Efficient gene replacements in ku70 disruption strain of Aspergillus chevalieri var. intermedius

Directory of Open Access Journals (Sweden)

Qingqing Huang

2017-01-01

Full Text Available Aspergillus chevalieri var. intermedius is a dominant filamentous fungal species in Fuzhuan tea and is associated with the quality and health benefits of this tea. The sexual or asexual reproduction of this fungus depends on the osmotic pressure of the tea. Efforts to enhance the beneficial effects of A. chevalieri var. intermedius are hampered by difficulties in disrupting its genes. To address this issue, we identified the A. chevalieri var. intermedius homolog (Acku70 of human Ku70 and generated an Acku70 disruption strain (ΔAcku70, aiming to improve the gene replacement efficiency. ΔAcku70 grew at a slightly lower rate in vitro than the wild-type strain; however, the two strains exhibited similar sensitivity to temperature, osmotic pressure and the effects of ethyl methane sulphonate and H2O2. The replacement efficiency of veA and flbA dramatically increased in ΔAcku70 compared to that in the wild type. The efficiency of flbA replacement increased from 2.6% to 80%, whereas the frequency of veA disruption increased from 15.2% to 83.9% and from 30.8% to 86.8%. Thus, ΔAcku70 is suitable for use as a type strain for large-scale functional genomic analysis of A. chevalieri var. intermedius.

Logistic Vehicle System Replacement Cost Estimate

National Research Council Canada - National Science Library

Stinson, Margaret

1998-01-01

The Logistics Vehicle System (LVS) was originally fielded from 1985-1989. Most of the LVS fleet will reach end-of-service life in 2005, therefore the goal of the Logistics Vehicle System Replacement (LVSR...

Modifications to Replacement Costs System

International Nuclear Information System (INIS)

Godec, M.

1989-01-01

The purpose of this memorandum is to document the improvements and modifications made to the Replacement Costs of Crude Oil (REPCO) Supply Analysis System. While some of this work was performed under our previous support contract to DOE/ASFE, we are presenting all modifications and improvements are presented here for completeness. The memo primarily documents revisions made to the Lower-48 Onshore Model. Revisions and modifications made to other components and models in the REPCO system which are documented elsewhere are only highlighted in this memo. Generally, the modifications made to the Lower-48 Onshore Model reflect changes that have occurred in domestic drilling, oil field costs, and reserves since 1982, the date of the most recent available data used for the original Replacement Costs report, published in 1985

SYBR safeTM efficiently replaces ethidium bromide in Aspergillus fumigatus gene disruption.

Science.gov (United States)

Canela, H M S; Takami, L A; Ferreira, M E S

2017-02-08

Invasive aspergillosis is a disease responsible for high mortality rates, caused mainly by Aspergillus fumigatus. The available drugs are limited and this disease continues to occur at an unacceptable frequency. Gene disruption is essential in the search for new drug targets. An efficient protocol for A. fumigatus gene disruption was described but it requires ethidium bromide, a genotoxic agent, for DNA staining. Therefore, the present study tested SYBR safe TM , a non-genotoxic DNA stain, in A. fumigatus gene disruption protocol. The chosen gene was cipC, which has already been disrupted successfully in our laboratory. A deletion cassette was constructed in Saccharomyces cerevisiae and used in A. fumigatus transformation. There was no statistical difference between the tested DNA stains. The success rate of S. cerevisiae transformation was 63.3% for ethidium bromide and 70% for SYBR safe TM . For A. fumigatus gene disruption, the success rate for ethidium bromide was 100 and 97% for SYBR safe TM . In conclusion, SYBR safe TM efficiently replaced ethidium bromide, making this dye a safe and efficient alternative for DNA staining in A. fumigatus gene disruption.

Contribution of V(H replacement products in mouse antibody repertoire.

Directory of Open Access Journals (Sweden)

Lin Huang

Full Text Available VH replacement occurs through RAG-mediated recombination between the cryptic recombination signal sequence (cRSS near the 3' end of a rearranged VH gene and the 23-bp RSS from an upstream unrearranged VH gene. Due to the location of the cRSS, VH replacement leaves a short stretch of nucleotides from the previously rearranged VH gene at the newly formed V-D junction, which can be used as a marker to identify VH replacement products. To determine the contribution of VH replacement products to mouse antibody repertoire, we developed a Java-based VH Replacement Footprint Analyzer (VHRFA program and analyzed 17,179 mouse IgH gene sequences from the NCBI database to identify VH replacement products. The overall frequency of VH replacement products in these IgH genes is 5.29% based on the identification of pentameric VH replacement footprints at their V-D junctions. The identified VH replacement products are distributed similarly in IgH genes using most families of VH genes, although different families of VH genes are used differentially. The frequencies of VH replacement products are significantly elevated in IgH genes derived from several strains of autoimmune prone mice and in IgH genes encoding autoantibodies. Moreover, the identified VH replacement footprints in IgH genes from autoimmune prone mice or IgH genes encoding autoantibodies preferentially encode positively charged amino acids. These results revealed a significant contribution of VH replacement products to the diversification of antibody repertoire and potentially, to the generation of autoantibodies in mice.

Ultrasound-targeted transfection of tissue-type plasminogen activator gene carried by albumin nanoparticles to dog myocardium to prevent thrombosis after heart mechanical valve replacement

Directory of Open Access Journals (Sweden)

Ji J

2012-06-01

Full Text Available Ji Jun, Ji Shang-Yi, Yang Jian-An, He Xia, Yang Xiao-Han, Ling Wen-Ping, Chen Xiao-LingDepartment of Pathology and Cardiovascular Surgery, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, Guangdong, People's Republic of ChinaBackground: There are more than 300,000 prosthetic heart valve replacements each year worldwide. These patients are faced with a higher risk of thromboembolic events after heart valve surgery and long-term or even life-long anticoagulative and antiplatelet therapies are necessary. Some severe complications such as hemorrhaging or rebound thrombosis can occur when the therapy ceases. Tissue-type plasminogen activator (t-PA is a thrombolytic agent. One of the best strategies is gene therapy, which offers a local high expression of t-PA over a prolonged time period to avoid both systemic hemorrhaging and local rebound thrombosis. There are some issues with t-PA that need to be addressed: currently, there is no up-to-date report on how the t-PA gene targets the heart in vivo and the gene vector for t-PA needs to be determined.Aims: To fabricate an albumin nano-t-PA gene ultrasound-targeted agent and investigate its targeting effect on prevention of thrombosis after heart mechanic valve replacement under therapeutic ultrasound.Methods: A dog model of mechanical tricuspid valve replacement was constructed. A highly expressive t-PA gene plasmid was constructed and packaged by nanoparticles prepared with bovine serum albumin. This nanopackaged t-PA gene plasmid was further cross-linked to ultrasonic microbubbles prepared with sucrose and bovine serum albumin to form the ultrasonic-targeted agent for t-PA gene transfection. The agent was given intravenously followed by a therapeutic ultrasound treatment (1 MHz, 1.5 w/cm2, 10 minutes of the heart soon after valve replacement had been performed. The expression of t-PA in myocardium was detected with multiclonal antibodies to t-PA by the indirect immunohistochemical method

Genetic stability of gene targeted immunoglobulin loci. I. Heavy chain isotype exchange induced by a universal gene replacement vector.

Science.gov (United States)

Kardinal, C; Selmayr, M; Mocikat, R

1996-11-01

Gene targeting at the immunoglobulin loci of B cells is an efficient tool for studying immunoglobulin expression or generating chimeric antibodies. We have shown that vector integration induced by human immunoglobulin G1 (IgG1) insertion vectors results in subsequent vector excision mediated by the duplicated target sequence, whereas replacement events which could be induced by the same constructs remain stable. We could demonstrate that the distribution of the vector homology strongly influences the genetic stability obtained. To this end we developed a novel type of a heavy chain replacement vector making use of the heavy chain class switch recombination sequence. Despite the presence of a two-sided homology this construct is universally applicable irrespective of the constant gene region utilized by the B cell. In comparison to an integration vector the frequency of stable incorporation was strongly increased, but we still observed vector excision, although at a markedly reduced rate. The latter events even occurred with circular constructs. Linearization of the construct at various sites and the comparison with an integration vector that carries the identical homology sequence, but differs in the distribution of homology, revealed the following features of homologous recombination of immunoglobulin genes: (i) the integration frequency is only determined by the length of the homology flank where the cross-over takes place; (ii) a 5' flank that does not meet the minimum requirement of homology length cannot be complemented by a sufficient 3' flank; (iii) free vector ends play a role for integration as well as for replacement targeting; (iv) truncating recombination events are suppressed in the presence of two flanks. Furthermore, we show that the switch region that was used as 3' flank is non-functional in an inverted orientation.

Replacement policy in a system under shocks following a Markovian arrival process

International Nuclear Information System (INIS)

Montoro-Cazorla, Delia; Perez-Ocon, Rafael; Carmen Segovia, Maria del

2009-01-01

We present a system subject to shocks that arrive following a Markovian arrival process. The system is minimally repaired. It is replaced when a certain number of shocks arrive. A general model where the replacements are governed by a discrete phase-type distribution is studied. For this system, the Markov process governing the system is constructed, and the interarrival times between replacements and the number of replacements are calculated. A special case of this system is when it can stand a prefixed number of shocks. For this new system, the same performance measures are calculated. The systems are considered in transient and stationary regime

Replacement policy in a system under shocks following a Markovian arrival process

Energy Technology Data Exchange (ETDEWEB)

Montoro-Cazorla, Delia [Department of Statistics and Operational Research, University of Jaen (Spain); Perez-Ocon, Rafael [Department of Statistics and Operational Research, University of Granada, Granada (Spain)], E-mail: rperezo@ugr.es; Carmen Segovia, Maria del [Departamento de Estadistica e I.O., University of Granada, Granada (Spain)

2009-02-15

We present a system subject to shocks that arrive following a Markovian arrival process. The system is minimally repaired. It is replaced when a certain number of shocks arrive. A general model where the replacements are governed by a discrete phase-type distribution is studied. For this system, the Markov process governing the system is constructed, and the interarrival times between replacements and the number of replacements are calculated. A special case of this system is when it can stand a prefixed number of shocks. For this new system, the same performance measures are calculated. The systems are considered in transient and stationary regime.

Service water system repair/replacement guidelines: Planning and implementation

International Nuclear Information System (INIS)

Frederick, G.J.; Gandy, D.W.; Peterson, A.G. Jr.; Findlan, S.J.

1993-11-01

Service water system failures have prompted concerns related to extended power plant operating life and plant availability. Selection and procurement of materials for repair or replacement of piping and components may be the most important factors in improving service water system reliability. The authors examined factors that contribute to reduced SWS reliability. The factors include material selection inadequacies, water treatment problems, operational/maintenance practices, fabrication procedures, environmental degradation mechanisms, and coating problems. The authors investigated material selection for replacement and repair, taking into account fabrication practices, environmental concerns, and cost comparisons of materials. They examined specific components such as piping, pumps, valves, and heat exchangers with regard to material selection and fabrication practice. Although proper material selection is essential in upgrading and maintaining the designed functions of a SWS, it is critical to address SWS repair/replacement activities with a systemwide approach. Degradation of materials in SWS applications are plant specific, depending on factors unique to each site such as geographic location, existing materials, operating procedures, and environment. All these characteristics must be addressed in making repair/replacement decisions. Criteria that must be integrated for successful long-term operation of SWS include the following: Materials selection (upgrade or in-kind replacement), Evaluation of root cause or nature of the failure mechanism, Scope of the repair/replacement activities, Material compatibility of the existing materials, Operational and maintenance procedures, Code or jurisdictional requirements, Economic considerations, Water treatment programs, System design improvements or modifications

Replication of alfalfa mosaic virus RNA 3 with movement and coat protein genes replaced by corresponding genes of Prunus necrotic ringspot ilarvirus.

Science.gov (United States)

Sánchez-Navarro, J A; Reusken, C B; Bol, J F; Pallás, V

1997-12-01

Alfalfa mosaic virus (AMV) and Prunus necrotic ringspot virus (PNRSV) are tripartite positive-strand RNA plant viruses that encode functionally similar translation products. Although the two viruses are phylogenetically closely related, they infect a very different range of natural hosts. The coat protein (CP) gene, the movement protein (MP) gene or both genes in AMV RNA 3 were replaced by the corresponding genes of PNRSV. The chimeric viruses were tested for heterologous encapsidation, replication in protoplasts from plants transformed with AMV replicase genes P1 and P2 (P12 plants) and for cell-to-cell transport in P12 plants. The chimeric viruses exhibited basic competence for encapsidation and replication in P12 protoplasts and for a low level of cell-to-cell movement in P12 plants. The potential involvement of the MP gene in determining host specificity in ilarviruses is discussed.

Replacement of the computerized control system at NPP under operation

International Nuclear Information System (INIS)

Ermolaev, A.D.; Rakitin, I.D.

1985-01-01

Reasons and preconditions for replacement of the computerized control systems (CCS) at NPP under operation are consi-- dered. Problems dealing with management of CCS replacement, maintenance of a new CCS as well as NPP personnel training for the new system maintenance are discussed. A necessity of NPP personnel participation in these works in order to adapt CCS to requirements of NPP operation personnel and to initiate the training process is underlined. Replacement of CCS at NPP under operation is associated, as a rule, with obsolescence of old systems not ensuring growing requirements to NPP workability and safety. Principles observed at CCS replacement are reduced, mainly, to the following; maximum utilizatian of existing equipment, metal strUctures, cables, instruments, power supplies, ventilation system minimum of construction works and new communications; the least change of acting panels and boxes; changes in control desks should be introduced on the basis of the analysis of operator actions '

Replacement of the instrumentation and control system of Tore Supra

International Nuclear Information System (INIS)

Leveque, P.

1995-02-01

The control system of the Tore-Supra is a wide and complex system that cannot be interrupted while running without significant consequences on the operating of the machine. Replacing the current system cannot be achieved in a global way without immobilisation and high costs. Therefore partial changes have been decided on. This work presents the detailed analysis of the arrangements and the operating of the system that will be replaced: the pro's and con's that have appeared through experience are related. The possibilities that the new apparatus offers are also examined. A method of step by step replacements had to be set up in order to assess the means, funds, term of achievement, performance and quality of the overall project. (TEC). 15 refs., 29 figs

Comparing replacement rates under private and federal retirement systems.

Science.gov (United States)

Martin, Patricia P

One measure of the adequacy of retirement income is replacement rate - the percentage of pre-retirement salary that is available to a worker in retirement. This article compares salary replacement rates for private-sector employees of medium and large private establishments with those for federal employees under the Civil Service Retirement System and the Federal Employees Retirement System. Because there is no standard benefit formula to represent the variety of formulas available in the private sector, a composite defined benefit formula was developed using the characteristics of plans summarized in the Bureau of Labor Statistics Medium and Large Employer Plan Survey. The resulting "typical" private-sector defined benefit plan, with an accompanying defined contribution plan, was then compared with the two federal systems. The Civil Service Retirement System (CSRS) is a stand-alone defined benefit plan whose participants are not covered by Social Security. Until passage of the 1983 Amendments to Social Security Act, it was the only retirement plan for most federal civilian employees. Provisions of the 1983 Amendments were designed to restore long-term financial stability to the Social Security trust funds. One provision created the Federal Employees Retirement System (FERS), which covers federal employees hired after 1983. It was one of the provisions designed to restore long-term financial stability to the Social Security trust funds. FERS employees contribute to and are covered by Social Security. FERS, which is a defined benefit plan, also includes a basic benefit and a 401(k)-type plan known as the Thrift Savings Plan (TSP). To compare how retirees would fare under the three different retirement systems, benefits of employees retiring at age 65 with 35 years of service were calculated using hypothetical workers with steady earnings. Workers were classified according to a percentage of the average wage in the economy: low earners (45 percent), average earners

A bivariate optimal replacement policy for a multistate repairable system

International Nuclear Information System (INIS)

Zhang Yuanlin; Yam, Richard C.M.; Zuo, Ming J.

2007-01-01

In this paper, a deteriorating simple repairable system with k+1 states, including k failure states and one working state, is studied. It is assumed that the system after repair is not 'as good as new' and the deterioration of the system is stochastic. We consider a bivariate replacement policy, denoted by (T,N), in which the system is replaced when its working age has reached T or the number of failures it has experienced has reached N, whichever occurs first. The objective is to determine the optimal replacement policy (T,N)* such that the long-run expected profit per unit time is maximized. The explicit expression of the long-run expected profit per unit time is derived and the corresponding optimal replacement policy can be determined analytically or numerically. We prove that the optimal policy (T,N)* is better than the optimal policy N* for a multistate simple repairable system. We also show that a general monotone process model for a multistate simple repairable system is equivalent to a geometric process model for a two-state simple repairable system in the sense that they have the same structure for the long-run expected profit (or cost) per unit time and the same optimal policy. Finally, a numerical example is given to illustrate the theoretical results

Environmental systems analysis of biogas systems-Part II: The environmental impact of replacing various reference systems

International Nuclear Information System (INIS)

Boerjesson, Pal; Berglund, Maria

2007-01-01

This paper analyses the overall environmental impact when biogas systems are introduced and replace various reference systems for energy generation, waste management and agricultural production. The analyses are based on Swedish conditions using a life-cycle perspective. The biogas systems included are based on different combinations of raw materials and final use of the biogas produced (heat, power and transportation fuel). A general conclusion is that biogas systems normally lead to environmental improvements, which in some cases are considerable. This is often due to indirect environmental benefits of changed land use and handling of organic waste products (e.g. reduced nitrogen leaching, emissions of ammonia and methane), which often exceed the direct environmental benefits achieved when fossil fuels are replaced by biogas (e.g. reduced emissions of carbon dioxide and air pollutants). Such indirect benefits are seldom considered when biogas is evaluated from an environmental point of view. The environmental impact from different biogas systems can, however, vary significantly due to factors such as the raw materials utilised, energy service provided and reference system replaced

Replacement of the control and instrumentation system with the microprocessor based systems in Japanese PWR plants

International Nuclear Information System (INIS)

Hayashi, N.

1998-01-01

In Ohi Units 3 and 4, Ikata Unit 3, and Genkai Units 3 and 4, the latest of PWR plants now under operation in Japan, the reactor control system and turbine control system employ the microprocessor base digital control systems with a view to improving reliability, operability and maintainability. In the next stage plants, another application of such digital system is also planned for the instrumentation rack for the reactor protection system for further improvement. On the other hand, in Mihama Unit 1, the first of domestic PWR plants, and later plants except for the latest 5 plants, analog control systems are employed for the instrumentation racks. For the analog control systems of these plants, FOXBORO H-Line instruments, equivalent domestic box type instruments or WH7300 Series card type instruments were initially employed, and later replaced with domestic card type control systems after 10-15 year operation. However, 8-12 years have passed since these replacements, so the 15th year generally quoted as an interval for replacing C and I systems is near at hand. This is the time to consider next replacement. This replacement will be based on the latest digital technology. However, it is not practical way for the existing plants to apply the same integrated digital C and I system configuration for the next stage plants, because it requires the drastic change of the C and I system configuration and significant cost-up. Therefore, we must investigate the optimum digital C and I system configuration for the existing system. (author)

An extended optimal replacement model for a deteriorating system with inspections

International Nuclear Information System (INIS)

Sheu, Shey-Huei; Tsai, Hsin-Nan; Wang, Fu-Kwun; Zhang, Zhe George

2015-01-01

This study considers a generalized replacement model for a deteriorating system in which failures can only be detected by inspection. The system is assumed to have two types of failures and is replaced at the occurrence of the Nth type I failure (minor failure), or the first type II failure (catastrophic failure), or at working age T, whichever occurs first. The probability of a type I or type II failure depends on the number of type I failures since the previous replacement. Such a system can be repaired after a type I failure, but is deteriorating stochastically. That is, the operating intervals are decreasing stochastically, whereas the durations of the repairs are increasing stochastically. Based on these assumptions, we determine the expected net cost rate and discuss various special cases of the model. Finally, we develop a computational algorithm for finding the optimal policy and present a numerical example to show the properties of the proposed model. - Highlight: • Replacement policy for system subject two types of failures or the system's working age. • Failures detected by inspections. • Decreasing operating times and increasing repair times. • Derive a cost function. • Determine the cost minimization policy

Replacement of the ISIS control system

International Nuclear Information System (INIS)

Mannix, R.P.; Barton, C.J.; Brownless, D.M.; Kerr, J.C.

1992-01-01

In operation since 1985, ISIS is the world's most powerful pulsed spallation neutron source. The decision has been taken to replace the existing ISIS control system, which has been in use for over ten years. The problems of such a project, given the legacy of processor specific hardware and software are discussed, a long with the problems associated with incorporating existing interface hardware into any new system. Present progress using commercial workstation based control software is presented with, an assessment of the benefits and pitfalls of such an approach. (author)

Status of clean gene (selection marker-free)technology | Afolabi ...

African Journals Online (AJOL)

... (2) site-specific recombination systems and (3) intra-chromosomal recombination. (B) Gene replacement or Targeted gene replacement; and (C) transformation with multiple T-DNAs, which could result in linked and/or unlinked co-integration of transgenes. Unlinked transgenes are then segregated out during meiosis.

A new type of gene-disruption cassette with a rescue gene for Pichia pastoris.

Science.gov (United States)

Shibui, Tatsuro; Hara, Hiroyoshi

2017-09-01

Pichia pastoris has been used for the production of many recombinant proteins, and many useful mutant strains have been created. However, the efficiency of mutant isolation by gene-targeting is usually low and the procedure is difficult for those inexperienced in yeast genetics. In order to overcome these issues, we developed a new gene-disruption system with a rescue gene using an inducible Cre/mutant-loxP system. With only short homology regions, the gene-disruption cassette of the system replaces its target-gene locus containing a mutation with a compensatory rescue gene. As the cassette contains the AOX1 promoter-driven Cre gene, when targeted strains are grown on media containing methanol, the DNA fragment, i.e., the marker, rescue and Cre genes, between the mutant-loxP sequences in the cassette is excised, leaving only the remaining mutant-loxP sequence in the genome, and consequently a target gene-disrupted mutant can be isolated. The system was initially validated on ADE2 gene disruption, where the disruption can easily be detected by color-change of the colonies. Then, the system was applied for knocking-out URA3 and OCH1 genes, reported to be difficult to accomplish by conventional gene-targeting methods. All three gene-disruption cassettes with their rescue genes replaced their target genes, and the Cre/mutant-loxP system worked well to successfully isolate their knock-out mutants. This study identified a new gene-disruption system that could be used to effectively and strategically knock out genes of interest, especially whose deletion is detrimental to growth, without using special strains, e.g., deficient in nonhomologous end-joining, in P. pastoris. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1201-1208, 2017. © 2017 American Institute of Chemical Engineers.

Nuclear reactor fuel replacement system

International Nuclear Information System (INIS)

Kayano, Hiroyuki; Joge, Toshio.

1976-01-01

Object: To permit the direction in which a fuel replacement unit is moving to be monitored by the operator. Structure: When a fuel replacement unit approaches an intermediate goal position preset in the path of movement, renewal of data display on a goal position indicator is made every time the goal position is changed. With this renewal, the prevailing direction of movement of the fuel replacement unit can be monitored by the operator. When the control of movement is initiated, the co-ordinates of the intermediate goal point A are displayed on a goal position indicator. When the replacement unit reaches point A, the co-ordinates of the next intermediate point B are displayed, and upon reaching point B the co-ordinates of the (last) goal point C are displayed. (Nakamura, S.)

A model for calculating the optimal replacement interval of computer systems

International Nuclear Information System (INIS)

Fujii, Minoru; Asai, Kiyoshi

1981-08-01

A mathematical model for calculating the optimal replacement interval of computer systems is described. This model is made to estimate the best economical interval of computer replacement when computing demand, cost and performance of computer, etc. are known. The computing demand is assumed to monotonously increase every year. Four kinds of models are described. In the model 1, a computer system is represented by only a central processing unit (CPU) and all the computing demand is to be processed on the present computer until the next replacement. On the other hand in the model 2, the excessive demand is admitted and may be transferred to other computing center and processed costly there. In the model 3, the computer system is represented by a CPU, memories (MEM) and input/output devices (I/O) and it must process all the demand. Model 4 is same as model 3, but the excessive demand is admitted to be processed in other center. (1) Computing demand at the JAERI, (2) conformity of Grosch's law for the recent computers, (3) replacement cost of computer systems, etc. are also described. (author)

Excretion of Antibiotic Resistance Genes by Dairy Calves Fed Milk Replacers with Varying Doses of Antibiotics

Science.gov (United States)

Thames, Callie H.; Pruden, Amy; James, Robert E.; Ray, Partha P.; Knowlton, Katharine F.

2012-01-01

Elevated levels of antibiotic resistance genes (ARGs) in soil and water have been linked to livestock farms and in some cases feed antibiotics may select for antibiotic resistant gut microbiota. The purpose of this study was to examine the establishment of ARGs in the feces of calves receiving milk replacer containing no antibiotics versus subtherapeutic or therapeutic doses of tetracycline and neomycin. The effect of antibiotics on calf health was also of interest. Twenty-eight male and female dairy calves were assigned to one of the three antibiotic treatment groups at birth and fecal samples were collected at weeks 6, 7 (prior to weaning), and 12 (5 weeks after weaning). ARGs corresponding to the tetracycline (tetC, tetG, tetO, tetW, and tetX), macrolide (ermB, ermF), and sulfonamide (sul1, sul2) classes of antibiotics along with the class I integron gene, intI1, were monitored by quantitative polymerase chain reaction as potential indicators of direct selection, co-selection, or horizontal gene transfer of ARGs. Surprisingly, there was no significant effect of antibiotic treatment on the absolute abundance (gene copies per gram wet manure) of any of the ARGs except ermF, which was lower in the antibiotic-treated calf manure, presumably because a significant portion of host bacterial cells carrying ermF were not resistant to tetracycline or neomycin. However, relative abundance (gene copies normalized to 16S rRNA genes) of tetO was higher in calves fed the highest dose of antibiotic than in the other treatments. All genes, except tetC and intI1, were detectable in feces from 6 weeks onward, and tetW and tetG significantly increased (P calves. Overall, the results provide new insight into the colonization of calf gut flora with ARGs in the early weeks. Although feed antibiotics exerted little effect on the ARGs monitored in this study, the fact that they also provided no health benefit suggests that the greater than conventional nutritional intake applied

Controlled expression of nif and isc iron-sulfur protein maturation components reveals target specificity and limited functional replacement between the two systems.

Science.gov (United States)

Dos Santos, Patricia C; Johnson, Deborah C; Ragle, Brook E; Unciuleac, Mihaela-Carmen; Dean, Dennis R

2007-04-01

The nitrogen-fixing organism Azotobacter vinelandii contains at least two systems that catalyze formation of [Fe-S] clusters. One of these systems is encoded by nif genes, whose products supply [Fe-S] clusters required for maturation of nitrogenase. The other system is encoded by isc genes, whose products are required for maturation of [Fe-S] proteins that participate in general metabolic processes. The two systems are similar in that they include an enzyme for the mobilization of sulfur (NifS or IscS) and an assembly scaffold (NifU or IscU) upon which [Fe-S] clusters are formed. Normal cellular levels of the Nif system, which supplies [Fe-S] clusters for the maturation of nitrogenase, cannot also supply [Fe-S] clusters for the maturation of other cellular [Fe-S] proteins. Conversely, when produced at the normal physiological levels, the Isc system cannot supply [Fe-S] clusters for the maturation of nitrogenase. In the present work we found that such target specificity for IscU can be overcome by elevated production of NifU. We also found that NifU, when expressed at normal levels, is able to partially replace the function of IscU if cells are cultured under low-oxygen-availability conditions. In contrast to the situation with IscU, we could not establish conditions in which the function of IscS could be replaced by NifS. We also found that elevated expression of the Isc components, as a result of deletion of the regulatory iscR gene, improved the capacity for nitrogen-fixing growth of strains deficient in either NifU or NifS.

CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations.

Science.gov (United States)

Fogleman, Sarah; Santana, Casey; Bishop, Casey; Miller, Alyssa; Capco, David G

2016-01-01

Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy.

Recurrent adenylation domain replacement in the microcystin synthetase gene cluster

Directory of Open Access Journals (Sweden)

Laakso Kati

2007-10-01

Full Text Available Abstract Background Microcystins are small cyclic heptapeptide toxins produced by a range of distantly related cyanobacteria. Microcystins are synthesized on large NRPS-PKS enzyme complexes. Many structural variants of microcystins are produced simulatenously. A recombination event between the first module of mcyB (mcyB1 and mcyC in the microcystin synthetase gene cluster is linked to the simultaneous production of microcystin variants in strains of the genus Microcystis. Results Here we undertook a phylogenetic study to investigate the order and timing of recombination between the mcyB1 and mcyC genes in a diverse selection of microcystin producing cyanobacteria. Our results provide support for complex evolutionary processes taking place at the mcyB1 and mcyC adenylation domains which recognize and activate the amino acids found at X and Z positions. We find evidence for recent recombination between mcyB1 and mcyC in strains of the genera Anabaena, Microcystis, and Hapalosiphon. We also find clear evidence for independent adenylation domain conversion of mcyB1 by unrelated peptide synthetase modules in strains of the genera Nostoc and Microcystis. The recombination events replace only the adenylation domain in each case and the condensation domains of mcyB1 and mcyC are not transferred together with the adenylation domain. Our findings demonstrate that the mcyB1 and mcyC adenylation domains are recombination hotspots in the microcystin synthetase gene cluster. Conclusion Recombination is thought to be one of the main mechanisms driving the diversification of NRPSs. However, there is very little information on how recombination takes place in nature. This study demonstrates that functional peptide synthetases are created in nature through transfer of adenylation domains without the concomitant transfer of condensation domains.

The restriction-modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities.

Science.gov (United States)

O'Neill, M; Chen, A; Murray, N E

1997-12-23

Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491-496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as "selfish" units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.

Development of remote replacement system for armor tiles of first wall of FER

International Nuclear Information System (INIS)

Adachi, Junichi; Yoshizawa, Shunji; Nakano, Yasuo; Kuboyama, Takashi; Shibanuma, Kiyoshi; Kakudate, Satoshi; Oka, Kiyoshi.

1993-01-01

A remote system has been developed to replace automatically armor tiles of first walls with a single manipulator arm for the Fusion Experimental Reactor (FER). The system is composed of a manipulator arm and an end-effector (a tile replacement hand), which have a gripper of the tiles, a nutrunner to rotate attatching bolts of them and a vision sensor to measure positions of them. The system can replace the tiles by means of a visual feedback system using vision sensor, even if the positions of the tiles would have changed. As a result of tests, it has been proved that the end-effector is useful and the control system is practicable. (author)

CORESAFE: A Formal Approach against Code Replacement Attacks on Cyber Physical Systems

Science.gov (United States)

2018-04-19

AFRL-AFOSR-JP-TR-2018-0035 CORESAFE:A Formal Approach against Code Replacement Attacks on Cyber Physical Systems Sandeep Shukla INDIAN INSTITUTE OF...Formal Approach against Code Replacement Attacks on Cyber Physical Systems 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386-16-1-4099 5c.  PROGRAM ELEMENT...SUPPLEMENTARY NOTES 14.  ABSTRACT Industrial Control Systems (ICS) used in manufacturing, power generators and other critical infrastructure monitoring and

Optimal replacement policy for safety-related multi-component multi-state systems

International Nuclear Information System (INIS)

Xu Ming; Chen Tao; Yang Xianhui

2012-01-01

This paper investigates replacement scheduling for non-repairable safety-related systems (SRS) with multiple components and states. The aim is to determine the cost-minimizing time for replacing SRS while meeting the required safety. Traditionally, such scheduling decisions are made without considering the interaction between the SRS and the production system under protection, the interaction being essential to formulate the expected cost to be minimized. In this paper, the SRS is represented by a non-homogeneous continuous time Markov model, and its state distribution is evaluated with the aid of the universal generating function. Moreover, a structure function of SRS with recursive property is developed to evaluate the state distribution efficiently. These methods form the basis to derive an explicit expression of the expected system cost per unit time, and to determine the optimal time to replace the SRS. The proposed methodology is demonstrated through an illustrative example.

Optimized preventive replacement policy for large cascade systems

International Nuclear Information System (INIS)

Kretzen, H.H.

1986-01-01

The repair-bottleneck problem as a limiting factor for system reliability can be overcome. Design need only cover the steady state, wearout induced accumulations of failures being precluded by preventive replacements with subsequent recycling. As a result, a reliable system appears to be feasible on an economic basis, optimization in detail to be left to more precised cost-benefit studies. As a reference system the radio-frequency-generator cascade of a single-cell linear accelerator is considered. (DG)

Replacement of the complete control system of the NPP Oskarshamn 1 by digital distributed control system

International Nuclear Information System (INIS)

Berger, E.

1998-01-01

As part of an ongoing modernization program, Oskarshamn 1's I and C system and control room will be upgraded by ABB using its Advant Power range of digital, programmable process control system. Besides ensuring the higher level of safety that is demanded today, the new equipment provides the plant with an integrated system which will improve operator overview of operation and reduce risk of human error and serve as a platform for further improvements of the control room. This paper discusses in the example of Oskarshamn 1 how the complete control system of a nuclear power plant may be exchanged, the technical solution and the time schedule. Oskarshamn 1 is the first nuclear power plant in Sweden. It is a boiling water reactor built by ABB ATOM in Sweden between 1966 and 1971. According to this age the control system is semiconductor based and the reactor protection system is relays based. This makes the maintenance expensive and extensions nearly impossible. To extend the life period of this plant the owner has decided to improve the safety system and to replace the reactor protection system and safety related control and the non safety related control by a state of the art digital distributed control system of ABB. In March 1997 ABB got the order to replace the reactor protection system, the safety control system, to start the replacement of all control systems and to replace the old control room by a new ergonomically designed control room. Together with the exchange of the control system an enhancement of the safety system and of the emergency power supply will be implemented

Genes and Gene Therapy

Science.gov (United States)

... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

Conditions for success of engineered underdominance gene drive systems.

Science.gov (United States)

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.

Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study

Directory of Open Access Journals (Sweden)

Skoog Lambert

2006-06-01

Full Text Available Abstract Background Postmenopausal hormone-replacement therapy (HRT increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. Methods We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. Results HRT use in patients with estrogen receptor (ER protein positive tumors (n = 72 was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. Conclusion Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.

Regulatory requirements for replacement of analog systems with digital upgrades

International Nuclear Information System (INIS)

Loeser, P.J.

1993-01-01

This paper reviews briefly the regulatory guidelines which must be met in order to replace analog systems in nuclear power plants with digital systems. There is a move to do such replacements for a number of reasons: analog systems are aging, and showing considerable drift; few vendors manufacture analog systems today; support and parts are hard to get; digital systems provide flexibility. There is a safety concern however about undesirable and unpredictable effects to digital safety equipment due to plant transients, accidents, post-accident condition, and EMI/RF environmental interferences. License holders must comply with the requirements of 10 C.F.R. 50.59, which deals with safety concerns with respect to any changes to operating plants which may have an impact on the safety of the plant. NRC staff is taking the position that all digital upgrades will require an evaluation under this regulation

Replacement of the complete control system of the NPP Oskarshamn 1 by digital distributed control system

International Nuclear Information System (INIS)

Berger, E.

1998-01-01

As part of an ongoing modernization program, the I and C system and the control room of Oskarshamn 1 will be upgraded by ABB using its 'Advant Power' range of digital, programmable process control system. Besides ensuring the higher level of safety that is demanded today, the new equipment provides the plant with an integrated system which will improve operator interaction with the plant and reduce the risk of human error. The newly installed DCS system will serve also as a platform for further improvements of the control room. This paper discusses Oskarshamn 1 exchange of the complete control system of a nuclear power plant, the technical solution and the time schedule. Oskarshamn 1 is the first nuclear power plant in Sweden. It is a boiling water reactor built between 1966 and 1971 by ABB ATOM in Sweden. According to the plant age the control system is relay-based, while instrumentation and analogue control is semiconductor-based. This makes maintenance expensive and even worse, makes extensions nearly impossible. According to the safety standards of the 1960s, there is no separation between safety and non safety control and no seismic qualification. To extend the life of this plant the owner has decided to improve the safety system as well as to replace the reactor protection system, the safety related control and the non safety related control by a state-of-the-art digital distributed control system from ABB. In March 1997, ABB got the order to replace the reactor protection system, the safety control system and to start the replacement of all control systems. The old control room has to be replaced by a new ergonomically design. Together with the exchange of the control system the safety features of the plant and the emergency power supply has to be extended. (author)

Development and evaluation of an efficient heterologous gene knock-in reporter system in Lactococcus lactis.

Science.gov (United States)

Lu, Yifei; Yan, Hongxiang; Deng, Jiezhong; Huang, Zhigang; Jin, Xurui; Yu, Yanlan; Hu, Qiwen; Hu, Fuquan; Wang, Jing

2017-09-18

Lactococcus lactis is a food grade probiotics and widely used to express heterologous proteins. Generally, target genes are knocked into the L. lactis genome through double-crossover recombination to express heterologous proteins stably. However, creating marker-less heterologous genes knocked-in clones is laborious. In this study, an efficient heterologous gene knock-in reporter system was developed in L. lactis NZ9000. Our knock-in reporter system consists of a temperature-sensitive plasmid pJW and a recombinant L. lactis strain named NZB. The pJW contains homologous arms, and was constructed to knock-in heterologous genes at a fixed locus of NZ9000 genome. lacZ (β-galactosidase) gene was knocked into the chromosome of NZ9000 as a counter-selective marker through the plasmid pJW to generate NZB. The engineered NZB strain formed blue colonies on X-Gal plate. The desired double-crossover mutants formed white colonies distinctive from the predominantly blue colonies (parental and plasmid-integrated clones) when the embedded lacZ was replaced with the target heterologous genes carried by pJW in NZB. By using the system, the heterologous gene knocked-in clones are screened by colony phenotype change rather than by checking colonies individually. Our new knock-in reporter system provides an efficient method to create heterologous genes knocked-in clones.

10 CFR 830 Major Modification Determination for Emergency Firewater Injection System Replacement

International Nuclear Information System (INIS)

Duckwitz, Noel

2011-01-01

The continued safe and reliable operation of the ATR is critical to the Department of Energy (DOE) Office of Nuclear Energy (NE) mission. While ATR is safely fulfilling current mission requirements, a variety of aging and obsolescence issues challenge ATR engineering and maintenance personnel's capability to sustain ATR over the long term. First documented in a series of independent assessments, beginning with an OA Environmental Safety and Health Assessment conducted in 2003, the issues were validated in a detailed Material Condition Assessment (MCA) conducted as a part of the ATR Life Extension Program in 2007. Accordingly, near term replacement of aging and obsolescent original ATR equipment has become important to ensure ATR capability in support of NE's long term national missions. To that end, a mission needs statement has been prepared for a non-major system acquisition which is comprised of three interdependent sub-projects. The first project will replace the existent diesel-electrical bus (E-3), switchgear, and the fifty year old antiquated marine diesels with commercial power that is backed with safety-related emergency diesel generators (EDGs), switchgear, and uninterruptible power supply. The second project will replace the four, obsolete, original primary coolant pumps and motors. The third project, the subject of this major modification determination, will replace the current emergency firewater injection system (EFIS). The replacement water injection system will function as the primary emergency water injection system with the EFIS being retained as a defense-in-depth backup. Completion of this and the two other age-related projects (replacement of the ATR diesel bus (E-3) and switchgear and replacement of the existent aged primary coolant pumps and motors) will resolve major age-related operational issues plus make a significant contribution in sustaining the ATR safety and reliability profile. The major modification criteria evaluation of the

The development of the conditionally replication-competent adenovirus: replacement of E4 orf1-4 region by exogenous gene.

Science.gov (United States)

Nam, Jae-Kook; Lee, Mi-Hyang; Seo, Hae-Hyun; Kim, Seok-Ki; Lee, Kang-Huyn; Kim, In-Hoo; Lee, Sang-Jin

2010-05-01

Tumor or tissue specific replicative adenovirus armed with a therapeutic gene has shown a promising anti-cancer therapeutic modality. However, because the genomic packaging capacity is constrained, only a few places inside it are available for transgene insertion. In the present study, we introduce a novel strategy utilizing the early E4 region for the insertion of therapeutic gene(s). We constructed the conditionally replication-competent adenovirus (CRAd), Ad5E4(mRFP) by: (i) replacing the E4/E1a promoter by the prostate-specific enhancer element; (ii) inserting mRFP inside the E4orf1-4 deletion region; and (iii) sub-cloning enhanced green fluorescent protein controlled by cytomegalovirus promoter in the left end of the viral genome. Subsequently, we evaluated its replication abilities and killing activities in vitro, as well as its in vivo anti-tumor efficacy in CWR22rv xenografts. When infected with Ad5E4(mRFP), the number and intensity of the mRFP gene products increased in a prostate cancer cell-specific manner as designed, suggesting that the mRFP gene and E4orfs other than E4orf1-4 were well synthesized from one transcript via alternative splicing as the recombinant adenovirus replicated. As expected from the confirmed virus replication capability, Ad5E4(mRFP) induced cell lysis as potent as the wild-type adenovirus and effectively suppressed tumor growth when tested in the CWR22rv xenografts in nude mice. Furthermore, Ad5E4(endo/angio) harboring an endostatin-angiostatin gene in E4orf1-4 was able to enhance CRAd by replacing mRFP with a therapeutic gene. The approach employed in the present study for the insertion of a therapeutic transgene in CRAd should facilitate the construction of CRAd containing multiple therapeutic genes in the viral genome that may have the potential to serve as highly potent cancer therapeutic reagents. Copyright (c) 2010 John Wiley & Sons, Ltd.

Adaptive Neuro-fuzzy Inference System as Cache Memory Replacement Policy

Directory of Open Access Journals (Sweden)

CHUNG, Y. M.

2014-02-01

Full Text Available To date, no cache memory replacement policy that can perform efficiently for all types of workloads is yet available. Replacement policies used in level 1 cache memory may not be suitable in level 2. In this study, we focused on developing an adaptive neuro-fuzzy inference system (ANFIS as a replacement policy for improving level 2 cache performance in terms of miss ratio. The recency and frequency of referenced blocks were used as input data for ANFIS to make decisions on replacement. MATLAB was employed as a training tool to obtain the trained ANFIS model. The trained ANFIS model was implemented on SimpleScalar. Simulations on SimpleScalar showed that the miss ratio improved by as high as 99.95419% and 99.95419% for instruction level 2 cache, and up to 98.04699% and 98.03467% for data level 2 cache compared with least recently used and least frequently used, respectively.

Light and heavy water replacing system in reactor container

International Nuclear Information System (INIS)

Miyamoto, Keiji.

1979-01-01

Purpose: To enable to determine the strength of a reactor container while neglecting the outer atmospheric pressure upon evacuation, by evacuating the gap between the reactor container and a biological thermal shield, as well as the container simultaneously upon light water - heavy water replacement. Method: Upon replacing light water with heavy water by vacuum evaporation system in a nuclear reactor having a biological thermal shield surrounding the reactor container incorporating therein a reactor core by way of a heat expansion absorbing gap, the reactor container and the havy water recycling system, as well as the inside of heat expansion absorbing gap are evacuated simultaneously. This enables to neglect the outer atmospheric outer pressure upon evacuation in the determination of the container strength, and the thickness of the container can be decreased by so much as the external pressure neglected. (Moriyama, K.)

Readiness of the Defense Message System to Replace the Automatic Digital Network

National Research Council Canada - National Science Library

1998-01-01

.... The Defense Information Systems Agency began developing the Defense Message System (DMS) in 1988 to replace messaging functions provided by AUTODIN and electronic mail systems. Audit Objectives...

REPLACEMENT SPARE PART INVENTORY MONITORING USING ADAPTIVE NEURO FUZZY INFERENCE SYSTEM

Directory of Open Access Journals (Sweden)

Hartono Hartono

2016-01-01

Full Text Available Abstract   The amount of inventory is determined on the basis of the demand. So that users can know the demand forecasts need to be done on the request. This study uses the data to implement a replacement parts on the electronic module production equipment in the telecommunications transmission systems, switching, access and power, ie by replacing the electronic module in the system is trouble  or damaged parts of a good electronic module spare parts inventory, while the faulty electronic modules shipped to the Repair Center for repaired again, so that the results of these improvements can replenish spare part  inventory. Parameters speed on improvement process of electronic module broken (repaired, in the form of an average repair time at the repair centers, in order to get back into the electronic module that is ready for used as spare parts in compliance with the safe supply inventory  warehouse.  This research using the method  of  Adaptive Neuro Fuzzy Inference System (ANFIS in developing a decision support system for inventory control of spare parts available in Warehouse Inventory taking into account several parameters supporters, namely demand, improvement and fulfillment of spare parts and repair time. This study uses a recycling input parameter repair faulty electronic module of the customer to immediately replace the module in inventory warehouse,  do improvements in the Repair Center. So the acceleration restoration factor is very influential as the input spare parts inventory supply in the warehouse and using the Adaptive Neuro-Fuzzy Inference System (ANFIS method.   Keywords: ANFIS, inventory control, replacement

Technology management: a perspective on system support, procurement, and replacement planning.

