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Sample records for counterselective gene replacement

  1. Counterselection method based on conditional silencing of antitoxin genes in Escherichia coli.

    Science.gov (United States)

    Tsukuda, Miyuki; Nakashima, Nobutaka; Miyazaki, Kentaro

    2015-11-01

    Counterselection is a genetic engineering technique to eliminate specific genetic fragments containing selectable marker genes. Although the technique is widely used in bacterial genome engineering and plasmid curing experiments, the repertoire of the markers usable in Escherichia coli is limited. Here we developed a novel counterselection method in E. coli based on antisense RNA (asRNA) technology directed against toxin-antitoxin (TA) modules. Under normal conditions, excess antitoxin neutralizes its cognate toxin and thus the module is stably maintained in the genome. We hypothesised that repression of an antitoxin gene would perturb cell growth due to the toxin being released. We designed asRNAs corresponding to all 19 type II antitoxins encoded in the E. coli genome. asRNAs were then conditionally expressed; repression of MqsA in the MqsR/MqsA module had the greatest inhibitory effect, followed by RnlB in the RnlA/RnlB module. The utility of asRNA(MqsA) as a counterselection marker was demonstrated by efficient plasmid curing and strain improvement experiments.

  2. Counter-selection recombineering of the baculovirus genome: a strategy for seamless modification of repeat-containing BACs.

    Science.gov (United States)

    Westenberg, Marcel; Soedling, Helen M; Mann, Derek A; Nicholson, Linda J; Dolphin, Colin T

    2010-09-01

    Recombineering is employed to modify large DNA clones such as fosmids, BACs and PACs. Subtle and seamless modifications can be achieved using counter-selection strategies in which a donor cassette carrying both positive and negative markers inserted in the target clone is replaced by the desired sequence change. We are applying counter-selection recombineering to modify bacmid bMON14272, a recombinant baculoviral genome, as we wish to engineer the virus into a therapeutically useful gene delivery vector with cell targeting characteristics. Initial attempts to replace gp64 with Fusion (F) genes from other baculoviruses resulted in many rearranged clones in which the counter-selection cassette had been deleted. Bacmid bMON14272 contains nine highly homologous regions (hrs) and deletions were mapped to recombination between hr pairs. Recombineering modifications were attempted to decrease intramolecular recombination and/or increase recombineering efficiency. Of these only the use of longer homology arms on the donor molecule proved effective permitting seamless modification. bMON14272, because of the presence of the hr sequences, can be considered equivalent to a highly repetitive BAC and, as such, the optimized method detailed here should prove useful to others applying counter-selection recombineering to modify BACs or PACs containing similar regions of significant repeating homologies.

  3. A suitable streptomycin-resistant mutant for constructing unmarked in-frame gene deletions using rpsL as a counter-selection marker.

    Directory of Open Access Journals (Sweden)

    Yu-Kuo Tsai

    Full Text Available The streptomycin counter-selection system is a useful tool for constructing unmarked in-frame gene deletions, which is a fundamental approach to study bacteria and their pathogenicity at the molecular level. A prerequisite for this system is acquiring a streptomycin-resistant strain due to rpsL mutations, which encodes the ribosomal protein S12. However, in this study no streptomycin resistance was found to be caused by rpsL mutations in all 127 clinical strains of Klebsiella pneumoniae isolated from liver abscess patients. By screening 107 spontaneous mutants of streptomycin resistance from a clinical strain of K. pneumoniae, nucleotide substitution or insertion located within the rpsL was detected in each of these strains. Thirteen different mutants with varied S12 proteins were obtained, including nine streptomycin-dependent mutants. The virulence of all four streptomycin-resistant mutants was further evaluated. Compared with the parental strain, the K42N, K42T and K87R mutants showed a reduction in growth rate, and the K42N and K42T mutants became susceptible to normal human serum. In the mice LD50 (the bacterial dose that caused 50% death assay, the K42N and K42T mutants were ∼ 1,000-fold less lethal (∼ 2 × 10(5 CFU and the K87R mutant was ∼ 50-fold less lethal (∼ 1 × 10(4 CFU than the parental strain (∼ 2 × 10(2 CFU. A K42R mutant showed non-observable effects on the above assays, while this mutant exhibited a small cost (P < 0.01 in an in vitro growth competition experiment. In summary, most of the K. pneumoniae strains with streptomycin resistance caused by rpsL mutations are less virulent than their parental strain in the absence of streptomycin. The K42R mutant showed similar pathogenicity to its parental strain and should be one of the best choices when using rpsL as a counter-selection marker.

  4. GAP1, a novel selection and counter-selection marker for multiple gene disruptions in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Regenberg, Birgitte; Hansen, J.

    2000-01-01

    We report on the use of a new homologous marker for use in multiple gene deletions in S, cerevisiae, the general amino acid permease gene (GAP1), A GAP1 strain can utilize L-citrulline as the sole nitrogen source but cannot grow in the presence of the toxic amino acid D-histidine, L-citrulline as......We report on the use of a new homologous marker for use in multiple gene deletions in S, cerevisiae, the general amino acid permease gene (GAP1), A GAP1 strain can utilize L-citrulline as the sole nitrogen source but cannot grow in the presence of the toxic amino acid D-histidine, L......-citrulline as well as D-histidine uptake is mediated solely by the general amino acid permease, and a gap1 strain is therefore able to grow in the presence of D-histidine but cannot utilize L-citrulline, Gene disruption is effected by transforming a gap1 strain with a gene cassette generated by PCR, containing GAP1...... the GAP1 gene. This is caused by recombination between two Salmonella typuimurium hisG direct repeats embracing GAP1, and will result in a sub-population of gap1 cells. Such cells are selected on a medium containing D-histidine, and may subsequently be used for a second gene disruption. Hence, multiple...

  5. Homologous gene replacement in Physarum

    Energy Technology Data Exchange (ETDEWEB)

    Burland, T.G. [Univ. of Wisconsin, Madison, WI (United States); Pallotta, D. [Laval Univ., Quebec (Canada)

    1995-01-01

    The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1 in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.

  6. Gene replacement in Penicillium roqueforti.

    Science.gov (United States)

    Goarin, Anne; Silar, Philippe; Malagnac, Fabienne

    2015-05-01

    Most cheese-making filamentous fungi lack suitable molecular tools to improve their biotechnology potential. Penicillium roqueforti, a species of high industrial importance, would benefit from functional data yielded by molecular genetic approaches. This work provides the first example of gene replacement by homologous recombination in P. roqueforti, demonstrating that knockout experiments can be performed in this fungus. To do so, we improved the existing transformation method to integrate transgenes into P. roqueforti genome. In the meantime, we cloned the PrNiaD gene, which encodes a NADPH-dependent nitrate reductase that reduces nitrate to nitrite. Then, we performed a deletion of the PrNiaD gene from P. roqueforti strain AGO. The ΔPrNiaD mutant strain is more resistant to chlorate-containing medium than the wild-type strain, but did not grow on nitrate-containing medium. Because genomic data are now available, we believe that generating selective deletions of candidate genes will be a key step to open the way for a comprehensive exploration of gene function in P. roqueforti.

  7. An upp-based markerless gene replacement method for genome reduction and metabolic pathway engineering in Pseudomonas mendocina NK-01 and Pseudomonas putida KT2440.

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    Wang, Yuanyuan; Zhang, Chi; Gong, Ting; Zuo, Zhenqiang; Zhao, Fengjie; Fan, Xu; Yang, Chao; Song, Cunjiang

    2015-06-01

    A markerless gene replacement method was adapted by combining a suicide plasmid, pEX18Tc, with a counterselectable marker, the upp gene encoding uracil phosphoribosyltransferase (UPRTase), for the medium-chain length polyhydroxyalkanoates (PHA(MCL))-producing strain Pseudomonas mendocina NK-01. An NK-01 5-fluorouracil (5-FU) resistant background strain was first constructed by deleting the chromosomal upp gene. The suicide plasmid pEX18Tc, carrying a functional allele of the upp gene of P. mendocina NK-01, was used to construct the vectors to delete the algA (encoding mannose-1-phosphate guanylyltransferase) and phaZ (encoding PHA(MCL) depolymerase) genes, and a 30 kb chromosomal fragment in the 5-FU resistant background host. The genes were removed efficiently from the genome of P. mendocina NK-01 and left a markerless chromosomal mutant. In addition, two exogenous genes were inserted into the phaC1 (PHA(MCL) polymerase) loci of Pseudomonas putida KT-∆UPP simultaneously. Thus, we constructed a genetically stable and marker-free P. putida KT2440 mutant with integrated mpd (encoding methyl parathion hydrolase (MPH)) and pytH (encoding a pyrethroid-hydrolyzing carboxylesterase (PytH)) gene on the chromosome. The upp-based counterselection system could be further adapted for P. mendocina NK-01 and P. putida KT2440 and used for genome reduction and metabolic pathway engineering.

  8. The apt/6-Methylpurine Counterselection System and Its Applications in Genetic Studies of the Hyperthermophilic Archaeon Sulfolobus islandicus

    Science.gov (United States)

    Bi, Hongkai; Whitaker, Rachel J.

    2016-01-01

    ABSTRACT Sulfolobus islandicus serves as a model for studying archaeal biology as well as linking novel biology to evolutionary ecology using functional population genomics. In the present study, we developed a new counterselectable genetic marker in S. islandicus to expand the genetic toolbox for this species. We show that resistance to the purine analog 6-methylpurine (6-MP) in S. islandicus M.16.4 is due to the inactivation of a putative adenine phosphoribosyltransferase encoded by M164_0158 (apt). The application of the apt gene as a novel counterselectable marker was first illustrated by constructing an unmarked α-amylase deletion mutant. Furthermore, the 6-MP counterselection feature was employed in a forward (loss-of-function) mutation assay to reveal the profile of spontaneous mutations in S. islandicus M.16.4 at the apt locus. Moreover, the general conservation of apt genes in the crenarchaea suggests that the same strategy can be broadly applied to other crenarchaeal model organisms. These results demonstrate that the apt locus represents a new tool for genetic manipulation and sequence analysis of the hyperthermophilic crenarchaeon S. islandicus. IMPORTANCE Currently, the pyrEF/5-fluoroorotic acid (5-FOA) counterselection system remains the sole counterselection marker in crenarchaeal genetics. Since most Sulfolobus mutants constructed by the research community were derived from genetic hosts lacking the pyrEF genes, the pyrEF/5-FOA system is no longer available for use in forward mutation assays. Demonstration of the apt/6-MP counterselection system for the Sulfolobus model renders it possible to again study the mutation profiles in mutants that have already been constructed by the use of strains with a pyrEF-deficient background. Furthermore, additional counterselectable markers will allow us to conduct more sophisticated genetic studies, i.e., investigate mechanisms of chromosomal DNA transfer and quantify recombination frequencies among S

  9. Gene replacement in Mycobacterium chelonae: application to the construction of porin knock-out mutants.

    Directory of Open Access Journals (Sweden)

    Vinicius Calado Nogueira de Moura

    Full Text Available Mycobacterium chelonae is a rapidly growing mycobacterial opportunistic pathogen closely related to Mycobacterium abscessus that causes cornea, skin and soft tissue infections in humans. Although M. chelonae and the emerging mycobacterial pathogen M. abscessus have long been considered to belong to the same species, these two microorganisms considerably differ in terms of optimum growth temperature, drug susceptibility, pathogenicity and the types of infection they cause. The whole genome sequencing of clinical isolates of M. chelonae and M. abscessus is opening the way to comparative studies aimed at understanding the biology of these pathogens and elucidating the molecular bases of their pathogenicity and biocide resistance. Key to the validation of the numerous hypotheses that this approach will raise, however, is the availability of genetic tools allowing for the expression and targeted mutagenesis of genes in these species. While homologous recombination systems have recently been described for M. abscessus, genetic tools are lacking for M. chelonae. We here show that two different allelic replacement methods, one based on mycobacteriophage-encoded recombinases and the other on a temperature-sensitive plasmid harboring the counterselectable marker sacB, can be used to efficiently disrupt genes in this species. Knock-out mutants for each of the three porin genes of M. chelonae ATCC 35752 were constructed using both methodologies, one of which displays a significantly reduced glucose uptake rate consistent with decreased porin expression.

  10. Counterselection employing mutated pheS for markerless genetic deletion in Bacteroides species.

    Science.gov (United States)

    Kino, Yasuhiro; Nakayama-Imaohji, Haruyuki; Fujita, Masashi; Tada, Ayano; Yoneda, Saori; Murakami, Kazuya; Hashimoto, Masahito; Hayashi, Tetsuya; Okazaki, Katsuichiro; Kuwahara, Tomomi

    2016-12-01

    Markerless gene deletion is necessary for multiple gene disruptions due to the limited number of antibiotic resistant markers for some bacteria. However, even in transformable strains, obtaining the expected mutation without a marker requires laborious screening of a large number of colonies. Previous studies had success in various bacteria with a counter-selection system where a conditional lethal gene was incorporated into the vector. We examined the efficacy of the mutated pheS gene (pheS*) as a counter-selective marker for gene deletion in Bacteroides. This mutation produces an amino acid substitution (A303G) in the alpha subunit of Bacteroides phenylalanyl tRNA synthetase, which in E. coli alters the specificity of the tRNA synthetase resulting in a conditional lethal mutation due to the incorporation of p-chloro-phenylalanine (p-Cl-Phe) into protein. B. fragilis YCH46 and B. thetaiotaomicron VPI-5482 transformed with a pheS*-harboring shuttle vector were clearly growth-inhibited in the presence of >5 mM p-Cl-Phe in liquid defined minimal media (DMM) and on DMM agar plates. A targeting plasmid was constructed to delete the genetic region for capsular polysaccharide PS2 in B. fragilis or PS1 in B. thetaiotaomicron. After counterselection, p-Cl-Phe-resistant colonies were generated at a frequency of 8.1 × 10(-3) for B. fragilis and 1.7 × 10(-3) for B. thetaiotaomicron. Of the p-Cl-Phe-resistant colonies, 4.2% and 72% harbored the correct genetic deletion for B. fragilis and B. thetaiotaomicron, respectively. These results indicate that mutated pheS is a useful counter-selective gene to construct markerless genetic deletions in Bacteroides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Bone Marrow Transplantation (BMT) and Gene Replacement ...

    African Journals Online (AJOL)

    Bone Marrow Transplantation (BMT) and Gene Replacement Therapy (GRT) In Sickle Cell Anemia. ... manifesting clinical disease, while the heterozygoste(AS) are clinically ... medicine, we argue here the case for Bone marrow transplantation

  12. Prospects for retinal gene replacement therapy.

    Science.gov (United States)

    Smith, Alexander J; Bainbridge, James W; Ali, Robin R

    2009-04-01

    Inherited retinal degeneration, which includes conditions such as retinitis pigmentosa and Leber congenital amaurosis (LCA), affects approximately 1/3000 of the population in the Western world. It is characterized by loss of vision and results from mutations in any one of >100 different genes. There are currently no effective treatments, but many of the genes have now been identified and their functions elucidated, providing a major impetus to develop gene-based treatments. Preliminary results from three clinical trials indicate that the treatment of a form of LCA by gene therapy can be safe and effective. Here, we discuss the potential for treating other forms of retinal degeneration by gene therapy, focusing on the gene defects that are likely to be the most amenable to treatment.

  13. Gene replacement therapy for retinal CNG channelopathies.

    Science.gov (United States)

    Schön, Christian; Biel, Martin; Michalakis, Stylianos

    2013-10-01

    Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

  14. [Gene replacement therapy in achromatopsia type 2].

    Science.gov (United States)

    Mühlfriedel, R; Tanimoto, N; Seeliger, M W

    2014-03-01

    Achromatopsia is an autosomal recessive inherited retinal disease caused by a complete loss of cone photoreceptor function. About 80 % of achromatopsia patients show mutations in the alpha or beta subunit (A3 and B3) of the cGMP controlled cation channel CNG (cyclic nucleotide-gated channel) of cone photoreceptors. Homologous to the human disease, CNGA3 deficient mice reveal a loss of cone specific functionality leading to degeneration of affected cone photoreceptors. The Institute for Ophthalmic Research in Tübingen has now succeeded in curing achromatopsia ACHM2 in an animal model. In this article, we explain the recombinant adeno-associated virus-based approach in detail. Furthermore, applied non-invasive diagnostic techniques for quality and success control, ERG, SLO and OCT, are described. The success of the therapy is indicated by a restored cone photoreceptor function as well as the neuronal processing of retinal signals resulting in a specific, cone-mediated behaviour. The outstanding results derived from the animal model are the starting point for the first human translation of a gene therapy for achromatopsia in Germany. Georg Thieme Verlag KG Stuttgart · New York.

  15. Targeted Curing of All Lysogenic Bacteriophage from Streptococcus pyogenes Using a Novel Counter-selection Technique.

    Science.gov (United States)

    Euler, Chad W; Juncosa, Barbara; Ryan, Patricia A; Deutsch, Douglas R; McShan, W Michael; Fischetti, Vincent A

    2016-01-01

    Streptococcus pyogenes is a human commensal and a bacterial pathogen responsible for a wide variety of human diseases differing in symptoms, severity, and tissue tropism. The completed genome sequences of >37 strains of S. pyogenes, representing diverse disease-causing serotypes, have been published. The greatest genetic variation among these strains is attributed to numerous integrated prophage and prophage-like elements, encoding several virulence factors. A comparison of isogenic strains, differing in prophage content, would reveal the effects of these elements on streptococcal pathogenesis. However, curing strains of prophage is often difficult and sometimes unattainable. We have applied a novel counter-selection approach to identify rare S. pyogenes mutants spontaneously cured of select prophage. To accomplish this, we first inserted a two-gene cassette containing a gene for kanamycin resistance (KanR) and the rpsL wild-type gene, responsible for dominant streptomycin sensitivity (SmS), into a targeted prophage on the chromosome of a streptomycin resistant (SmR) mutant of S. pyogenes strain SF370. We then applied antibiotic counter-selection for the re-establishment of the KanS/SmR phenotype to select for isolates cured of targeted prophage. This methodology allowed for the precise selection of spontaneous phage loss and restoration of the natural phage attB attachment sites for all four prophage-like elements in this S. pyogenes chromosome. Overall, 15 mutants were constructed that encompassed every permutation of phage knockout as well as a mutant strain, named CEM1ΔΦ, completely cured of all bacteriophage elements (a ~10% loss of the genome); the only reported S. pyogenes strain free of prophage-like elements. We compared CEM1ΔΦ to the WT strain by analyzing differences in secreted DNase activity, as well as lytic and lysogenic potential. These mutant strains should allow for the direct examination of bacteriophage relationships within S. pyogenes and

  16. Targeted Curing of All Lysogenic Bacteriophage from Streptococcus pyogenes Using a Novel Counter-selection Technique.

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    Chad W Euler

    Full Text Available Streptococcus pyogenes is a human commensal and a bacterial pathogen responsible for a wide variety of human diseases differing in symptoms, severity, and tissue tropism. The completed genome sequences of >37 strains of S. pyogenes, representing diverse disease-causing serotypes, have been published. The greatest genetic variation among these strains is attributed to numerous integrated prophage and prophage-like elements, encoding several virulence factors. A comparison of isogenic strains, differing in prophage content, would reveal the effects of these elements on streptococcal pathogenesis. However, curing strains of prophage is often difficult and sometimes unattainable. We have applied a novel counter-selection approach to identify rare S. pyogenes mutants spontaneously cured of select prophage. To accomplish this, we first inserted a two-gene cassette containing a gene for kanamycin resistance (KanR and the rpsL wild-type gene, responsible for dominant streptomycin sensitivity (SmS, into a targeted prophage on the chromosome of a streptomycin resistant (SmR mutant of S. pyogenes strain SF370. We then applied antibiotic counter-selection for the re-establishment of the KanS/SmR phenotype to select for isolates cured of targeted prophage. This methodology allowed for the precise selection of spontaneous phage loss and restoration of the natural phage attB attachment sites for all four prophage-like elements in this S. pyogenes chromosome. Overall, 15 mutants were constructed that encompassed every permutation of phage knockout as well as a mutant strain, named CEM1ΔΦ, completely cured of all bacteriophage elements (a ~10% loss of the genome; the only reported S. pyogenes strain free of prophage-like elements. We compared CEM1ΔΦ to the WT strain by analyzing differences in secreted DNase activity, as well as lytic and lysogenic potential. These mutant strains should allow for the direct examination of bacteriophage relationships within S

  17. Developing Universal Genetic Tools for Rapid and Efficient Deletion Mutation in Vibrio Species Based on Suicide T-Vectors Carrying a Novel Counterselectable Marker, vmi480.

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    Peng Luo

    Full Text Available Despite that Vibrio spp. have a significant impact on the health of humans and aquatic animals, the molecular basis of their pathogenesis is little known, mainly due to the limited genetic tools for the functional research of genes in Vibrio. In some cases, deletion of target DNAs in Vibrio can be achieved through the use of suicide vectors. However, these strategies are time-consuming and lack universality, and the widely used counterselectable gene sacB does not work well in Vibrio cells. In this study, we developed universal genetic tools for rapid and efficient deletion mutations in Vibrio species based on suicide T-Vectors carrying a novel counterselectable marker, vmi480. We explored two uncharacterized genes, vmi480 and vmi470, in a genomic island from Vibrio mimicus VM573 and confirmed that vmi480 and vmi470 constitute a two-component toxin-antitoxin system through deletion and expression of vmi480 and vmi470. The product of vmi480 exhibited strong toxicity to Escherichia coli cells. Based on vmi480 and the PBAD or PTAC promoter system, we constructed two suicide T-vectors, pLP11 and pLP12, and each of these vectors contained a multiple cloning region with two AhdI sites. Both vectors linearized by AhdI digestion could be stored and directly ligated with purified PCR products without a digestion step. By using pLP11 and pLP12 coupled with a highly efficient conjugation system provided by E. coli β2163, six genes from four representative Vibrio species were easily deleted. By using the counterselective marker vmi480, we obtained 3-12 positive colonies (deletion mutants among no more than 20 colonies randomly selected on counterselection plates. The strategy does not require the digestion of PCR products and suicide vectors every time, and it avoids large-scale screening colonies on counterselective plates. These results demonstrate that we successfully developed universal genetic tools for rapid and efficient gene deletion in Vibrio

  18. Replacement

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    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.

  19. Marker recycling via 5-fluoroorotic acid and 5-fluorocytosine counter-selection in the white-rot agaricomycete Pleurotus ostreatus.

    Science.gov (United States)

    Nakazawa, Takehito; Tsuzuki, Masami; Irie, Toshikazu; Sakamoto, Masahiro; Honda, Yoichi

    2016-09-01

    Of all of the natural polymers, lignin, an aromatic heteropolymer in plant secondary cell walls, is the most resistant to biological degradation. White-rot fungi are the only known organisms that can depolymerize or modify wood lignin. Investigating the mechanisms underlying lignin biodegradation by white-rot fungi would contribute to the ecofriendly utilization of woody biomass as renewable resources in the future. Efficient gene disruption, which is generally very challenging in the white-rot fungi, was established in Pleurotus ostreatus (the oyster mushroom). Some of the genes encoding manganese peroxidases, enzymes that are considered to be involved in lignin biodegradation, were disrupted separately, and the phenotype of each single-gene disruptant was analysed. However, it remains difficult to generate multi-gene disruptants in this fungus. Here we developed a new genetic transformation marker in P. ostreatus and demonstrated two marker recycling methods that use counter-selection to generate a multigene disruptant. This study will enable future genetic studies of white-rot fungi, and it will increase our understanding of the complicated mechanisms, which involve various enzymes, including lignin-degrading enzymes, underlying lignin biodegradation by these fungi. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  20. Recurrent adenylation domain replacement in the microcystin synthetase gene cluster

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    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.

  1. VH Replacement Footprint Analyzer-I, a Java-Based Computer Program for Analyses of Immunoglobulin Heavy Chain Genes and Potential VH Replacement Products in Human and Mouse.

    Science.gov (United States)

    Huang, Lin; Lange, Miles D; Zhang, Zhixin

    2014-01-01

    VH replacement occurs through RAG-mediated secondary recombination between a rearranged VH gene and an upstream unrearranged VH gene. Due to the location of the cryptic recombination signal sequence (cRSS, TACTGTG) at the 3' end of VH gene coding region, a short stretch of nucleotides from the previous rearranged VH gene can be retained in the newly formed VH-DH junction as a "footprint" of VH replacement. Such footprints can be used as markers to identify Ig heavy chain (IgH) genes potentially generated through VH replacement. To explore the contribution of VH replacement products to the antibody repertoire, we developed a Java-based computer program, VH replacement footprint analyzer-I (VHRFA-I), to analyze published or newly obtained IgH genes from human or mouse. The VHRFA-1 program has multiple functional modules: it first uses service provided by the IMGT/V-QUEST program to assign potential VH, DH, and JH germline genes; then, it searches for VH replacement footprint motifs within the VH-DH junction (N1) regions of IgH gene sequences to identify potential VH replacement products; it can also analyze the frequencies of VH replacement products in correlation with publications, keywords, or VH, DH, and JH gene usages, and mutation status; it can further analyze the amino acid usages encoded by the identified VH replacement footprints. In summary, this program provides a useful computation tool for exploring the biological significance of VH replacement products in human and mouse.

  2. Agrobacterium-mediated transformation leads to improved gene replacement efficiency in Aspergillus awamori.

    Science.gov (United States)

    Michielse, C B; Arentshorst, M; Ram, A F J; van den Hondel, C A M J J

    2005-01-01

    In this study, the efficiency of gene replacement in Aspergillus awamori between Agrobacterium-mediated transformation and CaCl(2)/PEG-mediated transformation was compared. For the genes, pyrG and gfaA, it was found that the homologous recombination frequencies obtained by Agrobacterium-mediated transformation were 3- to 6-fold higher than the frequencies obtained with CaCl(2)/PEG protoplast transformation. For the pyrG gene, it was found that Agrobacterium-mediated transformation allowed an efficient homologous recombination with shorter DNA flanks than CaCl(2)/PEG protoplast transformation. Finally, the addition of the dominant amdS marker as a second selection marker to the gene replacement cassette led to a further 2-fold enrichment in transformants with gene replacement events, resulting in a gene replacement frequency of 55%. Based on the data it can be concluded that Agrobacterium-mediated transformation is an efficient tool for gene replacement and that the amdS gene can be successfully used as a second selection marker to select transformants with putative gene replacement.

  3. The orotate transporter oroP from Lactococcus lactis is required for orotate uptake and can be used both as a food-grade selection and counter-selection marker

    DEFF Research Database (Denmark)

    Defoor, Els Marie Celine; Martinussen, Jan

    P. Since the corresponding open reading frame, OroP showed the features of a membrane protein, OroP most likely is an orotate transporter. A number of strains like L. lactis and Bacillus subtilus have been shown to be unable to metabolize orotate. If the oroP gene was introduced into these strains......-Fluoroorotate. Strains that have lost the oroP gene could easily be selected in the presence of 5-Fluoroorotate, thus being an efficient counter-selection marker. In addition to L. lactis and B. subtilus the system has been proven efficient in other strains including Escherichia coli and Bacillus licheniformis....

  4. Mitochondrial gene replacement in primate offspring and embryonic stem cells.

    Science.gov (United States)

    Tachibana, Masahito; Sparman, Michelle; Sritanaudomchai, Hathaitip; Ma, Hong; Clepper, Lisa; Woodward, Joy; Li, Ying; Ramsey, Cathy; Kolotushkina, Olena; Mitalipov, Shoukhrat

    2009-09-17

    Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.

  5. Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes.

    Science.gov (United States)

    Li, Ting; Huang, Sheng; Zhao, Xuefeng; Wright, David A; Carpenter, Susan; Spalding, Martin H; Weeks, Donald P; Yang, Bing

    2011-08-01

    Recent studies indicate that the DNA recognition domain of transcription activator-like (TAL) effectors can be combined with the nuclease domain of FokI restriction enzyme to produce TAL effector nucleases (TALENs) that, in pairs, bind adjacent DNA target sites and produce double-strand breaks between the target sequences, stimulating non-homologous end-joining and homologous recombination. Here, we exploit the four prevalent TAL repeats and their DNA recognition cipher to develop a 'modular assembly' method for rapid production of designer TALENs (dTALENs) that recognize unique DNA sequence up to 23 bases in any gene. We have used this approach to engineer 10 dTALENs to target specific loci in native yeast chromosomal genes. All dTALENs produced high rates of site-specific gene disruptions and created strains with expected mutant phenotypes. Moreover, dTALENs stimulated high rates (up to 34%) of gene replacement by homologous recombination. Finally, dTALENs caused no detectable cytotoxicity and minimal levels of undesired genetic mutations in the treated yeast strains. These studies expand the realm of verified TALEN activity from cultured human cells to an intact eukaryotic organism and suggest that low-cost, highly dependable dTALENs can assume a significant role for gene modifications of value in human and animal health, agriculture and industry.

  6. Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes

    Energy Technology Data Exchange (ETDEWEB)

    Li, T; Huang, S; Zhao, XF; Wright, DA; Carpenter, S; Spalding, MH; Weeks, DP; Yang, B

    2011-08-08

    Recent studies indicate that the DNA recognition domain of transcription activator-like (TAL) effectors can be combined with the nuclease domain of FokI restriction enzyme to produce TAL effector nucleases (TALENs) that, in pairs, bind adjacent DNA target sites and produce double-strand breaks between the target sequences, stimulating non-homologous end-joining and homologous recombination. Here, we exploit the four prevalent TAL repeats and their DNA recognition cipher to develop a 'modular assembly' method for rapid production of designer TALENs (dTALENs) that recognize unique DNA sequence up to 23 bases in any gene. We have used this approach to engineer 10 dTALENs to target specific loci in native yeast chromosomal genes. All dTALENs produced high rates of site-specific gene disruptions and created strains with expected mutant phenotypes. Moreover, dTALENs stimulated high rates (up to 34%) of gene replacement by homologous recombination. Finally, dTALENs caused no detectable cytotoxicity and minimal levels of undesired genetic mutations in the treated yeast strains. These studies expand the realm of verified TALEN activity from cultured human cells to an intact eukaryotic organism and suggest that low-cost, highly dependable dTALENs can assume a significant role for gene modifications of value in human and animal health, agriculture and industry.

  7. Agrobacterium-mediated transformation leads to improved gene replacement efficiency in Aspergillus awamori.

    NARCIS (Netherlands)

    Michielse, C.B.; Arentshorst, M.; Ram, A.F.; Hondel, C.A. van den

    2005-01-01

    In this study, the efficiency of gene replacement in Aspergillus awamori between Agrobacterium-mediated transformation and CaCl(2)/PEG-mediated transformation was compared. For the genes, pyrG and gfaA, it was found that the homologous recombination frequencies obtained by Agrobacterium-mediated tra

  8. An improved cloning vector for construction of gene replacements in Listeria monocytogenes.

    Science.gov (United States)

    Li, Guojie; Kathariou, S

    2003-05-01

    Listeria monocytogenes is a gram-positive, facultative intracellular bacterium implicated in severe food-borne illness (listeriosis) in humans. The construction of well-defined gene replacements in the genome of L. monocytogenes has been instrumental to several genetic studies of the virulence and other attributes of the organism. Construction of such mutations by currently available procedures, however, tends to be labor intensive, and gene replacement mutants are sometimes difficult to recover due to lack of direct selection for the construct. In this study we describe the construction and use of plasmid vector pGF-EM, which can be conjugatively transferred from Escherichia coli S17-1 to L. monocytogenes and which provides the genetic means for direct selection of gene replacements.

  9. Stable gene replacement in barley by targeted double-strand break induction.

    Science.gov (United States)

    Watanabe, Koichi; Breier, Ulrike; Hensel, Götz; Kumlehn, Jochen; Schubert, Ingo; Reiss, Bernd

    2016-03-01

    Gene targeting is becoming an important tool for precision genome engineering in plants. During gene replacement, a variant of gene targeting, transformed DNA integrates into the genome by homologous recombination (HR) to replace resident sequences. We have analysed gene targeting in barley (Hordeum vulgare) using a model system based on double-strand break (DSB) induction by the meganuclease I-SceI and a transgenic, artificial target locus. In the plants we obtained, the donor construct was inserted at the target locus by homology-directed DNA integration in at least two transformants obtained in a single experiment and was stably inherited as a single Mendelian trait. Both events were produced by one-sided integration. Our data suggest that gene replacement can be achieved in barley with a frequency suitable for routine application. The use of a codon-optimized nuclease and co-transfer of the nuclease gene together with the donor construct are probably the components important for efficient gene targeting. Such an approach, employing the recently developed synthetic nucleases/nickases that allow DSB induction at almost any sequence of a genome of interest, sets the stage for precision genome engineering as a routine tool even for important crops such as barley.

  10. Efficient four fragment cloning for the construction of vectors for targeted gene replacement in filamentous fungi

    DEFF Research Database (Denmark)

    Frandsen, Rasmus John Normand; Andersson, Jens A.; Kristensen, Matilde Bylov;

    2008-01-01

    technique that allows single step cloning of the two required homologous recombination sequences into different sites of a recipient vector. The advantages are: A simple experimental design, free choice of target sequence, few procedures and user convenience. The vectors are intented for Agrobacterium...... with an average efficiency of 84% for gene replacement and 80% for targeted overexpression. Conclusion: The new vectors designed for USER Friendly cloning provided a fast reliable method to construct vectors for targeted gene manipulations in fungi....

  11. The treatment of hemophilia A: from protein replacement to AAV-mediated gene therapy.

    Science.gov (United States)

    Youjin, Shen; Jun, Yin

    2009-03-01

    Factor VIII (FVIII) is an essential component in blood coagulation, a deficiency of which causes the serious bleeding disorder hemophilia A. Recently, with the development of purification level and recombinant techniques, protein replacement treatment to hemophiliacs is relatively safe and can prolong their life expectancy. However, because of the possibility of unknown contaminants in plasma-derived FVIII and recombinant FVIII, and high cost for hemophiliacs to use these products, gene therapy for hemophilia A is an attractive alternative to protein replacement therapy. Thus far, the adeno-associated virus (AAV) is a promising vector for gene therapy. Further improvement of the virus for clinical application depends on better understanding of the molecular structure and fate of the vector genome. It is likely that hemophilia will be the first genetic disease to be cured by somatic cell gene therapy.

  12. Efficient four fragment cloning for the construction of vectors for targeted gene replacement in filamentous fungi

    DEFF Research Database (Denmark)

    Frandsen, Rasmus John Normand; Andersson, Jens A.; Kristensen, Matilde Bylov

    2008-01-01

    Background: The rapid increase in whole genome fungal sequence information allows large scale functional analyses of target genes. Efficient transformation methods to obtain site-directed gene replacement, targeted over-expression by promoter replacement, in-frame epitope tagging or fusion...... of coding sequences with fluorescent markers such as GFP are essential for this process. Construction of vectors for these experiments depends on the directional cloning of two homologous recombination sequences on each side of a selection marker gene. Results: Here, we present a USER Friendly cloning based...... technique that allows single step cloning of the two required homologous recombination sequences into different sites of a recipient vector. The advantages are: A simple experimental design, free choice of target sequence, few procedures and user convenience. The vectors are intented for Agrobacterium...

  13. Conditional gene expression and promoter replacement in Zymoseptoria tritici using fungal nitrate reductase promoters.

    Science.gov (United States)

    Marchegiani, Elisabetta; Sidhu, Yaadwinder; Haynes, Ken; Lebrun, Marc-Henri

    2015-06-01

    Studying essential genes in haploid fungi requires specific tools. Conditional promoter replacement (CPR) is an efficient method for testing gene essentiality. However, this tool requires promoters that can be strongly down-regulated. To this end, we tested the nitrate reductase promoters of Magnaporthe oryzae (pMoNIA1) and Zymoseptoria tritici (pZtNIA1) for their conditional expression in Z. tritici. Expression of EGFP driven by pMoNIA1 or pZtNIA1 was induced on nitrate and down-regulated on glutamate (10-fold less than nitrate). Levels of differential expression were similar for both promoters, demonstrating that the Z. tritici nitrogen regulatory network functions with a heterologous promoter similarly to a native promoter. To establish CPR, the promoter of Z. tritici BGS1, encoding a β-1,3-glucan synthase, was replaced by pZtNIA1 using targeted sequence replacement. Growth of pZtNIA1::BGS1 CPR transformants was strongly reduced in conditions repressing pZtNIA1, while their growth was similar to wild type in conditions inducing pZtNIA1. This differential phenotype demonstrates that BGS1 is important for growth in Z. tritici. In addition, in inducing conditions, pZtNIA1::BGS1 CPR transformants were hyper-sensitive to Calcofluor white, a cell wall disorganizing agent. Nitrate reductase promoters are therefore suitable for conditional promoter replacement in Z. tritici. This tool is a major step toward identifying novel fungicide targets.

  14. Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases.

    Directory of Open Access Journals (Sweden)

    Tatiana Flisikowska

    Full Text Available Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification are lacking. We demonstrate that zinc finger nucleases (ZFNs introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate precise homologous recombination with a DNA gene-targeting vector to achieve the first gene knockout and targeted sequence replacement in rabbits. Two ZFN pairs were designed that target the rabbit immunoglobulin M (IgM locus within exons 1 and 2. ZFN mRNAs were microinjected into pronuclear stage fertilized oocytes. Founder animals carrying distinct mutated IgM alleles were identified and bred to produce offspring. Functional knockout of the immunoglobulin heavy chain locus was confirmed by serum IgM and IgG deficiency and lack of IgM(+ and IgG(+ B lymphocytes. We then tested whether ZFN expression would enable efficient targeted sequence replacement in rabbit oocytes. ZFN mRNA was co-injected with a linear DNA vector designed to replace exon 1 of the IgM locus with ∼1.9 kb of novel sequence. Double strand break induced targeted replacement occurred in up to 17% of embryos and in 18% of fetuses analyzed. Two major goals have been achieved. First, inactivation of the endogenous IgM locus, which is an essential step for the production of therapeutic human polyclonal antibodies in the rabbit. Second, establishing efficient targeted gene manipulation and homologous recombination in a refractory animal species. ZFN mediated genetic engineering in the rabbit and other mammals opens new avenues of experimentation in immunology and many other research fields.

  15. Analysis of the Influence of Hormone Replacement Therapy on Osteocalcin Gene Expression in Postmenopausal Women.

    Science.gov (United States)

    Rahnama, Mansur; Jastrzębska-Jamrogiewicz, Izabela; Jamrogiewicz, Rafał; Trybek, Grzegorz

    2015-01-01

    Osteocalcin (OC) contributes to the process of bone mineralization. Present study was designed to investigate the changes in OC gene expression of postmenopausal women treated with hormone replacement therapy (HRT). Study was also designed to evaluate OC gene expression in cells which are not part of connective tissue. Research was carried out on 30 postmenopausal women not treated and 30 treated with HRT. Examination of OC gene expression was conducted on peripheral blood lymphocytes (PBL) and buccal epithelial lining (BEL). Densitometry was conducted on femur and mandible. Tests revealed OC gene expression in BEL and PBL. BMD was higher in groups treated with HRT. Assessment of correlation between the OC gene expression in BEL and BMD of mandible revealed significant positive relation. OC gene expression can be stated BEL and PBL. Analysis of correlation between OC gene expression in oral cavity and mandible BMD showed significant correlation between local OC expression and local bone metabolism. The relation between OC gene expression and bone metabolism is complex and further research is needed to clear all of the uncertainties.

  16. 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.

  17. Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP.

    Science.gov (United States)

    Pawlyk, Basil S; Smith, Alexander J; Buch, Prateek K; Adamian, Michael; Hong, Dong-Hyun; Sandberg, Michael A; Ali, Robin R; Li, Tiansen

    2005-09-01

    Retinitis pigmentosa GTPase regulator (RPGR) is a photoreceptor protein anchored in the connecting cilia by an RPGR-interacting protein (RPGRIP). Loss of RPGRIP causes Leber congenital amaurosis (LCA), a severe form of photoreceptor degeneration. The current study was an investigation of whether somatic gene replacement could rescue degenerating photoreceptors in a murine model of LCA due to a defect in RPGRIP. An RPGRIP expression cassette, driven by a mouse opsin promoter, was packaged into recombinant adeno-associated virus (AAV). The AAV vector was delivered into the right eyes of RPGRIP(-/-) mice by a single subretinal injection into the superior hemisphere. The left eyes received a saline injection as a control. Full-field electroretinograms (ERGs) were recorded from both eyes at 2, 3, 4, and 5 months after injection. After the final follow-up, retinas were analyzed by immunostaining or by light and electron microscopy. Delivery of the AAV vector led to RPGRIP expression and restoration of normal RPGR localization at the connecting cilia. Photoreceptor preservation was evident by a thicker cell layer and well-developed outer segments in the treated eyes. Rescue was more pronounced in the superior hemisphere coincident with the site of delivery. Functional preservation was demonstrated by ERG. AAV-mediated RPGRIP gene replacement preserves photoreceptor structure and function in a mouse model of LCA, despite ongoing cell loss at the time of intervention. These results indicate that gene replacement therapy may be effective in patients with LCA due to a defect in RPGRIP and suggest that further preclinical development of gene therapy for this disorder is warranted.

  18. Natural replacement of vertically inherited lux-rib genes of Photobacterium aquimaris by horizontally acquired homologues.

    Science.gov (United States)

    Urbanczyk, Henryk; Furukawa, Takashi; Yamamoto, Yuki; Dunlap, Paul V

    2012-08-01

    We report here the first instance of a complete replacement of vertically inherited luminescence genes by horizontally acquired homologues. Different strains of Photobacterium aquimaris contain homologues of the lux-rib genes that have a different evolutionary history. Strain BS1 from the Black Sea contains a vertically inherited lux-rib operon, which presumably arose in the ancestor of this species, whereas the type strain NBRC 104633(T) , from Sagami Bay, lacks the vertically inherited lux-rib operon and instead carries a complete and functional lux-rib operon acquired horizontally from a bacterium related to Photobacterium mandapamensis. The results indicate that the horizontal acquisition of the lux genes expanded the pan-genome of P. aquimaris, but it did not influence the phylogenetic divergence of this species.

  19. SYBR safe(TM) 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.

  20. Inverse Medea as a novel gene drive system for local population replacement: a theoretical analysis.

    Science.gov (United States)

    Marshall, John M; Hay, Bruce A

    2011-01-01

    One strategy to control mosquito-borne diseases, such as malaria and dengue fever, on a regional scale is to use gene drive systems to spread disease-refractory genes into wild mosquito populations. The development of a synthetic Medea element that has been shown to drive population replacement in laboratory Drosophila populations has provided encouragement for this strategy but has also been greeted with caution over the concern that transgenes may spread into countries without their consent. Here, we propose a novel gene drive system, inverse Medea, which is strong enough to bring about local population replacement but is unable to establish itself beyond an isolated release site. The system consists of 2 genetic components--a zygotic toxin and maternal antidote--which render heterozygous offspring of wild-type mothers unviable. Through population genetic analysis, we show that inverse Medea will only spread when it represents a majority of the alleles in a population. The element is best located on an autosome and will spread to fixation provided any associated fitness costs are dominant and to very high frequency otherwise. We suggest molecular tools that could be used to build the inverse Medea system and discuss its utility for a confined release of transgenic mosquitoes.

  1. The dam replacing gene product enhances Neisseria gonorrhoeae FA1090 viability and biofilm formation.

    Science.gov (United States)

    Kwiatek, Agnieszka; Bacal, Pawel; Wasiluk, Adrian; Trybunko, Anastasiya; Adamczyk-Poplawska, Monika

    2014-01-01

    Many Neisseriaceae do not exhibit Dam methyltransferase activity and, instead of the dam gene, possess drg (dam replacing gene) inserted in the leuS/dam locus. The drg locus in Neisseria gonorrhoeae FA1090 has a lower GC-pairs content (40.5%) compared to the whole genome of N. gonorrhoeae FA1090 (52%). The gonococcal drg gene encodes a DNA endonuclease Drg, with GmeATC specificity. Disruption of drg or insertion of the dam gene in gonococcal genome changes the level of expression of genes as shown by transcriptome analysis. For the drg-deficient N. gonorrhoeae mutant, a total of 195 (8.94% of the total gene pool) genes exhibited an altered expression compared to the wt strain by at least 1.5 fold. In dam-expressing N. gonorrhoeae mutant, the expression of 240 genes (11% of total genes) was deregulated. Most of these deregulated genes were involved in translation, DNA repair, membrane biogenesis and energy production as shown by cluster of orthologous group analysis. In vivo, the inactivation of drg gene causes the decrease of the number of live neisserial cells and long lag phase of growth. The insertion of dam gene instead of drg locus restores cell viability. We have also shown that presence of the drg gene product is important for N. gonorrhoeae FA1090 in adhesion, including human epithelial cells, and biofilm formation. Biofilm produced by drg-deficient strain is formed by more dispersed cells, compared to this one formed by parental strain as shown by scanning electron and confocal microscopy. Also adherence assays show a significantly smaller biomass of formed biofilm (OD570 = 0.242 ± 0.038) for drg-deficient strain, compared to wild-type strain (OD570 = 0.378 ± 0.057). Dam-expressing gonococcal cells produce slightly weaker biofilm with cells embedded in an extracellular matrix. This strain has also a five times reduced ability for adhesion to human epithelial cells. In this context, the presence of Drg is more advantageous for N. gonorrhoeae biology than

  2. Tailor-made TALEN system for highly efficient targeted gene replacement in the rice blast fungus.

    Science.gov (United States)

    Arazoe, Takayuki; Ogawa, Tetsuo; Miyoshi, Kennosuke; Yamato, Tohru; Ohsato, Shuichi; Sakuma, Tetsushi; Yamamoto, Takashi; Arie, Tsutomu; Kuwata, Shigeru

    2015-07-01

    Genetic manipulation is key to unraveling gene functions and creating genetically modified strains of microbial organisms. Recently, engineered nucleases that can generate DNA double-strand breaks (DSBs) at a specific site in the desired locus within genome are utilized in a rapidly developing genome editing technology via DSBs repair. However, the use of engineered nucleases in filamentous fungi has not been validated. In this study, we demonstrated that tailor-made transcriptional activator-like effector nucleases (TALENs) system, Platinum-Fungal TALENs (PtFg TALENs), could improve the efficiency of homologous recombination-mediated targeted gene replacement by up to 100% in the rice blast fungus Pyricularia oryzae. This high-efficiency PtFg TALEN has great potential for basic and applied biological applications in filamentous fungi.

  3. 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

    Genome sequence data on fungal pathogens provide the opportunity to carry out a reverse genetics approach to uncover gene function. Efficient methods for targeted genome modifications such as knockout and in locus over-expression are in high demand. Here we describe two efficient single...... on specific structures in the binary vector. The available fungal binary vectors adapted for the USER system are described and protocols are provided for vector design and construction. A general protocol for verification of the resulting gene replacement events in the recipient fungal cells is also given....... The cloning systems described above are relevant for all transformation vector constructs, but here we describe their application for ATMT compatible binary vectors. Protocols are provided for ATMT exemplified by Fusarium graminearum. For large-scale reverse genetic projects, the USER technology...

  4. An alternative strategy for targeted gene replacement in plants using a dual-sgRNA/Cas9 design.

    Science.gov (United States)

    Zhao, Yongping; Zhang, Congsheng; Liu, Wenwen; Gao, Wei; Liu, Changlin; Song, Gaoyuan; Li, Wen-Xue; Mao, Long; Chen, Beijiu; Xu, Yunbi; Li, Xinhai; Xie, Chuanxiao

    2016-04-01

    Precision DNA/gene replacement is a promising genome-editing tool that is highly desirable for molecular engineering and breeding by design. Although the CRISPR/Cas9 system works well as a tool for gene knockout in plants, gene replacement has rarely been reported. Towards this end, we first designed a combinatory dual-sgRNA/Cas9 vector (construct #1) that successfully deleted miRNA gene regions (MIR169a and MIR827a). The deletions were confirmed by PCR and subsequent sequencing, yielding deletion efficiencies of 20% and 24% on MIR169a and MIR827a loci, respectively. We designed a second structure (construct #2) that contains sites homologous to Arabidopsis TERMINAL FLOWER 1 (TFL1) for homology-directed repair (HDR) with regions corresponding to the two sgRNAs on the modified construct #1. The two constructs were co-transformed into Arabidopsis plants to provide both targeted deletion and donor repair for targeted gene replacement by HDR. Four of 500 stably transformed T0 transgenic plants (0.8%) contained replaced fragments. The presence of the expected recombination sites was further confirmed by sequencing. Therefore, we successfully established a gene deletion/replacement system in stably transformed plants that can potentially be utilized to introduce genes of interest for targeted crop improvement.

  5. Novel Cellulase Profile of Trichoderma reesei Strains Constructed by cbh1 Gene Replacement with eg3 Gene Expression Cassette

    Institute of Scientific and Technical Information of China (English)

    Tian-Hong WANG; Ti LIU; Zhi-Hong WU; Shi-Li LIU; Yi LU; Yin-Bo QU

    2004-01-01

    To construct strains of the filamentous fungus Trichoderma reesei with low cellobiohydrolases while high endoglucanase activity, the Pcbh1-eg3-Tcbh1 cassette was constructed and the coding sequence of the cellobiohydrolase I (CBHI) gene was replaced with the coding sequence of the eg3 gene by homologous recombination. Disruption of the cbh1 gene was confirmed by PCR, Southern dot blot and Western hybridization analysis in two transforments denoted as L 13 and L29. The filter paper-hydrolyzing activity of strain L29 was 60% of the parent strain Rut C30, and the CMCase activity was increased by 33%. This relatively modest increase suggested that the eg3 cDNA under the control of the cbh1 promoter was not efficiently transcribed as the wild type cbhl gene. However our results confirmed that homologous recombination could be used to construct strains of the filamentous fungus Trichoderma reesei with novel cellulase profile. Such strains are of interest from the basic science perspective and also have potential industrial applications.

  6. Homologous recombination and gene replacement at the dihydrofolate reductase-thymidylate synthase locus in Toxoplasma gondii.

    Science.gov (United States)

    Donald, R G; Roos, D S

    1994-02-01

    To investigate the feasibility of genomic transgene expression and gene targeting in Toxoplasma gondii, parasites have been transfected with constructs differing in the length of contiguous genomic sequence spanning the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene. We have previously reported that vectors derived from a DHFR-TS cDNA 'minigene' containing mutations in the DHFR coding sequence confer pyrimethamine resistance to transfected parasites (Donald and Roos, 1993). Stably resistant parasite clones arise at high frequency, generally by virtue of transgene integration into parasite chromosomes at locations scattered throughout the genome. In contrast, using a vector which contains 8 kb of contiguous genomic sequence (vs. homologous recombination. Homologous recombination appears to occur at even higher frequency when a 16 kb genomic clone is used. Circular plasmids were more efficient than linearized molecules at producing homologous recombination in this system, integrating by reciprocal crossing-over to produce a duplication of the DHFR-TS locus. Double crossing-over (or gene conversion) was also observed at low frequency, resulting in complete allelic replacement in this haploid stage of the parasite. The ability to produce either homologous or non-homologous recombinants, by the selection of appropriate transformation constructs, has considerable genetic potential.

  7. Inhibition of RecBCD in Klebsiella pneumoniae by Gam and its effect on the efficiency of gene replacement.

    Science.gov (United States)

    Chen, Chuan; Wei, Dong; Liu, Pengfu; Wang, Min; Shi, Jiping; Jiang, Biao; Hao, Jian

    2016-02-01

    Gam protein is an inhibitor of the host RecBCD exonuclease, and this inhibition is essential to the proficiency of Red recombinase-mediated gene replacement. In Klebsiella pneumoniae, the efficiency of this gene replacement was lower than that in Escherichia coli, and the minimum length of homologous extensions required was longer. Thus, it was supposed that the inhibitory effect of Gam against RecBCD was weak in K. pneumoniae. To test this hypothesis, a Gam-deficient Red recombinase expression plasmid and a ΔrecB K. pneumoniae mutant were constructed. The Gam-deficient Red recombinase showed a reduced capacity for gene replacement compared with that of the complete Red recombinase. The efficiency of gene replacement in the ΔrecB mutant was 6-8 times higher than the wild-type strain, and the minimum length for the homologous extensions was reduced to 100 bp. These results indicate that Gam does inhibit the RecBCD exonuclease in K. pneumoniae, but that this inhibition is not stringent. Furthermore, mutation of recB presents a convenient and efficient method to enhance the Red recombinase assisted gene replacement in K. pneumoniae.

