern since Austria, as a non-nuclear state, propagates negative information about nuclear power to its citizens and other countries.« less

Fuel supply of nuclear power industry with the introduction of fast reactors

NASA Astrophysics Data System (ADS)

Muraviev, E. V.

2014-12-01

The results of studies conducted for the validation of the updated development strategy for nuclear power industry in Russia in the 21st century are presented. Scenarios with different options for the reprocessing of spent fuel of thermal reactors and large-scale growth of nuclear power industry based on fast reactors of inherent safety with a breeding ratio of ˜1 in a closed nuclear fuel cycle are considered. The possibility of enhanced fuel breeding in fast reactors is also taken into account in the analysis. The potential to establish a large-scale nuclear power industry that covers 100% of the increase in electric power requirements in Russia is demonstrated. This power industry may be built by the end of the century through the introduction of fast reactors (replacing thermal ones) with a gross uranium consumption of up to ˜1 million t and the termination of uranium mining even if the reprocessing of spent fuel of thermal reactors is stopped or suffers a long-term delay.

Strong dynamics and lattice gauge theory

NASA Astrophysics Data System (ADS)

Schaich, David

In this dissertation I use lattice gauge theory to study models of electroweak symmetry breaking that involve new strong dynamics. Electroweak symmetry breaking (EWSB) is the process by which elementary particles acquire mass. First proposed in the 1960s, this process has been clearly established by experiments, and can now be considered a law of nature. However, the physics underlying EWSB is still unknown, and understanding it remains a central challenge in particle physics today. A natural possibility is that EWSB is driven by the dynamics of some new, strongly-interacting force. Strong interactions invalidate the standard analytical approach of perturbation theory, making these models difficult to study. Lattice gauge theory is the premier method for obtaining quantitatively-reliable, nonperturbative predictions from strongly-interacting theories. In this approach, we replace spacetime by a regular, finite grid of discrete sites connected by links. The fields and interactions described by the theory are likewise discretized, and defined on the lattice so that we recover the original theory in continuous spacetime on an infinitely large lattice with sites infinitesimally close together. The finite number of degrees of freedom in the discretized system lets us simulate the lattice theory using high-performance computing. Lattice gauge theory has long been applied to quantum chromodynamics, the theory of strong nuclear interactions. Using lattice gauge theory to study dynamical EWSB, as I do in this dissertation, is a new and exciting application of these methods. Of particular interest is non-perturbative lattice calculation of the electroweak S parameter. Experimentally S ≈ -0.15(10), which tightly constrains dynamical EWSB. On the lattice, I extract S from the momentum-dependence of vector and axial-vector current correlators. I created and applied computer programs to calculate these correlators and analyze them to determine S. I also calculated the masses and other properties of the new particles predicted by these theories. I find S ≳ 0.1 in the specific theories I study. Although this result still disagrees with experiment, it is much closer to the experimental value than is the conventional wisdom S ≳ 0.3. These results encourage further lattice studies to search for experimentally viable strongly-interacting theories of EWSB.

Negative muon chemistry: the quantum muon effect and the finite nuclear mass effect.

PubMed

Posada, Edwin; Moncada, Félix; Reyes, Andrés

2014-10-09

The any-particle molecular orbital method at the full configuration interaction level has been employed to study atoms in which one electron has been replaced by a negative muon. In this approach electrons and muons are described as quantum waves. A scheme has been proposed to discriminate nuclear mass and quantum muon effects on chemical properties of muonic and regular atoms. This study reveals that the differences in the ionization potentials of isoelectronic muonic atoms and regular atoms are of the order of millielectronvolts. For the valence ionizations of muonic helium and muonic lithium the nuclear mass effects are more important. On the other hand, for 1s ionizations of muonic atoms heavier than beryllium, the quantum muon effects are more important. In addition, this study presents an assessment of the nuclear mass and quantum muon effects on the barrier of Heμ + H2 reaction.

Nuclear Electric Vehicle Optimization Toolset (NEVOT)

NASA Technical Reports Server (NTRS)

Tinker, Michael L.; Steincamp, James W.; Stewart, Eric T.; Patton, Bruce W.; Pannell, William P.; Newby, Ronald L.; Coffman, Mark E.; Kos, Larry D.; Qualls, A. Lou; Greene, Sherrell

2004-01-01

The Nuclear Electric Vehicle Optimization Toolset (NEVOT) optimizes the design of all major nuclear electric propulsion (NEP) vehicle subsystems for a defined mission within constraints and optimization parameters chosen by a user. The tool uses a genetic algorithm (GA) search technique to combine subsystem designs and evaluate the fitness of the integrated design to fulfill a mission. The fitness of an individual is used within the GA to determine its probability of survival through successive generations in which the designs with low fitness are eliminated and replaced with combinations or mutations of designs with higher fitness. The program can find optimal solutions for different sets of fitness metrics without modification and can create and evaluate vehicle designs that might never be considered through traditional design techniques. It is anticipated that the flexible optimization methodology will expand present knowledge of the design trade-offs inherent in designing nuclear powered space vehicles and lead to improved NEP designs.

CBP for Field Workers – Results and Insights from Three Usability and Interface Design Evaluations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oxstrand, Johanna Helene; Le Blanc, Katya Lee; Bly, Aaron Douglas

2015-09-01

Nearly all activities that involve human interaction with the systems in a nuclear power plant are guided by procedures. Even though the paper-based procedures (PBPs) currently used by industry have a demonstrated history of ensuring safety, improving procedure use could yield significant savings in increased efficiency as well as improved nuclear safety through human performance gains. The nuclear industry is constantly trying to find ways to decrease the human error rate, especially the human errors associated with procedure use. As a step toward the goal of improving procedure use and adherence, researchers in the Light-Water Reactor Sustainability (LWRS) Program, togethermore » with the nuclear industry, have been investigating the possibility and feasibility of replacing the current paper-based procedure process with a computer-based procedure (CBP) system. This report describes a field evaluation of new design concepts of a prototype computer-based procedure system.« less

Germline Genetic Modification and Identity: the Mitochondrial and Nuclear Genomes.

PubMed

Scott, Rosamund; Wilkinson, Stephen

2017-12-01

In a legal 'first', the UK removed a prohibition against modifying embryos in human reproduction, to enable mitochondrial replacement techniques (MRTs), a move the Government distanced from 'germline genetic modification', which it aligned with modifying the nuclear genome. This paper (1) analyzes the uses and meanings of this term in UK/US legal and policy debates; and (2) evaluates related ethical concerns about identity. It shows that, with respect to identity, MRTs and nuclear genome editing techniques such as CRISPR/Cas-9 (now a policy topic), are not as different as has been supposed. While it does not follow that the two should be treated exactly alike, one of the central reasons offered for treating MRTs more permissively than nuclear genetic modification, and for not regarding MRTs as 'germline genetic modification', is thereby in doubt. Identity cannot, by itself, do the work thus far assigned to it, explicitly or otherwise, in law and policy.

US defense policy, US Air Force doctrine and strategic nuclear weapon systems, 1958-1964: the case of the Minuteman ICBM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reed, G.A.

This study examines the efforts of the US Air Force during 1958-1964 to develop doctrine for strategic nuclear weapon systems. These years were characterized by rapid, extensive change in the technology of nuclear weapons delivery systems, centering in ICBMs replacing bombers as the chief vehicles. Simultaneously, national military strategy changed with the transfer of power from the Eisenhower to the Kennedy Administrations, shifting from reliance on overwhelming nuclear retaliation to emphasis on balanced conventional and nuclear forces. Against this background, the study poses the question: did the Air Force, when confronted with major changes in technology and national policy, developmore » doctrine for strategic nuclear weapon systems that was politically acceptable, technically feasible, and strategically sound. Using the development of the Minuteman ICBM as a case study, the study examines the evolution of Air Force doctrine and concludes that the Air Force did not, because of conceptual problems and bureaucratic exigencies, develop a doctrine adequate to the requirements of deterrence in the dawning era of solid-fuel ICBMs.« less

Investigation and Implementation of Commercially Available Optically Stimulated Luminescence Dosimeters for Use in Fixed Nuclear Accident Dosimeter Systems.

PubMed

Georgeson, David L; Christiansen, Byron H

2018-06-01

Idaho National Laboratory transitioned from an external dosimetry system reliant on thermoluminescent dosimeters to one that uses optically stimulated luminescence dosimeters in 2010. This change not only affected the dosimeters worn by personnel, but those found in the nuclear-accident dosimeters used across Idaho National Laboratory. The elimination of on-site use and processing of thermoluminescent dosimeters impacted Idaho National Laboratory's ability to process nuclear-accident dosimeters in a timely manner. This change in processes drove Idaho National Laboratory to develop an alternative method for fixed nuclear-accident dosimeter gamma-dose analyses. This new method was driven by the need to establish a simple, cost-effective, and rapid-turnaround alternative to the thermoluminescent-dosimeter-based fixed nuclear-accident dosimeter system. An adaptation of existing technologies proved to be the most efficient path to this end. The purpose of this article is to delineate the technical basis for replacing the thermoluminescent dosimeter contained within the Idaho National Laboratory fixed nuclear-accident dosimeter system with optically stimulated luminescence-based Landauer, Inc., nanoDot dosimeters.