Science.gov (United States)

Dickerson, M L; Jackson, M E

1992-01-01

The escalating costs associated with medical technology present a host of challenges for the hospital clinical engineering department. As service and support costs comprise ever larger portions of a system's life cycle cost, innovative management of service provider mix and mechanisms can provide substantial savings in operating expenses. In addition to full-service contracts, the use of demand service and independents has become commonplace. Medical equipment maintenance insurance programs provide yet another service alternative, combining the flexibility of demand service with the safety of a capped budget. These programs have gained acceptance among hospitals as their providers have become more focused on the healthcare market and its many needs. In view of the long-term cost impact surrounding technology procurement, the authors recommend that hospitals refine system evaluation methodologies and develop more comprehensive techniques directed at capital equipment replacement planning. One replacement planning approach, based on an estimation of system value changes, is described and illustrated using data collected through client consultations. Although the validity of this method has not been demonstrated, it represents a simplified approach to life cycle cost analysis and is intended to provide a standard method by which system replacement planning may be quantified. As a departure from system devaluation based solely on depreciation, this method estimates prospective system values derived from anticipated operations and maintenance costs, projected revenue, and the availability of new technology.

Androgen receptor gene CAG repeat polymorphism independently influences recovery of male sexual function after testosterone replacement therapy in postsurgical hypogonadotropic hypogonadism.

Science.gov (United States)

Tirabassi, Giacomo; Delli Muti, Nicola; Corona, Giovanni; Maggi, Mario; Balercia, Giancarlo

2014-05-01

Few and contradictory studies have evaluated the possible influence of androgen receptor (AR) gene CAG repeat polymorphism on male sexual function. In this study we evaluated the role of AR gene CAG repeat polymorphism in the recovery of sexual function after testosterone replacement therapy (TRT) in men affected by postsurgical hypogonadotropic hypogonadism, a condition which is often associated with hypopituitarism and in which the sexual benefits of TRT must be distinguished from those of pituitary-function replacement therapies. Fifteen men affected by postsurgical hypogonadotropic hypogonadism were retrospectively assessed before and after TRT. Main outcome measures included sexual parameters as assessed by the International Index of Erectile Function questionnaire, levels of pituitary dependent hormones (total testosterone, free T3, free T4, cortisol, insulin-like growth factor-1 [IGF-1], prolactin), and results of genetic analysis (AR gene CAG repeat number). Plasma concentrations of free T3, free T4, cortisol, and prolactin did not vary significantly between the two phases, while testosterone and IGF-1 increased significantly after TRT. A significant improvement in all sexual parameters studied was found. The number of CAG triplets was negatively and significantly correlated with changes in all the sexual parameters, while opposite correlations were found between changes in sexual parameters and changes in testosterone levels; no correlation of change in IGF1 with change in sexual parameters was reported. On multiple linear regression analysis, after correction for changes in testosterone, nearly all the associations between the number of CAG triplets and changes in sexual parameters were confirmed. Shorter length AR gene CAG repeat number is associated with the recovery of sexual function after TRT in postsurgical male hypogonadotropic hypogonadism, independently of the effects of concomitant pituitary-replacement therapies. © 2014 International Society

Replacement inhibitors for tank farm cooling coil systems

International Nuclear Information System (INIS)

Hsu, T.C.

1995-01-01

Sodium chromate has been an effective corrosion inhibitor for the cooling coil systems in Savannah River Site (SRS) waste tanks for over 40 years. Due to their age and operating history, cooling coils occasionally fail allowing chromate water to leak into the environment. When the leaks spill 10 lbs. or more of sodium chromate over a 24-hr period, the leak incidents are classified as Unusual Occurrences (UO) per CERCLA (Comprehensive Environmental Response, Compensation and Liability Act). The cost of reporting and cleaning up chromate spills prompted High Level Waste Engineering (HLWE) to initiate a study to investigate alternative tank cooling water inhibitor systems and the associated cost of replacement. Several inhibitor systems were investigated as potential alternatives to sodium chromate. All would have a lesser regulatory impact, if a spill occurred. However, the conversion cost is estimated to be $8.5 million over a period of 8 to 12 months to convert all 5 cooling systems. Although each of the alternative inhibitors examined is effective in preventing corrosion, there is no inhibitor identified that is as effective as chromate. Assuming 3 major leaks a year (the average over the past several years), the cost of maintaining the existing inhibitor was estimated at $0.5 million per year. Since there is no economic or regulatory incentive to replace the sodium chromate with an alternate inhibitor, HLWE recommends that sodium chromate continue to be used as the inhibitor for the waste tank cooling systems

Air Traffic Control: Status of FAA's Implementation of the Display System Replacement Project

National Research Council Canada - National Science Library

1999-01-01

...) implementation of the Display System Replacement (DSR) project. DSR, which replaces the controllers' workstations and other equipment in the nation's en route centers, is one of FAA's major projects under the air traffic control modernization program...

Replacement of the instrumentation and control system of Tore Supra; Remplacement du systeme de controle commande de Tore Supra

Energy Technology Data Exchange (ETDEWEB)

Leveque, P

1995-02-01

The control system of the Tore-Supra is a wide and complex system that cannot be interrupted while running without significant consequences on the operating of the machine. Replacing the current system cannot be achieved in a global way without immobilisation and high costs. Therefore partial changes have been decided on. This work presents the detailed analysis of the arrangements and the operating of the system that will be replaced: the pro`s and con`s that have appeared through experience are related. The possibilities that the new apparatus offers are also examined. A method of step by step replacements had to be set up in order to assess the means, funds, term of achievement, performance and quality of the overall project. (TEC). 15 refs., 29 figs.

Assessment of Consequences of Replacement of System of the Uniform Tax on Imputed Income Patent System of the Taxation

Directory of Open Access Journals (Sweden)

Galina A. Manokhina

2012-11-01

Full Text Available The article highlights the main questions concerning possible consequences of replacement of nowadays operating system in the form of a single tax in reference to imputed income with patent system of the taxation. The main advantages and drawbacks of new system of the taxation are shown, including the opinion that not the replacement of one special mode of the taxation with another is more effective, but the introduction of patent a taxation system as an auxilary system.

Gene replacement therapy for genetic hepatocellular jaundice.

Science.gov (United States)

van Dijk, Remco; Beuers, Ulrich; Bosma, Piter J

2015-06-01

Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (re)uptake is impaired due to the deficiency of two basolateral/sinusoidal hepatocellular membrane proteins, organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3. Dubin-Johnson syndrome is caused by a defect in the ATP-dependent canalicular transporter, multidrug resistance-associated protein 2 (MRP2), which mediates the export of conjugated bilirubin into bile. Both disorders are benign and not progressive and are characterised by elevated serum levels of mainly conjugated bilirubin. Uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) is responsible for the glucuronidation of bilirubin; deficiency of this enzyme results in unconjugated hyperbilirubinaemia. Gilbert syndrome is the mild and benign form of inherited unconjugated hyperbilirubinaemia and is mostly caused by reduced promoter activity of the UGT1A1 gene. Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated. Due to major disadvantages of the current standard treatments for Crigler-Najjar syndrome, phototherapy and liver transplantation, new effective therapeutic strategies are under development. Here, we review the clinical features, pathophysiology and genetic background of these inherited disorders of bilirubin metabolism and transport. We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy.

A shock and wear system under environmental conditions subject to internal failures, repair, and replacement

International Nuclear Information System (INIS)

Montoro-Cazorla, Delia; Pérez-Ocón, Rafael

2012-01-01

A system in a random environment is considered. The influence of the external conditions is governed by a Markovian arrival process. The internal structure of failure and repair are governed by phase-type distributions. The maintenance is performed by policy N. Under these assumptions, the Markov process governing the system is constructed, and it is studied in transient and stationary regime, calculating the availability and the rate of occurrence of failures. The renewal process due to the replacements of the system is studied, and expressions for the number of replacements and for the number of repairs between replacements are calculated. This paper extends other previously published since it incorporates a shock arrival process with dependence among the interarrival times and the renewal process associated to the replacements. A numerical application illustrates the calculations.

HVAC System Replacements for the Spanish Nuclear Fleet

Energy Technology Data Exchange (ETDEWEB)

Izquierdo, J.; Gensollen, T.; Pérez, C.

2015-07-01

The European Union and its Member States have established regulations to phase out ozone-depleting chlorofluorocarbons (CFCs). The chiller systems installed at the Spanish nuclear fleet contained zone depleting refrigerants (such as R-11, R-12, and R-22), which are being phased out of service. Due to the different material and thermodynamic properties of the replacement refrigerant (e.g. R-134A), a complete chiller system replacement is needed to comply with the EU regulations for CFCs. Delivering state of the art HVAC and Chiller systems that comply with the Nuclear Plant design basis, licensing basis, system and component specifications as well as European Union (EU) and Spanish codes and standards can be challenging for products purchased from US based manufacturers. Procurement specifications and Request for Quotes (RFQs) issued today for the procurement of original Plant components and systems will contain references to numerous codes and standards that were not in effect at the time the original components were specified and procured. The reference to EU and Spanish codes and standards that are unfamiliar to the HVAC suppliers can lead to uncertainty and concern related to specification compliance. The unnecessary burden of ambiguous codes and standards complicates the proposal process and introduces pricing uncertainty and contract risk. A review of the EU and Spanish national codes and standards that are often referenced in HVAC system related RFQs need to be performed to determine what codes and standards are applicable to HVAC systems designed, manufactured and tested in the US for export to Spain for installation in Spanish NPPs. Lessons learned and best practices should be applied to help both the Supplier (HVAC OEM) and the Purchaser Plant Operator) to optimize the procurement process and improve the quality of offerings to comply with applicable codes and standards. (Author)

Synthetic sustained gene delivery systems.

Science.gov (United States)

Agarwal, Ankit; Mallapragada, Surya K

2008-01-01

Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

Replacement cross-site transfer system project W-058 safety class upgrade summary report

International Nuclear Information System (INIS)

Schlosser, R.L.

1998-01-01

This report evaluates the design of the replacement cross-site transfer system structures, systems, and components for safety related applications as defined in the Tank Waste Remediation Systems Basis for Interim Operations

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

Science.gov (United States)

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.

Gene Therapy

Science.gov (United States)

Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

An optimal replacement policy for a repairable system based on its repairman having vacations

Energy Technology Data Exchange (ETDEWEB)

Yuan Li [School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai 200092 (China); Xu Jian, E-mail: xujian@tongji.edu.c [School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai 200092 (China)

2011-07-15

This paper studies a cold standby repairable system with two different components and one repairman who can take multiple vacations. If there is a component which fails and the repairman is on vacation, the failed component will wait for repair until the repairman is available. In the system, assume that component 1 has priority in use. After repair, component 1 follows a geometric process repair, while component 2 can be repaired as good as new after failures. Under these assumptions, a replacement policy N based on the failed times of component 1 is studied. The system will be replaced if the failure times of component 1 reach N. The explicit expression of the expected cost rate is given, so that the optimal replacement time N{sup *} is determined. Finally, a numerical example is given to illustrate the theoretical results of the model.

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

Science.gov (United States)

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

Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.

Science.gov (United States)

Su, Mei-Tsz; Lin, Sheng-Hsiang; Chen, Yi-Chi; Kuo, Pao-Lin

2014-06-01

Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. A total of 98 women with history of idiopathic RPL and 142 controls were included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1 and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. Ingenuity pathways analysis (IPA) was introduced to explore possible complex interactions. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that the KDR (Q472H) polymorphism was the best loci to be associated with RPL (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.

An inducible CRISPR-ON system for controllable gene activation in human pluripotent stem cells.

Science.gov (United States)

Guo, Jianying; Ma, Dacheng; Huang, Rujin; Ming, Jia; Ye, Min; Kee, Kehkooi; Xie, Zhen; Na, Jie

2017-05-01

Human pluripotent stem cells (hPSCs) are an important system to study early human development, model human diseases, and develop cell replacement therapies. However, genetic manipulation of hPSCs is challenging and a method to simultaneously activate multiple genomic sites in a controllable manner is sorely needed. Here, we constructed a CRISPR-ON system to efficiently upregulate endogenous genes in hPSCs. A doxycycline (Dox) inducible dCas9-VP64-p65-Rta (dCas9-VPR) transcription activator and a reverse Tet transactivator (rtTA) expression cassette were knocked into the two alleles of the AAVS1 locus to generate an iVPR hESC line. We showed that the dCas9-VPR level could be precisely and reversibly controlled by the addition and withdrawal of Dox. Upon transfection of multiplexed gRNA plasmid targeting the NANOG promoter and Dox induction, we were able to control NANOG gene expression from its endogenous locus. Interestingly, an elevated NANOG level promoted naïve pluripotent gene expression, enhanced cell survival and clonogenicity, and enabled hESCs to integrate with the inner cell mass (ICM) of mouse blastocysts in vitro. Thus, iVPR cells provide a convenient platform for gene function studies as well as high-throughput screens in hPSCs.

Apoptosis Gene Information System--AGIS.

Science.gov (United States)

Sakharkar, Kishore R; Clement, Marie V; Chow, Vincent T K; Pervaiz, Shazib

2006-05-01

Genes implicated in apoptosis have great relevance to biology, medicine and oncology. Here, we describe a unique resource, Apoptosis Gene Information System (AGIS) that provides data for over 2400 genes involved directly or indirectly, in apoptotic pathways of more than 350 different organisms. The organization of this information system is based on the principle of one-gene, one record. AGIS will be updated on a six monthly basis as new information becomes available. AGIS can be accessed at: http://www.cellfate.org/AGIS/.

Temelin NPP - IandC replacement

International Nuclear Information System (INIS)

Spalenka, I.

1997-01-01

The original instrumentation and control system of the Temelin nuclear power plant is being upgraded and replaced by a modern Westinghouse-supplied system which meets the requirements imposed on current nuclear power plant designs. The history and purpose of the IandC system replacement is given, and the design of the new system is described in some detail. (A.K.)

Global and Local Page Replacement Algorithms on Virtual Memory Systems for Image Processing

OpenAIRE

WADA, Ben Tsutom

1985-01-01

Three virtual memory systems for image processing, different one another in frame allocation algorithms and page replacement algorithms, were examined experimentally upon their page-fault characteristics. The hypothesis, that global page replacement algorithms are susceptible to thrashing, held in the raster scan experiment, while it did not in another non raster-scan experiment. The results of the experiments may be useful also in making parallel image processors more efficient, while they a...

Challenge of Replacing Obsolete Equipment and Systems on Brownfield Sites

International Nuclear Information System (INIS)

Teasdale, St.

2009-01-01

The Nuclear Decommissioning Authority (NDA) is responsible for the decommissioning and clean-up of the UK's civil public sector nuclear sites. One of their top priorities is the retrieval of sludge and fuel from the First Generation Magnox Fuel Storage Pond (FGMSP) at Sellafield site which is one of the most complex and compact nuclear sites in the world. The FGMSP plant is currently undergoing a series of major modifications in preparation for the retrievals operations. One of the most challenging modifications undertaken in the facility has been the Control and Surveillance Project which covered replacement of the existing Environmental Monitoring System, this presented the complex challenge of replacing an existing system whilst maintaining full functionality on a live radiological safety system with a constant radiological hazard. The Control and Surveillance Project involved the design, procurement, installation, changeover and commissioning of a new Radiological Surveillance System (alpha, beta and gamma monitoring) along with Building Evacuation Systems within the FGMSP complex to replace the existing obsolete system. This Project was a key enabler to future FGMSP retrievals and decommissioning activities. The project objective was to create and maintain a safe radiological working environment for over 450 personnel working in the plant up to 2020. The Legacy Ponds at Sellafield represent one of the biggest challenges in the civil nuclear clean up portfolio in the UK. Retrieval of sludge and fuel from the First Generation Magnox Fuel Storage Pond (FGMSP), and its safe long term storage is one of the NDA's top priorities. In June 2002 Sellafield Ltd contracted with the ACKtiv Nuclear Joint Venture to progress the risk mitigation, asset restoration and the early enabling works associated with preparation for clean up. Since then significant progress has been made in preparing the facility, and it's support systems, for the clean-up operations. This has been

The Analysis of Height System Definition and the High Precision GNSS Replacing Leveling Method

Directory of Open Access Journals (Sweden)

ZHANG Chuanyin

2017-08-01

Full Text Available Based on the definition of height system, the gravitational equipotential property of height datum surface is discussed in this paper, differences of the heights at ground points that defined in different height systems are tested and analyzed as well. A new method for replacing leveling using GNSS is proposed to ensure the consistency between GNSS replacing leveling and spirit leveling at mm accuracy level. The main conclusions include:①For determining normal height at centimeter accuracy level, the datum surface of normal height should be the geoid. The 1985 national height datum of China adopts normal height system, its datum surface is the geoid passing the Qingdao zero point.②The surface of equi-orthometric height in the near earth space is parallel to the geoid. The combination of GNSS precise positioning and geoid model can be directly used for orthometric height determination. However, the normal height system is more advantageous for describing the terrain and relief.③Based on the proposed method of GNSS replacing leveling, the errors in geodetic height affect more on normal height result than the errors of geoid model, the former is about 1.5 times of the latter.

Design and adjustment on test bed of replacing subassembly machine control system for China experimental fast reactor

International Nuclear Information System (INIS)

Dong Shengguo; Ma Hongsheng; Zhao Lixia

2008-01-01

The present research concerns in the design and adjustment of replacing sub- assembly machine control system of China Experimental Fast Reactor. The design of replacing subassembly machine control system adopts some electric equipments, such as programmable controllers, digital DC drivers. The designed control system was adjusted on the test bed. The results indicate that the operation of the control system is steady and reliable, and designed control system can meet the needs of the design specification. (authors)

The impact of steam generator replacement on PWR primary system contamination

International Nuclear Information System (INIS)

Dacquait, F.; Marteau, H.; Guinard, L.; Ranchoux, G.; Taunier, S.; Wintergerst, M.; Bretelle, J.L.; Rocher, A.

2010-01-01

This paper analyses the impact of Steam Generator Replacement (SGR) on PWR primary circuit contamination. It presents a comparison of the activities deposited inside the primary system and released during refuelling outages after SGR with three different SG tube alloys (600, 690 and 800) and different SG tube manufacturing processes. A SGR has a great impact on the primary system contamination. After SGR, whatever the SG tube material is, the typical variations are the following: The 58 Co contamination increases for 1 to 3 cycles, and then decreases to very low levels in some cases, mainly depending on the manufacturing process of the replacement SG tubes; The 60 Co Co contamination tends to decrease on the primary coolant pipes and increases by a lower rate on the new SG tubes. This analysis highlights the importance on contamination levels after SGR of both the corrosion product deposits on the primary surfaces before SGR and the surface finish of the SG tubes related to their manufacturing process. (author)

Turbine Control System Replacement at NPP NEK; System Specifics, Project Experience and Lessons Learned

International Nuclear Information System (INIS)

Mandic, D.; Zilavy, M. J.

2010-01-01

The main intention of this paper is to present feedback from the implementation of the new Turbine Control System (TCS) replacement project at Nuclear Power Plant (NPP) NEK - Krsko. From the plant construction time and the first plant start-up in 1981, the NPP NEK TG (Turbine-Generator) set was controlled and monitored by DEH (Digital Electro Hydraulic) Mod II Control System designed in 70's based on P2500 CPU and number of I/O controllers and modules. The P2500 CPU and associated controllers were built with discrete TTL components (TTL logic chips) and the P2500 CPU had 64k of 16 bit words of ferrite core memory. For that time, DEH Mod II had sophisticated MCR (Main Control Room) HMI (Human Machine Interface) based on digital functional keyboards, one alphanumeric black and white CRT monitor and printer. After twenty eight years of operation and because of several other reasons that are explained in the paper, NEK decided to replace the old DEH Mod II Control system with the new Emerson Ovation based DCS (Distributed Control System) on redundant platform for the control and monitoring of secondary plant systems in the NPP Krsko (NEK), and the new system was named PDEH (Programmable Digital Electro Hydraulic) TCS. In May 2007, NEK signed the turn-key contract with Westinghouse Electric Company (WEC) for the project of replacement of the TCS, Turbine Emergency Trip System (ETS), Moisture Separator Reheater (MSR) control and some other control and monitoring functions. WEC subcontracted a number of other companies for equipment delivery, AE (Architect Engineering Design) activities, specific software development tasks (changes of KFSS - Krsko Full Scope Simulator and PIS - Process Information System interface) and field installation activities. The subject project enveloped implementation of PDEH system on three application platforms: BG KFSS (Background KFSS), FG KFSS (Foreground KFSS) and PDEH system installed in the plant. The HMI for the BG KFSS platform

A trivariate optimal replacement policy for a deteriorating system based on cumulative damage and inspections

International Nuclear Information System (INIS)

Tsai, Hsin-Nan; Sheu, Shey-Huei; Zhang, Zhe George

2017-01-01

In this article, we study a trivariate replacement model for a deteriorating system consisting of two units. Failures of unit 1 can be classified into two types. Type I failure (minor failure) is fixed by a minimal repair and type II failure (catastrophic failure) is removed by a replacement. Both types of failures can only be detected through inspection. Each type I failure of unit 1 will result in a random amount of damage to unit 2 and the damages are cumulative. The probability of type I failure or type II failure is assumed to depend on the number of failures since the last replacement. We formulate a replacement policy based on the number of type I failure, the occurrence of the first type II failure, and the amount of accumulative damages. Hence the system is replaced either preventively or correctively at any of the following four conditions depend on whichever occurs first; preventively (a) at the Nth type I failure; or (b) when the total damage of unit 2 exceeds a pre-specified level Z (but less than the failure level l); and, correctively (c) at the first type II failure; or (d) when the total damage of unit 2 exceeds a failure level l, where Z and l represent the thresholds of total damage level for unit 2 to preventive and corrective replacements, respectively. Although a type I failure can be fixed by a minimal repair, but the operating period is stochastically decreasing and repair time is stochastically increasing as time goes on. The minimal total expected long-run net cost per unit time of the system is derived and a computational algorithm for determining the optimal policy is developed. A real-world application from electric power industry is provided. Several past studied are shown to be special cases of our model. Finally, a numerical example is presented. - Highlights: • A trivariate replacement policy for a deteriorating system with two units is proposed. • A real-world application from the electric power industry is provided. • The

Food-grade host/vector expression system for Lactobacillus casei based on complementation of plasmid-associated phospho-beta-galactosidase gene lacG.

Science.gov (United States)

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.

Functions and Requirements and Specifications for Replacement of the Computer Automated Surveillance System (CASS)

International Nuclear Information System (INIS)

SCAIEF, C.C.

1999-01-01

This functions, requirements and specifications document defines the baseline requirements and criteria for the design, purchase, fabrication, construction, installation, and operation of the system to replace the Computer Automated Surveillance System (CASS) alarm monitoring

Full Scale 3D Preoperative Planning System of the Ankle Joint Replacement Surgery with Multimedia System

Directory of Open Access Journals (Sweden)

Shuh-Ping Sun

2014-05-01

Full Text Available This study is intended to develop a computer-aided pre-surgical planning and simulating system in a multimedia environment for ankle joint replacement surgery. This system uses full-scale 3D reverse engineering techniques in design and development of the pre-surgical planning modules for ankle joint replacement surgery. This planning system not only develops the real-scale 3D image of the artificial ankle joint but also provides a detailed interior measurement of the ankle joint from various cutting planes. In this study, we apply the multimedia user interface to integrate different software functions into a surgical planning system with integrated functions. The functions include 3D model image acquisition, cutting, horizontal shifting and rotation of related bones (tibia and talus of the ankle joint in the predetermined time. For related bones of the ankle joint, it can also be used to design artificial ankle joints for adults in Taiwan. Those planning procedures can be recorded in this system for further research and investigation. Furthermore, since this system is a multimedia user interface, surgeons can use this system to plan and find a better and more efficient surgical approach before surgery. A database is available for this system to update and expand, which can provide different users with clinical cases as per their experience and learning.

Carbohydrates as Fat Replacers.

Science.gov (United States)

Peng, Xingyun; Yao, Yuan

2017-02-28

The overconsumption of dietary fat contributes to various chronic diseases, which encourages attempts to develop and consume low-fat foods. Simple fat reduction causes quality losses that impede the acceptance of foods. Fat replacers are utilized to minimize the quality deterioration after fat reduction or removal to achieve low-calorie, low-fat claims. In this review, the forms of fats and their functions in contributing to food textural and sensory qualities are discussed in various food systems. The connections between fat reduction and quality loss are described in order to clarify the rationales of fat replacement. Carbohydrate fat replacers usually have low calorie density and provide gelling, thickening, stabilizing, and other texture-modifying properties. In this review, carbohydrates, including starches, maltodextrins, polydextrose, gums, and fibers, are discussed with regard to their interactions with other components in foods as well as their performances as fat replacers in various systems.

Replacement of fine particle purification filter of the PHT purification system - 15083

International Nuclear Information System (INIS)

Lee, D.S.

2015-01-01

The increase of chalk river unidentified deposit (CRUD), a particulate corrosion product in PHT (primary heat transport) system with increased operating years of a nuclear power plant causes: -) the problems of increased heavy water decomposition and deuterium formation reaction due to catalytic reaction with CRUD, -) damage to PHT pump seal due to a corrosion product, -) damage to fuel channel closure seal, and increased radiation exposure of workers due to elevated dose rate in steam generator water chamber. Wolsung unit 3 and 4 have replaced fine filter media in PHT purification system in phases reducing the pore size of the filter media (5 μm → 2 μm → 1 μm → 0.45 μm) to solve this problem. The phased replacement of fine filter media by the one with a smaller pore size reduced CRUD in PHT system significantly and also radiation dose rate in steam generator water chamber. Accordingly, many problems related to the aging of a plant (including increased radiation exposure of workers during outage, damage to mechanical seal of PHT pump) have been solved. (author)

Application of deterministic and probabilistic methods in replacement of nuclear systems

International Nuclear Information System (INIS)

Vianna Filho, Alfredo Marques

2007-01-01

The economic equipment replacement problem is one of the oldest questions in Production Engineering. On the one hand, new equipment are more attractive given their best performance, better reliability, lower maintenance cost, etc. New equipment, however, require a higher initial investment and thus a higher opportunity cost, and impose special training of the labor force. On the other hand, old equipment represent the other way around, with lower performance, lower reliability and specially higher maintenance costs but in contrast having lower financial, insurance, and opportunity costs. The weighting of all these costs can be made with the various methods presented. The aim of this paper is to discuss deterministic and probabilistic methods applied to the study of equipment replacement. Two types of distinct problems will be examined, substitution imposed by the wearing and substitution imposed by the failures. In order to solve the problem of nuclear system substitution imposed by wearing, deterministic methods are discussed. In order to solve the problem of nuclear system substitution imposed by failures, probabilistic methods are discussed. (author)

A delay time model for a mission-based system subject to periodic and random inspection and postponed replacement

International Nuclear Information System (INIS)

Yang, Li; Ma, Xiaobing; Zhai, Qingqing; Zhao, Yu

2016-01-01

We propose an inspection and replacement policy for a single component system that successively executes missions with random durations. The failure process of the system can be divided into two states, namely, normal and defective, following the delay time concept. Inspections are carried out periodically and immediately after the completion of each mission (random inspections). The failed state is always identified immediately, whereas the defective state can only be revealed by an inspection. If the system fails or is defective at a periodic inspection, then replacement is immediate. If, however, the system is defective at a random inspection, then replacement will be postponed if the time to the subsequent periodic inspection is shorter than a pre-determined threshold, and immediate otherwise. We derive the long run expected cost per unit time and then investigate the optimal periodic inspection interval and postponement threshold. A numerical example is presented to demonstrate the applicability of the proposed maintenance policy. - Highlights: • A delay time model of inspection is introduced for mission-based systems. • Periodic and random inspections are performed to check the state. • Replacement of the defective system at a random inspection can be postponed.

The planned replacement of a functioning control system on the CERN 28 GEV accelerator

International Nuclear Information System (INIS)

Carpenter, B.E.; Daneels, A.; Perriollat, F.

1979-01-01

The subject is discussed under the following headings: the accelerators (in the 28 GeV accelerator complex) and the old control system; goals of the new control system; constraints (involved in planning a replacement for the control system); a pilot project; major software issues in the system design; portability; parallelism; transition; conclusion. (U.K.)

Replacement of heavy components of the Main Primary System (MPS). Recent innovations made by Framatome ANP

International Nuclear Information System (INIS)

Chanussot, J.M.; Thevenet, R.

2006-01-01

The replacement of heavy components is the result of widespread stress corrosion of Inconel 600 (and alloys 82/182) in the primary system. Following the corrosion of steam generator tubes, which led to the first steam generator replacement (SGR) operations, work has begun on reactor vessel head replacements (RVHR) and pressurizer replacements, pending treatment of the dissimilar butt welds (DBW). The replacement of sections of the Main Primary System is one way of optimizing plant lifetime besides preventing stress corrosion in primary components and combating phenomena as thermal fatigue or certain metallurgical weaknesses. The increase in the number of major operations carried out in the reactor building on PWR and BWR reactor geometries has called for major technical innovations. AREVA, has over the past twenty years carried out more than forty SGRs throughout the world, including the supply of 115 steam generators of all types. This equates to over 60% of all SGR operations performed in Europe and the USA. Today, most SGR operations are performed in the USA, though some still continue in Europe and Asia. Operations have been planned until 2015. The first RVHR operations were carried out in France in 1993, and have been widespread in Europe since 1996 (Spain and Belgium), and in the USA since 2002 (Davis Besse). Since 1993 AREVA, through its subsidiaries Framatome ANP, Jeumont SA and SGT, has performed 72 RVHRs, i.e. most of those carried out in Europe and the USA. Today, RVHR operations take place throughout the world and have been planned until 2014. The first pressurizer replacement took place in the fall of 2005 in Saint Lucie, USA. Others are to follow (Fort Calhoun, Millestone). A significant number of partial or complete pressurizer replacements are now being scheduled. Special focus must be given to this new operation, as a decision is required between the following types of replacements, taking into account the number of pressurizer heaters and the

Gene therapy: An overview

Directory of Open Access Journals (Sweden)

Sudip Indu

2013-01-01

Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli

Directory of Open Access Journals (Sweden)

Emily J. Parker

2013-08-01

Full Text Available The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse. This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis.

Why Replacing Legacy Systems Is So Hard in Global Software Development: An Information Infrastructure Perspective

DEFF Research Database (Denmark)

Matthiesen, Stina; Bjørn, Pernille

2015-01-01

We report on an ethnographic study of an outsourcing global software development (GSD) setup between a Danish IT company and an Indian IT vendor developing a system to replace a legacy system for social services administration in Denmark. Physical distance and GSD collaboration issues tend...... to be obvious explanations for why GSD tasks fail to reach completion; however, we account for the difficulties within the technical nature of software system task. We use the framework of information infrastructure to show how replacing a legacy system in governmental information infrastructures includes...... the work of tracing back to knowledge concerning law, technical specifications, as well as how information infrastructures have dynamically evolved over time. Not easily carried out in a GSD setup is the work around technical tasks that requires careful examination of mundane technical aspects, standards...

The replacement gag vibration monitoring system for Hinkley Point 'B' power station

International Nuclear Information System (INIS)

Bagwell, T.; Morrish, M.F.G.

1985-01-01

The original computerised system for monitoring the vibration of gags in each reactor channel of the Hinkley Point 'B' AGR Power Station did not meet the specification for a more stringent safety requirement. This paper describes the replacement of that original single processor system with an enhanced dual processor/multiple scanner computer system used to satisfy this new safety and reliability need. The specification and installation of the new hardware and software are discussed, and some of the problems encountered and their solutions are highlighted. (author)

Effects of partial replacement of fish meal by yeast hydrolysate on complement system and stress resistance in juvenile Jian carp (Cyprinus carpio var. Jian).

Science.gov (United States)

Yuan, Xiang-Yang; Liu, Wen-Bin; Liang, Chao; Sun, Cun-Xin; Xue, Yun-Fei; Wan, Zu-De; Jiang, Guang-Zhen

2017-08-01

A 10-week feeding trial was carried out to investigate the effects of dietary fish meal replacement by yeast hydrolysate (YH) on growth performance, complement system and stress resistance of juvenile Jian carp (Cyprinus carpio var. Jian) (initial average weight 19.44 ± 0.06 g). In the study, there were five groups: one control group was fed with a basal diet (YH0), and four treatment groups were fed with dietary fish meal replaced by 1% YH (YH1), 3% (YH3), 5% (YH5) and 7% (YH7), respectively. Each group had four replicates. At the end of feeding trial, twelve fish from each group (three fish per replicate) were randomly selected for assessing the growth and immunity. Meanwhile, 20 fish per replicate were injected by Aeromonas hydrophila. The results showed that (1) Replacement levels of YH significantly affected the growth of the fish with the highest values of weight gain (WG) occurred in fish fed YH3 diet. However, no significant difference in feed conversion ratios (FCR) was observed among all groups. (2) Pre-stressed plasma lysozyme activity, total protein and albumin contents and complement component 3 (C3) and complement component 4 (C4) levels of fish fed YH3 diet were significantly higher than those of fish fed YH0 diet. However, post-stressed immune parameters of fish in all groups were significantly lower. (3) There was a trend that the expression levels of the complement-related genes (c1r/s-A, c4-1, c3-H1, c5-1, fb/c2-A, mbl-2 and masp) initially increased and then decreased except mbl-2 and masp, with the maximum values observed in fish fed YH3 diet. Before stress, the expression levels of the inflammation-related genes (alp, il-1β and tnf-α) in the hepatopancreas and spleen of fish fed YH1 diet and YH7 diet were significant higher than that of fish fed YH0 diet. After stress, no significant difference in the expression levels of those genes was observed among all groups. These results indicated that FM replacement by YH could improve growth

Specific and Efficient Regression of Cancers Harboring KRAS Mutation by Targeted RNA Replacement.

Science.gov (United States)

Kim, Sung Jin; Kim, Ju Hyun; Yang, Bitna; Jeong, Jin-Sook; Lee, Seong-Wook

2017-02-01

Mutations in the KRAS gene, which persistently activate RAS function, are most frequently found in many types of human cancers. Here, we proposed and verified a new approach against cancers harboring the KRAS mutation with high cancer selectivity and efficient anti-cancer effects based on targeted RNA replacement. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically target and reprogram the mutant KRAS G12V transcript to induce therapeutic gene activity in cells. Adenoviral vectors containing the specific ribozymes with downstream suicide gene were constructed and then infection with the adenoviruses specifically downregulated KRAS G12V expression and killed KRAS G12V-harboring cancer cells additively upon pro-drug treatment, but it did not affect the growth of wild-type KRAS-expressing cells. Minimal liver toxicity was noted when the adenoviruses were administered systemically in vivo. Importantly, intratumoral injection of the adenoviruses with pro-drug treatment specifically and significantly impeded the growth of xenografted tumors harboring KRAS G12V through a trans-splicing reaction with the target RNA. In contrast, xenografted tumors harboring wild-type KRAS were not affected by the adenoviruses. Therefore, RNA replacement with a mutant KRAS-targeting trans-splicing ribozyme is a potentially useful therapeutic strategy to combat tumors harboring KRAS mutation. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Transgenic Arabidopsis Gene Expression System

Science.gov (United States)

Ferl, Robert; Paul, Anna-Lisa

2009-01-01

The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies.

Science.gov (United States)

Nichols, T C; Hough, C; Agersø, H; Ezban, M; Lillicrap, D

2016-05-01

Animal models of inherited bleeding disorders are important for understanding disease pathophysiology and are required for preclinical assessment of safety prior to testing of novel therapeutics in human and veterinary medicine. Experiments in these animals represent important translational research aimed at developing safer and better treatments, such as plasma-derived and recombinant protein replacement therapies, gene therapies and immune tolerance protocols for antidrug inhibitory antibodies. Ideally, testing is done in animals with the analogous human disease to provide essential safety information, estimates of the correct starting dose and dose response (pharmacokinetics) and measures of efficacy (pharmacodynamics) that guide the design of human trials. For nearly seven decades, canine models of hemophilia, von Willebrand disease and other inherited bleeding disorders have not only informed our understanding of the natural history and pathophysiology of these disorders but also guided the development of novel therapeutics for use in humans and dogs. This has been especially important for the development of gene therapy, in which unique toxicities such as insertional mutagenesis, germ line gene transfer and viral toxicities must be assessed. There are several issues regarding comparative medicine in these species that have a bearing on these studies, including immune reactions to xenoproteins, varied metabolism or clearance of wild-type and modified proteins, and unique tissue tropism of viral vectors. This review focuses on the results of studies that have been performed in dogs with inherited bleeding disorders that closely mirror the human condition to develop safe and effective protein and gene-based therapies that benefit both species. © 2016 International Society on Thrombosis and Haemostasis.

Dynamic optimization of maintenance and improvement planning for water main system: Periodic replacement approach

Energy Technology Data Exchange (ETDEWEB)

Kim, Jong Woo; Choi, Go Bong; Lee, Jong Min [Seoul National University, Seoul (Korea, Republic of); Suh, Jung Chul [Samchully Corporation, Seoul (Korea, Republic of)

2016-01-15

This paper proposes a Markov decision process (MDP) based approach to derive an optimal schedule of maintenance, rehabilitation and replacement of the water main system. The scheduling problem utilizes auxiliary information of a pipe such as the current state, cost, and deterioration model. The objective function and detailed algorithm of dynamic programming are modified to solve the periodic replacement problem. The optimal policy evaluated by the proposed algorithm is compared to several existing policies via Monte Carlo simulations. The proposed decision framework provides a systematic way to obtain an optimal policy.

Immune genes undergo more adaptive evolution than non-immune system genes in Daphnia pulex

Directory of Open Access Journals (Sweden)

McTaggart Seanna J

2012-05-01

Full Text Available Abstract Background Understanding which parts of the genome have been most influenced by adaptive evolution remains an unsolved puzzle. Some evidence suggests that selection has the greatest impact on regions of the genome that interact with other evolving genomes, including loci that are involved in host-parasite co-evolutionary processes. In this study, we used a population genetic approach to test this hypothesis by comparing DNA sequences of 30 putative immune system genes in the crustacean Daphnia pulex with 24 non-immune system genes. Results In support of the hypothesis, results from a multilocus extension of the McDonald-Kreitman (MK test indicate that immune system genes as a class have experienced more adaptive evolution than non-immune system genes. However, not all immune system genes show evidence of adaptive evolution. Additionally, we apply single locus MK tests and calculate population genetic parameters at all loci in order to characterize the mode of selection (directional versus balancing in the genes that show the greatest deviation from neutral evolution. Conclusions Our data are consistent with the hypothesis that immune system genes undergo more adaptive evolution than non-immune system genes, possibly as a result of host-parasite arms races. The results of these analyses highlight several candidate loci undergoing adaptive evolution that could be targeted in future studies.

Optimization of station battery replacement

International Nuclear Information System (INIS)

Jancauskas, J.R.; Shook, D.A.

1994-01-01

During a loss of ac power at a nuclear generating station (including diesel generators), batteries provide the source of power which is required to operate safety-related components. Because traditional lead-acid batteries have a qualified life of 20 years, the batteries must be replaced a minimum of once during a station's lifetime, twice if license extension is pursued, and more often depending on actual in-service dates and the results of surveillance tests. Replacement of batteries often occurs prior to 20 years as a result of systems changes caused by factors such as Station Blackout Regulations, control system upgrades, incremental load growth, and changes in the operating times of existing equipment. Many of these replacement decisions are based on the predictive capabilities of manual design basis calculations. The inherent conservatism of manual calculations may result in battery replacements occurring before actually required. Computerized analysis of batteries can aid in optimizing the timing of replacements as well as in interpreting service test data. Computerized analysis also provides large benefits in maintaining the as-configured load profile and corresponding design margins, while also providing the capability of quickly analyze proposed modifications and response to internal and external audits

Replacement of fishmeal for soy protein concentrate in diets for juvenile Litopenaeus vannamei in biofloc-based rearing system

Directory of Open Access Journals (Sweden)

Adolfo Jatobá

Full Text Available ABSTRACT This study aimed to assess the final body weight, weekly weight gain, yield, apparent feed efficiency, protein efficiency ratio, and feed intake of the Pacific white shrimp (Litopenaeus vannamei fed four diets containing different levels of soy protein concentrate (SPC as a replacement for fishmeal, reared in a super-intensive biofloc system. Diets consisted of replacing 209 g kg-1 fishmeal at 0, 33, 66, and 100% SPC. Shrimp were raised in a biofloc system using twelve experimental units stocked with 250 shrimp m-3 under constant aeration (O2>5mg L-1 and temperature (29±0.5 °C. No significant differences among treatments were observed based on water quality parameters. Shrimp fed diets with 0 and 33% substitution exhibited the highest weekly growth (1.88 and 1.79 g per week and final weights (15.2 and 14.7 g compared with shrimp fed the 66 and 100% replacement. A lower feed intake was observed for shrimp fed the 33% SPC diet (3.18 kg per experimental unit compared with 0% replacement (3.62 kg. Shrimp fed the 33% replacement achieved a similar performance and lower feed intake than animals fed diet without replacement.

Sub-Circuit Selection and Replacement Algorithms Modeled as Term Rewriting Systems

Science.gov (United States)

2008-12-16

of Defense, or the United States Government . AFIT/GCO/ENG/09-02 Sub-circuit Selection and Replacement Algorithms Modeled as Term Rewriting Systems... unicorns and random programs”. Communications and Computer Networks, 24–30. 2005. 87 Vita Eric D. Simonaire graduated from Granite Baptist Church School in...Service to attend the Air Force Institute of Technol- ogy in 2007. Upon graduation, he will serve the federal government in an Information Assurance

Evaluation of dietary soybean meal as fish meal replacer for juvenile whiteleg shrimp, Litopenaeus vannamei reared in biofloc system

Directory of Open Access Journals (Sweden)

Hyeonho Yun

2017-01-01

Full Text Available Abstract Different levels of dietary soybean meal (SBM as a fish meal (FM replacer, with and without amino acid supplementation, for whiteleg shrimp, Litopenaeus vannamei reared in the biofloc system was examined in eight weeks of feeding trial. Eight experimental diets consisted of a basal diet with 0% FM replacement by SBM provided in clear sea water without biofloc system (S0SW, four diets replacing FM at 0% (S0, 33% (S33, 67% (S67 and 100% (S100 by SBM, and three diets replacing FM at 33% (S33A, 67% (S67A and 100% (S100A by SBM supplemented with amino acids (methionine and lysine in the seawater biofloc system. Results of water quality analyses showed significantly lower total suspended solids and nitrate for S0SW group than all other treatments. Diets S0 and S33A resulted in higher weight gain and specific growth rate among all groups, with no significant differences with S33 group. In addition, whole-body protein and amino acid compositions of shrimp fed S0SW were lower than most biofloc groups. Haemolymph parameters showed significant differences in total protein, cholesterol and triglyceride between groups S0 and S0SW. Also, superoxide dismutase activity showed a decreasing trend with increasing replacement level. In conclusion, based on these results, SBM could replace up to 33% of FM with or without amino acid supplementation in juvenile whiteleg shrimp diets reared in the biofloc system.

Replacement of the murine leukemia virus (MLV) envelope gene with a truncated HIV envelope gene in MLV generates a virus with impaired replication capacity

International Nuclear Information System (INIS)

Nack, Ursula; Schnierle, Barbara S.