  8. Excretion of antibiotic resistance genes by dairy calves fed milk replacers with varying doses of antibiotics

    Directory of Open Access Journals (Sweden)

    Callie H. Thames

    2012-04-01

    Full Text Available 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/ g 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 onwards, and tetW and tetG significantly increased (P<0.10, even in control 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

  9. Three-Parent IVF: Gene Replacement for the Prevention of Inherited Mitochondrial Diseases

    Science.gov (United States)

    Amato, Paula; Tachibana, Masahito; Sparman, Michelle; Mitalipov, Shoukhrat

    2014-01-01

    Mitochondrial dysfunction has been recognized as a significant cause of a number of serious multi-organ diseases. Tissues with a high metabolic demand such as brain, heart, muscle, CNS are often affected. Mitochondrial disease can be due to mutations in mitochondrial DNA (mtDNA) or in nuclear genes involved in mitochondrial function. There is no curative treatment for patients with mitochondrial disease. Given the lack of treatments and the limitations of prenatal and preimplantation diagnosis, attention has focused on prevention of transmission of mitochondrial disease through germline gene replacement therapy. Since mtDNA is strictly maternally inherited, two approaches have been proposed. In the first, the nuclear genome from the pronuclear stage zygote of an affected woman is transferred to an enucleated donor zygote. A second technique involves transfer of the metaphase II spindle from the unfertilized oocyte of an affected woman to an enucleated donor oocyte. Our group recently reported successful spindle transfer between human oocytes resulting in blastocyst development and embryonic stem cell derivation, with very low levels of heteroplasmy. In this review, we summarize these novel assisted reproductive techniques and their use to prevent transmission of mitochondrial disorders. The promises and challenges are discussed, focusing on their potential clinical application. PMID:24382342

  10. Editing Transgenic DNA Components by Inducible Gene Replacement in Drosophila melanogaster.

    Science.gov (United States)

    Lin, Chun-Chieh; Potter, Christopher J

    2016-08-01

    Gene conversions occur when genomic double-strand DNA breaks (DSBs) trigger unidirectional transfer of genetic material from a homologous template sequence. Exogenous or mutated sequence can be introduced through this homology-directed repair (HDR). We leveraged gene conversion to develop a method for genomic editing of existing transgenic insertions in Drosophila melanogaster The clustered regularly-interspaced palindromic repeats (CRISPR)/Cas9 system is used in the H: omology A: ssisted C: RISPR K: nock-in (HACK) method to induce DSBs in a GAL4 transgene, which is repaired by a single-genomic transgenic construct containing GAL4 homologous sequences flanking a T2A-QF2 cassette. With two crosses, this technique converts existing GAL4 lines, including enhancer traps, into functional QF2 expressing lines. We used HACK to convert the most commonly-used GAL4 lines (labeling tissues such as neurons, fat, glia, muscle, and hemocytes) to QF2 lines. We also identified regions of the genome that exhibited differential efficiencies of HDR. The HACK technique is robust and readily adaptable for targeting and replacement of other genomic sequences, and could be a useful approach to repurpose existing transgenes as new genetic reagents become available.

  11. Efficient CRISPR-mediated gene targeting and transgene replacement in the beetle Tribolium castaneum.

    Science.gov (United States)

    Gilles, Anna F; Schinko, Johannes B; Averof, Michalis

    2015-08-15

    Gene-editing techniques are revolutionizing the way we conduct genetics in many organisms. The CRISPR/Cas nuclease has emerged as a highly versatile, efficient and affordable tool for targeting chosen sites in the genome. Beyond its applications in established model organisms, CRISPR technology provides a platform for genetic intervention in a wide range of species, limited only by our ability to deliver it to cells and to select mutations efficiently. Here, we test the CRISPR technology in an emerging insect model and pest, the beetle Tribolium castaneum. We use simple assays to test CRISPR/Cas activity, we demonstrate efficient expression of guide RNAs and Cas9 from Tribolium U6 and hsp68 promoters and we test the efficiency of knockout and knock-in approaches in Tribolium. We find that 55-80% of injected individuals carry mutations (indels) generated by non-homologous end joining, including mosaic bi-allelic knockouts; 71-100% carry such mutations in their germ line and transmit them to the next generation. We show that CRISPR-mediated gene knockout of the Tribolium E-cadherin gene causes defects in dorsal closure, which is consistent with RNAi-induced phenotypes. Homology-directed knock-in of marker transgenes was observed in 14% of injected individuals and transmitted to the next generation by 6% of injected individuals. Previous work in Tribolium mapped a large number of transgene insertions associated with developmental phenotypes and enhancer traps. We present an efficient method for re-purposing these insertions, via CRISPR-mediated replacement of these transgenes by new constructs.

  12. Replacement gene therapy with a human RPGRIP1 sequence slows photoreceptor degeneration in a murine model of Leber congenital amaurosis.

    Science.gov (United States)

    Pawlyk, Basil S; Bulgakov, Oleg V; Liu, Xiaoqing; Xu, Xiaoyun; Adamian, Michael; Sun, Xun; Khani, Shahrokh C; Berson, Eliot L; Sandberg, Michael A; Li, Tiansen

    2010-08-01

    RPGR-interacting protein-1 (RPGRIP1) is localized in the photoreceptor-connecting cilium, where it anchors the RPGR (retinitis pigmentosa GTPase regulator) protein, and its function is essential for photoreceptor maintenance. Genetic defect in RPGRIP1 is a known cause of Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. We evaluated the efficacy of replacement gene therapy in a murine model of LCA carrying a targeted disruption of RPGRIP1. The replacement construct, packaged in an adeno-associated virus serotype 8 (AAV8) vector, used a rhodopsin kinase gene promoter to drive RPGRIP1 expression. Both promoter and transgene were of human origin. After subretinal delivery of the replacement gene in the mutant mice, human RPGRIP1 was expressed specifically in photoreceptors, localized correctly in the connecting cilia, and restored the normal localization of RPGR. Electroretinogram and histological examinations showed better preservation of rod and cone photoreceptor function and improved photoreceptor survival in the treated eyes. This study demonstrates the efficacy of human gene replacement therapy and validates a gene therapy design for future clinical trials in patients afflicted with this condition. Our results also have therapeutic implications for other forms of retinal degenerations attributable to a ciliary defect.

  13. Efficient disruption and replacement of an effector gene in the oomycete Phytophthora sojae using CRISPR/Cas9.

    Science.gov (United States)

    Fang, Yufeng; Tyler, Brett M

    2016-01-01

    Phytophthora sojae is an oomycete pathogen of soybean. As a result of its economic importance, P. sojae has become a model for the study of oomycete genetics, physiology and pathology. The lack of efficient techniques for targeted mutagenesis and gene replacement have long hampered genetic studies of pathogenicity in Phytophthora species. Here, we describe a CRISPR/Cas9 system enabling rapid and efficient genome editing in P. sojae. Using the RXLR effector gene Avr4/6 as a target, we observed that, in the absence of a homologous template, the repair of Cas9-induced DNA double-strand breaks (DSBs) in P. sojae was mediated by non-homologous end-joining (NHEJ), primarily resulting in short indels. Most mutants were homozygous, presumably as a result of gene conversion triggered by Cas9-mediated cleavage of non-mutant alleles. When donor DNA was present, homology-directed repair (HDR) was observed, which resulted in the replacement of Avr4/6 with the NPT II gene. By testing the specific virulence of several NHEJ mutants and HDR-mediated gene replacements in soybean, we have validated the contribution of Avr4/6 to recognition by soybean R gene loci, Rps4 and Rps6, but also uncovered additional contributions to resistance by these two loci. Our results establish a powerful tool for the study of functional genomics in Phytophthora, which provides new avenues for better control of this pathogen.

  14. The efficient cell-SELEX strategy, Icell-SELEX, using isogenic cell lines for selection and counter-selection to generate RNA aptamers to cell surface proteins.

    Science.gov (United States)

    Takahashi, Masaki; Sakota, Eri; Nakamura, Yoshikazu

    2016-12-01

    Aptamers are short single-stranded nucleic acid molecules that are selected in vitro from a large random sequence library based on their high and specific affinity to a target molecule by a process known as SELEX. Cell-SELEX that employs whole living cells overexpressing the defined cell surface proteins (for selection) and appropriate mock cells (for counter-selection) has been widely used as a valid and feasible method for generating aptamers against specific cell surface proteins. However, the endogenous expression of target proteins in mock cells or the heterogeneity of surface proteins between selection and counter-selection cells often impeded the isolation of proper aptamers against target proteins. To solve this problem, we developed "Isogenic cell-SELEX" (Icell SELEX in short) method, in which isogenic cell lines were manipulated for counter-selection by microRNA-mediated silencing and for selection by overexpression of target proteins. As a model experiment, we targeted integrin alpha V (ITGAV), which is a major transmembrane receptor expressed in almost all the cells, and established ITGAV-overexpressed and -downregulated HEK293 cells for selection and counter-selection, respectively. By taking advantage of a hundred-fold difference in the expression level of ITGAV between these two isogenic cell lines, we easily isolated several anti-ITGAV aptamers, whose binding to the cell-surface ITGAV was confirmed by flow cytometry with the dissociation constant of 300-400 nM range. We assume that Icell-SELEX could be applicable to a wide range of cell-surface proteins including various transmembrane proteins of biological and pharmacological significance. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  15. Antibody repertoire diversification through VH gene replacement in mice cloned from an IgA plasma cell.

    Science.gov (United States)

    Kumar, Rashmi; Bach, Martina P; Mainoldi, Federica; Maruya, Mikako; Kishigami, Satoshi; Jumaa, Hassan; Wakayama, Teruhiko; Kanagawa, Osami; Fagarasan, Sidonia; Casola, Stefano

    2015-02-01

    In mammals, VDJ recombination is responsible for the establishment of a highly diversified preimmune antibody repertoire. Acquisition of a functional Ig heavy (H) chain variable (V) gene rearrangement is thought to prevent further recombination at the IgH locus. Here, we describe VHQ52(NT); Vκgr32(NT) Ig monoclonal mice reprogrammed from the nucleus of an intestinal IgA(+) plasma cell. In VHQ52(NT) mice, IgA replaced IgM to drive early B-cell development and peripheral B-cell maturation. In VHQ52(NT) animals, over 20% of mature B cells disrupted the single productive, nonautoimmune IgH rearrangement through VH replacement and exchanged it with a highly diversified pool of IgH specificities. VH replacement occurred in early pro-B cells, was independent of pre-B-cell receptor signaling, and involved predominantly one adjacent VH germ-line gene. VH replacement was also identified in 5% of peripheral B cells of mice inheriting a different productive VH rearrangement expressed in the form of an IgM H chain. In summary, editing of a productive IgH rearrangement through VH replacement can account for up to 20% of the IgH repertoire expressed by mature B cells.

  16. Establishment of a Counter-selectable Markerless Mutagenesis System in Veillonella atypica

    Science.gov (United States)

    Zhou, Peng; Li, Xiaoli; Qi, Fengxia

    2015-01-01

    Using an alternative sigma factor ecf3 as target, we successfully established the first markerless mutagenesis system in the Veillonella genus. This system will be a valuable tool for mutagenesis of multiple genes for gene function analysis as well as for gene regulation studies in Veillonella. PMID:25771833

  17. The structure-specific endonuclease Ercc1–Xpf is required for targeted gene replacement in embryonic stem cells

    Science.gov (United States)

    Niedernhofer, Laura J.; Essers, Jeroen; Weeda, Geert; Beverloo, Berna; de Wit, Jan; Muijtjens, Manja; Odijk, Hanny; Hoeijmakers, Jan H.J.; Kanaar, Roland

    2001-01-01

    The Ercc1–Xpf heterodimer, a highly conserved structure-specific endonuclease, functions in multiple DNA repair pathways that are pivotal for maintaining genome stability, including nucleotide excision repair, interstrand crosslink repair and homologous recombination. Ercc1–Xpf incises double-stranded DNA at double-strand/single-strand junctions, making it an ideal enzyme for processing DNA structures that contain partially unwound strands. Here we demonstrate that although Ercc1 is dispensable for recombination between sister chromatids, it is essential for targeted gene replacement in mouse embryonic stem cells. Surprisingly, the role of Ercc1–Xpf in gene targeting is distinct from its previously identified role in removing nonhomologous termini from recombination intermediates because it was required irrespective of whether the ends of the DNA targeting constructs were heterologous or homologous to the genomic locus. Our observations have implications for the mechanism of gene targeting in mammalian cells and define a new role for Ercc1–Xpf in mammalian homologous recombination. We propose a model for the mechanism of targeted gene replacement that invokes a role for Ercc1–Xpf in making the recipient genomic locus receptive for gene replacement. PMID:11707424

  18. Accumulation of VH Replacement Products in IgH Genes Derived from Autoimmune Diseases and Anti-Viral Responses in Human.

    Science.gov (United States)

    Lange, Miles D; Huang, Lin; Yu, Yangsheng; Li, Song; Liao, Hongyan; Zemlin, Michael; Su, Kaihong; Zhang, Zhixin

    2014-01-01

    VH replacement refers to RAG-mediated secondary recombination of the IgH genes, which renews almost the entire VH gene coding region but retains a short stretch of nucleotides as a VH replacement footprint at the newly generated VH-DH junction. To explore the biological significance of VH replacement to the antibody repertoire, we developed a Java-based VH replacement footprint analyzer program and analyzed the distribution of VH replacement products in 61,851 human IgH gene sequences downloaded from the NCBI database. The initial assignment of the VH, DH, and JH gene segments provided a comprehensive view of the human IgH repertoire. To our interest, the overall frequency of VH replacement products is 12.1%; the frequencies of VH replacement products in IgH genes using different VH germline genes vary significantly. Importantly, the frequencies of VH replacement products are significantly elevated in IgH genes derived from different autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and allergic rhinitis, and in IgH genes encoding various autoantibodies or anti-viral antibodies. The identified VH replacement footprints preferentially encoded charged amino acids to elongate IgH CDR3 regions, which may contribute to their autoreactivities or anti-viral functions. Analyses of the mutation status of the identified VH replacement products suggested that they had been actively involved in immune responses. These results provide a global view of the distribution of VH replacement products in human IgH genes, especially in IgH genes derived from autoimmune diseases and anti-viral immune responses.

  19. Direct evidence for redundant segmental replacement between multiple 18S rRNA genes in a single Prototheca strain.

    Science.gov (United States)

    Ueno, Ryohei; Huss, Volker A R; Urano, Naoto; Watabe, Shugo

    2007-11-01

    Informational genes such as those encoding rRNAs are related to transcription and translation, and are thus considered to be rarely subject to lateral gene transfer (LGT) between different organisms, compared to operational genes having metabolic functions. However, several lines of evidence have suggested or confirmed the occurrence of LGT of DNA segments encoding evolutionarily variable regions of rRNA genes between different organisms. In the present paper, we show, for the first time to our knowledge, that variable regions of the 18S rRNA gene are segmentally replaced by multiple copies of different sequences in a single strain of the green microalga Prototheca wickerhamii, resulting in at least 17 genotypes, nine of which were actually transcribed. Recombination between different 18S rRNA genes occurred in seven out of eight variable regions (V1-V5 and V7-V9) of eukaryotic small subunit (SSU) rRNAs. While no recombination was observed in V1, one to three different recombination loci were demonstrated for the other regions. Such segmental replacement was also implicated for helix H37, which is defined as V6 of prokaryotic SSU rRNAs. Our observations provide direct evidence for redundant recombination of an informational gene, which encodes a component of mature ribosomes, in a single strain of one organism.

  20. An Experimental Study on the Flexibility of Prevention against Thrombosis Following Mechanical Valve Replacement by tPA Gene Transduction

    Institute of Scientific and Technical Information of China (English)

    Shangyi Ji; Jun Ji; Xiaohan Yang; Jiangan Yang; Xiaolei Wang; Wenping Ling; Yuping Zhang

    2008-01-01

    Objectives Use a gene suture immersed recombinant tissue-type plasminogen activator (r-tPA)expression plasmid to transduce myocardia to prevent the thrombosis after mechanical tricuspid valve replacement in pigs. Methods A r-tPA gene plasmid was constructed and conjugated to a novel cationic phosphonolipid and a r-tPA gene suture was made. Eighteen pigs were selected and divided into two groups at randomization. There were 9 pigs in the experimental group and 9 in the control group, all the 18 pigs' tricuspids were replaced with mechanical valves. The gene threads were sutured into the right ventficular walls near mechanical valves and an ultrasound was used on the surfaces of the right ventricular walls for the gene transfer in the experimental group. Coagulative function, D-dimer level of the blood and the thrombosis on the surfaces of the valves were observed. Results r-tPA gene plasmid was successfully con-strutted and r-tPA protein was expressed in the ventricular cells around the gene sutures. D-dimer reached its peak level the experiment in experimental group. The thromboses around the valves were found in all the control group (100%)but only 1 (11.11%) case in experimental group. There were no changes in prothrombin time pre and post operation in two groups. Conclusions Using gene suture immersed r-tPA expression plasmid to transduce myocardia might be a best substitution for life long anti-coagulation therapy for the patients, who underwent operation.

  1. Silencing of potato virus X coat protein gene in transgenic tobaccos by codon replacement that confers resistance to PVX infection

    Institute of Scientific and Technical Information of China (English)

    FENG Dejiang; LIU Xiang; MENG Kun; LIAO Lili; WEI Xiaoli; XU Honglin; ZHU Zhen

    2003-01-01

    To understand the effect of rare codon on the silencing ratio of foreign gene, some preferred codon in potato virus X (PVX) coat protein gene (cp) were substituted with synonymous rare codons. The modified PVX coat protein gene (cpm) and wild-type cp gene (cpw) were inserted into binary vector under the control of CaMV35S promoter, and these two plant expression constructs were transferred into tobacco (Nicotiana tabacum cv. Xanthi) genomes via Agrobacterium mediated method and transgenic plants were generated. Northern blot analysis of RNA isolated from these plants showed that the silencing ratio of cpm gene in transgenic tobaccos was higher than that of cpw (35% and 6.25% respectively). Run on results indicate that the silencing of cp gene happened at post-transcriptional level. The resistance of transgenic tobaccos carrying cpm genes to PVX is increased compared with that of transformants carrying cpw genes. These results suggest that the resistance of transgenic tobacco to PVX can be enhanced by codon replacement.

  2. 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.

  3. Engineering of Promoter Replacement Cassettes for Fine-Tuning of Gene Expression in Saccharomyces cerevisiae

    OpenAIRE

    2006-01-01

    The strong overexpression or complete deletion of a gene gives only limited information about its control over a certain phenotype or pathway. Gene function studies based on these methods are therefore incomplete. To effect facile manipulation of gene expression across a full continuum of possible expression levels, we recently created a library of mutant promoters. Here, we provide the detailed characterization of our yeast promoter collection comprising 11 mutants of the strong constitutive...

  4. Counterselection of prokaryotic ribosomal RNA during reverse transcription using non-random hexameric oligonucleotides.

    Science.gov (United States)

    Gonzalez, J M; Robb, F T

    2007-12-01

    Ribosomal RNA (rRNA) is the major component in total RNA extracts, interfering with the synthesis of cDNA corresponding to messenger RNA (mRNA). In this study, we present a novel strategy for selectively discriminating against rRNA and favoring mRNA from prokaryotes during synthesis of cDNA by reverse transcriptase. Our technique is based on the fact that rRNA sequences, in many species, are G+C rich relative to the genome at large, and highly conserved among prokaryotes. The sequence TTTT is therefore rarely found in rRNA sequences. However, TTTT priming sites are found at a much higher frequency in protein-encoding gene sequences. We designed specific hexamers (HD/DHTTTT) to prime reverse transcription reactions resulting in a selective synthesis of cDNA corresponding to mRNA from prokaryotic total RNA extractions.

  5. Detection of essential genes in Streptococcus pneumoniae using bioinformatics and allelic replacement mutagenesis.

    Science.gov (United States)

    Song, Jae-Hoon; Ko, Kwan Soo

    2008-01-01

    Although the emergence and spread of antimicrobial resistance in major bacterial pathogens for the past decades poses a growing challenge to public health, discovery of novel antimicrobial agents from natural products or modification of existing antibiotics cannot circumvent the problem of antimicrobial resistance. The recent development of bacterial genomics and the availability of genome sequences allow the identification of potentially novel antimicrobial agents. The cellular targets of new antimicrobial agents must be essential for the growth, replication, or survival of the bacterium. Conserved genes among different bacterial genomes often turn out to be essential (1, 2). Thus, the combination of comparative genomics and the gene knock-out procedure can provide effective ways to identify the essential genes of bacterial pathogens (3). Identification of essential genes in bacteria may be utilized for the development of new antimicrobial agents because common essential genes in diverse pathogens could constitute novel targets for broad-spectrum antimicrobial agents.

  6. 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....

  7. Enhanced gene replacements in Ku80 disruption mutants of the dermatophyte, Trichophyton mentagrophytes.

    Science.gov (United States)

    Yamada, Tsuyoshi; Makimura, Koichi; Hisajima, Tatsuya; Ishihara, Yumiko; Umeda, Yoshiko; Abe, Shigeru

    2009-09-01

    The frequency of targeted gene disruption via homologous recombination is low in the clinically important dermatophyte, Trichophyton mentagrophytes. The Ku genes, Ku70 and Ku80, encode key components of the nonhomologous end-joining pathway involved in DNA double-strand break repair. Their deletion increases the homologous recombination frequency, facilitating targeted gene disruption. To improve the homologous recombination frequency in T. mentagrophytes, the Ku80 ortholog was inactivated. The nucleotide sequence of the Ku80 locus containing a 2788-bp ORF encoding a predicted product of 728 amino acids was identified, and designated as TmKu80. The predicted TmKu80 product showed a high degree of amino acid sequence similarity to known fungal Ku80 proteins. Ku80 disruption mutant strains of T. mentagrophytes were constructed by Agrobacterium tumefaciens-mediated genetic transformation. The average homologous recombination frequency was 73.3 +/- 25.2% for the areA/nit-2-like nitrogen regulatory gene (tnr) in Ku80(-) mutants, about 33-fold higher than that in wild-type controls. A high frequency (c. 67%) was also obtained for the Tri m4 gene encoding a putative serine protease. Ku80(-) mutant strains will be useful for large-scale reverse genetics studies of dermatophytes, including T. mentagrophytes, providing valuable information on the basic mechanisms of host invasion.

  8. The Gene Targeting Approach of Small Fragment Homologous Replacement (SFHR Alters the Expression Patterns of DNA Repair and Cell Cycle Control Genes

    Directory of Open Access Journals (Sweden)

    Silvia Pierandrei

    2016-01-01

    Full Text Available Cellular responses and molecular mechanisms activated by exogenous DNA that invades cells are only partially understood. This limits the practical use of gene targeting strategies. Small fragment homologous replacement (SFHR uses a small exogenous wild-type DNA fragment to restore the endogenous wild-type sequence; unfortunately, this mechanism has a low frequency of correction. In this study, we used a mouse embryonic fibroblast cell line with a stably integrated mutated gene for enhanced green fluorescence protein. The restoration of a wild-type sequence can be detected by flow cytometry analysis. We quantitatively analyzed the expression of 84 DNA repair genes and 84 cell cycle control genes. Peculiar temporal gene expression patterns were observed for both pathways. Different DNA repair pathways, not only homologous recombination, as well as the three main cell cycle checkpoints appeared to mediate the cellular response. Eighteen genes were selected as highly significant target/effectors of SFHR. We identified a wide interconnection between SFHR, DNA repair, and cell cycle control. Our results increase the knowledge of the molecular mechanisms involved in cell invasion by exogenous DNA and SFHR. Specific molecular targets of both the cell cycle and DNA repair machineries were selected for manipulation to enhance the practical application of SFHR.

  9. The prevalence of genome replacement in unisexual salamanders of the genus Ambystoma (Amphibia, Caudata revealed by nuclear gene genealogy

    Directory of Open Access Journals (Sweden)

    Bogart James P

    2008-05-01

    Full Text Available Abstract Background Unisexual salamanders of the genus Ambystoma exemplify the most ancient lineage of unisexual vertebrates and demonstrate an extremely flexible reproductive system. Unisexual Ambystoma interact with and incorporate genomes from two to four sexual species (A. laterale, A. jeffersonianum,A. texanum, and A. tigrinum, to generate more than 20 genome compositions or biotypes. Unisexual ploidy levels range from diploid to pentaploid, but all contain at least one A. laterale (L genome. Replacement of nuclear genomes might be responsible for the evolutionary longevity of unisexual Ambystoma but direct evidence for the prevalence of genome replacement in natural populations is absent. Two major puzzling questions have remained unanswered over the last few decades: 1 is genome replacement a common reproductive method in various unisexual populations and, 2 is there an ancient "L" genome that persists in various unisexual genome compositions. Results We examined 194 unisexual and 89 A. laterale specimens from 97 localities throughout their range and constructed a genealogy of the "L" genomes using a nuclear DNA marker (L-G1C12 to answer the above questions. Six L-G1C12 haplotypes (A-F were shared by individuals in various A. laterale and unisexual populations. The general geographical distribution of the haplotypes in unisexual populations conformed to those found in A. laterale, indicating that "L" genomes in unisexuals are obtained from sympatric or nearby populations of A. laterale. Conclusion Our data demonstrate that genome replacement frequently occurs in unisexual Ambystoma across their range, and support previous speculations that genome replacement is an important reproductive mechanism that can enhance their evolutionary longevity. Our results show that there is no ancient "L" genome in the unisexual lineages, and no particular "L" genome is favored in any unisexual individual. The presence of an "L" genome in all unisexuals

  10. Two Y genes can replace the entire Y chromosome for assisted reproduction in the mouse.

    Science.gov (United States)

    Yamauchi, Yasuhiro; Riel, Jonathan M; Stoytcheva, Zoia; Ward, Monika A

    2014-01-03

    The Y chromosome is thought to be important for male reproduction. We have previously shown that, with the use of assisted reproduction, live offspring can be obtained from mice lacking the entire Y chromosome long arm. Here, we demonstrate that live mouse progeny can also be generated by using germ cells from males with the Y chromosome contribution limited to only two genes, the testis determinant factor Sry and the spermatogonial proliferation factor Eif2s3y. Sry is believed to function primarily in sex determination during fetal life. Eif2s3y may be the only Y chromosome gene required to drive mouse spermatogenesis, allowing formation of haploid germ cells that are functional in assisted reproduction. Our findings are relevant, but not directly translatable, to human male infertility cases.

  11. 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

    Genome sequence data on fungal pathogens provide the opportunity to carry out a reverse genetics approach to uncover gene function. Efficient methods for targeted genome modifications such as knockout and in locus over-expression are in high demand. Here we describe two efficient single-step clon......Genome sequence data on fungal pathogens provide the opportunity to carry out a reverse genetics approach to uncover gene function. Efficient methods for targeted genome modifications such as knockout and in locus over-expression are in high demand. Here we describe two efficient single......-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...

  12. BRaf signaling principles unveiled by large-scale human mutation analysis with a rapid lentivirus-based gene replacement method.

    Science.gov (United States)

    Lim, Chae-Seok; Kang, Xi; Mirabella, Vincent; Zhang, Huaye; Bu, Qian; Araki, Yoichi; Hoang, Elizabeth T; Wang, Shiqiang; Shen, Ying; Choi, Sukwoo; Kaang, Bong-Kiun; Chang, Qiang; Pang, Zhiping P; Huganir, Richard L; Zhu, J Julius

    2017-03-15

    Rapid advances in genetics are linking mutations on genes to diseases at an exponential rate, yet characterizing the gene mutation-cell behavior relationships essential for precision medicine remains a daunting task. More than 350 mutations on small GTPase BRaf are associated with various tumors, and ∼40 mutations are associated with the neurodevelopmental disorder cardio-facio-cutaneous syndrome (CFC). We developed a fast cost-effective lentivirus-based rapid gene replacement method to interrogate the physiopathology of BRaf and ∼50 disease-linked BRaf mutants, including all CFC-linked mutants. Analysis of simultaneous multiple patch-clamp recordings from 6068 pairs of rat neurons with validation in additional mouse and human neurons and multiple learning tests from 1486 rats identified BRaf as the key missing signaling effector in the common synaptic NMDA-R-CaMKII-SynGap-Ras-BRaf-MEK-ERK transduction cascade. Moreover, the analysis creates the original big data unveiling three general features of BRaf signaling. This study establishes the first efficient procedure that permits large-scale functional analysis of human disease-linked mutations essential for precision medicine. © 2017 Lim et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases.

    Science.gov (United States)

    Amato, Paula; Tachibana, Masahito; Sparman, Michelle; Mitalipov, Shoukhrat

    2014-01-01

    The exchange of nuclear genetic material between oocytes and embryos offers a novel reproductive option for the prevention of inherited mitochondrial diseases. Mitochondrial dysfunction has been recognized as a significant cause of a number of serious multiorgan diseases. Tissues with a high metabolic demand, such as brain, heart, muscle, and central nervous system, are often affected. Mitochondrial disease can be due to mutations in mitochondrial DNA or in nuclear genes involved in mitochondrial function. There is no curative treatment for patients with mitochondrial disease. Given the lack of treatments and the limitations of prenatal and preimplantation diagnosis, attention has focused on prevention of transmission of mitochondrial disease through germline gene replacement therapy. Because mitochondrial DNA is strictly maternally inherited, two approaches have been proposed. In the first, the nuclear genome from the pronuclear stage zygote of an affected woman is transferred to an enucleated donor zygote. A second technique involves transfer of the metaphase II spindle from the unfertilized oocyte of an affected woman to an enucleated donor oocyte. Our group recently reported successful spindle transfer between human oocytes, resulting in blastocyst development and embryonic stem cell derivation, with very low levels of heteroplasmy. In this review we summarize these novel assisted reproductive techniques and their use to prevent transmission of mitochondrial disorders. The promises and challenges are discussed, focusing on their potential clinical application.

  14. Tailor-made CRISPR/Cas system for highly efficient targeted gene replacement in the rice blast fungus.

    Science.gov (United States)

    Arazoe, Takayuki; Miyoshi, Kennosuke; Yamato, Tohru; Ogawa, Tetsuo; Ohsato, Shuichi; Arie, Tsutomu; Kuwata, Shigeru

    2015-12-01

    CRISPR/Cas-derived RNA-guided nucleases (RGNs) that can generate DNA double-strand breaks (DSBs) at a specific sequence are widely used for targeted genome editing by induction of DSB repair in many organisms. The CRISPR/Cas system consists of two components: a single Cas9 nuclease and a single-guide RNA (sgRNA). Therefore, the system for constructing RGNs is simple and efficient, but the utilization of RGNs in filamentous fungi has not been validated. In this study, we established the CRISPR/Cas system in the model filamentous fungus, Pyricularia oryzae, using Cas9 that was codon-optimized for filamentous fungi, and the endogenous RNA polymerase (RNAP) III U6 promoter and a RNAP II fungal promoter for the expression of the sgRNA. We further demonstrated that RGNs could recognize the desired sequences and edit endogenous genes through homologous recombination-mediated targeted gene replacement with high efficiency. Our system will open the way for the development of various CRISPR/Cas-based applications in filamentous fungi.

  15. A fragile lattice: replacing bacteriophage lambda's head stability gene D with the shp gene of phage 21 generates the Mg2+-dependent virus, lambda shp.

    Science.gov (United States)

    Wendt, Jennifer L; Feiss, Michael

    2004-08-15

    Phage lambda DNA packaging is accompanied by prohead expansion, due to structural changes in gpE, the major capsid protein. Rearrangement of the gpE lattice creates binding sites for trimers of gpD, the head stabilization protein. lambda-Like phage 21's shp gene is homologous to lambda's D gene. gpD and gpShp share 49% amino acid identity. To ask whether gpShp could stabilize the lambda head shell, we replaced lambda's D gene with shp, creating lambda shp. Unlike lambda or 21, lambda shp was strictly dependent on the presence of 10(-2) M Mg2+, and lambda shp virions were very sensitive to chelating agents. Density gradient studies indicated that the lambda gpE lattice was underpopulated with gpShp. gpD's N-terminus has been proposed to contact gpE, and we found that lambda D/shp, which produces a chimeric protein with the N-terminus of gpD and the C-terminus of gpShp, was Mg2+-independent and more stable than lambda shp.

  16. 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

  17. Ankle replacement

    Science.gov (United States)

    Ankle arthroplasty - total; Total ankle arthroplasty; Endoprosthetic ankle replacement; Ankle surgery ... You may not be able to have a total ankle replacement if you have had ankle joint infections in ...

  18. 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 ...

  19. Predominance of a versatile-peroxidase-encoding gene, mnp4, as demonstrated by gene replacement via a gene targeting system for Pleurotus ostreatus.

    Science.gov (United States)

    Salame, Tomer M; Knop, Doriv; Tal, Dana; Levinson, Dana; Yarden, Oded; Hadar, Yitzhak

    2012-08-01

    Pleurotus ostreatus (the oyster mushroom) and other white rot filamentous basidiomycetes are key players in the global carbon cycle. P. ostreatus is also a commercially important edible fungus with medicinal properties and is important for biotechnological and environmental applications. Efficient gene targeting via homologous recombination (HR) is a fundamental tool for facilitating comprehensive gene function studies. Since the natural HR frequency in Pleurotus transformations is low (2.3%), transformed DNA is predominantly integrated ectopically. To overcome this limitation, a general gene targeting system was developed by producing a P. ostreatus PC9 homokaryon Δku80 strain, using carboxin resistance complemented by the development of a protocol for hygromycin B resistance protoplast-based DNA transformation and homokaryon isolation. The Δku80 strain exhibited exclusive (100%) HR in the integration of transforming DNA, providing a high efficiency of gene targeting. Furthermore, the Δku80 strains produced showed a phenotype similar to that of the wild-type PC9 strain, with similar growth fitness, ligninolytic functionality, and capability of mating with the incompatible strain PC15 to produce a dikaryon which retained its resistance to the corresponding selection and was capable of producing typical fruiting bodies. The applicability of this system is demonstrated by inactivation of the versatile peroxidase (VP) encoded by mnp4. This enzyme is part of the ligninolytic system of P. ostreatus, being one of the nine members of the manganese-peroxidase (MnP) gene family, and is the predominantly expressed VP in Mn(2+)-deficient media. mnp4 inactivation provided a direct proof that mnp4 encodes a key VP responsible for the Mn(2+)-dependent and Mn(2+)-independent peroxidase activity under Mn(2+)-deficient culture conditions.

  20. Enriching Glucoraphanin in Brassica rapa Through Replacement of BrAOP2.2/BrAOP2.3 with Non-functional Genes

    Directory of Open Access Journals (Sweden)

    Zhiyuan Liu

    2017-08-01

    Full Text Available Sulforaphane, the hydrolytic product of glucoraphanin glucosinolate, is a potent anticarcinogen that reduces the risk of several human cancers. However, in most B. rapa vegetables, glucoraphanin is undetectable or only present in trace amounts, since the glucoraphanin that is present is converted to gluconapin by three functional BrAOP2 genes. In this study, to enrich beneficial glucoraphanin content in B. rapa, the functional BrAOP2 alleles were replaced by non-functional counterparts through marker-assisted backcrossing (MAB. We identified non-functional mutations of two BrAOP2 genes from B. rapa. The backcross progenies with introgression of both non-functional braop2.2 and braop2.3 alleles significantly increased the glucoraphanin content by 18 times relative to the recurrent parent. In contrast, replacement or introgression of single non-functional braop2.2 or braop2.3 locus did not change glucoraphanin content. Our results suggest that replacement of these two functional BrAOP2 genes with non-functional alleles has the potential for producing improved Brassica crops with enriched beneficial glucoraphanin content.

  1. Gene replacement analysis of the Streptomyces virginiae barA gene encoding the butyrolactone autoregulator receptor reveals that BarA acts as a repressor in virginiamycin biosynthesis.

    Science.gov (United States)

    Nakano, H; Takehara, E; Nihira, T; Yamada, Y

    1998-07-01

    Virginiae butanolides (VBs), which are among the butyrolactone autoregulators of Streptomyces species, act as a primary signal in Streptomyces virginiae to trigger virginiamycin biosynthesis and possess a specific binding protein, BarA. To clarify the in vivo function of BarA in the VB-mediated signal pathway that leads to virginiamycin biosynthesis, two barA mutant strains (strains NH1 and NH2) were created by homologous recombination. In strain NH1, an internal 99-bp EcoT14I fragment of barA was deleted, resulting in an in-frame deletion of 33 amino acid residues, including the second helix of the probable helix-turn-helix DNA-binding motif. With the same growth rate as wild-type S. virginiae on both solid and liquid media, strain NH1 showed no apparent changes in its morphological behavior, indicating that the VB-BarA pathway does not participate in morphological control in S. virginiae. In contrast, virginiamycin production started 6 h earlier in strain NH1 than in the wild-type strain, demonstrating for the first time that BarA is actively engaged in the control of virginiamycin production and implying that BarA acts as a repressor in virginiamycin biosynthesis. In strain NH2, an internal EcoNI-SmaI fragment of barA was replaced with a divergently oriented neomycin resistance gene cassette, resulting in the C-terminally truncated BarA retaining the intact helix-turn-helix motif. In strain NH2 and in a plasmid-integrated strain containing both intact and mutated barA genes, virginiamycin production was abolished irrespective of the presence of VB, suggesting that the mutated BarA retaining the intact DNA-binding motif was dominant over the wild-type BarA. These results further support the hypothesis that BarA works as a repressor in virginiamycin production and suggests that the helix-turn-helix motif is essential to its function. In strain NH1, VB production was also abolished, thus indicating that BarA is a pleiotropic regulatory protein controlling not only

  2. 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

  3. Directed Replacement

    CERN Document Server

    Karttunen, L

    1996-01-01

    This paper introduces to the finite-state calculus a family of directed replace operators. In contrast to the simple replace expression, UPPER -> LOWER, defined in Karttunen (ACL-95), the new directed version, UPPER @-> LOWER, yields an unambiguous transducer if the lower language consists of a single string. It transduces the input string from left to right, making only the longest possible replacement at each point. A new type of replacement expression, UPPER @-> PREFIX ... SUFFIX, yields a transducer that inserts text around strings that are instances of UPPER. The symbol ... denotes the matching part of the input which itself remains unchanged. PREFIX and SUFFIX are regular expressions describing the insertions. Expressions of the type UPPER @-> PREFIX ... SUFFIX may be used to compose a deterministic parser for a ``local grammar'' in the sense of Gross (1989). Other useful applications of directed replacement include tokenization and filtering of text streams.

  4. Effects of insulin replacements, inhibitors of angiotensin, and PKCbeta's actions to normalize cardiac gene expression and fuel metabolism in diabetic rats.

    Science.gov (United States)

    Arikawa, Emi; Ma, Ronald C W; Isshiki, Keiji; Luptak, Ivan; He, Zhiheng; Yasuda, Yutaka; Maeno, Yasuhiro; Patti, Mary Elizabeth; Weir, Gordon C; Harris, Robert A; Zammit, Victor A; Tian, Rong; King, George L

    2007-05-01

    High-density oligonucleotide arrays were used to compare gene expression of rat hearts from control, untreated diabetic, and diabetic groups treated with islet cell transplantation (ICT), protein kinase C (PKC)beta inhibitor ruboxistaurin, or ACE inhibitor captopril. Among the 376 genes that were differentially expressed between untreated diabetic and control hearts included key metabolic enzymes that account for the decreased glucose and increased free fatty acid utilization in the diabetic heart. ICT or insulin replacements reversed these gene changes with normalization of hyperglycemia, dyslipidemia, and cardiac PKC activation in diabetic rats. Surprisingly, both ruboxistaurin and ACE inhibitors improved the metabolic gene profile (confirmed by real-time RT-PCR and protein analysis) and ameliorated PKC activity in diabetic hearts without altering circulating metabolites. Functional assessments using Langendorff preparations and (13)C nuclear magnetic resonance spectroscopy showed a 36% decrease in glucose utilization and an impairment in diastolic function in diabetic rat hearts, which were normalized by all three treatments. In cardiomyocytes, PKC inhibition attenuated fatty acid-induced increases in the metabolic genes PDK4 and UCP3 and also prevented fatty acid-mediated inhibition of basal and insulin-stimulated glucose oxidation. Thus, PKCbeta or ACE inhibitors may ameliorate cardiac metabolism and function in diabetes partly by normalization of fuel metabolic gene expression directly in the myocardium.

  5. Knee Replacement

    Science.gov (United States)

    ... need knee replacement surgery usually have problems walking, climbing stairs, and getting in and out of chairs. Some ... a total living space on one floor since climbing stairs can be difficult. Install safety bars or a ...

  6. 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

  7. Esophageal replacement.

    Science.gov (United States)

    Kunisaki, Shaun M; Coran, Arnold G

    2017-04-01

    This article focuses on esophageal replacement as a surgical option for pediatric patients with end-stage esophageal disease. While it is obvious that the patient׳s own esophagus is the best esophagus, persisting with attempts to retain a native esophagus with no function and at all costs are futile and usually detrimental to the overall well-being of the child. In such cases, the esophagus should be abandoned, and the appropriate esophageal replacement is chosen for definitive reconstruction. We review the various types of conduits used for esophageal replacement and discuss the unique advantages and disadvantages that are relevant for clinical decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Gene insertion and replacement in Schizosaccharomyces pombe mediated by the Streptomyces bacteriophage phiC31 site-specific recombination system.

    Science.gov (United States)

    Thomason, L C; Calendar, R; Ow, D W

    2001-08-01

    The site-specific recombination system used by the Streptomyces bacteriophage phiC31 was tested in the fission yeast Schizosaccharomyces pombe. A target strain with the phage attachment site attP inserted at the leu1 locus was co-transformed with one plasmid containing the bacterial attachment site attB linked to a ura4+ marker, and a second plasmid expressing the phiC31 integrase gene. High-efficiency transformation to the Ura+ phenotype occurred when the integrase gene was expressed. Southern analysis revealed that the attB-ura4+ plasmid integrated into the chromosomal attP site. Sequence analysis showed that the attBxattP recombination was precise. In another approach, DNA with a ura4+ marker flanked by two attB sites in direct orientation was used to transform S. pombe cells bearing an attP duplication. The phiC31 integrase catalyzed two reciprocal cross-overs, resulting in a precise gene replacement. The site-specific insertions are stable, as no excision (the reverse reaction) was observed on maintenance of the integrase gene in the integrant lines. The irreversibility of the phiC31 site-specific recombination system sets it apart from other systems currently used in eukaryotic cells, which reverse readily. Deployment of the phiC31 recombination provides new opportunities for directing transgene and chromosome rearrangements in eukaryotic systems.

  9. CRISPR/Cas9-mediated genome editing and gene replacement in plants: Transitioning from lab to field.

    Science.gov (United States)

    Schaeffer, Scott M; Nakata, Paul A

    2015-11-01

    The CRISPR/Cas9 genome engineering system has ignited and swept through the scientific community like wildfire. Owing largely to its efficiency, specificity, and flexibility, the CRISPR/Cas9 system has quickly become the preferred genome-editing tool of plant scientists. In plants, much of the early CRISPR/Cas9 work has been limited to proof of concept and functional studies in model systems. These studies, along with those in other fields of biology, have led to the development of several utilities of CRISPR/Cas9 beyond single gene editing. Such utilities include multiplexing for inducing multiple cleavage events, controlling gene expression, and site specific transgene insertion. With much of the conceptual CRISPR/Cas9 work nearly complete, plant researchers are beginning to apply this gene editing technology for crop trait improvement. Before rational strategies can be designed to implement this technology to engineer a wide array of crops there is a need to expand the availability of crop-specific vectors, genome resources, and transformation protocols. We anticipate that these challenges will be met along with the continued evolution of the CRISPR/Cas9 system particularly in the areas of manipulation of large genomic regions, transgene-free genetic modification, development of breeding resources, discovery of gene function, and improvements upon CRISPR/Cas9 components. The CRISPR/Cas9 editing system appears poised to transform crop trait improvement.

  10. Replacement of Imu-Cmu intron by NeoR gene alters Imu germ-line expression but has no effect on V(D)J recombination.

    Science.gov (United States)

    Haddad, Dania; Dougier, Hei-Lanne; Laviolette, Nathalie; Puget, Nadine; Khamlichi, Ahmed Amine

    2010-02-01

    The NeoR gene has often been used to unravel the mechanisms underlying long-range interactions between promoters and enhancers during V(D)J assembly and class switch recombination (CSR) in the immunoglobulin heavy chain (IgH) locus. This approach led to the notion that CSR is regulated through competition of germ-line (GL) promoters for activities displayed by the 3' regulatory region (3'RR). This polarized long-range effect of the 3'RR is disturbed upon insertion of NeoR gene in the IgH constant (C(H)) region, where only GL transcription derived from upstream GL promoters is impaired. In the context of V(D)J recombination, replacement of Emu enhancer or Emu core enhancer (cEmu) by NeoR gene fully blocked V(D)J recombination and mu0 GL transcription which originates 5' of DQ52 and severely diminished Imu GL transcription derived from Emu/Imu promoter, suggesting a critical role for cEmu in the regulation of V(D)J recombination and of mu0 and Imu expression. Here we focus on the effect of NeoR gene on mu0 and Imu GL transcription in a mouse line in which the Imu-Cmu intron was replaced by a NeoR gene in the sense-orientation. B cell development was characterized by a marked but incomplete block at the pro-B cell stage. However, V(D)J recombination was unaffected in sorted pro-B and pre-B cells excluding an interference with the accessibility control function of Emu. mu0 GL transcription initiation was relatively normal but the maturation step seemed to be affected most likely through premature termination at NeoR polyadenylation sites. In contrast, Imu transcription initiation was impaired suggesting an interference of NeoR gene with the IgH enhancers that control Imu expression. Surprisingly, in stark contrast with the NeoR effect in the C(H) region, LPS-induced NeoR expression restored Imu transcript levels to normal. The data suggest that Emu enhancer may be the master control element that counteracts the down-regulatory "Neo effect" on Imu expression upon LPS

  11. YB-1 gene expression is kept constant during myocyte differentiation through replacement of different transcription factors and then falls gradually under the control of neural activity.

    Science.gov (United States)

    Kobayashi, Shunsuke; Tanaka, Toru; Moue, Masamitsu; Ohashi, Sachiyo; Nishikawa, Taishi

    2015-11-01

    We have previously reported that translation of acetylcholine receptor α-subunit (AChR α) mRNA in skeletal muscle cells is regulated by Y-box binding protein 1 (YB-1) in response to neural activity, and that in the postnatal mouse developmental changes in the amount of YB-1 mRNA are similar to those of AChR α mRNA, which is known to be regulated by myogenic transcription factors. Here, we examined transcriptional regulation of the YB-1 gene in mouse skeletal muscle and differentiating C2C12 myocytes. Although neither YB-1 nor AChR α was detected at either the mRNA or protein level in adult hind limb muscle, YB-1 expression was transiently activated in response to denervation of the sciatic nerve and completely paralleled that of AChR α, suggesting that these genes are regulated by the same transcription factors. However, during differentiation of C2C12 cells to myotubes, the level of YB-1 remained constant even though the level of AChR α increased markedly. Reporter gene, gel mobility shift and ChIP assays revealed that in the initial stage of myocyte differentiation, transcription of the YB-1 gene was regulated by E2F1 and Sp1, and was then gradually replaced under the control of both MyoD and myogenin through an E-box sequence in the proximal region of the YB-1 gene promoter. These results suggest that transcription factors for the YB-1 gene are exchanged during skeletal muscle cell differentiation, perhaps playing a role in translational control of mRNAs by YB-1 in both myotube formation and the response of skeletal muscle tissues to neural stimulation.

  12. 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.

  13. Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von willebrand disease, and factor VII deficiency.

    Science.gov (United States)

    Nichols, Timothy C; Dillow, Aaron M; Franck, Helen W G; Merricks, Elizabeth P; Raymer, Robin A; Bellinger, Dwight A; Arruda, Valder R; High, Katherine A

    2009-01-01

    Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders.

  14. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Viviane F Botosso

    2009-01-01

    Full Text Available Human respiratory syncytial virus (HRSV is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  15. 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.

  16. Changes in adipocyte cell size, gene expression of lipid metabolism markers, and lipolytic responses induced by dietary fish oil replacement in gilthead sea bream (Sparus aurata L.).

    Science.gov (United States)

    Cruz-Garcia, Lourdes; Sánchez-Gurmaches, Joan; Bouraoui, Lamia; Saera-Vila, Alfonso; Pérez-Sánchez, Jaume; Gutiérrez, Joaquim; Navarro, Isabel

    2011-04-01

    The effects of fish oil (FO) substitution by 66% vegetable oils in a diet with already 75% vegetable protein (66VO) on adipose tissue lipid metabolism of gilthead sea bream were analysed after a 14-month feeding trial. In the last 3 months of the experiment, a FO diet was administrated to a 66VO group (group 66VO/FO) as a finishing diet. Hormone-sensitive lipase (HSL) activity was measured in adipose tissue and adipocyte size, and HSL, lipoprotein lipase and liver X receptor gene expression in isolated adipocytes, on which lipolysis and glucose uptake experiments were also performed. Lipolysis was measured after incubation with tumour necrosis factor-α (TNFα), linoleic acid, and two conjugated linoleic acid isomers. Glucose uptake was analysed after TNFα or insulin administration. Our results show that FO replacement increased lipolytic activity and adipocyte cell size. The higher proportion of large cells observed in the 66VO group could be involved in their observed lower response to fatty acid treatments and lower insulin sensitivity. The 66VO/FO group showed a moderate return to the FO conditions. Therefore, FO replacement can affect the morphology and metabolism of gilthead sea bream adipocytes which could potentially affect other organs such as the liver.

  17. 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.

  18. 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 ...

  19. The Clinical Phenotype of CNGA3-Related Achromatopsia: Pretreatment Characterization in Preparation of a Gene Replacement Therapy Trial.

    Science.gov (United States)

    Zobor, Ditta; Werner, Annette; Stanzial, Franco; Benedicenti, Francesco; Rudolph, Günther; Kellner, Ulrich; Hamel, Christian; Andréasson, Sten; Zobor, Gergely; Strasser, Torsten; Wissinger, Bernd; Kohl, Susanne; Zrenner, Eberhart

    2017-02-01

    The purpose of this study was to clinically characterize patients with CNGA3-linked achromatopsia (CNGA3-ACHM) in preparation of a gene therapy trial. Thirty-six patients (age 7-56 years) with complete (cACHM) or incomplete (iACHM) CNGA3-ACHM were examined, including detailed psychophysical tests, extended electrophysiology, and assessment of morphology by fundus autofluorescence and spectral-domain optical coherence tomography (SD-OCT). Mean best-corrected visual acuity was 0.78 ± 0.14 logMAR. Color vision tests were consistent with a rod-dominated function in every cACHM patient. Microperimetry indicated an overall lowered retinal sensitivity within 20° of visual field. In electroretinography (ERG), photopic responses were nondetectable in cACHM patients, but residual cone responses were observed in the iACHM patients. Scotopic responses were altered referring to anomalies of photoreceptor and postreceptor signaling, whereas in voltage versus intensity functions, Vmax was significantly below normal values (P < 0.05). In contrast, slope (n) and semisaturation intensity (K) were found to be within normal limits. Spectral-domain OCT examination showed no specific changes in 14.7%, disruption of the ellipsoid zone (EZ) at the fovea in 38.2%, absent EZ in 17.7%, a hyporeflective zone in 20.5%, and outer retinal atrophy in 8.9% of all cases and foveal hypoplasia in 29 patients (85%). No correlation of retinal morphology with visual function or with a specific genotype was found. The severity of morphologic and functional changes lacked a robust association with age. Our extended investigations prove that even among such a genetically homogenous group of patients, no specific correlations regarding function and morphology severity and age can be observed. Therefore, the therapeutic window seems to be wider than previously indicated.