Implementation and Assessment of Advanced Analog Vector-Matrix Processor

NASA Technical Reports Server (NTRS)

Gary, Charles K.; Bualat, Maria G.; Lum, Henry, Jr. (Technical Monitor)

1994-01-01

This paper discusses the design and implementation of an analog optical vecto-rmatrix coprocessor with a throughput of 128 Mops for a personal computer. Vector matrix calculations are inherently parallel, providing a promising domain for the use of optical calculators. However, to date, digital optical systems have proven too cumbersome to replace electronics, and analog processors have not demonstrated sufficient accuracy in large scale systems. The goal of the work described in this paper is to demonstrate a viable optical coprocessor for linear operations. The analog optical processor presented has been integrated with a personal computer to provide full functionality and is the first demonstration of an optical linear algebra processor with a throughput greater than 100 Mops. The optical vector matrix processor consists of a laser diode source, an acoustooptical modulator array to input the vector information, a liquid crystal spatial light modulator to input the matrix information, an avalanche photodiode array to read out the result vector of the vector matrix multiplication, as well as transport optics and the electronics necessary to drive the optical modulators and interface to the computer. The intent of this research is to provide a low cost, highly energy efficient coprocessor for linear operations. Measurements of the analog accuracy of the processor performing 128 Mops are presented along with an assessment of the implications for future systems. A range of noise sources, including cross-talk, source amplitude fluctuations, shot noise at the detector, and non-linearities of the optoelectronic components are measured and compared to determine the most significant source of error. The possibilities for reducing these sources of error are discussed. Also, the total error is compared with that expected from a statistical analysis of the individual components and their relation to the vector-matrix operation. The sufficiency of the measured accuracy of the processor is compared with that required for a range of typical problems. Calculations resolving alloy concentrations from spectral plume data of rocket engines are implemented on the optical processor, demonstrating its sufficiency for this problem. We also show how this technology can be easily extended to a 100 x 100 10 MHz (200 Cops) processor.

[Construction of a general AAV vector regulated by minimal and artificial hypoxic-responsive element].

PubMed

Nie, Xiao-wei; Sun, Li-jun; Hao, Yue-wen; Yang, Guang-xiao; Wang, Quan-ying

2011-03-01

To synthesize the minimal and artificial HRE, and to insert it into the anterior extremity of CMV promoter of a AAV plasmid, and then to construct the AAV regulated by hypoxic-responsive element which was introduced into 293 cell by method of Ca3(PO4)2 using three plasmids. Thus obtaining the adenoassociated virus vector regulated by hypoxic-responsive element was possibly used for gene therapy in ischemia angiocardiopathy and cerebrovascular disease. Artificially synthesize the 36 bp nucleotide sequences of four connection in series HIF-binding sites A/GCGTG(4×HBS)and a 35 bp nucleotide sequences spacing inserted into anterior extremity of CMV promoter TATA Box, then amplified by PCR. The cDNA fragment was confirmed to be right by DNA sequencing. Molecular biology routine method was used to construct a AAV vector regulated by minimal hypoxic-responsive element after the normal CMV promoter in AAV vector was replaced by the CMV promoter included minimal hypoxic-responsive element. Then, NT4-6His-PR39 fusogenic peptide was inserted into MCS of the plasmid, the recombinant AAV vector was obtained by three plasmid co-transfection in 293 cells, in which we can also investigate the expression of 6×His using immunochemistry in hypoxia environment. Artificial HRE was inserted into anterior extremity of CMV promoter and there was a correct spacing between the HRE and the TATA-box. The DNA sequencing and restriction enzyme digestion results indicated that the AAV regulated by hypoxic-responsive element was successfully constructed. Compared to the control group, the expressions of 6×His was significantly increased in the experimental groups in hypoxia environment, which confirmed that the AAV effectually regulated by the minimal HRE was inserted into anterior extremity of CMV promoter. The HRE is inserted into anterior extremity of CMV promoter to lack incision enzyme recognition site by PCR. And eukaryotic expression vector regulated by hypoxic-responsive is constructed. The AAV effectually regulated by the minimal HRE inserted into anterior extremity of CMV promoter. The vector is successfully constructed and it has important theoretical and practical value in the synteresis and therapy of ischemia angiocardiopathy and cerebrovascular disease.

Evaluation of the efficacy of DDT indoor residual spraying and long-lasting insecticidal nets against insecticide resistant populations of Anopheles arabiensis Patton (Diptera: Culicidae) from Ethiopia using experimental huts

PubMed Central

2014-01-01

Background Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal nets (LLINs) are major malaria vector control tools in Ethiopia. However, recent reports from different parts of the country showed that populations of Anopheles arabiensis, the principal malaria vector, have developed resistance to most families of insecticides recommended for public health use which may compromise the efficacy of both of these key vector control interventions. Thus, this study evaluated the efficacy of DDT IRS and LLINs against resistant populations of An. arabiensis using experimental huts in Asendabo area, southwestern Ethiopia. Methods The susceptibility status of populations of An. arabiensis was assessed using WHO test kits to DDT, deltamethrin, malathion, lambda-cyhalothrin, fenitrothion and bendiocarb. The efficacy of LLIN (PermaNet® 2.0), was evaluated using the WHO cone bioassay. Moreover, the effect of the observed resistance against malaria vector control interventions (DDT IRS and LLINs) were assessed using experimental huts. Results The findings of this study revealed that populations of An. arabiensis were resistant to DDT, deltamethrin, lambda-cyhalothrin and malathion with mortality rates of 1.3%, 18.8%, 36.3% and 72.5%, respectively but susceptible to fenitrothion and bendiocarb with mortality rates of 98.81% and 97.5%, respectively. The bio-efficacy test of LLIN (PermaNet® 2.0) against An. arabiensis revealed that the mosquito population showed moderate knockdown (64%) and mortality (78%). Moreover, mosquito mortalities in DDT sprayed huts and in huts with LLINs were not significantly different (p > 0.05) from their respective controls. Conclusion The evaluation of the efficacy of DDT IRS and LLINs using experimental huts showed that both vector control tools had only low to moderate efficacy against An. arabiensis populations from Ethiopia. Despite DDT being replaced by carbamates for IRS, the low efficacy of LLINs against the resistant population of An. arabiensis is still a problem. Thus, there is a need for alternative vector control tools and implementation of appropriate insecticide resistance management strategies as part of integrated vector management by the national malaria control program. PMID:24678605

Fuzzy inference enhanced information recovery from digital PIV using cross-correlation combined with particle tracking

NASA Technical Reports Server (NTRS)

Wernet, Mark P.

1995-01-01

Particle Image Velocimetry provides a means of measuring the instantaneous 2-component velocity field across a planar region of a seeded flowfield. In this work only two camera, single exposure images are considered where both cameras have the same view of the illumination plane. Two competing techniques which yield unambiguous velocity vector direction information have been widely used for reducing the single exposure, multiple image data: cross-correlation and particle tracking. Correlation techniques yield averaged velocity estimates over subregions of the flow, whereas particle tracking techniques give individual particle velocity estimates. The correlation technique requires identification of the correlation peak on the correlation plane corresponding to the average displacement of particles across the subregion. Noise on the images and particle dropout contribute to spurious peaks on the correlation plane, leading to misidentification of the true correlation peak. The subsequent velocity vector maps contain spurious vectors where the displacement peaks have been improperly identified. Typically these spurious vectors are replaced by a weighted average of the neighboring vectors, thereby decreasing the independence of the measurements. In this work fuzzy logic techniques are used to determine the true correlation displacement peak even when it is not the maximum peak on the correlation plane, hence maximizing the information recovery from the correlation operation, maintaining the number of independent measurements and minimizing the number of spurious velocity vectors. Correlation peaks are correctly identified in both high and low seed density cases. The correlation velocity vector map can then be used as a guide for the particle tracking operation. Again fuzzy logic techniques are used, this time to identify the correct particle image pairings between exposures to determine particle displacements, and thus velocity. The advantage of this technique is the improved spatial resolution which is available from the particle tracking operation. Particle tracking alone may not be possible in the high seed density images typically required for achieving good results from the correlation technique. This two staged approach offers a velocimetric technique capable of measuring particle velocities with high spatial resolution over a broad range of seeding densities.

Chagas Disease, Migration and Community Settlement Patterns in Arequipa, Peru

PubMed Central

Gilman, Robert H.; Cornejo del Carpio, Juan G.; Naquira, Cesar; Bern, Caryn; Levy, Michael Z.

2009-01-01

Background Chagas disease is one of the most important neglected tropical diseases in the Americas. Vectorborne transmission of Chagas disease has been historically rare in urban settings. However, in marginal communities near the city of Arequipa, Peru, urban transmission cycles have become established. We examined the history of migration and settlement patterns in these communities, and their connections to Chagas disease transmission. Methodology/Principal Findings This was a qualitative study that employed focus group discussions and in-depth interviews. Five focus groups and 50 in-depth interviews were carried out with 94 community members from three shantytowns and two traditional towns near Arequipa, Peru. Focus groups utilized participatory methodologies to explore the community's mobility patterns and the historical and current presence of triatomine vectors. In-depth interviews based on event history calendars explored participants' migration patterns and experience with Chagas disease and vectors. Focus group data were analyzed using participatory analysis methodologies, and interview data were coded and analyzed using a grounded theory approach. Entomologic data were provided by an ongoing vector control campaign. We found that migrants to shantytowns in Arequipa were unlikely to have brought triatomines to the city upon arrival. Frequent seasonal moves, however, took shantytown residents to valleys surrounding Arequipa where vectors are prevalent. In addition, the pattern of settlement of shantytowns and the practice of raising domestic animals by residents creates a favorable environment for vector proliferation and dispersal. Finally, we uncovered a phenomenon of population loss and replacement by low-income migrants in one traditional town, which created the human settlement pattern of a new shantytown within this traditional community. Conclusions/Significance The pattern of human migration is therefore an important underlying determinant of Chagas disease risk in and around Arequipa. Frequent seasonal migration by residents of peri-urban shantytowns provides a path of entry of vectors into these communities. Changing demographic dynamics of traditional towns are also leading to favorable conditions for Chagas disease transmission. Control programs must include surveillance for infestation in communities assumed to be free of vectors. PMID:20016830

Cranking of Nuclei at Finite Temperature:

NASA Astrophysics Data System (ADS)

Bartel, J.; Bencheikh, K.; Quentin, P.