2003-01-01

Murine leukemia virus (MLV) capsid particles can be efficiently pseudotyped with a variant of the HIV-1 envelope protein (Env) containing the surface glycoprotein gp120-SU and a carboxyl-terminally truncated transmembrane (TM) protein, with only seven cytoplasmic amino acids. MLV/HIV pseudotyped vector particles acquire the natural host tropism of HIV-1 and their entry is dependent on the presence of CD4 and an appropriate co-receptor on the surface of the target cell. We describe here the construction of chimeric MLV/HIV proviruses containing the truncated HIV envelope gene. The MLV/HIV provirus was generated by direct replacement of the MLV envelope gene with HIV Env coding sequences either with or without the additional inclusion of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Chimeric MLV/HIV particles could be generated from transfected 293T cells and were able to infect CD4/CXCR4-positive target cells. However, the second round of infection of target cells was severely impaired, despite the fact that the WPRE element enhanced the amount of viral mRNA detected. Viral particles released from infected cells showed reduced HIV Env incorporation, indicating that additional factors required for efficient replication of MLV/HIV pseudotyped viruses are missing

Impact of few failure data on the opportunistic replacement policy for multi-component systems

International Nuclear Information System (INIS)

Laggoune, Radouane; Chateauneuf, Alaa; Aissani, Djamil

2010-01-01

In continuous operating units, the production loss is often very large during the system shut down. Their economic profitability is conditioned by the implementation of suitable maintenance policy that could increase the availability and reduce the operating costs. In this paper, an opportunistic replacement policy is proposed for multi-component series system in the context of data uncertainty, where the expected total cost per unit time is minimized under general lifetime distribution. When the system is down, either correctively or preventively, the opportunity to replace preventively non-failed components is considered. To deal with the problem of the small size of failure data samples, the Bootstrap technique is applied, in order to model the uncertainties in parameter estimates. The Weibull parameters are considered as random variables rather than just deterministic point estimates. A solution procedure based on Monte Carlo simulations with informative search method is proposed and applied to the optimization of preventive maintenance plan for a hydrogen compressor in an oil refinery.

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

Science.gov (United States)

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.

Experiences from the Architectural Migration of a Joint Replacement Surgery Information System

Directory of Open Access Journals (Sweden)

Samuli Niiranen

2008-01-01

Full Text Available The goal of this study is to present the experiences gathered from the migration of an existing and deployed joint replacement surgery information system from a classical 2-tier architecture to a 4-tier architecture. These include discussion on the motivation for the migration and on the technical benefits of the chosen technical migration path and an evaluation of user experiences. The results from the analysis of clinical end-user and administrator experiences show an increase in the perceived performance and maintainability of the system and a high level of acceptance for the new system version.

Replacement of CFCs in thermodynamical systems; Remplacement des CFC dans les systemes thermodynamiques

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-12-31

Some chlorofluorocarbons (CFCs) are well-adapted to coldness production by vapour compression and thus are widely used in the storage of agriculture-food products from the production to the domestic consumer but also in air-conditioning systems and heat pumps. Atmospheric impacts of the use of CFCs (`ozone hole`) led the international community to adopt remedial measures which aim to prohibit the production of CFCs. These constraints led the users of refrigerating fluids to use substitution fluids and to develop new techniques of energy recovery and heat/coldness production. This workshop takes stock of this situation and of the problems encountered by the various actors involved in the replacement of CFCs in thermodynamical systems: evolutions of regulation, point of view of refrigerating fluid producers and of compressors and heat exchangers manufacturers, research studies on substitution fluids, recovery of CFCs and other refrigerating fluids, revival in the use of natural fluids (like ammonia), and use of new thermodynamical systems like compression/absorption (water/ammonia) cycles. (J.S.)

Advances in study of molecular imaging reporte gene systems

International Nuclear Information System (INIS)

Wu Tao; An Rui

2010-01-01

The use of molecular imaging reporter gene systems has allowed gene therapy to move from the laboratory to the clinical application, which provides methodology to monitor the expression of therapeutic gene noninvasively and achieve quantitative outcome in vivo. Recently, the radionuclide reporter gene still is the focus many studies, but MRI and optical reporter gene have gradually played a important part in reporter gene systems. On the basis of combination of multi-subject, for example applied chemistry and molecular biology, more and more new modified reporter genes and molecular probes have spread out. This paper mainly introduces the advantages and disadvantages of reporter gene system and development trends. (authors)

Recent Trends of Polymer Mediated Liposomal Gene Delivery System

Directory of Open Access Journals (Sweden)

Shyamal Kumar Kundu

2014-01-01

Full Text Available Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole.

AUTOMR: An automatic processing program system for the molecular replacement method

International Nuclear Information System (INIS)

Matsuura, Yoshiki

1991-01-01

An automatic processing program system of the molecular replacement method AUTMR is presented. The program solves the initial model of the target crystal structure using a homologous molecule as the search model. It processes the structure-factor calculation of the model molecule, the rotation function, the translation function and the rigid-group refinement successively in one computer job. Test calculations were performed for six protein crystals and the structures were solved in all of these cases. (orig.)

Replacement of the cooling system of the TRIGA Mainz reactor

International Nuclear Information System (INIS)

Menke, H.

1988-01-01

The inspection of the reactor facility resulted in a recommendation to install a new heat exchanger and at the same time to separate the primary cooling circuit and the water purification system. Due to possible the deposition of lime and organic matter on the tubes, the heat transfer rate has decreased. In the meantime a rule has been introduced, according to which the pressure in the secondary cooling circuit must be permanently higher than in the primary cooling circuit which prompted the design of a new cooling system. The detail planning was completed in December 1987. In response to the regulatory requirements a motion for a replacement of the cooling system was submitted to the authorities. The start of the procedure is possible a year after the obtaining of the licenses. In the planning of the changes an upgrading of the steady state power to 300 kW is envisioned

The Pathway From Genes to Gene Therapy in Glaucoma: A Review of Possibilities for Using Genes as Glaucoma Drugs.

Science.gov (United States)

Borrás, Teresa

2017-01-01

Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of re-placing the mutated gene causing the disease to the use of genes to con-trol nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular bi-ology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judg-ing by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration. Copyright© 2017 Asia-Pacific Academy of Ophthalmology.

Regeneration and replacement in the vertebrate inner ear.

Science.gov (United States)

Matsui, Jonathan I; Parker, Mark A; Ryals, Brenda M; Cotanche, Douglas A

2005-10-01

Deafness affects more than 40 million people in the UK and the USA, and many more world-wide. The primary cause of hearing loss is damage to or death of the sensory receptor cells in the inner ear, the hair cells. Birds can readily regenerate their cochlear hair cells but the mammalian cochlea has shown no ability to regenerate after damage. Current research efforts are focusing on gene manipulation, gene therapy and stem cell transplantation for repairing or replacing damaged mammalian cochlear hair cells, which could lead to therapies for treating deafness in humans.

Replacement of the Advanced Test Reactor control room

International Nuclear Information System (INIS)

Durney, J.L.; Klingler, W.B.

1989-01-01

The control room for the Advanced Test Reactor has been replaced to provide modern equipment utilizing current standards and meeting the current human factors requirements. The control room was designed in the early 1960 era and had not been significantly upgraded since the initial installation. The replacement did not change any of the safety circuits or equipment but did result in replacement of some of the recorders that display information from the safety systems. The replacement was completed in concert with the replacement of the control room simulator which provided important feedback on the design. The design successfully incorporates computer-based systems into the display of the plant variables. This improved design provides the operator with more information in a more usable form than was provided by the original design. The replacement was successfully completed within the scheduled time thereby minimizing the down time for the reactor. 1 fig., 1 tab

Replacement of the Advanced Test Reactor control room

International Nuclear Information System (INIS)

Durney, J.L.; Klingler, W.B.

1990-01-01

The control room for the Advanced Test Reactor has been replaced to provide modern equipment utilizing current standards and meeting the current human factors requirements. The control room was designed in the early 1960 era and had not been significantly upgraded since the initial installation. The replacement did not change any of the safety circuits or equipment but did result in replacement of some of the recorders that display information from the safety systems. The replacement was completed in concert with the replacement of the control room simulator which provided important feedback on the design. The design successfully incorporates computer-based systems into the display of the plant variables. This improved design provides the operator with more information in a more usable form than was provided by the original design. The replacement was successfully completed within the scheduled time thereby minimizing the down time for the reactor

Effect of estrogen receptor-alpha (ESR1 gene polymorphism on high density lipoprotein levels in response to hormone replacement therapy

Directory of Open Access Journals (Sweden)

N.C. Nogueira-de-Souza

2009-12-01

Full Text Available Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter serum levels of total, LDL and HDL cholesterol levels. However, HDL cholesterol levels in women vary considerably in response to hormone replacement therapy (HRT. A significant portion of the variability of these levels has been attributed to genetic factors. Therefore, we investigated the influence of estrogen receptor-alpha (ESR1 gene polymorphisms on HDL levels in response to postmenopausal HRT. We performed a prospective cohort study on 54 postmenopausal women who had not used HRT before the study and had no significant general medical illness. HRT consisted of conjugated equine estrogen and medroxyprogesterone acetate continuously for 1 year. The lipoprotein levels were measured from blood samples taken before the start of therapy and after 1 year of HRT. ESR1 polymorphism (MspI C>T, HaeIII C>T, PvuII C>T, and XbaI A>G frequencies were assayed by restriction fragment length polymorphism. A general linear model was used to describe the relationships between HDL levels and genotypes after adjusting for age. A significant increase in HDL levels was observed after HRT (P = 0.029. Women with the ESR1 PvuII TT genotype showed a statistically significant increase in HDL levels after HRT (P = 0.032. No association was found between other ESR1 polymorphisms and HDL levels. According to our results, the ESR1 PvuII TT genotype was associated with increased levels of HDL after 1 year of HRT.

REPLACEMENT CONTROL OF INNOVATION MANAGERS: ORGANIZATIONAL AND ECONOMIC ASPECTS

Directory of Open Access Journals (Sweden)

E. V. Gurina

2011-01-01

Full Text Available The paper substantiates phases of specialists’ replacement ensuring innovation development of the national economy in Belarus, i.e. managers of innovation activity. Realization of replacement phases is presented within the system consisting of four blocks – objective, managing, controllable and providing. Analysis results of the current state of the innovation activity managers replacement system reveal main problems in interaction of its basic agents. The paper considers solution of specified problems in the context of formation of organizational and economic approaches to managing the innovation activity managers replacement system which presupposes modernization of organizational interrelations between state- run public authorities in the managing block and micro-incentive structures in the controllable block as well as the usage of the process approach in every phase of the replacement process. 

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

Science.gov (United States)

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.

UGT2B17 gene deletion associated with an increase in bone mineral density similar to the effect of hormone replacement in postmenopausal women.

Science.gov (United States)

Giroux, S; Bussières, J; Bureau, A; Rousseau, F

2012-03-01

UGT2B17 is one of the most important enzymes for androgen metabolism. In addition, the UGT2B17 gene is one of the most commonly deleted regions of the human genome. The deletion was previously found associated with higher femoral bone density in men and women, and we replicated this association in a sample of postmenopausal who never used hormone therapy. Deletion of the UGT2B17 gene was previously shown to be associated with a higher hip bone mineral density (BMD). Using a PCR assay, we tried to replicate the association among a large group of 2,379 women. We examined the effect of the deletion on femoral neck BMD and lumbar spine BMD according to the menopausal status and hormone replacement therapy (HRT). We used a high-throughput PCR assay to identify the gene and the deletion in a population of well-characterized women. Two additional polymorphisms, UGT2B28 deletion and UGT2B15 rs1902023 G > T were also investigated. Only UGT2B17 deletion was associated with LS and FN BMD. Furthermore, the association was seen only among postmenopausal women who had never used hormone replacement as in the first reported association. We confirmed the association between UGT2B17 deletion and a higher LS and FN BMD. In addition, we show that the association is observed among postmenopausal women who never used HRT consistent with the enzymatic function of UGT2B17. The analysis shows that those having one or two UGT2B17 alleles benefit from HRT, which is not the case for null carriers.

Rapid replacement of Tangier Island bridges including lightweight and durable fiber-reinforced polymer deck systems.

Science.gov (United States)

2009-01-01

Fiber-reinforced polymer (FRP) composite cellular deck systems were used as new bridge decks on two replacement bridges on Tangier Island, Virginia. The most important characteristics of this application were reduced self-weight and increased durabil...

Reactor protection systems for the Replacement Research Reactor, ANSTO

International Nuclear Information System (INIS)

Morris, C.R.

2003-01-01

The 20-MW Replacement Research Reactor Project which is currently under construction at ANSTO will have a combination of a state of the art triplicated computer based reactor protection system, and a fully independent, and diverse, triplicated analogue reactor protection system, that has been in use in the nuclear industry, for many decades. The First Reactor Protection System (FRPS) consists of a Triconex triplicated modular redundant system that has recently been approved by the USNRC for use in the USA?s power reactor program. The Second Reactor Protection System is a hardwired analogue system supplied by Foxboro, the Spec 200 system, which is also Class1E qualified. The FRPS is used to drop the control rods when its safety parameter setpoints have been reached. The SRPS is used to drain the reflector tank and since this operation would result in a reactor poison out due to the time it would take to refill the tank the FRPS trip setpoints are more limiting. The FRPS and SRPS have limited hardwired indications on the control panels in the main control room (MCR) and emergency control centre (ECC), however all FRPS and SRPS parameters are capable of being displayed on the reactor control and monitoring system (RCMS) video display units. The RCMS is a Foxboro Series I/A control system which is used for plant control and monitoring and as a protection system for the cold neutron source. This paper will provide technical information on both systems, their trip logics, their interconnections with each other, and their integration into the reactor control and monitoring system and control panels. (author)

Optimal selection of Orbital Replacement Unit on-orbit spares - A Space Station system availability model

Science.gov (United States)

Schwaab, Douglas G.

1991-01-01

A mathematical programing model is presented to optimize the selection of Orbital Replacement Unit on-orbit spares for the Space Station. The model maximizes system availability under the constraints of logistics resupply-cargo weight and volume allocations.

Rapid replacement/construction of bridges.

Science.gov (United States)

2012-11-01

Bridges are a key element of the transportation system because they control system capacity and are normally built at : the highest cost to the system. Once a bridge reaches its useful design service life, it needs to be replaced or : reconstructed i...

A new multi-objective optimization model for preventive maintenance and replacement scheduling of multi-component systems

Science.gov (United States)

Moghaddam, Kamran S.; Usher, John S.

2011-07-01

In this article, a new multi-objective optimization model is developed to determine the optimal preventive maintenance and replacement schedules in a repairable and maintainable multi-component system. In this model, the planning horizon is divided into discrete and equally-sized periods in which three possible actions must be planned for each component, namely maintenance, replacement, or do nothing. The objective is to determine a plan of actions for each component in the system while minimizing the total cost and maximizing overall system reliability simultaneously over the planning horizon. Because of the complexity, combinatorial and highly nonlinear structure of the mathematical model, two metaheuristic solution methods, generational genetic algorithm, and a simulated annealing are applied to tackle the problem. The Pareto optimal solutions that provide good tradeoffs between the total cost and the overall reliability of the system can be obtained by the solution approach. Such a modeling approach should be useful for maintenance planners and engineers tasked with the problem of developing recommended maintenance plans for complex systems of components.

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

Science.gov (United States)

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

Replacing HDDs with Solid-State Flash Disks in PXIbus-Based Systems

International Nuclear Information System (INIS)

Zhao, Z W; Zeng, L

2006-01-01

New security features, constantly decreasing prices, solid-state Flash disks are becoming a popular alternative for replacing failure-prone mechanical Hard Disk Drives (HDDs) in PXIbus-based military systems. The key component in high-capacity solid-state Flash disks is NAND Flash, but with a specification that shows only 100,000-300,000 write/erase cycles, engineers may be concerned that the lifetime of Flash disks cannot meet their application requirements. With the right Flash management, Flash disks are able to provide the reliability and endurance that military applications need

A two-cassette reporter system for assessing target gene translation and target gene product inclusion body formation

DEFF Research Database (Denmark)

2016-01-01

The present invention relates to a dual cassette reporter system capable of assessing target gene translation and target gene product folding. The present invention further relates to vectors and host cells comprising the dual cassette reporter system. In addition the invention relates to the use...... of the dual cassette reporter system for assessing target gene translation and target gene product folding....

Gene Replacement and Fluorescent Labeling to Study the Functional Role of Exopolysaccharides in Bifidobacterium animalis subsp. lactis

Directory of Open Access Journals (Sweden)

Nuria Castro-Bravo

2017-07-01

Full Text Available An extracellular layer of exopolysaccharides (EPS covers the surface of some Bifidobacterium animalis subsp. lactis strains, which could be of relevance for its probiotic performance. In order to understand the functional characteristics of B. animalis subsp. lactis, two isogenic strains that differ in their EPS-producing phenotype, due to a single mutation in the gene Balat_1410, were studied. By means of a double crossover recombination strategy, successfully used for the first time in bifidobacteria, Balat_1410 in the type strain B. animalis subsp. lactis DSM10140 was replaced by a mutated gene containing a non-synonymous mutation previously associated with the appearance of a mucoid-ropy phenotype. Nuclear magnetic resonance and SEC-MALS analyses showed that the novel strain harboring the mutation acquired a ropy phenotype, due to the production of a high molecular weight (HMW-EPS that is not produced in the wild-type strain. Fluorescence labeling of both strains with two fluorescent proteins, m-Cherry and Green Fluorescent Protein, was achieved by expressing the corresponding genes under the control of a native selected promoter (the elongation factor Tu promoter. Remarkably, qualitative and quantitative fluorescence analyses demonstrated that the ropy strain displays a lower capability to adhere to human intestinal epithelial cells. In addition, the presence of the HMW-EPS reduced the capability of the producing strain to form biofilms upon three different abiotic surfaces. This work also highlights the fact that different EPS confer variable functional characteristics to the bifidobacterial surface, which may be relevant for the performance of B. animalis subsp. lactis as a probiotic. The construction of molecular tools allowing the functional characterization of surface structures in next generation probiotics is still a challenging issue that deserves further attention, given the relevant role that such molecules must play in the

Patterns of evolutionary conservation of essential genes correlate with their compensability.

Directory of Open Access Journals (Sweden)

Tobias Bergmiller

2012-06-01

Full Text Available Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes.

Feeder replacement tooling and processes

International Nuclear Information System (INIS)

Mallozzi, R.; Goslin, R.; Pink, D.; Askari, A.

2008-01-01

Primary heat transport system feeder integrity has become a concern at some CANDU nuclear plants as a result of thinning caused by flow accelerated corrosion (FAC). Feeder inspections are indicating that life-limiting wall thinning can occur in the region between the Grayloc hub weld and second elbow of some outlet feeders. In some cases it has become necessary to replace thinned sections of affected feeders to restore feeder integrity to planned end of life. Atomic Energy of Canada Limited (AECL) and Babcock and Wilcox Canada Ltd. (B and W) have developed a new capability for replacement of single feeders at any location on the reactor face without impacting or interrupting operation of neighbouring feeders. This new capability consists of deploying trained crews with specialized tools and procedures for feeder replacements during planned outages. As may be expected, performing single feeder replacement in the congested working environment of an operational CANDU reactor face involves overcoming many challenges with respect to access to feeders, available clearances for tooling, and tooling operation and performance. This paper describes some of the challenges encountered during single feeder replacements and actions being taken by AECL and B and W to promote continuous improvement of feeder replacement tooling and processes and ensure well-executed outages. (author)

48 CFR 908.7112 - Materials handling equipment replacement standards.

Science.gov (United States)

2010-10-01

... equipment replacement standards. 908.7112 Section 908.7112 Federal Acquisition Regulations System DEPARTMENT... Special Items 908.7112 Materials handling equipment replacement standards. Materials handling equipment shall be purchased for replacement purposes in accordance with the standards in FPMR 41 CFR 101-25.405...

THE REPLACEMENT-RENEWAL OF INDUSTRIAL EQUIPMENTS. THE MAPI FORMULAS

Directory of Open Access Journals (Sweden)

Meo Colombo Carlotta

2010-07-01

Full Text Available Since the production has been found to be an economical means for satisfying human wants, this process requires a complex industrial organization together with a large investment in equipments, plants and productive systems. These productive systems are employed to alter the physical environment and create consumer goods. As a result, they are consumed or become obsolete, inadequate, or otherwise candidates for replacement. When replacement is being considered, two assets must be evaluated: the present asset, the defender and its potential replacement, the challenger. Since the success of an industrial organization depends upon profit, replacement should generally occur if an economic advantage will result. Whatever the reason leading to the consideration of replacement, the analysis and decisions must be based upon estimates of what will occur in the future. In this paper we present the Mapi algorithm as a procedure for evaluating investments or for analyzing replacement opportunities.

Age replacement models: A summary with new perspectives and methods

International Nuclear Information System (INIS)

Zhao, Xufeng; Al-Khalifa, Khalifa N.; Magid Hamouda, Abdel; Nakagawa, Toshio

2017-01-01

Age replacement models are fundamental to maintenance theory. This paper summarizes our new perspectives and hods in age replacement models: First, we optimize the expected cost rate for a required availability level and vice versa. Second, an asymptotic model with simple calculation is proposed by using the cumulative hazard function skillfully. Third, we challenge the established theory such that preventive replacement should be non-random and only corrective replacement should be made for the unit with exponential failure. Fourth, three replacement policies with random working cycles are discussed, which are called overtime replacement, replacement first, and replacement last, respectively. Fifth, the policies of replacement first and last are formulated with general models. Sixth, age replacement is modified for the situation when the economical life cycle of the unit is a random variable with probability distribution. Finally, models of a parallel system with constant and random number of units are taken into considerations. The models of expected cost rates are obtained and optimal replacement times to minimize them are discussed analytically and computed numerically. Further studies and potential applications are also indicated at the end of discussions of the above models. - Highlights: • Optimization of cost rate for availability level is discussed and vice versa. • Asymptotic and random replacement models are discussed. • Overtime replacement, replacement first and replacement last are surveyed. • Replacement policy with random life cycle is given. • A parallel system with random number of units is modeled.

A reduce and replace strategy for suppressing vector-borne diseases: insights from a stochastic, spatial model.

Directory of Open Access Journals (Sweden)

Kenichi W Okamoto

Full Text Available Two basic strategies have been proposed for using transgenic Aedes aegypti mosquitoes to decrease dengue virus transmission: population reduction and population replacement. Here we model releases of a strain of Ae. aegypti carrying both a gene causing conditional adult female mortality and a gene blocking virus transmission into a wild population to assess whether such releases could reduce the number of competent vectors. We find this "reduce and replace" strategy can decrease the frequency of competent vectors below 50% two years after releases end. Therefore, this combined approach appears preferable to releasing a strain carrying only a female-killing gene, which is likely to merely result in temporary population suppression. However, the fixation of anti-pathogen genes in the population is unlikely. Genetic drift at small population sizes and the spatially heterogeneous nature of the population recovery after releases end prevent complete replacement of the competent vector population. Furthermore, releasing more individuals can be counter-productive in the face of immigration by wild-type mosquitoes, as greater population reduction amplifies the impact wild-type migrants have on the long-term frequency of the anti-pathogen gene. We expect the results presented here to give pause to expectations for driving an anti-pathogen construct to fixation by relying on releasing individuals carrying this two-gene construct. Nevertheless, in some dengue-endemic environments, a spatially heterogeneous decrease in competent vectors may still facilitate decreasing disease incidence.

Large scale replacement of fuel channels in the Pickering CANDU reactor using a man-in-the-loop remote control system

International Nuclear Information System (INIS)

Stratton, D.

1991-01-01

Spar Aerospace Limited of Toronto is presently under contract to Ontario Hydro to design a Remote Manipulation and Control System (RMCS) to be used during the large scale replacement of the fuel channels in the Pickering A Nuclear Generating Station. The system is designed to support the replacement of all 390 fuel channels in each of the four reactors at the Pickering A station in a safe manner that minimizes worker radiation exposure and unit outage time

Human gene therapy: novel approaches to improve the current gene delivery systems.

Science.gov (United States)

Cucchiarini, Magali

2016-06-01

Even though gene therapy made its way through the clinics to treat a number of human pathologies since the early years of experimental research and despite the recent approval of the first gene-based product (Glybera) in Europe, the safe and effective use of gene transfer vectors remains a challenge in human gene therapy due to the existence of barriers in the host organism. While work is under active investigation to improve the gene transfer systems themselves, the use of controlled release approaches may offer alternative, convenient tools of vector delivery to achieve a performant gene transfer in vivo while overcoming the various physiological barriers that preclude its wide use in patients. This article provides an overview of the most significant contributions showing how the principles of controlled release strategies may be adapted for human gene therapy.

Adjacent level effects of bi level disc replacement, bi level fusion and disc replacement plus fusion in cervical spine--a finite element based study.

Science.gov (United States)

Faizan, Ahmad; Goel, Vijay K; Biyani, Ashok; Garfin, Steven R; Bono, Christopher M

2012-03-01

Studies delineating the adjacent level effect of single level disc replacement systems have been reported in literature. The aim of this study was to compare the adjacent level biomechanics of bi-level disc replacement, bi-level fusion and a construct having adjoining level disc replacement and fusion system. In total, biomechanics of four models- intact, bi level disc replacement, bi level fusion and fusion plus disc replacement at adjoining levels- was studied to gain insight into the effects of various instrumentation systems on cranial and caudal adjacent levels using finite element analysis (73.6N+varying moment). The bi-level fusion models are more than twice as stiff as compared to the intact model during flexion-extension, lateral bending and axial rotation. Bi-level disc replacement model required moments lower than intact model (1.5Nm). Fusion plus disc replacement model required moment 10-25% more than intact model, except in extension. Adjacent level motions, facet loads and endplate stresses increased substantially in the bi-level fusion model. On the other hand, adjacent level motions, facet loads and endplate stresses were similar to intact for the bi-level disc replacement model. For the fusion plus disc replacement model, adjacent level motions, facet loads and endplate stresses were closer to intact model rather than the bi-level fusion model, except in extension. Based on our finite element analysis, fusion plus disc replacement procedure has less severe biomechanical effects on adjacent levels when compared to bi-level fusion procedure. Bi-level disc replacement procedure did not have any adverse mechanical effects on adjacent levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rapid breeding and varietal replacement are critical to adaptation of cropping systems in the developing world to climate change.

Science.gov (United States)

Atlin, Gary N; Cairns, Jill E; Das, Biswanath

2017-03-01

Plant breeding is a key mechanism for adaptation of cropping systems to climate change. Much discussion of breeding for climate change focuses on genes with large effects on heat and drought tolerance, but phenology and stress tolerance are highly polygenic. Adaptation will therefore mainly result from continually adjusting allele frequencies at many loci through rapid-cycle breeding that delivers a steady stream of incrementally improved cultivars. This will require access to elite germplasm from other regions, shortened breeding cycles, and multi-location testing systems that adequately sample the target population of environments. The objective of breeding and seed systems serving smallholder farmers should be to ensure that they use varieties developed in the last 10 years. Rapid varietal turnover must be supported by active dissemination of new varieties, and active withdrawal of obsolete ones. Commercial seed systems in temperate regions achieve this through competitive seed markets, but in the developing world, most crops are not served by competitive commercial seed systems, and many varieties date from the end of the Green Revolution (the late 1970s, when the second generation of modern rice and wheat varieties had been widely adopted). These obsolete varieties were developed in a climate different than today's, placing farmers at risk. To reduce this risk, a strengthened breeding system is needed, with freer international exchange of elite varieties, short breeding cycles, high selection intensity, wide-scale phenotyping, and accurate selection supported by genomic technology. Governments need to incentivize varietal release and dissemination systems to continuously replace obsolete varieties.

Analysis of human protein replacement stable cell lines established using snoMEN-PR vector.

Directory of Open Access Journals (Sweden)

Motoharu Ono

Full Text Available The study of the function of many human proteins is often hampered by technical limitations, such as cytotoxicity and phenotypes that result from overexpression of the protein of interest together with the endogenous version. Here we present the snoMEN (snoRNA Modulator of gene ExpressioN vector technology for generating stable cell lines where expression of the endogenous protein can be reduced and replaced by an exogenous protein, such as a fluorescent protein (FP-tagged version. SnoMEN are snoRNAs engineered to contain complementary sequences that can promote knock-down of targeted RNAs. We have established and characterised two such partial protein replacement human cell lines (snoMEN-PR. Quantitative mass spectrometry was used to analyse the specificity of knock-down and replacement at the protein level and also showed an increased pull-down efficiency of protein complexes containing exogenous, tagged proteins in the protein replacement cell lines, as compared with conventional co-expression strategies. The snoMEN approach facilitates the study of mammalian proteins, particularly those that have so far been difficult to investigate by exogenous expression and has wide applications in basic and applied gene-expression research.

Two fundamentally different classes of microbial genes.

Science.gov (United States)

Wolf, Yuri I; Makarova, Kira S; Lobkovsky, Alexander E; Koonin, Eugene V

2016-11-07

The evolution of bacterial and archaeal genomes is highly dynamic and involves extensive horizontal gene transfer and gene loss 1-4 . Furthermore, many microbial species appear to have open pangenomes, where each newly sequenced genome contains more than 10% ORFans, that is, genes without detectable homologues in other species 5,6 . Here, we report a quantitative analysis of microbial genome evolution by fitting the parameters of a simple, steady-state evolutionary model to the comparative genomic data on the gene content and gene order similarity between archaeal genomes. The results reveal two sharply distinct classes of microbial genes, one of which is characterized by effectively instantaneous gene replacement, and the other consists of genes with finite, distributed replacement rates. These findings imply a conservative estimate of the size of the prokaryotic genomic universe, which appears to consist of at least a billion distinct genes. Furthermore, the same distribution of constraints is shown to govern the evolution of gene complement and gene order, without the need to invoke long-range conservation or the selfish operon concept 7 .

Evolution of glutamate dehydrogenase genes: evidence for lateral gene transfer within and between prokaryotes and eukaryotes

Directory of Open Access Journals (Sweden)

Roger Andrew J

2003-06-01

Full Text Available Abstract Background Lateral gene transfer can introduce genes with novel functions into genomes or replace genes with functionally similar orthologs or paralogs. Here we present a study of the occurrence of the latter gene replacement phenomenon in the four gene families encoding different classes of glutamate dehydrogenase (GDH, to evaluate and compare the patterns and rates of lateral gene transfer (LGT in prokaryotes and eukaryotes. Results We extend the taxon sampling of gdh genes with nine new eukaryotic sequences and examine the phylogenetic distribution pattern of the various GDH classes in combination with maximum likelihood phylogenetic analyses. The distribution pattern analyses indicate that LGT has played a significant role in the evolution of the four gdh gene families. Indeed, a number of gene transfer events are identified by phylogenetic analyses, including numerous prokaryotic intra-domain transfers, some prokaryotic inter-domain transfers and several inter-domain transfers between prokaryotes and microbial eukaryotes (protists. Conclusion LGT has apparently affected eukaryotes and prokaryotes to a similar extent within the gdh gene families. In the absence of indications that the evolution of the gdh gene families is radically different from other families, these results suggest that gene transfer might be an important evolutionary mechanism in microbial eukaryote genome evolution.

Application of Shuttle Remote Manipulator System technology to the replacement of fuel channels in the Pickering CANDU reactor

International Nuclear Information System (INIS)

Stratton, D.; Butt, C.

1982-04-01

Spar Aerospace Limited of Toronto was the prime contractor to the National Research Council of Canada for the design and development of the Shuttle Remote Manipulator (SRMS). Spar is presently under contract to Ontario Hydro to design and build a Remote Manipulation Control System to replace the fuel channels in the Pickering A Nuclear Generating Station. The equipment may be used to replace the fuel channels in six other early generation CANDU reactors

48 CFR 908.7101-4 - Replacement of motor vehicles.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Replacement of motor....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with... Heads of Contracting Activities may arrange to sell, as exchange sales, used motor vehicles being...

Design and performance of BWC replacement steam generators for PWR systems

International Nuclear Information System (INIS)

Klarner, R.; Steinmoeller, F.; Millman, J.; Schneider, W.

1998-01-01

In recent years, Babcock and Wilcox Canada (BWC) has provided a number of PWR Replacement Steam Generators (RSGS) to replace units that had experienced extensive Alloy 600 tube degradation. BWC RSG units are in operation at Northeast Utilities' Millstone Unit 2, Rochester Gas and Electric's Ginna Station, Duke Energy's Catawba Unit 1, McGuire Unit 1 and 2, Florida Power and Light's St. Lucie Unit 1 and Commonwealth Edison's Byron 1 Station. Extensive start-up performance characteristics have been obtained for Millstone 2, Ginna, McGuire 1, and Catawba 1 RSGS. The Millstone 2, Ginna and Catawba 1 RSGs have also undergone extensive inspections following their first cycle of operation. The design and start-up performance characteristics of these RSGs are presented. The BWC Replacement Steam generators were designed to fit the existing envelope of pressure boundary dimensions to ensure licensability and integration into the Nuclear Steam Supply System. The RSGs were provided with a tube bundle of Alloy 690TT tubing, sized to match or exceed the original steam generator (OSG) thermal performance including provision for the reduced thermal conductivity of Alloy 690 relative to Alloy 600. The RSG tube bundle configurations provide a higher circulation design relative to the OSG, and feature corrosion resistant lattice grid and U-bend tube supports which provide effective anti-vibration support. The tube bundle supports accommodate relatively unobstructed flow and allow unrestrained structural interactions during thermal transients. Efficient steam separators assure low moisture carryover as well as high circulation. Performance measurements obtained during start-up verify that the BWC RSGs meet or exceed the specified thermal and moisture carryover performance requirements. RSG water level stability results at nor-mal operation and during plant transients have been excellent. Visual and ECT inspections have confirmed minimal deposition and 100% tube integrity following

Boiler feedwater quality improvement by replacing conventional pre-treatment with advanced membrane systems

Energy Technology Data Exchange (ETDEWEB)

Doll, Bernhard [Process Systems Pall GmbH, Dreieich (Germany). Marketing; Venkatadri, Ramraj [Pall Corporation, Port Washington, NY (United States). Global Marketing Energy

2013-09-01

Two case studies in different application fields highlight significant economical and operational improvements that were achieved by replacing conventional water treatment technologies by highly-sophisticated membrane systems. The first case study deals with boiler feedwater in a power plant, focusing on the challenges faced as well as the direct and indirect benefits gained by the new system within a utility station. The second case study deals with the conventional water treatment scheme for groundwater from 13 wells at a major oil sands facility. Operational performance as well as the cost improvements gained in both cases will be presented. (orig.)

Control of gene expression by CRISPR-Cas systems

Science.gov (United States)

2013-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated cas (CRISPR-associated) genes provide adaptive immunity against viruses (phages) and other mobile genetic elements in bacteria and archaea. While most of the early work has largely been dominated by examples of CRISPR-Cas systems directing the cleavage of phage or plasmid DNA, recent studies have revealed a more complex landscape where CRISPR-Cas loci might be involved in gene regulation. In this review, we summarize the role of these loci in the regulation of gene expression as well as the recent development of synthetic gene regulation using engineered CRISPR-Cas systems. PMID:24273648

A single - item replacement decision model for repairable spare ...

African Journals Online (AJOL)

In this paper, we present an analytical method for determining spare parts replacement over an infinite planning horizon. (The objective is to minimize the total system cost). We develop an exact and simple method for determining the time for equipment replacement or making decision about when to replace equipments, ...

Hip joint replacement

Science.gov (United States)

Hip arthroplasty; Total hip replacement; Hip hemiarthroplasty; Arthritis - hip replacement; Osteoarthritis - hip replacement ... Your hip joint is made up of 2 major parts. One or both parts may be replaced during surgery: ...

Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

Science.gov (United States)

Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

2016-08-01

Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

Multiplex editing system

DEFF Research Database (Denmark)

2015-01-01

The present invention relates to a multiplex editing system. The system allows multiple editing of nucleic acid sequences such as genomic sequences, such as knockins of genes of interest in a genome, knockouts of genomic sequences and/or allele replacement. Also provided herein are a method...... for editing nucleic acids and a cell comprising a stably integrated endonuclease....

Non-viral gene therapy for bone tissue engineering.

Science.gov (United States)

Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

2013-01-01

The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

A general approach to total repair cost limit replacement policies

Directory of Open Access Journals (Sweden)

F. Beichelt

2014-01-01

Full Text Available A common replacement policy for technical systems consists in replacing a system by a new one after its economic lifetime, i.e. at that moment when its long-run maintenance cost rate is minimal. However, the strict application of the economic lifetime does not take into account the individual deviations of maintenance cost rates of single systems from the average cost development. Hence, Beichet proposed the total repair cost limit replacement policy: the system is replaced by a new one as soon as its total repair cost reaches or exceeds a given level. He modelled the repair cost development by functions of the Wiener process with drift. Here the same policy is considered under the assumption that the one-dimensional probability distribution of the process describing the repair cost development is given. In the examples analysed, applying the total repair cost limit replacement policy instead of the economic life-time leads to cost savings of between 4% and 30%. Finally, it is illustrated how to include the reliability aspect into the policy.

Replacement Value of fermented millet ( Pennisetum americanum ...

African Journals Online (AJOL)

The replacement value of fermented millet for maize in the diets of Clarias gariepinus fingerlings reared in a recirculation system was determined. Five isonitrogenous diets were formulated to contain graded levels of fermented millet meal replacing 0, 20, 40, 60 and 80% of maize and fed to triplicate groups of fingerlings ...

Engineering development of a digital replacement protection system at an operating US PWR nuclear power plant: Installation and operational experiences

International Nuclear Information System (INIS)

Miller, M.H.

1995-01-01

The existing Reactor Protection Systems (RPSs) at most US PWRs are systems which reflect 25 to 30 year-old designs, components and manufacturing techniques. Technological improvements, especially in relation to modern digital systems, offer improvements in functionality, performance, and reliability, as well as reductions in maintenance and operational burden. The Nuclear power industry and the US nuclear regulators are poised to move forward with the issues that have slowed the transition to modern digital replacements for nuclear power plant safety systems. The electric utility industry is now more than ever being driven by cost versus benefit decisions. Properly designed, engineered, and installed digital systems can provide adequate cost-benefit and allow continued nuclear generated electricity. This paper describes various issues and areas related to an ongoing RPS replacement demonstration project which are pertinant for a typical US nuclear plant to consider cost-effective replacement of an aging analog RPS with a modern digital RPS. The following subject areas relative to the Oconee Nuclear Station ISAT trademark Demonstrator project are discussed: Operator Interface Development; Equipment Qualification; Validation and Verification of Software; Factory Testing; Field Changes and Verification Testing; Utility Operational, Engineering and Maintenance; Experiences with Demonstration System; and Ability to operate in parallel with the existing Analog RPS

Engineering development of a digital replacement protection system at an operating US PWR nuclear power plant: Installation and operational experiences

Energy Technology Data Exchange (ETDEWEB)

Miller, M.H. [Duke Power Co., Seneca, SC (United States)

1995-04-01

The existing Reactor Protection Systems (RPSs) at most US PWRs are systems which reflect 25 to 30 year-old designs, components and manufacturing techniques. Technological improvements, especially in relation to modern digital systems, offer improvements in functionality, performance, and reliability, as well as reductions in maintenance and operational burden. The Nuclear power industry and the US nuclear regulators are poised to move forward with the issues that have slowed the transition to modern digital replacements for nuclear power plant safety systems. The electric utility industry is now more than ever being driven by cost versus benefit decisions. Properly designed, engineered, and installed digital systems can provide adequate cost-benefit and allow continued nuclear generated electricity. This paper describes various issues and areas related to an ongoing RPS replacement demonstration project which are pertinant for a typical US nuclear plant to consider cost-effective replacement of an aging analog RPS with a modern digital RPS. The following subject areas relative to the Oconee Nuclear Station ISAT{trademark} Demonstrator project are discussed: Operator Interface Development; Equipment Qualification; Validation and Verification of Software; Factory Testing; Field Changes and Verification Testing; Utility Operational, Engineering and Maintenance; Experiences with Demonstration System; and Ability to operate in parallel with the existing Analog RPS.

Opportunity-based age replacement policy with minimal repair

International Nuclear Information System (INIS)

Jhang, J.P.; Sheu, S.H.

1999-01-01

This paper proposes an opportunity-based age replacement policy with minimal repair. The system has two types of failures. Type I failures (minor failures) are removed by minimal repairs, whereas type II failures are removed by replacements. Type I and type II failures are age-dependent. A system is replaced at type II failure (catastrophic failure) or at the opportunity after age T, whichever occurs first. The cost of the minimal repair of the system at age z depends on the random part C(z) and the deterministic part c(z). The opportunity arises according to a Poisson process, independent of failures of the component. The expected cost rate is obtained. The optimal T * which would minimize the cost rate is discussed. Various special cases are considered. Finally, a numerical example is given

Prioritizing equipment for replacement.

Science.gov (United States)

Capuano, Mike

2010-01-01

It is suggested that clinical engineers take the lead in formulating evaluation processes to recommend equipment replacement. Their skill, knowledge, and experience, combined with access to equipment databases, make them a logical choice. Based on ideas from Fennigkoh's scheme, elements such as age, vendor support, accumulated maintenance cost, and function/risk were used.6 Other more subjective criteria such as cost benefits and efficacy of newer technology were not used. The element of downtime was also omitted due to the data element not being available. The resulting Periop Master Equipment List and its rationale was presented to the Perioperative Services Program Council. They deemed the criteria to be robust and provided overwhelming acceptance of the list. It was quickly put to use to estimate required capital funding, justify items already thought to need replacement, and identify high-priority ranked items for replacement. Incorporating prioritization criteria into an existing equipment database would be ideal. Some commercially available systems do have the basic elements of this. Maintaining replacement data can be labor-intensive regardless of the method used. There is usually little time to perform the tasks necessary for prioritizing equipment. However, where appropriate, a clinical engineering department might be able to conduct such an exercise as shown in the following case study.

Polymorphisms in Th1/Th2 Cytokine Genes, Hormone Replacement Therapy, and Risk of Non-Hodgkin Lymphoma

International Nuclear Information System (INIS)

Zhu, Gongjian; Pan, Dongsheng; Zheng, Tongzhang; Lan, Qing; Chen, Xuezhong; Chen, Yingtai; Kim, Christopher; Bi, Xiaofeng; Holford, Theodore; Boyle, Peter; Leaderer, Brian; Chanock, Stephen J.; Rothman, Nathaniel; Zhang, Yawei

2011-01-01

We conducted a population-based case–control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between hormone replacement therapy (HRT) and risk of non-Hodgkin lymphoma (NHL). Compared to women without a history of HRT use, women with a history of HRT use had a significantly decreased risk of NHL if they carried IFNGR2 (rs1059293) CT/TT genotypes (OR = 0.5, 95%CI: 0.3–0.9), IL13 (rs20541) GG genotype (OR = 0.6, 95%CI: 0.4–0.9), and IL13 (rs1295686) CC genotype (OR = 0.6, 95%CI: 0.4–0.8), but not among women who carried IFNGR2 CC, IL13 AG/AA, and IL13CT/TT genotypes. A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. A statistically significant interaction was observed for IFNGR2 (rs1059293 P for interaction = 0.024), IL13(rs20541 P for interaction = 0.005), IL13 (rs1295686 P for interaction = 0.008), and IL15RA (rs2296135 P for interaction = 0.049) for NHL overall; IL13 (rs20541 P for interaction = 0.0009), IL13(rs1295686 P for interaction = 0.0002), and IL15RA (rs2296135 P for interaction = 0.041) for B-cell lymphoma. The results suggest that common genetic variation in Th1/Th pathway genes may modify the association between HRT and NHL risk.

A methodological framework applied to the choice of the best method in replacement of nuclear systems

International Nuclear Information System (INIS)

Vianna Filho, Alfredo Marques

2009-01-01

The economic equipment replacement problem is a central question in Nuclear Engineering. On the one hand, new equipment are more attractive given their best performance, better reliability, lower maintenance cost etc. New equipment, however, require a higher initial investment. On the other hand, old equipment represent the other way around, with lower performance, lower reliability and specially higher maintenance costs, but in contrast having lower financial and insurance costs. The weighting of all these costs can be made with deterministic and probabilistic methods applied to the study of equipment replacement. Two types of distinct problems will be examined, substitution imposed by the wearing and substitution imposed by the failures. In order to solve the problem of nuclear system substitution imposed by wearing, deterministic methods are discussed. In order to solve the problem of nuclear system substitution imposed by failures, probabilistic methods are discussed. The aim of this paper is to present a methodological framework to the choice of the most useful method applied in the problem of nuclear system substitution.(author)

Targeted Regression of Hepatocellular Carcinoma by Cancer-Specific RNA Replacement through MicroRNA Regulation.