  20. Genome engineering using a synthetic gene circuit in Bacillus subtilis.

    Science.gov (United States)

    Jeong, Da-Eun; Park, Seung-Hwan; Pan, Jae-Gu; Kim, Eui-Joong; Choi, Soo-Keun

    2015-03-31

    Genome engineering without leaving foreign DNA behind requires an efficient counter-selectable marker system. Here, we developed a genome engineering method in Bacillus subtilis using a synthetic gene circuit as a counter-selectable marker system. The system contained two repressible promoters (B. subtilis xylA (Pxyl) and spac (Pspac)) and two repressor genes (lacI and xylR). Pxyl-lacI was integrated into the B. subtilis genome with a target gene containing a desired mutation. The xylR and Pspac-chloramphenicol resistant genes (cat) were located on a helper plasmid. In the presence of xylose, repression of XylR by xylose induced LacI expression, the LacIs repressed the Pspac promoter and the cells become chloramphenicol sensitive. Thus, to survive in the presence of chloramphenicol, the cell must delete Pxyl-lacI by recombination between the wild-type and mutated target genes. The recombination leads to mutation of the target gene. The remaining helper plasmid was removed easily under the chloramphenicol absent condition. In this study, we showed base insertion, deletion and point mutation of the B. subtilis genome without leaving any foreign DNA behind. Additionally, we successfully deleted a 2-kb gene (amyE) and a 38-kb operon (ppsABCDE). This method will be useful to construct designer Bacillus strains for various industrial applications.

  1. [Estrogen replacement].

    Science.gov (United States)

    Søgaard, A J; Berntsen, G K; Magnus, J H; Tollan, A

    1998-02-10

    Recent research on long-term postmenopausal hormone replacement therapy (HRT) indicates a positive effect on both total mortality and morbidity. This has raised the question of widespread preventive long-term use of HRT. Possible side-effects and ideological issues related to preventive HRT have led to debate and uncertainty among health professionals, in the media, and in the population at large. In order to evaluate the level of knowledge about and attitudes towards HRT, a randomly selected group of 737 Norwegian women aged 16-79 was interviewed by the Central Bureau of Statistics. One in three women had received information about HRT in the last two years, mainly through weekly magazines and physicians. The proportion who answered the questions on knowledge correctly varied from 36% to 47%. Those who had been given information by a physician possessed accurate knowledge, had more positive attitudes towards HRT and were more willing to use HRT than women who had reviewed information through other channels. Women with a higher level of education were better informed and more knowledgeable than others, but were nevertheless more reluctant to use HRT than those who were less educated. The limited number of women who actually receive information on HRT, the low level of knowledge and the ambivalent attitudes toward HRT are a major challenge to the public health service.

  2. 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.

  3. Expression of NEP1 by Fusarium oxysporum f. sp. erythroxyli After Gene Replacement and Overexpression Using Polyethylene Glycol-Mediated Transformation.

    Science.gov (United States)

    Bailey, B A; Apel-Birkhold, Patricia C; Luster, Douglas G

    2002-08-01

    ABSTRACT The necrosis inducing extracellular protein Nep1 is produced by Fusarium oxysporum f. sp. erythroxyli in liquid culture. NEP1, the Nep1 protein structural gene, was disrupted in F. oxysporum f. sp. erythroxyli isolate EN-4 by gene replacement using polyethylene glycol (PEG)-mediated transformation. NEP1 disruption was verified by polymerase chain reaction (PCR), Southern blot, and northern blot analysis. NEP1-disrupted transformants failed to produce Nep1 in liquid culture. NEP1 disruption did not affect the pathogenicity of isolate EN-4 toward Erythroxylum coca. Transformation of isolate EN-4 with construct pPB-FO11-45 carrying NEP1 between the trpC promoter and terminator resulted in increased production of Nep1 in potato dextrose broth plus 1% casamino acids or Czapek-Dox broth plus 1% casamino acids but not in potato dextrose broth alone. Transformation of EN-4 with construct pPB-FO11-45 was verified by PCR and Southern blot analysis. Overexpression of NEP1 was confirmed by northern blot and Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. NEP1-overexpressing transformant 15 produced 64 to 128 times as much Nep1 as EN-4 wild type when grown in shake cultures. Transformants overexpressing Nep1 in liquid culture were no more or less pathogenic toward E. coca than wild-type isolates. Nep1 was not detected in E. coca seedlings infected with NEP1-overexpressing transformants or with EN-4 wild type. In large-scale fermentations of NEP1-overexpressing transformant 15, the amount of secreted protein including Nep1 was 15.1 times that of the wild-type EN-4, providing a ready source of Nep1 for future study.

  4. Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial.

    Science.gov (United States)

    Salmén, Timo; Heikkinen, Anna-Mari; Mahonen, Anitta; Kröger, Heikki; Komulainen, Marja; Pallonen, Heli; Saarikoski, Seppo; Honkanen, Risto; Mäenpää, Pekka H

    2003-02-01

    In women, the influence of androgens on bone health is not clear. It has been suggested that the androgen receptor (AR) genotype is associated with bone mineral density and serum androgen levels in pre- and perimenopausal women, but the association between AR genotype, bone mineral density, and fracture risk has not been studied in postmenopausal women. Therefore, we studied whether AR polymorphism affects bone mineral density, bone mineral density change, or fracture risk in a 5-year randomized hormone replacement therapy (HRT) trial on 331 early postmenopausal women (mean baseline age, 52.7 +/- 2.3 years). The participants consisted of two treatment groups: the HRT group (n = 151) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU + 93 mg calcium as lactate/day, and the non-HRT group (n = 180) received 93 mg calcium alone or in combination with vitamin D3, 100-300 IU/day for 5 years. Bone mineral density was measured from lumbar spine and proximal femur (DXA) before and after the 5-year trial. All new symptomatic, radiographically defined fractures were recorded during the follow-up. The length of CAG repeat in exon 1 of AR gene was evaluated after polymerase chain reaction (PCR) amplification. The subjects were divided into three repeat groups according to AR alleles. None of the baseline characteristics were associated with AR gene polymorphism and HRT treatment. The polymorphism did not influence the calculated annual changes of lumbar or femoral neck bone mineral density during the 5-year follow-up in the HRT (p = 0.926 and 0.146, respectively) or non-HRT (p = 0.818 and 0.917, respectively) groups. In all, 28 women sustained 33 fractures during the follow-up. Thus, the numbers of fractures were limited. The AR repeat length variation was not significantly associated with fracture risk in the HRT or non-HRT groups (p = 0.632 and 0.459, respectively; Cox proportional hazards model

  5. Replacing the Promoter of the Murine Gene Encoding P-selectin with the Human Promoter Confers Human-like Basal and Inducible Expression in Mice.

    Science.gov (United States)

    Liu, Zhenghui; Zhang, Nan; Shao, Bojing; Panicker, Sumith R; Fu, Jianxin; McEver, Rodger P

    2016-01-15

    In humans and mice, megakaryocytes/platelets and endothelial cells constitutively synthesize P-selectin and mobilize it to the plasma membrane to mediate leukocyte rolling during inflammation. TNF-α, interleukin 1β, and LPS markedly increase P-selectin mRNA in mice but decrease P-selectin mRNA in humans. Transgenic mice bearing the entire human SELP gene recapitulate basal and inducible expression of human P-selectin and reveal human-specific differences in P-selectin function. Differences in the human SELP and murine Selp promoters account for divergent expression in vitro, but their significance in vivo is not known. Here we generated knockin mice that replace the 1.4-kb proximal Selp promoter with the corresponding SELP sequence (Selp(KI)). Selp(KI) (/) (KI) mice constitutively expressed more P-selectin on platelets and more P-selectin mRNA in tissues but only slightly increased P-selectin mRNA after injection of TNF-α or LPS. Consistent with higher basal expression, leukocytes rolled more slowly on P-selectin in trauma-stimulated venules of Selp(KI) (/) (KI) mice. However, TNF-α did not further reduce P-selectin-dependent rolling velocities. Blunted up-regulation of P-selectin mRNA during contact hypersensitivity reduced P-selectin-dependent inflammation in Selp(KI) (/-) mice. Higher basal P-selectin in Selp(KI) (/) (KI) mice compensated for this defect. Therefore, divergent sequences in a short promoter mediate most of the functionally significant differences in expression of human and murine P-selectin in vivo.

  6. A Traceless Selection: Counter-selection System That Allows Efficient Generation of Transposon and CRISPR-modified T-cell Products

    Directory of Open Access Journals (Sweden)

    Riccardo Mezzadra

    2016-01-01

    Full Text Available Recent years have seen major breakthroughs in genome-engineering systems, such as transposon-mediated gene delivery systems and CRISPR-Cas9-mediated genome-editing tools. In these systems, transient expression of auxiliary genes is responsible for permanent genomic modification. For both systems, it would be valuable to select for cells that are likely to undergo stable genome modification. Importantly, in particular for clinical applications of genome-engineered cell products, it will also be of importance to remove those cells that, due to random vector integration, display an unwanted stable expression of the auxiliary gene. Here, we develop a traceless selection system that on the one hand allows efficient enrichment of modified cells, and on the other hand can be used to select against cells that retain expression of the auxiliary gene. The value of this system to produce highly enriched-auxiliary gene-free cell products is demonstrated.

  7. Significance of calcium binding, tyrosine phosphorylation, and lysine trimethylation for the essential function of calmodulin in vertebrate cells analyzed in a novel gene replacement system

    DEFF Research Database (Denmark)

    Panina, Svetlana; Stephan, Alexander; la Cour, Jonas Marstrand;

    2012-01-01

    Calmodulin (CaM) was shown to be essential for survival of lower eukaryotes by gene deletion experiments. So far, no CaM gene deletion was reported in higher eukaryotes. In vertebrates, CaM is expressed from several genes, which encode an identical protein, making it difficult to generate a model...

  8. HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C > A) and modified by glucocorticoid treatment

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; van den Berg, Gerrit; van der Knaap, Aafke M.; Dijck-Brouwer, Janneke; Dallinga-Thie, Geesje M.; Zelissen, Peter M. J.; Sluiter, Wim J.; van Beek, Andre P.

    2010-01-01

    Objective: GH replacement lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) in GH-deficient adults, but effects on high-density lipoprotein (HDL) cholesterol (HDL-C) are variable. Both GH and glucocorticoids decrease cholesteryl ester transfer protein (CETP) activity, which is

  9. Shoulder Joint Replacement

    Science.gov (United States)

    ... Shoulder Replacement Options Shoulder replacement surgery is highly technical. It should be performed by a surgical team ... area and will meet a doctor from the anesthesia department. You, your anesthesiologist, and your surgeon will ...

  10. 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 ...

  11. Dietary fish oil replacement by linseed oil: Effect on growth, nutrient utilization, tissue fatty acid composition and desaturase gene expression in silver barb (Puntius gonionotus) fingerlings.

    Science.gov (United States)

    Nayak, Madhusmita; Saha, Ashis; Pradhan, Avinash; Samanta, Mrinal; Giri, Shiba Shankar

    2017-03-01

    Silver barb (Puntius gonionotus) is considered a promising medium carp species for freshwater aquaculture in Asia. This study in silver barb was carried out to evaluate the effects of total or partial substitution of dietary fish oil (FO) with linseed oil (LO) on growth, nutrient utilization, whole-body composition, muscle and liver fatty acid composition. Fish (12.1±0.4g of initial body weight) were fed for 60days with five experimental iso-proteinous, iso-lipidic and iso-caloric diets in which FO (control diet) was replaced by 33.3%, 50%, 66.7% and 100% LO. Final weight, weight gain, percent weight gain, SGR decreased linearly (p0.05) affect the feed conversion ratio (FCR), protein efficiency ratio (PER) and whole body proximate composition. Furthermore, enhanced level of LO increased α-linolenic acid (ALA; 18:3n3) and linoleic acid (LA; 18:2n6) and decreased eicosapentaenoic acid (EPA; 20:5n3) and docosahexaenoic acid (DHA; 22:6n3) in muscle and liver. To understand the molecular mechanism of long chain-polyunsaturated fatty acid (LC-PUFA) biosynthesis, we cloned and characterized the fatty acyl Δ6 desaturase (Δ6 fad) cDNA and investigated its expression in various organs/tissues following replacement of FO with LO in the diet. The full-length Δ6 fad cDNA was 2056bp encoding 444 amino acids and was widely expressed in various organs/tissues. Replacement of FO with LO increased the expression of Δ6 fad mRNA in liver, muscle and intestine but no significant difference was found in the brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Use of transposase and ends of IS608 enables precise and scarless genome modification for modulating gene expression and metabolic engineering applications in Escherichia coli.

    Science.gov (United States)

    Thakker, Chandresh; Lin, Kevin; Martini-Stoica, Heidi; Bennett, George N

    2016-01-01

    Various methods have been developed for gene disruption in bacteria; however, extra in vitro manipulation steps or the residual presence of a scar in the host chromosome limits the use of such methods. By utilizing the unique properties of ISHp608, we have developed a simple and precise method for genome manipulation in Escherichia coli that alters the gene sequence without leaving foreign DNA in the chromosome. This strategy involves PCR amplification of a DNA cassette containing ISHp608-LE (left end)-antibiotic resistance gene-counterselection marker-ISHp608-RE (right end) by using primers containing extensions homologous to the adjacent regions of the target gene on the chromosome. The λ Red mediated recombination of the PCR product and antibiotic resistance screening results in transformants with a modified gene target. The ISHp608-LE-antibiotic resistance gene-counterselection marker-ISHp608-RE cassette can then be excised using a temperature sensitive plasmid expressing the TnpA transposase, which precisely cleaves ISHp608-LE and ISHp608-RE without leaving a scar sequence. We demonstrated lacZ gene point mutation repair, two precise disruptions of the lacZ gene and constructed a library of lacZ variants having variable β-galactosidase activity by changing its ribosome binding site sequences using the ISHp608 system. This technique can be used in E. coli genome modification and could be extended for use in other bacteria.

  13. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin.

    Science.gov (United States)

    Bienemann, Alison S; Martin-Rendon, Enca; Cosgrave, Anna S; Glover, Colin P J; Wong, Liang-Fong; Kingsman, Susan M; Mitrophanous, Kyriacos A; Mazarakis, Nicholas D; Uney, James B

    2003-05-01

    Due to the complexity of brain function and the difficulty in monitoring alterations in neuronal gene expression, the potential of lentiviral gene therapy vectors to treat disorders of the CNS has been difficult to fully assess. In this study, we have assessed the utility of a third-generation equine infectious anemia virus (EIAV) in the Brattleboro rat model of diabetes insipidus, in which a mutation in the arginine vasopressin (AVP) gene results in the production of nonfunctional mutant AVP precursor protein. Importantly, by using this model it is possible to monitor the success of the gene therapy treatment by noninvasive assays. Injection of an EIAV-CMV-AVP vector into the supraoptic nuclei of the hypothalamus resulted in expression of functional AVP peptide in magnocellular neurons. This was accompanied by a 100% recovery in water homeostasis as assessed by daily water intake, urine production, and urine osmolality lasting for a 1-year measurement period. These data show that a single gene defect leading to a neurological disorder can be corrected with a lentiviral-based strategy. This study highlights the potential of using viral gene therapy for the long-term treatment of disorders of the CNS.

  14. NifU and NifS are required for the maturation of nitrogenase and cannot replace the function of isc-gene products in Azotobacter vinelandii.

    Science.gov (United States)

    Johnson, D C; Dos Santos, P C; Dean, D R

    2005-02-01

    In recent years, it has become evident that [Fe-S] proteins, such as hydrogenase, nitrogenase and aconitase, require a complex machinery to assemble and insert their associated [Fe-S] clusters. So far, three different types of [Fe-S] cluster biosynthetic systems have been identified and these have been designated nif, isc and suf. In the present work, we show that the nif-specific [Fe-S] cluster biosynthetic system from Azotobacter vinelandii, which is required for nitrogenase maturation, cannot functionally replace the isc [Fe-S] cluster system used for the maturation of other [Fe-S] proteins, such as aconitase. The results indicate that, in certain cases, [Fe-S] cluster biosynthetic machineries have evolved to perform only specialized functions.

  15. Aeronautical Information System Replacement -

    Data.gov (United States)

    Department of Transportation — Aeronautical Information System Replacement is a web-enabled, automation means for the collection and distribution of Service B messages, weather information, flight...

  16. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.

    Science.gov (United States)

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

    2015-06-17

    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss.

  17. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome

    Science.gov (United States)

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

    2015-01-01

    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1−/− mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0–P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner’s membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1−/− mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. PMID:26084842

  18. Replacement of the human cytomegalovirus promoter with fish enhancer and core elements to control the expression of the G gene of viral haemorrhagic septicemia virus (VHSV).

    Science.gov (United States)

    Martinez-Lopez, A; Chinchilla, B; Encinas, P; Gomez-Casado, E; Estepa, A; Coll, J M

    2012-12-15

    This work explores some of the possibilities to replace human cytomegalovirus (CMV) core and/or enhancer promoter control elements to create new expression vectors for use with fish. The work is relevant to fish vaccination, since DNA vaccines use eukaryotic expression plasmids controlled by the human cytomegalovirus (CMV) promoter to be effective against novirhabdoviruses, such as viral haemorrhagic septicemia virus (VHSV), one of the most devastating fish viral European diseases. To reduce possible homologous recombination with fish genome, core and enhancer sequences from fish origin, such as trout interferon-inducible myxovirus protein (Mx), zebrafish retrovirus long terminal repeat (LTR) and carp β-actin (AE6), were combined with those of CMV to design alternative hybrid promoters. The substitution of CMV core and/or enhancer with the corresponding elements of Mx or the LTR core maintained a similar in vitro protein G expression level than that obtained by using the CMV promoter. Vectors using the dsRNA-inducible Mx enhancer followed either by the LTR or the AE6 cores showed the highest in vitro protein G expression levels. Furthermore, synthetic constructs using the Mx enhancer maintained their polyI:C induction capabilities despite the core used. Some of these hybrid promoters might contribute to the development of all-fish-vectors for DNA vaccines while others might be useful for more basic studies.

  19. Trials and Tribulations with VH Replacement

    Directory of Open Access Journals (Sweden)

    Wenzhao eMeng

    2014-01-01

    Full Text Available VH replacement is a type of antibody gene rearrangement in which an upstream heavy chain variable gene segment (VH invades a pre-existing rearrangement (VDJ. In this Hypothesis and Theory article, we begin by reviewing the mechanism of VH replacement, its developmental timing and its potential biological consequences. Then we explore the hypothesis that specific sequence motifs called footprints reflect VH replacement vs. other processes. We provide a compilation of footprint sequences from different regions of the antibody heavy chain, include data from the literature and from a high throughput sequencing experiment to evaluate the significance of footprint sequences. We conclude by discussing the difficulties of attributing footprints to VH replacement.

  20. 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.

  1. Association of Helicobacter pylori restriction endonuclease-replacing gene, hrgA with overt gastrointestinal diseases Associação entre o hrgA (Helicobacter pylori restriction endonuclease-replacing gene) com as principais doença gastrointestinais

    OpenAIRE

    Manoj G; Tiwari, Santosh K; Vishwas Sharma; Mohammed Aejaz Habeeb; Khan, Aleem A; Habibullah Cm

    2008-01-01

    BACKGROUND and AIM: Helicobacter pylori has been proven to be responsible for causing various gastrointestinal disorders including gastric adenocarcinoma. Several genes of pathogen (the genes of the cag-PAI, vacA, iceA, and babA) either in combination or independently have been reported to significantly increase the risk of ulceration/gastric carcinoma, with the cagA gene having the strongest predictive value. Pursuit to identify new genes which could serve as a marker of overt disease progre...

  2. Renal angiomyolipoma bleeding in a patient with TSC2/PKD1 contiguous gene syndrome after 17 years of renal replacement therapy.

    Science.gov (United States)

    Furlano, Mónica; Barreiro, Yaima; Martí, Teresa; Facundo, Carme; Ruiz-García, César; DaSilva, Iara; Ayasreh, Nadia; Cabrera-López, Cristina; Ballarín, José; Ars, Elisabet; Torra, Roser

    We report the case of a 32-year-old male diagnosed with TSC2/PKD1 contiguous gene syndrome, presenting with tuberous sclerosis (TS) and autosomal dominant polycystic kidney disease simultaneously. He progressed to end-stage renal disease and received a kidney transplant at the age of 12. The native kidneys presented angiomyolipomas (AML), which are common benign tumours in patients with TS. Seventeen years after transplantation, he presented with abdominal pain, anaemia and a retroperitoneal haematoma, the latter caused by renal AML bleeding. Selective embolisation was performed. Our patient could have benefited from the administration of mTOR inhibitors at transplant. This therapy is immunosuppressive and reduces the size of benign tumours in TS as well as the risk of rupture and bleeding. This patient did not receive mTOR inhibitors at the time of the transplant because the relationship between mTOR inhibitors and TS was unknown at that time. This case confirms the persistent risk of renal AML bleeding for both transplanted patients and patients on dialysis. As a result, we would recommend routine check-ups of native kidneys and nephrectomy assessment.

  3. Renal angiomyolipoma bleeding in a patient with TSC2/PKD1 contiguous gene syndrome after 17 years of renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Mónica Furlano

    2017-01-01

    Full Text Available We report the case of a 32-year-old male diagnosed with TSC2/PKD1 contiguous gene syndrome, presenting with tuberous sclerosis complex (TSC and autosomal dominant polycystic kidney disease simultaneously. He progressed to end-stage renal disease and received a kidney transplant at the age of 12. The native kidneys presented angiomyolipomas (AML, which are common benign tumours in patients with TSC. Seventeen years after transplantation, he presented with abdominal pain, anaemia and a retroperitoneal haematoma, the latter caused by renal AML bleeding. Selective embolisation was performed. Our patient could have benefited from the administration of mTOR inhibitors at transplant. This therapy is immunosuppressive and reduces the size of benign tumours in TSC as well as the risk of rupture and bleeding. This patient did not receive mTOR inhibitors at the time of the transplant because the relationship between mTOR inhibitors and TSC was unknown at that time. This case confirms the persistent risk of renal AML bleeding for both transplanted patients and patients on dialysis. As a result, we would recommend routine check-ups of native kidneys and nephrectomy assessment.

  4. Replacing a Missing Tooth

    Science.gov (United States)

    ... vessels in the tooth pulps are rather large. Drilling down these teeth for crowns may expose the ... porcelain replacement tooth is held in place by metal extensions cemented to the backs of the adjacent ...

  5. Hormone Replacement Therapy

    Science.gov (United States)

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  6. Knee joint replacement

    Science.gov (United States)

    ... of your kneecap. Your kneecap is called the patella. The replacement part is usually made from a ... long. Then your surgeon will: Move your kneecap (patella) out of the way, then cut the ends ...

  7. Knee joint replacement - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100088.htm Knee joint replacement - series—Normal anatomy To use the ... to slide 4 out of 4 Overview The knee is a complex joint. It contains the distal ...

  8. Product Platform Replacements

    DEFF Research Database (Denmark)

    Sköld, Martin; Karlsson, Christer

    2012-01-01

    Purpose – It is argued in this article that too little is known about product platforms and how to deal with them from a manager's point of view. Specifically, little information exists regarding when old established platforms are replaced by new generations in R&D and production environments...... originality and value is achieved by focusing on product platform replacements believed to represent a growing management challenge....

  9. 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

  10. Estabishment of techniques for gene replacement in Kluyveromyces fragilis%脆壁克鲁维酵母基因置换技术的建立

    Institute of Scientific and Technical Information of China (English)

    李杰; 曹宇婷; 徐欣; 张旭; 李璐; 吕洋; 卢松冲

    2013-01-01

    To estibish the homologous recombination and electroporation system in Kluyverom-yces fragilis, we constructed the plasmid pPkan was coustucted which with Homologous arms of the UAS of lactase gene from lactase product strain. Paper studied the effects of growth phase of cel s, electric para-meters, cultured time after electroporation on transformation efficiency. At the same time, we studied the relation that combined the electroporation with REMI. The result indicated that an efficient and stable system of electroporation in Kluyveromyces fragilis had been developed, providing a powerful tool for the transgenic research of Kluyveromyces fragilis. The results showed that a high transformation efficiency was achieved in Kluyveromyces fragilis cels at mid-log growth phase electroporated with voltage, electric intensity 7.5 kV·cm-1 and cultured time after electroporation was 90 min. However, when restriction enzyme was added to electroporation system at 10 μL, the transformation efficiency was not increased. And 87.5% of positive transformants was homologous recombination.%  以中性乳糖酶生产菌脆壁克鲁维酵母为材料,构建以kan基因为筛选标记、以脆壁克鲁维酵母乳糖酶基因上游调控区为同源臂的质粒pPkan.将质粒pPkan电击转化脆壁克鲁维酵母,对受体菌生长时期、电场强度、电击后培养时间等条件进行优化.结果表明,以OD600为0.8的脆壁克鲁维酵母为受体、电压1.5 kV、电场强度为7.5 kV·cm-1、电击后培养时间为90 min,可获得较高的转化率,最高转化效率为2.37×102转化子·μgDNA.在电击转化的同时加入限制性内切酶10μL,对电击转化的转化率无显著影响.经PCR筛选证实87.5%的转化子为同源重组,从而建立一套有效的脆壁克鲁维酵母基因置换技术.

  11. Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury.

    Science.gov (United States)

    Park, Kook In; Himes, B Timothy; Stieg, Philip E; Tessler, Alan; Fischer, Itzhak; Snyder, Evan Y

    2006-05-01

    Previously, we reported that, when clonal neural stem cells (NSCs) were transplanted into brains of postnatal mice subjected to unilateral hypoxic-ischemic (HI) injury (optimally 3-7 days following infarction), donor-derived cells homed preferentially (from even distant locations) to and integrated extensively within the large ischemic areas that spanned the hemisphere. A subpopulation of NSCs and host cells, particularly in the penumbra, "shifted" their differentiation towards neurons and oligodendrocytes, the cell types typically damaged following asphyxia and least likely to regenerate spontaneously and in sufficient quantity in the "post-developmental" CNS. That no neurons and few oligodendrocytes were generated from the NSCs in intact postnatal cortex suggested that novel signals are transiently elaborated following HI to which NSCs might respond. The proportion of "replacement" neurons was approximately 5%. Neurotrophin-3 (NT-3) is known to play a role in inducing neuronal differentiation during development and perhaps following injury. We demonstrated that NSCs express functional TrkC receptors. Furthermore, the donor cells continued to express a foreign reporter transgene robustly within the damaged brain. Therefore, it appeared feasible that neuronal differentiation of exogenous NSCs (as well as endogenous progenitors) might be enhanced if donor NSCs were engineered prior to transplantation to (over)express a bioactive gene such as NT-3. A subclone of NSCs transduced with a retrovirus encoding NT-3 (yielding >90% neurons in vitro) was implanted into unilaterally asphyxiated postnatal day 7 mouse brain (emulating one of the common causes of cerebral palsy). The subclone expressed NT-3 efficiently in vivo. The proportion of NSC-derived neurons increased to approximately 20% in the infarction cavity and >80% in the penumbra. The neurons variously differentiated further into cholinergic, GABAergic, or glutamatergic subtypes, appropriate to the cortex. Donor

  12. Association of Helicobacter pylori restriction endonuclease-replacing gene, hrgA with overt gastrointestinal diseases Associação entre o hrgA (Helicobacter pylori restriction endonuclease-replacing gene com as principais doença gastrointestinais

    Directory of Open Access Journals (Sweden)

    Manoj G

    2008-09-01

    Full Text Available BACKGROUND and AIM: Helicobacter pylori has been proven to be responsible for causing various gastrointestinal disorders including gastric adenocarcinoma. Several genes of pathogen (the genes of the cag-PAI, vacA, iceA, and babA either in combination or independently have been reported to significantly increase the risk of ulceration/gastric carcinoma, with the cagA gene having the strongest predictive value. Pursuit to identify new genes which could serve as a marker of overt disease progression, lead to the discovery of hrgA gene. METHODS: Fifty-six indigenous strains of H. pylori from subjects with various gastric disorder were screened to assess the status of hrgA gene along with the cagA gene using simple polymerase chain reaction using specific oligonucleotide primers. Post-amplification, amplicons were subjected for sequencing to identify any strain specific variations in sequences from the H. pylori isolated from different disease manifestations. Histopathological analysis was done to ascertain any significant change in the histological scores of subjects infected with cagA+/hrgA+ and cagA-/hrg+ strains. RESULTS: All the 56 (100% subjects amplified with the oligonucleotide primers specific to hrgA gene, whereas 81.71% subjects showed the presence of cagA gene. Sequencing of the amplimers showed 99% homology. Histology of the cagA+/hrgA+ and cagA-/hrg+ subjects did not show any significant difference. CONCLUSION: hrgA gene of Helicobacter pylori is not a ideal surrogate marker for identifying individuals with higher risk of developing overt gastro-duodenal diseases such as neoplasia of the stomach.RACIONAL e OBJETIVOS: O Helicobacter pylori tem sido incriminado como causador de vários distúrbios digestivos, incluindo o adenocarcinoma gástrico. Diversos genes patogênicos (os genes do cag-PAI, vacA, iceA e babA, em combinação ou independentes, têm sido reportados como fatores de aumento de risco para ulceração/carcinoma g

  13. Robotic mitral valve replacement.

    Science.gov (United States)

    Senay, Sahin; Gullu, Ahmet Umit; Kocyigit, Muharrem; Degirmencioglu, Aleks; Karabulut, Hasan; Alhan, Cem

    2014-01-01

    Robotic surgical techniques allow surgeons to perform mitral valve surgery. This procedure has gained acceptance, particularly for mitral valve repair in degenerative mitral disease. However, mitral repair may not always be possible, especially in severely calcified mitral valve of rheumatic origin. This study demonstrates the basic concepts and technique of robotic mitral valve replacement for valve pathologies that are not suitable for repair.

  14. Replacing America's Job Bank

    Science.gov (United States)

    Vollman, Jim

    2009-01-01

    The Job Central National Labor Exchange (www.jobcentral.com) has become the effective replacement for America's Job Bank with state workforce agencies and, increasingly, with community colleges throughout the country. The American Association of Community Colleges (AACC) has formed a partnership with Job Central to promote its use throughout the…

  15. Replacing America's Job Bank

    Science.gov (United States)

    Vollman, Jim

    2009-01-01

    The Job Central National Labor Exchange (www.jobcentral.com) has become the effective replacement for America's Job Bank with state workforce agencies and, increasingly, with community colleges throughout the country. The American Association of Community Colleges (AACC) has formed a partnership with Job Central to promote its use throughout the…

  16. Ulnar head replacement.

    Science.gov (United States)

    Herbert, Timothy J; van Schoonhoven, Joerg

    2007-03-01

    Recent years have seen an increasing awareness of the anatomical and biomechanical significance of the distal radioulnar joint (DRUJ). With this has come a more critical approach to surgical management of DRUJ disorders and a realization that all forms of "excision arthroplasty" can only restore forearm rotation at the expense of forearm stability. This, in turn, has led to renewed interest in prosthetic replacement of the ulnar head, a procedure that had previously fallen into disrepute because of material failures with early implants, in particular, the Swanson silicone ulnar head replacement. In response to these early failures, a new prosthesis was developed in the early 1990s, using materials designed to withstand the loads across the DRUJ associated with normal functional use of the upper limb. Released onto the market in 1995 (Herbert ulnar head prosthesis), clinical experience during the last 10 years has shown that this prosthesis is able to restore forearm function after ulnar head excision and that the materials (ceramic head and noncemented titanium stem), even with normal use of the limb, are showing no signs of failure in the medium to long term. As experience with the use of an ulnar head prosthesis grows, so does its acceptance as a viable and attractive alternative to more traditional operations, such as the Darrach and Sauve-Kapandji procedures. This article discusses the current indications and contraindications for ulnar head replacement and details the surgical procedure, rehabilitation, and likely outcomes.

  17. Drosophila lines with mutant and wild type human TDP-43 replacing the endogenous gene reveals phosphorylation and ubiquitination in mutant lines in the absence of viability or lifespan defects.

    Science.gov (United States)

    Chang, Jer-Cherng; Morton, David B

    2017-01-01

    Mutations in TDP-43 are associated with proteinaceous inclusions in neurons and are believed to be causative in neurodegenerative diseases such as frontotemporal dementia or amyotrophic lateral sclerosis. Here we describe a Drosophila system where we have engineered the genome to replace the endogenous TDP-43 orthologue with wild type or mutant human TDP-43(hTDP-43). In contrast to other models, these flies express both mutant and wild type hTDP-43 at similar levels to those of the endogenous gene and importantly, no age-related TDP-43 accumulation observed among all the transgenic fly lines. Immunoprecipitation of TDP-43 showed that flies with hTDP-43 mutations had increased levels of ubiquitination and phosphorylation of the hTDP-43 protein. Furthermore, histologically, flies expressing hTDP-43 M337V showed global, robust neuronal staining for phospho-TDP. All three lines: wild type hTDP-43, -G294A and -M337V were homozygous viable, with no defects in development, life span or behaviors observed. The primary behavioral defect was that flies expressing either hTDP-43 G294A or M337V showed a faster decline with age in negative geotaxis. Together, these observations implied that neurons could handle these TDP-43 mutations by phosphorylation- and ubiquitin-dependent proteasome systems, even in a background without the wild type TDP-43. Our findings suggest that these two specific TDP-43 mutations are not inherently toxic, but may require additional environmental or genetic factors to affect longevity or survival.

  18. CoCr wear particles generated from CoCr alloy metal-on-metal hip replacements, and cobalt ions stimulate apoptosis and expression of general toxicology-related genes in monocyte-like U937 cells

    Energy Technology Data Exchange (ETDEWEB)

    Posada, Olga M., E-mail: O.M.PosadaEstefan@leeds.ac.uk [Biomedical Engineering Department, University of Strathclyde, Wolfson Centre, Glasgow G4 0NW (United Kingdom); Gilmour, Denise [Pure and Applied Chemistry Department, University of Strathclyde, Thomas Graham Building, Glasgow G1 1XL (United Kingdom); Tate, Rothwelle J., E-mail: r.j.tate@strath.ac.uk [Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE (United Kingdom); Grant, M. Helen [Biomedical Engineering Department, University of Strathclyde, Wolfson Centre, Glasgow G4 0NW (United Kingdom)

    2014-11-15

    Cobalt-chromium (CoCr) particles in the nanometre size range and their concomitant release of Co and Cr ions into the patients' circulation are produced by wear at the articulating surfaces of metal-on-metal (MoM) implants. This process is associated with inflammation, bone loss and implant loosening and led to the withdrawal from the market of the DePuy ASR™ MoM hip replacements in 2010. Ions released from CoCr particles derived from a resurfacing implant in vitro and their subsequent cellular up-take were measured by ICP-MS. Moreover, the ability of such metal debris and Co ions to induce both apoptosis was evaluated with both FACS and immunoblotting. qRT-PCR was used to assess the effects on the expression of lymphotoxin alpha (LTA), BCL2-associated athanogene (BAG1), nitric oxide synthase 2 inducible (NOS2), FBJ murine osteosarcoma viral oncogene homolog (FOS), growth arrest and DNA-damage-inducible alpha (GADD45A). ICP-MS showed that the wear debris released significant (p < 0.05) amounts of Co and Cr ions into the culture medium, and significant (p < 0.05) cellular uptake of both ions. There was also an increase (p < 0.05) in apoptosis after a 48 h exposure to wear debris. Analysis of qRT-PCR results found significant up-regulation (p < 0.05) particularly of NOS2 and BAG1 in Co pre-treated cells which were subsequently exposed to Co ions + debris. Metal debris was more effective as an inducer of apoptosis and gene expression when cells had been pre-treated with Co ions. This suggests that if a patient receives sequential bilateral CoCr implants, the second implant may be more likely to produce adverse effects than the first one. - Highlights: • Effects of CoCr nanoparticles and Co ions on U937 cells were investigated. • Ions released from wear debris play an important role in cellular response, • Toxicity of Co ions could be related to NO metabolic processes and apoptosis. • CoCr particles were a more effective inducer of apoptosis after cell

  19. Aortic valve replacement

    DEFF Research Database (Denmark)

    Kapetanakis, Emmanouil I; Athanasiou, Thanos; Mestres, Carlos A

    2008-01-01

    BACKGROUND AND AIMS OF THE STUDY: Prompted by anecdotal evidence and observations by surgeons, an investigation was undertaken into the potential differences in implanted aortic valve prosthesis sizes, during aortic valve replacement (AVR) procedures, between northern and southern European...... countries. METHODS: A multi-institutional, non-randomized, retrospective analysis was conducted among 2,932 patients who underwent AVR surgery at seven tertiary cardiac surgery centers throughout Europe. Demographic and perioperative variables including valve size and type, body surface area (BSA) and early...

  20. Total ankle joint replacement.

    Science.gov (United States)

    2016-02-01

    Ankle arthritis results in a stiff and painful ankle and can be a major cause of disability. For people with end-stage ankle arthritis, arthrodesis (ankle fusion) is effective at reducing pain in the shorter term, but results in a fixed joint, and over time the loss of mobility places stress on other joints in the foot that may lead to arthritis, pain and dysfunction. Another option is to perform a total ankle joint replacement, with the aim of giving the patient a mobile and pain-free ankle. In this article we review the efficacy of this procedure, including how it compares to ankle arthrodesis, and consider the indications and complications.

  1. The Optimum Replacement of Weapon

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao; ZHANG Jin-chun

    2002-01-01

    The theory of LCC (Life Cycle Cost) is applied in this paper. The relation between the economic life of weapon and the optimum replacement is analyzed. The method to define the optimum replacement time of weapon is discussed.

  2. Search for genes essential for pneumococcal transformation: the RADA DNA repair protein plays a role in genomic recombination of donor DNA.

    Science.gov (United States)

    Burghout, Peter; Bootsma, Hester J; Kloosterman, Tomas G; Bijlsma, Jetta J E; de Jongh, Christa E; Kuipers, Oscar P; Hermans, Peter W M

    2007-09-01

    We applied a novel negative selection strategy called genomic array footprinting (GAF) to identify genes required for genetic transformation of the gram-positive bacterium Streptococcus pneumoniae. Genome-wide mariner transposon mutant libraries in S. pneumoniae strain R6 were challenged by transformation with an antibiotic resistance cassette and growth in the presence of the corresponding antibiotic. The GAF screen identified the enrichment of mutants in two genes, i.e., hexA and hexB, and the counterselection of mutants in 21 different genes during the challenge. Eight of the counterselected genes were known to be essential for pneumococcal transformation. Four other genes, i.e., radA, comGF, parB, and spr2011, have previously been linked to the competence regulon, and one, spr2014, was located adjacent to the essential competence gene comFA. Directed mutants of seven of the eight remaining genes, i.e., spr0459-spr0460, spr0777, spr0838, spr1259-spr1260, and spr1357, resulted in reduced, albeit modest, transformation rates. No connection to pneumococcal transformation could be made for the eighth gene, which encodes the response regulator RR03. We further demonstrated that the gene encoding the putative DNA repair protein RadA is required for efficient transformation with chromosomal markers, whereas transformation with replicating plasmid DNA was not significantly affected. The radA mutant also displayed an increased sensitivity to treatment with the DNA-damaging agent methyl methanesulfonate. Hence, RadA is considered to have a role in recombination of donor DNA and in DNA damage repair in S. pneumoniae.

  3. 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.

  4. Total disc replacement.

    Science.gov (United States)

    Vital, J-M; Boissière, L

    2014-02-01

    Total disc replacement (TDR) (partial disc replacement will not be described) has been used in the lumbar spine since the 1980s, and more recently in the cervical spine. Although the biomechanical concepts are the same and both are inserted through an anterior approach, lumbar TDR is conventionally indicated for chronic low back pain, whereas cervical TDR is used for soft discal hernia resulting in cervicobrachial neuralgia. The insertion technique must be rigorous, with precise centering in the disc space, taking account of vascular anatomy, which is more complex in the lumbar region, particularly proximally to L5-S1. All of the numerous studies, including prospective randomized comparative trials, have demonstrated non-inferiority to fusion, or even short-term superiority regarding speed of improvement. The main implant-related complication is bridging heterotopic ossification with resulting loss of range of motion and increased rates of adjacent segment degeneration, although with an incidence lower than after arthrodesis. A sufficiently long follow-up, which has not yet been reached, will be necessary to establish definitively an advantage for TDR, particularly in the cervical spine. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. REPLACEMENT OF FRENCH CARDS

    CERN Multimedia

    HR/SOC

    2001-01-01

    The French Ministry of Foreign Affairs has informed the Organization that it is shortly to replace all diplomatic cards, special cards and employment permits ('attestations de fonctions') now held by members of the personnel and their families. Between 2 July and 31 December 2001, these cards are to be replaced by secure, computerized equivalents. The old cards may continue to be used until 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015), in order to fill in a 'fiche individuelle' form, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format. The French card in their possession. An A4 photocopy of the same French card, certified by the cards office as being a true copy. Those members of the personnel whose cards (and/or cards belonging to members of their families) are shortly due to expire, or have recently done...

  6. REPLACEMENT OF FRENCH CARDS

    CERN Multimedia

    Human Resources Division; Cards.Service@cern.ch

    2001-01-01

    The French Ministry of Foreign Affairs is currently replacing all diplomatic cards, special cards and employment permits («attestations de fonctions») held by members of the personnel and their families. These cards are replaced by secure, computerized equivalents. The old cards may no longer be used after 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015) between 8h30 and 12h30, in order to fill in a «fiche individuelle» form, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format, the French card in their possession, an A4 photocopy of the same French card, certified by the cards office as being a true copy. Those members of the personnel whose cards (and/or cards belonging to members of their families) are shortly due to expire, or have recently done so, are also requested...

  7. REPLACEMENT OF FRENCH CARDS

    CERN Multimedia

    Human Resources Division

    2001-01-01

    The French Ministry of Foreign Affairs has informed the Organization that it is shortly to replace all diplomatic cards, special cards and employment permits ('attestations de fonctions') now held by members of the personnel and their families. Between 2 July and 31 December 2001, these cards are to be replaced by secure, computerized equivalents. The old cards may continue to be used until 31 December 2001. For the purposes of the handover, members of the personnel are asked to go to the cards office (33/1-015), taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format, The French card in their possession, an A4 photocopy of the same French card, certified by the cards office as being a true copy. Those members of the personnel whose cards (and/or cards belonging to members of their families) are shortly due to expire, or have recently done so, are also requested to take these items to the c...

  8. REPLACEMENT OF FRENCH CARDS

    CERN Multimedia

    Human Resources Division

    2001-01-01

    The French Ministry of Foreign Affairs has informed the Organization that it is shortly to replace all diplomatic cards, special cards and employment permits ('attestations de fonctions') now held by members of the personnel and their families. Between 2 July and 31 December 2001, these cards are to be replaced by secure, computerized equivalents. A 'personnel office' stamped photocopy of the old cards may continue to be used until 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015), between 8:30 and 12:30, in order to fill a 'fiche individuelle' form (in black ink only), which has to be personally signed by themselves and another separately signed by members of their family, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format (signed on the back) The French card in their possession an A4 photocopy of the same Fre...

  9. 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.

  10. Faster Replacement Paths

    CERN Document Server

    Williams, Virginia Vassilevska

    2010-01-01

    The replacement paths problem for directed graphs is to find for given nodes s and t and every edge e on the shortest path between them, the shortest path between s and t which avoids e. For unweighted directed graphs on n vertices, the best known algorithm runtime was \\tilde{O}(n^{2.5}) by Roditty and Zwick. For graphs with integer weights in {-M,...,M}, Weimann and Yuster recently showed that one can use fast matrix multiplication and solve the problem in O(Mn^{2.584}) time, a runtime which would be O(Mn^{2.33}) if the exponent \\omega of matrix multiplication is 2. We improve both of these algorithms. Our new algorithm also relies on fast matrix multiplication and runs in O(M n^{\\omega} polylog(n)) time if \\omega>2 and O(n^{2+\\eps}) for any \\eps>0 if \\omega=2. Our result shows that, at least for small integer weights, the replacement paths problem in directed graphs may be easier than the related all pairs shortest paths problem in directed graphs, as the current best runtime for the latter is \\Omega(n^{2.5...

  11. 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.

  12. Leptin replacement improves cognitive development.

    Directory of Open Access Journals (Sweden)

    Gilberto J Paz-Filho

    Full Text Available BACKGROUND: Leptin changes brain structure, neuron excitability and synaptic plasticity. It also regulates the development and function of feeding circuits. However, the effects of leptin on neurocognitive development are unknown. OBJECTIVE: To evaluate the effect of leptin on neurocognitive development. METHODOLOGY: A 5-year-old boy with a nonconservative missense leptin gene mutation (Cys-to-Thr in codon 105 was treated with recombinant methionyl human leptin (r-metHuLeptin at physiologic replacement doses of 0.03 mg/kg/day. Cognitive development was assessed using the Differential Ability Scales (DAS, a measure of general verbal and nonverbal functioning; and selected subtests from the NEPSY, a measure of neuropsychological functioning in children. PRINCIPAL FINDINGS: Prior to treatment, the patient was morbidly obese, hypertensive, dyslipidemic, and hyperinsulinemic. Baseline neurocognitive tests revealed slower than expected rates of development (developmental age lower than chronological age in a majority of the areas assessed. After two years, substantial increases in the rates of development in most neurocognitive domains were apparent, with some skills at or exceeding expectations based on chronological age. We also observed marked weight loss and resolution of hypertension, dyslipidemia and hyperinsulinemia. CONCLUSIONS: We concluded that replacement with r-metHuLeptin is associated with weight loss and changes in rates of development in many neurocognitive domains, which lends support to the hypothesis that, in addition to its role in metabolism, leptin may have a cognitive enhancing role in the developing central nervous system. TRIAL REGISTRATION: ClinicalTrials.gov NCT00659828.

  13. Trials and Tribulations with VH Replacement.

    Science.gov (United States)

    Meng, Wenzhao; Jayaraman, Sahana; Zhang, Bochao; Schwartz, Gregory W; Daber, Robert D; Hershberg, Uri; Garfall, Alfred L; Carlson, Christopher S; Luning Prak, Eline T

    2014-01-01

    VH replacement (VHR) is a type of antibody gene rearrangement in which an upstream heavy chain variable gene segment (VH) invades a pre-existing rearrangement (VDJ). In this Hypothesis and Theory article, we begin by reviewing the mechanism of VHR, its developmental timing and its potential biological consequences. Then we explore the hypothesis that specific sequence motifs called footprints reflect VHR versus other processes. We provide a compilation of footprint sequences from different regions of the antibody heavy chain, and include data from the literature and from a high throughput sequencing experiment to evaluate the significance of footprint sequences. We conclude by discussing the difficulties of attributing footprints to VHR.

  14. Toleration, Synthesis or Replacement?

    DEFF Research Database (Denmark)

    Holtermann, Jakob v. H.; Madsen, Mikael Rask

    2016-01-01

    to have considerable problems keeping a clear focus on the key question: What are the implications of this empirical turn in terms of philosophy of legal science, of the social understanding of IL, and, not least, of the place of doctrinal scholarship after the alleged Wende? What is needed, we argue......, in order to answer is not yet another partisan suggestion, but rather an attempt at making intelligible both the oppositions and the possibilities of synthesis between normative and empirical approaches to law. Based on our assessment and rational reconstruction of current arguments and positions, we...... therefore outline a taxonomy consisting of the following three basic, ideal-types in terms of the epistemological understanding of the interface of law and empirical studies: toleration, synthesis and replacement. This tripartite model proves useful with a view to teasing out and better articulating...

  15. 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.

  16. VH replacement in primary immunoglobulin repertoire diversification.

    Science.gov (United States)

    Sun, Amy; Novobrantseva, Tatiana I; Coffre, Maryaline; Hewitt, Susannah L; Jensen, Kari; Skok, Jane A; Rajewsky, Klaus; Koralov, Sergei B

    2015-02-01

    The genes encoding the variable (V) region of the B-cell antigen receptor (BCR) are assembled from V, D (diversity), and J (joining) elements through a RAG-mediated recombination process that relies on the recognition of recombination signal sequences (RSSs) flanking the individual elements. Secondary V(D)J rearrangement modifies the original Ig rearrangement if a nonproductive original joint is formed, as a response to inappropriate signaling from a self-reactive BCR, or as part of a stochastic mechanism to further diversify the Ig repertoire. VH replacement represents a RAG-mediated secondary rearrangement in which an upstream VH element recombines with a rearranged VHDHJH joint to generate a new BCR specificity. The rearrangement occurs between the cryptic RSS of the original VH element and the conventional RSS of the invading VH gene, leaving behind a footprint of up to five base pairs (bps) of the original VH gene that is often further obscured by exonuclease activity and N-nucleotide addition. We have previously demonstrated that VH replacement can efficiently rescue the development of B cells that have acquired two nonproductive heavy chain (IgH) rearrangements. Here we describe a novel knock-in mouse model in which the prerearranged IgH locus resembles an endogenously rearranged productive VHDHJH allele. Using this mouse model, we characterized the role of VH replacement in the diversification of the primary Ig repertoire through the modification of productive VHDHJH rearrangements. Our results indicate that VH replacement occurs before Ig light chain rearrangement and thus is not involved in the editing of self-reactive antibodies.

  17. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  18. Iron replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Coskun, Mehmet; Weiss, Günter

    2016-01-01

    PURPOSE OF REVIEW: Approximately, one-third of the world's population suffers from anemia, and at least half of these cases are because of iron deficiency. With the introduction of new intravenous iron preparations over the last decade, uncertainty has arisen when these compounds should be admini...... treatment, when to follow-up for relapse, which dosage and type of therapy should be recommended or not recommended, and if some patients should not be treated....... be administered and under which circumstances oral therapy is still an appropriate and effective treatment. RECENT FINDINGS: Numerous guidelines are available, but none go into detail about therapeutic start and end points or how iron-deficiency anemia should be best treated depending on the underlying cause...... of iron deficiency or in regard to concomitant underlying or additional diseases. SUMMARY: The study points to major issues to be considered in revisions of future guidelines for the true optimal iron replacement therapy, including how to assess the need for treatment, when to start and when to stop...

  19. Using your shoulder after replacement surgery

    Science.gov (United States)

    Joint replacement surgery - using your shoulder; Shoulder replacement surgery - after ... You have had shoulder replacement surgery to replace the bones of your shoulder joint with artificial parts. The parts include a stem made of metal and a ...

  20. Educating My Replacement

    Science.gov (United States)

    Tarter, Jill

    , in partnership with the dedicated teachers out there, I think I can help promote the critical thinking skills and scientific literacy of the next generation of voters. Hopefully, I can also help train my replacement to be a better scientist, capable of seizing all the opportunities generated by advances in technology and our improved understanding of the universe to craft search strategies with greater probability of success than those I have initiated.

  1. [Ascending aorta replacement late after aortic valve replacement].

    Science.gov (United States)

    Hayashi, Yasunari; Ito, Toshiaki; Maekawa, Atsuo; Sawaki, Sadanari; Fujii, Genyo; Hoshino, Satoshi; Tokoro, Masayoshi; Yanagisawa, Junji

    2013-07-01

    Replacement of the asceding aorta is indicated in patients undergoing aortic valve replacement( AVR), if the diameter of the ascending aorta is greater than 5.0 cm. If the diameter of the asceding aorta is from 4.0 to 5.0 cm, it was arguable whether replacement of the ascending aorta should be performed. Nine patients who underwent reoperative ascending aorta replacement after AVR were reviewed retrospectively. Reoperation on the asending aorta replacement was performed 11.8±7.2 years (range 1y5m~23y3m) after AVR. Mean patient age was 69.9±6.3 (range 60~81). In 2 cases, reoperations were performed early year after AVR. Although ascending aorta was dilated at the 1st operation, replacement wasn't performed for the age and minimally invasive cardiac surgery (MICS). In 3 cases, reoperations were performed more than 10 years later. On these cases, ascending aorta aneurysm and dissection occurred with no pain and were pointed out by computed tomography(CT) or ultrasonic cardiogram(UCG). We think that patients with dilatation of the ascending aorta should undergo AVR and aorta replacement at the 1st operation regardness of age. It is important that patients who underwent AVR should undergo a regular checkup on the ascending aorta.