We present a generalization of the Extended Thomas Fermi (ETF) theory to fermionic systems at finite temperature and finite angular momentum. In fact the present approach is more general in the sense that it is able to treat an excited system of fermions subject to an external vector field which in the case of nuclear rotations, developed more extensively here, is simply ěc{r}×ěc{ω }.

Support Vector Machine Model for Automatic Detection and Classification of Seismic Events

NASA Astrophysics Data System (ADS)

Barros, Vesna; Barros, Lucas

2016-04-01

The automated processing of multiple seismic signals to detect, localize and classify seismic events is a central tool in both natural hazards monitoring and nuclear treaty verification. However, false detections and missed detections caused by station noise and incorrect classification of arrivals are still an issue and the events are often unclassified or poorly classified. Thus, machine learning techniques can be used in automatic processing for classifying the huge database of seismic recordings and provide more confidence in the final output. Applied in the context of the International Monitoring System (IMS) - a global sensor network developed for the Comprehensive Nuclear-Test-Ban Treaty (CTBT) - we propose a fully automatic method for seismic event detection and classification based on a supervised pattern recognition technique called the Support Vector Machine (SVM). According to Kortström et al., 2015, the advantages of using SVM are handleability of large number of features and effectiveness in high dimensional spaces. Our objective is to detect seismic events from one IMS seismic station located in an area of high seismicity and mining activity and classify them as earthquakes or quarry blasts. It is expected to create a flexible and easily adjustable SVM method that can be applied in different regions and datasets. Taken a step further, accurate results for seismic stations could lead to a modification of the model and its parameters to make it applicable to other waveform technologies used to monitor nuclear explosions such as infrasound and hydroacoustic waveforms. As an authorized user, we have direct access to all IMS data and bulletins through a secure signatory account. A set of significant seismic waveforms containing different types of events (e.g. earthquake, quarry blasts) and noise is being analysed to train the model and learn the typical pattern of the signal from these events. Moreover, comparing the performance of the support-vector network to various classical learning algorithms used before in seismic detection and classification is an essential final step to analyze the advantages and disadvantages of the model.

FAST TRACK COMMUNICATION: Singularity theorems based on trapped submanifolds of arbitrary co-dimension

NASA Astrophysics Data System (ADS)

Galloway, Gregory J.; Senovilla, José M. M.

2010-08-01

Standard singularity theorems are proven in Lorentzian manifolds of arbitrary dimension n if they contain closed trapped submanifolds of arbitrary co-dimension. By using the mean curvature vector to characterize trapped submanifolds, a unification of the several possibilities for the boundary conditions in the traditional theorems and their generalization to an arbitrary co-dimension is achieved. The classical convergence conditions must be replaced by a condition on sectional curvatures, or tidal forces, which reduces to the former in the cases of the co-dimension 1, 2 or n.

Survival of a bacterioferritin deletion mutant of Brucella melitensis 16M in human monocyte-derived macrophages.

PubMed Central

Denoel, P A; Crawford, R M; Zygmunt, M S; Tibor, A; Weynants, V E; Godfroid, F; Hoover, D L; Letesson, J J

1997-01-01

A bacterioferritin (BFR) deletion mutant of Brucella melitensis 16M was generated by gene replacement. The deletion was complemented with a broad-host-range vector carrying the wild-type bfr gene, pBBR-bfr. The survival and growth of the mutant, B. melitensis PAD 2-78, were similar to those of its parental strain in human monocyte-derived macrophages (MDM). These results suggest that BFR is not essential for the intracellular survival of B. melitensis in human MDM. PMID:9317046

Generalization of the quasi-geostrophic Eliassen-Palm flux to include eddy forcing of condensation heating

NASA Technical Reports Server (NTRS)

Stone, P. H.; Salustri, G.

1984-01-01

A modified Eulerian form of the Eliassen-Palm flux which includes the effect of eddy forcing on condensation heating is defined. With the two-dimensional vector flux in the meridional plane which is a function of the zonal mean eddy fluxes replaced by the modified flux, both the Eliassen-Palm theorem and a modified but more general form of the nonacceleration theorem for quasi-geostrophic motion still hold. Calculations of the divergence of the modified flux and of the eddy forcing of the moisture field are presented.

Anomaly free cosmological perturbations with generalised holonomy correction in loop quantum cosmology

NASA Astrophysics Data System (ADS)

Han, Yu; Liu, Molin

2018-05-01

In the spatially flat case of loop quantum cosmology, the connection is usually replaced by the holonomy in effective theory. In this paper, instead of the standard scheme, we use a generalised, undetermined function to represent the holonomy and by using the approach of anomaly free constraint algebra we fix all the counter terms in the constraints and find the restriction in the form of , then we derive the gauge-invariant equations of motion of the scalar, tensor and vector perturbations and study the inflationary power spectra with generalised holonomy correction.

An Overview of Live Attenuated Recombinant Pseudorabies Viruses for Use as Novel Vaccines

PubMed Central

Dong, Bo; Zarlenga, Dante S.; Ren, Xiaofeng

2014-01-01

Pseudorabies virus (PRV) is a double-stranded, DNA-based swine virus with a genome approximating 150 kb in size. PRV has many nonessential genes which can be replaced with genes encoding heterologous antigens but without deleterious effects on virus propagation. Recombinant PRVs expressing both native and foreign antigens are able to stimulate immune responses. In this paper, we review the current status of live attenuated recombinant PRVs and live PRV-based vector vaccines with potential for controlling viral infections in animals. PMID:24995348

Special Issue: Gene Therapy with Emphasis on RNA Interference

PubMed Central

Lundstrom, Kenneth

2015-01-01

Gene therapy was originally thought to cover replacement of malfunctioning genes in treatment of various diseases. Today, the field has been expanded to application of viral and non-viral vectors for delivery of recombinant proteins for the compensation of missing or insufficient proteins, anti-cancer genes and proteins for destruction of tumor cells, immunostimulatory genes and proteins for stimulation of the host defense system against viral agents and tumors. Recently, the importance of RNA interference and its application in gene therapy has become an attractive alternative for drug development. PMID:26447255

Knock-in of Enhanced Green Fluorescent Protein or/and Human Fibroblast Growth Factor 2 Gene into β-Casein Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein.

PubMed

Lee, Sang Mi; Kim, Ji Woo; Jeong, Young-Hee; Kim, Se Eun; Kim, Yeong Ji; Moon, Seung Ju; Lee, Ji-Hye; Kim, Keun-Jung; Kim, Min-Kyu; Kang, Man-Jong

2014-11-01

Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo) as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5' arm and 3' arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP) was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands.

Knock-in of Enhanced Green Fluorescent Protein or/and Human Fibroblast Growth Factor 2 Gene into β-Casein Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein

PubMed Central

Lee, Sang Mi; Kim, Ji Woo; Jeong, Young-Hee; Kim, Se Eun; Kim, Yeong Ji; Moon, Seung Ju; Lee, Ji-Hye; Kim, Keun-Jung; Kim, Min-Kyu; Kang, Man-Jong

2014-01-01

Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo) as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5′ arm and 3′ arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP) was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands. PMID:25358326

Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis.

PubMed

Delgado, Diego; del Pozo-Rodríguez, Ana; Solinís, Maria Ángeles; Avilés-Triqueros, Marcelino; Weber, Bernhard H F; Fernández, Eduardo; Gascón, Alicia R

2012-04-01

The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muslim, Dato’ Dr Noramly, E-mail: noramlymuslim@yahoo.com

As Malaysia progresses towards 2020, the depleting resource of oil and gas has forced a re-look at alternatives to replace fossil fuels as energy sources. Among the viable options is nuclear energy, enabling us to meet energy needs and sustain national development in the twenty-first century. Three essential steps Malaysia must take to introduce nuclear power into its energy mix are: energy planning, infrastructure development, and deployment. Malaysia has to face a series of challenges, including public acceptance, waste management, minimizing proliferation risk, and ensuring the security of nuclear plants and materials. Timely development of qualified and competent manpower ismore » a key limiting factor in the development and transfer of nuclear technologies — and education and training take time, effort and money. There is a need for political will. Within the Asian region, China, Korea and Japan are in the forefront in utilizing nuclear power to meet electricity demands. Countries such as UAE, Bangladesh, Vietnam and Turkey are moving ahead with the nuclear option for electricity generation and they have begun planning and construction of nuclear power plants. Against this backdrop, what are Malaysia’s moves? This paper discusses various options and challenges, obstacles and repercussions in meeting future energy demands.« less

Expanding the functional human mitochondrial DNA database by the establishment of primate xenomitochondrial cybrids

PubMed Central

Kenyon, Lesley; Moraes, Carlos T.

1997-01-01

The nuclear and mitochondrial genomes coevolve to optimize approximately 100 different interactions necessary for an efficient ATP-generating system. This coevolution led to a species-specific compatibility between these genomes. We introduced mitochondrial DNA (mtDNA) from different primates into mtDNA-less human cells and selected for growth of cells with a functional oxidative phosphorylation system. mtDNA from common chimpanzee, pigmy chimpanzee, and gorilla were able to restore oxidative phosphorylation in the context of a human nuclear background, whereas mtDNA from orangutan, and species representative of Old-World monkeys, New-World monkeys, and lemurs were not. Oxygen consumption, a sensitive index of respiratory function, showed that mtDNA from chimpanzee, pigmy chimpanzee, and gorilla replaced the human mtDNA and restored respiration to essentially normal levels. Mitochondrial protein synthesis was also unaltered in successful “xenomitochondrial cybrids.” The abrupt failure of mtDNA from primate species that diverged from humans as recently as 8–18 million years ago to functionally replace human mtDNA suggests the presence of one or a few mutations affecting critical nuclear–mitochondrial genome interactions between these species. These cellular systems provide a demonstration of intergenus mtDNA transfer, expand more than 20-fold the number of mtDNA polymorphisms that can be analyzed in a human nuclear background, and provide a novel model for the study of nuclear–mitochondrial interactions. PMID:9256447

An assessment of coupling algorithms for nuclear reactor core physics simulations

DOE PAGES

Hamilton, Steven; Berrill, Mark; Clarno, Kevin; ...