Science.gov (United States)

Kim, Juhyun; Won, Ranhui; Ban, Guyee; Ju, Mi Ha; Cho, Kyung Sook; Young Han, Sang; Jeong, Jin-Sook; Lee, Seong-Wook

2015-07-20

Hepatocellular carcinoma (HCC) has a high fatality rate and limited therapeutic options with side effects and low efficacy. Here, we proposed a new anti-HCC approach based on cancer-specific post-transcriptional targeting. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically induce therapeutic gene activity through HCC-specific replacement of telomerase reverse transcriptase (TERT) RNA. To circumvent side effects due to TERT expression in regenerating liver tissue, liver-specific microRNA-regulated ribozymes were constructed by incorporating complementary binding sites for the hepatocyte-selective microRNA-122a (miR-122a), which is down-regulated in HCC. The ribozyme activity in vivo was assessed in mouse models orthotopically implanted with HCC. Systemic administration of adenovirus encoding the developed ribozymes caused efficient anti-cancer effect and the least hepatotoxicity with regulation of ribozyme expression by miR-122a in both xenografted and syngeneic orthotopic murine model of multifocal HCC. Of note, the ribozyme induced local and systemic antitumor immunity, thereby completely suppressing secondary tumor challenge in the syngeneic mouse. The cancer specific trans-splicing ribozyme system, which mediates tissue-specific microRNA-regulated RNA replacement, provides a clinically relevant, safe, and efficient strategy for HCC treatment.

Defining waste acceptance criteria for the Hanford Replacement Cross-Site Transfer System

International Nuclear Information System (INIS)

Hudson, J.D.

1996-04-01

This document provides a methodology for defining waste acceptance criteria for the Hanford Replacement Cross-Site Transfer System (RCSTS). This methodology includes characterization, transport analysis, and control. A framework is described for each of these functions. A tool was developed for performing the calculations associated with the transport analysis. This tool, a worksheet that is available in formats acceptable for a variety of PC spreadsheet programs, enables a comparison of the pressure required to transport a given slurry at a rate that particulate suspension is maintained to the pressure drop available from the RCSTS

Selection on the Major Color Gene Melanocortin-1-Receptor Shaped the Evolution of the Melanocortin System Genes

Directory of Open Access Journals (Sweden)

Linda Dib

2017-12-01

Full Text Available Modular genetic systems and networks have complex evolutionary histories shaped by selection acting on single genes as well as on their integrated function within the network. However, uncovering molecular coevolution requires the detection of coevolving sites in sequences. Detailed knowledge of the functions of each gene in the system is also necessary to identify the selective agents driving coevolution. Using recently developed computational tools, we investigated the effect of positive selection on the coevolution of ten major genes in the melanocortin system, responsible for multiple physiological functions and human diseases. Substitutions driven by positive selection at the melanocortin-1-receptor (MC1R induced more coevolutionary changes on the system than positive selection on other genes in the system. Contrarily, selection on the highly pleiotropic POMC gene, which orchestrates the activation of the different melanocortin receptors, had the lowest coevolutionary influence. MC1R and possibly its main function, melanin pigmentation, seems to have influenced the evolution of the melanocortin system more than functions regulated by MC2-5Rs such as energy homeostasis, glucocorticoid-dependent stress and anti-inflammatory responses. Although replication in other regulatory systems is needed, this suggests that single functional aspects of a genetic network or system can be of higher importance than others in shaping coevolution among the genes that integrate it.

Efficient in planta gene targeting in tomato using geminiviral replicons and the CRISPR/Cas9 system.

Science.gov (United States)

Dahan-Meir, Tal; Filler-Hayut, Shdema; Melamed-Bessudo, Cathy; Bocobza, Samuel; Czosnek, Henryk; Aharoni, Asaph; Levy, Avraham A

2018-04-18

Current breeding relies mostly on random mutagenesis and recombination to generate novel genetic variation. However, targeted genome editing is becoming an increasingly important tool for precise plant breeding. Using the CRISPR-Cas system combined with the bean yellow dwarf virus rolling circle replicon we optimized a method for targeted mutagenesis and gene replacement in tomato. The carotenoid isomerase (CRTISO) and phytoene synthase 1 (PSY1) genes from the carotenoid biosynthesis pathway were chosen as targets due to their easily detectable change of phenotype. We took advantage of the geminiviral replicon amplification as a mean to provide a large amount of donor template for the repair of a CRISPR-Cas-induced DNA double strand break (DSB) in the target gene, via homologous recombination. Mutagenesis experiments, performed in the Micro-Tom variety achieved precise modification of the CRTISO and PSY1 loci at an efficiency of up to 90%. In the gene targeting experiments, our target was a fast-neutron-induced crtiso allele that contained a 281bp deletion. This deletion was repaired with the wildtype sequence through homologous recombination between the CRISPR-Cas-induced DSB in the crtiso target and the amplified donor in 25% of the plants transformed. This shows that efficient gene targeting can be achieved in the absence of selection markers or reporters using a single and modular construct that is adaptable to other tomato targets and other crops. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Replacement of the Project Manager Reflected Through Activity Theory and Work-System Theory

Science.gov (United States)

Vartiainen, Tero; Aramo-Immonen, Heli; Jussila, Jari; Pirhonen, Maritta; Liikamaa, Kirsi

Replacement of the project manager (RPM) is a known phenomenon in information systems (IS) projects, but scant attention is given to it in the project management or IS literature. Given its critical effects on the project business, the organization, the project team, and the project manager, it should be studied in more depth. We identified factors which make RPM occurrences inherently different and we show that work-system theory and activity theory give comprehensive lenses to advance research on RPM. For the future research on RPM we identified three objectives: experiences on RPM, process model for RPM, and organizational culture's influence on RPM occurrences.

Robotic systems for the high level waste tank farm replacement project at INEL

International Nuclear Information System (INIS)

Berger, A.; White, D.; Thompson, B.; Christensen, M.

1993-01-01

Westinghouse Idaho Nuclear Company (WINCO) is specifying and designing a new high level waste tank farm at the Idaho National Engineering Laboratory (INEL). The farm consists of four underground storage tanks, which replace the existing tanks. The new facility includes provisions for remote operations. One of the planned remote operations is robotic inspection of the tank from the interior and exterior. This paper describes the process used to design the robotic system for the inspection tasks

HST Replacement Battery Initial Performance

Science.gov (United States)

Krol, Stan; Waldo, Greg; Hollandsworth, Roger

2009-01-01

The Hubble Space Telescope (HST) original Nickel-Hydrogen (NiH2) batteries were replaced during the Servicing Mission 4 (SM4) after 19 years and one month on orbit.The purpose of this presentation is to highlight the findings from the assessment of the initial sm4 replacement battery performance. The batteries are described, the 0 C capacity is reviewed, descriptions, charts and tables reviewing the State Of Charge (SOC) Performance, the Battery Voltage Performance, the battery impedance, the minimum voltage performance, the thermal performance, the battery current, and the battery system recharge ratio,

Insurance for replacement power costs

International Nuclear Information System (INIS)

Cleaver, A.

1980-01-01

Although careful consideration is given to insurance against physical damage to plant and equipment, little thought is given to the costs that will be incurred in replacing the power that is lost while a relatively efficient system is out of action. The results of an investigation carried out for a generating authority with an installed capacity of about 3000 MW is given. Replacement power costs for different cases of severity of damage range from Pound1.17m per month for damage to central services taking out all four units. (author)

Optimal strategies for a replacement model

NARCIS (Netherlands)

Bruns, P.B.

2000-01-01

We examine a replacement system with discrete-time Markovian deterioration and finite state space $\\{0,\\ldots,N\\}$. State 0 stands for a new system, and the higher the state the worse the system; a system in state $N$ is considered to be in a {\\it bad state}. We impose the condition that the

Integrative Functional Genomics for Systems Genetics in GeneWeaver.org.

Science.gov (United States)

Bubier, Jason A; Langston, Michael A; Baker, Erich J; Chesler, Elissa J

2017-01-01

The abundance of existing functional genomics studies permits an integrative approach to interpreting and resolving the results of diverse systems genetics studies. However, a major challenge lies in assembling and harmonizing heterogeneous data sets across species for facile comparison to the positional candidate genes and coexpression networks that come from systems genetic studies. GeneWeaver is an online database and suite of tools at www.geneweaver.org that allows for fast aggregation and analysis of gene set-centric data. GeneWeaver contains curated experimental data together with resource-level data such as GO annotations, MP annotations, and KEGG pathways, along with persistent stores of user entered data sets. These can be entered directly into GeneWeaver or transferred from widely used resources such as GeneNetwork.org. Data are analyzed using statistical tools and advanced graph algorithms to discover new relations, prioritize candidate genes, and generate function hypotheses. Here we use GeneWeaver to find genes common to multiple gene sets, prioritize candidate genes from a quantitative trait locus, and characterize a set of differentially expressed genes. Coupling a large multispecies repository curated and empirical functional genomics data to fast computational tools allows for the rapid integrative analysis of heterogeneous data for interpreting and extrapolating systems genetics results.

Shoulder replacement - discharge

Science.gov (United States)

Total shoulder arthroplasty - discharge; Endoprosthetic shoulder replacement - discharge; Partial shoulder replacement - discharge; Partial shoulder arthroplasty - discharge; Replacement - shoulder - discharge; Arthroplasty - shoulder - discharge

Replacing penalties

Directory of Open Access Journals (Sweden)

Vitaly Stepashin

2017-01-01

Full Text Available УДК 343.24The subject. The article deals with the problem of the use of "substitute" penalties.The purpose of the article is to identify criminal and legal criteria for: selecting the replacement punishment; proportionality replacement leave punishment to others (the formalization of replacement; actually increasing the punishment (worsening of legal situation of the convicted.Methodology.The author uses the method of analysis and synthesis, formal legal method.Results. Replacing the punishment more severe as a result of malicious evasion from serving accused designated penalty requires the optimization of the following areas: 1 the selection of a substitute punishment; 2 replacement of proportionality is serving a sentence other (formalization of replacement; 3 ensuring the actual toughening penalties (deterioration of the legal status of the convict. It is important that the first two requirements pro-vide savings of repression in the implementation of the replacement of one form of punishment to others.Replacement of punishment on their own do not have any specifics. However, it is necessary to compare them with the contents of the punishment, which the convict from serving maliciously evaded. First, substitute the punishment should assume a more significant range of restrictions and deprivation of certain rights of the convict. Second, the perfor-mance characteristics of order substitute the punishment should assume guarantee imple-mentation of the new measures.With regard to replacing all forms of punishment are set significant limitations in the application that, in some cases, eliminates the possibility of replacement of the sentence, from serving where there has been willful evasion, a stricter measure of state coercion. It is important in the context of the topic and the possibility of a sentence of imprisonment as a substitute punishment in cases where the original purpose of the strict measures excluded. It is noteworthy that the

System Biology Approach: Gene Network Analysis for Muscular Dystrophy.

Science.gov (United States)

Censi, Federica; Calcagnini, Giovanni; Mattei, Eugenio; Giuliani, Alessandro

2018-01-01

Phenotypic changes at different organization levels from cell to entire organism are associated to changes in the pattern of gene expression. These changes involve the entire genome expression pattern and heavily rely upon correlation patterns among genes. The classical approach used to analyze gene expression data builds upon the application of supervised statistical techniques to detect genes differentially expressed among two or more phenotypes (e.g., normal vs. disease). The use of an a posteriori, unsupervised approach based on principal component analysis (PCA) and the subsequent construction of gene correlation networks can shed a light on unexpected behaviour of gene regulation system while maintaining a more naturalistic view on the studied system.In this chapter we applied an unsupervised method to discriminate DMD patient and controls. The genes having the highest absolute scores in the discrimination between the groups were then analyzed in terms of gene expression networks, on the basis of their mutual correlation in the two groups. The correlation network structures suggest two different modes of gene regulation in the two groups, reminiscent of important aspects of DMD pathogenesis.

The Influence of SV40 polyA on Gene Expression of Baculovirus Expression Vector Systems.

Directory of Open Access Journals (Sweden)

Tamer Z Salem

Full Text Available The simian virus 40 polyadenylation signal (SV40 polyA has been routinely inserted downstream of the polyhedrin promoter in many baculovirus expression vector systems (BEVS. In the baculovirus prototype Autographa californica multiple nucleopolyhedrovirus (AcMNPV, the polyhedrin promoter (very late promoter transcribes its gene by a viral RNA polymerase therefore there is no supporting evidence that SV40 polyA is required for the proper gene expression under the polyhedrin promoter. Moreover, the effect of the SV40 polyA sequence on the polyhedrin promoter activity has not been tested either at its natural polyhedrin locus or in other loci in the viral genome. In order to test the significance of adding the SV40 polyA sequence on gene expression, the expression of the enhanced green fluorescent protein (egfp was evaluated with and without the presence of SV40 polyA under the control of the polyhedrin promoter at different genomic loci (polyherin, ecdysteroid UDP-glucosyltransferase (egt, and gp37. In this study, spectrofluorometry and western blot showed reduction of EGFP protein for all recombinant viruses with SV40 polyA, whereas qPCR showed an increase in the egfp mRNA levels. Therefore, we conclude that SV40 polyA increases mRNA levels but decreases protein production in the BEVS when the polyhedrin promoter is used at different loci. This work suggests that SV40 polyA in BEVSs should be replaced by an AcMNPV late gene polyA for optimal protein production or left untouched for optimal RNA production (RNA interference applications.

The Influence of SV40 polyA on Gene Expression of Baculovirus Expression Vector Systems

Science.gov (United States)

Salem, Tamer Z.; Seaborn, Craig P.; Turney, Colin M.; Xue, Jianli; Shang, Hui; Cheng, Xiao-Wen

2015-01-01

The simian virus 40 polyadenylation signal (SV40 polyA) has been routinely inserted downstream of the polyhedrin promoter in many baculovirus expression vector systems (BEVS). In the baculovirus prototype Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the polyhedrin promoter (very late promoter) transcribes its gene by a viral RNA polymerase therefore there is no supporting evidence that SV40 polyA is required for the proper gene expression under the polyhedrin promoter. Moreover, the effect of the SV40 polyA sequence on the polyhedrin promoter activity has not been tested either at its natural polyhedrin locus or in other loci in the viral genome. In order to test the significance of adding the SV40 polyA sequence on gene expression, the expression of the enhanced green fluorescent protein (egfp) was evaluated with and without the presence of SV40 polyA under the control of the polyhedrin promoter at different genomic loci (polyherin, ecdysteroid UDP-glucosyltransferase (egt), and gp37). In this study, spectrofluorometry and western blot showed reduction of EGFP protein for all recombinant viruses with SV40 polyA, whereas qPCR showed an increase in the egfp mRNA levels. Therefore, we conclude that SV40 polyA increases mRNA levels but decreases protein production in the BEVS when the polyhedrin promoter is used at different loci. This work suggests that SV40 polyA in BEVSs should be replaced by an AcMNPV late gene polyA for optimal protein production or left untouched for optimal RNA production (RNA interference applications). PMID:26659470

Economic analysis for upgrade decision-making using a control system replacement example

International Nuclear Information System (INIS)

De Grosbois, J.; Wichman, R.; Hepburn, G.A.; Basso, R.; Kumar, V.; Deregowska, D.

2006-01-01

This paper (3rd in a CNS series) provides insight on how nuclear power plants can achieve better efficiencies and reduced operations and maintenance (O and M) costs by making well-informed equipment upgrade decisions. An investment decision in a plant system upgrade will have various technical options and associated performance outcomes. These can be modelled and evaluated using economic and financial analysis methods. The economic analysis usually involves a comparison of an investment scenario versus a no-investment scenario called difference case analysis. The investment may include several scenarios due to the existence of various options, different investment timings, or desired performance results. Classical approaches, using financial tools such as net present value and internal rate of return calculations, may be used to quantify the financial benefits of the difference cases when certainty about the outcomes is assumed. When making decisions under risk, the classical approaches may be augmented with methods that consider life-cycle costs and benefits, the cost consequences of and probability of equipment failure, the timing of the replacement, and the uncertainties in estimating costs and benefits. The use of expected value and Monte Carlo simulation, among others, allow the incorporation of financial and technical uncertainty into the analysis. Finally, sensitivity analysis enables better understanding of the problem and may improve the decision and clarify the level of confidence that should be put in the outcomes. This paper illustrates the use of financial decision analysis methods for equipment replacements using a control system upgrade example. These methods may easily be generalized for other types of plant upgrades. (author)

Large-scale gene function analysis with the PANTHER classification system.

Science.gov (United States)

Mi, Huaiyu; Muruganujan, Anushya; Casagrande, John T; Thomas, Paul D

2013-08-01

The PANTHER (protein annotation through evolutionary relationship) classification system (http://www.pantherdb.org/) is a comprehensive system that combines gene function, ontology, pathways and statistical analysis tools that enable biologists to analyze large-scale, genome-wide data from sequencing, proteomics or gene expression experiments. The system is built with 82 complete genomes organized into gene families and subfamilies, and their evolutionary relationships are captured in phylogenetic trees, multiple sequence alignments and statistical models (hidden Markov models or HMMs). Genes are classified according to their function in several different ways: families and subfamilies are annotated with ontology terms (Gene Ontology (GO) and PANTHER protein class), and sequences are assigned to PANTHER pathways. The PANTHER website includes a suite of tools that enable users to browse and query gene functions, and to analyze large-scale experimental data with a number of statistical tests. It is widely used by bench scientists, bioinformaticians, computer scientists and systems biologists. In the 2013 release of PANTHER (v.8.0), in addition to an update of the data content, we redesigned the website interface to improve both user experience and the system's analytical capability. This protocol provides a detailed description of how to analyze genome-wide experimental data with the PANTHER classification system.

Design and performance of BWC replacement steam generators for PWR systems

Energy Technology Data Exchange (ETDEWEB)

Klarner, R.; Steinmoeller, F.; Millman, J.; Schneider, W. [Babcock and Wilcox Canada, Cambridge, Ontario (Canada)

1998-07-01

In recent years, Babcock and Wilcox Canada (BWC) has provided a number of PWR Replacement Steam Generators (RSGS) to replace units that had experienced extensive Alloy 600 tube degradation. BWC RSG units are in operation at Northeast Utilities' Millstone Unit 2, Rochester Gas and Electric's Ginna Station, Duke Energy's Catawba Unit 1, McGuire Unit 1 and 2, Florida Power and Light's St. Lucie Unit 1 and Commonwealth Edison's Byron 1 Station. Extensive start-up performance characteristics have been obtained for Millstone 2, Ginna, McGuire 1, and Catawba 1 RSGS. The Millstone 2, Ginna and Catawba 1 RSGs have also undergone extensive inspections following their first cycle of operation. The design and start-up performance characteristics of these RSGs are presented. The BWC Replacement Steam generators were designed to fit the existing envelope of pressure boundary dimensions to ensure licensability and integration into the Nuclear Steam Supply System. The RSGs were provided with a tube bundle of Alloy 690TT tubing, sized to match or exceed the original steam generator (OSG) thermal performance including provision for the reduced thermal conductivity of Alloy 690 relative to Alloy 600. The RSG tube bundle configurations provide a higher circulation design relative to the OSG, and feature corrosion resistant lattice grid and U-bend tube supports which provide effective anti-vibration support. The tube bundle supports accommodate relatively unobstructed flow and allow unrestrained structural interactions during thermal transients. Efficient steam separators assure low moisture carryover as well as high circulation. Performance measurements obtained during start-up verify that the BWC RSGs meet or exceed the specified thermal and moisture carryover performance requirements. RSG water level stability results at nor-mal operation and during plant transients have been excellent. Visual and ECT inspections have confirmed minimal deposition and 100

Nonviral Delivery Systems For Cancer Gene Therapy: Strategies And Challenges.

Science.gov (United States)

Shim, Gayong; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Kwon, Taekhyun; Oh, Yu-Kyoung

2018-01-19

Gene therapy has been receiving widespread attention due to its unique advantage in regulating the expression of specific target genes. In the field of cancer gene therapy, modulation of gene expression has been shown to decrease oncogenic factors in cancer cells or increase immune responses against cancer. Due to the macromolecular size and highly negative physicochemical features of plasmid DNA, efficient delivery systems are an essential ingredient for successful gene therapy. To date, a variety of nanostructures and materials have been studied as nonviral gene delivery systems. In this review, we will cover nonviral delivery strategies for cancer gene therapy, with a focus on target cancer genes and delivery materials. Moreover, we will address current challenges and perspectives for nonviral delivery-based cancer gene therapeutics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A periodic inspection and replacement policy for systems subject to competing failure modes due to degradation and traumatic events

Energy Technology Data Exchange (ETDEWEB)

Huynh, K.T., E-mail: tuan.huynh@utt.f [Universite de technologie de Troyes, Institut Charles Delaunay and STMR UMR CNRS 6279-12, rue Marie Curie, BP2060, 10010 Troyes cedex (France); Barros, A., E-mail: anne.barros@utt.f [Universite de technologie de Troyes, Institut Charles Delaunay and STMR UMR CNRS 6279-12, rue Marie Curie, BP2060, 10010 Troyes cedex (France); Berenguer, C., E-mail: christophe.berenguer@utt.f [Universite de technologie de Troyes, Institut Charles Delaunay and STMR UMR CNRS 6279-12, rue Marie Curie, BP2060, 10010 Troyes cedex (France); Castro, I.T., E-mail: inmatorres@unex.e [Departamento de Matematicas, Escuela Politecnica, 10071 Caceres (Spain)

2011-04-15

This paper deals with the condition-based maintenance of single-unit systems which are subject to the competing and dependent failures due deterioration and traumatic shock events. The main aim is to provide a model to assess the value of condition monitoring information for the maintenance decision-making. A condition-based periodic inspection/replacement policy is developed and compared with a benchmark time-based block replacement policy. Numerical results show that it is indeed useful to follow closely the actual evolution of the system to adapt the maintenance decisions to the true system state to improve the performance of maintenance policies. The analysis of the maintenance costs savings can be used to justify or not the choice to implement a policy based on condition monitoring information and to invest in condition monitoring devices.

A periodic inspection and replacement policy for systems subject to competing failure modes due to degradation and traumatic events

International Nuclear Information System (INIS)

Huynh, K.T.; Barros, A.; Berenguer, C.; Castro, I.T.

2011-01-01

This paper deals with the condition-based maintenance of single-unit systems which are subject to the competing and dependent failures due deterioration and traumatic shock events. The main aim is to provide a model to assess the value of condition monitoring information for the maintenance decision-making. A condition-based periodic inspection/replacement policy is developed and compared with a benchmark time-based block replacement policy. Numerical results show that it is indeed useful to follow closely the actual evolution of the system to adapt the maintenance decisions to the true system state to improve the performance of maintenance policies. The analysis of the maintenance costs savings can be used to justify or not the choice to implement a policy based on condition monitoring information and to invest in condition monitoring devices.

Molecular transformation, gene cloning, and gene expression systems for filamentous fungi

Science.gov (United States)

Gold, Scott E.; Duick, John W.; Redman, Regina S.; Rodriguez, Rusty J.

2001-01-01

This chapter discusses the molecular transformation, gene cloning, and gene expression systems for filamentous fungi. Molecular transformation involves the movement of discrete amounts of DNA into cells, the expression of genes on the transported DNA, and the sustainable replication of the transforming DNA. The ability to transform fungi is dependent on the stable replication and expression of genes located on the transforming DNA. Three phenomena observed in bacteria, that is, competence, plasmids, and restriction enzymes to facilitate cloning, were responsible for the development of molecular transformation in fungi. Initial transformation success with filamentous fungi, involving the complementation of auxotrophic mutants by exposure to sheared genomic DNA or RNA from wt isolates, occurred with low transformation efficiencies. In addition, it was difficult to retrieve complementing DNA fragments and isolate genes of interest. This prompted the development of transformation vectors and methods to increase efficiencies. The physiological studies performed with fungi indicated that the cell wall could be removed to generate protoplasts. It was evident that protoplasts could be transformed with significantly greater efficiencies than walled cells.

Replacement and inspection policies for products with random life cycle

International Nuclear Information System (INIS)

Yun, Won Young; Nakagawa, Toshio

2010-01-01

In this paper, we consider maintenance policies for products in which the economical life cycle of products is a random variable. First, we study a periodic replacement policy with minimal repair. The system is minimally repaired at failure and is replaced by new one at age T (periodic replacement policy with minimal repair of Barlow and Hunter). The expected present value of total maintenance cost of products with random life cycle is obtained and the optimal replacement interval minimizing the cost is found. Second, we consider an inspection policy for products with random life cycle to detect the system failure. The expected total cost is obtained and the optimal inspection interval is found. Numerical examples are also included.

Targeted Gene Replacement in Fungal Pathogens via Agrobacterium tumefaciens- Mediated Transformation

DEFF Research Database (Denmark)

Frandsen, Rasmus John Normand; Frandsen, Mette; Giese, Nanna Henriette

2012-01-01

-step cloning strategies for construction of vectors for Agrobacterium tumefaciens-mediated transformation (ATMT). Targeted genome modifications require integration by a homologous double crossover event, which is achieved by placing target sequences on either side of a selection marker gene in the vector....... Protocols are given for two single-step vector construction techniques. The In-Fusion cloning technique is independent of compatible restriction enzyme sites in the vector and the fragment to be cloned. The method can be directly applied to any vector of choice and it is possible to carry out four fragment...... cloning without the need for subcloning. The cloning efficiency is not always as high as desired, but it still presents an efficient alternative to restriction enzyme and ligase-based cloning systems. The USER technology offers a higher four fragment cloning efficiency than In-Fusion, but depends...

A multi-attribute decision model for portfolio selection aiming to replace technologies in industrial motor systems

International Nuclear Information System (INIS)

Vanderley Herrero Sola, Antonio; Mota, Caroline Maria de Miranda

2012-01-01

Highlights: ► We propose a multicriteria decision model for technology replacement. ► We prioritize induction motors in order to improve the energy efficiency. ► The best portfolio of options is selected based on decision maker’s utilities. ► The model contribute to surpass some organizational barriers. - Abstract: The energy efficient technologies offered by the market are in constant evolution, but their insertion in the productive sector comes up against organizational barriers, which obstruct decision making in firms. This paper proposes a multicriteria decision model in order to replace technologies in industrial energy systems, regarding organizational barriers for energy efficiency. The proposed model is applied in industrial motor systems, using Multi-Attribute Utility Theory (MAUT), in order to select the best portfolio of options based on the decision maker’s utilities. Portfolios of options from the prioritized set of motors compiled by the operational area of the studied industry are analyzed, including diverse suppliers and different classes of motors. The results show that it is essential to structure the proposed model in two steps, beginning with the operational level, to ensure that important technologies for the production system are prioritized, thus preserving the interests of the organization and improving the efficiency of industrial energy systems.

Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.

Science.gov (United States)

Macdonald, Lynn E; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T; Yasenchak, Jason; Frendewey, David; Valenzuela, David M; Giallourakis, Cosmas C; Alt, Frederick W; Yancopoulos, George D; Murphy, Andrew J

2014-04-08

Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.

Condition-based inspection/replacement policies for non-monotone deteriorating systems with environmental covariates

Energy Technology Data Exchange (ETDEWEB)

Zhao Xuejing [Universite de Technologie de Troyes, Institut Charles Delaunay and STMR UMR CNRS 6279, 12 rue Marie Curie, 10010 Troyes (France); School of mathematics and statistics, Lanzhou University, Lanzhou 730000 (China); Fouladirad, Mitra, E-mail: mitra.fouladirad@utt.f [Universite de Technologie de Troyes, Institut Charles Delaunay and STMR UMR CNRS 6279, 12 rue Marie Curie, 10010 Troyes (France); Berenguer, Christophe [Universite de Technologie de Troyes, Institut Charles Delaunay and STMR UMR CNRS 6279, 12 rue Marie Curie, 10010 Troyes (France); Bordes, Laurent [Universite de Pau et des Pays de l' Adour, LMA UMR CNRS 5142, 64013 PAU Cedex (France)

2010-08-15

The aim of this paper is to discuss the problem of modelling and optimising condition-based maintenance policies for a deteriorating system in presence of covariates. The deterioration is modelled by a non-monotone stochastic process. The covariates process is assumed to be a time-homogenous Markov chain with finite state space. A model similar to the proportional hazards model is used to show the influence of covariates on the deterioration. In the framework of the system under consideration, an appropriate inspection/replacement policy which minimises the expected average maintenance cost is derived. The average cost under different conditions of covariates and different maintenance policies is analysed through simulation experiments to compare the policies performances.

Condition-based inspection/replacement policies for non-monotone deteriorating systems with environmental covariates

International Nuclear Information System (INIS)

Zhao Xuejing; Fouladirad, Mitra; Berenguer, Christophe; Bordes, Laurent

2010-01-01

The aim of this paper is to discuss the problem of modelling and optimising condition-based maintenance policies for a deteriorating system in presence of covariates. The deterioration is modelled by a non-monotone stochastic process. The covariates process is assumed to be a time-homogenous Markov chain with finite state space. A model similar to the proportional hazards model is used to show the influence of covariates on the deterioration. In the framework of the system under consideration, an appropriate inspection/replacement policy which minimises the expected average maintenance cost is derived. The average cost under different conditions of covariates and different maintenance policies is analysed through simulation experiments to compare the policies performances.

Polymorphisms in Th1/Th2 Cytokine Genes, Hormone Replacement Therapy, and Risk of Non-Hodgkin Lymphoma

Energy Technology Data Exchange (ETDEWEB)

Zhu, Gongjian; Pan, Dongsheng [Gansu Provincial Academy of Medical Sciences, Gansu Provincial Tumor Hospital, Lanzhou (China); Yale University School of Public Health, New Haven, CT (United States); Zheng, Tongzhang [Yale University School of Public Health, New Haven, CT (United States); Lan, Qing [Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD (United States); Chen, Xuezhong [Gansu Provincial Academy of Medical Sciences, Gansu Provincial Tumor Hospital, Lanzhou (China); Chen, Yingtai [Yale University School of Public Health, New Haven, CT (United States); Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. (China); Kim, Christopher [Yale University School of Public Health, New Haven, CT (United States); Bi, Xiaofeng [Yale University School of Public Health, New Haven, CT (United States); Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. (China); Holford, Theodore [Yale University School of Public Health, New Haven, CT (United States); Boyle, Peter [International Prevention Research Institute, Lyon (France); Leaderer, Brian [Yale University School of Public Health, New Haven, CT (United States); Chanock, Stephen J. [Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD (United States); Core Genotyping Facility, Department of Health and Human Services, Advanced Technology Center, National Cancer Institute, National Institutes of Health, Gaithersburg, MD (United States); Rothman, Nathaniel [Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD (United States); Zhang, Yawei, E-mail: yawei.zhang@yale.edu [Yale University School of Public Health, New Haven, CT (United States)

2011-07-28

We conducted a population-based case–control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between hormone replacement therapy (HRT) and risk of non-Hodgkin lymphoma (NHL). Compared to women without a history of HRT use, women with a history of HRT use had a significantly decreased risk of NHL if they carried IFNGR2 (rs1059293) CT/TT genotypes (OR = 0.5, 95%CI: 0.3–0.9), IL13 (rs20541) GG genotype (OR = 0.6, 95%CI: 0.4–0.9), and IL13 (rs1295686) CC genotype (OR = 0.6, 95%CI: 0.4–0.8), but not among women who carried IFNGR2 CC, IL13 AG/AA, and IL13CT/TT genotypes. A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. A statistically significant interaction was observed for IFNGR2 (rs1059293 P{sub for} {sub interaction} = 0.024), IL13(rs20541 P{sub for} {sub interaction} = 0.005), IL13 (rs1295686 P{sub for} {sub interaction} = 0.008), and IL15RA (rs2296135 P{sub for} {sub interaction} = 0.049) for NHL overall; IL13 (rs20541 P{sub for} {sub interaction} = 0.0009), IL13(rs1295686 P{sub for} {sub interaction} = 0.0002), and IL15RA (rs2296135 P{sub for} {sub interaction} = 0.041) for B-cell lymphoma. The results suggest that common genetic variation in Th1/Th pathway genes may modify the association between HRT and NHL risk.

Ankle replacement

Science.gov (United States)

Ankle arthroplasty - total; Total ankle arthroplasty; Endoprosthetic ankle replacement; Ankle surgery ... Ankle replacement surgery is most often done while you are under general anesthesia. This means you will ...

From Genes to Genomes Chances and boundaries of the New Biology

CERN Document Server

Winnaker, E L

1997-01-01

The goal of my lecture is to show the new dimensions of genome research. It is replacing classic recombinant DNA technologies. The search for single genes is being replaced by the analysis of gene activities of whole cells, organs or organisms. This development changes radically basic biomedical research and points to new therapeutic strategies (examples:cancer,Alzheimer's disease). I will also show the rapid changes of our understanding of gene activity. Mendel's definition of genes is now replaced by molecular terms which teach us how gene expression is regulated and controlled. Finally I will try to outline the limits of genetic analysis and how it raises ethical and moral questions. If the analysis of changes in the genetic read-out are related to diseases for which there is no therapy or if such knowledge only predisposes to genetic diseases the handling of such information requires extraordinary care. The genome projects thus have to be and are being pursued in conjunction with careful ethical analyses ...

Engineered CRISPR Systems for Next Generation Gene Therapies.

Science.gov (United States)

Pineda, Michael; Moghadam, Farzaneh; Ebrahimkhani, Mo R; Kiani, Samira

2017-09-15

An ideal in vivo gene therapy platform provides safe, reprogrammable, and precise strategies which modulate cell and tissue gene regulatory networks with a high temporal and spatial resolution. Clustered regularly interspaced short palindromic repeats (CRISPR), a bacterial adoptive immune system, and its CRISPR-associated protein 9 (Cas9), have gained attention for the ability to target and modify DNA sequences on demand with unprecedented flexibility and precision. The precision and programmability of Cas9 is derived from its complexation with a guide-RNA (gRNA) that is complementary to a desired genomic sequence. CRISPR systems open-up widespread applications including genetic disease modeling, functional screens, and synthetic gene regulation. The plausibility of in vivo genetic engineering using CRISPR has garnered significant traction as a next generation in vivo therapeutic. However, there are hurdles that need to be addressed before CRISPR-based strategies are fully implemented. Some key issues center on the controllability of the CRISPR platform, including minimizing genomic-off target effects and maximizing in vivo gene editing efficiency, in vivo cellular delivery, and spatial-temporal regulation. The modifiable components of CRISPR systems: Cas9 protein, gRNA, delivery platform, and the form of CRISPR system delivered (DNA, RNA, or ribonucleoprotein) have recently been engineered independently to design a better genome engineering toolbox. This review focuses on evaluating CRISPR potential as a next generation in vivo gene therapy platform and discusses bioengineering advancements that can address challenges associated with clinical translation of this emerging technology.

A Novel Nonviral Gene Delivery System: Multifunctional Envelope-Type Nano Device

Science.gov (United States)

Hatakeyama, Hiroto; Akita, Hidetaka; Kogure, Kentaro; Harashima, Hideyoshi

In this review we introduce a new concept for developing a nonviral gene delivery system which we call "Programmed Packaging." Based on this concept, we succeeded in developing a multifunctional envelope-type nano device (MEND), which exerts high transfection activities equivalent to those of an adenovirus in a dividing cell. The use of MEND has been extended to in vivo applications. PEG/peptide/DOPE ternary conjugate (PPD)-MEND, a new in vivo gene delivery system for the targeting of tumor cells that dissociates surface-modified PEG in tumor tissue by matrix metalloproteinase (MMP) and exerts significant transfection activities, was developed. In parallel with the development of MEND, a quantitative gene delivery system, Confocal Image-assisted 3-dimensionally integrated quantification (CIDIQ), also was developed. This method identified the rate-limiting step of the nonviral gene delivery system by comparing it with adenoviral-mediated gene delivery. The results of this analysis provide a new direction for the development of rational nonviral gene delivery systems.

Effects of Partial Beef Fat Replacement with Gelled Emulsion on Functional and Quality Properties of Model System Meat Emulsions.

Science.gov (United States)

Serdaroğlu, Meltem; Nacak, Berker; Karabıyıkoğlu, Merve; Keser, Gökçen

2016-01-01

The objective of this study was to investigate the effects of partial beef fat replacement (0, 30, 50, 100%) with gelled emulsion (GE) prepared with olive oil on functional and quality properties of model system meat emulsion (MSME). GE consisted of inulin and gelatin as gelling agent and characteristics of gelled and model system meat emulsions were investigated. GE showed good initial stability against centrifugation forces and thermal stability at different temperatures. GE addition decreased the pH with respect to increase in GE concentration. Addition of GE increased lightness and yellowness but reduced redness compared to control samples. The results of the study showed that partial replacement of beef fat with GE could be used for improving cooking yield without negative effects on water holding capacity and emulsion stability compared to C samples when replacement level is up to 50%. The presence of GE significantly affected textural behaviors of samples ( p <0.05). In conclusion, our study showed that GE have promising impacts on developing healthier meat product formulations besides improving technological characteristics.

Software-based annunciator replacement: a tale of two projects

International Nuclear Information System (INIS)

Simmons, G.T.

2015-01-01

Annunciator upgrade projects are often included as parts of operating plant life extension projects as the systems are old and replacement parts are difficult to source. This paper contains case studies of the software-based annunciator replacement projects at the Westinghouse SNUPPS training simulator in Pennsylvania and the Axpo Beznau nuclear power plant in Switzerland. Software-based annunciator systems can offer a number of feature enhancements including improved readability and operator awareness, easy configuration, alarm suppression features, and alarm management at operator workstations. This paper provides an overview of each project and discusses advantages, challenges, and lessons learned from both annunciator-replacement projects. (author)

Software-based annunciator replacement: a tale of two projects

Energy Technology Data Exchange (ETDEWEB)

Simmons, G.T., E-mail: simmongt@westinghouse.com [Westinghouse Electric Company LLC, Cranberry Township, PA (United States)

2015-07-01

Annunciator upgrade projects are often included as parts of operating plant life extension projects as the systems are old and replacement parts are difficult to source. This paper contains case studies of the software-based annunciator replacement projects at the Westinghouse SNUPPS training simulator in Pennsylvania and the Axpo Beznau nuclear power plant in Switzerland. Software-based annunciator systems can offer a number of feature enhancements including improved readability and operator awareness, easy configuration, alarm suppression features, and alarm management at operator workstations. This paper provides an overview of each project and discusses advantages, challenges, and lessons learned from both annunciator-replacement projects. (author)

Nicotine replacement therapy

Science.gov (United States)

Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Before you start using a nicotine replacement product, here are some things to know: The more cigarettes you smoke, the higher the dose you may need to ...

Gene inactivation in the plant pathogen Glomerella cingulata: three strategies for the disruption of the pectin lyase gene pnlA.

Science.gov (United States)

Bowen, J K; Templeton, M D; Sharrock, K R; Crowhurst, R N; Rikkerink, E H

1995-01-20

The feasibility of performing routine transformation-mediated mutagenesis in Glomerella cingulata was analysed by adopting three one-step gene disruption strategies targeted at the pectin lyase gene pnlA. The efficiencies of disruption following transformation with gene replacement- or gene truncation-disruption vectors were compared. To effect replacement-disruption, G. cingulata was transformed with a vector carrying DNA from the pnlA locus in which the majority of the coding sequence had been replaced by the gene for hygromycin B resistance. Two of the five transformants investigated contained an inactivated pnlA gene (pnlA-); both also contained ectopically integrated vector sequences. The efficacy of gene disruption by transformation with two gene truncation-disruption vectors was also assessed. Both vectors carried at 5' and 3' truncated copy of the pnlA coding sequence, adjacent to the gene for hygromycin B resistance. The promoter sequences controlling the selectable marker differed in the two vectors. In one vector the homologous G. cingulata gpdA promoter controlled hygromycin B phosphotransferase expression (homologous truncation vector), whereas in the second vector promoter elements were from the Aspergillus nidulans gpdA gene (heterologous truncation vector). Following transformation with the homologous truncation vector, nine transformants were analysed by Southern hybridisation; no transformants contained a disrupted pnlA gene. Of nineteen heterologous truncation vector transformants, three contained a disrupted pnlA gene; Southern analysis revealed single integrations of vector sequence at pnlA in two of these transformants. pnlA mRNA was not detected by Northern hybridisation in pnlA- transformants. pnlA- transformants failed to produce a PNLA protein with a pI identical to one normally detected in wild-type isolates by silver and activity staining of isoelectric focussing gels. Pathogenesis on Capsicum and apple was unaffected by disruption of

Hip Replacement Surgery

Science.gov (United States)

... Outreach Initiative Breadcrumb Home Health Topics English Español Hip Replacement Surgery Basics In-Depth Download Download EPUB ... PDF What is it? Points To Remember About Hip Replacement Surgery Hip replacement surgery removes damaged or ...

Plant process computer replacements - techniques to limit installation schedules and costs

International Nuclear Information System (INIS)

Baker, M.D.; Olson, J.L.

1992-01-01

Plant process computer systems, a standard fixture in all nuclear power plants, are used to monitor and display important plant process parameters. Scanning thousands of field sensors and alarming out-of-limit values, these computer systems are heavily relied on by control room operators. The original nuclear steam supply system (NSSS) vendor for the power plant often supplied the plant process computer. Designed using sixties and seventies technology, a plant's original process computer has been obsolete for some time. Driven by increased maintenance costs and new US Nuclear Regulatory Commission regulations such as NUREG-0737, Suppl. 1, many utilities have replaced their process computers with more modern computer systems. Given that computer systems are by their nature prone to rapid obsolescence, this replacement cycle will likely repeat. A process computer replacement project can be a significant capital expenditure and must be performed during a scheduled refueling outage. The object of the installation process is to install a working system on schedule. Experience gained by supervising several computer replacement installations has taught lessons that, if applied, will shorten the schedule and limit the risk of costly delays. Examples illustrating this technique are given. This paper and these examples deal only with the installation process and assume that the replacement computer system has been adequately designed, and development and factory tested

Multi-stage type replacing method of iodine filter

International Nuclear Information System (INIS)

Kitamura, Masao; Kamiya, Kunio.

1976-01-01

Object: To effectively replace a filter into a removing device of radioactive impurities used in ventilation and air conditioning system or the like in an atomic power plant. Structure: A plurality of elements of a filter are arranged in series relative to fluid. In the first replacement, an ante-filter-element on inlet side of fluid is removed, and a post-filter-element is repositioned to that position of the ante-element. Then, a fresh element is newly mounted on that position of the post-element. Replacement after the second time may be effected by repeating the operation noted above. With this arrangement, the minimal value of collection efficiency at replacement of filter may be increased. (Ikeda, J.)

Replacement of Co-base alloy for radiation exposure reduction in the primary system of PWR

International Nuclear Information System (INIS)

Han, Jeong Ho; Nyo, Kye Ho; Lee, Deok Hyun; Lim, Deok Jae; Ahn, Jin Keun; Kim, Sun Jin

1996-01-01

Of numerous Co-free alloys developed to replace Co-base stellite used in valve hardfacing material, two iron-base alloys of Armacor M and Tristelle 5183 and one nickel-base alloy of Nucalloy 488 were selected as candidate Co-free alloys, and Stellite 6 was also selected as a standard hardfacing material. These four alloys were welded on 316SS substrate using TIG welding method. The first corrosion test loop of KAERI simulating the water chemistry and operation condition of the primary system of PWR was designed and fabricated. Corrosion behaviors of the above four kinds of alloys were evaluated using this test loop under the condition of 300 deg C, 1500 psi. Microstructures of weldment of these alloys were observed to identify both matrix and secondary phase in each weldment. Hardnesses of weld deposit layer including HAZ and substrate were measured using micro-Vickers hardness tester. The status on the technology of Co-base alloy replacement in valve components was reviewed with respect to the classification of valves to be replaced, the development of Co-free alloys, the application of Co-free alloys and its experiences in foreign NPPs, and the Co reduction program in domestic NPPs and industries. 18 tabs., 20 figs., 22 refs. (Author)

A new three-dimensional, print-on-demand temporomandibular prosthetic total joint replacement system: Preliminary outcomes.