  2. Electrocatalysts Prepared by Galvanic Replacement

    OpenAIRE

    Athanasios Papaderakis; Ioanna Mintsouli; Jenia Georgieva; Sotiris Sotiropoulos

    2017-01-01

    Galvanic replacement is the spontaneous replacement of surface layers of a metal, M, by a more noble metal, Mnoble, when the former is treated with a solution containing the latter in ionic form, according to the general replacement reaction: nM + mMnoblen+ → nMm+ + mMnoble. The reaction is driven by the difference in the equilibrium potential of the two metal/metal ion redox couples and, to avoid parasitic cathodic processes such as oxygen reduction and (in some cases) hydrogen evolution too...

  3. The orotate transporter oroP from Lactococcus lactis can be used both as a very efficient, food-grade selection and counter-selection marker for strain construction in many different organisms

    DEFF Research Database (Denmark)

    Defoor, Els Marie Celine; Martinussen, Jan

    frame oroP on pDBORO necessary for the uptake of orotate was identified. A number of industrial important strains like Lactococcus lactis, Bacillus subtilus, and Bacillus licheniformis have been shown to be unable to metabolize orotate. If the oroP gene was introduced into these strains they acquired...... on the chromosome in single-copy and episomal in multi-copy Functional in Gram-negative bacteria - Escherichia coli Gram-positive bacteria - Lactococcus lactis, Bacillus subtilus....

  4. Genome engineering and gene expression control for bacterial strain development.

    Science.gov (United States)

    Song, Chan Woo; Lee, Joungmin; Lee, Sang Yup

    2015-01-01

    In recent years, a number of techniques and tools have been developed for genome engineering and gene expression control to achieve desired phenotypes of various bacteria. Here we review and discuss the recent advances in bacterial genome manipulation and gene expression control techniques, and their actual uses with accompanying examples. Genome engineering has been commonly performed based on homologous recombination. During such genome manipulation, the counterselection systems employing SacB or nucleases have mainly been used for the efficient selection of desired engineered strains. The recombineering technology enables simple and more rapid manipulation of the bacterial genome. The group II intron-mediated genome engineering technology is another option for some bacteria that are difficult to be engineered by homologous recombination. Due to the increasing demands on high-throughput screening of bacterial strains having the desired phenotypes, several multiplex genome engineering techniques have recently been developed and validated in some bacteria. Another approach to achieve desired bacterial phenotypes is the repression of target gene expression without the modification of genome sequences. This can be performed by expressing antisense RNA, small regulatory RNA, or CRISPR RNA to repress target gene expression at the transcriptional or translational level. All of these techniques allow efficient and rapid development and screening of bacterial strains having desired phenotypes, and more advanced techniques are expected to be seen.

  5. 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....... The 30-day mortality rate for the 98 patients was zero, although 14 of the 98 mini-sternotomies had to be converted to complete sternotomies intraoperatively due to technical problems. Such conversion doubled the operative time over that of the planned full sternotomies. In the group of patients whose...... 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...

  6. A versatile and efficient markerless gene disruption system for Acidithiobacillus thiooxidans: application for characterizing a copper tolerance related multicopper oxidase gene.

    Science.gov (United States)

    Wen, Qing; Liu, Xiangmei; Wang, Huiyan; Lin, Jianqun

    2014-11-01

    The acidophilic bioleaching bacteria can usually survive in high concentrations of copper ions because of their special living environment. However, little is known about the copper homeostatic mechanisms of Acidithiobacillus thiooxidans, an important member of bioleaching bacteria. Here, a putative multicopper oxidase gene (cueO) was detected from the draft genome of A. thiooxidans ATCC 19377. The transcriptional level of cueO in response to 10 mM CuSO₄was upregulated 25.01 ± 2.59 folds. The response of P(cueO) to copper was also detected and might be stimulated by a putative CueR protein. Then, by using the counter-selectable marker lacZ and enhancing the expression of endonuclease I-SceI with tac promoter, a modified markerless gene disruption system was developed and the cueO gene disruption mutant (ΔcueO) of A. thiooxidans was successfully constructed with a markedly improved second homologous recombination frequency of 0.28 ± 0.048. The ΔcueO mutant was more sensitive to external copper and nearly completely lost the phenoloxidase activity; however, the activity could be restored after complementing the cueO gene. All results suggest the close relation of cueO gene to copper tolerance in A. thiooxidans. In addition, the developed efficient markerless gene knockout method can also be introduced into other Acidithiobacillus strains.

  7. Knee Replacement: What you can Expect

    Science.gov (United States)

    ... improves function lessen with each additional surgery. Artificial knees can wear out Another risk of knee replacement ... replacement surgery to last about two hours. After knee replacement surgery After surgery, you're wheeled to ...

  8. Nonclinical Development of BCG Replacement Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Bernd Eisele

    2013-04-01

    Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  9. Cobra Probes Containing Replaceable Thermocouples

    Science.gov (United States)

    Jones, John; Redding, Adam

    2007-01-01

    A modification of the basic design of cobra probes provides for relatively easy replacement of broken thermocouples. Cobra probes are standard tube-type pressure probes that may also contain thermocouples and that are routinely used in wind tunnels and aeronautical hardware. They are so named because in side views, they resemble a cobra poised to attack. Heretofore, there has been no easy way to replace a broken thermocouple in a cobra probe: instead, it has been necessary to break the probe apart and then rebuild it, typically at a cost between $2,000 and $4,000 (2004 prices). The modified design makes it possible to replace the thermocouple, in minimal time and at relatively low cost, by inserting new thermocouple wire in a tube.

  10. Renal replacement therapy in ICU

    Directory of Open Access Journals (Sweden)

    C Deepa

    2012-01-01

    Full Text Available Diagnosing and managing critically ill patients with renal dysfunction is a part of the daily routine of an intensivist. Acute kidney insufficiency substantially contributes to the morbidity and mortality of critically ill patients. Renal replacement therapy (RRT not only does play a significant role in the treatment of patients with renal failure, acute as well as chronic, but also has spread its domains to the treatment of many other disease conditions such as myaesthenia gravis, septic shock and acute on chronic liver failure. This article briefly outlines the role of renal replacement therapy in ICU.

  11. Prioritization methodology for chemical replacement

    Science.gov (United States)

    Goldberg, Ben; Cruit, Wendy; Schutzenhofer, Scott

    1995-01-01

    This methodology serves to define a system for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semi quantitative approach derived from quality function deployment techniques (QFD Matrix). QFD is a conceptual map that provides a method of transforming customer wants and needs into quantitative engineering terms. This methodology aims to weight the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives.

  12. Wafer Replacement Cluster Tool (Presentation);

    Energy Technology Data Exchange (ETDEWEB)

    Branz, H. M.

    2008-04-01

    This presentation on wafer replacement cluster tool discusses: (1) Platform for advanced R and D toward SAI 2015 cost goal--crystal silicon PV at area costs closer to amorphous Si PV, it's 15% efficiency, inexpensive substrate, and moderate temperature processing (<800 C); (2) Why silicon?--industrial and knowledge base, abundant and environmentally benign, market acceptance, and good efficiency; and (3) Why replace wafers?--expensive, high embedded energy content, and uses 50-100 times more silicon than needed.

  13. Gene doctoring: a method for recombineering in laboratory and pathogenic Escherichia coli strains

    Directory of Open Access Journals (Sweden)

    Penn Charles W

    2009-12-01

    Full Text Available Abstract Background Homologous recombination mediated by the λ-Red genes is a common method for making chromosomal modifications in Escherichia coli. Several protocols have been developed that differ in the mechanisms by which DNA, carrying regions homologous to the chromosome, are delivered into the cell. A common technique is to electroporate linear DNA fragments into cells. Alternatively, DNA fragments are generated in vivo by digestion of a donor plasmid with a nuclease that does not cleave the host genome. In both cases the λ-Red gene products recombine homologous regions carried on the linear DNA fragments with the chromosome. We have successfully used both techniques to generate chromosomal mutations in E. coli K-12 strains. However, we have had limited success with these λ-Red based recombination techniques in pathogenic E. coli strains, which has led us to develop an enhanced protocol for recombineering in such strains. Results Our goal was to develop a high-throughput recombineering system, primarily for the coupling of genes to epitope tags, which could also be used for deletion of genes in both pathogenic and K-12 E. coli strains. To that end we have designed a series of donor plasmids for use with the λ-Red recombination system, which when cleaved in vivo by the I-SceI meganuclease generate a discrete linear DNA fragment, allowing for C-terminal tagging of chromosomal genes with a 6 × His, 3 × FLAG, 4 × ProteinA or GFP tag or for the deletion of chromosomal regions. We have enhanced existing protocols and technologies by inclusion of a cassette conferring kanamycin resistance and, crucially, by including the sacB gene on the donor plasmid, so that all but true recombinants are counter-selected on kanamycin and sucrose containing media, thus eliminating the need for extensive screening. This method has the added advantage of limiting the exposure of cells to the potential damaging effects of the λ-Red system, which can lead

  14. Cloning-independent markerless gene editing in Streptococcus sanguinis: novel insights in type IV pilus biology.

    Science.gov (United States)

    Gurung, Ishwori; Berry, Jamie-Lee; Hall, Alexander M J; Pelicic, Vladimir

    2016-11-29

    Streptococcus sanguinis, a naturally competent opportunistic human pathogen, is a Gram-positive workhorse for genomics. It has recently emerged as a model for the study of type IV pili (Tfp)-exceptionally widespread and important prokaryotic filaments. To enhance genetic manipulation of Streptococcus sanguinis, we have developed a cloning-independent methodology, which uses a counterselectable marker and allows sophisticated markerless gene editing in situ We illustrate the utility of this methodology by answering several questions regarding Tfp biology by (i) deleting single or mutiple genes, (ii) altering specific bases in genes of interest, and (iii) engineering genes to encode proteins with appended affinity tags. We show that (i) the last six genes in the pil locus harbouring all the genes dedicated to Tfp biology play no role in piliation or Tfp-mediated motility, (ii) two highly conserved Asp residues are crucial for enzymatic activity of the prepilin peptidase PilD and (iii) that pilin subunits with a C-terminally appended hexa-histidine (6His) tag are still assembled into functional Tfp. The methodology for genetic manipulation we describe here should be broadly applicable.

  15. Double emulsions as fat replacers

    NARCIS (Netherlands)

    Oppermann, Anika

    2017-01-01

    The use of double (w1/o/w2) emulsions, in which part of the oil is replaced by small water droplets, is a promising strategy to reduce oil content in food products. For successful applications, (1) significant levels of fat reduction (i.e. significant amounts of water inside the oil droplets) have

  16. Replacement policies for dairy cows

    DEFF Research Database (Denmark)

    Nielsen, Lars Relund

    In a recent paper a hierarchical Markov decision processes (MDP) with finite state and action space was formulated for the dairy cow replacement problem with stage lengths of 1 d. Bayesian updating was used to predict the performance of each cow in the herd and economic decisions were based...

  17. Electrocatalysts Prepared by Galvanic Replacement

    Directory of Open Access Journals (Sweden)

    Athanasios Papaderakis

    2017-03-01

    Full Text Available Galvanic replacement is the spontaneous replacement of surface layers of a metal, M, by a more noble metal, Mnoble, when the former is treated with a solution containing the latter in ionic form, according to the general replacement reaction: nM + mMnoblen+ → nMm+ + mMnoble. The reaction is driven by the difference in the equilibrium potential of the two metal/metal ion redox couples and, to avoid parasitic cathodic processes such as oxygen reduction and (in some cases hydrogen evolution too, both oxygen levels and the pH must be optimized. The resulting bimetallic material can in principle have a Mnoble-rich shell and M-rich core (denoted as Mnoble(M leading to a possible decrease in noble metal loading and the modification of its properties by the underlying metal M. This paper reviews a number of bimetallic or ternary electrocatalytic materials prepared by galvanic replacement for fuel cell, electrolysis and electrosynthesis reactions. These include oxygen reduction, methanol, formic acid and ethanol oxidation, hydrogen evolution and oxidation, oxygen evolution, borohydride oxidation, and halide reduction. Methods for depositing the precursor metal M on the support material (electrodeposition, electroless deposition, photodeposition as well as the various options for the support are also reviewed.

  18. Bonding over Dentin Replacement Materials.

    Science.gov (United States)

    Meraji, Naghmeh; Camilleri, Josette

    2017-08-01

    Dentin replacement materials are necessary in large cavities to protect the pulp and reduce the bulk of filling material. These materials are layered with a composite resin restorative material. Microleakage caused by poor bonding of composite resin to underlying dentin replacement material will result in pulp damage. The aim of this study was to characterize the interface between dentin replacement materials and composite resin and to measure the shear bond strength after dynamic aging. Biodentine (Septodont, Saint Maur-des-Fosses, France), Theracal LC (Bisco, Schaumburg, IL), and Fuji IX (GC, Tokyo, Japan) were used as dentin replacement materials. They were then overlaid with a total-etch and bonding agent or a self-etch primer and composite resin or a glass ionomer cement. All combinations were thermocycled for 3000 cycles. The interface was characterized using scanning electron microscopy and elemental mapping. Furthermore, the shear bond strength was assessed. The Biodentine surface was modified by etching. The Theracal LC and Fuji IX microstructure was unchanged upon the application of acid etch. The Biodentine and glass ionomer interface showed an evident wide open space, and glass particles from the glass ionomer adhered to the Biodentine surface. Elemental migration was shown with aluminum, barium, fluorine, and ytterbium present in Biodentine from the overlying composite resin. Calcium was more stable. The bond strength between Theracal LC and composite using a total-etch technique followed by self-etch primer achieved the best bond strength values. Biodentine exhibited the weakest bond with complete failure of bonding shown after demolding and thermocycling. Dynamic aging is necessary to have clinically valid data. Bonding composite resin to water-based dentin replacement materials is still challenging, and further alternatives for restoration of teeth using such materials need to be developed. Copyright © 2017 American Association of Endodontists

  19. Urbanization, Ikization, and Replacement Dynamics

    CERN Document Server

    Chen, Yanguang

    2015-01-01

    The phenomenon of Iks was first found by anthropologists and biologists, but it is actually a problem of human geography. However, it has not yet drawn extensive attention of geographers. In this paper, a hypothesis of ikization is presented that sudden and violent change of geographical environments results in dismantling of traditional culture, which then result in collective depravity of a nationality. By quantitative analysis and mathematical modeling, the causality between urbanization and ikization is discussed, and the theory of replacement dynamics is employed to interpret the process of ikization. Urbanization is in essence a nonlinear process of population replacement. Urbanization may result in ikization because that the migration of population from rural regions to urban regions always give rise to abrupt changes of geographical environments and traditional culture. It is necessary to protect the geographical environment against disruption, and to inherit and develop traditional culture in order t...

  20. [MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT].

    Science.gov (United States)

    Tabata, Minoru

    2016-03-01

    Minimally invasive aortic valve replacement (MIAVR) is defined as aortic valve replacement avoiding full sternotomy. Common approaches include a partial sternotomy right thoracotomy, and a parasternal approach. MIAVR has been shown to have advantages over conventional AVR such as shorter length of stay and smaller amount of blood transfusion and better cosmesis. However, it is also known to have disadvantages such as longer cardiopulmonary bypass and aortic cross-clamp times and potential complications related to peripheral cannulation. Appropriate patient selection is very important. Since the procedure is more complex than conventional AVR, more intensive teamwork in the operating room is essential. Additionally, a team approach during postoperative management is critical to maximize the benefits of MIAVR.

  1. Mitochondrial Replacement: Ethics And Identity

    OpenAIRE

    Wrigley, Anthony; Wilkinson, Stephen; Appleby, John B

    2015-01-01

    Mitochondrial replacement techniques (MRTs) have the potential to allow prospective parents who are at risk of passing on debilitating or even life-threatening mitochondrial disorders to have healthy children to whom they are genetically related. Ethical concerns have however been raised about these techniques. This article focuses on one aspect of the ethical debate, the question of whether there is any moral difference between the two types of MRT proposed: Pronuclear Transfer (PNT) and Mat...

  2. Replacing magnets at the LHC

    CERN Multimedia

    LHC, LSI2, Point 4

    2013-01-01

    CERN engineers have been working through the night this week to move the final replacement dipole magnets into position on the Large Hadron Collider (LHC). Though there are several still to go, the teams expect to have completed the task by the end of this month. Dipole magnets bend the paths of particles as they travel around the circular accelerator. Of the LHC's 1232 dipoles – each 15 metres long and weighing 35 tonnes – 15 are being replaced as part of the long shutdown of CERN's accelerator complex. These 15 magnets suffered wear and tear during the LHC's first 4-year run. Three quadrupole-magnet assemblies – which help to focus particles into a tight beam – have also been replaced. Moving such heavy magnets requires specially adapted cranes and trailers both above and below ground. There are several access points on the LHC. Some, such as the 100-metre vertical access shaft down to the ALICE experiment, are equipped with lifts to allow technical personnel and visitors down to the caverns. Other ...

  3. Results of Austin Moore replacement.

    Directory of Open Access Journals (Sweden)

    Jadhav A

    1996-04-01

    Full Text Available Forty cases of Austin Moore Replacement done for transcervical fractures of the femur in patients were reviewed after a period of 12 to 48 months postoperatively (mean 26 mth. 30 cases (75% had mild to severe pain of non-infective origin, starting as early as 6 months postoperatively. This was irrespective of the make, size or position (varus/valgus of the prosthesis. Though the Aufranc and Sweet clinical scoring was satisfactory in 65% cases, radiological evidence of complications like sinking, protrusion, etc. were seen in majority of the cases. Calcar resorption was seen in 34 cases (85% as early as 4 months postoperatively. Results of THR and bipolar replacement done for transcervical fractures in recent literature show 85% pain-free cases at 5 years. We feel that Austin Moore Replacement should be reserved for patients more than 65 years of age and those who are less active or debilitated because of other factors, because of increased acetabular wear with time in the younger individual. This is corroborated by unsatisfactory results in patients less than 65 years of age (p < 0.05.

  4. The caudal septum replacement graft.

    Science.gov (United States)

    Foda, Hossam M T

    2008-01-01

    To describe a technique for reconstructing the lost tip support in cases involving caudal septal and premaxillary deficiencies. The study included 120 patients with aesthetic and functional nasal problems resulting from the loss of caudal septal and premaxillary support. An external rhinoplasty approach was performed to reconstruct the lost support using a cartilaginous caudal septum replacement graft and premaxillary augmentation with Mersilene mesh. The majority of cases (75%) involved revisions in patients who had previously undergone 1 or more nasal surgical procedures. A caudal septum replacement graft was combined with premaxillary augmentation in 93 patients (77.5%). The mean follow-up period was 3 years (range, 1-12 years). The technique succeeded in correcting the external nasal deformities in all patients and resulted in a significant improvement in breathing in 74 patients (86%) with preoperative nasal obstruction. There were no cases of infection, displacement, or extrusion. The caudal septum replacement graft proved to be very effective in restoring the lost tip support in patients with caudal septal deficiency. Combining the graft with premaxillary augmentation using Mersilene mesh helped increase support and stability over long-term follow-up.

  5. Fusion following failed total ankle replacement.

    Science.gov (United States)

    Wünschel, Markus; Leichtle, Ulf G; Leichtle, Carmen I; Walter, Christian; Mittag, Falk; Arlt, Eva; Suckel, Andreas

    2013-04-01

    Although mid- to long-term results after total ankle replacement have improved because of available second- and third-generation devices, failure of total ankle replacement is still more common compared with total hip replacement and total knee replacement. The portfolio of available total ankle replacement revision component options is small. Furthermore, the bone stock of the tibiotalar region is scarce making it difficult and in some situations impossible to perform revision total ankle replacement. In these cases tibiotalar and tibiotalocalcaneal fusions are valuable options. This article describes which surgical procedures should be performed depending on the initial situation and gives detailed advice on surgical technique, postoperative care, and clinical results.

  6. Radiology of total hip replacement

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, H.J.; Lovelock, J.E.; McCollister Evarts, C.; Geyer, D.

    1984-06-01

    The radiology of total hip replacement (THR) and its complications is reviewed in conjunction with a long-term follow-up study on 402 patients with 501 prostheses. The indications, contraindications, biomechanics, and operative management of these patients is discussed. Clinical complications such as deep vein thrombosis, pulmonary embolism, and hemorrhage are mentioned. Postoperative infections including granulomatous pseudotumors, dislocations and fractures, true loosening of the prosthesis, and heterotopic bone formation (HBF) are discussed and illustrated. The importance of differentiating the lucent line from true loosening is stressed. Mechanical and other clinical complications which are largely ignored by radiologists are also discussed. The uses of arthrography and bone scanning are included.

  7. [Proximal and total femur replacement].

    Science.gov (United States)

    Pennekamp, P H; Wirtz, D C; Dürr, H R

    2012-07-01

    Reconstruction of segmental bone defects of the proximal femur following wide tumor resection or revision arthroplasty. Aggressive benign or primary malignant bone tumors of the proximal femur; destructive metastases; massive segmental bone defects of the proximal femur; periprosthetic fractures. Local infection; very short life expectancy (acetabular bone stock. Anterolateral approach. Exposure and detachment of the iliopsoas and gluteus medius muscle from the proximal femur with a sufficient safety margin to the bone; distal transsection of the vastus lateralis/intermedius and rectus femoris muscle according to the extraosseous tumor extension; distal femur osteotomy al least 3 cm beyond the farthest point of tumor extension; in case of total femur replacement, additional lateral arthrotomy of the knee with resection of the ligaments and menisci; reaming of the medullary canal after securing the shaft with a Verbrugge clamp; trial assembly and reduction followed by the definitive implantation of the prosthesis with adjustment of the femoral neck anteversion in 5° increments; soft tissue reconstruction and fixation to an attachment tube covering the prosthesis; in case of total femur replacement, the preparation of the tibia is followed by the coupling of the tibial and femoral components. Infection prophylaxis, 20 kg partial weight bearing, continuous passive motion. A total of 20  patients with proximal femur replacement and 2 patients with total femur replacement implanted between June 2007 and December 2011 were retrospectively reviewed. Three patients had primary malignant bone tumors, while 19 patients underwent resection for metastatic disease. The mean age at surgery was 62.0 ± 18.1 years (18-82 years). Fifteen patients with a mean follow-up of 20.3 ± 17.2 months (4-51 months) were studied. Among the 22 cases, periprosthetic infection occurred in 3 patients (13.6%), dislocation in 2 patients (9.1%). Evaluation of the functional

  8. SINE retrotransposons cause epigenetic reprogramming of adjacent gene promoters.

    Science.gov (United States)

    Estécio, Marcos R H; Gallegos, Juan; Dekmezian, Mhair; Lu, Yue; Liang, Shoudan; Issa, Jean-Pierre J

    2012-10-01

    Almost half of the human genome and as much as 40% of the mouse genome is composed of repetitive DNA sequences. The majority of these repeats are retrotransposons of the SINE and LINE families, and such repeats are generally repressed by epigenetic mechanisms. It has been proposed that these elements can act as methylation centers from which DNA methylation spreads into gene promoters in cancer. Contradictory to a methylation center function, we have found that retrotransposons are enriched near promoter CpG islands that stay methylation-free in cancer. Clearly, it is important to determine which influence, if any, these repetitive elements have on nearby gene promoters. Using an in vitro system, we confirm here that SINE B1 elements can influence the activity of downstream gene promoters, with acquisition of DNA methylation and loss of activating histone marks, thus resulting in a repressed state. SINE sequences themselves did not immediately acquire DNA methylation but were marked by H3K9me2 and H3K27me3. Moreover, our bisulfite sequencing data did not support that gain of DNA methylation in gene promoters occurred by methylation spreading from SINE B1 repeats. Genome-wide analysis of SINE repeats distribution showed that their enrichment is directly correlated with the presence of USF1, USF2, and CTCF binding, proteins with insulator function. In summary, our work supports the concept that SINE repeats interfere negatively with gene expression and that their presence near gene promoters is counter-selected, except when the promoter is protected by an insulator element.

  9. B Plant process piping replacement feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Howden, G.F.

    1996-02-07

    Reports on the feasibility of replacing existing embedded process piping with new more corrosion resistant piping between cells and between cells and a hot pipe trench of a Hanford Site style canyon facility. Provides concepts for replacement piping installation, and use of robotics to replace the use of the canyon crane as the primary means of performing/supporting facility modifications (eg, cell lining, pipe replacement, equipment reinstallation) and operational maintenenace.

  10. REMINDER REPLACEMENT OF FRENCH CARDS

    CERN Multimedia

    Human Resources Division; Cards.Service@cern.ch

    2001-01-01

    The French Ministry of Foreign Affairs is currently replacing all diplomatic cards, special cards and employment permits («attestations de fonctions») held by members of the personnel and their families. These cards are replaced by secure, computerized equivalents. The old cards may no longer be used after 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015) between 8h30 and 12h30, in order to fill in a «fiche individuelle» form, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format, the French card in their possession, an A4 photocopy of the same French card, certified by the cards office as being a true copy. Those members of the personnel whose cards (and/or cards belonging to members of their families) are shortly due to expire, or have recently done so, are also requested...

  11. Total hip replacement in dancers.

    Science.gov (United States)

    Buyls, Inge R A E; Rietveld, A B M Boni; Ourila, Tiia; Emerton, Mark E; Bird, H A

    2013-04-01

    A case report of a professional contemporary dancer who successfully returned to the stage after bilateral total hip replacements (THR) for osteoarthritis is presented, together with her own commentary and a retrospective cohort study of total hip replacements in dancers. In the presented cohort, there were no post-operative dislocations or infections, the original pain had been relieved, rehabilitation was objectively normal and all resumed their dance (teaching) activities. Nevertheless, they were disappointed about the prolonged rehabilitation. Due to their high demands as professional dancers, post-operative expectations were too optimistic in view of the usual quick and favourable results of THR in the older and less physically active, general population. In all dancers with unilateral osteoarthritis, the left hip was involved, which may reflect the tendency to use the left leg as standing leg and be suggestive that strenuous physical activity may lead to osteoarthritis. Better rehabilitation guidelines are needed for dancer patients undergoing THR, especially drawing their attention to realistic post-operative expectations.

  12. Regulation of VH replacement by B cell receptor-mediated signaling in human immature B cells.

    Science.gov (United States)

    Liu, Jing; Lange, Miles D; Hong, Sang Yong; Xie, Wanqin; Xu, Kerui; Huang, Lin; Yu, Yangsheng; Ehrhardt, Götz R A; Zemlin, Michael; Burrows, Peter D; Su, Kaihong; Carter, Robert H; Zhang, Zhixin

    2013-06-01

    VH replacement provides a unique RAG-mediated recombination mechanism to edit nonfunctional IgH genes or IgH genes encoding self-reactive BCRs and contributes to the diversification of Ab repertoire in the mouse and human. Currently, it is not clear how VH replacement is regulated during early B lineage cell development. In this article, we show that cross-linking BCRs induces VH replacement in human EU12 μHC(+) cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling-induced VH replacement is dependent on the activation of Syk and Src kinases but is inhibited by CD19 costimulation, presumably through activation of the PI3K pathway. These results show that VH replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments.

  13. OPTIMUM ORDERING POLICY FOR PREVENTIVE AGE REPLACEMENT

    Institute of Scientific and Technical Information of China (English)

    Young T.PARK; Jing SUN

    2009-01-01

    Most of the spare ordering policies treated up to now have assumed that preventive and corrective replacement costs are equal, which implies in essential that there is no significant need for preventive replacement. This paper presents an ordering policy for preventive age replacement with minimal repair. Introducing the replacement, repair, inventory holding and shortage costs, the expected cost rate is derived. A procedure to determine jointly the ordering time for a spare and the preventive replacement time for the operating unit so as to minimize the expected cost rate is proposed. To explain the ordering policy and the optimization procedure, a numerical example is also included.

  14. ORO. The physical developer replacement?

    Science.gov (United States)

    Wood, Michael A; James, Tim

    2009-12-01

    In the process of fingerprint development Physical Developer has been largely the method of choice on porous surfaces after coming into contact with wet environments. It is only recently that a new technique has been identified which could replace this standard technique. This study aims to build on previous research and expand knowledge regarding the technique. The study built on previous research and compared Physical Developer to Oil Red O, testing both on four paper types, while being placed in three different water types and an accelerant for various amounts of time. Marks were placed with both heavily 'loaded' sebaceous fingers and 'normal' un-washed fingers. Results show that Oil Red O consistently produced clearer more detailed marks from the 'loaded' fingers, but neither technique proved to work better on the 'normal' marks. Neither technique developed any prints from the accelerant.

  15. Optimal randomized scheduling by replacement

    Energy Technology Data Exchange (ETDEWEB)

    Saias, I.

    1996-05-01

    In the replacement scheduling problem, a system is composed of n processors drawn from a pool of p. The processors can become faulty while in operation and faulty processors never recover. A report is issued whenever a fault occurs. This report states only the existence of a fault but does not indicate its location. Based on this report, the scheduler can reconfigure the system and choose another set of n processors. The system operates satisfactorily as long as, upon report of a fault, the scheduler chooses n non-faulty processors. We provide a randomized protocol maximizing the expected number of faults the system can sustain before the occurrence of a crash. The optimality of the protocol is established by considering a closely related dual optimization problem. The game-theoretic technical difficulties that we solve in this paper are very general and encountered whenever proving the optimality of a randomized algorithm in parallel and distributed computation.

  16. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  17. Replacement reactor to revolutionise magnets

    CERN Document Server

    Atkins, G

    2002-01-01

    Electric motors, hearing aids and magnetic resonance imaging are only some of the applications that will benefit from the first advances in magnets in a quarter of a century. Magnets achieve their characteristics when electrons align themselves to produce a unified magnetic field. Neutrons can probe these magnetic structures. The focus is not just on making more powerful magnets, but also identifying the characteristics that make magnets cheaper and easier for industry to manufacture. Staff from the ANSTO's Neutron Scattering Group have already performed a number of studies on the properties of magnets using using HIFAR, but the Replacement Research Reactor that will produce cold neutrons would allow scientists to investigate the atomic properties of materials with large molecules. A suite of equipment will enable studies at different temperatures, pressures and magnetic fields

  18. Renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Noordzij, Marlies; Kramer, Anneke; Abad Diez, José M

    2014-01-01

    BACKGROUND: This article provides a summary of the 2011 ERA-EDTA Registry Annual Report (available at www.era-edta-reg.org). METHODS: Data on renal replacement therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal registries in 30 countries in Europe and bordering the .......6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors....

  19. VNR CMS Pixel detector replacement

    CERN Document Server

    2017-01-01

    Joel Butler, spokesperson of the CMS collaboration explains how a team from many different partner institutes installed a new detector in CMS. This detector is the silicon pixel detector and they’ve been working on it for about five years, to replace one of our existing detectors. This detectors measures particles closer to the beam than any of the other components of this huge detector behind me. It gives us the most precise picture of tracks as they come out of the collisions and expand and travel through the detector. This particular device has twice as many pixels, 120 million, as opposed to about 68 million in the old detector and it can take data faster and pump it out to the analysis more quickly. 00’53’’ Images of the descent, insertion and installation of first piece of the Pixel detector on Tue Feb 28. Images of the descent, insertion and installation of second piece of the Pixel and the two cylinders being joined.

  20. Orthogonal Matching Pursuit with Replacement

    CERN Document Server

    Jain, Prateek; Dhillon, Inderjit S

    2011-01-01

    In this paper, we consider the problem of compressed sensing where the goal is to recover almost all the sparse vectors using a small number of fixed linear measurements. For this problem, we propose a novel partial hard-thresholding operator that leads to a general family of iterative algorithms. While one extreme of the family yields well known hard thresholding algorithms like ITI (Iterative Thresholding with Inversion) and HTP (Hard Thresholding Pursuit), the other end of the spectrum leads to a novel algorithm that we call Orthogonal Matching Pursuit with Replacement (OMPR). OMPR, like the classic greedy algorithm OMP, adds exactly one coordinate to the support at each iteration, based on the correlation with the current residual. However, unlike OMP, OMPR also removes one coordinate from the support. This simple change allows us to prove that OMPR has the best known guarantees for sparse recovery in terms of the Restricted Isometry Property (a condition on the measurement matrix). In contrast, OMP is kn...

  1. Visual Image Sensor Organ Replacement

    Science.gov (United States)

    Maluf, David A.

    2014-01-01

    This innovation is a system that augments human vision through a technique called "Sensing Super-position" using a Visual Instrument Sensory Organ Replacement (VISOR) device. The VISOR device translates visual and other sensors (i.e., thermal) into sounds to enable very difficult sensing tasks. Three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. Because the human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns, the translation of images into sounds reduces the risk of accidentally filtering out important clues. The VISOR device was developed to augment the current state-of-the-art head-mounted (helmet) display systems. It provides the ability to sense beyond the human visible light range, to increase human sensing resolution, to use wider angle visual perception, and to improve the ability to sense distances. It also allows compensation for movement by the human or changes in the scene being viewed.

  2. [Animal experiment, can we replace?

    Science.gov (United States)

    Combrisson, H

    2017-09-01

    Animal experiment is a subject of controversies. Some people, defenders of animals, think that it is not acceptable to use for scientific purposes at the risk of making them suffer or assert that the results obtained with animals are not transposable in the human beings. Others, in particular researchers in biology or medicine, think that the animal models are essential for the biomedical search. This confrontation of the opinions bases largely on an evolution of the place of animals in our society. The regulations authorize the use of animals for scientific purposes but oblige to make it under restrictive conditions. The application of 3Rs - replacement, reduction, and refinement - expressed in 1959 by Russel and Burch is an ethical guide to improve the welfare of animals in research. The alternative methods do not allow, in the present state of the knowledge, to answer all the scientific questions in biology and medicine research. They are, most of the time, complementary methods of the in vivo methods. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Establishing a Markerless Genetic Exchange System for Methanosarcina mazei Strain Gö1 for Constructing Chromosomal Mutants of Small RNA Genes

    Directory of Open Access Journals (Sweden)

    Claudia Ehlers

    2011-01-01

    Full Text Available A markerless genetic exchange system was successfully established in Methanosarcina mazei strain Gö1 using the hpt gene coding for hypoxanthine phosphoribosyltransferase. First, a chromosomal deletion mutant of the hpt gene was generated conferring resistance to the purine analog 8-aza-2,6-diaminopurine (8-ADP. The nonreplicating allelic exchange vector (pRS345 carrying the pac-resistance cassette for direct selection of chromosomal integration, and the hpt gene for counterselection was introduced into this strain. By a pop-in and ultimately pop-out event of the plasmid from the chromosome, allelic exchange is enabled. Using this system, we successfully generated a M. mazei deletion mutant of the gene encoding the regulatory non-coding RNA sRNA154. Characterizing M. mazei Δ154 under nitrogen limiting conditions demonstrated differential expression of at least three cytoplasmic proteins and reduced growth strongly arguing for a prominent role of sRNA154 in regulation of nitrogen fixation by posttranscriptional regulation.

  4. Biology of tooth replacement in amniotes

    Institute of Scientific and Technical Information of China (English)

    John A Whitlock; Joy M Richman

    2013-01-01

    Tooth replacement is a common trait to most vertebrates, including mammals. Mammals, however, have lost the capacity for continuous tooth renewal seen in most other vertebrates, and typically have only 1–2 generations of teeth. Here, we review the mechanisms of tooth replacement in reptiles and mammals, and discuss in detail the current and historical theories on control of timing and pattern of tooth replacement and development.

  5. Aortic valve replacement in octogenarians

    Directory of Open Access Journals (Sweden)

    Dark John H

    2007-07-01

    Full Text Available Abstract Background and Aims As our population ages and life expectancy increases the number of people aged over 80 and more referred for cardiac surgery is growing. This study sought to identify the outcome of aortic valve replacement (AVR in octogenarians. Methods 68 patients aged 80 years or more underwent AVR at the Freeman Hospital, between April 2001 and April 2004. A retrospective review of the notes and outcomes from the patients' GP and the NHS strategic tracking service was performed. 54% (37 underwent isolated AVR whilst 46% (31 underwent combined AVR and CABG. Results Follow up was 100% complete. The mean age was 83.1 ± s.d. 2.9 years, a mean gradient of 83 ± s.d. 31 mmHg and mean AVA of 0.56 cm2. The mean additive EuroSCORE was 8.6 ± s.d. 1.2, the logistic EuroSCORE mean 12.0 ± s.d. 5.9. In hospital 30 day mortality was 13 %. Survival was 80% at 1 year and 78% at 2 years. Median follow up was for 712 days. Stepwise logistic regression identified chronic obstructive airways disease as an independent predictor of mortality (p Conclusion Our study demonstrates that the operative mortality for AVR in the over eighties is good, whilst the mid to long term outcome is excellent There is a very low attrition rate with those undergoing the procedure living as long than their age matched population. This study confirms AVR is a safe, acceptable treatment for octogenarians with excellent mid term outcomes.

  6. Menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Ali Baziad

    2001-12-01

    Full Text Available The global population in the 21st century has reached 6.2 billion people, by the year 2025 it is to be around 8.3-8.5 billion, and will increase further. Elderly people are expected to grow rapidly than other groups. The fastest increase in the elderly population will take place in Asia. Life expectancy is increasing steadily throughout developed and developing countries. For many  menopausal women, increased life expectancy will accompanied by many health problems. The consequences of estrogen deficiency are the menopausal symptoms. The treatment of menopause related complaints and diseases became an  important socioeconomic and medical issue. Long term symptoms, such as the increase in osteoporosis fractures, cardio and cerebrovascular disesses and dementia, created a large financial burden on individuals and society. All these health problems can be lreated or prevented by hormone replacement therapy (HRT. Natural HRT is usually prefened. Synthetic  estrogen in oral contraceptives (oc are not recommended for HRT. Many contra-indications for oc, but now it is widely usedfor HRT. The main reasons for discontinuing HRT are unwanted bleeding, fear of cancer, and negative side effects. Until now there are sill debates about the rebrtonship between HRT and the incidence of breast cancer. Many data showed that there were no clear relationship between the use of HRT and breast cancer. ThereÎore, nwny experts advocate the use of HRTfrom the first sign of climacteric complaints until death. (Med J Indones 2001;10: 242-51Keywords: estrogen deficiency, climacteric phases, tibolone.

  7. Total joint replacement preadmission programs.

    Science.gov (United States)

    Messer, B

    1998-01-01

    Patients begin to formulate their expectations of the postoperative hospitalization during the preadmission program. The challenge is to better understand the factors patients consider when formulating judgments about the quality of preadmission education. For example, it may be that perceptions of the preadmission program are influenced by what patients believe about their postoperative pain and functional abilities. Specific attention needs to be given both preoperatively and postoperatively to instructing patients on realistic expectations for recovery. One other method of measuring patient outcomes is with the Health Status Profile (SF-36) (Response Healthcare Information Management, 1995). The SF-36 approach emphasizes the outcome of medical care as the patient sees it, in addition to a clinical evaluation of successful health care. This form is currently initiated in the physician's office and returned for scanning at the preadmission class. The patient then completes another SF-36 at 6 months and every year thereafter to compare measurable outcomes. Patients intending to have elective total joint replacements experience anxiety and require much support and education. An effective preadmission program is a major investment in a patient's recovery, as well as a unique marketing tool to customers. Preadmission programs can be viewed as an opportunity to enhance customer satisfaction. Preadmission clinics are an excellent means for nurses to improve the quality of patient care through patient education. the overall goal of preadmission testing programs is to ensure patient preparedness while increasing quality health care and overall customer satisfaction. To enhance program effectiveness, health care providers must lead collaborative efforts to improve the efficiency of systems.

  8. Transcatheter Aortic Valve Replacement in Europe

    DEFF Research Database (Denmark)

    Mylotte, Darren; Osnabrugge, Ruben L J; Windecker, Stephan;

    2013-01-01

    The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy.......The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy....

  9. 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 originates from

  10. Aortic valve replacement with the Nicks annulus enlargement procedure 12 years after mitral valve replacement.

    Science.gov (United States)

    Kazama, S; Kurata, A; Yamashita, Y

    1999-10-01

    An aortic valve replacement was successfully performed employing the Nicks annulus enlargement procedure in a case of aortic valve stenosis with small annulus 12 years after mitral valve replacement. Previous mitral valve replacement does not preclude feasibility of the Nicks procedure.

  11. What Is a Gene? (For Kids)

    Science.gov (United States)

    ... tested is replacing sick genes with healthy ones. Gene therapy trials — where the research is tested on people — and ... ON THIS TOPIC How to Deal With Hemophilia What's the Right Weight for Me? Do You ...

  12. Conceptual Design Plan SM-43 Replacement Project

    Energy Technology Data Exchange (ETDEWEB)

    University of California, Los Alamos National Laboratory, SCC Project Office

    2000-11-01

    The Los Alamos National Laboratory Conceptual Design Plan for the SM-43 Replacement Project outlines plans for replacing the SM-43 Administration Building. Topics include the reasons that replacement is considered a necessity; the roles of the various project sponsors; and descriptions of the proposed site and facilities. Also covered in this proposal is preliminary information on the project schedule, cost estimates, acquisition strategy, risk assessment, NEPA strategy, safety strategy, and safeguards and security. Spreadsheets provide further detail on space requirements, project schedules, and cost estimates.

  13. Percutaneous tricuspid valve replacement in childhood

    Directory of Open Access Journals (Sweden)

    Mathias Emmel

    2015-01-01

    Full Text Available Percutaneous replacement of the tricuspid valve with a bovine jugular venous valve (melody valve was successfully undertaken in a 9-year-old boy. The patient had a previous history of bacterial endocarditis of the native tricuspid valve in infancy. Initially, a pericardial patch valve was created, followed by surgical replacement of the valve using a biological tissue valve at 4 years of age. Progressive stenosis and regurgitation of the biological valve, with severe venous congestion and resulting hepatic dysfunction prompted percutaneous valve replacement.

  14. Gyrator-type circuits replace ungrounded inductors

    Science.gov (United States)

    Deboo, G. J.

    1968-01-01

    Gyrator circuits using only transistors, capacitors, and resistors which can replace both grounded and ungrounded inductors have been developed to permit complete microminiaturization of circuitry by integration of the components.

  15. Total ankle replacement. Design evolution and results.

    Science.gov (United States)

    van den Heuvel, Alexander; Van Bouwel, Saskia; Dereymaeker, Greta

    2010-04-01

    The ankle joint has unique anatomical, biomechanical and cartilaginous structural characteristics that allow the joint to withstand the very high mechanical stresses and strains over years. Any minor changes to any of these features predispose the joint to osteoarthritis. Total ankle replacement (TAR) is evolving as an alternative to ankle arthrodesis for the treatment of end-stage ankle osteoarthritis. Initial implant designs from the early 1970s had unacceptably high failure and complication rates. As a result many orthopaedic surgeons have restricted the use of TAR in favour of ankle arthrodesis. Long term follow-up studies following ankle arthrodesis show risks of developing adjacent joint osteoarthritis. Therefore research towards a successful ankle replacement continues. Newer designs and longer-term outcome studies have renewed the interest in ankle joint replacement. We present an overview of the evolution, results and current concepts of total ankle replacement.

  16. Minimally Invasive Transcatheter Aortic Valve Replacement (TAVR)

    Medline Plus

    Full Text Available Watch a Broward Health surgeon perform a minimally invasive Transcatheter Aortic Valve Replacement (TAVR) Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. ...

  17. Total ankle replacement - surgical treatment and rehabilitation.

    Science.gov (United States)

    Prusinowska, Agnieszka; Krogulec, Zbigniew; Turski, Piotr; Przepiórski, Emil; Małdyk, Paweł; Księżopolska-Orłowska, Krystyna

    2015-01-01

    Functions of the ankle joint are closely connected with the gait and ability to maintain an upright position. Degenerative lesions of the joint directly contribute to postural disorders and greatly restrict propulsion of the foot, thus leading to abnormal gait. Development of total ankle replacement is connected with the use of the method as an efficient treatment of joint injuries and continuation of achievements in hip and knee surgery. The total ankle replacement technique was introduced as an alternative to arthrodesis, i.e. surgical fixation, which made it possible to preserve joint mobility and to improve gait. Total ankle replacement is indicated in post-traumatic degenerative joint disease and joint destruction secondary to rheumatoid arthritis. In this paper, total ankle replacement and various types of currently used endoprostheses are discussed. The authors also describe principles of early postoperative rehabilitation as well as rehabilitation in the outpatient setting.

  18. 47 CFR 13.17 - Replacement license.

    Science.gov (United States)

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL RADIO OPERATORS General § 13.17 Replacement... Operator License, Marine Radio Operator Permit, First Class Radiotelegraph Operator's Certificate, Second... Radio Operator's License, Restricted GMDSS Radio Operator License, GMDSS Radio Maintainer's License,...

  19. Renal replacement therapy for acute renal failure.

    Science.gov (United States)

    Macedo, E; Bouchard, J; Mehta, R L

    2009-09-01

    Renal replacement therapy became a common clinical tool to treat patients with severe acute kidney injury (AKI) since the 1960s. During this time dialytic options have expanded considerably; biocompatible membranes, bicarbonate dialysate and dialysis machines with volumetric ultrafiltration control have improved the treatment for acute kidney injury. Along with advances in methods of intermittent hemodialysis, continuous renal replacement therapies have gained widespread acceptance in the treatment of dialysis-requiring AKI. However, many of the fundamental aspects of the renal replacement treatment such as indication, timing of dialytic intervention, and choice of dialysis modality are still controversial and may influence AKI patient's outcomes. This review outlines current concepts in the use of dialysis techniques for AKI and suggests an approach for selecting the optimal method of renal replacement therapy.

  20. Minimally Invasive Transcatheter Aortic Valve Replacement (TAVR)

    Medline Plus

    Full Text Available Watch a Broward Health surgeon perform a minimally invasive Transcatheter Aortic Valve Replacement (TAVR) Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. ...

  1. SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

    Science.gov (United States)

    The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.Didecyldimethylammonium chloride [DDAC] was...

  2. Gene conversion in human rearranged immunoglobulin genes.

    Science.gov (United States)

    Darlow, John M; Stott, David I

    2006-07-01

    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V(H) segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V(H) replacements with no addition of untemplated nucleotides at the V(H)-V(H) joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V(H) replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

  3. Infective endocarditis following percutaneous pulmonary valve replacement

    DEFF Research Database (Denmark)

    Cheung, Gary; Vejlstrup, Niels; Ihlemann, Nikolaj;

    2013-01-01

    Infective endocarditis (IE) following percutaneous pulmonary valve replacement (PPVR) with the Melody valve is rarely reported. Furthermore, there are challenges in this diagnosis; especially echocardiographic evidence of vegetation within the prosthesis may be difficult.......Infective endocarditis (IE) following percutaneous pulmonary valve replacement (PPVR) with the Melody valve is rarely reported. Furthermore, there are challenges in this diagnosis; especially echocardiographic evidence of vegetation within the prosthesis may be difficult....

  4. Comparison between poly hydroxy acrylic acid and Van-clear replacing the tradi-tional reagents to detect the cervical hTERC genes by adopting FISH technique%聚羟基丙烯酸和Van-clear替代传统试剂在FIS H法检测宫颈h TERC基因中的应用比较

    Institute of Scientific and Technical Information of China (English)

    陈志强; 代新珍; 王莹; 米贤军; 陈昂; 黄华勇; 钟守军; 邓文同; 刘超凡; 徐秀梅

    2016-01-01

    in Zhongshan Boai Ho-sipital were collected from Mar.2013 to Apr.2015.Four samples were taken from the same lesion site. All the cases were divided into 4 groups and named group A,B,C,and D.Group A used 4% neutral buffered formalin fixed and xylene dewaxing to make slices.Group B used poly hydroxy acrylic fixed and xylene dewaxing to make slices.Group C used 4% neutral buffered formalin fixed and Van-clear trans-parent to make slices.Group D used poly hydroxy acrylic fixed and Van-clear transparent dewaxing to make slices.The amplification of hTERC genes in the four groups of cervical specimens was also detected by FISH technique.Results:When the hTERC genes were detected by FISH method under the fluore-scence microscope,it was obvious that the tissue profile and the background of group A,B,C and D were all clear.The probe was fixed in the accurate position so that the bright red or green fluorescence signals were easily found in these four groups.Compared with the positive rate of group A,there was no statistical significance in that of group B,C and D (P>0.05).At the same time,the coincidence rate of the FISH results was high,which showed that the new environment-friendly reagent had no significant difference in the detection of cervical hTERC genes by FISH technique.Conclusion:It is possible for the environment-friendly reagent poly hydroxy acrylic acid and Van-clear to replace 4%neutral buffered for-malin and xylene separately or jointly to detect the cervical hTERC genes by adopting FISH technique.

  5. [Replacement of tracheo-esophageal Provox prosthesis].

    Science.gov (United States)

    Biacabe, B; Laccourreye, O; Ménard, M; Hans, S; Brasnu, D

    2000-02-01

    To compare anesthesic techniques used between 1992 and 1997 at Laënnec Hospital for replacement by tracheo-esophageal Provox prosthesis: local and general anesthesia. Theoretical financial cost for replacement was estimated according to anaesthetic techniques. Provox in situ lifetime was calculated in 58 patients who underwent 115 and 49 replacements under general and local anaesthesia respectively. Age, sex, surgical and radiotherapy backgrounds, complications and anaesthetic techniques were studied as potential factors correlated with Provox in situ lifetime. Theoretical financial cost for replacement was estimated according to anaesthetic techniques. In 1992, 12% of Provox prosthesis were inserted under local anaesthesia and 54% in 1997. Provox in situ lifetime was either not influenced by anaesthetic techniques or other factors under analysis. The theoretical financial cost was estimated at 14, 341 FFrs and 6,048 FFrs for replacement under general and local anaesthesia respectively. Due to increased control of health care costs, we advocated local anaesthesia for Provox prosthesis replacement if control endoscopy is not required.

  6. Strategic vehicle fleet management - the replacement problem

    Directory of Open Access Journals (Sweden)

    Adam Redmer

    2016-03-01

    Full Text Available Background: Fleets constitute the most important production means in transportation. Their appropriate management is crucial for all companies having transportation duties. The paper is the third one of a series of three papers that the author dedicates to the strategic vehicle fleet management topic. Material and methods: The paper discusses ways of building replacement strategies for companies' fleets of vehicles. It means deciding for how long to exploit particular vehicles in a fleet (the fleet replacement problem - FR. The essence of this problem lies in the minimization of vehicle / fleet exploitation costs by balancing ownership and utilization costs and taking into account budget limitations. In the paper an original mathematical model (an optimization method allowing for the FR analysis is proposed. Results: An application of the proposed optimization method in a real-life decision situation (the case study within the Polish environment and the obtained solution are presented. The solution shows that there exist optimal exploitation periods of particular vehicles in a fleet. However, combination of them gives a replacement plan for an entire fleet violating budget constraints. But it is possible to adjust individual age to replacement of particular vehicles to fulfill budget constraints without losing economical optimality of a developed replacement plan for an entire fleet. Conclusions: The paper is the last one of a series of three papers that the author dedicated to the strategic vehicle fleet management topic including the following managerial decision problems: MAKE-or-BUY, sizing / composition and replacement.

  7. The generation of successive unmarked mutations and chromosomal insertion of heterologous genes in Actinobacillus pleuropneumoniae using natural transformation.