2016-04-01

This paper evaluates the performance of multiphysics coupling algorithms applied to a light water nuclear reactor core simulation. The simulation couples the k-eigenvalue form of the neutron transport equation with heat conduction and subchannel flow equations. We compare Picard iteration (block Gauss–Seidel) to Anderson acceleration and multiple variants of preconditioned Jacobian-free Newton–Krylov (JFNK). The performance of the methods are evaluated over a range of energy group structures and core power levels. A novel physics-based approximation to a Jacobian-vector product has been developed to mitigate the impact of expensive on-line cross section processing steps. Furthermore, numerical simulations demonstrating the efficiency ofmore » JFNK and Anderson acceleration relative to standard Picard iteration are performed on a 3D model of a nuclear fuel assembly. Both criticality (k-eigenvalue) and critical boron search problems are considered.« less

An assessment of coupling algorithms for nuclear reactor core physics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, Steven; Berrill, Mark; Clarno, Kevin

This paper evaluates the performance of multiphysics coupling algorithms applied to a light water nuclear reactor core simulation. The simulation couples the k-eigenvalue form of the neutron transport equation with heat conduction and subchannel flow equations. We compare Picard iteration (block Gauss–Seidel) to Anderson acceleration and multiple variants of preconditioned Jacobian-free Newton–Krylov (JFNK). The performance of the methods are evaluated over a range of energy group structures and core power levels. A novel physics-based approximation to a Jacobian-vector product has been developed to mitigate the impact of expensive on-line cross section processing steps. Furthermore, numerical simulations demonstrating the efficiency ofmore » JFNK and Anderson acceleration relative to standard Picard iteration are performed on a 3D model of a nuclear fuel assembly. Both criticality (k-eigenvalue) and critical boron search problems are considered.« less

An assessment of coupling algorithms for nuclear reactor core physics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, Steven, E-mail: hamiltonsp@ornl.gov; Berrill, Mark, E-mail: berrillma@ornl.gov; Clarno, Kevin, E-mail: clarnokt@ornl.gov

This paper evaluates the performance of multiphysics coupling algorithms applied to a light water nuclear reactor core simulation. The simulation couples the k-eigenvalue form of the neutron transport equation with heat conduction and subchannel flow equations. We compare Picard iteration (block Gauss–Seidel) to Anderson acceleration and multiple variants of preconditioned Jacobian-free Newton–Krylov (JFNK). The performance of the methods are evaluated over a range of energy group structures and core power levels. A novel physics-based approximation to a Jacobian-vector product has been developed to mitigate the impact of expensive on-line cross section processing steps. Numerical simulations demonstrating the efficiency of JFNKmore » and Anderson acceleration relative to standard Picard iteration are performed on a 3D model of a nuclear fuel assembly. Both criticality (k-eigenvalue) and critical boron search problems are considered.« less

Plant maintenance and plant life extension issue, 2006

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnihotri, Newal

The focus of the March-April issue is on plant maintenance and plant life extension. Major articles/reports in this issue include: Spent fuel: myths and facts, by Jeffrey S. Merrifield, U.S. Nuclear Regulatory Commission; Critical pipe replacement procedure, by Geoff Gilmore, Climax Portable Machine Tools Inc.; Improving maintenance performance, by Larry Meyer and Joe Giuffre, DC Cook Nuclear Plant, American Electric Power; Equipment deficiency intolerance index, by Douglas F. Helms, Tennessee Valley Authority; Plant profile: I and C modernization at Dukovany, by Josef Rosol, CEZ Dukovany NPP, Czech Republic; and, Report: new plant activities.

Guidelines for Electromagnetic Interference Testing of Power Plant Equipment: Revision 3 to TR-102323

DOE Office of Scientific and Technical Information (OSTI.GOV)

J. Cunningham and J. Shank

2004-11-01

To continue meeting safety and reliability requirements while controlling costs, operators of nuclear power plants must be able to replace and upgrade equipment in a cost-effective manner. One issue that has been problematic for new plant equipment and especially for digital instrumentation and control (I&C) systems in recent years is electromagnetic compatibility (EMC). The EMC issue usually involves testing to show that critical equipment will not be adversely affected by electromagnetic interference (EMI) in the plant environment. This guide will help nuclear plant engineers address EMC issues and qualification testing in a consistent, comprehensive manner.

Progress in malaria vector control.

PubMed

Pant, C P; Rishikesh, N; Bang, Y H; Smith, A

1981-01-01

Malaria control, except in tropical Africa, will probably continue to be based to a large extent on the use of insecticides for many years. However, the development of resistance to insecticides in the vectors has caused serious difficulties and it is necessary to change the strategy of insecticide use to maximize their efficacy. A thorough knowledge of the ecology and behaviour of each vector species is required before the control strategy can be adapted to different epidemiological situations. The behavioural differences between sibling species have been recognized for several years, but study of this problem has recently been simplified by improved means of identification that involve chromosomal banding patterns and electrophoretic analysis. Behavioural differences have also been associated with certain chromosomal rearrangements.New records of insecticide resistance among anophelines continue to appear and the impact of this on antimalaria operations has been seriously felt in Central America (multi-resistance in Anopheles albimanus), Turkey (A. sacharovi), India and several Asian countries (A. culicifacies and A. stephensi), and some other countries. Work continues on the screening and testing of newer insecticides that can be used as alternatives, but DDT, malathion, temephos, fenitrothion, and propoxur continue to be used as the main insecticides in many malaria control projects. The search for simpler and innovative approaches to insecticide application also continues.Biological control of vectors is receiving increased attention, as it could become an important component of integrated vector control strategies, and most progress has been made with the spore-forming bacterium, serotype H-14 of Bacillus thuringiensis. Larvivorous fish such as Gambusia spp. and Poecilia spp. continue to be used in some programmes.Application of environmental management measures, such as source reduction, source elimination, flushing of drainage and irrigation channels, and intermittent irrigation have been re-examined and currently a great deal of interest is being shown in these approaches.There has been limited interest in the genetic control of mosquitos and the phenomenon of refractoriness in some strains of the disease vectors, with the idea of replacing the vector species with the refractory strain. More research is needed before this approach can become a practical tool.It is apparent that in future a more integrated approach will have to be used for vector control within the context of antimalaria programmes. Training of staff, research, and cooperation at all levels will be an essential requirement for this approach.

METHOD OF FABRICATING A GRAPHITE MODERATED REACTOR

DOEpatents

Kratz, H.R.

1963-05-01

S>A nuclear reactor formed of spaced bodies of uranium and graphite blocks is improved by diffusing helium through the graphite blocks in order to replace the air in the pores of the graphite with helium. The helium-impregnated graphite conducts heat better, and absorbs neutrons less, than the original air- impregnated graphite. (AEC)

Overview of reductants utilized in nuclear fuel reprocessing/recycling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paviet-Hartmann, P.; Riddle, C.; Campbell, K.

2013-07-01

The most widely used reductant to partition plutonium from uranium in the Purex process was ferrous sulfamate, other alternates were proposed such as hydrazine-stabilized ferrous nitrate or uranous nitrate, platinum catalyzed hydrogen, and hydrazine, hydroxylamine salts. New candidates to replace hydrazine or hydroxylamine nitrate (HAN) are pursued worldwide. They may improve the performance of the industrial Purex process towards different operations such as de-extraction of plutonium and reduction of the amount of hydrazine which will limit the formation of hydrazoic acid. When looking at future recycling technologies using hydroxamic ligands, neither acetohydroxamic acid (AHA) nor formohydroxamic acid (FHA) seem promisingmore » because they hydrolyze to give hydroxylamine and the parent carboxylic acid. Hydroxyethylhydrazine, HOC{sub 2}H{sub 4}N{sub 2}H{sub 3} (HEH) is a promising non-salt-forming reductant of Np and Pu ions because it is selective to neptunium and plutonium ions at room temperature and at relatively low acidity, it could serve as a replacement of HAN or AHA for the development of a novel used nuclear fuel recycling process.« less

Multi-Constraint Multi-Variable Optimization of Source-Driven Nuclear Systems

NASA Astrophysics Data System (ADS)

Watkins, Edward Francis

1995-01-01

A novel approach to the search for optimal designs of source-driven nuclear systems is investigated. Such systems include radiation shields, fusion reactor blankets and various neutron spectrum-shaping assemblies. The novel approach involves the replacement of the steepest-descents optimization algorithm incorporated in the code SWAN by a significantly more general and efficient sequential quadratic programming optimization algorithm provided by the code NPSOL. The resulting SWAN/NPSOL code system can be applied to more general, multi-variable, multi-constraint shield optimization problems. The constraints it accounts for may include simple bounds on variables, linear constraints, and smooth nonlinear constraints. It may also be applied to unconstrained, bound-constrained and linearly constrained optimization. The shield optimization capabilities of the SWAN/NPSOL code system is tested and verified in a variety of optimization problems: dose minimization at constant cost, cost minimization at constant dose, and multiple-nonlinear constraint optimization. The replacement of the optimization part of SWAN with NPSOL is found feasible and leads to a very substantial improvement in the complexity of optimization problems which can be efficiently handled.

"Mitochondrial Replacement" Technologies and Human Germline Nuclear Modification.