Science.gov (United States)

Dimitroulis, George; Austin, Stephen; Sin Lee, Peter Vee; Ackland, David

2018-05-16

The aim of this study is to present the preliminary clinical data on the OMX Temporomandibular Joint (TMJ) Prosthetic total joint replacement system. A prospective, cohort, clinical study was undertaken of consecutive adult patients with Category 5 end-stage joint disease who were implanted with the OMX TMJ prosthesis between May 2015 and April 2017. A total of 50 devices were implanted in 38 patients, with 12 patients receiving bilateral prosthetic joints. There were 31 females and 7 males in this cohort, who ranged in age from 20 to 66 years, with a mean of 43.8 years (±14.0 years). Ten of the 50 prosthetic joints (20%) were fully customized, while the remaining were patient matched using virtual planning software. Based on a mean follow-up period of 15.3 months (range 12-24 months) following the TMJ total joint replacement, preliminary results suggest the OMX TMJ prosthesis has made a positive impact on clinical outcomes, with a mean 74.4% reduction in joint pain levels and significant improvements (p < 0.05) in jaw function as measured by the visual analogue scales for mouth opening (30.8%), diet (77.1%), and function (59.2%). No device failures were reported during the study period. This study suggests that the print-on-demand OMX TMJ prosthesis, designed for rapid delivery of both patient-matched and fully customize devices, represents a safe, reliable and versatile implantable joint replacement system for the treatment of category 5 end-stage TMJ disease. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Knee Replacement

Science.gov (United States)

Knee replacement is surgery for people with severe knee damage. Knee replacement can relieve pain and allow you to ... Your doctor may recommend it if you have knee pain and medicine and other treatments are not ...

Nanobarcode gene expression monitoring system for potential miniaturized space applications

Science.gov (United States)

Ruan, Weiming; Eastman, P. Scott; Cooke, Patrick A.; Park, Jennifer S.; Chu, Julia S. F.; Gray, Joe W.; Li, Song; Chen, Fanqing Frank

Manned mission to space has been threatened by various cosmos risks including radiation, mirogravity, vacuum, confinement, etc., which may cause genetic variations of astronauts and eventually lead to damages of their health. Thus, the development of small biomedical devices, which can monitor astronaut gene expression changes, is useful for future long-term space missions. Using magnetic microbeads packed with nanocrystal quantum dots at controlled ratios, we were able to generate highly multiplexed nanobarcodes, which can encode a flexible panel of genes. Also, by using a reporter quantum dot, this nanobarcode platform can monitor and quantify gene expression level with improved speed and sensitivity. As a comparison, we studied TGF-β1 induced transcription changes in human bone marrow mesenchymal stem cells with both the nanobarcode microbead system and the Affymetrix GeneChip ® HTA system, which is currently considered as the industrial standard. Though using only 1/20 of the sample RNA, the nanobarcode system showed sensitivity equivalent to Affymetrix GeneChip ® system. The coefficient of variation, dynamic range, and accuracy of the nanobarcodes measurement is equivalent to that of the GeneChip ® HTA system. Therefore, this newly invented nanobarcode microbead platform is thought to be sensitive, flexible, cost-effective and accurate in a level equivalent to the conventional methods. As an extension of the use of this new platform, spacecrafts may carry this miniaturized system as a diagnostic tool for the astronauts.

Determination of D816V mutation in the c-kIt gene in the Slovenian patients with acute myeloid leukemia and systemic mastocytosis

Directory of Open Access Journals (Sweden)

Martina Fink

2012-12-01

Full Text Available Background: D816V mutation in the C-KIT gene is present in more than 90 % of patients with systemic mastocytosis (SM and 2–7 % of patients with acute myeloid leukemia (AML. D816V mutation is caused by the substitution of adenine with thymine at 2447 nucleotide sequence in the C-KIT gene. This nucleotide substitution causes the replacment of aspartate acid by valine at codon 816 of the KIT protein. KIT protein with D816V mutation acts as constitutively active tyrosine kinase that promotes cell proliferation and inhibits apoptosis. The purpose of our study was to determine the incidence of D816V mutation in the C-KIT gene in Slovenian patients with AML and in patients with suspected systemic mastocytosis. Patients and methods: In the retrospective study, 71 patients with AML and 25 patients with suspected systemic mastocytosis were included. D816V mutation in the C-KIT gene was determined by polymerase chain reaction (PCR and the resulting PCR products were analyzed by agarose gel electrophoresis. Results: D816V mutation in KIT protein was determined in 7 % of patients with AML and in 32 % patients with suspected systemic mastocytosis. Conclusions: Identification of D816V mutation in the C-KIT gene must always be performed in patients with suspected systemic mastocytosis. The determination of this mutation contributes to the diagnosis and treatment selection. The finding of D816V mutation in the C-KIT gene in patients with AML and concomitant genetic modifications RUNX-RUNX1T1 (typical translocation t(8; 21 (q22, q22 or CBFB-MYH11, which is the result of inversion on chromosome 16–(inv (16 (p13, q22, however, indicates a faster, more aggressive course of the disease and predicts a worse outcome. The finding of the mutation in other patients with AML may indicate the presence of concomitant AML and SM, which was not found in our patients.

Cadmium plating replacements

Energy Technology Data Exchange (ETDEWEB)

Nelson, M.J.; Groshart, E.C.

1995-03-01

The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

Proposed replacement and operation of the anhydrous hydrogen fluoride supply and fluidized-bed chemical processing systems at Building 9212, Y-12 Plant, Oak Ridge, Tennessee

International Nuclear Information System (INIS)

1995-09-01

The US Department of Energy (DOE) proposes to replace the existing anhydrous hydrogen fluoride (AHF) supply and fluidized-bed reactor systems for the Weapons Grade Highly Enriched Uranium Chemical Recovery and Recycle Facility, Building 9212, which is located within the Y-12 Plant on DOE's Oak Ridge Reservation in Oak Ridge, Tennessee. The proposed replacement system would be based upon modern design criteria and safety analyses. The replacement AHF supply and distribution system equipment would be located on the existing Dock 8/8A at Building 9212. Utilities would be extended to the dock to service the process equipment. The following process equipment modules would be prefabricated for installation at the modified dock: an AHF cylinder enclosure, an AHF supply manifold and vaporizer module, an AHF sump tank and transfer skid, and an AHF supply off-gas scrubber assembly module. The fluidized-bed reactor system would be constructed in an area adjacent to the existing system in Building 9212. The replacement equipment would consist of a new reduction fluidized-bed reactor, a hydrofluorination fluidized-bed reactor, and associated air emission control equipment. The no-action alternative, which is the continued operation of the existing AHF supply and fluidized-bed reactor systems, was also evaluated

Installation technology of reactor internals on shroud replacement work

International Nuclear Information System (INIS)

Miyano, Hiroshi

1999-01-01

Since the replacement of large welded reactor internals much as a core shroud did not have a precedent in the world, quite a few technologies had to be developed. Especially for the installation of new core shroud, jet pumps, core plate and top guide, the accurate weld and fit-up techniques for large structures was required to secure their integrity. The vessel shielding system was utilized to reduce general area dose rate such that all replacement work. For jet pump installation, automatic remote welding machines were used for high radiation area. As for the core shroud, shroud support weld prep machining tool with high accuracy, jacking system to support fit-up, new weld machine for small work space and low heat input weld joint were developed. Shroud replacement work in Fukushima Dai-ichi NPS Unit 3 (1F-3) with application of these development techniques, was successfully accomplished. The technology is applied for 1F-2 replacement work also. (author)

Myocardial gene expression of microRNA-133a and myosin heavy and light chains, in conjunction with clinical parameters, predict regression of left ventricular hypertrophy after valve replacement in patients with aortic stenosis.

Science.gov (United States)

Villar, Ana V; Merino, David; Wenner, Mareike; Llano, Miguel; Cobo, Manuel; Montalvo, Cecilia; García, Raquel; Martín-Durán, Rafael; Hurlé, Juan M; Hurlé, María A; Nistal, J Francisco

2011-07-01

Left ventricular (LV) reverse remodelling after valve replacement in aortic stenosis (AS) has been classically linked to the hydraulic performance of the replacement device, but myocardial status at the time of surgery has received little attention. To establish predictors of LV mass (LVM) regression 1 year after valve replacement in a surgical cohort of patients with AS based on preoperative clinical and echocardiographic parameters and the myocardial gene expression profile at surgery. Transcript levels of remodelling-related proteins and regulators were determined in LV intraoperative biopsies from 46 patients with AS by RT-PCR. Using multiple linear regression analysis, an equation was developed (adjusted R²=0.73; pregression analysis identified microRNA-133a as a significant positive predictor of LVM normalisation, whereas β-myosin heavy chain and BMI constituted negative predictors. Hypertrophy regression 1 year after pressure overload release is related to the preoperative myocardial expression of remodelling-related genes, in conjunction with the patient's clinical background. In this scenario, miR-133 emerges as a key element of the reverse remodelling process. Postoperative improvement of valve haemodynamics does not predict the degree of hypertrophy regression or LVM normalisation. These results led us to reconsider the current reverse remodelling paradigm and (1) to include criteria of hypertrophy reversibility in the decision algorithm used to decide timing for the operation; and (2) to modify other prevailing factors (overweight, diabetes, etc) known to maintain LV hypertrophy.

Nymphal RNAi: systemic RNAi mediated gene knockdown in juvenile grasshopper

Directory of Open Access Journals (Sweden)

Dong Ying

2005-10-01

Full Text Available Abstract Background Grasshopper serves as important model system in neuroscience, development and evolution. Representatives of this primitive insect group are also highly relevant targets of pest control efforts. Unfortunately, the lack of genetics or gene specific molecular manipulation imposes major limitations to the study of grasshopper biology. Results We investigated whether juvenile instars of the grasshopper species Schistocerca americana are conducive to gene silencing via the systemic RNAi pathway. Injection of dsRNA corresponding to the eye colour gene vermilion into first instar nymphs triggered suppression of ommochrome formation in the eye lasting through two instars equivalent to 10–14 days in absolute time. QRT-PCR analysis revealed a two fold decrease of target transcript levels in affected animals. Control injections of EGFP dsRNA did not result in detectable phenotypic changes. RT-PCR and in situ hybridization detected ubiquitous expression of the grasshopper homolog of the dsRNA channel protein gene sid-1 in embryos, nymphs and adults. Conclusion Our results demonstrate that systemic dsRNA application elicits specific and long-term gene silencing in juvenile grasshopper instars. The conservation of systemic RNAi in the grasshopper suggests that this pathway can be exploited for gene specific manipulation of juvenile and adult instars in a wide range of primitive insects.

Replacing the Engine In Your Car While You Are Still Driving It

Energy Technology Data Exchange (ETDEWEB)

Bjorklund, Eric A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-11-04

Replacing your accelerator’s timing system with a completely different architecture is not something that happens very often. Perhaps even rarer is the requirement that the replacement not interfere with the accelerator’s normal operational cycle. In 2011, The Los Alamos Neutron Science Center (LANSCE) began the purchasing and installation phase of a nine-year rolling upgrade project which will eventually result in the complete replacement of the low-level RF system, the timing system, the industrial I/O system, the beam-synchronized data acquisition system, the fastprotect reporting system, and much of the diagnostic equipment. These projects are mostly independent of each other, with their own installation schedules, priorities, and time-lines. All of them, however, must interface with the timing system.

Gene Therapy with the Sleeping Beauty Transposon System.

Science.gov (United States)

Kebriaei, Partow; Izsvák, Zsuzsanna; Narayanavari, Suneel A; Singh, Harjeet; Ivics, Zoltán

2017-11-01

The widespread clinical implementation of gene therapy requires the ability to stably integrate genetic information through gene transfer vectors in a safe, effective, and economical manner. The latest generation of Sleeping Beauty (SB) transposon vectors fulfills these requirements, and may overcome limitations associated with viral gene transfer vectors and transient nonviral gene delivery approaches that are prevalent in ongoing clinical trials. The SB system enables high-level stable gene transfer and sustained transgene expression in multiple primary human somatic cell types, thereby representing a highly attractive gene transfer strategy for clinical use. Here, we review the most important aspects of using SB for gene therapy, including vectorization as well as genomic integration features. We also illustrate the path to successful clinical implementation by highlighting the application of chimeric antigen receptor (CAR)-modified T cells in cancer immunotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reducing replacement donors in Sub-Saharan Africa: challenges and affordability.

Science.gov (United States)

Bates, I; Manyasi, G; Medina Lara, A

2007-12-01

In 1975, the World Health Assembly recommended that blood for transfusion should come from voluntary, non-remunerated donors; yet, in Africa, 75-80% of blood for transfusion still comes from hospital-based replacement donors. Although comprehensive economic data are scarce, evidence indicates that blood from voluntary donors recruited and screened at centralized transfusion centres, costs four to eight times as much as blood from a hospital-based, replacement donor system. Donor recruitment, quality assurance systems and distribution mechanisms in the centralized system are major reasons for the cost difference. There are concerns about the sustainability of centralized voluntary donor systems and their compatibility with the levels of health care that exist in many poor countries yet burdening patients' families with the responsibility of finding replacement blood donors will exacerbate poverty and reduce the safety of the blood supply. There are measures that can be introduced into hospital-based systems to improve safe blood supply in Africa but their effectiveness in different contexts needs to be evaluated.

Defining line replaceable units

NARCIS (Netherlands)

Parada Puig, J. E.; Basten, R. J I

2015-01-01

Defective capital assets may be quickly restored to their operational condition by replacing the item that has failed. The item that is replaced is called the Line Replaceable Unit (LRU), and the so-called LRU definition problem is the problem of deciding on which item to replace upon each type of

Short- and Long-Term Lead Release after Partial Lead Service Line Replacements in a Metropolitan Water Distribution System.

Science.gov (United States)

Deshommes, Elise; Laroche, Laurent; Deveau, Dominique; Nour, Shokoufeh; Prévost, Michèle

2017-09-05

Thirty-three households were monitored in a full-scale water distribution system, to investigate the impact of recent (sampling over a period of 1-20 months. Point-of-entry filters were installed to capture sporadic release of particulate lead from the lead service lines (LSLs). Mean concentrations increased immediately after PLSLRs and erratic particulate lead spikes were observed over the 18 month post-PLSLR monitoring period. The mass of lead released during this time frame indicates the occurrence of galvanic corrosion and scale destabilization. System-wide, lead concentrations were however lower in households with PLSLRs as compared to those with no replacement, especially for old PLSLRs. Nonetheless, 61% of PLSLR samples still exceeded 10 μg/L, reflecting the importance of implementing full LSL replacement and efficient risk communication. Acute concentrations measured immediately after PLSLRs demonstrate the need for appropriate flushing procedures to prevent lead poisoning.

Principles of Human Joint Replacement Design and Clinical Application

CERN Document Server

Buechel, Frederick F

2012-01-01

Drs. Buechel, an orthopaedic surgeon, and Pappas, a professor of Mechanical Engineering, are the designers of several successful joint replacement systems. The most well-known of these is the pioneering LCS knee replacement. They have written this book for the users and designers of joint replacements. It is an attempt to convey to the reader the knowledge accumulated by the authors during their thirty five year effort on the development of replacement devices for the lower limb for the purpose of aiding the reader in their design and evaluation of joint replacement devices. The early chapters describe the engineering, scientific and medical principles needed for replacement joint evaluation. One must understand the nature and performance of the materials involved and their characteristics in vivo, i.e. the response of the body to implant materials. It is also essential to understand the response of the implants to applied loading and motion, particularly in the hostile physiological environment. A chapter de...

Hardware replacements and software tools for digital control computers

International Nuclear Information System (INIS)

Walker, R.A.P.; Wang, B-C.; Fung, J.

1996-01-01

Technological obsolescence is an on-going challenge for all computer use. By design, and to some extent good fortune, AECL has had a good track record with respect to the march of obsolescence in CANDU digital control computer technology. Recognizing obsolescence as a fact of life, AECL has undertaken a program of supporting the digital control technology of existing CANDU plants. Other AECL groups are developing complete replacement systems for the digital control computers, and more advanced systems for the digital control computers of the future CANDU reactors. This paper presents the results of the efforts of AECL's DCC service support group to replace obsolete digital control computer and related components and to provide friendlier software technology related to the maintenance and use of digital control computers in CANDU. These efforts are expected to extend the current lifespan of existing digital control computers through their mandated life. This group applied two simple rules; the product, whether new or replacement should have a generic basis, and the products should be applicable to both existing CANDU plants and to 'repeat' plant designs built using current design guidelines. While some exceptions do apply, the rules have been met. The generic requirement dictates that the product should not be dependent on any brand technology, and should back-fit to and interface with any such technology which remains in the control design. The application requirement dictates that the product should have universal use and be user friendly to the greatest extent possible. Furthermore, both requirements were designed to anticipate user involvement, modifications and alternate user defined applications. The replacements for hardware components such as paper tape reader/punch, moving arm disk, contact scanner and Ramtek are discussed. The development of these hardware replacements coincide with the development of a gateway system for selected CANDU digital control

Gene expression programming for power system static security ...

African Journals Online (AJOL)

user

Keywords: static security, gene expression programming, probabilistic neural network ... Hence digital computers are usually installed in operations control centers to gather ...... power system protection, and applications of AI in power systems.

Prioritization methodology for chemical replacement

Science.gov (United States)

Cruit, Wendy; Goldberg, Ben; Schutzenhofer, Scott

1995-01-01

Since United States of America federal legislation has required ozone depleting chemicals (class 1 & 2) to be banned from production, The National Aeronautics and Space Administration (NASA) and industry have been required to find other chemicals and methods to replace these target chemicals. This project was initiated as a development of a prioritization methodology suitable for assessing and ranking existing processes for replacement 'urgency.' The methodology was produced in the form of a workbook (NASA Technical Paper 3421). The final workbook contains two tools, one for evaluation and one for prioritization. The two tools are interconnected in that they were developed from one central theme - chemical replacement due to imposed laws and regulations. This workbook provides matrices, detailed explanations of how to use them, and a detailed methodology for prioritization of replacement technology. The main objective is to provide a GUIDELINE to help direct the research for replacement technology. The approach for prioritization called for a system which would result in a numerical rating for the chemicals and processes being assessed. A Quality Function Deployment (QFD) technique was used in order to determine numerical values which would correspond to the concerns raised and their respective importance to the process. This workbook defines the approach and the application of the QFD matrix. This technique: (1) provides a standard database for technology that can be easily reviewed, and (2) provides a standard format for information when requesting resources for further research for chemical replacement technology. Originally, this workbook was to be used for Class 1 and Class 2 chemicals, but it was specifically designed to be flexible enough to be used for any chemical used in a process (if the chemical and/or process needs to be replaced). The methodology consists of comparison matrices (and the smaller comparison components) which allow replacement technology

Meal Replacement Mass Reduction and Integration Acceptability Study

Science.gov (United States)

Sirmons, T.; Barrett, A.; Richardson, M.; Arias, D.; Schneiderman, J.; Slack, K.; Williams, T.; Douglas, G.

2017-01-01

NASA, in planning for long-duration missions, has an imperative to provide a food system with the necessary nutrition, acceptability, and safety to ensure sustainment of crew health and performance. The Orion Multi-Purpose Crew Vehicle (MPCV) and future exploration missions are mass constrained; therefore the team is challenged to reduce the mass of the food system by 10% while maintaining product safety, nutrition, and acceptability. Commercially available products do not meet the nutritional requirements for a full meal replacement in the spaceflight food system, and it is currently unknown if daily meal replacements will impact crew food intake and psychosocial health over time. The purpose of this study was to develop a variety of nutritionally balanced breakfast replacement bars that meet spaceflight nutritional, microbiological, sensorial, and shelf-life requirements, while enabling a 10% savings in food mass. To date, six nutrient-dense meal replacement bars (approximately 700 calories per bar) have been developed, using traditional methods of compression as well as novel ultrasonic compression technologies developed by Creative Resonance Inc. (Phoenix, AZ). The four highest rated bars were evaluated in the Human Exploration Research Analog (HERA) to assess the frequency with which actual meal replacement options may be implemented. Specifically, overall impact of bars on mood, satiety, digestive discomfort, and satisfaction with food. These factors are currently being analyzed to inform successful implementation strategies where crew maintain adequate food intake. In addition, these bars are currently undergoing shelf-life testing to determine long-term sensory acceptability, nutritional stability, qualitative stability of analytical measurements (i.e. water activity and texture), and microbiological compliance over two years of storage at room temperature and potential temperature abuse conditions to predict long-term acceptability. It is expected that

Transmission of the PabI family of restriction DNA glycosylase genes: mobility and long-term inheritance.

Science.gov (United States)

Kojima, Kenji K; Kobayashi, Ichizo

2015-10-19

R.PabI is an exceptional restriction enzyme that functions as a DNA glycosylase. The enzyme excises an unmethylated base from its recognition sequence to generate apurinic/apyrimidinic (AP) sites, and also displays AP lyase activity, cleaving the DNA backbone at the AP site to generate the 3'-phospho alpha, beta-unsaturated aldehyde end in addition to the 5'-phosphate end. The resulting ends are difficult to religate with DNA ligase. The enzyme was originally isolated in Pyrococcus, a hyperthermophilic archaeon, and additional homologs subsequently identified in the epsilon class of the Gram-negative bacterial phylum Proteobacteria, such as Helicobacter pylori. Systematic analysis of R.PabI homologs and their neighboring genes in sequenced genomes revealed co-occurrence of R.PabI with M.PabI homolog methyltransferase genes. R.PabI and M.PabI homolog genes are occasionally found at corresponding (orthologous) loci in different species, such as Helicobacter pylori, Helicobacter acinonychis and Helicobacter cetorum, indicating long-term maintenance of the gene pair. One R.PabI and M.PabI homolog gene pair is observed immediately after the GMP synthase gene in both Campylobacter and Helicobacter, representing orthologs beyond genera. The mobility of the PabI family of restriction-modification (RM) system between genomes is evident upon comparison of genomes of sibling strains/species. Analysis of R.PabI and M.PabI homologs in H. pylori revealed an insertion of integrative and conjugative elements (ICE), and replacement with a gene of unknown function that may specify a membrane-associated toxin (hrgC). In view of the similarity of HrgC with toxins in type I toxin-antitoxin systems, we addressed the biological significance of this substitution. Our data indicate that replacement with hrgC occurred in the common ancestor of hspAmerind and hspEAsia. Subsequently, H. pylori with and without hrgC were intermixed at this locus, leading to complex distribution of hrgC in East

21 CFR 866.5900 - Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system.

Science.gov (United States)

2010-04-01

... regulator (CFTR) gene mutation detection system. 866.5900 Section 866.5900 Food and Drugs FOOD AND DRUG...) gene mutation detection system. (a) Identification. The CFTR gene mutation detection system is a device... Guidance Document: CFTR Gene Mutation Detection System.” See § 866.1(e) for the availability of this...

Optimal inspection and replacement periods of the safety system in Wolsung Nuclear Power Plant Unit 1 with an optimized cost perspective

International Nuclear Information System (INIS)

Jinil Mok; Poong Hyun Seong

1996-01-01

In this work, a model for determining the optimal inspection and replacement periods of the safety system in Wolsung Nuclear Power Plant Unit 1 is developed, which is to minimize economic loss caused by inadvertent trip and the system failure. This model uses cost benefit analysis method and the part for optimal inspection period considers the human error. The model is based on three factors as follows: (i) The cumulative failure distribution function of the safety system, (ii) The probability that the safety system does not operate due to failure of the system or human error when the safety system is needed at an emergency condition and (iii) The average probability that the reactor is tripped due to the failure of system components or human error. The model then is applied to evaluate the safety system in Wolsung Nuclear Power Plant Unit 1. The optimal replacement periods which are calculated with proposed model differ from those used in Wolsung NPP Unit 1 by about a few days or months, whereas the optimal inspection periods are in about the same range. (author)

Replacement energy, capacity, and reliability costs for permanent nuclear reactor shutdowns

International Nuclear Information System (INIS)

VanKuiken, J.C., Buehring, W.A.; Hamilton, S.; Kavicky, J.A.; Cavallo, J.D.; Veselka, T.D.; Willing, D.L.

1993-10-01

Average replacement power costs are estimated for potential permanent shutdowns of nuclear electricity-generating units. Replacement power costs are considered to include replacement energy, capacity, and reliability cost components. These estimates were developed to assist the US Nuclear Regulatory Commission in evaluating regulatory issues that potentially affect changes in serious reactor accident frequencies. Cost estimates were derived from long-term production-cost and capacity expansion simulations of pooled utility-system operations. Factors that affect replacement power cost, such as load growth, replacement sources of generation, and capital costs for replacement capacity, were treated in the analysis. Costs are presented for a representative reactor and for selected subcategories of reactors, based on estimates for 112 individual reactors

A DNA fragment from Xq21 replaces a deleted region containing the entire FVIII gene in a severe hemophilia A patient

Energy Technology Data Exchange (ETDEWEB)

Murru, S.; Casula, L.; Moi, P. [Insituto di Clinica e Biologia dell` Eta Evolutiva, Cagliari (Italy)] [and others

1994-09-15

In this paper the authors report the molecular characterization of a large deletion that removes the entire Factor VIII gene in a severe hemophilia A patient. Accurate DNA analysis of the breakpoint region revealed that a large DNA fragment replaced the 300-kb one, which was removed by the deletion. Pulsed-field gel electrophoresis analysis revealed that the size of the inserted fragment is about 550 kb. In situ hybridization demonstrated that part of the inserted region normally maps to Xq21 and to the tip of the short arm of the Y chromosome (Yp). In this patient this locus is present both in Xq21 and in Xq28, in addition to the Yp, being thus duplicated in the X chromosome. Sequence analysis of the 3` breakpoint suggested that an illegitimate recombination is probably the cause of this complex rearrangement. 52 refs., 7 figs.

Functional Analysis of an ATP-Binding Cassette Transporter Gene in Botrytis cinerea by Gene Disruption

OpenAIRE

Masami, NAKAJIMA; Junko, SUZUKI; Takehiko, HOSAKA; Tadaaki, HIBI; Katsumi, AKUTSU; School of Agriculture, Ibaraki University; School of Agriculture, Ibaraki University; School of Agriculture, Ibaraki University; Department of Agriculture and Environmental Biology, The University of Tokyo; School of Agriculture, Ibaraki University

2001-01-01

The BMR1 gene encoding an ABC transporter was cloned from Botrytis cinerea. To examine the function of BMR1 in B.cinerea, we isolated BMR1-deficient mutants after gene disruption. Disruption vector pBcDF4 was constructed by replacing the BMR1-coding region with a hygromycin B phosphotransferase gene(hph)cassette. The BMR1 disruptants had an increased sensitivity to polyoxin and iprobenfos. Polyoxin and iprobenfos, structurally unrelated compounds, may therefore be substrates of BMR1.

Handbook of camera monitor systems the automotive mirror-replacement technology based on ISO 16505

CERN Document Server

2016-01-01

This handbook offers a comprehensive overview of Camera Monitor Systems (CMS), ranging from the ISO 16505-based development aspects to practical realization concepts. It offers readers a wide-ranging discussion of the science and technology of CMS as well as the human-interface factors of such systems. In addition, it serves as a single reference source with contributions from leading international CMS professionals and academic researchers. In combination with the latest version of UN Regulation No. 46, the normative framework of ISO 16505 permits CMS to replace mandatory rearview mirrors in series production vehicles. The handbook includes scientific and technical background information to further readers’ understanding of both of these regulatory and normative texts. It is a key reference in the field of automotive CMS for system designers, members of standardization and regulation committees, engineers, students and researchers.

Genome-wide analysis of immune system genes by EST profiling

Science.gov (United States)

Giallourakis, Cosmas; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Zukerberg, Lawrence R.; Daly, Mark J.; Rioux, John D.; Xavier, Ramnik J.

2013-01-01

Profiling studies of mRNA and miRNA, particularly microarray-based studies, have been extensively used to create compendia of genes that are preferentially expressed in the immune system. In some instances, functional studies have been subsequently pursued. Recent efforts such as ENCODE have demonstrated the benefit of coupling RNA-Seq analysis with information from expressed sequence tags (ESTs) for transcriptomic analysis. However, the full characterization and identification of transcripts that function as modulators of human immune responses remains incomplete. In this study, we demonstrate that an integrated analysis of human ESTs provides a robust platform to identify the immune transcriptome. Beyond recovering a reference set of immune-enriched genes and providing large-scale cross-validation of previous microarray studies, we discovered hundreds of novel genes preferentially expressed in the immune system, including non-coding RNAs. As a result, we have established the Immunogene database, representing an integrated EST “road map” of gene expression in human immune cells, which can be used to further investigate the function of coding and non-coding genes in the immune system. Using this approach, we have uncovered a unique metabolic gene signature of human macrophages and identified PRDM15 as a novel overexpressed gene in human lymphomas. Thus we demonstrate the utility of EST profiling as a basis for further deconstruction of physiologic and pathologic immune processes. PMID:23616578

Development of a remote handling system for replacement of armor tiles in the Fusion Experimental Reactor

International Nuclear Information System (INIS)

Adachi, J.; Kakudate, S.; Oka, K.; Seki, M.

1995-01-01

The armor tiles of the Fusion Experimental Reactor (FER) planned by JAERI are categorized as scheduled maintenance components, since they are damaged by severe heat and particle loads from the plasma during operation. A remote handling system is thus required to replace a large number of tiles rapidly in the highly activated reactor. However, the simple teaching-playback method cannot be adapted to this system because of deflection of the tiles caused by thermal deformation and so on. We have developed a control system using visual feedback control to adapt to this deflection and an end-effector for a single arm. We confirm their performance in tests. (orig.)

Gene delivery systems by the combination of lipid bubbles and ultrasound.

Science.gov (United States)

Negishi, Yoichi; Endo-Takahashi, Yoko; Maruyama, Kazuo

2016-11-28

Gene therapy is promising for the treatment of many diseases including cancers and genetic diseases. From the viewpoint of safety, ultrasound (US)-mediated gene delivery with nano/ microbubbles was recently developed as a novel non-viral vector system. US-mediated gene delivery using nano/microbubbles are able to produce transient changes in the permeability of the cell membrane after US-induced cavitation while reducing cellular damage and enables the tissue-specific or the site-specific intracellular delivery of gene both in vitro and in vivo. We have recently developed novel lipid nanobubbles (Lipid Bubbles). These nanobubbles can also be used to enhance the efficacy of the US-mediated genes (plasmid DNA, siRNA, and miRNA etc.) delivery. In this review, we describe US-mediated delivery systems combined with nano/microbubbles and discuss their feasibility as non-viral vector systems.

Integration technique of digital I and C replacement and its Critical Digital Review procedure

International Nuclear Information System (INIS)

Huang, Hui-Wen; Yang, Wen-Long

2013-01-01

Highlights: ► A digital I and C replacement integration technique have been developed. ► Establishment of Nuclear Power Plant Digital Replacement Integration Guideline. ► Preliminary Investigation on I and C System Digitalization. ► Evaluation on I and C System Digitalization. ► Establishment of I and C System Digitalization Architectures. -- Abstract: Institute 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: (1) Establishment of Nuclear Power Plant Digital 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 Institute (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 (SV and V), Failure Mode and Effects Analysis (FMEA), Evaluation of Diversity and Defense-in-depth (D3), Evaluation of

Transcatheter aortic valve replacement

Science.gov (United States)

... gov/ency/article/007684.htm Transcatheter aortic valve replacement To use the sharing features on this page, please enable JavaScript. Transcatheter aortic valve replacement (TAVR) is surgery to replace the aortic valve. ...

Gene annotation from scientific literature using mappings between keyword systems.

Science.gov (United States)

Pérez, Antonio J; Perez-Iratxeta, Carolina; Bork, Peer; Thode, Guillermo; Andrade, Miguel A

2004-09-01

The description of genes in databases by keywords helps the non-specialist to quickly grasp the properties of a gene and increases the efficiency of computational tools that are applied to gene data (e.g. searching a gene database for sequences related to a particular biological process). However, the association of keywords to genes or protein sequences is a difficult process that ultimately implies examination of the literature related to a gene. To support this task, we present a procedure to derive keywords from the set of scientific abstracts related to a gene. Our system is based on the automated extraction of mappings between related terms from different databases using a model of fuzzy associations that can be applied with all generality to any pair of linked databases. We tested the system by annotating genes of the SWISS-PROT database with keywords derived from the abstracts linked to their entries (stored in the MEDLINE database of scientific references). The performance of the annotation procedure was much better for SWISS-PROT keywords (recall of 47%, precision of 68%) than for Gene Ontology terms (recall of 8%, precision of 67%). The algorithm can be publicly accessed and used for the annotation of sequences through a web server at http://www.bork.embl.de/kat

A systemic gene silencing method suitable for high throughput, reverse genetic analyses of gene function in fern gametophytes

Directory of Open Access Journals (Sweden)

Tanurdzic Milos

2004-04-01

Full Text Available Abstract Background Ceratopteris richardii is a useful experimental system for studying gametophyte development and sexual reproduction in plants. However, few tools for cloning mutant genes or disrupting gene function exist for this species. The feasibility of systemic gene silencing as a reverse genetics tool was examined in this study. Results Several DNA constructs targeting a Ceratopteris protoporphyrin IX magnesium chelatase (CrChlI gene that is required for chlorophyll biosynthesis were each introduced into young gametophytes by biolistic delivery. Their transient expression in individual cells resulted in a colorless cell phenotype that affected most cells of the mature gametophyte, including the meristem and gametangia. The colorless phenotype was associated with a 7-fold decrease in the abundance of the endogenous transcript. While a construct designed to promote the transient expression of a CrChlI double stranded, potentially hairpin-forming RNA was found to be the most efficient in systemically silencing the endogenous gene, a plasmid containing the CrChlI cDNA insert alone was sufficient to induce silencing. Bombarded, colorless hermaphroditic gametophytes produced colorless embryos following self-fertilization, demonstrating that the silencing signal could be transmitted through gametogenesis and fertilization. Bombardment of young gametophytes with constructs targeting the Ceratopteris filamentous temperature sensitive (CrFtsZ and uroporphyrin dehydrogenase (CrUrod genes also produced the expected mutant phenotypes. Conclusion A method that induces the systemic silencing of target genes in the Ceratopteris gametophyte is described. It provides a simple, inexpensive and rapid means to test the functions of genes involved in gametophyte development, especially those involved in cellular processes common to all plants.

ARP/wARP and molecular replacement: the next generation

International Nuclear Information System (INIS)

Cohen, Serge X.; Ben Jelloul, Marouane; Long, Fei; Vagin, Alexei; Knipscheer, Puck; Lebbink, Joyce; Sixma, Titia K.; Lamzin, Victor S.; Murshudov, Garib N.; Perrakis, Anastassis

2008-01-01

A systematic test shows how ARP/wARP deals with automated model building for structures that have been solved by molecular replacement. A description of protocols in the flex-wARP control system and studies of two specific cases are also presented. Automatic iterative model (re-)building, as implemented in ARP/wARP and its new control system flex-wARP, is particularly well suited to follow structure solution by molecular replacement. More than 100 molecular-replacement solutions automatically solved by the BALBES software were submitted to three standard protocols in flex-wARP and the results were compared with final models from the PDB. Standard metrics were gathered in a systematic way and enabled the drawing of statistical conclusions on the advantages of each protocol. Based on this analysis, an empirical estimator was proposed that predicts how good the final model produced by flex-wARP is likely to be based on the experimental data and the quality of the molecular-replacement solution. To introduce the differences between the three flex-wARP protocols (keeping the complete search model, converting it to atomic coordinates but ignoring atom identities or using the electron-density map calculated from the molecular-replacement solution), two examples are also discussed in detail, focusing on the evolution of the models during iterative rebuilding. This highlights the diversity of paths that the flex-wARP control system can employ to reach a nearly complete and accurate model while actually starting from the same initial information

Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters

NARCIS (Netherlands)

Tetteh, Paul W.; Basak, Onur; Farin, Henner F.; Wiebrands, Kay; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; De Sauvage, Frederic; Van Es, Johan H.; Van Oudenaarden, Alexander; Clevers, Hans

2016-01-01

Intestinal crypts display robust regeneration upon injury. The relatively rare secretory precursors can replace lost stem cells, but it is unknown if the abundant enterocyte progenitors that express the Alkaline phosphate intestinal (Alpi) gene also have this capacity. We created an

Selective Constraints on Coding Sequences of Nervous System Genes Are a Major Determinant of Duplicate Gene Retention in Vertebrates.

Science.gov (United States)

Roux, Julien; Liu, Jialin; Robinson-Rechavi, Marc

2017-11-01

The evolutionary history of vertebrates is marked by three ancient whole-genome duplications: two successive rounds in the ancestor of vertebrates, and a third one specific to teleost fishes. Biased loss of most duplicates enriched the genome for specific genes, such as slow evolving genes, but this selective retention process is not well understood. To understand what drives the long-term preservation of duplicate genes, we characterized duplicated genes in terms of their expression patterns. We used a new method of expression enrichment analysis, TopAnat, applied to in situ hybridization data from thousands of genes from zebrafish and mouse. We showed that the presence of expression in the nervous system is a good predictor of a higher rate of retention of duplicate genes after whole-genome duplication. Further analyses suggest that purifying selection against the toxic effects of misfolded or misinteracting proteins, which is particularly strong in nonrenewing neural tissues, likely constrains the evolution of coding sequences of nervous system genes, leading indirectly to the preservation of duplicate genes after whole-genome duplication. Whole-genome duplications thus greatly contributed to the expansion of the toolkit of genes available for the evolution of profound novelties of the nervous system at the base of the vertebrate radiation. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Replacement of HCFC-225 Solvent for Cleaning NASA Propulsion Oxygen Systems

Science.gov (United States)

Mitchell, Mark A.; Lowrey, Nikki M.

2015-01-01

Since the 1990's, when the Class I Ozone Depleting Substance (ODS) chlorofluorocarbon-113 (CFC-113) was banned, NASA's rocket propulsion test facilities at Marshall Space Flight Center (MSFC) and Stennis Space Center (SSC) have relied upon hydrochlorofluorocarbon-225 (HCFC-225) to safely clean and verify the cleanliness of large scale propulsion oxygen systems. Effective January 1, 2015, the production, import, export, and new use of HCFC-225, a Class II ODS, was prohibited by the Clean Air Act. In 2012 through 2014, leveraging resources from both the NASA Rocket Propulsion Test Program and the Defense Logistics Agency - Aviation Hazardous Minimization and Green Products Branch, test labs at MSFC, SSC, and Johnson Space Center's White Sands Test Facility (WSTF) collaborated to seek out, test, and qualify a replacement for HCFC-225 that is both an effective cleaner and safe for use with oxygen systems. Candidate solvents were selected and a test plan was developed following the guidelines of ASTM G127, Standard Guide for the Selection of Cleaning Agents for Oxygen Systems. Solvents were evaluated for materials compatibility, oxygen compatibility, cleaning effectiveness, and suitability for use in cleanliness verification and field cleaning operations. Two solvents were determined to be acceptable for cleaning oxygen systems and one was chosen for implementation at NASA's rocket propulsion test facilities. The test program and results are summarized. This project also demonstrated the benefits of cross-agency collaboration in a time of limited resources.

Plant Core Environmental Stress Response Genes Are Systemically Coordinated during Abiotic Stresses

Directory of Open Access Journals (Sweden)

Kenneth W. Berendzen

2013-04-01

Full Text Available Studying plant stress responses is an important issue in a world threatened by global warming. Unfortunately, comparative analyses are hampered by varying experimental setups. In contrast, the AtGenExpress abiotic stress experiment displays intercomparability. Importantly, six of the nine stresses (wounding, genotoxic, oxidative, UV-B light, osmotic and salt can be examined for their capacity to generate systemic signals between the shoot and root, which might be essential to regain homeostasis in Arabidopsis thaliana. We classified the systemic responses into two groups: genes that are regulated in the non-treated tissue only are defined as type I responsive and, accordingly, genes that react in both tissues are termed type II responsive. Analysis of type I and II systemic responses suggest distinct functionalities, but also significant overlap between different stresses. Comparison with salicylic acid (SA and methyl-jasmonate (MeJA responsive genes implies that MeJA is involved in the systemic stress response. Certain genes are predominantly responding in only one of the categories, e.g., WRKY genes respond mainly non-systemically. Instead, genes of the plant core environmental stress response (PCESR, e.g., ZAT10, ZAT12, ERD9 or MES9, are part of different response types. Moreover, several PCESR genes switch between the categories in a stress-specific manner.

Systemic gene delivery to the central nervous system using Adeno-associated virus

Directory of Open Access Journals (Sweden)

Mathieu eBOURDENX

2014-06-01

Full Text Available Adeno-associated virus (AAV-mediated gene delivery has emerged as an effective and safe tool for both preclinical and clinical studies of neurological disorders. The recent discovery that several serotypes are able to cross the blood-brain-barrier when administered systemically has been a real breakthrough in the field of neurodegenerative diseases. Widespread transgene expression after systemic injection could spark interest as a therapeutic approach. Such strategy will avoid invasive brain surgery and allow non-focal gene therapy promising for CNS diseases affecting large portion of the brain. Here, we will review the recent results achieved through different systemic routes of injection generated in the last decade using systemic AAV-mediated delivery and propose a brief assessment of their values. In particular, we emphasize how the methods used for virus engineering could improve brain transduction after peripheral delivery.

Different polyamine pathways from bacteria have replaced eukaryotic spermidine biosynthesis in ciliates Tetrahymena thermophila and Paramecium tetaurelia.

Science.gov (United States)

Li, Bin; Kim, Sok Ho; Zhang, Yang; Hanfrey, Colin C; Elliott, Katherine A; Ealick, Steven E; Michael, Anthony J

2015-09-01

The polyamine spermidine is absolutely required for growth and cell proliferation in eukaryotes, due to its role in post-translational modification of essential translation elongation factor eIF5A, mediated by deoxyhypusine synthase. We have found that free-living ciliates Tetrahymena and Paramecium lost the eukaryotic genes encoding spermidine biosynthesis: S-adenosylmethionine decarboxylase (AdoMetDC) and spermidine synthase (SpdSyn). In Tetrahymena, they were replaced by a gene encoding a fusion protein of bacterial AdoMetDC and SpdSyn, present as three copies. In Paramecium, a bacterial homospermidine synthase replaced the eukaryotic genes. Individual AdoMetDC-SpdSyn fusion protein paralogues from Tetrahymena exhibit undetectable AdoMetDC activity; however, when two paralogous fusion proteins are mixed, AdoMetDC activity is restored and spermidine is synthesized. Structural modelling indicates a functional active site is reconstituted by sharing critical residues from two defective protomers across the heteromer interface. Paramecium was found to accumulate homospermidine, suggesting it replaces spermidine for growth. To test this concept, a budding yeast spermidine auxotrophic strain was found to grow almost normally with homospermidine instead of spermidine. Biosynthesis of spermidine analogue aminopropylcadaverine, but not exogenously provided norspermidine, correlated with some growth. Finally, we found that diverse single-celled eukaryotic parasites and multicellular metazoan Schistosoma worms have lost the spermidine biosynthetic pathway but retain deoxyhypusine synthase. © 2015 John Wiley & Sons Ltd.

LS1 Report: Replacing an antique

CERN Multimedia

CERN Bulletin

2013-01-01

At the PS Booster, the old beam dump and the shielding blocks surrounding it have been removed (see here). Installation of the new beam dump is now under way (see video).   The new PSB beam dump during its installation. At the PS, replacement of the old cooling and ventilation system, which dated back to 1957, is progressing well. The dismantling phase has just been completed and the tunnel is being prepared to receive a brand new ventilation system offering more efficient aeration of radioactive areas. At the same time, testing of the newly installed access system is under way. At the SPS, all the equipment of the Long Straight Section 1 (LSS1) has been removed to make way for the campaign to replace the irradiated cables, which started this week. In the LHC, the Radiation to Electronics (R2E) campaign is still progressing at a good clip, especially at Point 1, where the teams are two and a half months ahead of schedule. The Superconducting Magnets and Circuits Consolidation (SMACC) proje...

Ankle replacement - discharge

Science.gov (United States)

... total - discharge; Total ankle arthroplasty - discharge; Endoprosthetic ankle replacement - discharge; Osteoarthritis - ankle ... You had an ankle replacement. Your surgeon removed and reshaped ... an artificial ankle joint. You received pain medicine and were ...

Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

Science.gov (United States)

Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

2014-01-01

Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

[Construction and Function Verification of a Novel Shuttle Vector Containing a Marker Gene Self-deletion System].

Science.gov (United States)

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.

Patients Unicondylar Knee Replacement vs. Total Knee Replacement

OpenAIRE

Hedra Eskander

2017-01-01

The aim of this review article is to analyse the clinical effectiveness of total knee replacement (TKR) compared to unicondylar knee replacement (UKR) on patients. In terms of survival rates, revision rates and postoperative complications. The keywords used were: knee arthroplasty. Nearly three thousand articles were found on 25 August 2016. Of those, only twenty-five were selected and reviewed because they were strictly focused on the topic of this article. Compared with those who have TKR, ...