    Directory of Open Access Journals (Sweden)

    Janine T Bossé

    Full Text Available We have developed a simple method of generating scarless, unmarked mutations in Actinobacillus pleuropneumoniae by exploiting the ability of this bacterium to undergo natural transformation, and with no need to introduce plasmids encoding recombinases or resolvases. This method involves two successive rounds of natural transformation using linear DNA: the first introduces a cassette carrying cat (which allows selection by chloramphenicol and sacB (which allows counter-selection using sucrose flanked by sequences to either side of the target gene; the second transformation utilises the flanking sequences ligated directly to each other in order to remove the cat-sacB cassette. In order to ensure efficient uptake of the target DNA during transformation, A. pleuropneumoniae uptake sequences are added into the constructs used in both rounds of transformation. This method can be used to generate multiple successive deletions and can also be used to introduce targeted point mutations or insertions of heterologous genes into the A. pleuropneumoniae chromosome for development of live attenuated vaccine strains. So far, we have applied this method to highly transformable isolates of serovars 8 (MIDG2331, which is the most prevalent in the UK, and 15 (HS143. By screening clinical isolates of other serovars, it should be possible to identify other amenable strains.

  8. The Scandinavian Total Ankle Replacement and the ideal biomechanical requirements of ankle replacements.

    Science.gov (United States)

    Robati, Shibby; Salih, Alan; Ghosh, Koushik; Vinayakam, Parthiban

    2016-03-01

    The complex anatomy of the articular bone surfaces, ligaments, tendon attachments and muscles makes the ankle joint difficult to replicate in prosthetic replacements. Ever since the early 1970s, which saw the dawn of the first total ankle replacements, there have been numerous other attempts at replicating the joint, often with poor clinical outcomes. The anatomy of the ankle is discussed, followed by evidence of the normal ankle biomechanics and the ideal requirements of an ankle replacement. We focus on the Scandinavian Total Ankle Replacement and evaluate whether these requirements have been met.

  9. Testosterone replacement therapy and prostate health.

    Science.gov (United States)

    Polackwich, A Scott; Ostrowski, Kevin A; Hedges, Jason C

    2012-12-01

    There is an emerging evolution in the understanding of the relationship between the prostate and testosterone. It has long been generally believed that with testosterone replacement therapy (TRT), increasing serum testosterone levels led to prostatic growth and worsening of voiding dysfunction and associated complications. A new theory, the Saturation Model of Testosterone and its effect on the Prostate has gained attention. This theory suggests that the prostate's response to increasing levels of serum testosterone reaches a limit beyond which there is minimal effect. This model predicts that testosterone replacement therapy occurs above this saturation point, and replacing testosterone to eugonadal levels should not worsen prostate related benign disease. We evaluated the recent published data, with an emphasis on clinical studies done within the last 3 years, for the effects of testosterone supplementation on benign prostatic disease.

  10. Postmenopausal hormone replacement therapy--clinical implications

    DEFF Research Database (Denmark)

    Ravn, S H; Rosenberg, J; Bostofte, E

    1994-01-01

    in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin....... Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke...... suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular...

  11. Double Valve Replacement for Lupus Valvulitis

    Science.gov (United States)

    Ferraris, Victor A.; Hawksley, Vaughn C.; Rabinowitz, Max; Coyne, Carolyn M.; Sullivan, Thomas J.; Sprague, Merle S.

    1990-01-01

    Hemodynamically significant lupus valvulitis, requiring valve replacement, is rare: 21 cases have been reported so far in the literature, and only 2 of these have involved double valve replacement. We describe an additional case of double valve replacement in a patient with systemic lupus erythematosus. The histopathologic and clinical features of this case suggest that valvular involvement resulted from both acute and chronic disease processes. Medical success in the treatment of systemic lupus erythematosus, especially that achieved through prolonged or high-dose steroid therapy, may cause chronic valvular disease to become a more common surgical problem. A review of the literature supports this contention. (Texas Heart Institute Journal 1990;17:56-60) Images PMID:15227191

  12. Renal function after elective total hip replacement

    DEFF Research Database (Denmark)

    Perregaard, Helene; Damholt, Mette B; Solgaard, Søren

    2016-01-01

    and the prevalence of chronic kidney disease (CKD) in an elective population of orthopedic patients undergoing primary total hip replacement, hypothesizing that chronic kidney disease predisposes to AKI. Patients and methods - This was a single-center, population-based, retrospective, registry-based cohort study...... involving all primary elective total hip replacements performed from January 2003 through December 2012. Patient demographics and creatinine values were registered. We evaluated the presence of CKD and AKI according to the international guidelines for kidney disease (KDIGO Acute Kidney Injury Workgroup 2013...... ). Results - 3,416 patients were included (2,064 females (60%)). AKI (according to KDIGO criteria) was seen in 75 patients (2.2%, 95% CI: 1.7-2.7) in the course of primary total hip replacement. Of these, 26 had pre-existing CKD of class 3-5. Pre-existing CKD of class 3-5, indicating moderately to severely...

  13. OPTIMAL MAINTENANCE AND REPLACEMENT OF EXTRACTION MACHINERY

    Institute of Scientific and Technical Information of China (English)

    Suresh P.SETHI; Hong-Mo YEH; Rong ZHANG; Andrew K.S.JARDINE

    2008-01-01

    This paper considers a problem of optimal preventive maintenance and replacement schedule ofequipment devoted to extracting resources from known deposits. Typical examples are oil drills, mine shovels, etc. At most one replacement of the existing machinery by a new one is allowed. The problem is formulated as an optimal control problem subject to the state constraint that the remaining deposit at any given time is nonnegative. We show that the optimal preventive maintenance, production rates, and the replacement and salvage times of the existing machinery and the new one, if required, can be obtained by solving sequentially a series of free-end-point optimal control problems. Moreover, an algorithm based on this result is developed and used to solve two illustrative examples.

  14. Dead pixel replacement in LWIR microgrid polarimeters.

    Science.gov (United States)

    Ratliff, Bradley M; Tyo, J Scott; Boger, James K; Black, Wiley T; Bowers, David L; Fetrow, Matthew P

    2007-06-11

    LWIR imaging arrays are often affected by nonresponsive pixels, or "dead pixels." These dead pixels can severely degrade the quality of imagery and often have to be replaced before subsequent image processing and display of the imagery data. For LWIR arrays that are integrated with arrays of micropolarizers, the problem of dead pixels is amplified. Conventional dead pixel replacement (DPR) strategies cannot be employed since neighboring pixels are of different polarizations. In this paper we present two DPR schemes. The first is a modified nearest-neighbor replacement method. The second is a method based on redundancy in the polarization measurements.We find that the redundancy-based DPR scheme provides an order-of-magnitude better performance for typical LWIR polarimetric data.

  15. Hip or knee replacement - after - what to ask your doctor

    Science.gov (United States)

    ... replacement Hip pain Knee joint replacement Knee pain Osteoarthritis ... Ma, MD, Assistant Professor, Chief, Sports Medicine and Shoulder Service, UCSF Department of Orthopaedic Surgery, San Francisco, ...

  16. Hip or knee replacement - before - what to ask your doctor

    Science.gov (United States)

    ... replacement Hip pain Knee joint replacement Knee pain Osteoarthritis ... Ma, MD, Assistant Professor, Chief, Sports Medicine and Shoulder Service, UCSF Department of Orthopaedic Surgery, San Francisco, ...

  17. Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics

    NARCIS (Netherlands)

    Sikkema-Raddatz, B.; Johansson, L.F.; de Boer, E.N.; Almomani, R.; Boven, L.G.; van den Berg, M.P.; van Spaendonck-Zwarts, K.Y.; van Tintelen, J.P.; Sijmons, R.H.; Jongbloed, J.D.H.; Sinke, R.J.

    2013-01-01

    Mutation detection through exome sequencing allows simultaneous analysis of all coding sequences of genes. However, it cannot yet replace Sanger sequencing (SS) in diagnostics because of incomplete representation and coverage of exons leading to missing clinically relevant mutations. Targeted next-g

  18. Swapping symbionts in spittlebugs: evolutionary replacement of a reduced genome symbiont.

    Science.gov (United States)

    Koga, Ryuichi; Moran, Nancy A

    2014-06-01

    Bacterial symbionts that undergo long-term maternal transmission experience elevated fixation of deleterious mutations, resulting in massive loss of genes and changes in gene sequences that appear to limit efficiency of gene products. Potentially, this dwindling of symbiont functionality impacts hosts that depend on these bacteria for nutrition. One evolutionary escape route is the acquisition of a novel symbiont with a robust genome and metabolic capabilities. Such an acquisition has occurred in an ancestor of Philaenus spumarius, the meadow spittlebug (Insecta: Cercopoidea), which has replaced its ancient association with the tiny genome symbiont Zinderia insecticola (Betaproteobacteria) with an association with a symbiont related to Sodalis glossinidius (Gammaproteobacteria). Spittlebugs feed exclusively on xylem sap, a diet that is low both in essential amino acids and in sugar or other substrates for energy production. The new symbiont genome has undergone proliferation of mobile elements resulting in many gene inactivations; nonetheless, it has selectively maintained genes replacing functions of its predecessor for amino-acid biosynthesis. Whereas ancient symbiont partners typically retain perfectly complementary sets of amino-acid biosynthetic pathways, the novel symbiont introduces some redundancy as it retains some pathways also present in the partner symbionts (Sulcia muelleri). Strikingly, the newly acquired Sodalis-like symbiont retains genes underlying efficient routes of energy production, including a complete TCA cycle, potentially relaxing the severe energy limitations of the xylem-feeding hosts. Although evolutionary replacements of ancient symbionts are infrequent, they potentially enable evolutionary and ecological novelty by conferring novel metabolic capabilities to host lineages.

  19. The echocardiography of replacement heart valves

    Science.gov (United States)

    2016-01-01

    This is a practical description of how replacement valves are assessed using echocardiography. Normal transthoracic appearances including normal variants are described. The problem of differentiating normal function, patient–prosthesis mismatch and pathological obstruction in aortic replacement valves with high gradients is discussed. Obstruction and abnormal regurgitation is described for valves in the aortic, mitral and right-sided positions and when to use echocardiography in suspected infective endocarditis. The roles of transoesophageal and stress echocardiography are described and finally when other imaging techniques may be useful. PMID:27600454

  20. Upgrade or replace?: The effect of the EPBD on the choice between improvement or replacement

    NARCIS (Netherlands)

    Thomsen, A.F.; Van der Flier, C.L.

    2010-01-01

    What is better: improvement or replacement by new construction? The choice between life cycle extension and replacement of existing buildings is at itself a vital but very difficult decision, involving a wide range of different aspects and affecting several contrary and often conflicting interests.

  1. Gene deletion strategy to examine the involvement of the two chondroitin lyases in Flavobacterium columnare virulence.

    Science.gov (United States)

    Li, Nan; Qin, Ting; Zhang, Xiao Lin; Huang, Bei; Liu, Zhi Xin; Xie, Hai Xia; Zhang, Jin; McBride, Mark J; Nie, Pin

    2015-11-01

    Flavobacterium columnare is an important bacterial pathogen of freshwater fish that causes high mortality of infected fish and heavy economic losses in aquaculture. The pathogenesis of this bacterium is poorly understood, in part due to the lack of efficient methods for genetic manipulation. In this study, a gene deletion strategy was developed and used to determine the relationship between the production of chondroitin lyases and virulence. The F. johnsoniae ompA promoter (PompA) was fused to sacB to construct a counterselectable marker for F. columnare. F. columnare carrying PompA-sacB failed to grow on media containing 10% sucrose. A suicide vector carrying PompA-sacB was constructed, and a gene deletion strategy was developed. Using this approach, the chondroitin lyase-encoding genes, cslA and cslB, were deleted. The ΔcslA and ΔcslB mutants were both partially deficient in digestion of chondroitin sulfate A, whereas a double mutant (ΔcslA ΔcslB) was completely deficient in chondroitin lyase activity. Cells of F. columnare wild-type strain G4 and of the chondroitin lyase-deficient ΔcslA ΔcslB mutant exhibited similar levels of virulence toward grass carp in single-strain infections. Coinfections, however, revealed a competitive advantage for the wild type over the chondroitin lyase mutant. The results indicate that chondroitin lyases are not essential virulence factors of F. columnare but may contribute to the ability of the pathogen to compete and cause disease in natural infections. The gene deletion method developed in this study may be employed to investigate the virulence factors of this bacterium and may have wide application in many other members of the phylum Bacteroidetes.

  2. Dithizone staining of intracellular zinc: an unexpected and versatile counterscreen for auxotrophic marker genes in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Daniel S Yuan

    Full Text Available Auxotrophic marker genes such as URA3, LEU2, and HIS3 in Saccharomyces cerevisiae have long been used to select cells that have been successfully transformed with recombinant DNA. A longstanding challenge in working with these genes is that counterselection procedures are often lacking. This paper describes the unexpected discovery of a simple plate assay that imparts a bright red stain to cells experiencing nutritional stress from the lack of a marker gene. The procedure specifically stains a zinc-rich vesicular compartment analogous to the zinc-rich secretory vesicles found in insulin-secreting pancreatic islet cells and glutamate-secreting neurons. Staining was greatly diminished in zap1 mutants, which lack a homeostatic activator of zinc uptake, and in cot1 zrc1 double mutants, which lack the two yeast homologs of mammalian vesicle-specific zinc export proteins. Only one of 93 strains with temperature-sensitive alleles of essential genes exhibited an increase in dithizone staining at its non-permissive temperature, indicating that staining is not simply a sign of growth-arrested or dying cells. Remarkably, the procedure works with most commonly used marker genes, highlights subtle defects, uses no reporter constructs or expensive reagents, requires only a few hours of incubation, yields visually striking results without any instrumentation, and is not toxic to the cells. Many potential applications exist for dithizone staining, both as a versatile counterscreen for auxotrophic marker genes and as a powerful new tool for the genetic analysis of a biomedically important vesicular organelle.

  3. Potential of Microbubbles as Fat Replacer

    NARCIS (Netherlands)

    Rovers, T.A.M.; Sala, Guido; Linden, Van der Erik; Meinders, M.B.J.

    2016-01-01

    The potential of microbubbles as fat replacers and texture modifiers was assessed by comparison of the rheological and tribological properties of model food systems that contained (1) microbubbles, (2) emulsion droplets or (3) no added colloidal structures. We used (a) liquids with thickener, (b)

  4. Predictors of mortality after aortic valve replacement

    NARCIS (Netherlands)

    Tjang, Yanto Sandy; van Hees, Yvonne; Koerfer, Reiner; Grobbee, Diederick E.; van der Heijden, Geert J. M. G.

    Aortic valve replacement (AVR) is recommended as a standard surgical procedure for aortic valve disease. Still the evidence for commonly claimed predictors of post-AVR prognosis, in particular mortality, appears scant. This systematic review reports on the evidence for predictors of post-AVR

  5. Is physiological glucocorticoid replacement important in children?

    Science.gov (United States)

    Porter, John; Blair, Joanne; Ross, Richard J

    2017-01-01

    Cortisol has a distinct circadian rhythm with low concentrations at night, rising in the early hours of the morning, peaking on waking and declining over the day to low concentrations in the evening. Loss of this circadian rhythm, as seen in jetlag and shift work, is associated with fatigue in the short term and diabetes and obesity in the medium to long term. Patients with adrenal insufficiency on current glucocorticoid replacement with hydrocortisone have unphysiological cortisol concentrations being low on waking and high after each dose of hydrocortisone. Patients with adrenal insufficiency complain of fatigue, a poor quality of life and there is evidence of poor health outcomes including obesity potentially related to glucocorticoid replacement. New technologies are being developed that deliver more physiological glucocorticoid replacement including hydrocortisone by subcutaneous pump, Plenadren, a once-daily modified-release hydrocortisone and Chronocort, a delayed and sustained absorption hydrocortisone formulation that replicates the overnight profile of cortisol. In this review, we summarise the evidence regarding physiological glucocorticoid replacement with a focus on relevance to paediatrics. PMID:27582458

  6. 25 CFR 700.53 - Dwelling, replacement.

    Science.gov (United States)

    2010-04-01

    ... § 700.55. (b) May include existing dwellings for resale, new construction, modular homes, mobile homes... person if, after he receives a replacement housing payment and any available housing assistance payments... supplemental income payments received from public agencies. If the person's monthly income pattern is...

  7. Prosthesis infections after orthopedic joint replacement

    DEFF Research Database (Denmark)

    Song, Zhijun; Borgwardt, Lotte; Høiby, Niels

    2013-01-01

    Prosthesis-related infection is a serious complication for patients after orthopedic joint replacement, which is currently difficult to treat with antibiotic therapy. Consequently, in most cases, removal of the infected prosthesis is the only solution to cure the infection. It is, therefore...

  8. Criteria for the replacement of restorations

    DEFF Research Database (Denmark)

    Wilson, Nairn; Lynch, Christopher; Brunton, Paul Brunton

    2016-01-01

    The replacement of a restoration is one of the most common procedures in dentistry. However, the criteria for such intervention, excluding catastrophic failure and persistent discomfort and pain, continue to be the subject of considerable debate. The decision-making process remains subjective...

  9. Measure Guideline: Window Repair, Rehabilitation, and Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Baker, P.

    2012-12-01

    This measure guideline provides information and guidance on rehabilitating, retrofitting, and replacing existing window assemblies in residential construction. The intent is to provide information regarding means and methods to improve the energy and comfort performance of existing wood window assemblies in a way that takes into consideration component durability, in-service operation, and long term performance of the strategies.

  10. Segmental blood pressure after total hip replacement

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Henriksen, Jens Henrik Sahl

    1992-01-01

    Twenty-nine patients due to have a total hip replacement had their systemic systolic and segmental blood pressures measured prior to operation and 1 and 6 weeks postoperatively. No patients had signs of ischemia. The segmental blood pressure was measured at the ankle and at the toes. A significant...

  11. Method of replacing corrupted audio data

    NARCIS (Netherlands)

    Stemerdink, J.; Meijerink, Arjan

    2006-01-01

    A decoding method for coded data representing original data. Corrupted data is detected and replaced with buffered data. The buffered data is stored in the buffer a time interval corresponding to an estimated periodicity or an integer multiple thereof before the corrupted data was received. The esti

  12. Analogue Assessment of the Replacement Behavior

    Science.gov (United States)

    Cipani, Ennio

    2008-01-01

    The use of experimental analyses in determining behavioral function for problems behaviors is well established. Such analyses lead to functional treatment prescriptions for the target problem behavior. However, data indicative of the strength of the replacement behavior are often not collected during a functional behavioral assessment. I examine…

  13. Hormone replacement therapy and risk of glioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper;

    2013-01-01

    Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

  14. Aggression Replacement Training and Childhood Trauma

    Science.gov (United States)

    Amendola, A. Mark; Oliver, Robert W.

    2013-01-01

    Aggression Replacement Training (ART) was developed by the late Arnold Goldstein of Syracuse University to teach positive alternatives to children and youth with emotional and behavioral problems (Glick & Gibbs, 2011; Goldstein, Glick, & Gibbs, 1998). ART provides cognitive, affective, and behavioral interventions to build competence in…

  15. Probability Issues in without Replacement Sampling

    Science.gov (United States)

    Joarder, A. H.; Al-Sabah, W. S.

    2007-01-01

    Sampling without replacement is an important aspect in teaching conditional probabilities in elementary statistics courses. Different methods proposed in different texts for calculating probabilities of events in this context are reviewed and their relative merits and limitations in applications are pinpointed. An alternative representation of…

  16. [Acute renal replacement therapy in pediatrics].

    Science.gov (United States)

    Gaillot, T; Ozanne, B; Bétrémieux, P; Tirel, O; Ecoffey, C

    2013-12-01

    In pediatric intensive care unit, the available modalities of acute renal replacement therapy include intermittent hemodialysis, peritoneal dialysis and continuous renal replacement therapies. No prospective studies have evaluated to date the effect of dialysis modality on the outcomes of children. The decision about dialysis modality should therefore be based on local expertise, resources available, and the patient's clinical status. Poor hemodynamic tolerance of intermittent hemodialysis is a common problem in critically ill patients. Moreover, many pediatric intensive care units are not equipped with dedicated water circuit. Peritoneal dialysis, a simple and inexpensive alternative, is the most widely available form of acute renal replacement therapy. However, its efficacy may be limited in critically ill patients. The use of continuous renal replacement therapy permits usually to reach a greater estimated dialysis dose, a better control of fluid balance, and additionally, to provide adequate nutrition. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  17. Revision Total Hip Replacement: A Case Report

    Directory of Open Access Journals (Sweden)

    Md Hafizur Rahman

    2013-07-01

    Full Text Available Total hip replacement is a reconstructive procedure that has improved the management of those diseases of the hip joint that have responded poorly to conventional medical therapy. Conventional, primary total hip replacement is a durable operation in the majority of patients. A hip replacement is a mechanical device with parts that are assembled before and during the operation. But the possible complications of total hip arthroplasty, and its clinical performance over time, is a challenging occasion to the surgeons, and such a challenge we faced with our presenting patient. A 68 year old lady with history of cemented bipolar hemiarthroplasty done in a tertiary care hospital, due to fracture neck of the left femur having the history of diabetes, chronic kidney disease, heart disease, anaemia, and mental disorders presented with loosened prosthesis, thinning of medial proximal cortex of the femur which had broken within few months after surgery. She complained of painful walking at left hip joint. There was also evidence of chronic infective and degenerative arthritis of acetabular component of the affected hip joint. Cemented revision total hip replacement surgery was performed with expert multidisciplinary involvement. On 2nd postoperative day the patient was allowed to walk on operated limb with the aid of walker. On 12th postoperative day all the stitches were removed and wound was found healthy.

  18. [Hormone replacement therapy: curse or blessing?].

    Science.gov (United States)

    Schmidt, M; Fink, D; Lang, U; Kimmig, R

    2006-01-01

    There is a controversial discussion on the risks and benefits of hormonal replacement therapy (HRT), and many women and doctors have revised their opinions of HRT over the last few years. Complementary and alternative therapies can be considered an option to treat menopausal symptoms. The following issue summarizes the actual knowledge of treatment options of menopausal symptoms.

  19. Enzyme replacement therapy for alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J

    2013-01-01

    Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intrave...... intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment....

  20. 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.

  1. 25 CFR 700.183 - Determination of replacement housing benefit.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Determination of replacement housing benefit. 700.183... RELOCATION PROCEDURES Replacement Housing Payments § 700.183 Determination of replacement housing benefit. (a) Amount of benefit. The replacement housing benefit for a certified eligible head-of-household is...

  2. 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.

  3. 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.

    2016-01-01

    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

  4. 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.; Borne, van den J.J.G.C.; Hendriks, W.H.; Schols, H.A.; Gerrits, W.J.J.

    2016-01-01

    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

  5. 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

  6. The road we travelled: discovery, choreography, and significance of brain replaceable neurons.

    Science.gov (United States)

    Nottebohm, Fernando

    2004-06-01

    Neurons are constantly added to the telencephalon of songbirds. In the high vocal center (HVC), where this has been studied, new neurons replace older ones that died. Peaks in replacement are seasonal and affect some neuronal classes but not others. Peaks in replacement coincide with peaks in information acquisition. The new neurons are produced by division of cells in the wall of the lateral ventricle. Where studied closely, the neuronal stem cells proved to be radial glia. Life expectancy of the new neurons ranges from weeks to months. New neuron survival is regulated by vacancies, hormones, and activity. The immediate agent of new neuron survival is, in some cases, brain-derived neurotrophic factor (BDNF). The effect of BDNF is maximal 14-20 days after the cells are born, when they are establishing their connections. These observations are now being extended to other vertebrates and may apply, to varying degrees, to all of them. The function of neuronal replacement in healthy adult brain remains unclear. If synaptic number and efficacy sufficed as mechanisms for long-term memory storage and could be adjusted again and again to incorporate new memories, then neuronal replacement would seem unnecessary. Since it occurs, it seems reasonable to suppose that replacement serves to maintain learning potential in a way that could not be done just by synaptic change. Long-term memories may be encoded by long-term changes in gene expression akin to a last step in cell differentiation. If so, neuronal replacement may be the adult brain's way of striking a balance between limited memory space and the need to acquire new memories. The testing of this hypothesis remains in the future. This chapter tells how neuronal replacement was discovered in the adult songbird brain.

  7. Transcatheter aortic valve replacement in elderly patients

    Institute of Scientific and Technical Information of China (English)

    Dimytri Siqueira; Alexandre Abizaid; Magaly Arrais J.; Eduardo Sousa

    2012-01-01

    Aortic stenosis is the most common native valve disease, affecting up to 5% of the elderly population. Surgical aortic valve replacement reduces symptoms and improves survival, and is the definitive therapy in patients with symptomatic severe aortic stenosis. However, despite the good results of classic surgery, risk is markedly increased in elderly patients with co-morbidities. Transcatheter aortic valve replacement (TAVR) allows implantation of a prosthetic heart valve within the diseased native aortic valve without the need for open heart surgery and cardiopulmonary bypass, offering a new therapeutic option to elderly patients considered at high surgical risk or with contraindications to surgery. To date, several multicenter registries and a randomized trial have confirmed the safety and efficacy of TAVR in those patients. In this chapter, we review the background and clinical applications of TAVR in elderly patients.

  8. Mitochondrial replacement therapy in reproductive medicine.

    Science.gov (United States)

    Wolf, Don P; Mitalipov, Nargiz; Mitalipov, Shoukhrat

    2015-02-01

    Mitochondrial dysfunction is implicated in disease and age-related infertility. Mitochondrial replacement therapies (MRT) in oocytes or zygotes, such as pronuclear (PNT), spindle (ST), or polar body (PBT) transfer, could prevent second-generation transmission of mitochondrial DNA (mtDNA) defects. PNT, associated with high levels of mtDNA carryover in mice but low levels in human embryos, carries ethical issues secondary to donor embryo destruction. ST, developed in primates, supports normal development to adults and low mtDNA carryover. PBT in mice, coupled with PN or ST, may increase the yield of reconstructed embryos with low mtDNA carryover. MRT also offers replacement of the deficient cytoplasm in oocytes from older patients, with the expectation of high pregnancy rates following in vitro fertilization.

  9. Nicotine replacement therapies: patient safety and persistence

    Directory of Open Access Journals (Sweden)

    Ferguson SG

    2011-06-01

    Full Text Available Stuart G Ferguson1,2, Saul Shiffman3,4, Joseph G Gitchell51School of Pharmacy, 2Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia; 3Pinney Associates, 4University of Pittsburgh, Pittsburgh, PA, USA; 5Pinney Associates, Bethesda, MD, USAAbstract: Nicotine replacement therapy (NRT has become a central part of the treatment of nicotine dependence. However, NRT’s potential efficacy is limited to some extent by patient adherence and persistence. Here we review the relationship between NRT compliance and adherence, and overall treatment outcome. We then examine the factors that likely impact on treatment compliance and persistence, with a special focus on users’ perceptions of treatment safety and efficacy as possible mediators. Potential clinical strategies for improving suboptimal medication use are also discussed.Keywords: nicotine replacement therapy, compliance, safety

  10. Replacements For Ozone-Depleting Foaming Agents

    Science.gov (United States)

    Blevins, Elana; Sharpe, Jon B.

    1995-01-01

    Fluorinated ethers used in place of chlorofluorocarbons and hydrochlorofluorocarbons. Replacement necessary because CFC's and HCFC's found to contribute to depletion of ozone from upper atmosphere, and manufacture and use of them by law phased out in near future. Two fluorinated ethers do not have ozone-depletion potential and used in existing foam-producing equipment, designed to handle liquid blowing agents soluble in chemical ingredients that mixed to make foam. Any polyurethane-based foams and several cellular plastics blown with these fluorinated ethers used in processes as diverse as small batch pours, large sprays, or double-band lamination to make insulation for private homes, commercial buildings, shipping containers, and storage tanks. Fluorinated ethers proved useful as replacements for CFC refrigerants and solvents.

  11. The pure relationship and below replacement fertility

    Directory of Open Access Journals (Sweden)

    David R. Hall

    2003-12-01

    interest from demographers. Despite the fact that researchers have extensively modeled recent demographic changes such as skyrocketing divorce rates, rising common-law union formation, delayed childbearing, and the decline to belowreplacement fertility levels, our understanding of the causes of these trends, and the possible connections between them remains theoretically fragmented and incomplete. The goal of this paper is to advance our understanding in this area by exploring the insights on modern family formation of prominent sociologist Anthony Giddens. Specifically, this study examines whether Giddens’ “pure relationship” concept can shed light on the trend toward very low fertility. The results of this inquiry suggest that couples in both marriages and common-law unions who conform to key aspects of Giddens pure relationship are more likely to have uncertain or below-replacement fertility intentions, and less likely to embrace above-replacement fertility goals.

  12. Autogenous Transplantation for Replacing a Hopeless Tooth

    Science.gov (United States)

    Zakershahrak, Mehrsa; Moshari, Amirabbas; Vatanpour, Mehdi; Khalilak, Zohreh; Jalali Ara, Afsoon

    2017-01-01

    Autogenous tooth transplantation (ATT) is a simple and reasonable choice for replacing the missing teeth when a proper donor tooth is available. This report presents a case of successful ATT of a maxillary right third molar for replacement of mandibular right second molar with a concomitant endodontic-periodontal disease. The mandibular second molar was believed to be hopeless due to a severe damage to coronal tooth structure, inappropriate root canal treatment and apical radiolucency. After extraction of mandibular second molar and maxillary third molar (the donor), the tooth was re-implanted into the extracted socket of second molar site. Root canal therapy was then performed. After 3 years, clinical and radiographic examinations revealed satisfying results, with no signs and symptoms. The patient is asymptomatic and the transplanted tooth is still functional with no signs of marginal periodontal pathosis. Radiographies showed bone regeneration in the site of previous extensive periapical lesion, normal periodontal ligament with no signs of root resorption. PMID:28179939

  13. Liver replacement for alpha1-antitrypsin deficiency

    Science.gov (United States)

    Putnam, Charles W.; Porter, Kendrick A.; Peters, Robert L.; Ashcavai, Mary; Redeker, Allan G.; Starzl, Thomas E.

    2010-01-01

    A 16-year-old girl with advanced cirrhosis and severe alpha1-antitrypsin deficiency of the homozygous PiZZ phenotype was treated by orthotopic liver transplantation. After replacement of the liver with a homograft from a donor with the normal PiMM phenotype, the alpha1-antitrypsin concentration in the recipient’s serum rose to normal; it had the PiMM phenotype. Two and a third years later, chronic rejection necessitated retransplantation. Insertion of a homograft from a heterozygous PiMZ donar was followed by the identification of that phenotype in the recipient’s serum. Neither liver graft developed the alpha1-antitrypsin glycoprotein deposits seen with the deficiency state. These observations confirm that this hepatic- based inborn error metabolism is metabolically cured by liver replacement. PMID:320694

  14. Current practice in primary total hip replacement: results from the National Hip Replacement Outcome Project

    OpenAIRE

    Best, A. J.; Fender, D.; Harper, W. M.; McCaskie, A. W.; Oliver, K; Gregg, P J

    1999-01-01

    As part of the National Study of Primary Hip Replacement Outcome, 402 consultant orthopaedic surgeons from three regions were contacted by postal questionnaire which covered all aspects of total hip replacement (THR). There was a 70% response rate of which 71 did not perform hip surgery, a further 33 refused to take part, leaving 181 valid responses. Preoperative assessment clinics were used by 89% of surgeons, but anaesthetists and rehabilitation services were rarely involved at this stage. ...

  15. Risks of testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    E Charles Osterberg

    2014-01-01

    Full Text Available Testosterone replacement therapy (TRT is a widely used treatment for men with symptomatic hypogonadism. The benefits seen with TRT, such as increased libido and energy level, beneficial effects on bone density, strength and muscle as well as cardioprotective effects, have been well-documented. TRT is contraindicated in men with untreated prostate and breast cancer. Men on TRT should be monitored for side-effects such as polycythemia, peripheral edema, cardiac and hepatic dysfunction.

  16. Alternatives to testosterone replacement: testosterone restoration.

    Science.gov (United States)

    McCullough, Andrew

    2015-01-01

    The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH.

  17. Alternatives to testosterone replacement: testosterone restoration

    OpenAIRE

    Andrew McCullough

    2014-01-01

    The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supp...

  18. Current concepts in total femoral replacement

    OpenAIRE

    Ramanathan, Deepak; Siqueira, Marcelo BP; Klika, Alison K.; Higuera, Carlos A.; Barsoum, Wael K.; Joyce, Michael J

    2015-01-01

    Total femoral replacement (TFR) is a salvage arthroplasty procedure used as an alternative to lower limb amputation. Since its initial description in the mid-20th century, this procedure has been used in a variety of oncologic and non-oncologic indications. The most compelling advantage of TFR is the achievement of immediate fixation which permits early mobilization. It is anticipated that TFR will be increasingly performed as the rate of revision arthroplasty rises worldwide. The existing li...

  19. Mitochondrial Replacement Therapy in Reproductive Medicine

    OpenAIRE

    Wolf, Don P; Mitalipov, Nargiz; Mitalipov, Shoukhrat

    2014-01-01

    Mitochondrial dysfunction is implicated in disease and in age-related infertility. Mitochondrial replacement therapies (MRT) in oocytes or zygotes such as pronuclear (PNT), spindle (ST) or polar body (PBT) transfer could prevent second generation transmission of mitochondrial DNA (mtDNA) defects. PNT, associated with high levels of mtDNA carryover in mice but low levels in human embryos, carries ethical issues secondary to donor embryo destruction. ST, developed in primates, supports normal d...

  20. Mineralogical correlation between primary and replacement dolomites

    Institute of Scientific and Technical Information of China (English)

    黄志诚; 杨守业; 陈智娜

    1997-01-01

    Primary dolostones occur in the Upper Sinian Dengying Formation. Based on mineralogieal study the indicators for correlation between the primary dolomites which are not influenced by the diagenesis and the replacement dolomites of different periods have been obtained. It is shown that the primary dolomites are characterized by crystal forms precipitated and deposited directly from sea water, stable and homogeneous distribution of Mg and Ca, ideal chemical composition, regular modulated microstructures, low positive δ13C and low negative δ18O.

  1. Drug Dosing During Continuous Renal Replacement Therapies

    OpenAIRE

    Thompson, A. Jill

    2008-01-01

    Continuous renal replacement therapies (CRRT) are used to manage fluid overload and/or renal failure. The continuous nature of the fluid and solute removal has less impact on hemodynamic variables in critically ill patients, making CRRT preferred over intermittent hemodialysis for some patients in the intensive care arena. The impact of CRRT on drug removal is variable depending on the CRRT modality, the ultrafiltrate and dialysate flow rates, the filter, and the patient's residual renal func...

  2. Transdermal testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    Ullah MI

    2014-01-01

    Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

  3. The pure relationship and below replacement fertility

    Directory of Open Access Journals (Sweden)

    Hall, David R.

    2003-01-01

    Full Text Available Of the many changes which have characterized the second demographic transition, shifts in fertility and union formation have attracted a great deal of interest from demographers. Despite the fact that researchers have extensively modeled recent demographic changes such as skyrocketing divorce rates, rising common-law union formation, delayed childbearing, and the decline to below-replacement fertility levels, our understanding of the causes of these trends, and the possible connections between them remains theoretically fragmented and incomplete. The goal of this paper is to advance our understanding in this area by exploring the insights on modern family formation of prominent sociologist Anthony Giddens. Specifically, this study examines whether Giddens' "pure relationship" concept can shed light on the trend toward very low fertility. The results of this inquiry suggest that couples in both marriages and common-law unions who conform to key aspects of Giddens pure relationship are morel likely to have uncertain or below-replacement fertility intentions, and less likely to embrace above-replacement fertility goals.

  4. Flow boiling test of GDP replacement coolants

    Energy Technology Data Exchange (ETDEWEB)

    Park, S.H. [comp.

    1995-08-01

    The tests were part of the CFC replacement program to identify and test alternate coolants to replace CFC-114 being used in the uranium enrichment plants at Paducah and Portsmouth. The coolants tested, C{sub 4}F{sub 10} and C{sub 4}F{sub 8}, were selected based on their compatibility with the uranium hexafluoride process gas and how well the boiling temperature and vapor pressure matched that of CFC-114. However, the heat of vaporization of both coolants is lower than that of CFC-114 requiring larger coolant mass flow than CFC-114 to remove the same amount of heat. The vapor pressure of these coolants is higher than CFC-114 within the cascade operational range, and each coolant can be used as a replacement coolant with some limitation at 3,300 hp operation. The results of the CFC-114/C{sub 4}F{sub 10} mixture tests show boiling heat transfer coefficient degraded to a minimum value with about 25% C{sub 4}F{sub 10} weight mixture in CFC-114 and the degree of degradation is about 20% from that of CFC-114 boiling heat transfer coefficient. This report consists of the final reports from Cudo Technologies, Ltd.

  5. Retention Benefit Based Intelligent Cache Replacement

    Institute of Scientific and Technical Information of China (English)

    李凌达; 陆俊林; 程旭

    2014-01-01

    The performance loss resulting from different cache misses is variable in modern systems for two reasons: 1) memory access latency is not uniform, and 2) the latency toleration ability of processor cores varies across different misses. Compared with parallel misses and store misses, isolated fetch and load misses are more costly. The variation of cache miss penalty suggests that the cache replacement policy should take it into account. To that end, first, we propose the notion of retention benefit. Retention benefits can evaluate not only the increment of processor stall cycles on cache misses, but also the reduction of processor stall cycles due to cache hits. Then, we propose Retention Benefit Based Replacement (RBR) which aims to maximize the aggregate retention benefits of blocks reserved in the cache. RBR keeps track of the total retention benefit for each block in the cache, and it preferentially evicts the block with the minimum total retention benefit on replacement. The evaluation shows that RBR can improve cache performance significantly in both single-core and multi-core environment while requiring a low storage overhead. It also outperforms other state-of-the-art techniques.

  6. Experimental replacement of an obligate insect symbiont.

    Science.gov (United States)

    Moran, Nancy A; Yun, Yueli

    2015-02-17

    Symbiosis, the close association of unrelated organisms, has been pivotal in biological diversification. In the obligate symbioses found in many insect hosts, organisms that were once independent are permanently and intimately associated, resulting in expanded ecological capabilities. The primary model for this kind of symbiosis is the association between the bacterium Buchnera and the pea aphid (Acyrthosiphon pisum). A longstanding obstacle to efforts to illuminate genetic changes underlying obligate symbioses has been the inability to experimentally disrupt and reconstitute symbiont-host partnerships. Our experiments show that Buchnera can be experimentally transferred between aphid matrilines and, furthermore, that Buchnera replacement has a massive effect on host fitness. Using a recipient pea aphid matriline containing Buchnera that are heat sensitive because of an allele eliminating the heat shock response of a small chaperone, we reduced native Buchnera through heat exposure and introduced a genetically distinct Buchnera from another matriline, achieving complete replacement and stable inheritance. This transfer disrupted 100 million years (∼ 1 billion generations) of continuous maternal transmission of Buchnera in its host aphids. Furthermore, aphids with the Buchnera replacement enjoyed a dramatic increase in heat tolerance, directly demonstrating a strong effect of symbiont genotype on host ecology.

  7. STATE-OF-THE-ART HUMAN GENE THERAPY: PART II. GENE THERAPY STRATEGIES AND APPLICATIONS

    OpenAIRE

    2014-01-01

    In Part I of this Review, we introduced recent advances in gene delivery technologies and explained how they have powered some of the current human gene therapy applications. In Part II, we expand the discussion on gene therapy applications, focusing on some of the most exciting clinical uses. To help readers to grasp the essence and to better organize the diverse applications, we categorize them under four gene therapy strategies: (1) gene replacement therapy for monogenic diseases, (2) gene...

  8. Gene therapy for brain tumors.

    Science.gov (United States)

    Bansal, K; Engelhard, H H

    2000-09-01

    "Gene therapy" can be defined as the transfer of genetic material into a patient's cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug ("suicide gene") therapy, oncolytic therapy, replacement/therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.

  9. Experimental replacement of aragonite by hydroxyapatite

    Science.gov (United States)

    Kasioptas, A.; Perdikouri, C.; Geisler, T.; Putnis, A.

    2009-04-01

    Hydrothermal treatment of aragonite with (NH4)2HPO4 solution has been shown to produce hydroxyapatite (HAP) with an overall identical and thus pre-determined morphology (Kasioptas et al, 2008). The preservation of the morphology is an outcome of the pseudomorphic nature of this particular reaction. We have investigated the mechanism of the replacement of aragonite by HAP using single, natural, inorganic aragonite crystals. Isothermal experiments were carried out with small crystals placed and sealed in autoclaves with (NH4)2HPO4 solution. After the experiments the aragonite crystals are partly replaced by a new phase. X-ray powder diffraction confirmed that the product phase is indeed HAP; however electron microprobe measurements revealed that the HAP is probably non-stoichiometric. Even when completely converted to HAP, scanning electron microscopy showed that the fine-structure of the aragonite has perfectly been retained. It was also observed that the HAP product phase exhibited a high porosity and was separated from the aragonite parent phase by a sharp interface (on the micrometer scale). The replacement of aragonite by HAP in an aqueous solution can be described in terms of a coupled dissolution-reprecipitation mechanism that takes place at an inward moving reaction front (Putnis& Putnis, 2007). The porosity in the HAP product phase allows the solution to reach the reaction interface. In addition, we have performed experiments with (NH4)2HPO4 solutions prepared with H2O enriched with 97 at.% 18O. The solutions were pre-heated separately to equilibrate the oxygen isotopes in the solution. Raman spectroscopy of the HAP product was used to identify the different vibration modes in the PO43-molecule due to the exchange of 16O with 18O atoms. Apart from the main ?1(PO4) band located near 962 cm-1, we observed four new bands near 945, 931, 919 and 908 cm-1. We have attributed the generation of these new bands to four different degrees of 18O atomic substitutions in

  10. Lower limb joint replacement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Clement Nicholas D

    2012-06-01

    Full Text Available Abstract Introduction There is limited literature regarding the peri-operative and surgical management of patients with rheumatoid disease undergoing lower limb arthroplasty. This review article summarises factors involved in the peri-operative management of major lower limb arthroplasty surgery for patients with rheumatoid arthritis. Methods We performed a search of the medical literature, using the PubMed search engine (http://www.pubmed.gov. We used the following terms: ‘rheumatoid’ ‘replacement’ ‘arthroplasty’ and ‘outcome’. Findings The patient should be optimised pre-operatively using a multidisciplinary approach. The continued use of methotrexate does not increase infection risk, and aids recovery. Biologic agents should be stopped pre-operatively due the increased infection rate. Patients should be made aware of the increased risk of infection and periprosthetic fracture rates associated with their disease. The surgical sequence is commonly hip, knee and then ankle. Cemented total hip replacement (THR and total knee replacement (TKR have superior survival rates over uncemented components. The evidence is not clear regarding a cruciate sacrificing versus retaining in TKR, but a cruciate sacrificing component limits the risk early instability and potential revision. Patella resurfacing as part of a TKR is associated with improved outcomes. The results of total ankle replacement remain inferior to THR and TKR. RA patients achieve equivalent pain relief, but their rehabilitation is slower and their functional outcome is not as good. However, the key to managing these complicated patients is to work as part of a multidisciplinary team to optimise their outcome.

  11. Mactaquac intake tendons removal and replacement

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, I. [NB Power Generation Corp., Mactaquac Generating Station, Keswick Ridge, NB (Canada); Mee, A. [Hatch Energy, Niagara Falls, ON (Canada)

    2007-07-01

    In 1988 and 1989, multi-strand tendons were installed in the intake structure of the Mactaquac generating station. In order to control displacements caused by alkali aggregate reaction (AAR), they were installed in preparation for a slot cutting program in the intake structure to guard against the possibility of a sliding failure of a section of the structure along a plane coincident with the bottom of the water passage. Unique problems for the designers were present in the expansion affect of AAR that were compounded by field conditions that resulted in further difficulties. For example, concrete expansion required the installation of a thick shim pack under the upper anchor head and the periodic testing of the tendons. Once tested, shims could be gradually removed to maintain the correct load over the life of the tendon. However, during the first round of testing and de-stressing five years after the original installation, it was found that some of the tendons had already failed. Over half of the tendons have been replaced in the 20 years since the installation. This paper discussed the original design considerations and examined the conditions that contributed to the premature failure of the tendons. It outlined the history of tendon testing procedures, tendon failure modes and tendon replacement methods. Specifically, the paper discussed the remedial techniques that were employed and the iterations that lead to the current repair approach, while considering the unique field conditions. The application of various corrosion protection schemes and installation and testing methodologies were discussed. It was concluded that tendons were successfully installed in numerous concrete dams around the world but have needed replacement for a variety of reasons. 1 ref., 10 figs.

  12. Alternatives to testosterone replacement: testosterone restoration

    Directory of Open Access Journals (Sweden)

    Andrew McCullough

    2015-04-01

    Full Text Available The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH.

  13. Sex hormone replacement in Turner syndrome

    DEFF Research Database (Denmark)

    Trolle, Christian; Hjerrild, Britta; Cleemann, Line Hartvig

    2012-01-01

    osteoporosis seen in Turner syndrome. But sex hormone insufficiency is also involved in the increased cardiovascular risk, state of physical fitness, insulin resistance, body composition, and may play a role in the increased incidence of autoimmunity. Severe morbidity and mortality affects females with Turner...... syndrome. Recent research emphasizes the need for proper sex hormone replacement therapy (HRT) during the entire lifespan of females with TS and new hypotheses concerning estrogen receptors, genetics and the timing of HRT offers valuable new information. In this review, we will discuss the effects...

  14. Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

    Science.gov (United States)

    Sriaroon, Panida; Ballow, Mark

    2015-11-01

    Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration.

  15. Segmental blood pressure after total hip replacement

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Henriksen, Jens Henrik Sahl

    1992-01-01

    Twenty-nine patients due to have a total hip replacement had their systemic systolic and segmental blood pressures measured prior to operation and 1 and 6 weeks postoperatively. No patients had signs of ischemia. The segmental blood pressure was measured at the ankle and at the toes. A significant...... drop was found in all pressures 1 week postoperatively. The decrease followed the systemic pressure and was restored to normal after 6 weeks. In a group of six patients with preoperatively decreased ankle pressure, a significant transient further decrease in the ankle-toe gradient pressure was found...

  16. To learn more about BHT replacement

    CERN Document Server

    2002-01-01

    Following the article 'An improved financial tool to replace BHT' which appeared in Bulletin No 41/2002, dates of 4 general presentations were published. Please note that the time of the first presentation has changed from 16.00 hrs to 14.00 hrs. The dates/times are now as follows: Wednesday 16 October 14.00 hrs* IT Auditorium (English) *note change of time. Friday 18 October 16.00 hrs, SL Auditorium (French) Monday 21 October 10.00 hrs, LHC Auditorium (French) Wednesday 23 October 10.00 hrs, Council Chamber (English)

  17. Infective endocarditis following transcatheter aortic valve replacement-

    DEFF Research Database (Denmark)

    Loh, Poay Huan; Bundgaard, Henning; S�ndergaard, Lars

    2013-01-01

    Transcatheter aortic valve replacement (TAVR) can improve the symptoms and prognosis of patients with severe aortic stenosis who, due to a high expected operative risk, would not have otherwise been treated surgically. If these patients develop prosthetic valve endocarditis, their presentations may...... be atypical causing a delay in the diagnosis and treatment. The management is also complicated by their comorbidities, and surgical treatment may not be feasible leading to a significant morbidity and mortality. We describe a case of an 85-year-old man with TAVI prosthetic valve endocarditis successfully...

  18. Aortic Annular Enlargement during Aortic Valve Replacement

    Directory of Open Access Journals (Sweden)

    Selman Dumani

    2016-09-01

    Full Text Available In the surgery of aortic valve replacement is always attempted, as much as possible, to implant the larger prosthesis with the mains goals to enhance the potential benefits, to minimise transvalvular gradient, decrease left ventricular size and avoid the phenomenon of patient-prosthesis mismatch. Implantation of an ideal prosthesis often it is not possible, due to a small aortic annulus. A variety of aortic annulus enlargement techniques is reported to avoid patient-prosthesis mismatch. We present the case that has submitted four three times open heart surgery. We used Manouguian technique to enlarge aortic anulus with excellent results during the fourth time of surgery.

  19. Can electronic stability control replace studded tyres?

    Science.gov (United States)

    Elvik, Rune

    2015-12-01

    Based on recent studies, this paper examines whether an increased use of electronic stability control can replace studded tyres. A re-analysis of a study that evaluated the effects on accidents of changes in the use of studded tyres in major cities in Norway is presented. It is found that if all cars have electronic stability control, the use of studded tyres can be reduced to about 15 percent before any increase in the number of accidents occurs. Even if studded tyres were eliminated entirely, any increase in the number of accidents is likely to be considerably smaller than it would have been if electronic stability control had never been invented.

  20. Replacing the Beam Dump at the Booster

    CERN Multimedia

    2013-01-01

    The PS Booster Dump, designed in the 1960’s to cope with beam energies in the order of 800 MeV, has been dismantled and replaced with a new one, capable of withstanding the 2 GeV beam provided by the upcoming LINAC4 at CERN. This video shows the installation of that new dump core inside a one-metre diameter cavity, surrounded by five shielding rings made of concrete and steel. It is the culmination of months of preparation, an interdisciplinary work involving several teams from the Engineering, Beams and Technology Departments, as well as the collaboration and supervision of radio-protection experts.

  1. Replacing the Beam Dump at the Booster

    CERN Multimedia

    2013-01-01

    The PS Booster Dump, designed in the 1960’s to cope with beam energies in the order of 800 MeV, has been dismantled and replaced with a new one, capable of withstanding the 2 GeV beam provided by the upcoming LINAC4 at CERN. This video shows the installation of that new dump core inside a one-metre diameter cavity, surrounded by five shielding rings made of concrete and steel. It is the culmination of months of preparation, an interdisciplinary work involving several teams from the Engineering, Beams and Technology Departments, as well as the collaboration and supervision of radio-protection experts.

  2. 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.

  3. Gene therapy in periodontics

    Directory of Open Access Journals (Sweden)

    Anirban Chatterjee

    2013-01-01

    Full Text Available 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.

  4. Regulated Gene Therapy.

    Science.gov (United States)

    Breger, Ludivine; Wettergren, Erika Elgstrand; Quintino, Luis; Lundberg, Cecilia

    2016-01-01

    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system.

  5. 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.

  6. 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.

  7. The effect of fat replacers on batter and cake properties.

    Science.gov (United States)

    Psimouli, Vassiliki; Oreopoulou, Vassiliki

    2013-10-01

    Fat was replaced at 35% to 100% in cakes by maltodextrin (dextrose equivalent = 3), inulin (high performance and granulated), oligofructose, citrus pectin, and microparticulated protein. Fat replacement by 35% did not induce significant differences in general. Above 65% fat replacement resulted in statistically significant (P < 0.05) decreased viscosity (except for pectin) that was followed by statistically significant decrease in air incorporation and broader bubble size distribution. The starch gelatinization temperature showed a statistically significant increase when fat was replaced by fructose oligosaccharides. The cakes presented statistically significant increase of hardness, elasticity, and decrease of volume development as fat replacement increased above 65%. Also cakes with increased fat replacement received lower scores on taste and flavor, whereas at total fat replacement they were evaluated as not acceptable. Nevertheless, at 65% fat replacement, the samples presented acceptable textural, physical, and sensorial attributes. © 2013 Institute of Food Technologists®

  8. The use of limestone powder as an alternative cement replacement ...

    African Journals Online (AJOL)

    The use of limestone powder as an alternative cement replacement material: An ... The laboratory test results revealed that up to 15% replacement of clinker by fine ... Early strength, Limestone filler, Loss on ignition, Portland limestone cement ...

  9. Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder

    Science.gov (United States)

    ... 1999 Spotlight on Research 2014 February 2014 (historical) Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder Replacing a protein that is crucial to ensuring that the skin’s ...

  10. Cardiovascular implantable electronic device replacement infections and prevention: results from the REPLACE Registry.