PubMed

Lane, Alyssa; Nisker, Jeff

2016-08-01

In 2015 the United Kingdom became the first jurisdiction to approve "mitochondrial replacement techniques" (MRT), thereby dropping prohibitions against creating human embryos with a permanently altered genetic make-up for purposes of reproduction. MRT is a misnomer because in fact it is the nucleus of the oocyte of the woman who wants a genetically related child that is transferred to the enucleated oocyte of a woman paid to undergo IVF to provide the oocyte. MRT thus constitutes nuclear transfer, which is prohibited by criminal sanctions under sections of laws on reproductive cloning in Canada, the United States, Australia, and European countries that regulate assisted reproduction. By adopting policies permitting the use of MRT, the United Kingdom has become the first jurisdiction to counteract an international consensus prohibiting germline modification. Analyses of the legal, ethical, and societal implications of MRT in assisted human reproduction are essential. Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

Formation of AAV Single Stranded DNA Genome from a Circular Plasmid in Saccharomyces cerevisiae

PubMed Central

Cervelli, Tiziana; Backovic, Ana; Galli, Alvaro

2011-01-01

Adeno-associated virus (AAV)-based vectors are promising tools for targeted transfer in gene therapy studies. Many efforts have been accomplished to improve production and purification methods. We thought to develop a simple eukaryotic system allowing AAV replication which could provide an excellent opportunity for studying AAV biology and, more importantly, for AAV vector production. It has been shown that yeast Saccharomyces cerevisiae is able to replicate and form the capsid of many viruses. We investigated the ability of the yeast Saccharomyces cerevisiae to carry out the replication of a recombinant AAV (rAAV). When a plasmid containing a rAAV genome in which the cap gene was replaced with the S. cerevisiae URA3 gene, was co-transformed in yeast with a plasmid expressing Rep68, a significant number of URA3+ clones were scored (more than 30-fold over controls). Molecular analysis of low molecular weight DNA by Southern blotting revealed that single stranded DNA is formed and that the plasmid is entirely replicated. The ssDNA contains the ITRs, URA3 gene and also vector sequences suggesting the presence of two distinct molecules. Its formation was dependent on Rep68 expression and ITR. These data indicate that DNA is not obtained by the canonical AAV replication pathway. PMID:21853137

Formation of AAV single stranded DNA genome from a circular plasmid in Saccharomyces cerevisiae.

PubMed

Cervelli, Tiziana; Backovic, Ana; Galli, Alvaro

2011-01-01

Adeno-associated virus (AAV)-based vectors are promising tools for targeted transfer in gene therapy studies. Many efforts have been accomplished to improve production and purification methods. We thought to develop a simple eukaryotic system allowing AAV replication which could provide an excellent opportunity for studying AAV biology and, more importantly, for AAV vector production. It has been shown that yeast Saccharomyces cerevisiae is able to replicate and form the capsid of many viruses. We investigated the ability of the yeast Saccharomyces cerevisiae to carry out the replication of a recombinant AAV (rAAV). When a plasmid containing a rAAV genome in which the cap gene was replaced with the S. cerevisiae URA3 gene, was co-transformed in yeast with a plasmid expressing Rep68, a significant number of URA3(+) clones were scored (more than 30-fold over controls). Molecular analysis of low molecular weight DNA by Southern blotting revealed that single stranded DNA is formed and that the plasmid is entirely replicated. The ssDNA contains the ITRs, URA3 gene and also vector sequences suggesting the presence of two distinct molecules. Its formation was dependent on Rep68 expression and ITR. These data indicate that DNA is not obtained by the canonical AAV replication pathway.

Lentiviral Gene Therapy Using Cellular Promoters Cures Type 1 Gaucher Disease in Mice

PubMed Central

Dahl, Maria; Doyle, Alexander; Olsson, Karin; Månsson, Jan-Eric; Marques, André R A; Mirzaian, Mina; Aerts, Johannes M; Ehinger, Mats; Rothe, Michael; Modlich, Ute; Schambach, Axel; Karlsson, Stefan

2015-01-01

Gaucher disease is caused by an inherited deficiency of the enzyme glucosylceramidase. Due to the lack of a fully functional enzyme, there is progressive build-up of the lipid component glucosylceramide. Insufficient glucosylceramidase activity results in hepatosplenomegaly, cytopenias, and bone disease in patients. Gene therapy represents a future therapeutic option for patients unresponsive to enzyme replacement therapy and lacking a suitable bone marrow donor. By proof-of-principle experiments, we have previously demonstrated a reversal of symptoms in a murine disease model of type 1 Gaucher disease, using gammaretroviral vectors harboring strong viral promoters to drive glucosidase β-acid (GBA) gene expression. To investigate whether safer vectors can correct the enzyme deficiency, we utilized self-inactivating lentiviral vectors (SIN LVs) with the GBA gene under the control of human phosphoglycerate kinase (PGK) and CD68 promoter, respectively. Here, we report prevention of, as well as reversal of, manifest disease symptoms after lentiviral gene transfer. Glucosylceramidase activity above levels required for clearance of glucosylceramide from tissues resulted in reversal of splenomegaly, reduced Gaucher cell infiltration and a restoration of hematological parameters. These findings support the use of SIN-LVs with cellular promoters in future clinical gene therapy protocols for type 1 Gaucher disease. PMID:25655314

Face recognition using total margin-based adaptive fuzzy support vector machines.

PubMed

Liu, Yi-Hung; Chen, Yen-Ting

2007-01-01

This paper presents a new classifier called total margin-based adaptive fuzzy support vector machines (TAF-SVM) that deals with several problems that may occur in support vector machines (SVMs) when applied to the face recognition. The proposed TAF-SVM not only solves the overfitting problem resulted from the outlier with the approach of fuzzification of the penalty, but also corrects the skew of the optimal separating hyperplane due to the very imbalanced data sets by using different cost algorithm. In addition, by introducing the total margin algorithm to replace the conventional soft margin algorithm, a lower generalization error bound can be obtained. Those three functions are embodied into the traditional SVM so that the TAF-SVM is proposed and reformulated in both linear and nonlinear cases. By using two databases, the Chung Yuan Christian University (CYCU) multiview and the facial recognition technology (FERET) face databases, and using the kernel Fisher's discriminant analysis (KFDA) algorithm to extract discriminating face features, experimental results show that the proposed TAF-SVM is superior to SVM in terms of the face-recognition accuracy. The results also indicate that the proposed TAF-SVM can achieve smaller error variances than SVM over a number of tests such that better recognition stability can be obtained.

De novo formed satellite DNA-based mammalian artificial chromosomes and their possible applications.

PubMed

Katona, Robert L

2015-02-01

Mammalian artificial chromosomes (MACs) are non-integrating, autonomously replicating natural chromosome-based vectors that may carry a vast amount of genetic material, which in turn enable potentially prolonged, safe, and regulated therapeutic transgene expression and render MACs as attractive genetic vectors for "gene replacement" or for controlling differentiation pathways in target cells. Satellite-DNA-based artificial chromosomes (SATACs) can be made by induced de novo chromosome formation in cells of different mammalian and plant species. These artificially generated accessory chromosomes are composed of predictable DNA sequences, and they contain defined genetic information. SATACs have already passed a number of obstacles crucial to their further development as gene therapy vectors, including large-scale purification, transfer of purified artificial chromosomes into different cells and embryos, generation of transgenic animals and germline transmission with purified SATACs, and the tissue-specific expression of a therapeutic gene from an artificial chromosome in the milk of transgenic animals. SATACs could be used in cell therapy protocols. For these methods, the most versatile target cell would be one that was pluripotent and self-renewing to address multiple disease target cell types, thus making multilineage stem cells, such as adult derived early progenitor cells and embryonic stem cells, as attractive universal host cells.

Complete mitochondrial genome of Lutzomyia (Nyssomyia) umbratilis (Diptera: Psychodidae), the main vector of Leishmania guyanensis.

PubMed

Kocher, Arthur; Gantier, Jean-Charles; Holota, Hélène; Jeziorski, Céline; Coissac, Eric; Bañuls, Anne-Laure; Girod, Romain; Gaborit, Pascal; Murienne, Jérôme

2016-11-01

The nearly complete mitochondrial genome of Lutzomyia umbratilis Ward & Fraiha, 1977 (Psychodidae: Phlebotominae), considered as the main vector of Leishmania guyanensis, is presented. The sequencing has been performed on an Illumina Hiseq 2500 platform, with a genome skimming strategy. The full nuclear ribosomal RNA segment was also assembled. The mitogenome of L. umbratilis was determined to be at least 15,717 bp-long and presents an architecture found in many mitogenomes of insect (13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and one non-coding region also referred as the control region). The control region contains a large repeated element of c. 370 bp and a poly-AT region of unknown length. This is the first mitogenome of Psychodidae to be described.

REVIEWS OF TOPICAL PROBLEMS: Helium-isotope mass-spectrometric method for studying tritium beta decay (idea, experiment, nuclear and molecular physics applications)

NASA Astrophysics Data System (ADS)

Akulov, Yuii A.; Mamyrin, Boris A.

2003-11-01

Experimental data on the variation of tritium nucleus beta decay constant caused by the interaction of the resulting beta-electron with orbital electrons and shell vacancies are reviewed for free atomic tritium and molecular tritium and used to obtain the half-life of atomic tritium (T1/2)a=(12.264±0.018) y, the half-life of the free triton (T1/2)t=(12.238±0.020) y, the axial-vector-to-vector weak-interaction coupling constant ratio (GA/GV)t=-1.2646 ± 0.0035 for beta decay of the triton, and an independent estimate of the free neutron lifetime τn= (890.3 ± 3.9stat ± 1.4syst) s.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dayman, Ken J; Ade, Brian J; Weber, Charles F

High-dimensional, nonlinear function estimation using large datasets is a current area of interest in the machine learning community, and applications may be found throughout the analytical sciences, where ever-growing datasets are making more information available to the analyst. In this paper, we leverage the existing relevance vector machine, a sparse Bayesian version of the well-studied support vector machine, and expand the method to include integrated feature selection and automatic function shaping. These innovations produce an algorithm that is able to distinguish variables that are useful for making predictions of a response from variables that are unrelated or confusing. We testmore » the technology using synthetic data, conduct initial performance studies, and develop a model capable of making position-independent predictions of the coreaveraged burnup using a single specimen drawn randomly from a nuclear reactor core.« less

A single EBV-based vector for stable episomal maintenance and expression of GFP in human embryonic stem cells.