GeneLab: A Systems Biology Platform for Spaceflight Omics Data

Science.gov (United States)

Reinsch, Sigrid S.; Lai, San-Huei; Chen, Rick; Thompson, Terri; Berrios, Daniel; Fogle, Homer; Marcu, Oana; Timucin, Linda; Chakravarty, Kaushik; Coughlan, Joseph

2015-01-01

NASA's mission includes expanding our understanding of biological systems to improve life on Earth and to enable long-duration human exploration of space. Resources to support large numbers of spaceflight investigations are limited. NASA's GeneLab project is maximizing the science output from these experiments by: (1) developing a unique public bioinformatics database that includes space bioscience relevant "omics" data (genomics, transcriptomics, proteomics, and metabolomics) and experimental metadata; (2) partnering with NASA-funded flight experiments through bio-sample sharing or sample augmentation to expedite omics data input to the GeneLab database; and (3) developing community-driven reference flight experiments. The first database, GeneLab Data System Version 1.0, went online in April 2015. V1.0 contains numerous flight datasets and has search and download capabilities. Version 2.0 will be released in 2016 and will link to analytic tools. In 2015 Genelab partnered with two Biological Research in Canisters experiments (BBRIC-19 and BRIC-20) which examine responses of Arabidopsis thaliana to spaceflight. GeneLab also partnered with Rodent Research-1 (RR1), the maiden flight to test the newly developed rodent habitat. GeneLab developed protocols for maxiumum yield of RNA, DNA and protein from precious RR-1 tissues harvested and preserved during the SpaceX-4 mission, as well as from tissues from mice that were frozen intact during spaceflight and later dissected. GeneLab is establishing partnerships with at least three planned flights for 2016. Organism-specific nationwide Science Definition Teams (SDTs) will define future GeneLab dedicated missions and ensure the broader scientific impact of the GeneLab missions. GeneLab ensures prompt release and open access to all high-throughput omics data from spaceflight and ground-based simulations of microgravity and radiation. Overall, GeneLab will facilitate the generation and query of parallel multi-omics data, and

Artificial Disc Replacement

Science.gov (United States)

... Spondylolisthesis BLOG FIND A SPECIALIST Treatments Artificial Disc Replacement (ADR) Patient Education Committee Jamie Baisden The disc ... Disc An artificial disc (also called a disc replacement, disc prosthesis or spine arthroplasty device) is a ...

Product Platform Replacements

DEFF Research Database (Denmark)

Sköld, Martin; Karlsson, Christer

2012-01-01

. To shed light on this unexplored and growing managerial concern, the purpose of this explorative study is to identify operational challenges to management when product platforms are replaced. Design/methodology/approach – The study uses a longitudinal field-study approach. Two companies, Gamma and Omega...... replacement was chosen in each company. Findings – The study shows that platform replacements primarily challenge managers' existing knowledge about platform architectures. A distinction can be made between “width” and “height” in platform replacements, and it is crucial that managers observe this in order...... to challenge their existing knowledge about platform architectures. Issues on technologies, architectures, components and processes as well as on segments, applications and functions are identified. Practical implications – Practical implications are summarized and discussed in relation to a framework...

Candidate innate immune system gene expression in the ecological model Daphnia.

Science.gov (United States)

Decaestecker, Ellen; Labbé, Pierrick; Ellegaard, Kirsten; Allen, Judith E; Little, Tom J

2011-10-01

The last ten years have witnessed increasing interest in host-pathogen interactions involving invertebrate hosts. The invertebrate innate immune system is now relatively well characterised, but in a limited range of genetic model organisms and under a limited number of conditions. Immune systems have been little studied under real-world scenarios of environmental variation and parasitism. Thus, we have investigated expression of candidate innate immune system genes in the water flea Daphnia, a model organism for ecological genetics, and whose capacity for clonal reproduction facilitates an exceptionally rigorous control of exposure dose or the study of responses at many time points. A unique characteristic of the particular Daphnia clones and pathogen strain combinations used presently is that they have been shown to be involved in specific host-pathogen coevolutionary interactions in the wild. We choose five genes, which are strong candidates to be involved in Daphnia-pathogen interactions, given that they have been shown to code for immune effectors in related organisms. Differential expression of these genes was quantified by qRT-PCR following exposure to the bacterial pathogen Pasteuria ramosa. Constitutive expression levels differed between host genotypes, and some genes appeared to show correlated expression. However, none of the genes appeared to show a major modification of expression level in response to Pasteuria exposure. By applying knowledge from related genetic model organisms (e.g. Drosophila) to models for the study of evolutionary ecology and coevolution (i.e. Daphnia), the candidate gene approach is temptingly efficient. However, our results show that detection of only weak patterns is likely if one chooses target genes for study based on previously identified genome sequences by comparison to homologues from other related organisms. Future work on the Daphnia-Pasteuria system will need to balance a candidate gene approach with more comprehensive

Step by step replacement of aging electronic equipment: a way to maintain high capacity factors

International Nuclear Information System (INIS)

Wilder, O.

1990-01-01

The paper discusses the following topics: replacement concept, aging, replacement, strategy and the Swedish situation. The replacement of important central systems started already 1986 in Oskarshamn 1

Replacement

Directory of Open Access Journals (Sweden)

S. Radhakrishnan

2014-03-01

Full Text Available The fishmeal replaced with Spirulina platensis, Chlorella vulgaris and Azolla pinnata and the formulated diet fed to Macrobrachium rosenbergii postlarvae to assess the enhancement ability of non-enzymatic antioxidants (vitamin C and E, enzymatic antioxidants (superoxide dismutase (SOD and catalase (CAT and lipid peroxidation (LPx were analysed. In the present study, the S. platensis, C. vulgaris and A. pinnata inclusion diet fed groups had significant (P < 0.05 improvement in the levels of vitamins C and E in the hepatopancreas and muscle tissue. Among all the diets, the replacement materials in 50% incorporated feed fed groups showed better performance when compared with the control group in non-enzymatic antioxidant activity. The 50% fishmeal replacement (best performance diet fed groups taken for enzymatic antioxidant study, in SOD, CAT and LPx showed no significant increases when compared with the control group. Hence, the present results revealed that the formulated feed enhanced the vitamins C and E, the result of decreased level of enzymatic antioxidants (SOD, CAT and LPx revealed that these feeds are non-toxic and do not produce any stress to postlarvae. These ingredients can be used as an alternative protein source for sustainable Macrobrachium culture.

New energy replacement method for resonant power supplies

International Nuclear Information System (INIS)

Karady, G.G.; Thiessen, H.A.

1989-01-01

The Resonant Power Supply is an economically and technically advanced solution for Rapid Cycling Accelerators. Several papers dealt with the design and operation of these power supplies, however, the energy replacement methods were not discussed in the past. This paper analyzes different energy-replacement methods and presents a new method. This method uses a 24-pulse converter to regulate the magnet current during flat-top and injection periods and replaces the energy loss by charging the accelerator capacitor bank during the flat-top, reset and injection periods, charge is injected in the circuit during the acceleration period, when it replaces the energy loss. This paper compares the new method with the existing ones. The analyses proved the feasibility of the proposed method. The operation of the proposed method was verified by a model experiment, which showed that the new circuit can be controlled accurately and operates with smaller disturbances to the power line than the existing systems. 2 refs., 6 figs., 1 tab

PPARγ regulates the expression of cholesterol metabolism genes in alveolar macrophages

International Nuclear Information System (INIS)

Baker, Anna D.; Malur, Anagha; Barna, Barbara P.; Kavuru, Mani S.; Malur, Achut G.; Thomassen, Mary Jane

2010-01-01

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear transcription factor involved in lipid metabolism that is constitutively expressed in the alveolar macrophages of healthy individuals. PPARγ has recently been implicated in the catabolism of surfactant by alveolar macrophages, specifically the cholesterol component of surfactant while the mechanism remains unclear. Studies from other tissue macrophages have shown that PPARγ regulates cholesterol influx, efflux, and metabolism. PPARγ promotes cholesterol efflux through the liver X receptor-alpha (LXRα) and ATP-binding cassette G1 (ABCG1). We have recently shown that macrophage-specific PPARγ knockout (PPARγ KO) mice accumulate cholesterol-laden alveolar macrophages that exhibit decreased expression of LXRα and ABCG1 and reduced cholesterol efflux. We hypothesized that in addition to the dysregulation of these cholesterol efflux genes, the expression of genes involved in cholesterol synthesis and influx was also dysregulated and that replacement of PPARγ would restore regulation of these genes. To investigate this hypothesis, we have utilized a Lentivirus expression system (Lenti-PPARγ) to restore PPARγ expression in the alveolar macrophages of PPARγ KO mice. Our results show that the alveolar macrophages of PPARγ KO mice have decreased expression of key cholesterol synthesis genes and increased expression of cholesterol receptors CD36 and scavenger receptor A-I (SRA-I). The replacement of PPARγ (1) induced transcription of LXRα and ABCG1; (2) corrected suppressed expression of cholesterol synthesis genes; and (3) enhanced the expression of scavenger receptors CD36. These results suggest that PPARγ regulates cholesterol metabolism in alveolar macrophages.

Bone marrow transplantations to study gene function in hematopoietic cells

NARCIS (Netherlands)

de Winther, Menno P. J.; Heeringa, Peter

2011-01-01

Immune cells are derived from hematopoietic stem cells in the bone marrow. Experimental replacement of bone marrow offers the unique possibility to replace immune cells, to study gene function in mouse models of disease. Over the past decades, this technique has been used extensively to study, for

Penentuan Interval Waktu Penggantian Optimal Komponen Berdasarkan Model Opportunity Based-Age Replacement

OpenAIRE

Giatman, Muhammad

2008-01-01

Maintenance system, especially replacement that is not good, can cause much lose out for the company. The lose out is caused production process disturbing bay unexpectadly or unscheduled replacement. This will lose out for factory that have continue flow shop type, because replacement of the component that is need shut down machine will cause all machine in the process production stop. To anticipate of lose out that cause by replacement activity, so in this research will search interval of op...

BABAR IFR Replacement R and D

CERN Document Server

Berry, M

2003-01-01

The Instrumented Flux Return (IFR) of the BaBar detector will soon need to be replaced by a more robust muon detection system. Scintillator bars with embedded Wavelength Shifting (WLS) fibers and Limited Streamer Tubes are two replacement technology options. The scintillator bars are tested for attenuation length; and causes for the large width of the Photo Multiplier Tube (PMT) signal are analyzed by Monte Carlo simulation. Cooling techniques for Avalanche Photo Diodes (APD) are investigated. The fairly high attenuation length coupled with the narrow PMT signal make the scintillator a viable option for a muon detecting system. Continuing work will focus on increasing timing resolution using an APD to read the signal from the WLS fibers, and investigating the lifetime of the APD. The ability to read a signal from the LST on external copper strips is tested and signals are found to be clearly distinguishable from noise. The voltage is compared to count rate to find that the optimal operating voltage for the LS...

Capital Equipment Replacement Decisions

OpenAIRE

Batterham, Robert L.; Fraser, K.I.

1995-01-01

This paper reviews the literature on the optimal replacement of capital equipment, especially farm machinery. It also considers the influence of taxation and capital rationing on replacement decisions. It concludes that special taxation provisions such as accelerated depreciation and investment allowances are unlikely to greatly influence farmers' capital equipment replacement decisions in Australia.

Replacing lactose from calf milk replacers : effects on digestion and post-absorptive metabolism

NARCIS (Netherlands)

Gilbert, M.S.

2015-01-01

Summary PhD thesis Myrthe S. Gilbert

Replacing lactose from calf milk replacers – Effects on digestion and post-absorptive metabolism

Veal calves are fed milk replacer (MR) and solid feed. The largest part of the energy provided to veal calves

[The influence of hormonal replacement therapy on bone density in postmenopausal women depending on polymorphism of vitamin D receptor (VDR) and estrogen receptor (ER) genes].

Science.gov (United States)

Brodowska, Agnieszka

2003-01-01

genes? 3. What estrogen concentration is necessary to protect bone tissue depending on the polymorphism of VDR and ER genes? The study group included 44 postmenopausal women aged 44-75 years with primary osteoporosis on cyclic HRT (hormonal replacement therapy). Two hormonal preparations were administered: Systen 50 (Jansen Cilag) transdermal system twice per week between day 1 and 21 of the cycle; Provera (Upjohn) 5 mg tablets daily between day 16 and 27 of the cycle. This therapy was supplemented with vitamin D analogue (Alphacalcidolum, Glaxo-Poznan) orally at 0.25 microg per day, calcium-enriched (1200 mg daily) diet and regular physical exercise. Patients were qualified to the study on the basis of a questionnaire. Women with secondary osteoporosis were excluded. TSH, FT3, and FT4 concentrations, as well as fasting glucose were measured. 24 h glycemia was established in women with elevated glucose levels. Polymorphism of the ER gene was studied with Xba I and Pvu II restrictases. Polymorphism of the VDR gene was studied with Bsm I restrictase. Age and BMI were recorded. Spine BMD was determined with DEXA (Dual Energy X-ray Absorptiometry (Lunar instrument) before treatment and after 12 months of HRT. Serum estradiol concentrations were measured before treatment and after 2 months of HTR. The following conclusions were drawn: 1. There is no connection between VDR and ER gene polymorphism and degree of osteoporosis before treatment. 2. XX, PP and Bb markers or X, P, B alleles are associated with a significant decrease in therapeutic efficacy. Nevertheless, satisfactory results were achieved in each woman with primary osteoporosis. 3. Estradiol concentration in serum before and during HRT does not depend on the polymorphism of VDR and ER genes.

Flued head replacement alternatives

International Nuclear Information System (INIS)

Smetters, J.L.

1987-01-01

This paper discusses flued head replacement options. Section 2 discusses complete flued head replacement with a design that eliminates the inaccessible welds. Section 3 discusses alternate flued head support designs that can drastically reduce flued head installation costs. Section 4 describes partial flued head replacement designs. Finally, Section 5 discusses flued head analysis methods. (orig./GL)

The new frontier in muscular dystrophy research: booster genes

DEFF Research Database (Denmark)

Engvall, Eva; Wewer, Ulla M

2003-01-01

More than 30 different forms of muscular dystrophy (MD) have been molecularly characterized and can be diagnosed, but progress toward treatment has been slow. Gene replacement therapy has met with great difficulty because of the large size of the defective genes and because of difficulties...... of the boosters are better understood, drugs may be developed to provide the boost to muscle. Some of the experiences in models of muscular dystrophy may inspire new approaches in other genetic degenerative diseases as well....... in delivering a gene to all muscle groups. Cell replacement therapy has also been difficult to realize. Will it even be possible to design specific therapy protocols for all MDs? Or is a more realistic goal to treat some of the secondary manifestations that are common to several forms of MD, such as membrane...

A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

Science.gov (United States)

Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

2004-04-29

Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC system

Directory of Open Access Journals (Sweden)

Golemis Erica A

2004-04-01

Full Text Available Abstract Background Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. Results In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. Conclusion This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

Type II dehydroquinase: molecular replacement with many copies

International Nuclear Information System (INIS)

Stewart, Kirsty Anne; Robinson, David Alexander; Lapthorn, Adrian Jonathan

2007-01-01

The type II dehydroquinase enzyme is a symmetrical dodecameric protein which crystallizes in either high-symmetry cubic space groups or low-symmetry crystal systems with multiple copies in the asymmetric unit. Both systems have provided challenging examples for molecular replacement; for example, a triclinic crystal form has 16 dodecamers (192 monomers) in the unit cell. Three difficult examples are discussed and two are used as test cases to compare the performance of four commonly used molecular-replacement packages. Type II dehydroquinase is a small (150-amino-acid) protein which in solution packs together to form a dodecamer with 23 cubic symmetry. In crystals of this protein the symmetry of the biological unit can be coincident with the crystallographic symmetry, giving rise to cubic crystal forms with a single monomer in the asymmetric unit. In crystals where this is not the case, multiple copies of the monomer are present, giving rise to significant and often confusing noncrystallographic symmetry in low-symmetry crystal systems. These different crystal forms pose a variety of challenges for solution by molecular replacement. Three examples of structure solutions, including a highly unusual triclinic crystal form with 16 dodecamers (192 monomers) in the unit cell, are described. Four commonly used molecular-replacement packages are assessed against two of these examples, one of high symmetry and the other of low symmetry; this study highlights how program performance can vary significantly depending on the given problem. In addition, the final refined structure of the 16-dodecamer triclinic crystal form is analysed and shown not to be a superlattice structure, but rather an F-centred cubic crystal with frustrated crystallographic symmetry

Primary total hip replacement for displaced subcapital fractures of the femur.

Science.gov (United States)

Taine, W H; Armour, P C

1985-03-01

The management of displaced subcapital fracture of the hip is still controversial because of the high incidence of complications after internal fixation or hemiarthroplasty. To avoid some of these complications we have used primary total hip replacement for independently mobile patients over 65 years of age. A total of 163 cases, operated on over four years, have been reviewed. There were relatively more dislocations after operation for fracture than after total replacement for arthritis, and these were associated with a posterior approach to the hip. Only seven revision operations have been required. Of 57 patients who were interviewed an average of 42 months after replacement, 62% had excellent or good results as assessed by the Harris hip score. All the others had major systemic disease which affected their assessment. This inadequacy of current systems of hip assessment is discussed. It is concluded that total hip replacement is the best management for a selected group of patients with this injury, and that further prospective studies are indicated.

Steam generator replacement from ALARA aspects

International Nuclear Information System (INIS)

Terry, I.; Breznik, B.

2003-01-01

This paper is going to consider radiological related parameters important for steam generator replacement (SGR) implementation. These parameters are identified as ALARA related parameters, owner-contractor relationship, planning, health physics with logistic services, and time required for the replacement. ALARA related parameters such as source or initial dose rate and plant system configuration define the initial conditions for the planning. There is room to optimise work planning. managerial procedures and also the staff during the implementation phase. The overview of these general considerations is based on the following background: using internationally available data and the experience of one of the vendors, i.e. Siemens-Framatome, and management experience of SG replacement which took place at Krsko NPP in the spring of 2000. Generally plant decisions on maintenance or repair procedures under radiation conditions take into account ALARA considerations. But in the main it is difficult to adjudge the results of an ALARA study, usually in the form of a collective dose estimate, because a comparison standard is missing. That is, very often the planned work is of a one-off nature so comparisons are not possible or the scopes are not the same. In such a case the collective doses for other types of work are looked at and a qualitative evaluation is made. In the case of steam generator replacement this is not the case. Over years of steam generator replacements world-wide a standard has been developed gradually. The first part of the following displays an overview of SGR and sets the Krsko SGR in perspective by applying dose analysis. The second part concentrates on the Krsko SGR itself and its ALARA aspects. (authors)

Implementing Replacement Cost Accounting

Science.gov (United States)

1976-12-01

cost accounting Clickener, John Ross Monterey, California. Naval Postgraduate School http://hdl.handle.net/10945/17810 Downloaded from NPS Archive...Calhoun IMPLEMENTING REPLACEMENT COST ACCOUNTING John Ross CHckener NAVAL POSTGRADUATE SCHOOL Monterey, California THESIS IMPLEMENTING REPLACEMENT COST ...Implementing Replacement Cost Accounting 7. AUTHORS John Ross Clickener READ INSTRUCTIONS BEFORE COMPLETING FORM 3. RECIPIENT’S CATALOG NUMBER 9. TYRE OF

Implementation of in vitro replacement technologies in regulatory drug testing - An innovation systems perspective

NARCIS (Netherlands)

Kooijman, M.; Van Meer, P.J.K.; Moors, E.H.M.; Hekkert, M.P.; Schellekens, H.

2011-01-01

The replacement of in vivo methods by in vitro methods in regulatory drug testing is rare. The aim of this research is to identify barriers and drivers of the replacement of in vivo methods by in vitro methods in Europe. We studied two cases. The first case is the Draize eye test. Since 2009, the in

The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

Science.gov (United States)

Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

2013-01-01

The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Simplified Method for Gene Knockout and Direct Screening of Recombinant Clones for Application in Paenibacillus polymyxa.

Directory of Open Access Journals (Sweden)

Seong-Bin Kim

Full Text Available Paenibacillus polymyxa is a bacterium widely used in agriculture, industry, and environmental remediation because it has multiple functions including nitrogen fixation and produces various biologically active compounds. Among these compounds are the antibiotics polymyxins, and the bacterium is currently being reassessed for medical application. However, a lack of genetic tools for manipulation of P. polymyxa has limited our understanding of the biosynthesis of these compounds.To facilitate an understanding of the genetic determinants of the bacterium, we have developed a system for marker exchange mutagenesis directly on competent cells of P. polymyxa under conditions where homologous recombination is enhanced by denaturation of the suicide plasmid DNA. To test this system, we targeted P. polymyxa α-and β-amylase genes for disruption. Chloramphenicol or erythromycin resistance genes were inserted into the suicide plasmid pGEM7Z-f+ (Promega. To mediate homologous recombination and replacement of the targeted genes with the antibiotic resistance genes nucleotide sequences of the α-and β-amylase genes were cloned into the plasmid flanking the antibiotic resistance genes.We have created a simple system for targeted gene deletion in P. polymyxa E681. We propose that P. polymyxa isogenic mutants could be developed using this system of marker exchange mutagenesis. α-and β-amylase genes provide a useful tool for direct recombinant screening in P. polymyxa.

Pipe replacement in a water supply network: coordinated versus uncoordinated replacement and budget effects

NARCIS (Netherlands)

Dijk, van D.; Hendrix, E.M.T.

2016-01-01

Operators of underground water supply networks are challenged with pipe replacement
decisions, because pipes are subject to increased failure rates as they age and financial resources
are often limited.We study the optimal replacement time and optimal number of pipe replacements
such

Ortholog-based screening and identification of genes related to intracellular survival.

Science.gov (United States)

Yang, Xiaowen; Wang, Jiawei; Bing, Guoxia; Bie, Pengfei; De, Yanyan; Lyu, Yanli; Wu, Qingmin

2018-04-20

Bioinformatics and comparative genomics analysis methods were used to predict unknown pathogen genes based on homology with identified or functionally clustered genes. In this study, the genes of common pathogens were analyzed to screen and identify genes associated with intracellular survival through sequence similarity, phylogenetic tree analysis and the λ-Red recombination system test method. The total 38,952 protein-coding genes of common pathogens were divided into 19,775 clusters. As demonstrated through a COG analysis, information storage and processing genes might play an important role intracellular survival. Only 19 clusters were present in facultative intracellular pathogens, and not all were present in extracellular pathogens. Construction of a phylogenetic tree selected 18 of these 19 clusters. Comparisons with the DEG database and previous research revealed that seven other clusters are considered essential gene clusters and that seven other clusters are associated with intracellular survival. Moreover, this study confirmed that clusters screened by orthologs with similar function could be replaced with an approved uvrY gene and its orthologs, and the results revealed that the usg gene is associated with intracellular survival. The study improves the current understanding of intracellular pathogens characteristics and allows further exploration of the intracellular survival-related gene modules in these pathogens. Copyright © 2018. Published by Elsevier B.V.

Power Plant Replacement Study

Energy Technology Data Exchange (ETDEWEB)

Reed, Gary

2010-09-30

This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University's aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

Power Plant Replacement Study

Energy Technology Data Exchange (ETDEWEB)

Reed, Gary

2010-09-30

This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University’s aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining

Directory of Open Access Journals (Sweden)

Lan Chung-Yu

2008-09-01

Full Text Available Abstract Background Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease. However, it is difficult to recognize and evaluate relevant biological processes from the huge quantities of experimental data. It is hence appealing to find an algorithm which can generate a gene regulatory network of systemic inflammation from high-throughput genomic studies of human diseases. Such network will be essential for us to extract valuable information from the complex and chaotic network under diseased conditions. Results In this study, we construct a gene regulatory network of inflammation using data extracted from the Ensembl and JASPAR databases. We also integrate and apply a number of systematic algorithms like cross correlation threshold, maximum likelihood estimation method and Akaike Information Criterion (AIC on time-lapsed microarray data to refine the genome-wide transcriptional regulatory network in response to bacterial endotoxins in the context of dynamic activated genes, which are regulated by transcription factors (TFs such as NF-κB. This systematic approach is used to investigate the stochastic interaction represented by the dynamic leukocyte gene expression profiles of human subject exposed to an inflammatory stimulus (bacterial endotoxin. Based on the kinetic parameters of the dynamic gene regulatory network, we identify important properties (such as susceptibility to infection of the immune system, which may be useful for translational research. Finally, robustness of the inflammatory gene network is also inferred by analyzing the hubs and "weak ties" structures of the gene network

Chloroplast two-component systems: evolution of the link between photosynthesis and gene expression.

Science.gov (United States)

Puthiyaveetil, Sujith; Allen, John F

2009-06-22

Two-component signal transduction, consisting of sensor kinases and response regulators, is the predominant signalling mechanism in bacteria. This signalling system originated in prokaryotes and has spread throughout the eukaryotic domain of life through endosymbiotic, lateral gene transfer from the bacterial ancestors and early evolutionary precursors of eukaryotic, cytoplasmic, bioenergetic organelles-chloroplasts and mitochondria. Until recently, it was thought that two-component systems inherited from an ancestral cyanobacterial symbiont are no longer present in chloroplasts. Recent research now shows that two-component systems have survived in chloroplasts as products of both chloroplast and nuclear genes. Comparative genomic analysis of photosynthetic eukaryotes shows a lineage-specific distribution of chloroplast two-component systems. The components and the systems they comprise have homologues in extant cyanobacterial lineages, indicating their ancient cyanobacterial origin. Sequence and functional characteristics of chloroplast two-component systems point to their fundamental role in linking photosynthesis with gene expression. We propose that two-component systems provide a coupling between photosynthesis and gene expression that serves to retain genes in chloroplasts, thus providing the basis of cytoplasmic, non-Mendelian inheritance of plastid-associated characters. We discuss the role of this coupling in the chronobiology of cells and in the dialogue between nuclear and cytoplasmic genetic systems.

Heterologous expression of pikromycin biosynthetic gene cluster using Streptomyces artificial chromosome system.

Science.gov (United States)

Pyeon, Hye-Rim; Nah, Hee-Ju; Kang, Seung-Hoon; Choi, Si-Sun; Kim, Eung-Soo

2017-05-31

Heterologous expression of biosynthetic gene clusters of natural microbial products has become an essential strategy for titer improvement and pathway engineering of various potentially-valuable natural products. A Streptomyces artificial chromosomal conjugation vector, pSBAC, was previously successfully applied for precise cloning and tandem integration of a large polyketide tautomycetin (TMC) biosynthetic gene cluster (Nah et al. in Microb Cell Fact 14(1):1, 2015), implying that this strategy could be employed to develop a custom overexpression scheme of natural product pathway clusters present in actinomycetes. To validate the pSBAC system as a generally-applicable heterologous overexpression system for a large-sized polyketide biosynthetic gene cluster in Streptomyces, another model polyketide compound, the pikromycin biosynthetic gene cluster, was preciously cloned and heterologously expressed using the pSBAC system. A unique HindIII restriction site was precisely inserted at one of the border regions of the pikromycin biosynthetic gene cluster within the chromosome of Streptomyces venezuelae, followed by site-specific recombination of pSBAC into the flanking region of the pikromycin gene cluster. Unlike the previous cloning process, one HindIII site integration step was skipped through pSBAC modification. pPik001, a pSBAC containing the pikromycin biosynthetic gene cluster, was directly introduced into two heterologous hosts, Streptomyces lividans and Streptomyces coelicolor, resulting in the production of 10-deoxymethynolide, a major pikromycin derivative. When two entire pikromycin biosynthetic gene clusters were tandemly introduced into the S. lividans chromosome, overproduction of 10-deoxymethynolide and the presence of pikromycin, which was previously not detected, were both confirmed. Moreover, comparative qRT-PCR results confirmed that the transcription of pikromycin biosynthetic genes was significantly upregulated in S. lividans containing tandem

Safety benefits from CANDU reactor replacement - a case study

International Nuclear Information System (INIS)

Mottram, R.; Millard, J.W.F.; Purdy, P.

2011-01-01

Both total core replacement and core retubing have been used in the CANDU industry. For future plant refurbishments, based on experience both in new construction and in recent refurbishments, the concept of total core replacement has been revisited. This builds on practices for replacement of other large plant equipment like boilers. The Bruce CANDU reactors, with their local shield tanks built around the Calandria and containment closely located around that Calandria Shield Tank Assembly (CSTA), are believed to be good candidates for core replacement. A structured process was used to design a replacement CSTA suitable for Bruce A use. The work started with a study of opportunities for safety enhancements in the core. This progressed into design studies and related design assist safety analysis on the reactor. A key element of the work involved consideration of how verified features from later CANDU designs, and from our new reactor design work, could be tailored to fit this replacement core. The replacement reactor core brings in structural improvements in both calandria and end shield, and safety improvements like the natural circulation enhancing moderator cooling layout and further optimized reactivity layouts to improve shutdown system performance. Bruce Power are currently studying the business implications of this and retube techniques as part of preparation for future refurbishments. The work explained in this paper is in the context of the safety related changes and the work to choose and quantify them. (author)

Safety benefits from CANDU reactor replacement. A case study

International Nuclear Information System (INIS)

Mottram, R.; Millard, J.W.F.; Purdy, P.

2011-01-01

Both total core replacement and core retubing have been used in the CANDU industry. For future plant refurbishments, based on experience both in new construction and in recent refurbishments, the concept of total core replacement has been revisited. This builds on practices for replacement of other large plant equipment like boilers. The Bruce CANDU reactors, with their local shield tanks built around the Calandria and containment closely located around that Calandria Shield Tank Assembly (CSTA), are believed to be good candidates for core replacement. A structured process was used to design a replacement CSTA suitable for Bruce A use. The work started with a study of opportunities for safety enhancements in the core. This progressed into design studies and related design assist safety analysis on the reactor. A key element of the work involved consideration of how verified features from later CANDU designs, and from our new reactor design work, could be tailored to fit this replacement core. The replacement reactor core brings in structural improvements in both calandria and end shield, and safety improvements like the natural circulation enhancing moderator cooling layout and further optimized reactivity layouts to improve shutdown system performance. Bruce Power are currently studying the business implications of this and retube techniques as part of preparation for future refurbishments. The work explained in this paper is in the context of the safety related changes and the work to choose and quantify them. (author)

Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.

Science.gov (United States)

Johnson, Michael R; Shkura, Kirill; Langley, Sarah R; Delahaye-Duriez, Andree; Srivastava, Prashant; Hill, W David; Rackham, Owen J L; Davies, Gail; Harris, Sarah E; Moreno-Moral, Aida; Rotival, Maxime; Speed, Doug; Petrovski, Slavé; Katz, Anaïs; Hayward, Caroline; Porteous, David J; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Starr, John M; Liewald, David C; Visconti, Alessia; Falchi, Mario; Bottolo, Leonardo; Rossetti, Tiziana; Danis, Bénédicte; Mazzuferi, Manuela; Foerch, Patrik; Grote, Alexander; Helmstaedter, Christoph; Becker, Albert J; Kaminski, Rafal M; Deary, Ian J; Petretto, Enrico

2016-02-01

Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease-associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease.

Meal Replacement Mass Reduction Integration and Acceptability Study

Science.gov (United States)

Sirmons, T.; Douglas, G.; Schneiderman, J.; Slack, K.; Whitmire, A.; Williams, T.; Young, M.

2018-01-01

The Orion Multi-Purpose Crew Vehicle (MPCV) and future exploration missions are mass constrained; therefore we are challenged to reduce the mass of the food system by 10% while maintaining safety, nutrition, and acceptability to support crew health and performance for exploration missions. Meal replacement with nutritionally balanced, 700-900 calorie bars was identified as a method to reduce mass. However, commercially available products do not meet the requirements for a meal replacement in the spaceflight food system. The purpose of this task was to develop a variety of nutritionally balanced, high quality, breakfast replacement bars, which enable a 10% food mass savings. To date, six nutrient-dense meal replacement bars have been developed, all of which meet spaceflight nutritional, microbiological, sensory, and shelf-life requirements. The four highest scoring bars were evaluated based on final product sensory acceptability, nutritional stability, qualitative stability of analytical measurements (i.e. color and texture), and microbiological compliance over a period of two years to predict long-term acceptability. All bars maintained overall acceptability throughout the first year of storage, despite minor changes in color and texture. However, added vitamins C, B1, and B9 degraded rapidly in fortified samples of Banana Nut bars, indicating the need for additional development. In addition to shelf-life testing, four bar varieties were evaluated in the Human Exploration Research Analog (HERA), campaign 3, to assess the frequency with which actual meal replacement options may be implemented, based on impact to satiety and psychosocial measurements. Crewmembers (n=16) were asked to consume meal replacement bars every day for the first fifteen days of the mission and every three days for the second half of the mission. Daily surveys assessed the crew's responses to bar acceptability, mood, food fatigue and perceived stress. Preliminary results indicate that the

Fiber-reinforced Composite for Chairside Replacement of Anterior ...

African Journals Online (AJOL)

Fiber-reinforced Composite for Chairside Replacement of Anterior Teeth: A Case Report. ... investigation will be required to provide additional information on the survival of directly-bonded anterior fixed prosthesis made with FRC systems.

Influence of Total Knee Arthroplasty on Gait Mechanics of the Replaced and Non-Replaced Limb During Stair Negotiation.

Science.gov (United States)

Standifird, Tyler W; Saxton, Arnold M; Coe, Dawn P; Cates, Harold E; Reinbolt, Jeffrey A; Zhang, Songning

2016-01-01

This study compared biomechanics during stair ascent in replaced and non-replaced limbs of total knee arthroplasty (TKA) patients with control limbs of healthy participants. Thirteen TKA patients and fifteen controls performed stair ascent. Replaced and non-replaced knees of TKA patients were less flexed at contact compared to controls. The loading response peak knee extension moment was greater in control and non-replaced knees compared with replaced. The push-off peak knee abduction moment was elevated in replaced limbs compared to controls. Loading and push-off peak hip abduction moments were greater in replaced limbs compared to controls. The push-off peak hip abduction moment was greater in non-replaced limbs compared to controls. Future rehabilitation protocols should consider the replaced knee and also the non-replaced knee and surrounding joints. Copyright © 2016 Elsevier Inc. All rights reserved.

Steam generator replacement in Bruce A Unit 1 and Unit 2

International Nuclear Information System (INIS)

Hart, R.S.

2006-01-01

The Bruce A Generating Station consists of four 900 MW class CANDU units. The reactor and Primary Heat Transport System for each Unit are housed within a reinforced concrete reactor vault. A large duct running below the reactor vaults accommodates the shared fuel handling system, and connects the four reactor vaults to the vacuum building. The reactor vaults, fuelling system duct and the vacuum building constitute the station vacuum containment system. Bruce A Unit 2 was shut down in 1995 and Bruce A Units 1, 3 and 4 were shutdown in 1997. Bruce A Units 3 and 4 were returned to service in late 2003 and are currently operating. Units 1 and 2 remain out of service. Bruce Power is currently undertaking a major rehabilitation of Bruce A Unit 1 and Units 2 that will extend the in-service life of these units by at least 25 years. Replacement of the Steam Generators (eight in each unit) is required; this work was awarded to SNC-Lavalin Nuclear (SLN). The existing steam drums (which house the steam separation and drying equipment) will be retained. Unit 2 is scheduled to be synchronized with the grid in 2009, followed by Unit 1 in 2009. Each Bruce A unit has two steam generating assemblies, one located above and to each end of the reactor. Each steam generating assembly consists of a horizontal cylindrical steam drum and four vertical Steam Generators. The vertical Steam Generators connect to individual nozzles that are located on the underside of the Steam Drum (SD). The steam drums are located in concrete shielding structures (steam drum enclosures). The lower sections of the Steam Generators penetrate the top of the reactor vaults: the containment pressure boundary is established by bellows assemblies that connect between the reactor vault roof slab and the Steam Generators. Each Steam Generators is supported from the bottom by a trapeze that is suspended from the reactor vault top structure. The Steam Generator Replacement (SGR) methodology developed by SLN for Unit 1

Genes for 7S RNAs can replace the gene for 4.5S RNA in growth of Escherichia coli

DEFF Research Database (Denmark)

Brown, S

1991-01-01

4.5S RNAs of eubacteria and 7S RNAs of archaebacteria and eukaryotes exist in a hairpin conformation. The apex of this hairpin displays structural and sequence similarities among both 4.5S and 7S RNAs. Furthermore, a hyphenated sequence of 16 nucleotides is conserved in all eubacterial 4.5S RNAs...... examined. In this article I report that 7S RNAs that contain this 16-nucleotide sequence are able to replace 4.5S RNAs and permit growth of Escherichia coli....

Improved osteogenic vector for non-viral gene therapy

Directory of Open Access Journals (Sweden)

ARA Hacobian

2016-03-01

Full Text Available Therapeutic compensation of deficient bone regeneration is a challenging task and a topic of on-going search for novel treatment strategies. One promising approach for improvement involves non-viral gene delivery using the bone morphogenetic protein-2 (BMP-2 gene to provide transient, local and sustained expression of the growth factor. However, since efficiency of non-viral gene delivery is low, this study focused on the improvement of a BMP-2 gene expression system, aiming for compensation of poor transfection efficiency. First, the native BMP-2 gene sequence was modified by codon optimisation and altered by inserting a highly truncated artificial intron (96 bp. Transfection of multiple cell lines and rat adipose-derived mesenchymal stem cells with plasmids harbouring the improved BMP-2 sequence led to a several fold increased expression rate and subsequent osteogenic differentiation. Additionally, comparing expression kinetics of elongation factor 1 alpha (EF1α promoter with a state of the art CMV promoter revealed significantly higher BMP-2 expression when under the influence of the EF1α promoter. Results obtained by quantification of bone markers as well as osteogenic assays showed reduced sensitivity to promoter silencing effects of the EF1α promoter in rat adipose-derived mesenchymal stem cells. Finally, screening of several protein secretion signals using either luciferase or BMP-2 as reporter protein revealed no superior candidates for potential replacement of the native BMP-2 secretion signal. Taken together, by enhancing the exogenous BMP-2 expression system, low transfection efficiencies in therapeutic applications can be compensated, making safe non-viral systems even more suitable for tissue regeneration approaches.

Replacing OSE with Real Time capable Linux

OpenAIRE

Boman, Simon; Rutgersson, Olof

2009-01-01

For many years OSE has been a common used operating system, with real time extensions enhancements, in embed-ded systems. But in the last decades, Linux has grown and became a competitor to common operating systems and, in recent years, even as an operating system with real time extensions. With this in mind, ÅF was interested in replacing the quite expensive OSE with some distribution of the open source based Linux on a PowerPC MPC8360. Therefore, our purpose with thesis is to implement Linu...

Mechanisms of metasomatism in the calcite-pitchblende system: 2. Replacement of pitchblende by calcite

International Nuclear Information System (INIS)

Dymkov, Yu.M.

1996-01-01

The principal mechanisms of the nasturan replacement by calcite -intrametasomatism, frontal metasomatism, dispersive metasomatism, and transformative metasomatism - are discussed in terms of G.L. Pospelov's (1973) concept. The main chemical condition required by the process is an oxidized environment, in which the tetravalent uranium of pitchblende or transitional reduced phases (coffinite) oxidizes to yield readily soluble uranyl compounds. The latter are replaced by calcite

Hip Replacement: MedlinePlus Health Topic

Science.gov (United States)

... invasive hip replacement (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Hip Replacement updates ... replacement - precautions Minimally invasive hip replacement Related Health Topics Hip Injuries and Disorders National Institutes of Health ...

Aorto-right atrial fistula after ascending aortic replacement or aortic value replacement

International Nuclear Information System (INIS)

Zhi Aihua; Dai Ruping; Jiang Shiliang; Lu Bin

2012-01-01

Objective: To evaluate the CT features of aorto-right atrial fistula after aortic valve replacement (AVR) or ascending aortic replacement. Methods: Eighty-seven patients with aortic-right atrial fistula underwent CT after operation. The CT features were retrospectively analyzed. Fistula was measured according to maximum width of the shunt. Results: Aorto-right atrial fistula was detected in 87 patients after aortic valve replacement or ascending aortic replacement by CT scan. Among them, 25 patients were diagnosed as mild aorto-right atrial fistula, 47 patients as moderate, and 15 patients as severe. Thirty-seven patients underwent follow-up CT.Among them, 10 patients with mild to moderate aorto-right atrial fistula were considered to have complete regression, 8 patients with mild aorto-right atrial fistula considered to have incomplete regression, 14 patients with mild to moderate aorto-right atrial fistula considered to have stable condition, and 5 patients with moderate aorto-right atrial fistula considered to have progression at the 3-month follow-up. Conclusion: CT is a useful tool for defining aorto-right atrial fistula after AVR or ascending aortic replacement and for evaluating it in follow-up. (authors)

Tumor-directed gene therapy in mice using a composite nonviral gene delivery system consisting of the piggyBac transposon and polyethylenimine

International Nuclear Information System (INIS)

Kang, Yu; Zhang, Xiaoyan; Jiang, Wei; Wu, Chaoqun; Chen, Chunmei; Zheng, Yufang; Gu, Jianren; Xu, Congjian

2009-01-01

Compared with viral vectors, nonviral vectors are less immunogenic, more stable, safer and easier to replication for application in cancer gene therapy. However, nonviral gene delivery system has not been extensively used because of the low transfection efficiency and the short transgene expression, especially in vivo. It is desirable to develop a nonviral gene delivery system that can support stable genomic integration and persistent gene expression in vivo. Here, we used a composite nonviral gene delivery system consisting of the piggyBac (PB) transposon and polyethylenimine (PEI) for long-term transgene expression in mouse ovarian tumors. A recombinant plasmid PB [Act-RFP, HSV-tk] encoding both the herpes simplex thymidine kinase (HSV-tk) and the monomeric red fluorescent protein (mRFP1) under PB transposon elements was constructed. This plasmid and the PBase plasmid were injected into ovarian cancer tumor xenografts in mice by in vivo PEI system. The antitumor effects of HSV-tk/ganciclovir (GCV) system were observed after intraperitoneal injection of GCV. Histological analysis and TUNEL assay were performed on the cryostat sections of the tumor tissue. Plasmid construction was confirmed by PCR analysis combined with restrictive enzyme digestion. mRFP1 expression could be visualized three weeks after the last transfection of pPB/TK under fluorescence microscopy. After GCV admission, the tumor volume of PB/TK group was significantly reduced and the tumor inhibitory rate was 81.96% contrasted against the 43.07% in the TK group. Histological analysis showed that there were extensive necrosis and lymphocytes infiltration in the tumor tissue of the PB/TK group but limited in the tissue of control group. TUNEL assays suggested that the transfected cells were undergoing apoptosis after GCV admission in vivo. Our results show that the nonviral gene delivery system coupling PB transposon with PEI can be used as an efficient tool for gene therapy in ovarian cancer

Optimal replacement policies for dairy cows based on daily yield measurements

DEFF Research Database (Denmark)

Nielsen, Lars Relund; Jørgensen, Erik; Kristensen, Anders Ringgaard

2010-01-01

describes the first step of developing an MDP model that can be integrated into a modern herd management system. A hierarchical MDP was formulated for the dairy cow replacement problem with stage lengths of 1 d. It can be used to assist the farmer in replacement decisions on a daily basis and is based...

Perinatal systemic gene delivery using adeno-associated viral vectors

Directory of Open Access Journals (Sweden)

Rajvinder eKarda

2014-11-01

Full Text Available Neurodegenerative monogenic diseases can also affect a broad range of tissues and organs throughout the body. An effective treatment would require a systemic approach. The intravenous administration of novel therapies is ideal but is hampered by the inability of such drugs to cross the blood-brain barrier and precludes efficacy in the central nervous system. A number of these early lethal intractable diseases also present devastating irreversible pathology at birth or soon after. Therefore, any therapy would ideally be administered during the perinatal period to prevent, stop or ameliorate disease progression. The concept of perinatal gene therapy has moved a step further towards being a feasible approach to treating such disorders. This has primarily been driven by the recent discoveries that particular serotypes of adeno-associated virus (AAV gene delivery vectors have the ability to cross the blood-brain barrier following intravenous administration. Furthermore, this has been safely demonstrated in perinatal mice and non-human primates. This review focuses on the progress made in using AAV to achieve systemic transduction and what this means for developing perinatal gene therapy for early lethal neurodegenerative diseases.

Preliminary study of possible ORELA replacement options

International Nuclear Information System (INIS)

Olsen, D.K.; Martin, J.A.; Horen, D.J.