    Science.gov (United States)

    Uslan, Daniel Z; Gleva, Marye J; Warren, David K; Mela, Theofanie; Chung, Mina K; Gottipaty, Venkateshwar; Borge, Richard; Dan, Dan; Shinn, Timothy; Mitchell, Kevin; Holcomb, Richard G; Poole, Jeanne E

    2012-01-01

    Infection following cardiovascular implantable electronic device (CIED) replacement is a serious complication, and rates of infection have increased. Analysis of procedural and clinical data from device replacement procedures collected by the REPLACE Registry may provide insights into infection prevention strategies and outcomes. We prospectively evaluated procedural complications in patients undergoing CIED replacement over 6 months from 72 U.S. sites. Major and minor infections were predefined and adjudicated by an independent blinded clinical events committee. Data regarding infection prevention strategies and infectious outcomes were analyzed for their potential relationships. A total of 1,744 patients were included in REPLACE. All patients received preoperative intravenous antibiotics and 68.7% received postoperative systemic antibiotic therapy. CIED infection developed in 22 patients (1.3%), of which 14 cases were major (0.8%, 95% confidence interval [CI] 0.4%-1.3%) and eight were minor (0.5%, 95% CI 0.2%-0.9%). Patients with infections were more likely to have had postoperative hematomas (five of 22 [22.7%] vs 17 of 1,722 [0.98%], P = 0.002). Participating sites experiencing infection rates >5% were more likely to use povidone-iodine for topical antisepsis, had lower implantation volume, and had patients with higher Charlson Comorbidity Index (2.79 vs 2.32, 95% CI for difference 0.08-0.86, P = 0.019). In this multicenter prospective study with 6 months of follow-up, infections associated with CIED replacements were surprisingly infrequent, possibly due to the use of preoperative antibiotics. Patients with infections were more likely to have had a postoperative hematoma, and sites with higher infection rates had sicker patients and lower overall procedural volume. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

  11. Property Assessment of Sponge Cake Added with Egg Replacer

    OpenAIRE

    Yaqiang He; Linlin Wang; Qian Lu

    2015-01-01

    Chicken egg which is always used in sponge cake production is likely to deteriorate during storage or transportation. This weakness prevents the wide use of chicken egg in sponge cake making. In order to solve this problem, egg replacer has been developed. In this study, effect of egg replacer on the property of sponge cake was analyzed. The result indicated egg replacer could improve the yield rate and specific volume of sponge cake. However, high content of egg replacer would negatively imp...

  12. Transdermal testosterone replacement therapy in men.

    Science.gov (United States)

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.

  13. Testosterone replacement therapy in obese males.

    Science.gov (United States)

    Drewa, Tomasz; Olszewska-Słonina, Dorota; Chlosta, Piotr

    2011-01-01

    Controversy surrounds testosterone replacement therapy in obese ageing due to no generally accepted lower limits of normal testosterone level and high prevalence of hypogonadal symptoms in the ageing male population and the non-specific nature of these symptoms. Late onset hypogonadism is a clinical and biochemical syndrome associated with advancing age, often coexisting with obesity and metabolic syndrome. High fat and carbohydrates (fructose) consumption is responsible for development of obesity and metabolic syndrome which is one of risk factors for hypogonadism in older men. High fructose intake has been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Obesity and lack of physical activity negatively influence testosterone level. Low testosterone level should be regarded as an effect of obesity, but reverse relationship has not been proved yet. The management of late-onset hypogonadism symptoms has to be treated by a change of a life style and prevented with healthy nutrition and physical activity. The question related to rational indications for testosterone replacement therapy in obese males seems to be still actual.

  14. An improved financial tool to replace BHT

    CERN Multimedia

    2002-01-01

    In November, the BHT tool used to control financial data will be replaced by an improved and more powerful system, called CET for CERN Expenditure Tracking. The team in charge of CET. From left to right, sitting, Martyn Rankin, David McGlashan, standing, Per Gunnar Jonsson, James Purvis and Mikael Angberg. After 10 years of BHT at CERN, in order to face the challenges of the LHC era, and following the recommendations of the External Review Committee, the BHT application will be replaced by an improved and more powerful expenditure tracking tool called CET for CERN Expenditure Tracking. For those who are not familiar with it, the BHT, Budget Holders Toolkit, is a utility that provides a way to view CERN financial data. It is available for users who have access to at least one budget code. The new CET represents a tool that not only allows powerful analysis of the past, but also assists in forecasting the future. CET will offer significantly more functionality than BHT, including extended contract analysis, ...

  15. 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...

  16. Toward replacement fertility in Egypt and Tunisia.

    Science.gov (United States)

    Eltigani, Eltigani E

    2009-09-01

    Egypt and Tunisia began their fertility transition at almost identical fertility levels and at roughly the same time period, yet the difference in the pace of decline has been such that the total fertility rate (TFR) in Tunisia reached replacement level by the year 2001, whereas the TFR in Egypt remains above three live births per woman. This article draws on the secondary literature and on several nationally representative surveys from the two countries between 1978 and 2005 to provide empirical evidence of the difference in the pace of fertility decline and to analyze the determinants of the differential. Findings include (a) variation across the two countries in the consistency of fertility decline among the segments of the population leading the transition; (b) that the success of each country's family planning program was influenced by the role of political leaders and the extent of the program's integration within socioeconomic development objectives; (c) that the impact of contraception on TFR decline became an important factor in the mid-1980s; and (d) that the greatest determinant of the discrepancy in the pace of fertility decline is the disparity in age at marriage, which rose more significantly in Tunisia than in Egypt. The latter finding indicates that reaching replacement fertility in Egypt hinges primarily on further declines in marital fertility, resulting from reduction of wanted fertility and from an expansion of family planning program coverage and improved efficiency of service delivery and use.

  17. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2015-12-01

    Full Text Available Hypoparathyroidism (HypoPT is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH. Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84 as well as therapy with the N-terminal PTH fragment (rhPTH(1-34 have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

  18. Concomitant aortic valve replacement and myocardial revascularization.

    Science.gov (United States)

    Craver, J M; Jones, E L; Hatcher, C R; Farmer, J H

    1977-01-01

    Twenty-six consecutive patients underwent combined aortic valve replacement and myocardial revascularization at the Emory University Affiliated Hospitals between May, 1973 and March, 1976. Acute myocardial infarction resulted in two operative deaths (8%). There have been four late deaths, all Class IV preoperative. The age range was 37 to 79 years with an average age of 60. Preoperatively all patients were Class IV or late Class III. Twenty-three patients had symptoms of angina pectoris; congestive heart failure was evident in 56%. Postoperatively, 70% are now Class 1 or II. Single coronary bypass was performed in 16 patients, double in 6, and triple in three. Double bypass plus mitral valve replacement was required in two with aneurysmectomy in one. The rate of intraoperative infarction was 27% for the series but only 7% in the last year. The methods of intraoperative myocardial preservation and the technical approach for the operative procedures were variable. Results with each method are correlated, and currently preferred techniques are presented and discussed. Best results were obtained in patients who presented early in their symptomatic course with isolated proximal coronary lesions and good renoff vessels. Excellent results could be achieved despite advanced age of patients, requirement for multiple bypass grafts, and correction of other associated cardiac lesions. Poorest results were obtained when long-standing ventricular failure was combined with poor vessels distal to coronary stenoses. PMID:860881

  19. 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...

  20. Limitations to fluid replacement during exercise.

    Science.gov (United States)

    Maughan, R J; Leiper, J B

    1999-04-01

    Fluid replacement during exercise is essential for endurance exercise performance and reducing the risk of heat illness. Fluids supply water, which ameliorates dehydration, and also substrate for the working muscles. Absorption of water and nutrients occurs in the upper part of the small intestine, and replacement may be limited by the rate at which fluid is emptied from the stomach or absorbed in the intestine. Gastric emptying of liquids is influenced primarily by the volume of fluid in the stomach and by its energy density. Increasing the volume will speed emptying, but increasing the nutrient content will slow emptying. Osmolality, temperature, and pH of drinks, as well as exercise intensity, are of minor importance. Intestinal water absorption is a passive process: water follows osmotic gradients but will also follow the active absorption of nutrients, especially glucose, which is actively co-transported with sodium. Water transport is maximised by the presence in the intestine of hypotonic solutions of glucose and sodium. Hypertonic solutions promote net water secretion into the intestinal lumen, resulting in a temporary net loss of water from the body. The amount of fluid ingested by athletes is normally much less than can be tolerated, therefore issues such as palatability and practising drinking during training are important.

  1. Neutron scattering at Australia's replacement research reactor

    Science.gov (United States)

    Robinson, R. A.; Kennedy, S. J.

    2002-01-01

    On August 25 1999, the Australian government gave final approval to build a research reactor to replace the existing HIFAR reactor at Lucas Heights. The replacement reactor, which will commence operation in 2005, will be multipurpose in function, with capabilities for both neutron-beam research and radioisotope production. Regarding beams, cold and thermal neutron sources are to be installed and the intent is to use supermirror guides, with coatings with critical angles up to 3 times that of natural Ni, to transport cold and thermal neutron beams into a large modern guide hall. The reactor and all the associated infrastructure, with the exception of the neutron beam instruments, is to be built by INVAP, SE and subcontractors in a turnkey contract. The goal is to have at least eight leading-edge neutron-beam instruments ready in 2005, and they will be developed by ANSTO and other contracted organisations, in consultation with the Australian user community and interested overseas parties. A review of the planned scientific capabilities, a description of the facility and a status report on the activities so far is given.

  2. Postoperative Autologous Reinfusion in Total Knee Replacement

    Directory of Open Access Journals (Sweden)

    A. Crescibene

    2015-01-01

    Full Text Available Surgeries for total knee replacement (TKR are increasing and in this context there is a need to develop new protocols for management and use of blood transfusion therapy. Autologous blood reduces the need for allogeneic blood transfusion and the aim of the present study was to verify the safety and the clinical efficacy. An observational retrospective study has been conducted on 124 patients, undergoing cemented total knee prosthesis replacement. Observed population was stratified into two groups: the first group received reinfusion of autologous blood collected in the postoperative surgery and the second group did not receive autologous blood reinfusion. Analysis of data shows that patients undergoing autologous blood reinfusion received less homologous blood bags (10.6% versus 30%; p=0.08 and reduced days of hospitalization (7.88 ± 0.7 days versus 8.96 ± 2.47 days for the control group; p=0.03. Microbiological tests were negative in all postoperatively salvaged and reinfused units. Our results emphasize the effectiveness of this procedure and have the characteristics of simplicity, low cost (€97.53 versus €103.79; p<0.01, and easy reproducibility. Use of autologous drainage system postoperatively is a procedure that allows reducing transfusion of homologous blood bags in patients undergoing TKR.

  3. Recombinant Enzyme Replacement Therapy in Hypophosphatasia.

    Science.gov (United States)

    Hofmann, Christine; Jakob, Franz; Seefried, Lothar; Mentrup, Birgit; Graser, Stephanie; Plotkin, Horacio; Girschick, Hermann J; Liese, Johannes

    2015-01-01

    Hypophosphatasia (HPP) is a rare monogenetic and multisystemic disease with involvement of different organs, including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The exact metabolic mechanisms of the effects of TNAP deficiency in different tissues are not understood in detail. There is no approved specific treatment for HPP; therefore symptomatic treatment in order to improve the clinical features is of major interest. Enzyme replacement therapy (ERT) is a relatively new type of treatment based on the principle of administering a medical treatment replacing a defective or absent enzyme. Recently ERT with a bone targeted recombinant human TNAP molecule has been reported to be efficient in ten severely affected patients and improved survival of life threatening forms. These results are very promising especially with regard to the skeletal phenotype but it is unclear whether ERT also has beneficial effects for craniosynostosis and in other affected tissues in HPP such as brain and kidney. Long-term data are not yet available and further systematic clinical trials are needed. It is also necessary to establish therapeutic approaches to help patients who are affected by less severe forms of HPP but also suffer from a significant reduction in quality of life. Further basic research on TNAP function and role in different tissues and on its physiological substrates is critical to gain a better insight in the pathogenesis in HPP. This and further experiences in new therapeutic strategies may improve the prognosis and quality of life of patients with all forms of HPP.

  4. 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...

  5. 21 CFR 874.3450 - Partial ossicular replacement prosthesis.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Partial ossicular replacement prosthesis. 874.3450 Section 874.3450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... replacement prosthesis. (a) Identification. A partial ossicular replacement prosthesis is a device intended...

  6. 21 CFR 874.3495 - Total ossicular replacement prosthesis.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Total ossicular replacement prosthesis. 874.3495 Section 874.3495 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... replacement prosthesis. (a) Identification. A total ossicular replacement prosthesis is a device intended...

  7. 21 CFR 870.3710 - Pacemaker repair or replacement material.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

  8. 14 CFR 21.9 - Replacement and modification articles.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Replacement and modification articles. 21.9... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.9 Replacement and modification articles. (a) If a person knows, or should know, that a replacement or modification article is reasonably likely to...

  9. Orthodontic retraction of autotransplanted premolar to replace ankylosed maxillary incisor with replacement resorption.

    Science.gov (United States)

    Choi, Yoon Jeong; Shin, Sujung; Kim, Kyung-Ho; Chung, Chooryung J

    2014-04-01

    This case report describes the successful treatment of an adult with lip protrusion and a previously traumatized maxillary central incisor that had experienced replacement root resorption. An extracted premolar was transplanted into the incisor space and retracted orthodontically. Autotransplantation was successful with complete root formation and, combined with orthodontic treatment, provided a satisfying esthetic outcome.

  10. Revision of the aseptic and septic total ankle replacement.

    Science.gov (United States)

    Espinosa, Norman; Wirth, Stephan Hermann

    2013-04-01

    Total ankle replacement has become a popular treatment of symptomatic end-stage ankle osteoarthritis. Contemporary total ankle replacement systems provide more anatomic and biomechanically sound function. However, longevity is still limited and long-term results of modern total ankle replacement designs are not available. In the case of failure, conversion into arthrodesis has remained the treatment of choice but at the cost of hindfoot function and potential degeneration of the adjacent joints. Thus, revision total ankle replacement by exchange of the prosthetic components represents an attractive solution. This article focuses on revision total ankle replacement and conversion to ankle arthrodesis.

  11. Testosterone Replacement Therapy and the Cardiovascular System.

    Science.gov (United States)

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  12. Segmental blood pressure after total hip replacement

    DEFF Research Database (Denmark)

    Gebuhr, Peter Henrik; Soelberg, M; Henriksen, Jens Henrik

    1992-01-01

    drop was found in all pressures 1 week postoperatively. The decrease followed the systemic pressure and was restored to normal after 6 weeks. In a group of six patients with preoperatively decreased ankle pressure, a significant transient further decrease in the ankle-toe gradient pressure was found......Twenty-nine patients due to have a total hip replacement had their systemic systolic and segmental blood pressures measured prior to operation and 1 and 6 weeks postoperatively. No patients had signs of ischemia. The segmental blood pressure was measured at the ankle and at the toes. A significant...... on the operated side. None of the patients had symptoms from the lowered pressure. We conclude that in patients without signs of ischemia, the postoperative segmental pressure decrease is reversible and therefore not dangerous....

  13. [Interventional mitral valve replacement. Current status].

    Science.gov (United States)

    Lutter, G; Frank, D

    2016-02-01

    Approximately 30 % of patients suffering from severe valvular heart disease, such as mitral valve regurgitation are non-compliant to the gold standard of minimally invasive surgery, reconstruction or valve replacement. The number of these mostly old patients with severe comorbidities is increasing; therefore, transcatheter interventions have been developed to address an unmet clinical need and may be an alternative therapeutic option to the reference standard. Apart from the successful MitraClip therapy, alternative transcatheter reconstruction technologies are being developed. As with transcatheter aortic valve implantation (TAVI) procedures, the off-pump implantation of a valved stent into the mitral position mainly via a transapical approach will be of great benefit. Recently, the feasibility of transcatheter mitral valved stent implantation in high-risk patients has already been reported.

  14. Strategies for Revision Total Ankle Replacement

    Directory of Open Access Journals (Sweden)

    Thomas S. Roukis, DPM, PhD, FACFAS

    2014-12-01

    Full Text Available As the frequency of primary total ankle replacement (TAR continues to build, revision will become more commonplace. At present there are no “standard principles” associated with revision TAR. What is clear is that the current approaches are technically complex, fraught with complications and no one approach represents the only answer. Exchange of TAR metallic components to the same system standard or dedicated revision components are viable options with limited occurrence of complications. Explantation and conversion to custom-design long stemmed components has limited availability. Explantation and conversion to another TAR system is high-risk and has strong potential for complications. The use of metal reinforced polymethylmethacrylate cement augmentation of failed TAR systems and tibio-talo-calcaneal arthrodesis should be reserved for very select situations where other options are not possible. There is a real need for long-term survivorship following revision TAR and future efforts ought to be directed in this area.

  15. The cost of standing strong for replacement.

    Science.gov (United States)

    Brown, Katy

    2015-03-01

    The testimonies of these individuals largely speak for themselves. The responses point to the importance of specific institutions or research groups that focus on the development and use of alternatives, and these should, of course, be better supported. Those who find themselves outside such institutions or teams, are more likely to feel stranded and isolated. Then again, Liz did have the support of a research group dedicated to replacement, but she has still had a significant struggle to find funding. The interviews with some of these particular young researchers indeed pointed toward a tangible ‘cost’ in terms of having to steer their career on the often difficult path toward the use of non-animal based methods.

  16. Stationary populations with below-replacement fertility

    Directory of Open Access Journals (Sweden)

    Carl Schmertmann

    2012-04-01

    Full Text Available BACKGROUND A population with sustained below-replacement fertility and constant immigration eventually becomes stationary. Stationary-through-immigration (SI populations have unusual age structures that depend on the distribution of immigrants' arrival ages. OBJECTIVE I summarize known formal relationships between the distribution of immigrants' entry ages and the long-run size and structure of SI populations. I clarify a previously published result about SI dependency ratios. RESULTS The long-run size and age structure of an SI population depend on the remaining life expectancies of arriving immigrants, but are also sensitive to the expected numbers of native children born after arrival. Numerical calculations with contemporary Austrian data show (1 contrary to previously published results, immigration flows need not be concentrated in early working ages in order to ensure low overall dependency, and (2 the SI dependency ratio is minimized when all immigrants are in their mid-30s.

  17. Replacement collision sequence studies in iron

    CERN Document Server

    Hou, M; Becquart, C S

    2002-01-01

    The properties of replacement collision sequences (RCS) in iron and their contribution to radiation damage are studied as they are generated in atomic collision cascades with the binary collision approximation Marlowe. Length distributions of RCS in collision cascades generated by primaries with a couple of ten keV kinetic energies are predicted short. Whatever the interatomic potential employed, at least 90% of the generated RCS have a length of no more than three successive collisions, whatever the directions. This property was found for all the known phases of iron at standard pressure (bcc and fcc). The RCS length distributions are not significantly influenced by the temperature nor by the accurate form of the model describing the energy loss in RCS. Close to 50% of the stable Frenkel pairs (FP) created result from RCS that are shorter than the vacancy-interstitial recombination distance estimated on the basis of molecular dynamics calculations. The other half results from longer RCS (about five successiv...

  18. Replacement of Swiss "Attestations de fonctions"

    CERN Multimedia

    DG Unit

    2009-01-01

    The Swiss Permanent Mission has informed CERN that the "attestations de fonctions" issued to certain members of the personnel and the "attestations" issued to their family members will gradually be replaced by P-type "cartes de légitimation" (see specimen copies below). This card’s name, together with its more contemporary design compared with old-style "Attestations" issued in the 1970s, will make the holder’s daily life much easier, e.g. when crossing borders, renting accommodation or setting up a telephone line. The Users Office (PH Department) and the Cards Office (HR Department), which are responsible for handling requests for "cartes de légitimation", will provide information in due course on how they intend to organise the exchange of "attestations" (priority will be given to residents of Switzerland, in parti...

  19. The Research of Artificial Cervical Disc Replacement

    Institute of Scientific and Technical Information of China (English)

    Zhao Zhua; Qiang Shenb

    2008-01-01

    Cervical arthroplasty after anterior decompression with insertion of a prosthetic total disc replacement has been suggested as an alternate to anterior cervical fusion. It develops quickly during recent years. Currently there are several cervical arthroplasty devices. Each device varies in terms of materials, range of motion and constraint. Early studies suggest that in the short term, the complication rate and efficacy is no worse than fusion surgery. Long-term results have not yet been reported. This review examines the current prostheses as well as discussing issues regarding indications and technique. It is hoped that an improvement of cervical arthroplasty occurs in terms of materials and design as spinal surgeons enter a new dines of the management of cervical spine disease.

  20. Growth hormone replacement therapy in Costello syndrome.

    Science.gov (United States)

    Triantafyllou, Panagiota; Christoforidis, Athanasios; Vargiami, Euthymia; Zafeiriou, Dimitrios I

    2014-12-01

    Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

  1. Renal Replacement Therapy in Austere Environments

    Directory of Open Access Journals (Sweden)

    Christina M. Yuan

    2011-01-01

    Full Text Available Myoglobinuric renal failure is the classically described acute renal event occurring in disaster environments—commonly after an earthquake—which most tests the ingenuity and flexibility of local and regional nephrology resources. In recent decades, several nephrology organizations have developed response teams and planning protocols to address disaster events, largely focusing on patients at risk for, or with, acute kidney injury (AKI. In this paper we briefly review the epidemiology and outcomes of patients with dialysis-requiring AKI after such events, while providing greater focus on the management of the end-stage renal disease population after a disaster which incapacitates a pre-existing nephrologic infrastructure (if it existed at all. “Austere” dialysis, as such, is defined as the provision of renal replacement therapy in any setting in which traditional, first-world therapies and resources are limited, incapacitated, or nonexistent.

  2. Cellular processing and nuclear targeting of non-viral gene delivery systems

    NARCIS (Netherlands)

    Aa, M.A.E.M. van der

    2005-01-01

    Gene therapy utilizes genetic material in order to cure patients either by DNA vaccines or by replacement of a defective gene with a normal one. For successful gene therapy certain elements are required: gene delivery systems with low toxicity and immunity, with efficient gene transfer and high gene

  3. Testosterone replacement therapy for older men

    Directory of Open Access Journals (Sweden)

    Stephen E Borst

    2008-01-01

    Full Text Available Stephen E Borst, Thomas MulliganGeriatrics Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USAAbstract: Despite intensive research on testosterone therapy for older men, important questions remain unanswered. The evidence clearly indicates that many older men display a partial androgen deficiency. In older men, low circulating testosterone is correlated with low muscle strength, with high adiposity, with insulin resistance and with poor cognitive performance. Testosterone replacement in older men has produced benefits, but not consistently so. The inconsistency may arise from differences in the dose and duration of testosterone treatment, as well as selection of the target population. Generally, studies reporting anabolic responses to testosterone have employed higher doses of testosterone for longer treatment periods and have targeted older men whose baseline circulating bioavailable testosterone levels were low. Most studies of testosterone replacement have reported anabolic that are modest compared to what can be achieved with resistance exercise training. However, several strategies currently under evaluation have the potential to produce greater anabolic effects and to do so in a safe manner. At this time, testosterone therapy can not be recommended for the general population of older men. Older men who are hypogonadal are at greater risk for the catabolic effects associated with a number of acute and chronic medical conditions. Future research is likely to reveal benefits of testosterone therapy for some of these special populations. Testosterone therapy produces a number of adverse effects, including worsening of sleep apnea, gynecomastia, polycythemia and elevation of PSA. Efficacy and adverse effects should be assessed frequently throughout the course of therapy.Keywords: aging, testosterone, hypogonadism, physical function

  4. Renal replacement therapy in Korea, 2012

    Directory of Open Access Journals (Sweden)

    Dong Chan Jin

    2014-03-01

    Full Text Available The Korean Society of Nephrology (KSN launched the official end-stage renal disease (ESRD patient registry in 1985, and an Internet online registry program was opened in 2001 and revised in 2013. The ESRD Registry Committee of KSN has collected data on dialysis therapy in Korea through the online registry program in the KSN Internet website. The status of renal replacement therapy in Korea at the end of 2012 is described in the following. The total number of ESRD patients was 70,211 at the end of 2012, which included 48,531 hemodialysis (HD patients, 7,552 peritoneal dialysis (PD patients, and 14,128 functioning kidney transplant (KT patients. The prevalence of ESRD was 1,353.3 patients per million population (PMP, and the distribution of renal replacement therapy among ESRD patients was as follows: HD, 69.1%; PD, 10.8%; and KT, 20.2%. The number of new ESRD patients in 2012 was 11,742 (HD, 8,811; PD, 923; and KT, 1,738; the incidence rate was 221.1 PMP. The primary causes of ESRD were diabetic nephropathy (50.6%, hypertensive nephrosclerosis (18.5%, and chronic glomerulonephritis (18.1%. The mean urea reduction ratio was 67.9% in male and 74.1% in female HD patients. The mean Kt/V was 1.382 in male and 1.652 in female HD patients. The 5-year survival rates of male and female dialysis patients were 70.6% and 73.5%, respectively.

  5. Neonatal varicella pneumonia, surfactant replacement therapy

    Directory of Open Access Journals (Sweden)

    Mousa Ahmadpour-kacho

    2015-12-01

    Full Text Available Background: Chickenpox is a very contagious viral disease that caused by varicella-zoster virus, which appears in the first week of life secondary to transplacental transmission of infection from the affected mother. When mother catches the disease five days before and up to two days after the delivery, the chance of varicella in neonate in first week of life is 17%. A generalized papulovesicular lesion is the most common clinical feature. Respiratory involvement may lead to giant cell pneumonia and respiratory failure. The mortality rate is up to 30% in the case of no treatment, often due to pneumonia. Treatment includes hospitalization, isolation and administration of intravenous acyclovir. The aim of this case report is to introduce the exogenous surfactant replacement therapy after intubation and mechanical ventilation for respiratory failure in neonatal chickenpox pneumonia and respiratory distress. Case Presentation: A seven-day-old neonate boy was admitted to the Neonatal Intensive Care Unit at Amirkola Children’s Hospital, Babol, north of Iran, with generalized papulovesicular lesions and respiratory distress. His mother has had a history of Varicella 4 days before delivery. He was isolated and given supportive care, intravenous acyclovir and antibiotics. On the second day, he was intubated and connected to mechanical ventilator due to severe pneumonia and respiratory failure. Because of sever pulmonary involvement evidenced by Chest X-Ray and high ventilators set-up requirement, intratracheal surfactant was administered in two doses separated by 12 hours. He was discharged after 14 days without any complication with good general condition. Conclusion: Exogenous surfactant replacement therapy can be useful as an adjunctive therapy for the treatment of respiratory failure due to neonatal chickenpox.

  6. Transcatheter Aortic Valve Replacement: A Review Article

    Directory of Open Access Journals (Sweden)

    Juan A Siordia

    2016-06-01

    Full Text Available Transcatheter aortic valve replacement (TAVR is a novel therapeutic intervention for the replacement of severely stenotic aortic valves in high-risk patients for standard surgical procedures. Since the initial PARTNER trial results, use of TAVR has been on the rise each year. New delivery methods and different valves have been developed and modified in order to promote the minimally invasive procedure and reduce common complications, such as stroke. This review article focuses on the current data on the indications, risks, benefits, and future directions of TAVR. Recently, TAVR has been considered as a standard-of-care procedure. While this technique is used frequently in high-risk surgical candidates, studies have been focusing on the application of this method for younger patients with lower surgical risk. Moreover, several studies have proposed promising results regarding the use of valve-in-valve technique or the procedure in which the valve is placed within a previously implemented bioprosthetic valve. However, ischemic strokes and paravalvular leak remain a matter of debate in these surgeries. New methods and devices have been developed to reduce the incidence of post-procedural stroke. While the third generation of TAVR valves (i.e., Edwards Sapien 3 and Medtronic Evolut R addresses the issue of paravalvular leak structurally, results on their efficacy in reducing the risk of paravalvular leak are yet to be obtained. Furthermore, TAVR enters the field of hybrid methods in the treatment of cardiac issues via both surgical and catheter-based approaches. Finally, while TAVR is primarily performed on cases with aortic stenosis, new valves and methods have been proposed regarding the application of this technique in aortic regurgitation, as well as other aortic pathologies. TAVR is a suitable therapeutic approach for the treatment of aortic stenosis in high-risk patients. Considering the promising results in the current patient population

  7. Urban chaos and replacement dynamics in nature and society

    Science.gov (United States)

    Chen, Yanguang

    2014-11-01

    Replacements resulting from competition are ubiquitous phenomena in both nature and society. The evolution of a self-organized system is always a physical process substituting one type of components for another type of components. A logistic model of replacement dynamics has been proposed in terms of technical innovation and urbanization, but it fails to arouse widespread attention in the academia. This paper is devoted to laying the foundations of general replacement principle by using analogy and induction. The empirical base of this study is urban replacement, including urbanization and urban growth. The sigmoid functions can be employed to model various processes of replacement. Many mathematical methods such as allometric scaling and head/tail breaks can be applied to analyzing the processes and patterns of replacement. Among varied sigmoid functions, the logistic function is the basic and the simplest model of replacement dynamics. A new finding is that replacement can be associated with chaos in a nonlinear system, e.g., urban chaos is just a part of replacement dynamics. The aim of developing replacement theory is at understanding complex interaction and conversion. This theory provides a new way of looking at urbanization, technological innovation and diffusion, Volterra-Lotka’s predator-prey interaction, man-land relation, and dynastic changes resulting from peasant uprising, and all that. Especially, the periodic oscillations and chaos of replacement dynamics can be used to explain and predict the catastrophic occurrences in the physical and human systems.

  8. Property Assessment of Sponge Cake Added with Egg Replacer

    Directory of Open Access Journals (Sweden)

    Yaqiang He

    2015-08-01

    Full Text Available Chicken egg which is always used in sponge cake production is likely to deteriorate during storage or transportation. This weakness prevents the wide use of chicken egg in sponge cake making. In order to solve this problem, egg replacer has been developed. In this study, effect of egg replacer on the property of sponge cake was analyzed. The result indicated egg replacer could improve the yield rate and specific volume of sponge cake. However, high content of egg replacer would negatively impact the internal structure and sensory property of sponge cake. Based on the result of this research, optimum content of egg replacer in sponge cake is 3.6 g. In the industrial production of sponge cake, different types of wheat flour and additives would be used. The optimum content of egg replacer may be different from the result of this research. Therefore, in the industrial production, the optimum content of egg replacer should be determined based on experiment.

  9. 毒素蛋白基因mazF在基因修饰系统中的应用进展%Application Progress ofmazF Gene in Genetic Modification System

    Institute of Scientific and Technical Information of China (English)

    石杨; 董会娜; 张大伟

    2014-01-01

    毒素-抗毒素系统(Toxin-antitoxin system,TA系统)存在于大部分细菌中。mazEF是大肠杆菌中一种毒素-抗毒素系统。毒素基因mazF编码的MazF毒素蛋白可以特异性地剪切自由mRNA的ACA序列,从而抑制蛋白合成、引起细胞生长停滞;近些年,许多学者利用mazF基因作为反向筛选标记对不同种微生物建立了无标记或无痕的基因修饰系统,并实现了不同菌株的基因组修饰。主要综述了大肠杆菌mazF基因作为反向筛选基因的应用原理及其在不同种类微生物的基因修饰系统中的应用进展,然后对mazF基因及其他毒素基因在基因修饰系统中的应用进行了展望。%Toxin-antitoxin system(TA)exists in most of the genetic material of bacteria.mazEF is a kind of toxin-antitoxin system in E. coli. MazF encoded bymazF is an mRNA interferase that specifically cleaves free mRNAs at ACA sequences, resulting in inhibited protein synthesis and cell growth arrest. Recently, some scholars have usedmazF as a counter-selection marker in genetic modification systems, and achieved modifications of the genome in various strains. In this article, the research advances of E. coli mazF used as counter-selection marker in bacterial genetic modification were reviewed, followed by application of other toxin gene. Finally, perspective of the possible new pathways for developing new genetic modification methods were addressed.

  10. Evolution of high tooth replacement rates in sauropod dinosaurs.

    Directory of Open Access Journals (Sweden)

    Michael D D'Emic

    Full Text Available BACKGROUND: Tooth replacement rate can be calculated in extinct animals by counting incremental lines of deposition in tooth dentin. Calculating this rate in several taxa allows for the study of the evolution of tooth replacement rate. Sauropod dinosaurs, the largest terrestrial animals that ever evolved, exhibited a diversity of tooth sizes and shapes, but little is known about their tooth replacement rates. METHODOLOGY/PRINCIPAL FINDINGS: We present tooth replacement rate, formation time, crown volume, total dentition volume, and enamel thickness for two coexisting but distantly related and morphologically disparate sauropod dinosaurs Camarasaurus and Diplodocus. Individual tooth formation time was determined by counting daily incremental lines in dentin. Tooth replacement rate is calculated as the difference between the number of days recorded in successive replacement teeth. Each tooth family in Camarasaurus has a maximum of three replacement teeth, whereas each Diplodocus tooth family has up to five. Tooth formation times are about 1.7 times longer in Camarasaurus than in Diplodocus (315 vs. 185 days. Average tooth replacement rate in Camarasaurus is about one tooth every 62 days versus about one tooth every 35 days in Diplodocus. Despite slower tooth replacement rates in Camarasaurus, the volumetric rate of Camarasaurus tooth replacement is 10 times faster than in Diplodocus because of its substantially greater tooth volumes. A novel method to estimate replacement rate was developed and applied to several other sauropodomorphs that we were not able to thin section. CONCLUSIONS/SIGNIFICANCE: Differences in tooth replacement rate among sauropodomorphs likely reflect disparate feeding strategies and/or food choices, which would have facilitated the coexistence of these gigantic herbivores in one ecosystem. Early neosauropods are characterized by high tooth replacement rates (despite their large tooth size, and derived titanosaurs and

  11. White adipose tissue resilience to insulin deprivation and replacement.

    Science.gov (United States)

    Hadji, Lilas; Berger, Emmanuelle; Soula, Hédi; Vidal, Hubert; Géloën, Alain

    2014-01-01

    Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. The initial body weight of the rats was 465±5.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues.

  12. White Adipose Tissue Resilience to Insulin Deprivation and Replacement

    Science.gov (United States)

    Hadji, Lilas; Berger, Emmanuelle; Soula, Hédi; Vidal, Hubert; Géloën, Alain

    2014-01-01

    Introduction Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Methods Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. Results The initial body weight of the rats was 465±5.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Conclusion Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues. PMID:25170835

  13. 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.

  14. The Effects of Leptin Replacement on Neural Plasticity

    Directory of Open Access Journals (Sweden)

    Gilberto J. Paz-Filho

    2016-01-01

    Full Text Available Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function.

  15. Estrogen replacement therapy and cardioprotection: mechanisms and controversies

    Directory of Open Access Journals (Sweden)

    M.T.R. Subbiah

    2002-03-01

    Full Text Available Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD. This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL and to increases in high density lipoproteins (HDL. Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors alpha and ß, there is evidence for `immediate non-genomic' effects. The role of HDL in interacting with 17ß-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc. in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.

  16. The Use of Viral Vectors in Gene Transfer Therapy

    OpenAIRE

    Dziaková, A.; Valenčáková, A.; Hatalová, E.; J. Kalinová

    2016-01-01

    Gene therapy is strategy based on using genes as pharmaceuticals. Gene therapy is a treatment that involves altering the genes inside body's cells to stop disease. Genes contain DNA- the code controlling body form and function. Genes that do not work properly can cause disease. Gene therapy replaces a faulty gene or adds a new gene in an attempt to cure disease or improve the ability of the body to fight disease. Gene therapy holds promise for treating a wide range of diseases, including canc...

  17. Surfactant replacement therapy--economic impact.

    Science.gov (United States)

    Pejaver, R K; al Hifzi, I; Aldussari, S

    2001-06-01

    Surfactant replacement is an effective treatment for neonatal respiratory distress syndrome. (RDS). As widespread use of surfactant is becoming a reality, it is important to assess the economic implications of this new form of therapy. A comparison study was carried out at the Neonatal Intensive Care Unit (NICU) of Northwest Armed Forces Hospital, Saudi Arabia. Among 75 infants who received surfactant for RDS and similar number who were managed during time period just before the surfactant was available, but by set criteria would have made them eligible for surfactant. All other management modalities except surfactant were the same for all these babies. Based on the intensity of monitoring and nursing care required by the baby, the level of care was divided as: Level IIIA, IIIB, Level II, Level I. The cost per day per bed for each level was calculated, taking into account the use of hospital immovable equipment, personal salaries of nursing, medical, ancillary staff, overheads and maintenance, depreciation and replacement costs. Medications used, procedures done, TPN, oxygen, were all added to individual patient's total expenditure. 75 infants in the Surfactant group had 62 survivors. They spent a total of 4300 days in hospital. (av 69.35) Out of which 970 d (av 15.65 per patient) were ventilated days. There were 56 survivors in the non-surfactant group of 75. They had spent a total of 5023 days in the hospital (av 89.69/patient) out of which 1490 were ventilated days (av 26.60 d). Including the cost of surfactant (two doses), cost of hospital stay for each infant taking the average figures of stay would be SR 118, 009.75 per surfactant treated baby and SR 164, 070.70 per non-surfactant treated baby. The difference of 46,061 SR is 39.03% more in non-surfactant group. One Saudi rial = 8 Rs (approx at the time study was carried out.) Medical care cost varies from place to place. However, it is definitely cost-effective where surfactant is concerned. Quality adjusted

  18. Mineral replacement reactions and element mobilization

    Science.gov (United States)

    Putnis, Christine V.; Ruiz-Agudo, Encarnacion; King, Helen E.; Hövelmann, Jörn; Renard, François

    2016-04-01

    When a mineral is out of equilibrium with an aqueous fluid, reactions will take place in an attempt to reach a new equilibrium. Commonly in the Earth dissolution at a mineral-fluid interface initiates a coupled reaction involving dissolution and precipitation (Ruiz-Agudo et al., 2014). This is a ubiquitous reaction during such processes as metamorphism, metasomatism and weathering. When rock-forming minerals such as feldspars, olivine, pyroxenes are in contact with aqueous fluids (typically NaCl-rich) resultant new phases are formed and elements present in the parent mineral are released to the fluid and therefore mobilized for transport elsewhere. This has been shown in a number of systems such as the albitisation of feldspars (Hövelmann et al., 2010) when a Ca-bearing plagioclase is replaced by albite (NaAlSi3O8). However during this reaction not only is Ca released to the fluid but most other minor elements, such as Mg, Pb, rare earth elements amongst others, are almost totally mobilized and removed in solution. This interface-coupled dissolution-precipitation reaction has many implications for the redistributon of elements in the crust of the Earth. It is also of note that albitisation occurs often in areas of high mineralization, such as in the Curnamona Province in S. Australia (Au-Cu and Ag-Pb-Zn deposits) and the Bamble District of S. Norway. Secondly atomic force microscopy (AFM) has been used to image these reactions at a nanoscale, especially at the calcite-fluid interface, such as the formation of apatite from phosphate-bearing solutions, and the sequestration of toxic elements, eg., Se and As. References Ruiz-Agudo E., Putnis C.V., Putnis A. (2014) Coupled dissolution and precipitation at mineral-fluid interfaces. Chemical Geology, 383, 132-146. Putnis C.V. and Ruiz-Agudo E. (2013) The mineral-water interface: where minerals react with the environment. Elements, 9, 177-182. Hövelmann J., Putnis A., Geisler T., Schmidt B.C., Golla-Schindler U. (2009

  19. Gene therapy in ophthalmology.

    Science.gov (United States)

    Uthra, Satagopan; Kumaramanickavel, Govindasamy

    2009-09-01

    It has been more than a year since ophthalmologists and scientists under Dr. Robin Ali's team at the Moorsfield Eye Hospital and the Institute of Ophthalmology, University College London, successfully treated patients with a severely blinding disease, Leber's congenital amaurosis (LCA) using gene therapy. This success does not look to be transient, and this achievement in gene replacement therapy clinical trial for LCA has instilled hope in numerous families with patients suffering from this and similar retinal degenerative diseases, for whom restoration of lost vision has remained a distant dream so far. The encouragement that this success has given is expected to also lead to start of clinical trials for other blinding ocular diseases for which gene therapy experiments at the laboratory and animal levels have been successful. This article reviews the various studies that have led to the understanding of gene therapy outcomes in human ocular diseases and attempts to provide a brief sketch of successful clinical trials.

  20. Delivering enhanced testosterone replacement therapy through nanochannels.

    Science.gov (United States)

    Ferrati, Silvia; Nicolov, Eugenia; Bansal, Shyam; Zabre, Erika; Geninatti, Thomas; Ziemys, Arturas; Hudson, Lee; Ferrari, Mauro; Goodall, Randal; Khera, Mohit; Palapattu, Ganesh; Grattoni, Alessandro

    2015-02-18

    Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism.

  1. Acute Renal Replacement Therapy in Pediatrics

    Directory of Open Access Journals (Sweden)

    Rajit K. Basu

    2011-01-01

    Full Text Available Acute kidney injury (AKI independently increases morbidity and mortality in children admitted to the hospital. Renal replacement therapy (RRT is an essential therapy in the setting of AKI and fluid overload. The decision to initiate RRT is complex and often complicated by concerns related to patient hemodynamic and thermodynamic instability. The choice of which RRT modality to use depends on numerous criteria that are both patient and treatment center specific. Surprisingly, despite decades of use, no randomized, controlled trial study involving RRT in pediatrics has been performed. Because of these factors, clear-cut consensus is lacking regarding key questions surrounding RRT delivery. In this paper, we will summarize existing data concerning RRT use in children. We discuss the major modalities and the data-driven specifics of each, followed by controversies in RRT. As no standard of care is in widespread use for RRT in AKI or in multiorgan disease, we conclude in this paper that prospective studies of RRT are needed to identify best practice guidelines.

  2. Current concepts in total femoral replacement.

    Science.gov (United States)

    Ramanathan, Deepak; Siqueira, Marcelo Bp; Klika, Alison K; Higuera, Carlos A; Barsoum, Wael K; Joyce, Michael J

    2015-12-18

    Total femoral replacement (TFR) is a salvage arthroplasty procedure used as an alternative to lower limb amputation. Since its initial description in the mid-20(th) century, this procedure has been used in a variety of oncologic and non-oncologic indications. The most compelling advantage of TFR is the achievement of immediate fixation which permits early mobilization. It is anticipated that TFR will be increasingly performed as the rate of revision arthroplasty rises worldwide. The existing literature is mainly composed of a rather heterogeneous mix of retrospective case series and a wide assortment of case reports. Numerous TFR prostheses are currently available and the surgeon must understand the unique implications of each implant design. Long-term functional outcomes are dependent on adherence to proper technique and an appropriate physical therapy program for postoperative rehabilitation. Revision TFR is mainly performed for periprosthetic infection and the severe femoral bone loss associated with aseptic revisions. Depending on the likelihood of attaining infection clearance, it may sometimes be advisable to proceed directly to hip disarticulation without attempting salvage of the TFR. Other reported complications of TFR include hip joint instability, limb length discrepancy, device failure, component loosening, patellar maltracking and delayed wound healing. Further research is needed to better characterize the long-term functional outcomes and complications associated with this complex procedure.

  3. Can Smartwatches Replace Smartphones for Posture Tracking?

    Directory of Open Access Journals (Sweden)

    Bobak Mortazavi

    2015-10-01

    Full Text Available This paper introduces a human posture tracking platform to identify the human postures of sitting, standing or lying down, based on a smartwatch. This work develops such a system as a proof-of-concept study to investigate a smartwatch’s ability to be used in future remote health monitoring systems and applications. This work validates the smartwatches’ ability to track the posture of users accurately in a laboratory setting while reducing the sampling rate to potentially improve battery life, the first steps in verifying that such a system would work in future clinical settings. The algorithm developed classifies the transitions between three posture states of sitting, standing and lying down, by identifying these transition movements, as well as other movements that might be mistaken for these transitions. The system is trained and developed on a Samsung Galaxy Gear smartwatch, and the algorithm was validated through a leave-one-subject-out cross-validation of 20 subjects. The system can identify the appropriate transitions at only 10 Hz with an F-score of 0.930, indicating its ability to effectively replace smart phones, if needed.

  4. Can smartwatches replace smartphones for posture tracking?

    Science.gov (United States)

    Mortazavi, Bobak; Nemati, Ebrahim; VanderWall, Kristina; Flores-Rodriguez, Hector G; Cai, Jun Yu Jacinta; Lucier, Jessica; Naeim, Arash; Sarrafzadeh, Majid

    2015-10-22

    This paper introduces a human posture tracking platform to identify the human postures of sitting, standing or lying down, based on a smartwatch. This work develops such a system as a proof-of-concept study to investigate a smartwatch's ability to be used in future remote health monitoring systems and applications. This work validates the smartwatches' ability to track the posture of users accurately in a laboratory setting while reducing the sampling rate to potentially improve battery life, the first steps in verifying that such a system would work in future clinical settings. The algorithm developed classifies the transitions between three posture states of sitting, standing and lying down, by identifying these transition movements, as well as other movements that might be mistaken for these transitions. The system is trained and developed on a Samsung Galaxy Gear smartwatch, and the algorithm was validated through a leave-one-subject-out cross-validation of 20 subjects. The system can identify the appropriate transitions at only 10 Hz with an F-score of 0.930, indicating its ability to effectively replace smart phones, if needed.

  5. TOTAL ANKLE REPLACEMENT: WHY, WHEN AND HOW?

    Science.gov (United States)

    Bonasia, Davide Edoardo; Dettoni, Federico; Femino, John E; Phisitkul, Phinit; Germano, Margherita; Amendola, Annunziato

    2010-01-01

    Total ankle replacement (TAR) was first attempted in the 1970s, but poor results led to its being considered inferior to ankle fusion until the late 1980s and early 1990s. By that time, newer designs which more closely replicated the natural anatomy of the ankle, showed improved clinical outcomes.1 Currently, even though controversy still exists about the effectiveness of TAR compared to ankle fusion, TAR has shown promising mid-term results and should no longer be considered an experimental procedure. Factors related to improved TAR outcomes include: 1) better patient selection, 2) more precise knowledge and replication of ankle biomechanics, 3) the introduction of less-constrained designs with reduced bone resection and no need for cementation, and 4) greater awareness of soft-tissue balance and component alignment. When TAR is performed, a thorough knowledge of ankle anatomy, pathologic anatomy and biomechanics is needed along with a careful pre-operative plan. These are fundamental in obtaining durable and predictable outcomes. The aim of this paper is to outline these aspects through a literature review. PMID:21045984

  6. Total ankle replacement for posttraumatic arthritis

    Science.gov (United States)

    Weme, Rebecca A Nieuwe; van Solinge, Guido; N Doornberg, Job; Sierevelt, Inger; Haverkamp, Daniël; Doets, H Cornelis

    2015-01-01

    Background and purpose Most studies on total ankle replacement (TAR) have used a case mix of patients. We evaluated the outcome of TAR performed for end-stage arthritis either because of fracture or ligamentous injury. Patients and methods We prospectively followed 88 consecutive patients (50 postfracture ankles and 40 ankles with instability arthritis (2 bilateral)) who underwent TAR between 2001 and 2009. Mean follow-up for both groups was 5 years. Results Preoperative varus deformity of 10° or more was present in 23 ankles in the instability group. At 6 years, survival with revision or salvage fusion as an endpoint was 87% (95% CI: 74–99) in the postfracture group and 79% (95% CI: 63–94) in the instability group. Progressive periprosthetic osteolysis was seen in 23 ankles, and required salvage fusion in 6. The number of reoperations was similar in both groups. Clinical outcome, as assessed with 2 ankle scores and 2 questionnaires, showed good results and was similar at the latest follow-up. Interpretation The outcome was similar in the postfracture and instability groups and also similar to that reported in series including a case mix of patients. In contrast to earlier reports, preoperative frontal plane deformity in this series was not identified as a risk factor for failure. PMID:25772269

  7. Ulnar Head Replacement and Related Biomechanics

    Science.gov (United States)

    Sauerbier, Michael; Arsalan-Werner, Annika; Enderle, Elena; Vetter, Miriam; Vonier, Daniel

    2013-01-01

    A stable distal radioulnar joint (DRUJ) is mandatory for the function and load transmission in the wrist and forearm. Resectional salvage procedures such as the Darrach procedure, Bowers arthroplasty, and Sauvé-Kapandji procedure include the potential risk of radioulnar instability and impingement, which can lead to pain and weakness. Soft tissue stabilizing techniques have only limited success rates in solving these problems. In an attempt to stabilize the distal forearm mechanically following ulnar head resection, various endoprostheses have been developed to replace the ulnar head. The prostheses can be used for secondary treatment of failed ulnar head resection, but they can also achieve good results in the primary treatment of osteoarthritis of the DRUJ. Our experience consists of twenty-five patients (follow-up 30 months) with DRUJ osteoarthritis who were treated with an ulnar head prosthesis, with improvement in pain, range of motion, and grip strength. An ulnar head prosthesis should be considered as a treatment option for a painful DRUJ. PMID:24436786

  8. The quest for physiologic insulin replacement.

    Science.gov (United States)

    Owens, David R

    2004-11-01

    Historically, the objective of insulin replacement has been to simulate the 2 major components of insulin secretion in individuals without diabetes mellitus: the low-level basal secretion during the night and periods of fasting, and the prandial secretion in response to food intake. The variable pharmacokinetic and pharmacodynamic characteristics of conventional insulin preparations have made mimicking these physiologic profiles virtually impossible. Balancing the effects of diet, exercise, and the numerous factors contributing to intra- and inter-individual variations in insulin absorption and action, such as type, site of injection, and dosage of insulin, while avoiding the very serious side effect of hypoglycemia in seeking normoglycemia, presents a further challenge. Recently, these limitations have been addressed by recombinant DNA-mediated development of insulin analogues, such as rapid-acting insulin lispro, aspart and glulisine, and the long-acting insulin preparations, insulin glargine and detemir. The molecular structures of these analogues have produced time-action profiles that better approach prandial and basal insulin secretion, thus allowing for easier, safer, and more flexible treatment regimens.

  9. MRI after patellofemoral replacement: The preserved compartments

    Energy Technology Data Exchange (ETDEWEB)

    Heyse, Thomas J., E-mail: heyse@med.uni-marburg.de [Department of Orthopedics and Rheumatology, University Hospital Marburg, Baldingerstrasse, 35043 Marburg (Germany); Figiel, Jens [Department of Radiology, University Hospital Marburg, Marburg (Germany); Hähnlein, Ulrike [Department of Orthopedics and Rheumatology, University Hospital Marburg, Baldingerstrasse, 35043 Marburg (Germany); Timmesfeld, Nina [Institute for Medical Biometry and Epidemiology, Marburg (Germany); Lakemeier, Stefan; Schofer, Markus D.; Fuchs-Winkelmann, Susanne; Efe, Turgay [Department of Orthopedics and Rheumatology, University Hospital Marburg, Baldingerstrasse, 35043 Marburg (Germany)

    2012-09-15

    Introduction: The aim of this study was to assess the reproducibility of magnet resonance imaging (MRI) analysis of preserved anatomic structures of the knee after patellofemoral replacement (PFR). It was hypothesized that evaluation of cartilage, ligaments, meniscus and tendons would result in high inter-observer reliability after PFR. Material and methods: MRI, tailored to reduce metallic artefacts of the knee, after PFR was performed in seven patients. Two independent investigators evaluated cartilage, menisci, collateral and cruciate ligaments, the quadriceps and patellar tendons and the presence of joint effusion. The reviewers used a five-point scale to give a degree of confidence to their evaluation of each parameter. Inter-observer reliability was determined by calculation of Cohen's Kappas. Results: Artefact provoked by the implants was not observed. For all assessed structures, there was excellent inter-observer reliability, with high Cohen's Kappas. There were also high levels of inter-observer agreement and observer confidence in the evaluation of cartilage, meniscus, tendons, ligaments and joint effusion. Conclusion: Tailored MRI allows reproducible analysis of the preserved knee joint structures after PFR. It might prove helpful in assessment of painful knee joints after PFR.