PubMed

Thyagarajan, Bhaskar; Scheyhing, Kelly; Xue, Haipeng; Fontes, Andrew; Chesnut, Jon; Rao, Mahendra; Lakshmipathy, Uma

2009-03-01

Stable expression of transgenes in stem cells has been a challenge due to the nonavailability of efficient transfection methods and the inability of transgenes to support sustained gene expression. Several methods have been reported to stably modify both embryonic and adult stem cells. These methods rely on integration of the transgene into the genome of the host cell, which could result in an expression pattern dependent on the number of integrations and the genomic locus of integration. To overcome this issue, site-specific integration methods mediated by integrase, adeno-associated virus or via homologous recombination have been used to generate stable human embryonic stem cell (hESC) lines. In this study, we describe a vector that is maintained episomally in hESCs. The vector used in this study is based on components derived from the Epstein-Barr virus, containing the Epstein-Barr virus nuclear antigen 1 expression cassette and the OriP origin of replication. The vector also expresses the drug-resistance marker gene hygromycin, which allows for selection and long-term maintenance of cells harboring the plasmid. Using this vector system, we show sustained expression of green fluorescent protein in undifferentiated hESCs and their differentiating embryoid bodies. In addition, the stable hESC clones show comparable expression with and without drug selection. Consistent with this observation, bulk-transfected adipose tissue-derived mesenchymal stem cells showed persistent marker gene expression as they differentiate into adipocytes, osteoblasts and chondroblasts. Episomal vectors offer a fast and efficient method to create hESC reporter lines, which in turn allows one to test the effect of overexpression of various genes on stem cell growth, proliferation and differentiation.

Peptide-matrix-mediated gene transfer of an oxygen-insensitive hypoxia-inducible factor-1alpha variant for local induction of angiogenesis.

PubMed

Trentin, Diana; Hall, Heike; Wechsler, Sandra; Hubbell, Jeffrey A

2006-02-21

Hypoxia-inducible factor (HIF) constitutes a target in therapeutic angiogenesis. HIF-1alpha functions as a sensor of hypoxia and induces expression of vascular endothelial growth factor (VEGF), which then induces angiogenesis. To explore the potential of HIF-1alpha gene therapy in stimulating wound healing, we delivered a gene encoding a stabilized form of HIF-1alpha, lacking the oxygen-sensitive degradation domain, namely HIF-1alpha deltaODD, by using a previously characterized peptide-based gene delivery vector in fibrin as a surgical matrix. The peptide vector consisted of multiple domains: (i) A cysteine-flanked lysine hexamer provided DNA interactions that were stable extracellularly but destabilized intracellularly after reduction of the formed disulfide bonds. This DNA-binding domain was fused to either (ii) a fibrin-binding peptide for entrapment within the matrix or (iii) a nuclear localization sequence for efficient nuclear targeting. The HIF-1alpha deltaODD gene was expressed and translocated to the nucleus under normoxic conditions, leading to up-regulation of vascular endothelial growth factor (VEGF)-A165 mRNA and protein levels in vitro. When the peptide-DNA nanoparticles entrapped in fibrin matrices were applied to full-thickness dermal wounds in the mouse (10 microg per wound in 30 microl of fibrin), angiogenesis was increased comparably strongly to that induced by VEGF-A165 protein (1.25 microg per wound in 30 microl of fibrin). However, the maturity of the vessels induced by HIF-1alpha deltaODD was significantly higher than that induced by VEGF-A165 protein, as shown by stabilization of the neovessels with smooth muscle. Nonviral, local administration of this potent angiogenesis-inducing gene by using this peptide vector represents a powerful approach in tissue engineering and therapeutic angiogenesis.

Production of transgenic Korean native cattle expressing enhanced green fluorescent protein using a FIV-based lentiviral vector injected into MII oocytes.

PubMed

Xu, Yong-Nan; Uhm, Sang-Jun; Koo, Bon-Chul; Kwon, Mo-Sun; Roh, Ji-Yeol; Yang, Jung-Seok; Choi, Hyun-Yong; Heo, Young-Tae; Cui, Xiang-Shun; Yoon, Joon-Ho; Ko, Dae-Hwan; Kim, Teoan; Kim, Nam-Hyung

2013-01-20

The potential benefits of generating and using transgenic cattle range from improvements in agriculture to the production of large quantities of pharmaceutically relevant proteins. Previous studies have attempted to produce transgenic cattle and other livestock by pronuclear injection and somatic cell nuclear transfer, but these approaches have been largely ineffective; however, a third approach, lentivirus-mediated transgenesis, has successfully produced transgenic livestock. In this study, we generated transgenic (TG) Korean native cattle using perivitelline space injection of viral vectors, which expressed enhanced green fluorescent protein (EGFP) systemically. Two different types of lentiviral vectors derived from feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) carrying EGFP were injected into the perivitelline space of MII oocytes. EGFP expression at 8-cell stage was significantly higher in the FIV group compared to the HIV group (47.5%±2.2% v.s. 22.9%±2.9%). Eight-cell embryos that expressed EGFP were cultured into blastocysts and then transferred into 40 heifers. Ten heifers were successfully impregnated and delivered 10 healthy calves. All of these calves expressed EGFP as detected by in vivo imaging, PCR and Southern blotting. In addition, we established an EGFP-expressing cell line from TG calves, which was followed by nuclear transfer (NT). Recloned 8-cell embryos also expressed EGFP, and there were no differences in the rates of fusion, cleavage and development between cells derived from TG and non-TG calves, which were subsequently used for NT. These results illustrate that FIV-based lentiviruses are useful for the production of TG cattle. Moreover, our established EGFP cell line can be used for additional studies that involve induced pluripotent stem cells. Copyright © 2013. Published by Elsevier Ltd.

Robust Principal Component Analysis Regularized by Truncated Nuclear Norm for Identifying Differentially Expressed Genes.

PubMed

Wang, Ya-Xuan; Gao, Ying-Lian; Liu, Jin-Xing; Kong, Xiang-Zhen; Li, Hai-Jun

2017-09-01

Identifying differentially expressed genes from the thousands of genes is a challenging task. Robust principal component analysis (RPCA) is an efficient method in the identification of differentially expressed genes. RPCA method uses nuclear norm to approximate the rank function. However, theoretical studies showed that the nuclear norm minimizes all singular values, so it may not be the best solution to approximate the rank function. The truncated nuclear norm is defined as the sum of some smaller singular values, which may achieve a better approximation of the rank function than nuclear norm. In this paper, a novel method is proposed by replacing nuclear norm of RPCA with the truncated nuclear norm, which is named robust principal component analysis regularized by truncated nuclear norm (TRPCA). The method decomposes the observation matrix of genomic data into a low-rank matrix and a sparse matrix. Because the significant genes can be considered as sparse signals, the differentially expressed genes are viewed as the sparse perturbation signals. Thus, the differentially expressed genes can be identified according to the sparse matrix. The experimental results on The Cancer Genome Atlas data illustrate that the TRPCA method outperforms other state-of-the-art methods in the identification of differentially expressed genes.

Use of mock-up training to reduce personnel exposure at the North Anna Unit 1 Steam Generator Replacement Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, H.G.; Reilly, B.P.

1995-03-01

The North Anna Power Station is located on the southern shore of Lake Anna in Louisa County, approximately forty miles northwest of Richmond, Virginia. The two 910 Mw nuclear units located on this site are owned by Virginia Electric and Power Company (Virginia Power) and Old Dominion Electric Cooperative and operated by Virginia Power. Fuel was loaded into Unit 1 in December 1977, and it began commercial operation in June 1978. Fuel was loaded into Unit 2 in April 1980 and began commercial operation in December 1980. Each nuclear unit includes a three-coolant-loop pressurized light water reactor nuclear steam supplymore » system that was furnished by Westinghouse Electric Corporation. Included within each system were three Westinghouse Model 51 steam generators with alloy 600, mill-annealed tubing material. Over the years of operation of Unit 1, various corrosion-related phenomena had occurred that affected the steam generators tubing and degraded their ability to fulfill their heat transfer function. Advanced inspection and repair techniques helped extend the useful life of the steam generators, but projections based on the results of the inspections indicated that the existing steam generators tubing and degraded their ability to fullfill their heat transfer function. Advanced inspection and repair techniques helped extend the useful life of the steam generators, but projections based on the results of the inspections indicated that the existing steam generators would not last their design life and must be repaired. To this end Virginia Power determined that a steam generator replacement (SGR) program was necessary to remove the old steam generator tube bundles and lower shell sections, including the channel heads (collectively called the lower assemblies), and replace them with new lower assemblies incorporating design features that will prevent the degradation problems that the old steam generators had experienced.« less

First Molecular Identification and Phylogeny of Moroccan Anopheles sergentii (Diptera: Culicidae) Based on Second Internal Transcribed Spencer (ITS2) and Cytochrome c Oxidase I (COI) Sequences.