1984-06-01

Based on two conceptual design studies performed by the LANL Accelerator Technology Division, the possibilities in terms of accelerator systems for replacing ORELA with a more intense Maxwellian-type continuous-energy neutron source are summarized and discussed. The neutron intensities from ORELA are compared with those from existing or potential accelerator systems used for cross-section and condensed-matter studies. The best replacement options seem to involve a spallation source from 200- to 400-MeV protons on an ORELA-like target. Pulsing and intensity desiderata with such a source are discussed which correspond to a spectrum-averaged 100-fold improved figure of merit over ORELA for TOF measurements with only a tenfold increased source strength. Existing accelerator designs seem to be inadequate for such a source. Consequently, two conceptual designs were developed for this study by the LANL Accelerator Technology Division. The first conceptual design is for a 200-MeV large linac capable of accelerating 1.3 A during a macropulse; this linac standing alone could serve as an ORELA replacement source. The second conceptual design is for a much smaller 250-MeV PIGMI linac with a 28-mA macropulse current which feeds a proton accumulator ring and bunch-compressor transport line. This linac-ring-compressor (LIRIC) option would give a more cost-effective neutron source for cross-section measurements, whereas the large linac, or a modified version of it, would give a much simpler system more suitable for expansion. In particular, both conceptual designs would incorporate the present ORELA building and would provide approximately 100-fold improved neutron sources over ORELA for cross-section measurements. The total estimated cost of the LIRIC system would be $43M (1984), whereas the cost of the large linac would be about a factor of two more. 55 references, 11 figures, 19 tables

Steam generator replacement at the Obrigheim nuclear power station

International Nuclear Information System (INIS)

Pickel, E.; Schenk, H.; Huemmler, A.

1984-01-01

The Obrigheim Nuclear Power Station (KWO) is equipped with a dual-loop pressurized water reactor of 345 MW electric power; it was built by Siemens in the period 1965 to 1968. By the end of 1983, KWO had produced some 35 billion kWh in 109,000 hours of operation. Repeated leaks in the heater tubes of the two steam generators had occurred since 1971. Both steam generators were replaced in the course of the 1983 annual revision. Kraftwerk Union AG (KWU) was commissioned to plant and carry out the replacement work. Despite the leakages the steam generators had been run safely and reliably over a period of 14 years until their replacement. Replacing the steam generators was completed within twelve weeks. In addition to the KWO staff and the supervising crew of KWU, some 400 external fitters were employed on the job at peak work-load periods. For the revision of the whole plant, work on the emergency systems and replacement of the steam generators a maximum number of approx. 900 external fitters were employed in the plant in addition to some 250 members of the plant crew. The exposure dose of the personnel sustained in the course of the steam generator replacement was 690 man-rem, which was clearly below previous estimates. (orig.) [de

Minimally invasive aortic valve replacement

DEFF Research Database (Denmark)

Foghsgaard, Signe; Schmidt, Thomas Andersen; Kjaergard, Henrik K

2009-01-01

In this descriptive prospective study, we evaluate the outcomes of surgery in 98 patients who were scheduled to undergo minimally invasive aortic valve replacement. These patients were compared with a group of 50 patients who underwent scheduled aortic valve replacement through a full sternotomy...... operations were completed as mini-sternotomies, 4 died later of noncardiac causes. The aortic cross-clamp and perfusion times were significantly different across all groups (P replacement...... is an excellent operation in selected patients, but its true advantages over conventional aortic valve replacement (other than a smaller scar) await evaluation by means of randomized clinical trial. The "extended mini-aortic valve replacement" operation, on the other hand, is a risky procedure that should...

Bacterial toxin-antitoxin gene system as containment control in yeast cells

DEFF Research Database (Denmark)

Kristoffersen, P.; Jensen, G. B.; Gerdes, K.

2000-01-01

The potential of a bacterial toxin-antitoxin gene system for use in containment control in eukaryotes was explored. The Escherichia coli relE and relB genes were expressed in the yeast Saccharomyces cerevisiae, Expression of the relE gene was highly toxic to yeast cells. However, expression...... fermentation processes in which the escape of genetically modified cells would be considered highly risky....

Gene disruption in Salmonella typhimurim by modified λ Red disruption system.

Science.gov (United States)

Ahani Azari, A; Zahraei Salehi, T; Nayeri Fasaei, B; Alebouyeh, M

2015-01-01

There are many techniques to knock out directed genes in bacteria, some of which have been described in Salmonella species. In this study, a combination of SOEing PCR method and the λ Red disruption system were used to disrupt phoP gene in wild type and standard strains of Salmonella typhimurium. Three standards PCR and one fusion PCR reactions were performed to construct a linear DNA including upstream and downstream of phoP gene and Kanamycin cassette. As a template plasmid, we used pKD4 which carries kanamycin gene flanked by FRT (FLP recognition target) sites. The resulting construct was electroporated into prepared competent cells of S. typhimurium. The transformants colonies related to the standard strain appeared on the LB-Km-agar plates after incubation, but there was no colony on LB-Km-agar plates corresponding to the wild type strain. The failure in transformation of the wild type strain may be because of inflexibility of the λ Red disruption system in this strain or its unique restriction-modification system. However, by this construct we are able to generate phoP mutant in many of the Salmonella species due to high homology of the phoP gene which exists in different species.

Gene therapy in periodontics.

Science.gov (United States)

Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

2013-03-01

GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is 'the use of genes as medicine'. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

Potential consequences of replacing a retail alcohol monopoly with a private licence system: results from Sweden.

Science.gov (United States)

Norström, Thor; Miller, Ted; Holder, Harold; Osterberg, Esa; Ramstedt, Mats; Rossow, Ingeborg; Stockwell, Tim

2010-12-01

To examine the potential effects of replacing the Swedish alcohol retail system with a private licensing system on alcohol consumption and alcohol-related harm. Two possible scenarios were analysed: (1) replacing the current alcohol retail monopoly with private licensed stores that specialize in alcohol sales or (2) making all alcohol available in grocery stores. We utilized a multiplicative model that projected effects of changes in a set of key factors including hours of sale, retail prices, promotion and advertising and outlet density. Next, we estimated the effect of the projected consumption increase on a set of harm indicators. Values for the model parameters were obtained from the research literature. Measures of alcohol-related harm included explicitly alcohol-related mortality, accident mortality, suicide, homicide, assaults, drinking driving and sickness absence. According to the projections, scenario 1 yields a consumption increase of 17% (1.4 litres/capita), which in turn would cause an additional 770 deaths, 8500 assaults, 2700 drinking driving offences and 4.5 million sick days per year. The corresponding figures for scenario 2 are a consumption increase of 37.4% (3.1 litres/capita) leading to an additional annual toll of 2000 deaths, 20 000 assaults, 6600 drinking driving offences and 11.1 million days of sick leave. Projections based on the research literature suggest that privatization of the Swedish alcohol retail market would significantly increase alcohol consumption and alcohol-related harm. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Partial knee replacement - slideshow

Science.gov (United States)

... page: //medlineplus.gov/ency/presentations/100225.htm Partial knee replacement - series—Normal anatomy To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Knee Replacement A.D.A.M., Inc. is accredited ...

24 CFR 891.405 - Replacement reserve.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 891.405....405 Replacement reserve. (a) Establishment of reserve. The Owner shall establish and maintain a replacement reserve to aid in funding extraordinary maintenance and repair and replacement of capital items...

Local Gene Delivery System by Bubble Liposomes and Ultrasound Exposure into Joint Synovium

Directory of Open Access Journals (Sweden)

Yoichi Negishi

2011-01-01

Full Text Available Recently, we have developed novel polyethylene glycol modified liposomes (bubble liposomes; BL entrapping an ultrasound (US imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated the usefulness of US-mediated gene transfer systems with BL into synoviocytes in vitro and joint synovium in vivo. Highly efficient gene transfer could be achieved in the cultured primary synoviocytes transfected with the combination of BL and US exposure, compared to treatment with plasmid DNA (pDNA alone, pDNA plus BL, or pDNA plus US. When BL was injected into the knee joints of mice, and US exposure was applied transcutaneously to the injection site, highly efficient gene expression could be observed in the knee joint transfected with the combination of BL and US exposure, compared to treatment with pDNA alone, pDNA plus BL, or pDNA plus US. The localized and prolonged gene expression was also shown by an in vivo luciferase imaging system. Thus, this local gene delivery system into joint synovium using the combination of BL and US exposure may be an effective means for gene therapy in joint disorders.

The replacement of technically obsolete equipments

International Nuclear Information System (INIS)

Anglaret, Ph.; Patouillaud, M.

1987-01-01

The paper covers the analysis of procedures for replacement of technically obsolete but still operational equipments in use in a nuclear power plant. The Three Mile Island accident showed that operators in the control room reqire additional information at their disposal. In 1986 CGEE Alsthom received two orders for improvements to control systems, for the South African nuclear power plant Koeberg and the Dutch nuclear power plant Borssele. The new systems will provide support to normal operation and offer additional help in accident situations. 4 figs

ATNT: an enhanced system for expression of polycistronic secondary metabolite gene clusters in Aspergillus niger.

Science.gov (United States)

Geib, Elena; Brock, Matthias

2017-01-01

Fungi are treasure chests for yet unexplored natural products. However, exploitation of their real potential remains difficult as a significant proportion of biosynthetic gene clusters appears silent under standard laboratory conditions. Therefore, elucidation of novel products requires gene activation or heterologous expression. For heterologous gene expression, we previously developed an expression platform in Aspergillus niger that is based on the transcriptional regulator TerR and its target promoter P terA . In this study, we extended this system by regulating expression of terR  by the doxycycline inducible Tet-on system. Reporter genes cloned under the control of the target promoter P terA remained silent in the absence of doxycycline, but were strongly expressed when doxycycline was added. Reporter quantification revealed that the coupled system results in about five times higher expression rates compared to gene expression under direct control of the Tet-on system. As production of secondary metabolites generally requires the expression of several biosynthetic genes, the suitability of the self-cleaving viral peptide sequence P2A was tested in this optimised expression system. P2A allowed polycistronic expression of genes required for Asp-melanin formation in combination with the gene coding for the red fluorescent protein tdTomato. Gene expression and Asp-melanin formation was prevented in the absence of doxycycline and strongly induced by addition of doxycycline. Fluorescence studies confirmed the correct subcellular localisation of the respective enzymes. This tightly regulated but strongly inducible expression system enables high level production of secondary metabolites most likely even those with toxic potential. Furthermore, this system is compatible with polycistronic gene expression and, thus, suitable for the discovery of novel natural products.

PPAR{gamma} regulates the expression of cholesterol metabolism genes in alveolar macrophages

Energy Technology Data Exchange (ETDEWEB)

Baker, Anna D.; Malur, Anagha; Barna, Barbara P.; Kavuru, Mani S. [Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, East Carolina University (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, East Carolina University (United States); Department of Microbiology and Immunology, East Carolina University (United States)

2010-03-19

Peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) is a nuclear transcription factor involved in lipid metabolism that is constitutively expressed in the alveolar macrophages of healthy individuals. PPAR{gamma} has recently been implicated in the catabolism of surfactant by alveolar macrophages, specifically the cholesterol component of surfactant while the mechanism remains unclear. Studies from other tissue macrophages have shown that PPAR{gamma} regulates cholesterol influx, efflux, and metabolism. PPAR{gamma} promotes cholesterol efflux through the liver X receptor-alpha (LXR{alpha}) and ATP-binding cassette G1 (ABCG1). We have recently shown that macrophage-specific PPAR{gamma} knockout (PPAR{gamma} KO) mice accumulate cholesterol-laden alveolar macrophages that exhibit decreased expression of LXR{alpha} and ABCG1 and reduced cholesterol efflux. We hypothesized that in addition to the dysregulation of these cholesterol efflux genes, the expression of genes involved in cholesterol synthesis and influx was also dysregulated and that replacement of PPAR{gamma} would restore regulation of these genes. To investigate this hypothesis, we have utilized a Lentivirus expression system (Lenti-PPAR{gamma}) to restore PPAR{gamma} expression in the alveolar macrophages of PPAR{gamma} KO mice. Our results show that the alveolar macrophages of PPAR{gamma} KO mice have decreased expression of key cholesterol synthesis genes and increased expression of cholesterol receptors CD36 and scavenger receptor A-I (SRA-I). The replacement of PPAR{gamma} (1) induced transcription of LXR{alpha} and ABCG1; (2) corrected suppressed expression of cholesterol synthesis genes; and (3) enhanced the expression of scavenger receptors CD36. These results suggest that PPAR{gamma} regulates cholesterol metabolism in alveolar macrophages.

STS-39: OMS Pod Thruster Removal/Replace

Science.gov (United States)

1991-01-01

Shown is the removal and replacement of the Discovery's orbital maneuvering systems (OMS) pod thruster. The OMS engine will be used to propel Discovery north, off of its previous orbital groundtrack, without changing the spacecraft's altitude. A burn with this lateral effect is known as "out-of-plane."

24 CFR 880.602 - Replacement reserve.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 880.602... Replacement reserve. (a) A replacement reserve must be established and maintained in an interest-bearing account to aid in funding extraordinary maintenance and repair and replacement of capital items. (1) Part...

Are output measurements always necessary after CT tube replacement?

Directory of Open Access Journals (Sweden)

Paul J Stauduhar

2014-03-01

Full Text Available Purpose: TX regulations and the ACR require that CT radiation output be measured within 30 days of major service. The most common major service is tube replacement. We hypothesized that historical QC data could be used instead to determine if output measurements are necessary, reducing the need for costly output measurements.Methods: We reviewed 66 records of tube replacements to determine with what frequency output falls outside specifications. We also conducted an experiment to verify that clinically significant output changes could be identified by comparing image noise in historical QC data with the same data after tube replacement. We used 30 days of historical QC data to establish a baseline noise level and 95% confidence interval (CI for individual noise measurements. To simulate output changes, we acquired phantom images with our QC protocol while manually changing output (mA. We acquired 10 images using the baseline output and 10 images at each different “output”. We evaluated individual images and subsets of images at each “output” to determine if the system was within the manufacturer’s specifications.Results: None of the 66 tube replacements resulted in an output change that exceeded specifications. Analysis of 30 days of historic QC data for our experimental system indicated a mean noise of 5.4 HU with 95% CI of 5.1 ‒ 5.7 HU. When using the mean noise of 10 images acquired at each of the varying outputs, we were able to identify, with 100% accuracy, images acquired at outputs outside manufacturer’s specifications.Conclusion: The results of our review of historical tube replacement data indicated the likelihood of output falling outside manufacturer’s specifications is low. Considering this, it is likely that by using QC data from programs required by regulation and the ACR physicists can reliably verify radiation output stability remotely instead of making physical measurements.--------------------Cite this article

GENE DOPING IN SPORT – PERSPECTIVES AND RISKS

OpenAIRE

E Brzeziańska; D Domańska; A Jegier

2014-01-01

In the past few years considerable progress regarding the knowledge of the human genome map has been achieved. As a result, attempts to use gene therapy in patients’ management are more and more often undertaken. The aim of gene therapy is to replace defective genes in vivo and/or to promote the long-term endogenous synthesis of deficient protein. In vitro studies improve the production of human recombinant proteins, such as insulin (INS), growth hormone (GH), insulin-like growth factor-1 (IG...

Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs

Directory of Open Access Journals (Sweden)

Jafar Ezzati Nazhad Dolatabadi

2015-06-01

Full Text Available In recent years, nanomaterials have been widely applied as advanced drug and gene delivery nanosystems. Among them, solid lipid nanoparticles (SLNs have attracted great attention as colloidal drug delivery systems for incorporating hydrophilic or lipophilic drugs and various macromolecules as well as proteins and nucleic acids. Therefore, SLNs offer great promise for controlled and site specific drug and gene delivery. This article includes general information about SLN structures and properties, production procedures, characterization. In addition, recent progress on development of drug and gene delivery systems using SLNs was reviewed.

24 CFR 891.855 - Replacement reserves.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserves. 891.855... § 891.855 Replacement reserves. (a) The mixed-finance owner shall establish and maintain a replacement... the funds will be used to pay for capital replacement costs for the Section 202 or 811 supportive...

A model of gene expression based on random dynamical systems reveals modularity properties of gene regulatory networks.

Science.gov (United States)

Antoneli, Fernando; Ferreira, Renata C; Briones, Marcelo R S

2016-06-01

Here we propose a new approach to modeling gene expression based on the theory of random dynamical systems (RDS) that provides a general coupling prescription between the nodes of any given regulatory network given the dynamics of each node is modeled by a RDS. The main virtues of this approach are the following: (i) it provides a natural way to obtain arbitrarily large networks by coupling together simple basic pieces, thus revealing the modularity of regulatory networks; (ii) the assumptions about the stochastic processes used in the modeling are fairly general, in the sense that the only requirement is stationarity; (iii) there is a well developed mathematical theory, which is a blend of smooth dynamical systems theory, ergodic theory and stochastic analysis that allows one to extract relevant dynamical and statistical information without solving the system; (iv) one may obtain the classical rate equations form the corresponding stochastic version by averaging the dynamic random variables (small noise limit). It is important to emphasize that unlike the deterministic case, where coupling two equations is a trivial matter, coupling two RDS is non-trivial, specially in our case, where the coupling is performed between a state variable of one gene and the switching stochastic process of another gene and, hence, it is not a priori true that the resulting coupled system will satisfy the definition of a random dynamical system. We shall provide the necessary arguments that ensure that our coupling prescription does indeed furnish a coupled regulatory network of random dynamical systems. Finally, the fact that classical rate equations are the small noise limit of our stochastic model ensures that any validation or prediction made on the basis of the classical theory is also a validation or prediction of our model. We illustrate our framework with some simple examples of single-gene system and network motifs. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-excising Cre/mutant lox marker recycling system for multiple gene integrations and consecutive gene deletions in Aspergillus oryzae.

Science.gov (United States)

Zhang, Silai; Ban, Akihiko; Ebara, Naoki; Mizutani, Osamu; Tanaka, Mizuki; Shintani, Takahiro; Gomi, Katsuya

2017-04-01

In this study, we developed a self-excising Cre/loxP-mediated marker recycling system with mutated lox sequences to introduce a number of biosynthetic genes into Aspergillus oryzae. To construct the self-excising marker cassette, both the selectable marker, the Aspergillus nidulans adeA gene, and the Cre recombinase gene (cre), conditionally expressed by the xylanase-encoding gene promoter, were designed to be located between the mutant lox sequences, lox66 and lox71. However, construction of the plasmid failed, possibly owing to a slight expression of cre downstream of the fungal gene promoter in Escherichia coli. Hence, to avoid the excision of the cassette in E. coli, a 71-bp intron of the A. oryzae xynG2 gene was inserted into the cre gene. The A. oryzae adeA deletion mutant was transformed with the resulting plasmid in the presence of glucose, and the transformants were cultured in medium containing xylose as the sole carbon source. PCR analysis of genomic DNA from resultant colonies revealed the excision of both the marker and Cre expression construct, indicating that the self-excising marker cassette was efficient at removing the selectable marker. Using the marker recycling system, hyperproduction of kojic acid could be achieved in A. oryzae by the introduction of two genes that encode oxidoreductase and transporter. Furthermore, we also constructed an alternative marker recycling cassette bearing the A. nidulans pyrithiamine resistant gene (ptrA) as a dominant selectable marker. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Gene expression of endothelin receptors in replaced rheumatic mitral stenotic valves Expressão gênica de receptores de endotelina em valvas mitrais reumáticas estenóticas substituídas

Directory of Open Access Journals (Sweden)

Sydney Correia Leão

2012-12-01

Full Text Available OBJECTIVES: Rheumatic fever is a highly prevalent disease in Brazil, and it poses a major public health problem. It is the leading cause of acquired heart disease in childhood and adolescence. The aim of this study was to evaluate the gene expression of ET-3 and its receptors, in replaced rheumatic mitral valves. METHODS: We studied the gene expression of endothelin-3 (ET-3 and its receptors, endothelin receptor A and endothelin receptor B (ETr-A and ETr-B, in the rheumatic mitral valves of 17 patients who underwent valve replacement surgery. The samples also underwent a histological analysis. RESULTS: Our data showed that almost all patients, regardless of individual characteristics such as gender or age, expressed the endothelin receptor genes, but did not express the genes for ET-3. In quantitative analysis, the ETr-A/GAPDH mean ratio was 33.04 ± 18.09%; while the ETr-B/GAPDH mean ratio was 114.58 ± 42.30%. Regarding histopathological individual features, the frequency of fibrosis is 100%, 88.23% of mononuclear infiltrate, 52.94% of neovascularization, 58.82% of calcification and absence of ossification. CONCLUSION: The presence of receptors ETr-A and ETr-B in rheumatic mitral valves suggests its interaction with the system of circulating endothelins, particularly ETr-B (known for acting in the removal of excess endothelin detected in a greater proportion, which could explain the lack of expression of endothelin in rheumatic mitral valve, process to be elucidated.OBJETIVOS: A febre reumática é uma doença altamente prevalente no Brasil, e representa um importante problema de saúde pública. É a principal causa de cardiopatia adquirida na infância e adolescência. O objetivo deste estudo foi avaliar a expressão gênica de ET-3 e seus receptores, em valvas mitrais reumáticas substituídas. Métodos: Estudamos a expressão gênica de endotelina-3 (ET-3 e de seus receptores, receptor da endotelina A e receptor da endotelina B (ETr-A e

25 CFR 700.53 - Dwelling, replacement.

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE... Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means a dwelling selected by the head of a household as a replacement dwelling that meets the criteria of this...

The Influence of Gene Expression Time Delays on Gierer–Meinhardt Pattern Formation Systems

KAUST Repository

Seirin Lee, S.

2010-03-23

There are numerous examples of morphogen gradients controlling long range signalling in developmental and cellular systems. The prospect of two such interacting morphogens instigating long range self-organisation in biological systems via a Turing bifurcation has been explored, postulated, or implicated in the context of numerous developmental processes. However, modelling investigations of cellular systems typically neglect the influence of gene expression on such dynamics, even though transcription and translation are observed to be important in morphogenetic systems. In particular, the influence of gene expression on a large class of Turing bifurcation models, namely those with pure kinetics such as the Gierer-Meinhardt system, is unexplored. Our investigations demonstrate that the behaviour of the Gierer-Meinhardt model profoundly changes on the inclusion of gene expression dynamics and is sensitive to the sub-cellular details of gene expression. Features such as concentration blow up, morphogen oscillations and radical sensitivities to the duration of gene expression are observed and, at best, severely restrict the possible parameter spaces for feasible biological behaviour. These results also indicate that the behaviour of Turing pattern formation systems on the inclusion of gene expression time delays may provide a means of distinguishing between possible forms of interaction kinetics. Finally, this study also emphasises that sub-cellular and gene expression dynamics should not be simply neglected in models of long range biological pattern formation via morphogens. © 2010 Society for Mathematical Biology.

Could wind replace nuclear?

International Nuclear Information System (INIS)

2017-01-01

This article aims at assessing the situation produced by a total replacement of nuclear energy by wind energy, while facing consumption demand at any moment, notably in December. The authors indicate the evolution of the French energy mix during December 2016, and the evolution of the rate between wind energy production and the sum of nuclear and wind energy production during the same month, and then give briefly some elements regarding necessary investments in wind energy to wholly replace nuclear energy. According to them, such a replacement would be ruinous

A strategy for the phased replacement of CANDU digital control computers

International Nuclear Information System (INIS)

Hepburn, G.A.

2001-01-01

Significant developments have occurred with respect to the replacement of the Plant Digital Control Computers (DCCs) on CANDU plants in the past six months. This paper summarises the conclusions of the condition assessment carried out on these machines at Point Lepreau Generating Station, and describes a strategy for a phased transition to a replacement system based on today's technology. Most elements of the strategy are already in place, and sufficient technical work has been done to allow those components which have been assessed as requiring prompt attention to be replaced in a matter of months. (author)

Cloning and Characterization of the Polyether Salinomycin Biosynthesis Gene Cluster of Streptomyces albus XM211

Science.gov (United States)

Jiang, Chunyan; Wang, Hougen; Kang, Qianjin; Liu, Jing

2012-01-01

Salinomycin is widely used in animal husbandry as a food additive due to its antibacterial and anticoccidial activities. However, its biosynthesis had only been studied by feeding experiments with isotope-labeled precursors. A strategy with degenerate primers based on the polyether-specific epoxidase sequences was successfully developed to clone the salinomycin gene cluster. Using this strategy, a putative epoxidase gene, slnC, was cloned from the salinomycin producer Streptomyces albus XM211. The targeted replacement of slnC and subsequent trans-complementation proved its involvement in salinomycin biosynthesis. A 127-kb DNA region containing slnC was sequenced, including genes for polyketide assembly and release, oxidative cyclization, modification, export, and regulation. In order to gain insight into the salinomycin biosynthesis mechanism, 13 gene replacements and deletions were conducted. Including slnC, 7 genes were identified as essential for salinomycin biosynthesis and putatively responsible for polyketide chain release, oxidative cyclization, modification, and regulation. Moreover, 6 genes were found to be relevant to salinomycin biosynthesis and possibly involved in precursor supply, removal of aberrant extender units, and regulation. Sequence analysis and a series of gene replacements suggest a proposed pathway for the biosynthesis of salinomycin. The information presented here expands the understanding of polyether biosynthesis mechanisms and paves the way for targeted engineering of salinomycin activity and productivity. PMID:22156425

Gene doping detection: evaluation of approach for direct detection of gene transfer using erythropoietin as a model system.

Science.gov (United States)

Baoutina, A; Coldham, T; Bains, G S; Emslie, K R

2010-08-01

As clinical gene therapy has progressed toward realizing its potential, concern over misuse of the technology to enhance performance in athletes is growing. Although 'gene doping' is banned by the World Anti-Doping Agency, its detection remains a major challenge. In this study, we developed a methodology for direct detection of the transferred genetic material and evaluated its feasibility for gene doping detection in blood samples from athletes. Using erythropoietin (EPO) as a model gene and a simple in vitro system, we developed real-time PCR assays that target sequences within the transgene complementary DNA corresponding to exon/exon junctions. As these junctions are absent in the endogenous gene due to their interruption by introns, the approach allows detection of trace amounts of a transgene in a large background of the endogenous gene. Two developed assays and one commercial gene expression assay for EPO were validated. On the basis of ability of these assays to selectively amplify transgenic DNA and analysis of literature on testing of gene transfer in preclinical and clinical gene therapy, it is concluded that the developed approach would potentially be suitable to detect gene doping through gene transfer by analysis of small volumes of blood using regular out-of-competition testing.

NextGen Technologies on the FAA's Standard Terminal Automation Replacement System

Science.gov (United States)

Witzberger, Kevin; Swenson, Harry; Martin, Lynne; Lin, Melody; Cheng, Jinn-Hwei

2014-01-01

This paper describes the integration, evaluation, and results from a high-fidelity human-in-the-loop (HITL) simulation of key NASA Air Traffic Management Technology Demonstration - 1 (ATD- 1) technologies implemented in an enhanced version of the FAA's Standard Terminal Automation Replacement System (STARS) platform. These ATD-1 technologies include: (1) a NASA enhanced version of the FAA's Time-Based Flow Management, (2) a NASA ground-based automation technology known as controller-managed spacing (CMS), and (3) a NASA advanced avionics airborne technology known as flight-deck interval management (FIM). These ATD-1 technologies have been extensively tested in large-scale HITL simulations using general-purpose workstations to study air transportation technologies. These general purpose workstations perform multiple functions and are collectively referred to as the Multi-Aircraft Control System (MACS). Researchers at NASA Ames Research Center and Raytheon collaborated to augment the STARS platform by including CMS and FIM advisory tools to validate the feasibility of integrating these automation enhancements into the current FAA automation infrastructure. NASA Ames acquired three STARS terminal controller workstations, and then integrated the ATD-1 technologies. HITL simulations were conducted to evaluate the ATD-1 technologies when using the STARS platform. These results were compared with the results obtained when the ATD-1 technologies were tested in the MACS environment. Results collected from the numerical data show acceptably minor differences, and, together with the subjective controller questionnaires showing a trend towards preferring STARS, validate the ATD-1/STARS integration.

Gene expression studies of reference genes for quantitative real-time PCR: an overview in insects.

Science.gov (United States)

Shakeel, Muhammad; Rodriguez, Alicia; Tahir, Urfa Bin; Jin, Fengliang

2018-02-01

Whenever gene expression is being examined, it is essential that a normalization process is carried out to eliminate non-biological variations. The use of reference genes, such as glyceraldehyde-3-phosphate dehydrogenase, actin, and ribosomal protein genes, is the usual method of choice for normalizing gene expression. Although reference genes are used to normalize target gene expression, a major problem is that the stability of these genes differs among tissues, developmental stages, species, and responses to abiotic factors. Therefore, the use and validation of multiple reference genes are required. This review discusses the reasons that why RT-qPCR has become the preferred method for validating results of gene expression profiles, the use of specific and non-specific dyes and the importance of use of primers and probes for qPCR as well as to discuss several statistical algorithms developed to help the validation of potential reference genes. The conflicts arising in the use of classical reference genes in gene normalization and their replacement with novel references are also discussed by citing the high stability and low stability of classical and novel reference genes under various biotic and abiotic experimental conditions by employing various methods applied for the reference genes amplification.

Modulator reliability and bandwidth improvement: replacing tetrodes with MOSFETs

International Nuclear Information System (INIS)

Donaldson, A.R.

1982-01-01

Three types of power MOS field effect transistors were studied with the intent of replacing a parallel pair of vacuum tube tetrodes in a linear modulator. The tetrodes have the shortest lifetimes of any other tubes in the system. The FETs offer definite performance advantages when compared to bipolar transistors and definite cost advantages when compared to vacuum tubes. Replacement of the tetrodes does however require careful consideration of voltage, current and to a lesser extent bandwidth capability in order to enhance overall modulator reliability without compromising present performance

A Comprehensive Review of Retinal Gene Therapy

OpenAIRE

Boye, Shannon E; Boye, Sanford L; Lewin, Alfred S; Hauswirth, William W

2013-01-01

Blindness, although not life threatening, is a debilitating disorder for which few, if any treatments exist. Ocular gene therapies have the potential to profoundly improve the quality of life in patients with inherited retinal disease. As such, tremendous focus has been given to develop such therapies. Several factors make the eye an ideal organ for gene-replacement therapy including its accessibility, immune privilege, small size, compartmentalization, and the existence of a contralateral co...

Project Plan 7930 Cell G PaR Remote Handling System Replacement

International Nuclear Information System (INIS)

Kinney, Kathryn A.

2009-01-01

For over 40 years the US Department of Energy (DOE) and its predecessors have made Californium-252 ( 252 Cf) available for a wide range of industries including medical, nuclear fuels, mining, military and national security. The Radiochemical Engineering Development Center (REDC) located within the Oak Ridge National Laboratory (ORNL) processes irradiated production targets from the High Flux Isotope Reactor (HFIR). Operations in Building 7930, Cell G provide over 70% of the world's demand for 252 Cf. Building 7930 was constructed and equipped in the mid-1960s. Current operations for 252 Cf processing in Building 7930, Cell G require use of through-the-wall manipulators and the PaR Remote Handling System. Maintenance and repairs for the manipulators is readily accomplished by removal of the manipulator and relocation to a repair shop where hands-on work can be performed in glove boxes. Contamination inside cell G does not currently allow manned entry and no provisions were created for a maintenance area inside the cell. There has been no maintenance of the PaR system or upgrades, leaving operations vulnerable should the system have a catastrophic failure. The Cell G PaR system is currently being operated in a run to failure mode. As the manipulator is now 40+ years old there is significant risk in this method of operation. In 2006 an assessment was completed that resulted in recommendations for replacing the manipulator operator control and power centers which are used to control and power the PaR manipulator in Cell G. In mid-2008 the chain for the bridge drive failed and subsequent examinations indicated several damaged links (see Figure 1). To continue operations the PaR manipulator arm is being used to push and pull the bridge as a workaround. A retrieval tool was fabricated, tested and staged inside Cell G that will allow positioning of the bridge and manipulator arm for removal from the cell should the PaR system completely fail. A fully functioning and

Food-grade double emulsions as effective fat replacers in meat systems

NARCIS (Netherlands)

Eisinaite, Viktorija; Juraite, Dovile; Schroën, Karin; Leskauskaite, Daiva

2017-01-01

Double emulsions were used to not only replace 7 and 11% of animal fat in meat products, but also as a way to enhance the product colour. The coarse emulsion containing native beetroot juice as inner water phase, sunflower oil as oil phase and 0.5% whey protein isolate as outer water phase was

Cost feasibility of a pre-checking medical tourism system for U.S. patients undertaking joint replacement surgery in Taiwan.

Science.gov (United States)

Haung, Ching-Ying; Wang, Sheng-Pen; Chiang, Chih-Wei

2010-01-01

Medical tourism is a relatively recent global economic and political phenomenon that has assumed increasing importance for developing countries, particularly in Asia. In fact, Taiwan possesses a niche for developing medical tourism because many hospitals provide state-of-the-art medicine in all disciplines and many doctors are trained in the United States (US). Among the most common medical procedures outsourced, joint replacements such as total knee replacement (TKR) and total hip replacement (THR) are two surgeries offered to US patients at a lower cost and shorter waiting time than in the US. This paper proposed a pre-checking medical tourism system (PCMTS) and evaluated the cost feasibility of recruiting American clients traveling to Taiwan for joint replacement surgery. Cost analysis was used to estimate the prime costs for each stage in the proposed PCMTS. Sensitivity analysis was implemented to examine how different pricings for medical checking and a surgical operation (MC&SO) and recovery, can influence the surplus per patient considering the PCMTS. Finally, the break-even method was adopted to test the tradeoff between the sunk costs of investment in the PCMTS and the annual surplus for participating hospitals. A novel business plan was built showing that pre-checking stations in medical tourism can provide post-operative care and recovery follow-up. Adjustable pricing for hospital administrators engaged in the PCMTS consisted of two main costs: US$3,700 for MC&SO and US$120 for the hospital stay. Guidelines for pricing were provided to maximize the annual surplus from this plan with different number of patients participating in PCMTS. The maximal profit margin from each American patient undertaking joint surgery is about US$24,315. Using cost analysis, this article might be the first to evaluate the feasibility of PCMTS for joint replacement surgeries. The research framework in this article is applicable when hospital administrators evaluate the

A model for an economically optimal replacement of a breeder flock.

Science.gov (United States)

Yassin, Hurria; Velthuis, Annet G J; Giesen, Gerard W J; Oude Lansink, Alfons G J M

2012-12-01

A deterministic model is developed to support the tactical and operational replacement decisions at broiler breeder farms. The marginal net revenue approach is applied to determine the optimal replacement age of a flock. The objective function of the model maximizes the annual gross margin over the flock's production cycle. To calculate the gross margin, future egg production, fertility, or hatchability of the eggs, revenues and variable costs of a flock were estimated. For tactical decisions, the optimal laying length is the age at which the average gross margin of an average flock is maximal. For operational decisions, a flock should be replaced when the marginal gross margin of a replaceable flock is less than the average gross margin of an average flock. To demonstrate the model, a broiler breeder flock from a Dutch breeder farm was used. A sensitivity analysis showed that the optimal replacement decision, for both tactical and operational management, is sensitive to the decrease in the weekly egg production after the peak and the prices of feed and hatching eggs. The effect of the decrease in weekly fertility after the peak on the replacement decision is related to the payment system for hatching eggs.

Relations between Three Dopaminergic System Genes, School Attachment, and Adolescent Delinquency

Science.gov (United States)

Fine, Adam; Mahler, Alissa; Simmons, Cortney; Chen, Chuansheng; Moyzis, Robert; Cauffman, Elizabeth

2016-01-01

Both environmental factors and genetic variation, particularly in genes responsible for the dopaminergic system such as "DRD4," "DRD2," and "DAT1" ("SLC6A3"), affect adolescent delinquency. The school context, despite its developmental importance, has been overlooked in gene-environment research. Using data…

USH2A Gene Editing Using the CRISPR System

Directory of Open Access Journals (Sweden)

Carla Fuster-García

2017-09-01

Full Text Available Usher syndrome (USH is a rare autosomal recessive disease and the most common inherited form of combined visual and hearing impairment. Up to 13 genes are associated with this disorder, with USH2A being the most prevalent, due partially to the recurrence rate of the c.2299delG mutation. Excluding hearing aids or cochlear implants for hearing impairment, there are no medical solutions available to treat USH patients. The repair of specific mutations by gene editing is, therefore, an interesting strategy that can be explored using the CRISPR/Cas9 system. In this study, this method of gene editing is used to target the c.2299delG mutation on fibroblasts from an USH patient carrying the mutation in homozygosis. Successful in vitro mutation repair was demonstrated using locus-specific RNA-Cas9 ribonucleoproteins with subsequent homologous recombination repair induced by an engineered template supply. Effects on predicted off-target sites in the CRISPR-treated cells were discarded after a targeted deep-sequencing screen. The proven effectiveness and specificity of these correction tools, applied to the c.2299delG pathogenic variant of USH2A, indicates that the CRISPR system should be considered to further explore a potential treatment of USH. Keywords: Usher syndrome, USH2A, c.2299delG, CRISPR, gene editing, RNPs

Advances in detection systems of gene and chromosome abnormalities

International Nuclear Information System (INIS)

Yatagai, Takeo

2002-01-01

This review is described from the aspect of radiation biology. For analysis at gene level, oxidative lesion of DNA like 7,8-dihydro-8-oxoguanine formation and its repair by DNA polymerase η etc in bacteria, yeast and mammalian cells are suggested to be a useful index of radiation mutation. Transgenic mice with E. coli and/or phage gene as a reporter can be a tool for gene analysis for specific organ mutation: data obtained by irradiation of X-ray, γ-ray and accelerated carbon beam to the mouse gpt delta are presented. For analysis from gene to chromosome levels, loss of heterozygosity of a specific gene is a key for analysis of chromosome aberration at the molecular level. Studies in yeast and mammalian cells are presented. The author also described data of gene mutation in TK6 cells irradiated by 2 Gy of X-ray and 10 cGy of carbon beam (135 MeV/u) generated by ring-cycrotron. Human-hamster hybrid cell is an alternative tool. Concerning significance at the individual level, the author quoted studies of irradiation of parent mice resulting in increased incidence of somatic cell mutation and of cancer in offspring. Future systems for gene mutation will be a use of transgenic mice or of markers like a specific cancer. (K.H.)

Radiation Source Replacement Workshop

Energy Technology Data Exchange (ETDEWEB)

Griffin, Jeffrey W.; Moran, Traci L.; Bond, Leonard J.

2010-12-01

This report summarizes a Radiation Source Replacement Workshop in Houston Texas on October 27-28, 2010, which provided a forum for industry and researchers to exchange information and to discuss the issues relating to replacement of AmBe, and potentially other isotope sources used in well logging.

The use of synthetic ligaments in the design of an enhanced stability total knee joint replacement.

Science.gov (United States)

Stokes, Michael D; Greene, Brendan C; Pietrykowski, Luke W; Gambon, Taylor M; Bales, Caroline E; DesJardins, John D

2018-03-01

Current total knee replacement designs work to address clinically desired knee stability and range of motion through a balance of retained anatomy and added implant geometry. However, simplified implant geometries such as bearing surfaces, posts, and cams are often used to replace complex ligamentous constraints that are sacrificed during most total knee replacement procedures. This article evaluates a novel total knee replacement design that incorporates synthetic ligaments to enhance the stability of the total knee replacement system. It was hypothesized that by incorporating artificial cruciate ligaments into a total knee replacement design at specific locations and lengths, the stability of the total knee replacement could be significantly altered while maintaining active ranges of motion. The ligament attachment mechanisms used in the design were evaluated using a tensile test, and determined to have a safety factor of three with respect to expected ligamentous loading in vivo. Following initial computational modeling of possible ligament orientations, a physical prototype was constructed to verify the function of the design by performing anterior/posterior drawer tests under physiologic load. Synthetic ligament configurations were found to increase total knee replacement stability up to 94% compared to the no-ligament case, while maintaining total knee replacement flexion range of motion between 0° and 120°, indicating that a total knee replacement that incorporates synthetic ligaments with calibrated location and lengths should be able to significantly enhance and control the kinematic performance of a total knee replacement system.

Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy

Directory of Open Access Journals (Sweden)

Alexander L. Pan

2012-01-01

Full Text Available Spontaneous coronary artery dissection is a rare condition, usually presenting as an acute coronary syndrome, and is often seen in states associated with high systemic estrogen levels such as pregnancy or oral contraceptive use. While topical hormonal replacement therapy may result in increased estrogen levels similar to those documented with oral contraceptive use, there are no reported cases of spontaneous coronary dissection with topical hormonal replacement therapy. We describe a 53-year-old female who developed two spontaneous coronary dissections while on topical hormonal replacement therapy. The patient had no other risk factors for coronary dissection. After withdrawal from topical hormonal therapy, our patient has done well and has not had recurrent coronary artery dissections over a one-year follow-up period. The potential contributory role of topical hormonal therapy as a cause of spontaneous coronary dissection should be recognized.

Can photovoltaic replace nuclear?

International Nuclear Information System (INIS)

2017-01-01

As the French law on energy transition for a green growth predicts that one third of nuclear energy production is to be replaced by renewable energies (wind and solar) by 2025, and while the ADEME proposes a 100 per cent renewable scenario for 2050, this paper proposes a brief analysis of the replacement of nuclear energy by solar photovoltaic energy. It presents and discusses some characteristics of photovoltaic production: production level during a typical day for each month (a noticeable lower production in December), evolution of monthly production during a year, evolution of the rate between nuclear and photovoltaic production. A cost assessment is then proposed for energy storage and for energy production, and a minimum cost of replacement of nuclear by photovoltaic is assessed. The seasonal effect is outlined, as well as the latitude effect. Finally, the authors outline the huge cost of such a replacement, and consider that public support to new photovoltaic installations without an at least daily storage mean should be cancelled

Expression of the lysostaphin gene of Staphylococcus simulans in a eukaryotic system.

OpenAIRE

Williamson, C M; Bramley, A J; Lax, A J

1994-01-01

The lysostaphin gene of Staphylococcus simulans was cloned into Escherichia coli. The 5' end of the gene was modified to include a eukaryotic start codon, the Kozak expression start site consensus sequence, and an enzyme site to facilitate manipulation of the gene. Transcription of the modified gene in vitro yielded an RNA transcript which, when added to a rabbit reticulocyte cell-free translation system, directed the synthesis of several products. The largest product, migrating at approximat...

Effects of replacing lactose from milk replacer by glucose, fructose, or glycerol on energy partitioning in veal calves

NARCIS (Netherlands)

Gilbert, M. S.; Pantophlet, A. J.; van den Borne, J. J. G. C.; Hendriks, W. H.; Schols, H. A.; Gerrits, W. J. J.

Calf milk replacers contain 40 to 50% lactose. Fluctuating dairy prices are a major economic incentive to replace lactose from milk replacers by alternative energy sources. Our objective was, therefore, to determine the effects of replacement of lactose with glucose, fructose, or glycerol on energy

Protein replacement by receptor-mediated endocytosis corrects the sensitivity of Fanconi anemia group C cells to mitomycin C

NARCIS (Netherlands)

Youssoufian, H; Kruyt, FAE; Li, XT

1999-01-01

Current methods for direct gene transfer into hematopoietic cells are inefficient. Here we show that functional complementation of Fanconi anemia (FA) group C cells by protein replacement can be as efficacious as by transfection with wild-type FAC cDNA, We expressed a chimeric protein (called

DNA-transporting nanoparticles : design and in vitro evaluation of DNA and formulation for non-viral gene delivery

NARCIS (Netherlands)

van Gaal, E.V.B.

2010-01-01

The aim of gene therapy is to treat, cure or prevent a disease by replacing defective genes, introducing new genes or changing the expression of a person’s genes. Success of gene therapy is dependent on successful delivery of DNA from the site of administration into cell nuclei. Naturally occurring

Development of a virus-induced gene silencing (VIGS) system for Spinacia oleracea L

DEFF Research Database (Denmark)

Lee, Jungmin; Cao, Dang Viet; Kim, Jiwon

2017-01-01

Virus-induced gene silencing (VIGS) is known as a rapid and efficient system for studying functions of interesting genes in plants. Tobacco rattle virus (TRV) is widely applied for the gene silencing of many plants. Although spinach is a TRV-susceptible plant, a TRV-based VIGS system has not yet ...

Delirium After Transcatheter Aortic Valve Replacement.