  10. MMIC Replacement for Gunn Diode Oscillators

    Science.gov (United States)

    Crowe, Thomas W.; Porterfield, David

    2011-01-01

    An all-solid-state replacement for high-frequency Gunn diode oscillators (GDOs) has been proposed for use in NASA s millimeter- and submillimeter-wave sensing instruments. Highly developed microwave oscillators are used to achieve a low-noise and highly stable reference signal in the 10-40-GHz band. Compact amplifiers and high-power frequency multipliers extend the signal to the 100-500-GHz band with minimal added phase noise and output power sufficient for NASA missions. This technology can achieve improved output power and frequency agility, while maintaining phase noise and stability comparable to other GDOs. Additional developments of the technology include: a frequency quadrupler to 145 GHz with 18 percent efficiency and 15 percent fixed tuned bandwidth; frequency doublers featuring 124, 240, and 480 GHz; an integrated 874-GHz subharmonic mixer with a mixer noise temperature of 3,000 K DSB (double sideband) and mixer conversion loss of 11.8 dB DSB; a high-efficiency frequency tripler design with peak output power of 23 mW and 14 mW, and efficiency of 16 and 13 percent, respectively; millimeter-wave integrated circuit (MMIC) power amplifiers to the 30-40 GHz band with high DC power efficiency; and an 874-GHz radiometer suitable for airborne observation with state-of-the-art sensitivity at room temperature and less than 5 W of total power consumption.

  11. [Renal replacement therapy for refractory heart failure].

    Science.gov (United States)

    Schwenger, V; Remppis, A B

    2012-07-01

    After broad cardiological and nephrological evaluation and consideration of optimal conservative options according to national and international guidelines, renal replacement therapy might be helpful in patients with refractory heart failure even if they are not dialysis-dependent. This is even more important as renal failure is a strong predictor for mortality in patients with severe congestive heart failure (CHF) and CHF is one of the fastest growing morbidities in western countries. Although peritoneal dialysis (PD) is frequently used in patients with CHF its role remains unclear. Acute chronic volume overload in refractory CHF is still an unresolved clinical problem. In patients with acute heart and renal failure with need of management in an intensive care unit, extracorporeal ultrafiltration or a dialysis modality should be preferred. In patients with chronic refractory CHF, volume overload and renal failure, peritoneal dialysis should be the therapy of choice. Due to the limited data available, treatment and outcome parameters should be recorded in the registry of the German Society of Nephrology (http://www.herz-niere.de).

  12. Replacement of Swiss "Attestations de fonctions"

    CERN Multimedia

    DG Unit

    2009-01-01

    The Swiss Permanent Mission has informed CERN that the "attestations de fonctions" issued to certain members of the personnel and the "attestations" issued to their family members will gradually be replaced by P-type "cartes de légitimation" (see specimen copies in the printed Bulletin). This card’s name, together with its more contemporary design compared with old-style "Attestations" issued in the 1970s, will make the holder’s daily life much easier, e.g. when crossing borders, renting accommodation or setting up a telephone line. The Users Office (PH Department) and the Cards Office (HR Department), which are responsible for handling requests for "cartes de légitimation", will provide information in due course on how they intend to organise the exchange of "attestations" (priority will be given to residents of Switzerland, in particular those requiring a visa for the Schengen area). In this context, we remind you that the Swiss Permanent Mission is systematically in...

  13. Cortical bone total ossicular replacement prosthesis

    Directory of Open Access Journals (Sweden)

    Manu Malhotra

    2014-01-01

    Full Text Available Objectives: Evaluate an autologous cortical bone total ossicular replacement prosthesis (B TORP made of cortical bone for cost effective and sustainable hearing results. Materials and Methods: A prospective study was undertaken in the patients who underwent tympanoplasty with new B-TORP from January 2011 to December 2011. All patients had an absent superstructure of the stapes and long process of the incus due to chronic otitis media. Totally 40 patients were evaluated. Hearing results were evaluated using four-frequency average pure tone air conduction and air-bone gap (ABG measured at 0.5, 1, 2, and 3 kHz after a period of 12 months. Pre- and post-operative continuous variables were compared using a paired t-test and data from unequal groups were assessed for significant differences using unpaired t-test. Results: Successful rehabilitation of the ABG to 20 dB or less was achieved in 95% of patients. Overall mean improvement in ABG was 25.8 ± 5.6 dB, which was statistically significant (t = 26.8, P 0.5. Conclusion: The new autologous B-TORP provides sustainable hearing improvement and is bio-compatible, stable, and magnetic resonance imaging compatible.

  14. Flash-Aware Page Replacement Algorithm

    Directory of Open Access Journals (Sweden)

    Guangxia Xu

    2014-01-01

    Full Text Available Due to the limited main memory resource of consumer electronics equipped with NAND flash memory as storage device, an efficient page replacement algorithm called FAPRA is proposed for NAND flash memory in the light of its inherent characteristics. FAPRA introduces an efficient victim page selection scheme taking into account the benefit-to-cost ratio for evicting each victim page candidate and the combined recency and frequency value, as well as the erase count of the block to which each page belongs. Since the dirty victim page often contains clean data that exist in both the main memory and the NAND flash memory based storage device, FAPRA only writes the dirty data within the victim page back to the NAND flash memory based storage device in order to reduce the redundant write operations. We conduct a series of trace-driven simulations and experimental results show that our proposed FAPRA algorithm outperforms the state-of-the-art algorithms in terms of page hit ratio, the number of write operations, runtime, and the degree of wear leveling.

  15. Testosterone Replacement Therapy: The Emperor's New Clothes.

    Science.gov (United States)

    Sansone, Andrea; Sansone, Massimiliano; Lenzi, Andrea; Romanelli, Francesco

    2017-02-01

    The mean age of the world population has steadily increased in the last decades, as a result of increased life expectancy and reduced birth rate. Global aging has led to a greater worldwide cost for healthcare: hormonal alterations contribute to the pathogenesis of several conditions and might cause a significant reduction in the perceived sense of well-being. Menopause is archetypal of hormonal alterations occurring during aging: in males, sex hormones do not decrease abruptly, yet testosterone levels decrease steadily and continuously during aging, ultimately resulting in late-onset hypogonadism. Treatment of this condition might mitigate most symptoms; however, testosterone replacement therapy (TRT) should be prescribed only in selected patients and it should not be considered as an antiaging treatment. In recent years, different authors have questioned health risks associated with testosterone treatment; while position statements from many scientific societies seem to be reassuring, the Food and Drug Administration has issued a warning in regard to the possible side effects of this therapy. We aim to review recent controversies and discoveries in regard to TRT.

  16. Licensing of the Australian replacement research reactor

    Energy Technology Data Exchange (ETDEWEB)

    Garea, Veronica B. [INVAP S.E., San Carlos de Bariloche (Argentina)

    2002-07-01

    The Australian Nuclear Science and Technology Organisation (ANSTO)'s Replacement Research Reactor has been submitted to a comprehensive licensing process of which peer review has been a fundamental part. Following Australian Regulation, an application for a site licence was the first step supported by an Environmental Impact Statement approved by The Minister for the Environment and Heritage, and a Reference Accident Analysis. After the site licence had been granted and the contract awarded to the Designer and Constructor, INVAP S.E:, a 2500 page Preliminary Safety Analysis Report was submitted by ANSTO to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA), which conducted its review. ARPANSA requested that the PSAR be also reviewed by an experts mission from the International Atomic Energy Agency. The PSAR was also reviewed by the Argentine Regulatory Body, it was submitted to public examination in Australia and it was reviewed by international experts hired as consultants by several Australian organisations. A public forum was also held in Sydney. The Regulator, the applicant and the Designer-Constructor maintained constant interaction during the whole process, so that questions, comments and observations that arose from the review of the PSAR were fed back to the designers. This process allowed for a robust, safe design enriched by the results of the safety analysis and review process. (author)

  17. Process optimized minimally invasive total hip replacement

    Directory of Open Access Journals (Sweden)

    Philipp Gebel

    2012-02-01

    Full Text Available The purpose of this study was to analyse a new concept of using the the minimally invasive direct anterior approach (DAA in total hip replacement (THR in combination with the leg positioner (Rotex- Table and a modified retractor system (Condor. We evaluated retrospectively the first 100 primary THR operated with the new concept between 2009 and 2010, regarding operation data, radiological and clinical outcome (HOOS. All surgeries were perfomed in a standardized operation technique including navigation. The average age of the patients was 68 years (37 to 92 years, with a mean BMI of 26.5 (17 to 43. The mean time of surgery was 80 min. (55 to 130 min. The blood loss showed an average of 511.5 mL (200 to 1000 mL. No intra-operative complications occurred. The postoperative complication rate was 6%. The HOOS increased from 43 points pre-operatively to 90 (max 100 points 3 months after surgery. The radiological analysis showed an average cup inclination of 43° and a leg length discrepancy in a range of +/- 5 mm in 99%. The presented technique led to excellent clinic results, showed low complication rates and allowed correct implant positions although manpower was saved.

  18. Antimicrobial dosing in acute renal replacement.

    Science.gov (United States)

    Fissell, William H

    2013-01-01

    Acute kidney injury (AKI) is a common problem in hospitalized patients and is associated with significant morbidity and mortality. Two large trials showed no benefit from increased doses of renal replacement therapy (RRT) despite previous clinical data suggesting that increased clearance from RRT has beneficial effects. Since infection is the leading cause of death in AKI, my group and others hypothesized that increased RRT antibiotic clearance might create a competing morbidity. The data from my group, as well as those of other groups, show that many patients are underdosed when routine "1 size fits all" antibiotic dosing is used in patients with AKI receiving continuous RRT (CRRT). Here, concepts of drug distribution and clearance in AKI are briefly discussed and then 1 antibiotic (piperacillin) is discussed in depth to illustrate the challenges in applying the medical literature to clinical practice. The fact that published data on drug dosing in AKI and dialysis reflect the evolution of practice patterns and often do not apply to present prescribing habits is also discussed. A more general approach to drug dosing facilitates situation-specific prescribing by the nephrologist and critical care specialist. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  19. Drug dosing during continuous renal replacement therapies.

    Science.gov (United States)

    Thompson, A Jill

    2008-04-01

    Continuous renal replacement therapies (CRRT) are used to manage fluid overload and/or renal failure. The continuous nature of the fluid and solute removal has less impact on hemodynamic variables in critically ill patients, making CRRT preferred over intermittent hemodialysis for some patients in the intensive care arena. The impact of CRRT on drug removal is variable depending on the CRRT modality, the ultrafiltrate and dialysate flow rates, the filter, and the patient's residual renal function; all of these may change from patient to patient or even in the same patient depending on the clinical status. However, CRRT modalities are generally more efficient than intermittent hemodialysis at drug removal, in some cases approximating or even exceeding normal renal function, resulting in a significant risk of subtherapeutic dosing if conventional hemodialysis dosing recommendations are followed. This annotated bibliography provides a summary of publications analyzing drug removal during CRRT, including CRRT settings and drug clearance values found in each study. Caution is warranted as findings from one study may not be generalizable to all patients due to the many factors that influence drug removal. Serum drug concentrations should be monitored when available, and patient clinical status is exceedingly important for following expected and unexpected responses to drug therapies. Reviews on general drug dosing calculations in CRRT are available elsewhere.

  20. Drug dosing during continuous renal replacement therapy.

    Science.gov (United States)

    Churchwell, Mariann D; Mueller, Bruce A

    2009-01-01

    Continuous renal replacement therapy (CRRT) has given clinicians an important option in the care of critically ill patients. The slow and continuous dialysate and ultrafiltrate flow rates that are employed with CRRT can yield drug clearances similar to an analogous glomerular filtration rate of the native kidneys. Advantages such as superior volume control, excellent metabolic control, and hemodynamic tolerance by critically ill patients are well documented, but an understanding of drug dosing for CRRT is still a bit of a mystery. Although some pharmaceutical companies have dedicated postmarket research in this direction, many pharmaceutical companies have chosen not to pursue this information as it is not mandated and represents a relatively small part of their market. This lack of valuable information has created many challenges in the care of the critically ill patient as intermittent hemodialysis drug dosing recommendations cannot be extrapolated to CRRT. This drug dosing review will highlight factors that clinicians should consider when determining a pharmacotherapy regimen for a patient receiving CRRT.

  1. Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc

    Science.gov (United States)

    Ahtiainen, Katja; Mauno, Jari; Ellä, Ville; Hagström, Jaana; Lindqvist, Christian; Miettinen, Susanna; Ylikomi, Timo; Kellomäki, Minna; Seppänen, Riitta

    2013-01-01

    The temporomandibular joint (TMJ) disc lacks functional replacement after discectomy. We investigated tissue-engineered bilayer polylactide (PLA) discs and autologous adipose stem cells (ASCs) as a potential replacement for the TMJ disc. These ASC discs were pre-cultured either in control or in differentiation medium, including transforming growth factor (TGF)-β1 for one week. Prior to implantation, expression of fibrocartilaginous genes was measured by qRT-PCR. The control and differentiated ASC discs were implanted, respectively, in the right and left TMJs of rabbits for six (n = 5) and 12 months (n = 5). Thereafter, the excised TMJ areas were examined with cone beam computed tomography (CBCT) and histology. No signs of infection, inflammation or foreign body reactions were detected at histology, whereas chronic arthrosis and considerable condylar hypertrophy were observed in all operated joints at CBCT. The left condyle treated with the differentiated ASC discs appeared consistently smoother and more sclerotic than the right condyle. The ASC disc replacement resulted in dislocation and morphological changes in the rabbit TMJ. The ASC discs pre-treated with TGF-β1 enhanced the condylar integrity. While adverse tissue reactions were not shown, the authors suggest that with improved attachment and design, the PLA disc and biomaterial itself would hold potential for TMJ disc replacement. PMID:23720535

  2. Autologous adipose stem cells and polylactide discs in the replacement of the rabbit temporomandibular joint disc.

    Science.gov (United States)

    Ahtiainen, Katja; Mauno, Jari; Ellä, Ville; Hagström, Jaana; Lindqvist, Christian; Miettinen, Susanna; Ylikomi, Timo; Kellomäki, Minna; Seppänen, Riitta

    2013-08-06

    The temporomandibular joint (TMJ) disc lacks functional replacement after discectomy. We investigated tissue-engineered bilayer polylactide (PLA) discs and autologous adipose stem cells (ASCs) as a potential replacement for the TMJ disc. These ASC discs were pre-cultured either in control or in differentiation medium, including transforming growth factor (TGF)-β1 for one week. Prior to implantation, expression of fibrocartilaginous genes was measured by qRT-PCR. The control and differentiated ASC discs were implanted, respectively, in the right and left TMJs of rabbits for six (n = 5) and 12 months (n = 5). Thereafter, the excised TMJ areas were examined with cone beam computed tomography (CBCT) and histology. No signs of infection, inflammation or foreign body reactions were detected at histology, whereas chronic arthrosis and considerable condylar hypertrophy were observed in all operated joints at CBCT. The left condyle treated with the differentiated ASC discs appeared consistently smoother and more sclerotic than the right condyle. The ASC disc replacement resulted in dislocation and morphological changes in the rabbit TMJ. The ASC discs pre-treated with TGF-β1 enhanced the condylar integrity. While adverse tissue reactions were not shown, the authors suggest that with improved attachment and design, the PLA disc and biomaterial itself would hold potential for TMJ disc replacement.

  3. 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...

  4. Principles of human joint replacement design and clinical application

    CERN Document Server

    Buechel, Frederick F

    2015-01-01

    This book is written for the users and designers of joint replacements. In its second extended edition it conveys to the reader the knowledge accumulated by the authors during their forty 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 describes the design methodology now required for joint replacement in the USA and EU countries. The remaining chapters provide a history of joint replacement, an evaluation of earlier and current devices and sample case hist...

  5. Dual mobility total hip replacement in a high risk population

    Science.gov (United States)

    Luthra, Jatinder Singh; Al Riyami, Amur; Allami, Mohamad Kasim

    2016-01-01

    Objective: The purpose of the study was to evaluate results of dual mobility total replacement in a high risk population who take hip into hyperflexed position while sitting and praying on the floor. Method: The study included 65 (35 primary total replacement and 30 complex total hip replacement) cases of total hip replacement using avantage privilege dual mobility cup system from biomet. A cemented acetabular component and on femoral side a bimetric stem, either cemented or uncemented used depending on the canal type. Ten cases were examined fluoroscopically in follow up. Result: There was dislocation in one patient undergoing complex hip replacement. Fluoroscopy study showed no impingement between the neck of prosthesis and acetabular shell at extremes of all movements. Conclusion: The prevalence of dislocation is low in our high risk population and we consider it preferred concept for patients undergoing complex total hip replacement. PMID:27924742

  6. Dual mobility total hip replacement in a high risk population

    Directory of Open Access Journals (Sweden)

    Luthra Jatinder Singh

    2016-01-01

    Full Text Available Objective: The purpose of the study was to evaluate results of dual mobility total replacement in a high risk population who take hip into hyperflexed position while sitting and praying on the floor. Method: The study included 65 (35 primary total replacement and 30 complex total hip replacement cases of total hip replacement using avantage privilege dual mobility cup system from biomet. A cemented acetabular component and on femoral side a bimetric stem, either cemented or uncemented used depending on the canal type. Ten cases were examined fluoroscopically in follow up. Result: There was dislocation in one patient undergoing complex hip replacement. Fluoroscopy study showed no impingement between the neck of prosthesis and acetabular shell at extremes of all movements. Conclusion: The prevalence of dislocation is low in our high risk population and we consider it preferred concept for patients undergoing complex total hip replacement.

  7. New Firm Performance and the Replacement of Founder-CEOs

    DEFF Research Database (Denmark)

    Chen, Jing; Thompson, Peter

    2015-01-01

    We study the causes and consequences of the replacement of founder-CEOs in a sample of 4,172 Danish start-ups. We propose that founder-CEO replacement is driven in part by mismatches between business quality and founder ability. Our framework suggests that replacements are more likely among the w...... considerably faster. Our empirical results are consistent with these proposed predictions. Copyright © 2015 Strategic Management Society....... the worst- and best-performing firms, with low (high)-ability founders replaced by manager with higher (lower) ability. Replacement is not unambiguously associated with better subsequent performance. Firms that replaced the founder were much more likely to fail, but the surviving firms among them grew...

  8. The Comparative study of Automated Face replacement Techniques for Video

    Directory of Open Access Journals (Sweden)

    Harmesh Sanghvi

    2014-03-01

    Full Text Available For entertaining purposes, a computerized special effect referred to as “morphing” has enlarged huge attention and face replacement is one of the interesting tasks. Face replacement in video is a useful application in the amusement and special effect industries. Though various techniques for face replacement have been developed for single image and generally applied in animation and morphing, there are few mechanisms to spread out these techniques to handle videos automatically. Face replacement in video automatically is not only a fascinating application, but a challenging problem. For face replacement in video, the frame-by-frame manipulation process using the software is often time consuming and labor-intensive. Hence, the paper compares numerous latest Automatic face replacement techniques in video to understand the various problems to be solved, their shortcomings and benefits over others.

  9. 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.

  10. Unusual redo mitral valve replacement for bleeding in Glanzmann thrombasthenia.

    Science.gov (United States)

    Garcia-Villarreal, Ovidio A; Fernández-Ceseña, Ernesto; Solano-Ricardi, Mercedes; Aguilar-García, Alma L; Vega-Hernández, Raquel; Del Angel-Soto, Gustavo

    2016-01-01

    We report the case of 23-year-old man with mitral valve regurgitation and Glanzmann thrombasthenia, who underwent mechanical mitral valve replacement. Warfarin therapy was devastating, causing bilateral hemothorax, pericardial effusion, gastrointestinal bleeding, and hematuria. Redo mitral valve replacement with a biological prosthesis was required to resolve this critical situation. To our knowledge, this is the first report of mitral valve replacement in Glanzmann thrombasthenia, highlighting the danger of oral anticoagulation in this pathology.

  11. UK annuity rates and pension replacement ratios 1957-2002

    OpenAIRE

    Cannon, Edmund; Tonks, Ian

    2003-01-01

    This paper constructs a time series of annuity rates in the UK for 1957-2002, and examines the pricing of UK annuities, and the relationship between the accumulation and decumulation phases of a defined contribution pension scheme by focusing on the properties of the pension replacement ratio. Using data on annuity returns and the returns on other financial assets, the paper simulates replacement ratios, to build up a frequency distribution of the pension replacement ratio for a UK individual...

  12. Arthroscopic Management of Complications Following Total Ankle Replacement.

    Science.gov (United States)

    Lui, Tun Hing; Roukis, Thomas S

    2015-10-01

    There is great potential of managing the complications of total ankle replacement arthroscopically and endoscopically, and these procedures can be summarized into 3 groups. Group 1 includes procedures of the ankle joint proper with close proximity to the articular components of the total ankle replacement. Group 2 includes procedures of the tibia and talus with close proximity to the nonarticular parts of the total ankle replacement. Group 3 includes procedures that are away from the total ankle replacement. However, these remain master arthroscopist procedures and should be performed by foot and ankle surgeons who perform them with regularity.

  13. Total hip and total knee replacement: preoperative nursing management.

    Science.gov (United States)

    Lucas, Brian

    Total hip replacement (THR) and total knee replacement (TKR) surgery are carried out for the relief of hip or knee pain, usually caused by osteoarthritis. This is the first of two articles on THR and TKR. It will outline the different types of replacement used in lower limb joint replacement surgery. Preparation of patients for surgery requires attention to physical, psychological and social factors and these are explored in detail. The organization of services along the patient pathway to ensure comprehensive preparation is considered and the nursing role highlighted. The second article, to be published in the next issue, will discuss recovery and rehabilitation from THR and TKR surgery.

  14. Mitochondrial replacement techniques: egg donation, genealogy and eugenics.

    Science.gov (United States)

    Palacios-González, César

    2016-03-01

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

  15. Volume of Requests for Internet Medicare Replacement Cards

    Data.gov (United States)

    Social Security Administration — This dataset provides monthly volumes at the national level from federal fiscal year 2008 onwards for Internet Medicare Replacement Card. The dataset includes only...

  16. Replacing fallow by cover crops: economic sustainability

    Science.gov (United States)

    Gabriel, José Luis; Garrido, Alberto; Quemada, Miguel

    2013-04-01

    Replacing fallow by cover crops in intensive fertilized systems has been demonstrated as an efficient tool for reducing nitrate leaching. However, despite the evident environmental services provided and the range of agronomic benefits documented in the literature, farmers' adoption of this new technology is still limited because they are either unwilling or unable, although adoption reluctance is frequently rooted in low economic profitability, low water se efficiency or poor knowledge. Economic analyses permit a comparison between the profit that farmers obtain from agricultural products and the cost of adopting specific agricultural techniques. The goal of this study was to evaluate the economic impact of replacing the usual winter fallow with cover crops (barley (Hordeum vulgare L., cv. Vanessa), vetch (Vicia villosa L., cv. Vereda) and rapeseed (Brassica napus L., cv. Licapo)) in irrigated maize systems and variable Mediterranean weather conditions using stochastic Monte-Carlo simulations of key farms' financial performance indicators. The three scenarios studied for each cover crop were: i) just leaving the cover crop residue in the ground, ii) leaving the cover crop residue but reduce following maize fertilization according to the N available from the previous cover crop and iii) selling the cover crop residue for animal feeding. All the scenarios were compared with respect to a typical maize-fallow rotation. With observed data from six different years and in various field trials, looking for different weather conditions, probability distribution functions of maize yield, cover crop biomass production and N fertilizer saving was fitted. Based in statistical sources maize grain price, different forage prices and the cost of fertilizer were fitted to probability distribution functions too. As result, introducing a cover crop involved extra costs with respect to fallow as the initial investment, because new seed, herbicide or extra field operations. Additional

  17. Can postmortem fetal MR imaging replace autopsy?

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jeong Yeon; Song, Mi Jin [Sungkyunkwan Univ. School of Medicine, Seoul (Korea, Republic of); Kim, Seoung Hyup [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-02-01

    The purposes of this study were to compare postmortem fetal MRI findings with autopsy findings and to assess whether postmortem MRI can replace autopsy. The study group consisted of 13 stillborn fetuses, seven that died immediately after birth, and five terminated because of anomalies seen on prenatal sonograms. A total 17 were male, and eight were female, and their gestational ages were from 20 to 41 (average;28.2) weeks. Spin-echo T1-and T2-weighted axial, sagittal, and coronal MR images were obtained, and autopsy findings were divided into major and minor. A major finding was defined as an anomaly or syndrome which caused fetal death or termination of the pregnancy: minor findings were classified, on the basis of gross inspection, as internal or external. MR images were retrospectively analyzed by two radiologists unaware of the autopsy findings, and by comparison with these, the postmortem MRI detection rates for major and minor findings was then determined. In seven of 25 fetuses, MR imaging revealed major findings, a dietction rate of 100%. There were two cases of anencephaly, two of trisomy-18, and one each of hydrops fetalis with large cystic hygroma, diaphragmatic hernia, and Dandy-Walker malformation. Twenty-three of 60 minor findings (38.3%) were detected by MRI. The detection rates for external and internal findings were 29.6%(8/27) and 45.5%(15/33), respectively. Although a limitation of our study is the low detection rate for minor findings, postmortem fetal MRI may help diagnose the major cause of fetal death.

  18. Why Lumbar Artificial Disk Replacements (LADRs) Fail.

    Science.gov (United States)

    Pettine, Kenneth; Ryu, Robert; Techy, Fernando

    2017-07-01

    A retrospective review of prospectively collected data. To determine why artificial disk replacements (ADRs) fail by examining results of 91 patients in FDA studies performed at a single investigational device exemption (IDE) site with minimum 2-year follow-up. Patients following lumbar ADR generally achieve their 24-month follow-up results at 3 months postoperatively. Every patient undergoing ADR at 1 IDE site by 2 surgeons was evaluated for clinical success. Failure was defined as Maverick, 25 patients; Charité, 31 patients; and Kineflex, 35 patients. All procedures were 1-level operations performed at L4-L5 or L5-S1. Demographics and inclusion/exclusion criteria were similar and will be discussed. Overall clinical failure occurred in 26% (24 of 91 patients) at 2-year follow-up. Clinical failure occurred in: 28% (Maverick) (7 of 25 patients), 39% (Charité) (12 of 31 patients), and 14% (Kineflex) (5 of 35 patients). Causes of failure included facet pathology, 50% of failure patients (12 of 24). Implant complications occurred in 5% of total patients and 21% of failure patients (5 of 24). Only 5 patients went from a success to failure after 3 months. Only 1 patient went from a failure to success after a facet rhizotomy 1 year after ADR. Seventy-four percent of patients after ADR met strict clinical success after 2-year follow-up. The clinical success versus failure rate did not change from their 3-month follow-up in 85 of the 91 patients (93%). Overall clinical success may be improved most by patient selection and implant type.

  19. Investigation of Biodentine as dentine replacement material.

    Science.gov (United States)

    Camilleri, Josette

    2013-07-01

    Biodentine was compared to glass ionomer and resin modified cements in an "open sandwich" restoration. Fuji IX, Vitrebond and Biodentine were characterised using various techniques. The effect of etching with 35% phosphoric acid was investigated by assessment of surface topography, Fourier transform infrared (FT-IR) spectroscopy, surface micro-hardness and micro-leakage using tagged carboxylated-modified fluorescent microspheres and tracing the presence of these particles with a confocal microscope. Acid etching resulted in erosion of the material surface with exposure of the glass particles in the glass ionomer-based materials. Biodentine exhibited a reduction in the chlorine peak and the calcium-silicon ratio. There was no difference in the micro-hardness in etched and un-etched materials. The FT-IR plots did not show any chemical changes caused by etching for all the materials investigated. Both Vitrebond and Fuji IX exhibited no leakage at the dentine to material interface while Biodentine exhibited leakage both when it was etched and also when the surface was left unprepared. The sandwich technique was effective and prevented micro-leakage with glass ionomer-based materials but micro-leakage occurred with Biodentine. Biodentine demonstrated both structural and chemical changes when etched with 37% phosphoric acid. Biodentine exhibited a lower calcium to silicon ratio and a reduction in the chloride peak height when etched. When used as a dentine replacement material in the sandwich technique overlayed with composite, significant leakage occurred at the dentine to material interface. On the other hand materials based on glass ionomer cement were etched successfully and no chemical and physical changes or micro-leakage were detected when the materials were used as bases under composite restorations. The micro-hardness of all the materials was unaffected by etching. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Hormone Replacement Therapy After Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mueck AO

    2008-01-01

    Full Text Available So far, patient samples in all studies investigating hormone replacement therapy (HRT after breast cancer have been small.Therefore, HRT should only be used if alternatives such as specifically not contraindicated phytopreparations or selective sero-tonin reuptake inhibitors (SSRIs are not effective. This is primarily due to forensic reasons since clinical data on the risk ofalternatives (based on present evidence are even more sparse. Regarding HRT, four prospective randomized studies and at least15 observational studies after breast cancer are available. Only the HABITS study shows an increased risk of relapse. The authorssuggest that this is probably associated with the relatively high number of patients with HRT treatment after ER-positive cancersas well as due to the preferred use of estrogen/progestin-combined preparations. Based on the results of the randomized pla-cebo-controlled study Women’s Health Initiative (WHI as well as of at least 12 observational studies, the progestin componentseems to be mainly responsible for the probability of increased diagnosis frequency of primary breast cancer. However, no dataare available on the impact of progestin on the use of combined HRT after breast cancer. However, also with estrogen only anincreased risk of relapse must be expected and patients should be informed about it. This has to be concluded due to biologicalplausibility and observational studies although the estrogen-only arm in WHI did not show any increased primary risk. Thus, anyform of HRT should only be performed in exceptional cases, and treatment duration should be as short as possible with thelowest effective dose.

  1. Activation of Complement Following Total Hip Replacement.

    Science.gov (United States)

    Thordardottir, S; Vikingsdottir, T; Bjarnadottir, H; Jonsson, H; Gudbjornsson, B

    2016-03-01

    The aim of this study was to investigate whether complement activation, via the classical and alternative pathways, occurs following a cemented total hip replacement (THR) surgery due to osteoarthritis. Blood samples were collected systematically from 12 patients - six male and six women, with a median age of 75 (range: 59-90 years) - preoperatively, 6 h post-operatively and on the first, second and third post-operative day. Total function of classical (CH50) and alternative pathways (AH50) was evaluated, along with the determination of serum concentrations of the complement proteins C3, C4, C3d, the soluble terminal complement complex (sTCC) sC5b-9, as well as C-reactive protein (CRP) and albumin. Measurements of CRP and albumin levels elucidated a marked inflammatory response following the operation. The CH50, AH50 and C3 and C4 levels were significantly lower 6 h after the surgery compared with the preoperative levels, but elevated above the preoperative levels during the following 3 days. The complement activation product C3d levels increased continually during the whole observation period, from 13.5 AU/ml (range: 8-19 AU/ml) preoperative to 20 AU/ml (range: 12-34 AU/ml) on the third post-operative day. Furthermore, we observed an increase in the sC5b-9 levels between the preoperative and the third post-operative day. These results demonstrate a significant activation of the complement system following cemented THR. Further studies are needed to elucidate the time frame and the pathogenic role of this observed complement activation.

  2. Blood donation and testosterone replacement therapy.

    Science.gov (United States)

    Chin-Yee, Benjamin; Lazo-Langner, Alejandro; Butler-Foster, Terrie; Hsia, Cyrus; Chin-Yee, Ian

    2017-03-01

    Polycythemia is the most common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events. Current Canadian guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L). This threshold has been interpreted by some physicians and patients to indicate the need for phlebotomy or blood donation while on TRT. We reviewed all male blood donors in Southwestern Ontario at Canadian Blood Services from December 2013 to March 2016 who self-identified or were found on donor screening to be on TRT. Hemoglobin concentration was measured at the time of donation or clinic visit and with each subsequent appointment in repeat donors. We identified 39 patients on TRT who presented for blood donation over a 2-year period. The mean hemoglobin level at all clinic visits was 173 g/L (range, 134-205 g/L; n = 108). Hemoglobin concentrations of 180 g/L or more (calculated hematocrit, ≥54%) were measured at 25% of appointments. Of the 27 repeat donors, 12 (44%) had persistently elevated hemoglobin levels (≥180 g/L) at subsequent donations. Hemoglobin concentrations were elevated in donors on TRT, and significant numbers had hemoglobin levels above those recommended by current guidelines. These data also suggest that repeat blood donation was insufficient to maintain a hematocrit below 54%. Our findings raise concerns about the persistent risk of vascular events in these donors, particularly when coupled with the misperception by patients and health care providers that donation has reduced or eliminated the risks of TRT-induced polycythemia. © 2017 AABB.

  3. Transcriptional changes during neuronal death and replacement in the olfactory epithelium.

    Science.gov (United States)

    Shetty, Ranjit S; Bose, Soma C; Nickell, Melissa D; McIntyre, Jeremy C; Hardin, Debra H; Harris, Andrew M; McClintock, Timothy S

    2005-12-01

    The olfactory epithelium has the unusual ability to replace its neurons.We forced replacement of mouse olfactory sensory neurons by bulbectomy. Microarray, bioinformatics, and in situ hybridization techniques detected a rapid shift in favor of pro-apoptotic proteins, a progressive immune response by macrophages and dendritic cells, and identified or predicted 439 mRNAs enriched in olfactory sensory neurons, including gene silencing factors and sperm flagellar proteins. Transcripts encoding cell cycle regulators, axonogenesis proteins, and transcription factors and signaling proteins that promote proliferation and differentiation were increased at 5-7 days after bulbectomy and were expressed by basal progenitor cells or immature neurons. The transcription factors included Nhlhl, Hes6, Lmycl, c-Myc, Mxd4, Idl,Nmycl, Cited2, c-Myb, Mybll, Tead2, Dpl, Gata2, Lmol, and Soxll. The data reveal significant similarities with embryonic neurogenesis and make several mechanistic predictions, including the roles of the transcription factors in the olfactory sensory neuron lineage.

  4. Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease.

    Science.gov (United States)

    Oder, Daniel; Nordbeck, Peter; Wanner, Christoph

    2016-01-01

    Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future.

  5. 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

  6. 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....

  7. Prethrombotic state gene predictions and diagnosis of venous thromboembolism after large traumatic surgery including orthopedic joint replacement and implant placement%骨科关节置换、植入物置入等较大创伤型手术后静脉血栓前状态的基因预测诊断

    Institute of Scientific and Technical Information of China (English)

    王强; 赵学凌

    2012-01-01

    BACKGROUND: At present, we pay more attention on the early genetic diagnosis of venous thromboembolism after traumatic or orthopedic surgery.OBJECTIVE: To summarize the mature gene research used to diagnosis the venous thromboembolism after orthopedic surgery.METHODS: CNKI database and PubMed database (2000-01/2011-01) were searched through Web with the key words of “venous thrombosis, deep venous thrombosis, pulmonary embolism, genes, diagnosis” or “thrombosis, DVT, PE, gene”.RESULTS AND CONCLUSION: Recent clinical and basic research showed that venous thromboembolism was a typical polygenic hereditary disease. And we also found some mutant gene related to high blood coagulation was closely related with venous thrombosis. These mutant gene included prothrombinase V, antithrombin Ⅲ, protein C, protein S, plasminogen, fibrinogen, heparin cofactor Ⅱ, thrombomodulin and prothrombinase Ⅻ. Understanding of the hereditary pathogenic gene mechanism for venous thromboembolism was in favor of early diagnosis and treatment and reduced the harm.%背景:目前创伤或骨科手术后的静脉血栓栓塞症早期基因诊断日益受到重视.目的:综述目前用于预测诊断骨科术后静脉血栓栓塞症较为成熟的一些基因的研究进展.方法:通过网络检索CNKI和PubMed数据库等2000-01/2011-01关于骨科术后静脉血栓基因诊断的文章,在标题和摘要中以"静脉血栓形成,深静脉血栓,肺栓塞,基因,诊断"或"thrombosis;DVT;PE;gene"为关键词.结果与结论:近年来临床和基础研究证实,骨科术后的静脉血栓栓塞症是人类典型的多基因遗传性疾病,至今发现了一些和血液高凝有关的突变基因与静脉血栓形成有密切关系,分别是:凝血因子V,抗凝血酶Ⅲ,蛋白C,蛋白S,纤溶酶原,纤维蛋白原,肝素辅因子Ⅱ,血栓调节蛋白和凝血因子Ⅻ.了解骨科术后静脉血栓栓塞症的遗传性致病基因机制,有利于早诊断、早治疗,降低其危害.

  8. Relapsing hypocupraemic myelopathy requiring high‐dose oral copper replacement

    OpenAIRE

    Prodan, C.I.; Bottomley, S S; Holland, N R; Lind, S. E.

    2006-01-01

    Adult‐onset copper deficiency with neurological manifestations is a newly recognised syndrome. Long‐term oral copper replacement therapy has been the mainstay of treatment in the literature. A case of relapsing hypocupraemic myelopathy responsive to increased doses of copper replacement is reported. Standard doses of copper may not be sufficient for all patients.

  9. Improving compliance with hormonal replacement therapy in primary osteoporosis prevention

    DEFF Research Database (Denmark)

    Vestergaard, P; Hermann, A P; Gram, J

    1997-01-01

    To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule.......To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule....

  10. Total joint replacement in multiplex congenita contractures: a case report

    OpenAIRE

    Cameron, Hugh U.

    1998-01-01

    A 34-year-old man with multiplex congenita contractures underwent replacement of 2 hips and 1 knee. Even though a good range of movement was achieved at surgery and intensive physiotherapy, his joints returned to their preoperative status within 2 years. This outcome suggests that total joint replacement has little to offer the patient with multiplex congenita contractures who has immobile joints.

  11. Synovial hypertrophy causing recurrent hemarthrosis after total knee replacement.

    Science.gov (United States)

    Gajjar, Shreyash M; Platts, Andrew; Dowd, George

    2010-03-01

    Recurrent hemarthrosis following total knee replacement is relatively uncommon and can result from causes that may not always be easy to diagnose. We report three patients with late-onset recurrent hemarthrosis following total knee replacement due to synovial hypertrophy and impingement, which were successfully treated by embolization.

  12. Studies on the replacement policies in dairy cattle

    NARCIS (Netherlands)

    Arendonk, van J.A.M.

    1985-01-01

    In The Netherlands dairy farmers replace on average 25-30% of their cows each year. The decision to replace instead of to keep a cow is based mainly on economic considerations rather than because a cow is no longer able to produce.

    The investigations described in this thesis were

  13. Renal replacement therapy after cardiac surgery; renal function recovers

    DEFF Research Database (Denmark)

    Steinthorsdottir, Kristin Julia; Kandler, Kristian; Agerlin Windeløv, Nis

    2013-01-01

    To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy.......To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy....

  14. Replacement corn for jackfruit silage in diets for feedlot lambs

    Directory of Open Access Journals (Sweden)

    José Augusto Gomes Azevêdo

    2015-06-01

    Full Text Available The objective was to evaluate the effects of replacement corn by jackfruit silage on intake, coefficient of apparent digestibility and performance in diets for feedlot confined lambs. Santa Inês crossbred castrated male lambs were used, in the completely randomized design. The replacement levels were 0. 333. 666. 1000 g kg-1 in dry matter (DM of corn as the concentrate component. The intake DM, crude protein (CP (g day-1, neutral detergent fiber (NDF in g kg-1 and g kg-1 body weight (BW increased linearly with replacement. The intake of organic matter (OM, ethereal extract (EE, total carbohydrates (TC and non-fiber carbohydrates (NFC decreased linearly, while for total digestible nutrients (TDN quadratic behavior with replacement. The coefficients of apparent digestibility of OM, TC and NFC decreased linearly with replacement, while the coefficient of digestibility of CP and TDN showed quadratic behavior with replacement. The BW and average daily gain decreased linearly with the replacement of corn for jackfruit silage. The jackfruit silage can be used to replace corn in diets of lambs and their use is dependent on economic factors, the availability of fruit and purpose of animal productivity to be reached

  15. 7 CFR 274.6 - Replacement issuances to households.

    Science.gov (United States)

    2010-01-01

    ... recipient's signature on the authorization document matches the signature on the ID card. In a Photo ID area... matches the serial number on the recipient's ID card; (3) Issue a replacement in accordance with... recipient's ID card. Any replacement which results in duplicate participation shall be considered...

  16. The metabolic consequences of thyroxine replacement in adult hypopituitary patients

    DEFF Research Database (Denmark)

    Filipsson Nyström, Helena; Feldt-Rasmussen, Ulla; Kourides, Ione;

    2012-01-01

    The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database...

  17. Dilatation of the aneurysmal sac after total arch replacement.

    Science.gov (United States)

    Watanuki, Hirotaka; Ogino, Hitoshi; Matsuda, Hitoshi; Minatoya, Kenji; Sasaki, Hiroaki; Fukuda, Tetsuya; Kitamura, Soichiro

    2008-02-01

    In our institution, total arch replacement for distal arch aneurysms is performed through a median sternotomy with antegrade selective cerebral perfusion. The distal anastomosis to the completely transected descending aorta is made through the aneurysmal sac. We report on three interesting cases presenting late dilatation of the aneurysmal sac due to collateral flow after total arch replacement.

  18. Functionality of Inulin as a Sucrose Replacer in Cookie Baking

    Science.gov (United States)

    Inulin was evaluated as a sucrose replacer for healthy cookie production with benefits of low glycemic impact and prebiotic soluble fiber. Sucrose (as a reference) and three inulin products of different concentrations (as soluble fibers) were used to explore the effects of sugar-replacer type on so...

  19. A.R.T. – Aggression Replacement Training

    DEFF Research Database (Denmark)

    Harbo, Lotte Junker; Domben, Eskil

    2015-01-01

    Artiklen indeholder en kort introduktion, eksemplificeret ved case, af det manualbaserede program til behandling af udadreagerende unge Aggression Replacement Training.......Artiklen indeholder en kort introduktion, eksemplificeret ved case, af det manualbaserede program til behandling af udadreagerende unge Aggression Replacement Training....

  20. Inspection-replacement policy of system under predictive maintenance

    Institute of Scientific and Technical Information of China (English)

    LIU Bao-you; FANG You-tong; WEI Jin-xiang; WANG Yong-liang

    2007-01-01

    In general, every system is in one of the three states: normal, abnormal, or failure state. When the system is diagnosed as abnormal state, it needs predictive maintenance. If the system fails, an identical new one will replace it. The predictive maintenance cannot make the system "as good as new". Under these assumptions, the reliability index and the inspection-replacement policy of a system were studied. The explicit expression of the reliability index and the average income rate (i.e., the long-runaverage income per unit time) are derived by using probability analysis and vector Markov process method. The criterion of feasibility for the optimal inspection-replacement policy under the maximum average income rate is obtained. The numerical example shows the optimal inspection-replacement policy can raise the average income rate when the optimal inspection-replacement policy is feasible.

  1. 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. 

  2. Knockdown and replacement therapy mediated by artificial mirtrons in spinocerebellar ataxia 7.

    Science.gov (United States)

    Curtis, Helen J; Seow, Yiqi; Wood, Matthew J A; Varela, Miguel A

    2017-07-27

    We evaluate a knockdown-replacement strategy mediated by mirtrons as an alternative to allele-specific silencing using spinocerebellar ataxia 7 (SCA7) as a model. Mirtrons are introns that form pre-microRNA hairpins after splicing, producing RNAi effectors not processed by Drosha. Mirtron mimics may therefore avoid saturation of the canonical processing pathway. This method combines gene silencing mediated by an artificial mirtron with delivery of a functional copy of the gene such that both elements of the therapy are always expressed concurrently, minimizing the potential for undesirable effects and preserving wild-type function. This mutation- and single nucleotide polymorphism-independent method could be crucial in dominant diseases that feature both gain- and loss-of-function pathologies or have a heterogeneous genetic background. Here we develop mirtrons against ataxin 7 with silencing efficacy comparable to shRNAs, and introduce silent mutations into an ataxin 7 transgene such that it is resistant to their effect. We successfully express the transgene and one mirtron together from a single construct. Hence, we show that this method can be used to silence the endogenous allele of ataxin 7 and replace it with an exogenous copy of the gene, highlighting the efficacy and transferability across patient genotypes of this approach. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Can Geothermal Power Replace Fossil Fuels?

    Science.gov (United States)

    Klenner, R.; Gosnold, W. D.

    2009-12-01

    is scaled up to produce power in the MW range. Values needed for these systems are temperatures of 92+ °C and flow rates of 140-1000 gpm. In a detailed analysis of the North Dakota part of the Williston Basin, we used heat flow, bottom-hole temperatures, and measured temperature gradients to calculate the energy contained within specific formations having temperatures in the range of 100 °C to 150 °C. We find that at a 2% recovery factor, approximately 4500 MW/hr can be recovered at depths of 3-4 km. North Dakota currently produces approximately 3100 MW/hr from non-renewable sources such as coal and petroleum. We conclude that the geothermal resource in the Williston Basin could completely replace fossil fuels as an electrical power supply for North Dakota.

  4. Gene delivery with cationic lipids : fundamentals and potential applications

    NARCIS (Netherlands)

    Wasungu, Luc Bakomma

    2006-01-01

    Principle of gene therapy. Although the objectives and principles of gene therapy have been well-defined over the last decades, its application as a versatile, therapeutically successful approach has not yet met expectations. At the onset, the primary goal of gene therapy was to replace a deficient

  5. Gene delivery with cationic lipids : fundamentals and potential applications

    NARCIS (Netherlands)

    Wasungu, Luc Bakomma

    2006-01-01

    Principle of gene therapy. Although the objectives and principles of gene therapy have been well-defined over the last decades, its application as a versatile, therapeutically successful approach has not yet met expectations. At the onset, the primary goal of gene therapy was to replace a deficient

  6. Gene delivery with cationic lipids : fundamentals and potential applications

    NARCIS (Netherlands)

    Wasungu, L.B.

    2006-01-01

    Principle of gene therapy.Although the objectives and principles of gene therapy have been well-defined over the last decades, its application as a versatile, therapeutically successful approach has not yet met expectations. At the onset, the primary goal of gene therapy was to replace a deficient g

  7. The use of Xenopus oocytes and embryos as a route towards cell replacement

    Indian Academy of Sciences (India)

    J B Gurdon

    2005-02-01

    When nuclei of somatic cells are transplanted to enucleated eggs of Xenopus, a complete reprogramming of nuclear function can take place. To identify mechanisms of nuclear reprogramming, somatic nuclei can be transplanted to growing meiotic oocytes of Xenopus, and stem cell genes activated without DNA replication. The combination of somatic cell nuclear transfer with morphogen signalling and the community effect may lead towards the possibility of cell replacement therapy. When mechanisms of nuclear reprogramming are understood, it may eventually be possible to directly reprogramme human somatic cell nuclei without the use of eggs.

  8. Do meal replacement drinks have a role in diabetes management?

    Science.gov (United States)

    Ditschuneit, Herwig H

    2006-01-01

    The poor effectiveness of conventional dietary treatment for weight loss and weight maintenance in patients with type-2 diabetes may be improved by a meal replacement strategy that provides a strong structured meal plan with reasonable opportunity for dietary variety. Typical meal replacement programs fix the intake of one or two meals per day with a calorie-controlled, nutritionally balanced commercial formulation, and allow prudent additional meals and snacks. In obese subjects, diets with meal replacements have proven to be more efficient than conventional diets. Patients on the meal replacement regimen lost 7.3 and 8.4% of initial body weight after 12 weeks and 4 years, respectively, whereas the patients on the conventional diet had lost 1.4% and 3.2% of initial body weight after 12 weeks and 4 years, respectively. The meal replacement plan has also proven to be effective in patients with type-2 diabetes. After 6 and 12 months, patients in the meal replacement group achieved on average a weight loss of 5.24 and 4.35% of their initial body weight, respectively. In contrast, after 6 and 12 months, patients on the individualized diet plan achieved on average a weight loss of 2.85 and 2.36% of their initial body weight, respectively. Meal replacements offer a promising strategy for treating obese patients with type-2 diabetes.

  9. Studying Genes

    Science.gov (United States)

    ... NIGMS NIGMS Home > Science Education > Studying Genes Studying Genes Tagline (Optional) Middle/Main Content Area Other Fact Sheets What are genes? Genes are segments of DNA that contain instructions ...

  10. Registry data trends of total ankle replacement use.

    Science.gov (United States)

    Roukis, Thomas S; Prissel, Mark A

    2013-01-01

    Joint arthroplasty registry data are meaningful when evaluating the outcomes of total joint replacement, because they provide unbiased objective information regarding survivorship and incidence of use. Critical evaluation of the registry data information will benefit the surgeon, patient, and industry. However, the implementation and acceptance of registry data for total ankle replacement has lagged behind that of hip and knee implant arthroplasty. Currently, several countries have national joint arthroplasty registries, with only some procuring information for total ankle replacement. We performed an electronic search to identify publications and worldwide registry databanks with pertinent information specific to total ankle replacement to determine the type of prostheses used and usage trends over time. We identified worldwide registry data from 33 countries, with details pertinent to total ankle replacement identified in only 6 countries. The obtained information was arbitrarily stratified into 3 distinct periods: 2000 to 2006, 2007 to 2010, and 2011. Within these study periods, the data from 13 total ankle replacement systems involving 3,980 ankles were identified. The vast majority (97%) of the reported ankle replacements were 3-component, mobile-bearing, uncemented prostheses. Three usage trends were identified: initial robust embracement followed by abrupt disuse, minimal use, and initial embracement followed by sustained growth in implantation. Before the widespread acceptance of new total ankle replacements, the United States should scrutinize and learn from the international registry data and develop its own national joint registry that would include total ankle replacement. Caution against the adoption of newly released prostheses, especially those without readily available revision components, is recommended.

  11. Minimally Invasive Transaortic Mitral Decalcification During Aortic Valve Replacement.

    Science.gov (United States)

    Totsugawa, Toshinori; Sakaguchi, Taichi; Hiraoka, Arudo; Matsushita, Hiroshi; Hirai, Yuki; Yoshitaka, Hidenori

    2015-01-01

    Mitral annular calcification accompanied by aortic stenosis is hazardous for both double-valve replacement and transcatheter aortic valve implantation. Less invasive mitral procedure is required in this condition, and minimally invasive approach may further reduce the operative risk in high-risk patients. Here, we report minimally invasive transaortic mitral decalcification during aortic valve replacement through minithoracotomy. We believe that this option is feasible in patients who are at prohibitive risk for double-valve replacement or transcatheter aortic valve implantation because of severe mitral annular calcification.

  12. DETERMINATION OF REPLACEMENT EFFICIENCY OF TRANSFORMERS WITH LONG SERVICE LIFE

    Directory of Open Access Journals (Sweden)

    M. I. Fursanov

    2014-01-01

    Full Text Available The paper shows non-efficient application of the existing economical models for determination of replacement time for transformers with long service life because these models do not take into account real changes in transformer parameters during its operational period. An improved mathematical model for estimation of replacement efficiency of power transformers which are used at substations of power distribution networks has been developed in the paper. The model makes it possible to determine an optimum replacement time and economically justified operational service life of the transformers.

  13. Dinoflagellate nuclear SSU rRNA phylogeny suggests multiple plastid losses and replacements.

    Science.gov (United States)

    Saldarriaga, J F; Taylor, F J; Keeling, P J; Cavalier-Smith, T

    2001-09-01

    Dinoflagellates are a trophically diverse group of protists with photosynthetic and non-photosynthetic members that appears to incorporate and lose endosymbionts relatively easily. To trace the gain and loss of plastids in dinoflagellates, we have sequenced the nuclear small subunit rRNA gene of 28 photosynthetic and four non-photosynthetic species, and produced phylogenetic trees with a total of 81 dinoflagellate sequences. Patterns of plastid gain, loss, and replacement were plotted onto this phylogeny. With the exception of the apparently early-diverging Syndiniales and Noctilucales, all non-photosynthetic dinoflagellates are very likely to have had photosynthetic ancestors with peridinin-containing plastids. The same is true for all dinoflagellates with plastids other than the peridinin-containing plastid: their ancestors have replaced one type of plastid for another, in some cases most likely through a non-photosynthetic intermediate. Eight independent instances of plastid loss and three of replacement can be inferred from existing data, but as more non-photosynthetic lineages are characterized these numbers will surely grow.