PubMed

Benabdelkrim Filali, Oumama; Kabine, Mostafa; El Hamouchi, Adil; Lemrani, Meryem; Debboun, Mustapha; Sarih, M'hammed

2018-06-05

Anopheles sergentii known as the "oasis vector" or the "desert malaria vector" is considered the main vector of malaria in the southern parts of Morocco. Its presence in Morocco is confirmed for the first time through sequencing of mitochondrial DNA (mDNA) cytochrome c oxidase subunit I (COI) barcodes and nuclear ribosomal DNA (rDNA) second internal transcribed spacer (ITS2) sequences and direct comparison with specimens of A. sergentii of other countries. The DNA barcodes (n = 39) obtained from A. sergentii collected in 2015 and 2016 showed more diversity with 10 haplotypes, compared with 3 haplotypes obtained from ITS2 sequences (n = 59). Moreover, the comparison using the ITS2 sequences showed closer evolutionary relationship between the Moroccan and Egyptian strains than the Iranian strain. Nevertheless, genetic differences due to geographical segregation were also observed. This study provides the first report on the sequence of rDNA-ITS2 and mtDNA COI, which could be used to better understand the biodiversity of A. sergentii.

Realistic model for a fifth force explaining anomaly in Be8* →8Bee+e- decay

NASA Astrophysics Data System (ADS)

Gu, Pei-Hong; He, Xiao-Gang

2017-06-01

We propose a theoretical model to explain a 6.8 σ anomaly recently reported in the opening angle and invariant mass distributions of e+e- pairs produced in excited Be8* nuclear transition to its ground state 8B e. The anomaly is explained by a fifth force mediated by a 17 MeV X boson through the decay Be8* →8Be X followed by X →e+e-. The X boson comes from extension of the standard model with two additional U(1) gauge symmetries producing a protophobic pure vector current interaction with quarks. The model also contains axial-vector current interaction. Although the existent axial-vector current interactions are strongly constrained by the measurement of parity violation in e-quark scattering, their contributions cancel out in the iso-scalar interaction for Be8* →8Be X. It is remarkable that the model parameters need to explain the anomaly survive all known low energy experimental constraints. The model may also alleviate the long-standing (g - 2)μ anomaly problem and can be probed by the LHCb experiment.

Vector-boson-tagged jet production in heavy ion collisions at energies available at the CERN Large Hadron Collider [Vector boson-tagged jet production in heavy ion collisions at the LHC

DOE PAGES

Kang, Zhong -Bo; Vitev, Ivan Mateev; Xing, Hongxi

2017-07-25

Here, vector-boson-tagged jet production in collisions of heavy nuclei opens new opportunities to study parton shower formation and propagation in strongly interacting matter. It has been argued to provide a golden channel that can constrain the energy loss of jets in the quark-gluon plasma created in heavy ion reactions. We present theoretical results for isolated-photon-tagged and Z 0-boson-tagged jet production in Pb + Pb collisions with √s NN = 5.02TeV at the LHC. Specifically, we evaluate the transverse momentum imbalance x JV distribution and nuclear modification factor I AA of tagged jets and compare our theoretical calculations to recent experimentalmore » measurements by ATLAS and CMS collaborations. Our analysis, which includes both collisional and radiative energy losses, sheds light on their relative importance versus the strength of jet-medium interactions and helps quantify the amount of out-of-cone radiation of predominantly prompt quark-initiated jets.« less

Renormalization of the weak hadronic current in the nuclear medium

NASA Astrophysics Data System (ADS)

Siiskonen, T.; Hjorth-Jensen, M.; Suhonen, J.

2001-05-01

The renormalization of the weak charge-changing hadronic current as a function of the reaction energy release is studied at the nucleonic level. We have calculated the average quenching factors for each type of current (vector, axial vector, and induced pseudoscalar). The obtained quenching in the axial vector part is, at zero momentum transfer, 19% for the 1s0d shell and 23% in the 1p0f shell. We have extended the calculations also to heavier systems such as 56Ni and 100Sn, where we obtain stronger quenchings, 44% and 59%, respectively. Gamow-Teller-type transitions are discussed, along with the higher-order matrix elements. The quenching factors are constant up to roughly 60 MeV momentum transfer. Therefore the use of energy-independent quenching factors in beta decay is justified. We also found that going beyond the zeroth and first order operators (in inverse nucleon mass) does not give any substantial contribution. The extracted renormalization to the ratio CP/CA at q=100 MeV is -3.5%, -7.1%, -28.6%, and +8.7% for mass 16, 40, 56, and 100, respectively.

Friendly fire: redirecting herpes simplex virus-1 for therapeutic applications.

PubMed

Advani, S J; Weichselbaum, R R; Whitley, R J; Roizman, B

2002-09-01

Herpes simplex virus-1 (HSV-1) is a relatively large double-stranded DNA virus encoding at least 89 proteins with well characterized disease pathology. An understanding of the functions of viral proteins together with the ability to genetically engineer specific viral mutants has led to the development of attenuated HSV-1 for gene therapy. This review highlights the progress in creating attenuated genetically engineered HSV-1 mutants that are either replication competent (viral non-essential gene deleted) or replication defective (viral essential gene deleted). The choice between a replication-competent or -defective virus is based on the end-goal of the therapeutic intervention. Replication-competent HSV-1 mutants have primarily been employed as antitumor oncolytic viruses, with the lytic nature of the virus harnessed to destroy tumor cells selectively. In replacement gene therapy, replication-defective viruses have been utilized as delivery vectors. The advantages of HSV-1 vectors are that they infect quiescent and dividing cells efficiently and can encode for relatively large transgenes.

Methods of Constructing a Blended Performance Function Suitable for Formation Flight

NASA Technical Reports Server (NTRS)

Ryan, John J.

2017-01-01

This paper presents two methods for constructing an approximate performance function of a desired parameter using correlated parameters. The methods are useful when real-time measurements of a desired performance function are not available to applications such as extremum-seeking control systems. The first method approximates an a priori measured or estimated desired performance function by combining real-time measurements of readily available correlated parameters. The parameters are combined using a weighting vector determined from a minimum-squares optimization to form a blended performance function. The blended performance function better matches the desired performance function mini- mum than single-measurement performance functions. The second method expands upon the first by replacing the a priori data with near-real-time measurements of the desired performance function. The resulting blended performance function weighting vector is up- dated when measurements of the desired performance function are available. Both methods are applied to data collected during formation- flight-for-drag-reduction flight experiments.

Initiation of small-satellite formations via satellite ejector

NASA Astrophysics Data System (ADS)

McMullen, Matthew G

Small satellites can be constructed at a fraction of the cost of a full-size satellite. One full-size satellite can be replaced with a multitude of small satellites, offering expanded area coverage through formation flight. However, the shortcoming to the smaller size is usually a lack of thrusting capabilities. Furthermore, current designs for small satellite deployment mechanisms are only capable of love deployment velocities (on the order of meters per second). Motivated to address this shortcoming, a conceived satellite ejector would offer a significant orbit change by ejecting the satellite at higher deployment velocities (125-200 m/s). Focusing on the applications of the ejector, it is sought to bridge the gap in prior research by offering a method to initiate formation flight. As a precursor to the initiation, the desired orbit properties to initiate the formation are specified in terms of spacing and velocity change vector. From this, a systematic method is developed to find the relationship among velocity change vector, the desired orbit's orientation, and the spacing required to initiate the formation.

Multitasking the Davidson algorithm for the large, sparse eigenvalue problem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Umar, V.M.; Fischer, C.F.

1989-01-01

The authors report how the Davidson algorithm, developed for handling the eigenvalue problem for large and sparse matrices arising in quantum chemistry, was modified for use in atomic structure calculations. To date these calculations have used traditional eigenvalue methods, which limit the range of feasible calculations because of their excessive memory requirements and unsatisfactory performance attributed to time-consuming and costly processing of zero valued elements. The replacement of a traditional matrix eigenvalue method by the Davidson algorithm reduced these limitations. Significant speedup was found, which varied with the size of the underlying problem and its sparsity. Furthermore, the range ofmore » matrix sizes that can be manipulated efficiently was expended by more than one order or magnitude. On the CRAY X-MP the code was vectorized and the importance of gather/scatter analyzed. A parallelized version of the algorithm obtained an additional 35% reduction in execution time. Speedup due to vectorization and concurrency was also measured on the Alliant FX/8.« less

Current Perspectives on Plague Vector Control in Madagascar: Susceptibility Status of Xenopsylla cheopis to 12 Insecticides.

PubMed

Miarinjara, Adélaïde; Boyer, Sébastien

2016-02-01

Plague is a rodent disease transmissible to humans by infected flea bites, and Madagascar is one of the countries with the highest plague incidence in the world. This study reports the susceptibility of the main plague vector Xenopsylla cheopis to 12 different insecticides belonging to 4 insecticide families (carbamates, organophosphates, pyrethroids and organochlorines). Eight populations from different geographical regions of Madagascar previously resistant to deltamethrin were tested with a World Health Organization standard bioassay. Insecticide susceptibility varied amongst populations, but all of them were resistant to six insecticides belonging to pyrethroid and carbamate insecticides (alphacypermethrin, lambdacyhalothrin, etofenprox, deltamethrin, bendiocarb and propoxur). Only one insecticide (dieldrin) was an efficient pulicide for all flea populations. Cross resistances were suspected. This study proposes at least three alternative insecticides (malathion, fenitrothion and cyfluthrin) to replace deltamethrin during plague epidemic responses, but the most efficient insecticide may be different for each population studied. We highlight the importance of continuous insecticide susceptibility surveillance in the areas of high plague risk in Madagascar.

Efficient design of gain-flattened multi-pump Raman fiber amplifiers using least squares support vector regression

NASA Astrophysics Data System (ADS)

Chen, Jing; Qiu, Xiaojie; Yin, Cunyi; Jiang, Hao

2018-02-01

An efficient method to design the broadband gain-flattened Raman fiber amplifier with multiple pumps is proposed based on least squares support vector regression (LS-SVR). A multi-input multi-output LS-SVR model is introduced to replace the complicated solving process of the nonlinear coupled Raman amplification equation. The proposed approach contains two stages: offline training stage and online optimization stage. During the offline stage, the LS-SVR model is trained. Owing to the good generalization capability of LS-SVR, the net gain spectrum can be directly and accurately obtained when inputting any combination of the pump wavelength and power to the well-trained model. During the online stage, we incorporate the LS-SVR model into the particle swarm optimization algorithm to find the optimal pump configuration. The design results demonstrate that the proposed method greatly shortens the computation time and enhances the efficiency of the pump parameter optimization for Raman fiber amplifier design.