Science.gov (United States)

Giuseffi, Jennifer L; Borges, Nyal E; Boehm, Leanne M; Wang, Li; McPherson, John A; Fredi, Joseph L; Ahmad, Rashid M; Ely, E Wesley; Pandharipande, Pratik P

2017-07-01

Postoperative delirium is associated with increased mortality. Patients undergoing transcatheter aortic valve replacement are at risk for delirium because of comorbid conditions. To compare the incidence, odds, and mortality implications of delirium between patients undergoing transcatheter replacement and patients undergoing surgical replacement. The Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the Intensive Care Unit were used to assess arousal level and delirium prospectively in all patients with severe aortic stenosis who had transcatheter or surgical aortic valve replacement at an academic medical center. Multivariable logistic regression was used to determine the relationship between procedure type and occurrence of delirium. Cox regression was used to assess the association between postoperative delirium and 6-month mortality. A total of 105 patients had transcatheter replacement and 121 had surgical replacement. Patients in the transcatheter group were older (median age, 81 vs 68 years; P replacement. Delirium is less likely to develop in the transcatheter group but is associated with higher mortality in both groups. ©2017 American Association of Critical-Care Nurses.

Environmental assessment for the electric utility system distribution, replacements and upgrades at Lawrence Livermore National Laboratory

International Nuclear Information System (INIS)

1992-04-01

This Environmental Assessment evaluates the environmental effects resulting from the distribution of new electrical service, replacement of inadequate or aging equipment, and upgrade of the existing electrical utility system at Lawrence Livermore National Laboratory. The projects assessed herein do not impact cultural or historic resources, sensitive habitats or wetlands and are not a source of air emissions. The potential environmental effects that do result from the action are fugitive dust and noise from construction and the disposal of potentially contaminated soil removed from certain limited areas of the LLNL site as a result of trenching for underground transmission lines. The actions described in this assessment represent an improved safety and reliability to the existing utility system. Inherent in the increased reliability and upgrades is a net increase in electrical capacity, with future expansion reserve. As with any electrical device, the electrical utility system has associated electric and magnetic fields that present a potential source of personnel exposure. The potential is not increased, however, beyond that which already exists for the present electrical utility system

Systemic virus-induced gene silencing allows functional characterization of maize genes during biotrophic interaction with Ustilago maydis.

Science.gov (United States)

van der Linde, Karina; Kastner, Christine; Kumlehn, Jochen; Kahmann, Regine; Doehlemann, Gunther

2011-01-01

Infection of maize (Zea mays) plants with the corn smut fungus Ustilago maydis leads to the formation of large tumors on the stem, leaves and inflorescences. In this biotrophic interaction, plant defense responses are actively suppressed by the pathogen, and previous transcriptome analyses of infected maize plants showed massive and stage-specific changes in host gene expression during disease progression. To identify maize genes that are functionally involved in the interaction with U. maydis, we adapted a virus-induced gene silencing (VIGS) system based on the brome mosaic virus (BMV) for maize. Conditions were established that allowed successful U. maydis infection of BMV-preinfected maize plants. This set-up enabled quantification of VIGS and its impact on U. maydis infection using a quantitative real-time PCR (qRT-PCR)-based readout. In proof-of-principle experiments, an U. maydis-induced terpene synthase was shown to negatively regulate disease development while a protein involved in cell death inhibition was required for full virulence of U. maydis. The results suggest that this system is a versatile tool for the rapid identification of maize genes that determine compatibility with U. maydis. © (2010) Max Planck Society. Journal compilation © New Phytologist Trust (2010).

Packet loss replacement in voip using a recursive low-order autoregressive modelbased speech

International Nuclear Information System (INIS)

Miralavi, Seyed Reza; Ghorshi, Seyed; Mortazavi, Mohammad; Choupan, Jeiran

2011-01-01

In real-time packet-based communication systems one major problem is misrouted or delayed packets which results in degraded perceived voice quality. When some speech packets are not available on time, the packet is known as lost packet in real-time communication systems. The easiest task of a network terminal receiver is to replace silence for the duration of lost speech segments. In a high quality communication system in order to avoid quality reduction due to packet loss a suitable method and/or algorithm is needed to replace the missing segments of speech. In this paper, we introduce a recursive low order autoregressive (AR) model for replacement of lost speech segment. The evaluation results show that this method has a lower mean square error (MSE) and low complexity compared to the other efficient methods like high-order AR model without any substantial degradation in perceived voice quality.

Africanization in the United States: replacement of feral European honeybees (Apis mellifera L.) by an African hybrid swarm.

Science.gov (United States)

Pinto, M Alice; Rubink, William L; Patton, John C; Coulson, Robert N; Johnston, J Spencer

2005-08-01

The expansion of Africanized honeybees from South America to the southwestern United States in feral population from the southern United States undergoing Africanization. Our microsatellite data showed that (1) the process of Africanization involved both maternal and paternal bidirectional gene flow between European and Africanized honeybees and (2) the panmitic European population was replaced by panmitic mixtures of A. m. scutellata and European genes within 5 years after Africanization. The post-Africanization gene pool (1998-2001) was composed of a diverse array of recombinant classes with a substantial European genetic contribution (mean 25-37%). Therefore, the resulting feral honeybee population of south Texas was best viewed as a hybrid swarm.

[Gene method for inconsistent hydrological frequency calculation. 2: Diagnosis system of hydrological genes and method of hydrological moment genes with inconsistent characters].

Science.gov (United States)

Xie, Ping; Zhao, Jiang Yan; Wu, Zi Yi; Sang, Yan Fang; Chen, Jie; Li, Bin Bin; Gu, Hai Ting

2018-04-01

The analysis of inconsistent hydrological series is one of the major problems that should be solved for engineering hydrological calculation in changing environment. In this study, the diffe-rences of non-consistency and non-stationarity were analyzed from the perspective of composition of hydrological series. The inconsistent hydrological phenomena were generalized into hydrological processes with inheritance, variability and evolution characteristics or regulations. Furthermore, the hydrological genes were identified following the theory of biological genes, while their inheritance bases and variability bases were determined based on composition of hydrological series under diffe-rent time scales. To identify and test the components of hydrological genes, we constructed a diagnosis system of hydrological genes. With the P-3 distribution as an example, we described the process of construction and expression of the moment genes to illustrate the inheritance, variability and evolution principles of hydrological genes. With the annual minimum 1-month runoff series of Yunjinghong station in Lancangjiang River basin as an example, we verified the feasibility and practicability of hydrological gene theory for the calculation of inconsistent hydrological frequency. The results showed that the method could be used to reveal the evolution of inconsistent hydrological series. Therefore, it provided a new research pathway for engineering hydrological calculation in changing environment and an essential reference for the assessment of water security.

Optimization on replacement period of plant equipment

International Nuclear Information System (INIS)

Kasai, Masao; Asano, Hiromi

2002-01-01

Optimization of the replacement period of plant equipment is one of the main items to rationalize the activities on plant maintenance. There are several models to replace the equipment and the formulations for optimizing the replacement period are different among these models. In this study, we calculated the optimum replacement periods for some equipment parts based on the replacement models and found that the optimum solutions are not so largely differ from the replacement models as far as the replacement period is not so large. So we will be able to use the most usable model especially in the early phase of rationalization on plant maintenance, since there are large uncertainties in data for optimization. (author)

Metagenomic analysis of antibiotic resistance genes in coastal industrial mariculture systems.

Science.gov (United States)

Wang, Jian-Hua; Lu, Jian; Zhang, Yu-Xuan; Wu, Jun; Luo, Yongming; Liu, Hao

2018-04-01

The overuse of antibiotics has posed a propagation of antibiotic resistance genes (ARGs) in aquaculture systems. This study firstly explored the ARGs profiles of the typical mariculture farms including conventional and recirculating systems using metagenomics approach. Fifty ARGs subtypes belonging to 21 ARGs types were identified, showing the wide-spectrum profiles of ARGs in the coastal industrial mariculture systems. ARGs with multiple antibiotics resistance have emerged in the mariculure systems. The co-occurrence pattern between ARGs and microbial taxa showed that Proteobacteria and Bacteroidetes were potential dominant hosts of ARGs in the industrial mariculture systems. Typical nitrifying bacteria such as Nitrospinae in mariculture systems also carried with some resistance genes. Relative abundance of ARGs in fish ponds and wastewater treatment units was relatively high. The investigation showed that industrial mariculture systems were important ARGs reservoirs in coastal area, indicating the critical role of recirculating systems in the terms of ARGs pollution control. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design verification for reactor head replacement

International Nuclear Information System (INIS)

Dwivedy, K.K.; Whitt, M.S.; Lee, R.

2005-01-01

This paper outlines the challenges of design verification for reactor head replacement for PWR plants and the program for qualification from the prospective of the utility design engineering group. This paper is based on the experience with the design confirmation of four reactor head replacements for two plants, and their interfacing components, parts, appurtenances, and support structures. The reactor head replacement falls under the jurisdiction of the applicable edition of the ASME Section XI code, with particular reference to repair/replacement activities. Under any repair/replacement activities, demands may be encountered in the development of program and plan for replacement due to the vintage of the original design/construction Code and the design reports governing the component qualifications. Because of the obvious importance of the reactor vessel, these challenges take on an added significance. Additional complexities are introduced to the project, when the replacement components are fabricated by vendors different from the original vendor. Specific attention is needed with respect to compatibility with the original design and construction of the part and interfacing components. The program for reactor head replacement requires evaluation of welding procedures, applicable examination, test, and acceptance criteria for material, welds, and the components. Also, the design needs to take into consideration the life of the replacement components with respect to the extended period of operation of the plant after license renewal and other plant improvements. Thus, the verification of acceptability of reactor head replacement provides challenges for development and maintenance of a program and plan, design specification, design report, manufacturer's data report and material certification, and a report of reconciliation. The technical need may also be compounded by other challenges such as widely scattered global activities and organizational barriers, which

Tetracycline-inducible gene expression system in Leishmania mexicana

Czech Academy of Sciences Publication Activity Database

Kraeva, N.; Ishemgulova, A.; Lukeš, Julius; Yurchenko, Vyacheslav

2014-01-01

Roč. 198, č. 1 (2014), s. 11-13 ISSN 0166-6851 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : Leishmania mexicana * Gene expression * Tet-inducible system Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.787, year: 2014

Assessing gene function in the ruminant placenta.

Science.gov (United States)

Anthony, R V; Cantlon, J D; Gates, K C; Purcell, S H; Clay, C M

2010-01-01

The placenta provides the means for nutrient transfer from the mother to the fetus, waste transfer from the fetus to the mother, protection of the fetus from the maternal immune system, and is an active endocrine organ. While many placental functions have been defined and investigated, assessing the function of specific genes expressed by the placenta has been problematic, since classical ablation-replacement methods are not feasible with the placenta. The pregnant sheep has been a long-standing animal model for assessing in vivo physiology during pregnancy, since surgical placement of indwelling catheters into both maternal and fetal vasculature has allowed the assessment of placental nutrient transfer and utilization, as well as placental hormone secretion, under unanesthetized-unstressed steady state sampling conditions. However, in ruminants the lack of well-characterized trophoblast cell lines and the inefficiency of creating transgenic pregnancies in ruminants have inhibited our ability to assess specific gene function. Recently, sheep and cattle primary trophoblast cell lines have been reported, and may further our ability to investigate trophoblast function and transcriptional regulation of genes expressed by the placenta. Furthermore, viral infection of the trophoectoderm layer of hatched blastocysts, as a means for placenta-specific transgenesis, holds considerable potential to assess gene function in the ruminant placenta. This approach has been used successfully to "knockdown" gene expression in the developing sheep conceptus, and has the potential for gain-of-function experiments as well. While this technology is still being developed, it may provide an efficient approach to assess specific gene function in the ruminant placenta.

Is the crowd better as an assistant or a replacement in ontology engineering? An exploration through the lens of the Gene Ontology.

Science.gov (United States)

Mortensen, Jonathan M; Telis, Natalie; Hughey, Jacob J; Fan-Minogue, Hua; Van Auken, Kimberly; Dumontier, Michel; Musen, Mark A

2016-04-01

Biomedical ontologies contain errors. Crowdsourcing, defined as taking a job traditionally performed by a designated agent and outsourcing it to an undefined large group of people, provides scalable access to humans. Therefore, the crowd has the potential to overcome the limited accuracy and scalability found in current ontology quality assurance approaches. Crowd-based methods have identified errors in SNOMED CT, a large, clinical ontology, with an accuracy similar to that of experts, suggesting that crowdsourcing is indeed a feasible approach for identifying ontology errors. This work uses that same crowd-based methodology, as well as a panel of experts, to verify a subset of the Gene Ontology (200 relationships). Experts identified 16 errors, generally in relationships referencing acids and metals. The crowd performed poorly in identifying those errors, with an area under the receiver operating characteristic curve ranging from 0.44 to 0.73, depending on the methods configuration. However, when the crowd verified what experts considered to be easy relationships with useful definitions, they performed reasonably well. Notably, there are significantly fewer Google search results for Gene Ontology concepts than SNOMED CT concepts. This disparity may account for the difference in performance - fewer search results indicate a more difficult task for the worker. The number of Internet search results could serve as a method to assess which tasks are appropriate for the crowd. These results suggest that the crowd fits better as an expert assistant, helping experts with their verification by completing the easy tasks and allowing experts to focus on the difficult tasks, rather than an expert replacement. Copyright © 2016 Elsevier Inc. All rights reserved.

Provision of faultiness of technical objects on the computerized simulation base of their elements replacements

International Nuclear Information System (INIS)

Muzdybaev, M.S.; Kul'seitov, A.Zh.

2002-01-01

It is noted, that on the base of technical system reliability analysis items of replacements (repair) of a good's parts are considered. It is shown, that one of the way of a good reliability task solution is formation of groups of a good parts joint replacements. Advantages which under similar approach are first of al revealing both the high faultiness level and the system work ability. It is determined, that it is purposively parts limiting of a good reliability joint in groups of its joint replacements, at that its amount it is necessary to achieving a minimum

[Gene therapy and cell transplantation for Parkinson's disease].

Science.gov (United States)

Muramatsu, Shin-ichi

2005-11-01

Increasing enthusiasm in the field of stem cell research is raising the hope of novel cell replacement therapies for Parkinson's disease (PD), but it also raises both scientific and ethical concerns. In most cases, dopaminergic cells are transplanted ectopically into the striatum instead of the substantia nigra. If the main mechanism underlying any observed functional recovery with these cell replacement therapies is restoration of dopaminergic neurotransmission, then viral vector-mediated gene delivery of dopamine-synthesizing enzymes is a more straight forward approach. The development of a recombinant adeno-associated viral (AAV) vector is making gene therapy for PD a feasible therapeutic option in the clinical arena. Efficient and long-term expression of genes for dopamine-synthesizing enzymes in the striatum restored local dopamine production and allowed behavioral recovery in animal models of PD. A clinical trial to evaluate the safety and efficacy of AAV vector-mediated gene transfer of aromatic L-amino acid decarboxylase, an enzyme that converts L-dopa to dopamine, is underway. With this strategy patients would still need to take L-dopa to control their PD symptoms, however, dopamine production could be regulated by altering the dose of L-dopa. Another AAV vector-based clinical trial is also ongoing in which the subthalamic nucleus is transduced to produce inhibitory transmitters.

A non-inheritable maternal Cas9-based multiple-gene editing system in mice

OpenAIRE

Takayuki Sakurai; Akiko Kamiyoshi; Hisaka Kawate; Chie Mori; Satoshi Watanabe; Megumu Tanaka; Ryuichi Uetake; Masahiro Sato; Takayuki Shindo

2016-01-01

The CRISPR/Cas9 system is capable of editing multiple genes through one-step zygote injection. The preexisting method is largely based on the co-injection of Cas9 DNA (or mRNA) and guide RNAs (gRNAs); however, it is unclear how many genes can be simultaneously edited by this method, and a reliable means to generate transgenic (Tg) animals with multiple gene editing has yet to be developed. Here, we employed non-inheritable maternal Cas9 (maCas9) protein derived from Tg mice with systemic Cas9...

Gene therapy for ocular diseases.

Science.gov (United States)

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Diagenetic replacement of Micas by Carbonates

NARCIS (Netherlands)

Oele, E.

1961-01-01

In the Ordovician sandstones of the Cantabrian Mountains a replacement of the micas by carbonate minerals could be observed. The absence of metamorphic minerals suggests a diagenetic replacement. This is supported by the finding of the same type of replacement in some undisturbed Pliocene sediments

A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila.

Science.gov (United States)

Chen, Chun-Hong; Huang, Haixia; Ward, Catherine M; Su, Jessica T; Schaeffer, Lorian V; Guo, Ming; Hay, Bruce A

2007-04-27

One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.

Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

OpenAIRE

Morille , Marie; Passirani , Catherine; Vonarbourg , Arnaud; Clavreul , Anne; Benoit , Jean-Pierre

2008-01-01

International audience; Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection...

47 CFR 13.17 - Replacement license.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Replacement license. 13.17 Section 13.17 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL RADIO OPERATORS General § 13.17 Replacement... request a replacement. The application must be accompanied by the required fee and submitted to the...

24 CFR 891.605 - Replacement reserve.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 891.605... 8 Assistance § 891.605 Replacement reserve. (a) Establishment of reserve. The Borrower shall establish and maintain a replacement reserve to aid in funding extraordinary maintenance, and repair and...

7 CFR 3015.167 - Replacement of equipment.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Replacement of equipment. 3015.167 Section 3015.167..., DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE REGULATIONS Property § 3015.167 Replacement of equipment. (a) If needed, equipment may be exchanged for replacement equipment. Replacement of equipment may be...

International examples of steam generator replacement

International Nuclear Information System (INIS)

Wiechmann, K.

1993-01-01

Since 1979-1980 a total of twelve nuclear power plants world-wide have had their steam generators replaced. The replacement of the Combustion steam generators in the Millstone-2 plant in the United States was completed very recently. Steam generator replacement activities are going on at present in four plants. In North Anna, the steam generators have been under replacement since January 1990. In Japan, preparations have been started for Genkai-1. Since January 1992, the two projects in Beznau-1, Switzerland, and Doel-3, Belgium, have bee planned and executed in parallel. Why steam generator replacement? There are a number of defect mechanisms which give rise to the need for early steam generator replacement. One of the main reasons is the use of Inconel-600 as material for the heating tubes. Steam generator heating tubes made of Inconel-600 have been known to exhibit their first defects due to stress corrosion cracking after less than one year of operation. (orig.) [de

Positive impact of hormone replacement therapy on the fibrinolytic system

DEFF Research Database (Denmark)

Madsen, J S; Kristensen, S R; Gram, J

2003-01-01

be of importance. OBJECTIVES: To investigate the prolonged effect of HRT on the fibrinolytic system and to determine whether two common polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) genes modulate this effect. Methods: Healthy postmenopausal women (n...... = 248) were randomized to HRT (n = 122) or no substitution (n = 126) 5 years prior to investigation. RESULTS: Significantly higher values of t-PA activity and lower values of PAI-1 activity and PAI-1 antigen were found in the HRT group compared with the control group. This effect was independent...... of smoking and without influence from the two common polymorphisms PAI-1 -675(4G/5G) and t-PA intron8ins311. Furthermore, no difference between opposed estrogen (with norethisterone acetate as the gestagen component) and unopposed estrogen therapy was found. Both an intention-to-treat and a per...

Psychosocial determinants of outcomes in knee replacement.

Science.gov (United States)

Lopez-Olivo, Maria A; Landon, Glenn C; Siff, Sherwin J; Edelstein, David; Pak, Chong; Kallen, Michael A; Stanley, Melinda; Zhang, Hong; Robinson, Kausha C; Suarez-Almazor, Maria E

2011-10-01

To identify potential psychosocial and educational barriers to clinical success following knee replacement. The authors evaluated 241 patients undergoing total knee replacement, preoperatively and 6 months after surgery. Outcomes included the Western Ontario McMaster (WOMAC) scale and the Knee Society rating system (KSRS). Independent variables included: the medical outcome study-social support scale; depression, anxiety and stress scale; brief COPE inventory; health locus of control; arthritis self-efficacy scale and the life orientation test-revised. Multiple regression models evaluated associations of baseline demographic and psychosocial variables with outcomes at 6 months, controlling for body mass index, comorbidities and baseline outcome scores. Patients' mean age was 65 ± 9 years; 65% were women. Most patients improved outcomes after surgery. Several psychosocial variables were associated with outcomes. Regression analyses indicated lower education, less tangible support, depression, less problem-solving coping, more dysfunctional coping, lower internal locus of control were associated with worse WOMAC scores (R(2) contribution of psychosocial variables for pain 0.07; for function, 0.14). Older age, lower education, depression and less problem-solving coping were associated with poorer total KSRS scores (R(2) contribution of psychosocial variables to total KSRS model 0.09). Psychosocial variables as a set contributed from 25% to 74% of total explained variance across the models tested. Patients' level of education, tangible support, depression, problem-solving coping, dysfunctional coping and internal locus of control were associated with pain and functional outcomes after knee replacement. The findings suggest that, in addition to medical management, perioperative psychosocial evaluation and intervention are crucial in enhancing knee replacement outcomes.

Targeting Herpetic Keratitis by Gene Therapy

Directory of Open Access Journals (Sweden)

Hossein Mostafa Elbadawy

2012-01-01

Full Text Available Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1 can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.

30 CFR 800.30 - Replacement of bonds.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Replacement of bonds. 800.30 Section 800.30... REQUIREMENTS FOR SURFACE COAL MINING AND RECLAMATION OPERATIONS UNDER REGULATORY PROGRAMS § 800.30 Replacement... replacement performance bonds. Replacement of a performance bond pursuant to this section shall not constitute...

24 CFR 572.125 - Replacement reserves.

Science.gov (United States)

2010-04-01

...) Homeownership Program Requirements-Implementation Grants § 572.125 Replacement reserves. (a) Purpose. A single replacement reserve may be established for the homeownership program only if HUD determines it is necessary to... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Replacement reserves. 572.125...

Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

International Nuclear Information System (INIS)

Hader, H.; Gadoth, N.; Heifetz, H.

1983-01-01

The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen

Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

Energy Technology Data Exchange (ETDEWEB)

Hader, H.; Gadoth, N.; Heifetz, H.

1983-11-01

The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen.

Gene Profiling in Patients with Systemic Sclerosis Reveals the Presence of Oncogenic Gene Signatures

Directory of Open Access Journals (Sweden)

Marzia Dolcino

2018-03-01

Full Text Available Systemic sclerosis (SSc is a rare connective tissue disease characterized by three pathogenetic hallmarks: vasculopathy, dysregulation of the immune system, and fibrosis. A particular feature of SSc is the increased frequency of some types of malignancies, namely breast, lung, and hematological malignancies. Moreover, SSc may also be a paraneoplastic disease, again indicating a strong link between cancer and scleroderma. The reason of this association is still unknown; therefore, we aimed at investigating whether particular genetic or epigenetic factors may play a role in promoting cancer development in patients with SSc and whether some features are shared by the two conditions. We therefore performed a gene expression profiling of peripheral blood mononuclear cells (PBMCs derived from patients with limited and diffuse SSc, showing that the various classes of genes potentially linked to the pathogenesis of SSc (such as apoptosis, endothelial cell activation, extracellular matrix remodeling, immune response, and inflammation include genes that directly participate in the development of malignancies or that are involved in pathways known to be associated with carcinogenesis. The transcriptional analysis was then complemented by a complex network analysis of modulated genes which further confirmed the presence of signaling pathways associated with carcinogenesis. Since epigenetic mechanisms, such as microRNAs (miRNAs, are believed to play a central role in the pathogenesis of SSc, we also evaluated whether specific cancer-related miRNAs could be deregulated in the serum of SSc patients. We focused our attention on miRNAs already found upregulated in SSc such as miR-21-5p, miR-92a-3p, and on miR-155-5p, miR 126-3p and miR-16-5p known to be deregulated in malignancies associated to SSc, i.e., breast, lung, and hematological malignancies. miR-21-5p, miR-92a-3p, miR-155-5p, and miR-16-5p expression was significantly higher in SSc sera compared to

Long-life slab replacement concrete.

Science.gov (United States)

2015-03-01

This research was initiated following reports of high incidence of cracking on FDOT concrete pavement replacement : slab projects. Field slabs were instrumented for data acquisition from high-early-strength concrete pavement : replacement slabs place...

Replacement of fluid-filter elements without interruption of flow

Science.gov (United States)

Kotler, R. A.; Ward, J. B.

1969-01-01

Gatling-type filter assembly, preloaded with several filter elements enables filter replacement without breaking into the operative fluid system. When the filter element becomes contaminated, a unit inner subassembly is rotated 60 degrees to position a clean filter in the line.

Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy

Science.gov (United States)

McGreevy, Joe W.; Hakim, Chady H.; McIntosh, Mark A.; Duan, Dongsheng

2015-01-01

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. PMID:25740330

Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy.

Science.gov (United States)

McGreevy, Joe W; Hakim, Chady H; McIntosh, Mark A; Duan, Dongsheng

2015-03-01

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. © 2015. Published by The Company of Biologists Ltd.

Improvements in algal lipid production: a systems biology and gene editing approach.

Science.gov (United States)

Banerjee, Avik; Banerjee, Chiranjib; Negi, Sangeeta; Chang, Jo-Shu; Shukla, Pratyoosh

2018-05-01

In the wake of rising energy demands, microalgae have emerged as potential sources of sustainable and renewable carbon-neutral fuels, such as bio-hydrogen and bio-oil. For rational metabolic engineering, the elucidation of metabolic pathways in fine detail and their manipulation according to requirements is the key to exploiting the use of microalgae. Emergence of site-specific nucleases have revolutionized applied research leading to biotechnological gains. Genome engineering as well as modulation of the endogenous genome with high precision using CRISPR systems is being gradually employed in microalgal research. Further, to optimize and produce better algal platforms, use of systems biology network analysis and integration of omics data is required. This review discusses two important approaches: systems biology and gene editing strategies used on microalgal systems with a focus on biofuel production and sustainable solutions. It also emphasizes that the integration of such systems would contribute and compliment applied research on microalgae. Recent advances in microalgae are discussed, including systems biology, gene editing approaches in lipid bio-synthesis, and antenna engineering. Lastly, it has been attempted here to showcase how CRISPR/Cas systems are a better editing tool than existing techniques that can be utilized for gene modulation and engineering during biofuel production.

Measure Guideline: Air Conditioner Diagnostics, Maintenance, and Replacement

Energy Technology Data Exchange (ETDEWEB)

Springer, D.; Dakin, B.

2013-03-01

This guideline responds to the need for an efficient means of identifying, diagnosing, and repairing faults in air conditioning systems in existing homes that are undergoing energy upgrades. Inadequate airflow due to constricted ducts or undersized filters, improper refrigerant charge, and other system defects can be corrected at a fraction of the cost of equipment replacement and can yield significant savings. The guideline presents a two-step approach to diagnostics and repair.

Measure Guideline. Air Conditioner Diagnostics, Maintenance, and Replacement

Energy Technology Data Exchange (ETDEWEB)

Springer, David [Alliance for Residential Building Innovation (ARBI), Davis, CA (United States); Dakin, Bill [Alliance for Residential Building Innovation (ARBI), Davis, CA (United States)

2013-03-01

This guideline responds to the need for an efficient means of identifying, diagnosing, and repairing faults in air conditioning systems in existing homes that are undergoing energy upgrades. Inadequate airflow due to constricted ducts or undersized filters, improper refrigerant charge, and other system defects can be corrected at a fraction of the cost of equipment replacement and can yield significant savings. The guideline presents a two-step approach to diagnostics and repair.

24 CFR 970.31 - Replacement units.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement units. 970.31 Section... PUBLIC HOUSING PROGRAM-DEMOLITION OR DISPOSITION OF PUBLIC HOUSING PROJECTS § 970.31 Replacement units. Notwithstanding any other provision of law, replacement public housing units may be built on the original public...

Age Replacement and Service Rate Control of Stochastically Degrading Queues

National Research Council Canada - National Science Library

Chapin, Patrick

2004-01-01

This thesis considers the problem of optimally selecting a periodic replacement time for a multiserver queueing system in which each server is subject to degradation as a function of the mean service...

In vivo characterization of a reporter gene system for imaging hypoxia-induced gene expression.

Science.gov (United States)

Carlin, Sean; Pugachev, Andrei; Sun, Xiaorong; Burke, Sean; Claus, Filip; O'Donoghue, Joseph; Ling, C Clifton; Humm, John L

2009-10-01

To characterize a tumor model containing a hypoxia-inducible reporter gene and to demonstrate utility by comparison of reporter gene expression to the uptake and distribution of the hypoxia tracer (18)F-fluoromisonidazole ((18)F-FMISO). Three tumors derived from the rat prostate cancer cell line R3327-AT were grown in each of two rats as follows: (1) parental R3327-AT, (2) positive control R3327-AT/PC in which the HSV1-tkeGFP fusion reporter gene was expressed constitutively, (3) R3327-AT/HRE in which the reporter gene was placed under the control of a hypoxia-inducible factor-responsive promoter sequence (HRE). Animals were coadministered a hypoxia-specific marker (pimonidazole) and the reporter gene probe (124)I-2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-iodouracil ((124)I-FIAU) 3 h prior to sacrifice. Statistical analysis of the spatial association between (124)I-FIAU uptake and pimonidazole fluorescent staining intensity was then performed on a pixel-by-pixel basis. Utility of this system was demonstrated by assessment of reporter gene expression versus the exogenous hypoxia probe (18)F-FMISO. Two rats, each bearing a single R3327-AT/HRE tumor, were injected with (124)I-FIAU (3 h before sacrifice) and (18)F-FMISO (2 h before sacrifice). Statistical analysis of the spatial association between (18)F-FMISO and (124)I-FIAU on a pixel-by-pixel basis was performed. Correlation coefficients between (124)I-FIAU uptake and pimonidazole staining intensity were: 0.11 in R3327-AT tumors, -0.66 in R3327-AT/PC and 0.76 in R3327-AT/HRE, confirming that only in the R3327-AT/HRE tumor was HSV1-tkeGFP gene expression associated with hypoxia. Correlation coefficients between (18)F-FMISO and (124)I-FIAU uptakes in R3327-AT/HRE tumors were r=0.56, demonstrating good spatial correspondence between the two tracers. We have confirmed hypoxia-specific expression of the HSV1-tkeGFP fusion gene in the R3327-AT/HRE tumor model and demonstrated the utility of this model for the

In vivo characterization of a reporter gene system for imaging hypoxia-induced gene expression

International Nuclear Information System (INIS)

Carlin, Sean; Pugachev, Andrei; Sun Xiaorong; Burke, Sean; Claus, Filip; O'Donoghue, Joseph; Ling, C. Clifton; Humm, John L.

2009-01-01

Purpose: To characterize a tumor model containing a hypoxia-inducible reporter gene and to demonstrate utility by comparison of reporter gene expression to the uptake and distribution of the hypoxia tracer 18 F-fluoromisonidazole ( 18 F-FMISO). Methods: Three tumors derived from the rat prostate cancer cell line R3327-AT were grown in each of two rats as follows: (1) parental R3327-AT, (2) positive control R3327-AT/PC in which the HSV1-tkeGFP fusion reporter gene was expressed constitutively, (3) R3327-AT/HRE in which the reporter gene was placed under the control of a hypoxia-inducible factor-responsive promoter sequence (HRE). Animals were coadministered a hypoxia-specific marker (pimonidazole) and the reporter gene probe 124 I-2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil ( 124 I-FIAU) 3 h prior to sacrifice. Statistical analysis of the spatial association between 124 I-FIAU uptake and pimonidazole fluorescent staining intensity was then performed on a pixel-by-pixel basis. Utility of this system was demonstrated by assessment of reporter gene expression versus the exogenous hypoxia probe 18 F-FMISO. Two rats, each bearing a single R3327-AT/HRE tumor, were injected with 124 I-FIAU (3 h before sacrifice) and 18 F-FMISO (2 h before sacrifice). Statistical analysis of the spatial association between 18 F-FMISO and 124 I-FIAU on a pixel-by-pixel basis was performed. Results: Correlation coefficients between 124 I-FIAU uptake and pimonidazole staining intensity were: 0.11 in R3327-AT tumors, -0.66 in R3327-AT/PC and 0.76 in R3327-AT/HRE, confirming that only in the R3327-AT/HRE tumor was HSV1-tkeGFP gene expression associated with hypoxia. Correlation coefficients between 18 F-FMISO and 124 I-FIAU uptakes in R3327-AT/HRE tumors were r=0.56, demonstrating good spatial correspondence between the two tracers. Conclusions: We have confirmed hypoxia-specific expression of the HSV1-tkeGFP fusion gene in the R3327-AT/HRE tumor model and demonstrated the utility of

Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia.

Science.gov (United States)

Balan, Shabeesh; Yamada, Kazuo; Iwayama, Yoshimi; Hashimoto, Takanori; Toyota, Tomoko; Shimamoto, Chie; Maekawa, Motoko; Takagai, Shu; Wakuda, Tomoyasu; Kameno, Yosuke; Kurita, Daisuke; Yamada, Kohei; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Yoshikawa, Takeo

2017-07-01

Involvement of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia pathogenesis through disrupted neurodevelopment has been highlighted in numerous studies. However, the function of common genetic variants of this system in determining schizophrenia risk is unknown. We therefore tested the association of 375 tagged SNPs in genes derived from the GABAergic system, such as GABA A receptor subunit genes, and GABA related genes (glutamate decarboxylase genes, GABAergic-marker gene, genes involved in GABA receptor trafficking and scaffolding) in Japanese schizophrenia case-control samples (n=2926; 1415 cases and 1511 controls). We observed nominal association of SNPs in nine GABA A receptor subunit genes and the GPHN gene with schizophrenia, although none survived correction for study-wide multiple testing. Two SNPs located in the GABRA1 gene, rs4263535 (P allele =0.002; uncorrected) and rs1157122 (P allele =0.006; uncorrected) showed top hits, followed by rs723432 (P allele =0.007; uncorrected) in the GPHN gene. All three were significantly associated with schizophrenia and survived gene-wide multiple testing. Haplotypes containing associated variants in GABRA1 but not GPHN were significantly associated with schizophrenia. To conclude, we provided substantiating genetic evidence for the involvement of the GABAergic system in schizophrenia susceptibility. These results warrant further investigations to replicate the association of GABRA1 and GPHN with schizophrenia and to discern the precise mechanisms of disease pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

31 CFR 361.8 - Claim for replacement.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Claim for replacement. 361.8 Section... § 361.8 Claim for replacement. Claim for replacement shall be made in writing to the Secretary, to the..., Parkersburg, WV 26106-1328. The claim, accompanied by a recommendation regarding the manner of replacement...

New Clox Systems for rapid and efficient gene disruption in Candida albicans.

Directory of Open Access Journals (Sweden)

Shahida Shahana

Full Text Available Precise genome modification is essential for the molecular dissection of Candida albicans, and is yielding invaluable information about the roles of specific gene functions in this major fungal pathogen of humans. C. albicans is naturally diploid, unable to undergo meiosis, and utilizes a non-canonical genetic code. Hence, specialized tools have had to be developed for gene disruption in C. albicans that permit the deletion of both target alleles, and in some cases, the recycling of the Candida-specific selectable markers. Previously, we developed a tool based on the Cre recombinase, which recycles markers in C. albicans with 90-100% efficiency via site-specific recombination between loxP sites. Ironically, the utility of this system was hampered by the extreme efficiency of Cre, which prevented the construction in Escherichia coli of stable disruption cassettes carrying a methionine-regulatable CaMET3p-cre gene flanked by loxP sites. Therefore, we have significantly enhanced this system by engineering new Clox cassettes that carry a synthetic, intron-containing cre gene. The Clox kit facilitates efficient transformation and marker recycling, thereby simplifying and accelerating the process of gene disruption in C. albicans. Indeed, homozygous mutants can be generated and their markers resolved within two weeks. The Clox kit facilitates strategies involving single marker recycling or multi-marker gene disruption. Furthermore, it includes the dominant NAT1 marker, as well as URA3, HIS1 and ARG4 cassettes, thereby permitting the manipulation of clinical isolates as well as genetically marked strains of C. albicans. The accelerated gene disruption strategies afforded by this new Clox system are likely to have a profound impact on the speed with which C. albicans pathobiology can be dissected.

Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

DEFF Research Database (Denmark)

Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

2004-01-01

We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

24 CFR 891.745 - Replacement reserve.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 891.745... and Individuals-Section 162 Assistance § 891.745 Replacement reserve. The general requirements for the replacement reserve are provided in § 891.605. For projects funded under §§ 891.655 through 891.790, the...

Replacement of CFCs in thermodynamical systems; Remplacement des C.F.C. dans les systemes thermodynamiques

Energy Technology Data Exchange (ETDEWEB)

Fleurance, M.

1996-12-31

Following the Montreal protocol and the withdrawal of the CFC-type refrigerating fluids, York France company has developed and adapted its equipments to new refrigerants. Each user will have to know how to define the best option for his installation: opting for or ignoring the withdrawal of CFCs, confining the installations, changing for new intermediate substitutes (HCFC-type), or changing or replacing with new long term substitutes (HFCs). (J.S.)

A novel Listeria monocytogenes-based DNA delivery system for cancer gene therapy.

LENUS (Irish Health Repository)

van Pijkeren, Jan Peter

2012-01-31

Bacteria-mediated transfer of plasmid DNA to mammalian cells (bactofection) has been shown to have significant potential as an approach to express heterologous proteins in various cell types. This is achieved through entry of the entire bacterium into cells, followed by release of plasmid DNA. In a murine model, we show that Listeria monocytogenes can invade and spread in tumors, and establish the use of Listeria to deliver genes to tumors in vivo. A novel approach to vector lysis and release of plasmid DNA through antibiotic administration was developed. Ampicillin administration facilitated both plasmid transfer and safety control of vector. To further improve on the gene delivery system, we selected a Listeria monocytogenes derivative that is more sensitive to ampicillin, and less pathogenic than the wild-type strain. Incorporation of a eukaryotic-transcribed lysin cassette in the plasmid further increased bacterial lysis. Successful gene delivery of firefly luciferase to growing tumors in murine models and to patient breast tumor samples ex vivo was achieved. The model described encompasses a three-phase treatment regimen, involving (1) intratumoral administration of vector followed by a period of vector spread, (2) systemic ampicillin administration to induce vector lysis and plasmid transfer, and (3) systemic administration of combined moxifloxacin and ampicillin to eliminate systemic vector. For the first time, our results reveal the potential of Listeria monocytogenes for in vivo gene delivery.

Remote replacement of TF [toroidal field] and PF [poloidal field] coils for the compact ignition tokamak

International Nuclear Information System (INIS)

Macdonald, D.; Watkin, D.C.; Hollis, M.J.; DePew, R.E.; Kuban, D.P.

1990-01-01

The use of deuterium-tritium fuel in the Compact Ignition Tokamak will require applying remote handling technology for ex-vessel maintenance and replacement of machine components. Highly activated and contaminated components of the fusion devices auxiliary systems, such as diagnostics and RF heating, must be replaced using remotely operated maintenance equipment in the test cell. In-vessel remote maintenance included replacement of divertor and first wall hardware, faraday shields, and for an in-vessel inspection system. Provision for remote replacement of a vacuum vessel sector, toroidal field coil or poloidal field ring coil was not included in the project baseline. As a result of recent coil failures experienced at a number of facilities, the CIT project decided to reconsider the question of remote recovery from a coil failure and, in January of 1990, initiated a coil replacement study. This study focused on the technical requirements and impact on fusion machine design associated with remote recovery from any coil failure

Prolonged Intermittent Renal Replacement Therapy.

Science.gov (United States)

Edrees, Fahad; Li, Tingting; Vijayan, Anitha

2016-05-01

Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Wages Paid in Kind in Self-Replacing Economies

Directory of Open Access Journals (Sweden)

Alberto Benítez Sánchez

2014-05-01

Full Text Available This paper studies the two systems of production equations corresponding respectively to wages paid entirely or partialy in kind in Sraffa's self-replacing economies. Regarding the first system, the paper introduces the concept of ρ-shaped matrix, which is relevant to the subject and allows also for the addition of a complementary remark to the theory of semi-positive square matrices. In relation to the second system, it points out some differences between the cases studied here and those where the whole wage is paid in value.

Comparison of additional costs for several replacement strategies of randomly ageing reinforced concrete pipes

OpenAIRE

SCHOEFS , Franck; Aduriz , X.; Bernard , Olivier; Capra , Bruno

2009-01-01

International audience; One of the uses of reinforced concrete pipes (RCPs) is the distribution of aggressive water in industrial systems, for example, in water-cooling systems of nuclear power plants. Some of them carry seawater and can deteriorate with time because of internal corrosion. Because of the low O(2) content of aggressive water, slow corrosion is expected for such applications. If the RCPs are not periodically replaced, they will eventually fail. Replacement strategies for these ...

Gene-gene interactions of IRF5, STAT4, IKZF1 and ETS1 in systemic lupus erythematosus.

Science.gov (United States)

Dang, J; Shan, S; Li, J; Zhao, H; Xin, Q; Liu, Y; Bian, X; Liu, Q

2014-06-01

Interferon (IFN) activation signaling and T helper 17 (Th17)-cell/B-cell regulation play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Several studies have provided convincing evidence that polymorphisms in IRF5, STAT4, IKZF1 and ETS1 from these pathways may be involved in SLE by affecting gene expression or epistasis. We analyzed the genetic interaction in known SLE susceptibility loci from the four genes in northern Han Chinese. A total of 946 northern Han Chinese participated in this study (370 unrelated SLE patients and 576 healthy controls). Subjects underwent genotyping for the single-nucleotide polymorphisms (SNPs) rs2004640 in IRF5, rs7574865 in STAT4, rs4917014 in IKZF1 and rs1128334 in ETS1 by use of a TaqMan SNP genotyping assay and direct sequencing. Gene-gene interaction analysis involved direct counting, multifactor dimensionality reduction (MDR) and linear regression analysis. SLE patients and controls differed in allele frequencies of rs7574865, rs1128334 (P < 0.001) and rs4917014 (P < 0.01). Direct counting revealed that the frequency of risk homozygote combinations was higher for SLE patients than controls (P < 0.01). Furthermore, 2-, 3- and 4-way gene-gene epistasis in SLE was confirmed by parametric methods and MDR analysis. Gene expression analysis partially supported the findings. Our study confirmed the association of the IFN pathway or Th17/B-cells and the pathogenesis of SLE, and gene-gene interaction in this pathway may increase the risk of SLE. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Novel Tightly Regulated Gene Expression System for the Human Intestinal Symbiont Bacteroides thetaiotaomicron

Directory of Open Access Journals (Sweden)

Regis Stentz

2016-07-01

Full Text Available There is considerable interest in studying the function of Bacteroides species resident in the human gastrointestinal (GI-tract and the contribution they make to host health. Reverse genetics and protein expression techniques, such as those developed for well-characterised Escherichia coli cannot be applied to Bacteroides species as they and other members of the Bacteriodetes phylum have unique promoter structures. The availability of useful Bacteroides-specific genetic tools is therefore limited. Here we describe the development of an effective mannan-controlled gene expression system for Bacteroides thetaiotaomicron containing the mannan-inducible promoter–region of an α-1,2-mannosidase gene (BT_3784, a ribosomal binding site designed to modulate expression, a multiple cloning site to facilitate the cloning of genes of interest, and a transcriptional terminator. Using the Lactobacillus pepI as a reporter gene, mannan induction resulted in an increase of reporter activity in a time- and concentration-dependent manner with a wide range of activity. The endogenous BtcepA cephalosporinase gene was used to demonstrate the suitability of this novel expression system, enabling the isolation of a His-tagged version of BtCepA. We have also shown with experiments performed in mice that the system can be induced in vivo in the presence of an exogenous source of mannan. By enabling the controlled expression of endogenous and exogenous genes in B. thetaiotaomicron this novel inducer-dependent expression system will aid in defining the physiological role of individual genes and the functional analyses of their products.

A PCA3 gene-based transcriptional amplification system targeting primary prostate cancer

OpenAIRE

Neveu, Bertrand; Jain, Pallavi; T?tu, Bernard; Wu, Lily; Fradet, Yves; Pouliot, Fr?d?ric

2015-01-01

Targeting specifically primary prostate cancer (PCa) cells for immune therapy, gene therapy or molecular imaging is of high importance. The PCA3 long non-coding RNA is a unique PCa biomarker and oncogene that has been widely studied. This gene has been mainly exploited as an accurate diagnostic urine biomarker for PCa detection. In this study, the PCA3 promoter was introduced into a new transcriptional amplification system named the 3-Step Transcriptional Amplification System (PCA3-3STA) and ...

IMU-based Real-time Pose Measurement system for Anterior Pelvic Plane in Total Hip Replacement Surgeries.