Results of solar electric thrust vector control system design, development and tests

NASA Technical Reports Server (NTRS)

Fleischer, G. E.

1973-01-01

Efforts to develop and test a thrust vector control system TVCS for a solar-energy-powered ion engine array are described. The results of solar electric propulsion system technology (SEPST) III real-time tests of present versions of TVCS hardware in combination with computer-simulated attitude dynamics of a solar electric multi-mission spacecraft (SEMMS) Phase A-type spacecraft configuration are summarized. Work on an improved solar electric TVCS, based on the use of a state estimator, is described. SEPST III tests of TVCS hardware have generally proved successful and dynamic response of the system is close to predictions. It appears that, if TVCS electronic hardware can be effectively replaced by control computer software, a significant advantage in control capability and flexibility can be gained in future developmental testing, with practical implications for flight systems as well. Finally, it is concluded from computer simulations that TVCS stabilization using rate estimation promises a substantial performance improvement over the present design.

Measuring the Spin Correlation of Nuclear Muon Capture in HELIUM-3.

NASA Astrophysics Data System (ADS)

McCracken, Dorothy Jill

1996-06-01

We have completed the first measurement of the spin correlation of nuclear muon capture in ^3 He: mu^- + ^3He to nu _{mu} + ^3 H. From this spin correlation, we can extract the induced pseudoscalar form factor, F_{ rm p}, of the weak charged nuclear current. This form factor is not well known experimentally. If nuclear muon capture were a purely leptonic weak interaction, the current would have no pseudoscalar coupling, and therefore F_{rm p} arises from QCD contributions. Since ^3He is a fairly well understood system, a precise measurement of F_{rm p} could provide a direct test of the theories which describe QCD at low energies. This experiment was performed at TRIUMF in Vancouver, BC, using a muon beam. We stopped unpolarized muons in a laser polarized target filled with ^3 He and Rb vapor. The muons were captured into atomic orbitals, forming muonic ^3He which was then polarized via collisions with the optically pumped Rb vapor. When polarized muons undergo nuclear capture in ^3He, the total capture rate is proportional to (1 + {rm A_ {v}P_{v}cos} theta) where theta is the angle between the muon polarization and the triton recoil direction, P_{rm v} is the muon vector polarization and A_ {rm v} is the vector analyzing power. The partially conserved axial current hypothesis (PCAC) predicts that A_{rm v} = 0.524 +/- 0.006 Our measurement of A_{rm v} is in agreement with this prediction: A_{rm v } = 0.604 +/- 0.093 (stat.) _sp{-.142}{+.112}(syst.). This thesis will describe the design, construction, and operation of the device which simultaneously served as a polarized target and a gridded ion chamber. The ion chamber apparatus enabled us to identify recoil tritons as well as determine their direction of motion. The directional information was obtained by fitting the shapes of the pulses generated by the tritons. In addition, this thesis will describe in detail the analysis of these pulses which resulted in a measurement of the raw forward/backward asymmetry of the triton recoil direction. This asymmetry was measured to a precision of 11.5%. With the techniques employed in this experiment, a clear path exists to obtaining a precise measurement of the induced pseudoscalar coupling of the charged weak nuclear current. Plans for a future run, in which we will improve upon these techniques, are underway.

Analysis of Muon Induced Neutrons in Detecting High Z Nuclear Materials

DTIC Science & Technology

2015-03-01

mass distributions, delayed fission probabilities, and prompt to delayed fission ratios [16]. 10 2.3 Muon Catalyzed Fusion Fusion occurs when two light ...proton number; A is the atomic mass; ⇢ is the material density; = v/c where v is the velocity of the particle and c is the speed of light ; is the...8217) %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% 81 % Combine all neutron events time stamps into one vector %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% timeindex of

cis-Acting elements important for retroviral RNA packaging specificity.

PubMed

Beasley, Benjamin E; Hu, Wei-Shau

2002-05-01

Spleen necrosis virus (SNV) proteins can package RNA from distantly related murine leukemia virus (MLV), whereas MLV proteins cannot package SNV RNA efficiently. We used this nonreciprocal recognition to investigate regions of packaging signals that influence viral RNA encapsidation specificity. Although the MLV and SNV packaging signals (Psi and E, respectively) do not contain significant sequence homology, they both contain a pair of hairpins. This hairpin pair was previously proposed to be the core element in MLV Psi. In the present study, MLV-based vectors were generated to contain chimeric SNV/MLV packaging signals in which the hairpins were replaced with the heterologous counterpart. The interactions between these chimeras and MLV or SNV proteins were examined by virus replication and RNA analyses. SNV proteins recognized all of the chimeras, indicating that these chimeras were functional. We found that replacing the hairpin pair did not drastically alter the ability of MLV proteins to package these chimeras. These results indicate that, despite the important role of the hairpin pair in RNA packaging, it is not the major motif responsible for the ability of MLV proteins to discriminate between the MLV and SNV packaging signals. To determine the role of sequences flanking the hairpins in RNA packaging specificity, vectors with swapped flanking regions were generated and evaluated. SNV proteins packaged all of these chimeras efficiently. In contrast, MLV proteins strongly favored chimeras with the MLV 5'-flanking regions. These data indicated that MLV Gag recognizes multiple elements in the viral packaging signal, including the hairpin structure and flanking regions.

Magnetic excitations in iron chalcogenide superconductors.

PubMed

Kotegawa, Hisashi; Fujita, Masaki

2012-10-01

Nuclear magnetic resonance and neutron scattering experiments in iron chalcogenide superconductors are reviewed to make a survey of the magnetic excitations in FeSe, FeSe 1- x Te x and alkali-metal-doped A x Fe 2- y Se 2 ( A = K, Rb, Cs, etc). In FeSe, the intimate relationship between the spin fluctuations and superconductivity can be seen universally for the variations in the off-stoichiometry, the Co-substitution and applied pressure. The isovalent compound FeTe has a magnetic ordering with different wave vector from that of other Fe-based magnetic materials. The transition temperature T c of FeSe increases with Te substitution in FeSe 1- x Te x with small x , and decreases in the vicinity of the end member FeTe. The spin fluctuations are drastically modified by the Te substitution. In the vicinity of the end member FeTe, the low-energy part of the spin fluctuation is dominated by the wave vector of the ordered phase of FeTe; however, the reduction of T c shows that it does not support superconductivity. The presence of same wave vector as that of other Fe-based superconductors in FeSe 1- x Te x and the observation of the resonance mode demonstrate that FeSe 1- x Te x belongs to the same group as most of other Fe-based superconductors in the entire range of x , where superconductivity is mediated by the spin fluctuations whose wave vector is the same as the nesting vector between the hole pockets and the electron pockets. On the other hand, the spin fluctuations differ for alkali-metal-doped A x Fe 2- y Se 2 and FeSe or other Fe-based superconductors in their wave vector and strength in the low-energy part, most likely because of the different Fermi surfaces. The resonance mode with different wave vector suggests that A x Fe 2- y Se 2 has an exceptional superconducting symmetry among Fe-based superconductors.

Thrust Vector Control for Nuclear Thermal Rockets

NASA Technical Reports Server (NTRS)

Ensworth, Clinton B. F.

2013-01-01

Future space missions may use Nuclear Thermal Rocket (NTR) stages for human and cargo missions to Mars and other destinations. The vehicles are likely to require engine thrust vector control (TVC) to maintain desired flight trajectories. This paper explores requirements and concepts for TVC systems for representative NTR missions. Requirements for TVC systems were derived using 6 degree-of-freedom models of NTR vehicles. Various flight scenarios were evaluated to determine vehicle attitude control needs and to determine the applicability of TVC. Outputs from the models yielded key characteristics including engine gimbal angles, gimbal rates and gimbal actuator power. Additional factors such as engine thrust variability and engine thrust alignment errors were examined for impacts to gimbal requirements. Various technologies are surveyed for TVC systems for the NTR applications. A key factor in technology selection is the unique radiation environment present in NTR stages. Other considerations including mission duration and thermal environments influence the selection of optimal TVC technologies. Candidate technologies are compared to see which technologies, or combinations of technologies best fit the requirements for selected NTR missions. Representative TVC systems are proposed and key properties such as mass and power requirements are defined. The outputs from this effort can be used to refine NTR system sizing models, providing higher fidelity definition for TVC systems for future studies.

NMR studies of the helical antiferromagnetic compound EuCo 2P 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higa, N.; Ding, Q. -P.; Johnston, D. C.

In EuCo 2P 2, 4 f electron spins of Eu 2+ ions order antiferromagnetically below a Neel temperature T N = 66.5K. The magnetic structure below T N was reported to be helical with the helix axis along the c-axis from the neutron diffraction study. We report the results of 153Eu, 59Co and 31P nuclear magnetic resonance (NMR) measurements on EuCo 2P 2 using a single crystal and a powdered sample. In the antiferromagnetic (AFM) state, we succeeded in observing 153Eu, 59Co and 31P NMR spectra in zero magnetic field. The sharp 153Eu zero field NMR (ZF NMR) lines indicatemore » homogeneous Eu ordered moment. The 59Co and 31P ZF NMR spectra showed an asymmetric spectral shape, indicating a distribution of the internal magnetic induction at each nuclear position. The AFM propagation vector k characterizing the helical AFM state can be determined from the internal magnetic induction at Co site. In conclusion, we have determined the model-independent value of the AFM propagation vector k distributed from (0, 0, 0.86)2π/c to (0, 0, 0.73)2π/c, where c is the lattice parameter.« less