  14. Polyurethane scaffold with in situ swelling capacity for nucleus pulposus replacement.

    Science.gov (United States)

    Li, Zhen; Lang, Gernot; Chen, Xu; Sacks, Hagit; Mantzur, Carmit; Tropp, Udi; Mader, Kerstin T; Smallwood, Thomas C; Sammon, Chris; Richards, R Geoff; Alini, Mauro; Grad, Sibylle

    2016-04-01

    Nucleus pulposus (NP) replacement offers a minimally invasive alternative to spinal fusion or total disc replacement for the treatment of intervertebral disc (IVD) degeneration. This study aimed to develop a cytocompatible NP replacement material, which is feasible for non-invasive delivery and tunable design, and allows immediate mechanical restoration of the IVD. A bi-phasic polyurethane scaffold was fabricated consisting of a core material with rapid swelling property and a flexible electrospun envelope. The scaffold was assessed in a bovine whole IVD organ culture model under dynamic load for 14 days. Nucleotomy was achieved by incision through the endplate without damaging the annulus fibrosus. After implantation of the scaffold and in situ swelling, the dynamic compressive stiffness and disc height were restored immediately. The scaffold also showed favorable cytocompatibility for native disc cells. Implantation of the scaffold in a partially nucleotomized IVD down-regulated catabolic gene expression, increased proteoglycan and type II collagen intensity and decreased type I collagen intensity in remaining NP tissue, indicating potential to retard degeneration and preserve the IVD cell phenotype. The scaffold can be delivered in a minimally invasive manner, and the geometry of the scaffold post-hydration is tunable by adjusting the core material, which allows individualized design.

  15. Evolutionary replacement of obligate symbionts in an ancient and diverse insect lineage.

    Science.gov (United States)

    Koga, Ryuichi; Bennett, Gordon M; Cryan, Jason R; Moran, Nancy A

    2013-07-01

    Many insect groups depend on ancient obligate symbioses with bacteria that undergo long-term genomic degradation due to inactivation and loss of ancestral genes. Sap-feeding insects in the hemipteran suborder Auchenorrhyncha show complex symbioses with at least two obligate bacterial symbionts, inhabiting specialized host cells (bacteriocytes). We explored the symbiotic relationships of the spittlebugs (Auchenorrhyncha: Cercopoidea) using phylogenetic and microscopy methods. Results show that most spittlebugs contain the symbionts Sulcia muelleri (Bacteroidetes) and Zinderia insecticola (Betaproteobacteria) with each restricted to its own bacteriocyte type. However, the ancestral Zinderia symbiont has been replaced with a novel symbiont closely related to Sodalis glossinidius (Enterobacteriaceae) in members of the ecologically successful spittlebug tribe Philaenini. At least one spittlebug species retains Sulcia and Zinderia, but also has acquired a Sodalis-like symbiont, possibly representing a transitional stage in the evolutionary succession of symbioses. Phylogenetic analyses including symbionts of other Auchenorrhyncha lineages suggest that Zinderia, like Sulcia, descends from an ancestral symbiont present in the common ancestor of Auchenorrhyncha. This betaproteobacterial symbiont has been repeatedly replaced by other symbionts, such as the Sodalis-like symbiont of spittlebugs. Symbiont replacement may offer a route for hosts to escape dependence on an ancient, degraded and potentially inefficient symbiont. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

  16. Gene therapy for hemophilia.

    Science.gov (United States)

    Hortelano, G; Chang, P L

    2000-01-01

    Hemophilia A and B are X-linked genetic disorders caused by deficiency of the coagulation factors VIII and IX, respectively. Because of the health hazards and costs of current product replacement therapy, much effort is devoted to the development of gene therapy for these disorders. Approaches to gene therapy for the hemophilias include: ex vivo gene therapy in which cells from the intended recipients are explanted, genetically modified to secrete Factor VIII or IX, and reimplanted into the donor; in vivo gene therapy in which Factor VIII or IX encoding vectors are directly injected into the recipient; and non-autologous gene therapy in which universal cell lines engineered to secrete Factor VIII or IX are enclosed in immuno-protective devices before implantation into recipients. Research into these approaches is aided by the many murine and canine models available. While problems of achieving high and sustained levels of factor delivery, and issues related to efficacy, safety and cost are still to be resolved, progress in gene therapy for the hemophilias has been encouraging and is likely to reach human clinical trial in the foreseeable future.

  17. Effect of curd suppression in a milk replacer on physiological ...

    African Journals Online (AJOL)

    ... to determine the effect of abomasal curd suppression on selected blood profiles. ... Fasting (0 h) plasma free essential amino acid (EAA) concentration tended to be ... Keywords: Blood profiles, calves, casein curd formation, milk replacers, ...

  18. Total ankle replacement – surgical treatment and rehabilitation

    Science.gov (United States)

    Krogulec, Zbigniew; Turski, Piotr; Przepiórski, Emil; Małdyk, Paweł; Księżopolska-Orłowska, Krystyna

    2015-01-01

    Functions of the ankle joint are closely connected with the gait and ability to maintain an upright position. Degenerative lesions of the joint directly contribute to postural disorders and greatly restrict propulsion of the foot, thus leading to abnormal gait. Development of total ankle replacement is connected with the use of the method as an efficient treatment of joint injuries and continuation of achievements in hip and knee surgery. The total ankle replacement technique was introduced as an alternative to arthrodesis, i.e. surgical fixation, which made it possible to preserve joint mobility and to improve gait. Total ankle replacement is indicated in post-traumatic degenerative joint disease and joint destruction secondary to rheumatoid arthritis. In this paper, total ankle replacement and various types of currently used endoprostheses are discussed. The authors also describe principles of early postoperative rehabilitation as well as rehabilitation in the outpatient setting. PMID:27407223

  19. Macronutrient replacement options for saturated fat: effects on cardiovascular health.

    Science.gov (United States)

    Flock, Michael R; Fleming, Jennifer A; Kris-Etherton, Penny M

    2014-02-01

    The purpose of this review is to discuss macronutrient replacement options for saturated fatty acids (SFAs) to optimize cardiovascular disease (CVD) risk reduction. Dietary recommendations advise decreasing SFAs. There is convincing evidence that replacing SFAs with unsaturated fat, both omega-6 and omega-3 polyunsaturated fatty acids, reduces CVD risk. Monounsaturated fatty acid substitution for SFAs also decreases CVD risk. Replacing SFAs with refined carbohydrate does little to alter CVD risk, whereas whole-grain CHO or lean protein substitutions beneficially affect CVD risk. Modifying the macronutrient composition of the diet by replacing SFAs with unsaturated fatty acids, as well as lean protein and carbohydrate from whole grains, all lower CVD risk. Research is needed to identify food sources of macronutrients that optimize CVD risk reduction.

  20. Prosthetic valve thrombosis in a patient with mitral valve replacement.

    Science.gov (United States)

    Bilal, Muhammad; Khan, Muhammad Shahzeb; Haseeb, Abdul; Khan, Abdul Bari

    2015-07-01

    Prosthetic valve thrombosis within one year after mitral valve replacement is rarely seen in patients on warfarin therapy and without any risk factor. Here, we describe a case of a 39-year- old female, who presented with dyspnoea and shortness of breath 11 months after mitral valve replacement. The echocardiogram revealed severe valvular stenosis due to presence of clots on the mitral valve and restricted motion of the mitral leaflets. As a result of deterioration of general condition and haemodynamic un-stability, plan was made to re-operate for her valve replacement surgery. This case report highlights the diagnosis, prevention and management of patients with prosthetic valve thrombosis following mitral valve replacement.

  1. Hormone replacement for osteoporosis in women with primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Rudic, Jelena S; Poropat, Goran; Krstic, Miodrag N

    2011-01-01

    Women with primary biliary cirrhosis often suffer from postmenopausal osteoporosis due to their age, or osteoporosis secondary to their liver disease, or treatments provided for their liver disease. Hormone replacement increases bone mineral density and reduces fractures in postmenopausal women...

  2. the influence of replacing maize with chrysophyllum albidum seed ...

    African Journals Online (AJOL)

    AGROSEARCH UIL

    Production Technology, Moor Plantation, PMB 5029, Ibadan ... including; Coffee pulp (Fagbenro and Arowosoge, 1991a); plantain peel and yam peel (Fagbenro .... Aderolu et al (2011) fed biscuit waste as a replacer of maize to Clarias ...

  3. Laboratory Evaluation of LED T8 Replacement Lamp Products

    Energy Technology Data Exchange (ETDEWEB)

    Richman, Eric E.; Kinzey, Bruce R.; Miller, Naomi J.

    2011-05-23

    A report on a lab setting analysis involving LED lamps intended to directly replace T8 fluorescent lamps (4') showing light output, power, and economic comparisons with other fluorescent options.

  4. Performance and economic effects of partially replacing soybean ...

    African Journals Online (AJOL)

    Performance and economic effects of partially replacing soybean meal with palm kernel ... to determine the optimal level of inclusion for maximum production in broilers. ... while no PKC was used in treatment I, which also served as the control.

  5. A new bread improver to replace traditional gluten fortifier

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Scientists with the CAS Changchun Institute for Applied Chemistry recently developed a new plant derivative of polysaccharide to replace the traditional agent of gluten fortifier in the bread-baking industry.

  6. Comprehensive Care For Joint Replacement Model - Provider Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Comprehensive Care for Joint Replacement Model - provider data. This data set includes provider data for two quality measures tracked during an episode of care:...

  7. Set Covering with Ordered Replacement -- Additive and Multiplicative Gaps

    CERN Document Server

    Eisenbrand, Friedrich; Rothvoß, Thomas; Sanità, Laura

    2010-01-01

    We consider set covering problems where the underlying set system satisfies a particular replacement property w.r.t. a given partial order on the elements: Whenever a set is in the set system then a set stemming from it via the replacement of an element by a smaller element is also in the set system. Many variants of BIN PACKING that have appeared in the literature are such set covering problems with ordered replacement. We provide a rigorous account on the additive and multiplicative integrality gap and approximability of set covering with replacement. In particular we provide a polylogarithmic upper bound on the additive integrality gap that also yields a polynomial time additive approximation algorithm if the linear programming relaxation can be efficiently solved. We furthermore present an extensive list of covering problems that fall into our framework and consequently have polylogarithmic additive gaps as well.

  8. evaluation of early calves' weaning diet as milk replacer for ...

    African Journals Online (AJOL)

    ACSS

    This results in depressed calves' growth rates, high calf mortality rates, late ... additive can be an effective milk- replacer in smallholder dairy production systems to wean dairy calves at 28-35 ... consumption, but also increases cash income for.

  9. An all MMIC Replacement for Gunn Diode Oscillators Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose to replace the Gunn Diode Oscillators (GDOs) in NASA?s millimeter- and submillimeter-wave sensing instruments. Our new solution will rely on modern and...

  10. 39 CFR 777.24 - Replacement housing payments.

    Science.gov (United States)

    2010-07-01

    ... replacement dwelling). They include: (1) Legal, closing, and related costs, including those for title search... assurance of title. (7) Escrow agent's fee. (8) State revenue or documentary stamps, sales or transfer...

  11. Knee Replacement for Women with Patient-Specific Instructions

    Medline Plus

    Full Text Available Knee Replacement for Women with Patient-Specific Instructions Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. All rights reserved.

  12. Hormone Replacement Therapy: Can It Cause Vaginal Bleeding?

    Science.gov (United States)

    Hormone replacement therapy: Can it cause vaginal bleeding? I'm taking hormone therapy for menopause symptoms, and my monthly menstrual periods have returned. Is this normal? Answers from Shannon K. Laughlin- ...

  13. performance of concrete with partial replacement of fine aggregates ...

    African Journals Online (AJOL)

    user

    Key Words: compressive strength, concrete, crushed waste glass, flexural strength, setting time, water absorption and workability. ... powder as partial replacement of fine aggregates up to ... water in cement paste and reactive silica in the WG.

  14. Knee Replacement for Women with Patient-Specific Instructions

    Medline Plus

    Full Text Available Knee Replacement for Women with Patient-Specific Instructions Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. All rights reserved.

  15. Implications of human evolution and admixture for mitochondrial replacement therapy

    National Research Council Canada - National Science Library

    Rishishwar, Lavanya; Jordan, I. King

    2017-01-01

    Mitochondrial replacement (MR) therapy is a new assisted reproductive technology that allows women with mitochondrial disorders to give birth to healthy children by combining their nuclei with mitochondria from unaffected egg donors...

  16. State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications.

    Science.gov (United States)

    Wang, Dan; Gao, Guangping

    2014-09-01

    In Part I of this Review (Wang and Gao, 2014), we introduced recent advances in gene delivery technologies and explained how they have powered some of the current human gene therapy applications. In Part II, we expand the discussion on gene therapy applications, focusing on some of the most exciting clinical uses. To help readers to grasp the essence and to better organize the diverse applications, we categorize them under four gene therapy strategies: (1) gene replacement therapy for monogenic diseases, (2) gene addition for complex disorders and infectious diseases, (3) gene expression alteration targeting RNA, and (4) gene editing to introduce targeted changes in host genome. Human gene therapy started with the simple idea that replacing a faulty gene with a functional copy can cure a disease. It has been a long and bumpy road to finally translate this seemingly straightforward concept into reality. As many disease mechanisms unraveled, gene therapists have employed a gene addition strategy backed by a deep knowledge of what goes wrong in diseases and how to harness host cellular machinery to battle against diseases. Breakthroughs in other biotechnologies, such as RNA interference and genome editing by chimeric nucleases, have the potential to be integrated into gene therapy. Although clinical trials utilizing these new technologies are currently sparse, these innovations are expected to greatly broaden the scope of gene therapy in the near future.

  17. Rescue Surgery 19 Years after Composite Root and Hemiarch Replacement

    Directory of Open Access Journals (Sweden)

    Konstantin von Aspern

    2013-01-01

    Full Text Available A 59-year-old male patient with Marfan's syndrome was referred to our clinic due to acute chest pain. His medical history contains complex surgery for type A aortic dissection 19 years ago including composite root replacement using a mechanical aortic valve. Immediate computed tomography indicated perforation at the distal ascending aortic anastomosis plus complete avulsion of both coronary ostia. The patient underwent successful rescue surgery with ascending aortic and arch replacement using a modified Cabrol technique.

  18. Transvalvular mitral regurgitation following mitral valve replacement a diagnostic dilemma

    OpenAIRE

    U S Dinesh Kumar; Umesh Nareppa; Shyam Prasad Shetty; Murugesh Wali

    2015-01-01

    After mitral valve replacement with a prosthetic valve, the valve should be competent and there should not be any residual prosthetic valve regurgitation. Transvalvular residual prosthetic valve regurgitation are difficult to diagnose and quantify. we are reporting interesting TEE images as a diagnostic dilemma in a case of transvalvular mitral regurgitation following mitral valve replacement secondary to entrapment of sub-valvular apparatus in a Chitra mechanical heart valve.

  19. The Business of Bundling: Joining Forces on Joint Replacement.

    Science.gov (United States)

    Kaldy, Joanne

    2016-03-01

    A mandated bundled-payment program for joint replacement is in place in several regions across the country, and practitioners such as pharmacists are still sorting out their roles in this federal initiative. To get involved, pharmacists need to establish connections with area hospitals and physician groups to promote and document their ability to manage medications, reduce and eliminate medication-related problems and rehospitalizations, and work with patients to maximize adherence and improve communication for those undergoing hip and knee replacement.

  20. Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy

    OpenAIRE

    2012-01-01

    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...

  1. SERDP-ESTCP Depot Cd/Chromate Replacement Initiative

    Science.gov (United States)

    2014-11-18

    ESTCP SERDP Environmental Technology Development Process Office of the Deputy Under Secretary of Defense - Installations and Environment 4...SERDP-ESTCP Depot Cd/ Chromate Replacement Initiative Robin Nissan Weapons Systems and Platforms Program Manager ASETSDefense 18 November 2014...NOV 2014 2. REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE SERDP-ESTCP Depot Cd/ Chromate Replacement Initiative 5a

  2. Transcatheter aortic valve prosthesis surgically replaced 4 months after implantation

    DEFF Research Database (Denmark)

    Thyregod, Hans Gustav; Lund, Jens Teglgaard; Engstrøm, Thomas;

    2010-01-01

    Transcatheter aortic valve implantation is a new and rapidly evolving treatment option for high-risk surgical patients with degenerative aortic valve stenosis. Long-term results with these new valve prostheses are lacking, and potential valve dysfunction and failure would require valve replacement....... We report the first case of surgical valve replacement in a patient with a dysfunctional transcatheter-implanted aortic valve prosthesis 4 months after implantation....

  3. Transcatheter aortic valve replacement: techniques, complications, and bailout strategies.

    Science.gov (United States)

    Singh, Vikas; Macon, Conrad J; Scot Shaw, Eric; Londoño, Juan C; Martinez, Claudia A

    2013-09-01

    Transcatheter aortic valve replacement has emerged as an alternative option for inoperable or very high-risk patients with severe aortic stenosis-however, there are serious complications associated with the procedure, such as patient mortality, stroke, conduction disturbances, paravalvular regurgitation, and vascular concerns. Our review focuses on the most common complications related to transcatheter aortic valve replacement procedures and potential bailout strategies and techniques.

  4. Nursing procedures during continuous renal replacement therapies: a national survey

    OpenAIRE

    Ricci, Zaccaria; Benelli, Sonia; Barbarigo, Fabio; Cocozza, Giulia; Pettinelli, Noemi; Di Luca, Emanuela; Mettifogo, Mariangela; Toniolo, Andrea; Ronco, Claudio

    2015-01-01

    Introduction The current role of nurses in the management of critically ill patients needing continuous renal replacement therapies is clearly fundamental. The care of these complex patients is typically shared by critical care and dialysis nurses: their precise duties may vary from country to country. Methods To clarify this issue we conducted a national-level survey at a recent Italian course on nursing practices during continuous renal replacement therapies. Results A total of 119 question...

  5. Renal Replacement Therapy in Support of Combat Operations

    Science.gov (United States)

    2008-07-01

    was used to create viable sets; pediatric chest tubes were used as PD catheters and dialysate was made using either intravenous saline solution with...important logistic factor in performing RRT is the volume of fluid required for dialysate (for hemodi- alysis and peritoneal dialysis) or replace- ment...treatment may range on the order of 100 to 1000 L per day per patient. Both the dialysate and replacement fluid must be sterile, and no approach for

  6. Optimization criteria for the design of orbital replacement units (ORUs)

    Science.gov (United States)

    Schulze, Manfred W.

    A reduction of life cycle costs of spacecraft or Space Station elements can be achieved by a modular build up which allows an in orbit replacement, maintenance, and service of functional units named Orbital Replacement Units (ORUs). The criteria for an optimal design for an ORU is presented. Requirements involving the user spacecraft configuration, the servicing vehicle, the handling by astronauts and remote manipulator system are considered.

  7. Suboptimal B-cell antigen receptor signaling activity in vivo elicits germinal center counterselection mechanisms.

    Science.gov (United States)

    Königsberger, Sebastian; Weis, Vanessa; Prodöhl, Jan; Stehling, Martin; Hobeika, Elias; Reth, Michael; Kiefer, Friedemann

    2015-02-01

    Syk and Zap-70 constitute a closely related nonreceptor protein tyrosine kinase family, of which both members are functionally indispensable for conferring their respective antigen receptors with enzymatic activity. In this study, we analyze the impact of altering BCR signaling output on B-cell germinal center (GC) fate selection by constitutive, as well as inducible, monoallelic Syk kinase loss in the presence of a Zap-70 knock-in rescue allele. Cre-mediated Syk deletion in Syk(flox/Zap-70) B cells lowers pErk, but not pAkt-mediated signaling. Surprisingly, the use of a B-cell-specific constitutive mb1-cre deleter mouse model showed that a small cohort of peripheral Syk(flox/Zap-70);mb1-cre B cells efficiently circumvents deletion, which ultimately favors these Syk-sufficient cells to contribute to the GC reaction. Using a developmentally unbiased Syk(flox/Zap-70);mb1-creER(T2) approach in combination with an inducible tdRFP allele, we further demonstrate that this monoallelic deletion escape is not fully explained by leakiness of Cre expression, but is possibly the result of differential Syk locus accessibility in maturing B cells. Altogether, this underscores the importance of proper Syk kinase function not only during central and peripheral selection processes, but also during GC formation and maintenance.

  8. Midterm Results of Aortic Valve Replacement with Cryopreserved Homografts

    Directory of Open Access Journals (Sweden)

    Emre Özker

    2012-06-01

    Full Text Available Objective: The aim of this study was to analyze the midterm clinical results of aortic valve replacement with cryopreserved homografts.Materials and Methods: Aortic valve replacement was performed in 40 patients with cryopreserved homograft. The indications were aortic valve endocarditis in 20 patients (50%, truncus arteriosus in 6 patients (15%, and re-stenosis or regurtitation after aortic valve reconstruction in 14 (35% patients. The valve sizes ranged from 10 to 27mm. A full root replacement technique was used for homograft replacement in all patients.Results: The 30-day postoperative mortality rate was 12.5% (5 patients. There were four late deaths. Only one of them was related to cardiac events. Overall mortality was 22.5%. Thirty-three patients were followed up for 67±26 months. Two patients needed reoperation due to aortic aneurysm caused by endocarditis. The mean transvalvular gradient significantly decreased after valve replacement (p<0.003. The last follow up showed that the 27 (82% patients had a normal left ventricular function.Conclusion: Cryopreserved homografts are safe alternatives to mechanical valves that can be used when there are proper indications. Although it has a high perioperative mortality rate, cryopreserved homograft implantation is an alternative for valve replacement, particularly in younger patients and for complex surgical problems such as endocarditis that must be minimalized.

  9. Urban chaos and replacement dynamics in nature and society

    CERN Document Server

    Chen, Yanguang

    2011-01-01

    Many growing phenomena in both nature and society can be predicted with sigmoid function. The growth curve of the level of urbanization is a typical S-shaped one, and can be described by using logistic function. The logistic model implies a replacement process, and the logistic substitution suggests non-linear dynamical behaviors such as bifurcation and chaos. Using mathematical transform and numerical computation, we can demonstrate that the 1-dimensional map comes from a 2-dimensional two-group interaction map. By analogy with urbanization, a general theory of replacement dynamics is presented in this paper, and the replacement process can be simulated with the 2-dimansional map. If the rate of replacement is too high, periodic oscillations and chaos will arise, and the system maybe breaks down. The replacement theory can be used to interpret various complex interaction and conversion in physical and human systems. The replacement dynamics provides a new way of looking at Volterra-Lotka's predator-prey inte...

  10. Controversy in mitral valve repair, resection or chordal replacement?

    Science.gov (United States)

    Sawazaki, Masaru; Tomari, Shiro; Zaikokuji, Kenta; Imaeda, Yusuke

    2014-10-01

    Mitral valve plasty has superseded valve replacement as the standard technique for treating degenerative mitral valve prolapse. Quadrangular resection is considered the gold standard for posterior leaflet prolapse. Chordal replacement was first developed to treat the anterior leaflet and subsequently became widely used for the posterior leaflet, after which a new version of posterior leaflet resection was developed that did not involve local annular plication. In the era of the mini-thoracotomy, the premeasured loop technique is simple to adopt and is as durable as quadrangular resection. However, there is controversy surrounding whether resection or chordal replacement is the optimal technique. The resection technique is curative because it removes the main pathologic lesion. The disadvantage of the resection is that it can be complicated and often requires advanced surgical skills. In contrast, chordal replacement is not pathologically curative because it leaves behind a redundant leaflet. However, the long-term results appear to be equivalent in many reports. Functionally, chordal replacement retains greater posterior leaflet motion with a lower trans-mitral pressure gradient than quadrangular resection. Moreover, chordal replacement is simple and yields uniform results. The optimal technique depends on whether the anterior leaflet or posterior leaflet is involved, the Barlow or non-Barlow disease state, and whether a mini-thoracotomy or standard sternotomy approach is used. For mitral valve repair, the most superior and reliable technique for the posterior leaflet is resection using the newer resection technique with a sternotomy approach, which requires a skilled surgeon.

  11. Development of Therapeutic Chimeric Uricase by Exon Replacement/Restoration and Site-Directed Mutagenesis

    Directory of Open Access Journals (Sweden)

    Guangrong Xie

    2016-05-01

    Full Text Available The activity of urate oxidase was lost during hominoid evolution, resulting in high susceptibility to hyperuricemia and gout in humans. In order to develop a more “human-like” uricase for therapeutic use, exon replacement/restoration and site-directed mutagenesis were performed to obtain porcine–human uricase with higher homology to deduced human uricase (dHU and increased uricolytic activity. In an exon replacement study, substitution of exon 6 in wild porcine uricase (wPU gene with corresponding exon in dhu totally abolished its activity. Substitutions of exon 5, 3, and 1–2 led to 85%, 60%, and 45% loss of activity, respectively. However, replacement of exon 4 and 7–8 did not significantly change the enzyme activity. When exon 5, 6, and 3 in dhu were replaced by their counterparts in wpu, the resulting chimera H1-2P3H4P5-6H7-8 was active, but only about 28% of wPU. Multiple sequence alignment and homology modeling predicted that mutations of E24D and E83G in H1-2P3H4P5-6H7-8 were favorable for further increase of its activity. After site-directed mutagenesis, H1-2P3H4P5-6H7-8 (E24D & E83G with increased homology (91.45% with dHU and higher activity and catalytic efficiency than the FDA-approved porcine–baboon chimera (PBC was obtained. It showed optimum activity at pH 8.5 and 35 °C and was stable in a pH range of 6.5–11.0 and temperature range of 20–40 °C.

  12. Delivery systems for gene therapy

    Directory of Open Access Journals (Sweden)

    Shrikant Mali

    2013-01-01

    Full Text Available The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

  13. Explaining Below-Replacement Fertility and Increasing Childlessness in Wealthy Countries: Legacy Drive and the “Transmission Competition” Hypothesis

    OpenAIRE

    Aarssen, Lonnie W; Stephanie Tzipporah Altman

    2006-01-01

    We propose a novel evolutionary perspective for explaining why, in most wealthy countries, female fertility has recently dropped below replacement level, with an increasing incidence of childlessness. Our hypothesis is based on the proposition that throughout human evolution, behaviors that promoted gene transmission (offspring production), and hence fitness, have involved not just those associated with a strong “sex drive,” but also those associated with a strong “legacy drive”—the desire to...

  14. Immunoglobulin genes

    Energy Technology Data Exchange (ETDEWEB)

    Honjo, T. (Kyoto Univ. (Japan)); Alt, F.W. (Columbia Univ., Dobbs Ferry, NY (USA). Hudson Labs.); Rabbitts, T.H. (Medical Research Council, Cambridge (UK))

    1989-01-01

    This book reports on the structure, function, and expression of the genes encoding antibodies in normal and neoplastic cells. Topics covered are: B Cells; Organization and rearrangement of immunoglobin genes; Immunoglobin genes in disease; Immunoglobin gene expression; and Immunoglobin-related genes.

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

    NARCIS (Netherlands)

    van Gaal, E.V.B.|info:eu-repo/dai/nl/30483629X

    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

  16. Impact of genetic selection on management of boar replacement.

    Science.gov (United States)

    Robinson, J A B; Buhr, M M

    2005-01-15

    Boars in an artificial insemination centre have been selected for their superior genetic potential, with 'superior' being defined as having traits the customer wants transmitted to his herd. The ability to meet the customers' needs depends on the heritability of the trait, the geneticist's success in devising a selection scheme for the trait in balance with other economically important traits, and the boar's ability to produce sperm that can fertilise oocytes. Genetic evaluation research over the past 20 years has greatly increased the number of traits for which a boar can be selected: currently in the Canadian national program, these include age at 100 kg, backfat at 100 kg, feed efficiency, lean yield and litter size. In the near future, traits that are very likely to be added to this selection list include piglet survival, marbling, loin eye area and structure traits. In Canada, sires are ranked on two estimated breeding value (EBV) indices; one, focused on development of terminal sire lines, is based on the growth and yield traits and another, primarily focused on maternal line development, de-emphasises these traits and incorporates litter size. Boars that are in Canadian AI centres because of their excellent growth traits are typically in the top 5-10% of the national population for terminal sire line index, but they may be only average or substandard for litter size. Conversely, boars selected to be in the top 5-10% for conveying such reproductive traits as litter size may only be in the top 33% for growth traits. The more offspring from a superior boar in either of these indices, the faster the population average for the trait improves. The original sire gets knocked out of the elite group, is culled and replaced by a higher ranked young boar from the now improved general population. Although genetic superiority should govern an AI centre's selection and culling of boars, decision-making in real life is seldom that simple. Selection criteria may be

  17. Valve replacement in pediatric patients:a single center experience

    Institute of Scientific and Technical Information of China (English)

    YU Jian-hua; GUO Hong-wei; ZHANG Gong; WU Shu-ming; SONG Guang-min; SUN Wen-yu

    2011-01-01

    Background Reconstructive surgery is the primary goal in pediatric patients with valve disease.However,in cases with irreparable valve lesions,valve replacement is the only option.This study aimed to retrospectively analyze the clinical experience of heart valve prosthesis replacement in children.Methods Between January 1990 and July 2009,35 pediatric patients (16 boys,19 girls) underwent mechanical valve replacement in Shandong University Qilu Hospital.The ages ranged from 2.5 to 14 years (mean,(8.8±3.8) years) and body weight varied from 11 to 37 kg (mean,(22.1±5.2) kg).Mechanical valve replacement was performed because of congenital heart disease in 23 patients,rheumatic disease in ten patients and infective endocarditis in two patients.St.Jude bileaflet mechanical valves were implanted in all the 35 patients including mitral valve replacement (MVR) in 18,aortic valve replacement (AVR) in 12,tricuspid valve replacement (TVR) in two,AVR and MVR in two and MVR and TVR in one.The size of the prostheses ranged between 19 and 27 mm.All patients received long-term anticoagulation treatment with sodium warfarin,aiming to maintain an international normalized ratio between 1.5 to 2.0.Follow-up was performed in all the patients with a total follow-up of 119.4 patient-years.Results The operative mortality was 8.57% (3/35).One patient,who underwent cardiac debridement and AVR,died 2 hours after being admitted to the intensive care unit because of severe low cardiac output syndrome and ventricular fibrillation.Two patients died of cardiogenic shock and renal failure during initial hospitalization after the operation.One patient who received replacement of a tricuspid valve developed complete heart block requiring temporary pacing and recovered sinus rhythm 4 days later.Thirty-two patients survived and their cardiac function was in New York Heart Association (NYHA) class Ⅰ to class Ⅱ when discharged.Late events included hemorrhage and endocarditis.Two patients required

  18. Immunoglobulin Replacement Therapy: When You Need It -- and When You Don't

    Science.gov (United States)

    ... Videos Lists Search Patient Resources Immunoglobulin Replacement Therapy Immunoglobulin Replacement Therapy When you need it—and when ... enough germ-fighting antibodies. A treatment known as immunoglobulin replacement (IgG) therapy can be a lifesaver for ...

  19. Menopausal depression:comparison of hormone replacement therapy and hormone replacement therapy plus fiuoxetine

    Institute of Scientific and Technical Information of China (English)

    刘平; 何方方; 白文佩; 郁琦; 史蔚; 吴宜勇; 贺丹军; 肖计划; 郑晔; 廖秦平

    2004-01-01

    Background To compare the efficacy and safety of hormone replacement therapy (HRT) combined with fluoxetine, with HRT alone, in post-menopausal women suffering from depression.Methods A randomized, open-label, parallel trial was applied. HRT was administered to all patients for 2 cycles, with ]4 days of estrogen therapy and 14 days of estrogen plus progesterone. Patients who were randomly assigned to the HRT plus fluoxetine group were given fluoxetine in combination with HRT. Hamilton Depression Rating Scale (HAMD), Kupperman Menopausal Index (KMI), and Clinical Global Impressions scale were used to measure the efficacy. Results One hundred and twenty-three post-menopausal patients with depression were enrolled in the study. Among them, 120 had at least one post-treatment visit and entered into the statistical analysis. The mean total HAMD scores were significantly lower, and the percentages of HAMD score reductions were higher in the HRT plus fluoxetine Group compared with the HRT Group, after at least 3 weeks of treatment, with an average difference of 5 points at the endpoint. The Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores were significantly different in the 2 groups, in favor of the combination therapy. The mean total KMI was significantly lower in the Combination Group compared with the HRT Group, after at least 6 weeks of treatment, with an average 4. 5-point difference between the groups. No statistically significant differences were found in most of the adverse events reported in the Combination Group compared with the HRT group, with the exception of 3 symptoms, i. e., dry mouth, loss of appetite, and abdominal distention. They were mild to moderate in severity. Two patients in the HRT group, but none in the combination group, dropped out due to adverse events. Conclusion HRT plus fluoxetine therapy was effective in the treatment of menopausal depression with a satisfactory safety profile.

  20. 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.

  1. Transcatheter Aortic Valve Replacement: Comprehensive Review and Present Status

    Science.gov (United States)

    Misenheimer, Jacob A.; Ramaraj, Radhakrishnan

    2017-01-01

    Aortic stenosis is the most common valvular heart disease in the developed world. About 7% of the population over age 65 years suffers from degenerative aortic stenosis. The prognosis of patients with symptomatic severe aortic stenosis is dismal without valve replacement. Even though the American College of Cardiology recommends aortic valve replacement to treat this condition as a class I recommendation, approximately one third of these patients over the age of 75 years are not referred for surgery. Typically, this is from concern about prohibitive surgical risk associated with patient frailty, comorbidities, age, and severe left ventricular dysfunction. The advent in France of transcatheter aortic valve replacement has raised the hope in the United States for an alternative, less invasive treatment for aortic stenosis. Two recent trials—the Placement of AoRTic TraNscathetER Valve Trial Edwards SAPIEN Transcatheter Heart Valve (Partner) and the CoreValve US Pivotal—have established transcatheter aortic valve replacement as the preferred approach in patients who are at high or prohibitive surgical risk. The more recently published Partner 2 trial has shown the feasibility of transcatheter aortic valve replacement in intermediate-surgical-risk patients as well. With a profile that promises easier use and better valve performance and delivery, newer-generation valves have shown their potential for further improvement in safety profile and overall outcomes. We review the history and status of this topic. PMID:28265210

  2. Continuous Renal Replacement Therapy for Severe Obstetric Sepsis

    Directory of Open Access Journals (Sweden)

    D. L. Shukevich

    2010-01-01

    Full Text Available Objective: to improve the results of treatment for severe obstetric sepsis by pathogenetically founded continuous renal replacement therapies as extracorporeal homeostatic correction. Subjects and methods. Forty-two women with severe abdominal sepsis were divided into 3 groups: 1 14 women with severe extragenital abdominal sepsis who received standard intensive care (a control group; 2 12 women with severe obstetric sepsis who had standard intensive care (a study group; 3 16 with severe obstetric sepsis who had the standard intensive care supplemented with continuous renal replacement therapy (an intervention group. Results. In Group 2, endogenous intoxication and multiple organ dysfunction were controlled later than in Group 1, mortality rates being 41.7 and 7.1%, respectively. Clinical laboratory differences were due to gestosis recorded in 100% of the patients with severe obstetric sepsis. When continuous renal replacement therapy was incorporated into the complex therapy of severe obstetric sepsis, there was a prompter regression of endogenous intoxication and multiple organ dysfunction, mortality was decreased by an average of 35% as compared with that during standard therapy. Conclusion. The inclusion of continuous renal replacement therapy into the complex treatment program for severe obstetric sepsis made it possible to reduce control time _ for endogenous intoxication and multiple organ dysfunction and to decrease mortality by an average of 35% as compared with that during standard intensive care. Key words: obstetric sepsis, abdominal sepsis, gestosis, endogenous intoxication, multiple organ dysfunction, renal replacement therapy.

  3. PERFORMANCE OF PRIVATE CACHE REPLACEMENT POLICIES FOR MULTICORE PROCESSORS

    Directory of Open Access Journals (Sweden)

    Matthew Lentz

    2014-07-01

    Full Text Available Multicore processors have become ubiquitous, both in general-purpose and special-purpose applications. With the number of transistors in a chip continuing to increase, the number of cores in a processor is also expected to increase. Cache replacement policy is an important design parameter of a cache hierarchy. As most of the processor designs have become multicore, there is a need to study cache replacement policies for multi-core systems. Previous studies have focused on the shared levels of the multicore cache hierarchy. In this study, we focus on the top level of the hierarchy, which bears the brunt of the memory requests emanating from each processor core. We measure the miss rates of various cache replacement policies, as the number of cores is steadily increased from 1 to 16. The study was done by modifying the publicly available SESC simulator, which models in detail a multicore processor with a multilevel cache hierarchy. Our experimental results show that for the private L1 caches, the LRU (Least Recently Used replacement policy outperforms all of the other replacement policies. This is in contrast to what was observed in previous studies for the shared L2 cache. The results presented in this paper are useful for hardware designers to optimize their cache designs or the program codes.

  4. Face-specific Replacement of Calcite by Amorphous Silica Nanoparticles

    Science.gov (United States)

    Liesegang, M.; Milke, R.; Neusser, G.; Mizaikoff, B.

    2016-12-01

    Amorphous silica, composed of nanoscale spheres, is an important biomineral, alteration product of silicate rocks on the Earth's surface, and precursor material for stable silicate minerals. Despite constant progress in silica sphere synthesis, fundamental knowledge of natural silica particle interaction and ordering processes leading to colloidal crystals is absent so far. To understand the formation pathways of silica spheres in a geologic environment, we investigated silicified Cretaceous mollusk shell pseudomorphs from Coober Pedy (South Australia) using focused ion beam (FIB)-SEM tomography, petrographic microscopy, µ-XRD, and EMPA. The shells consist of replaced calcite crystals (product, the advancement of synchronized dissolution and precipitation fronts along lattice planes is essential. We assume that the volume-preserving replacement process proceeds via a face-specific dissolution-precipitation mechanism with intermediate subparticle aggregation and subsequent layer-by-layer deposition of spheres along a planar surface. Porosity created during the replacement reaction allows permanent fluid access to the propagating reaction interface. Fluid pH and ionic strength remain constant throughout the replacement process, permitting continuous silica nanoparticle formation and diffusion-limited colloid aggregation. Our study provides a natural example of the transformation of an atomic crystal to an amorphous, mesoscale ordered material; thus, links the research fields of natural colloidal crystal formation, carbonate-silica replacement, and crystallization by oriented particle aggregation (CPA).

  5. Synthetic Versus Tissue-Engineered Implants for Joint Replacement

    Directory of Open Access Journals (Sweden)

    Duncan E. T. Shepherd

    2007-01-01

    Full Text Available Human synovial joints are remarkable as they can last for a lifetime. However, they can be affected by disease that may lead to destruction of the joint surface. The most common treatment in the advanced stages of joint disease is artificial joint replacement, where the diseased synovial joint is replaced with an artificial implant made from synthetic materials, such as metals and polymers. A new technique for repairing diseased synovial joints is tissue engineering where cells are used to grow replacement tissue. This paper explores the relative merits of synthetic and tissue-engineered implants, using joint replacement as an example. Synthetic joint replacement is a well-established procedure with the advantages of early mobilisation, pain relief and high patient satisfaction. However, synthetic implants are not natural tissues; they can cause adverse reactions to the body and there could be a mismatch in mechanical properties compared to natural tissues. Tissue-engineered implants offer great potential and have major advantages over synthetic implants as they are natural tissue, which should ensure that they are totally biocompatible, have the correct mechanical properties and integrate well with the existing tissue. However, there are still many limitations to be addressed in tissue engineering such as scaling up for production, bioreactor design, appropriate regulation and the potential for disease to attack the new tissue-engineered implant.

  6. Candida orthopsilosis and Candida metapsilosis spp. nov. to replace Candida parapsilosis groups II and III.

    Science.gov (United States)

    Tavanti, Arianna; Davidson, Amanda D; Gow, Neil A R; Maiden, Martin C J; Odds, Frank C

    2005-01-01

    Two new species, Candida orthopsilosis and C. metapsilosis, are proposed to replace the existing designations of C. parapsilosis groups II and III, respectively. The species C. parapsilosis is retained for group I isolates. Attempts to construct a multilocus sequence typing scheme to differentiate individual strains of C. parapsilosis instead revealed fixed DNA sequence differences between pairs of subgroups in four genes: COX3, L1A1, SADH, and SYA1. PCR amplicons for sequencing were obtained for these four plus a further seven genes from 21 group I isolates. For nine group II isolates, PCR products were obtained from only 5 of the 11 genes, and for two group III isolates PCR products were obtained from a different set of 5 genes. Three of the PCR products from group II and III isolates differed in size from the group I products. Cluster analysis of sequence polymorphisms from COX3, SADH, and SYA1, which were common to the three groups, consistently separated the isolates into three distinct sets. All of these differences, together with DNA sequence similarities orthopsilosis suggest that the former species may have evolved very recently from the latter.

  7. Multilocus sequence typing (MLST) analysis of Candida albicans isolates colonizing acrylic dentures before and after denture replacement.

    Science.gov (United States)

    Choo, Khai How; Lee, Hee Ji; Knight, Nicholas J; Holmes, Ann R; Cannon, Richard D

    2017-08-01

    Yeast, in particular Candida albicans, are the principal fungal cause of denture stomatitis, and can also be present as a commensal in many individuals. Few studies, however, have examined oral retention of yeast strains over time. We analyzed the yeast present in saliva samples and from the dentures of 10 individuals colonized with yeast but with no signs of stomatitis, before new complete maxillary dentures were fitted and also at 1, 3, and 6 months after denture replacement. Yeast species were presumptively identified on selective agar plates and were present in nine individuals before denture replacement and in six at the 6-month time point. C. albicans was detected in seven individuals pre-replacement, and in three by 6 months post-replacement. Sixty-two isolates (up to five from each C. albicans-positive sample) were analyzed by multilocus sequence typing (MLST) (33 from saliva and 29 from dentures). Six MLST allele profiles were identified that were common to several individuals. These profiles included three previously reported diploid sequence types (DSTs) and three novel DSTs. Two of the novel DSTs were closely related variants of a previously reported DST, and both showed loss of heterozygosity polymorphisms within one of the seven MLST gene sequences. For three individuals, at least one DST that was present before denture replacement was still detected in either saliva or on dentures at subsequent sampling times. Our results indicate that denture replacement reduces but does not remove, colonising yeast and confirm previous observations of C. albicans strain microevolution. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Total ankle replacement. Early experiences with STAR prosthesis.

    Science.gov (United States)

    Murnaghan, J. M.; Warnock, D. S.; Henderson, S. A.

    2005-01-01

    Early designs of Total Ankle Replacement (TAR) had a high failure rate. More recent experience with the 3-piece, meniscal bearing, total ankle replacement has been more promising. We report a review of the early results of our first 22 prostheses in 20 patients undergoing Scandinavian Total Ankle Replacement (STAR) in Northern Ireland. There was a mean follow-up time of 26 months. Seventeen patients are pain-free at the ankle joint during normal daily activities. Two of the early cases have required revision surgery due to technical errors. Other complications have included malleolar fractures, poor wound healing and postoperative stiffness. These early results show high levels of patient satisfaction, and we are encouraged to continue with total ankle arthroplasty. There is a steep initial learning curve and use of TAR should be restricted to foot and ankle surgeons. Images Fig 1 Figs 2a and b Figs 2 c and d PMID:16022128

  9. SERUM MAGNESIUM LEVELS IN AORTIC AND MITRAL VALVE REPLACEMENT SURGERIES

    Directory of Open Access Journals (Sweden)

    Srinivasa Rao

    2015-08-01

    Full Text Available BACKGROUND : The purpose of the study was to analyze serum magnesium concentration in patients undergoing Aortic and Mitral Valve replacement surgeries. METHODS: This prospective study was conducted in 60 patients who underwent elective Aortic and Mitral va lve replacement surgeries. Blood samples from radial artery were collected just before induction of anesthesia and three days post - operatively for estimation of serum magnesium. RESULTS: Magnesium level was 2.02mg/dl at baseline, 2.28mg/dl, 2.08mg/dl and 1 .90mg/dl respectively on three consecutive days post - operatively. CONCLUSION: The lowering of serum magnesium in Aortic and Mitral valve replacement surgeries postoperatively recommends the use of routine serum magnesium determination and administration to prevent post - operative arrhythmias.

  10. Salto Talaris fixed-bearing total ankle replacement system.

    Science.gov (United States)

    Rush, Shannon M; Todd, Nicholas

    2013-01-01

    The Salto Talaris total ankle replacement is an anatomically designed fixed bearing prosthesis available in the United States based on the successful design of the mobile-bearing Salto prosthesis available outside the United States. The original mobile-bearing design was modified and the mobile-bearing was transferred to the precision instrumentation at the trial phase evaluation. Instrumentation and technique allow the surgeon to determine the functional joint axis before final implantation. The Salto Talaris total ankle replacement design blends minimal bone resection and optimizes surface area, cortical contact, and ultra-high molecular weight polyethylene conformity. The authors present an overview of the Salto Talaris total ankle replacement surgical technique and pearls for successful application.

  11. Stresses in the ankle joint and total ankle replacement design.

    Science.gov (United States)

    Kakkar, Rahul; Siddique, M S

    2011-06-01

    The ankle is a highly congruent joint with a surface area of 11-13 cm(2). Total ankle replacements have been attempted since the early 1970s and design has continually evolved as the early designs were a failure. This was because the stresses involved and the mutiaxial motion of the ankle has not been understood until recently. It has been shown that the talus slides as well as rolls during the ankle arc of motion from plantarflexion to dorsiflexion. Furthermore, the articular surfaces and the calcaneofibular and tibiocalcaneal ligaments have been shown to form a four bar linkage dictating ankle motion. A new design ankle replacement has been suggested recently which allows multiaxial motion at the ankle while maintaining congruency throughout the arc of motion. The early results of this ankle replacement have been encouraging without any reported failures due to mechanical loosening.

  12. Applications of molecular replacement to G protein-coupled receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kruse, Andrew C.; Manglik, Aashish; Kobilka, Brian K., E-mail: kobilka@stanford.edu [Stanford University, 279 Campus Drive, Stanford, CA 94305 (United States); Weis, William I., E-mail: kobilka@stanford.edu [Stanford University, 279 Campus Drive, Stanford, CA 94305 (United States); Stanford University, Fairchild Building, Stanford, CA 94305 (United States)

    2013-11-01

    The use of molecular replacement in solving the structures of G protein-coupled receptors is discussed, with specific examples being described in detail. G protein-coupled receptors (GPCRs) are a large class of integral membrane proteins involved in regulating virtually every aspect of human physiology. Despite their profound importance in human health and disease, structural information regarding GPCRs has been extremely limited until recently. With the advent of a variety of new biochemical and crystallographic techniques, the structural biology of GPCRs has advanced rapidly, offering key molecular insights into GPCR activation and signal transduction. To date, almost all GPCR structures have been solved using molecular-replacement techniques. Here, the unique aspects of molecular replacement as applied to individual GPCRs and to signaling complexes of these important proteins are discussed.

  13. Respondent-Driven Sampling – Testing Assumptions: Sampling with Replacement

    Directory of Open Access Journals (Sweden)

    Barash Vladimir D.

    2016-03-01

    Full Text Available Classical Respondent-Driven Sampling (RDS estimators are based on a Markov Process model in which sampling occurs with replacement. Given that respondents generally cannot be interviewed more than once, this assumption is counterfactual. We join recent work by Gile and Handcock in exploring the implications of the sampling-with-replacement assumption for bias of RDS estimators. We differ from previous studies in examining a wider range of sampling fractions and in using not only simulations but also formal proofs. One key finding is that RDS estimates are surprisingly stable even in the presence of substantial sampling fractions. Our analyses show that the sampling-with-replacement assumption is a minor contributor to bias for sampling fractions under 40%, and bias is negligible for the 20% or smaller sampling fractions typical of field applications of RDS.

  14. Greedy feature replacement for online value function approximation

    Institute of Scientific and Technical Information of China (English)

    Feng-fei ZHAO; Zheng QIN; Zhuo SHAO; Jun FANG; Bo-yan REN

    2014-01-01

    Reinforcement learning (RL) in real-world problems requires function approximations that depend on selecting the appropriate feature representations. Representational expansion techniques can make linear approximators represent value functions more effectively;however, most of these techniques function well only for low dimensional problems. In this paper, we present the greedy feature replacement (GFR), a novel online expansion technique, for value-based RL algorithms that use binary features. Given a simple initial representation, the feature representation is expanded incrementally. New feature dependencies are added automatically to the current representation and conjunctive features are used to replace current features greedily. The virtual temporal difference (TD) error is recorded for each conjunctive feature to judge whether the replacement can improve the approximation. Correctness guarantees and computational complexity analysis are provided for GFR. Experimental results in two domains show that GFR achieves much faster learning and has the capability to handle large-scale problems.

  15. 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.

  16. Failure rate of cemented and uncemented total hip replacements

    DEFF Research Database (Denmark)

    Makela, K. T.; Matilainen, M.; Pulkkinen, P.

    2014-01-01

    Objective To assess the failure rate of cemented, uncemented, hybrid, and reverse hybrid total hip replacements in patients aged 55 years or older. Design Register study. Setting Nordic Arthroplasty Register Association database (combined data from Sweden, Norway, Denmark, and Finland......). Participants 347 899 total hip replacements performed during 1995-2011. Main outcome measures Probability of implant survival (Kaplan-Meier analysis) along with implant survival with revision for any reason as endpoint (Cox multiple regression) adjusted for age, sex, and diagnosis in age groups 55-64, 65......-74, and 75 years or older. Results The proportion of total hip replacements using uncemented implants increased rapidly towards the end of the study period. The 10 year survival of cemented implants in patients aged 65 to 74 and 75 or older (93.8%, 95% confidence interval 93.6% to 94.0% and 95.9%, 95...

  17. Recent patents and designs on hip replacement prostheses.

    Science.gov (United States)

    Derar, H; Shahinpoor, M

    2015-01-01

    Hip replacement surgery has gone through tremendous evolution since the first procedure in 1840. In the past five decades the advances that have been made in technology, advanced and smart materials innovations, surgical techniques, robotic surgery and methods of fixations and sterilization, facilitated hip implants that undergo multiple design revolutions seeking the least problematic implants and a longer survivorship. Hip surgery has become a solution for many in need of hip joint remedy and replacement across the globe. Nevertheless, there are still long-term problems that are essential to search and resolve to find the optimum implant. This paper reviews several recent patents on hip replacement surgery. The patents present various designs of prostheses, different materials as well as methods of fixation. Each of the patents presents a new design as a solution to different issues ranging from the longevity of the hip prostheses to discomfort and inconvenience experienced by patients in the long-term.

  18. Replacement Attack: A New Zero Text Watermarking Attack

    Science.gov (United States)

    Bashardoost, Morteza; Mohd Rahim, Mohd Shafry; Saba, Tanzila; Rehman, Amjad

    2017-03-01

    The main objective of zero watermarking methods that are suggested for the authentication of textual properties is to increase the fragility of produced watermarks against tampering attacks. On the other hand, zero watermarking attacks intend to alter the contents of document without changing the watermark. In this paper, the Replacement attack is proposed, which focuses on maintaining the location of the words in the document. The proposed text watermarking attack is specifically effective on watermarking approaches that exploit words' transition in the document. The evaluation outcomes prove that tested word-based method are unable to detect the existence of replacement attack in the document. Moreover, the comparison results show that the size of Replacement attack is estimated less accurate than other common types of zero text watermarking attacks.

  19. The replacement of serum by hormones in cell culture media.

    Science.gov (United States)

    Sato, G; Hayashi, I

    1976-12-01

    The replacement of serum by hormones in cell culture media. (Reemplazo del suero por hormonas en el medio de cultivo de células). Arch. Biol. Med. Exper. 10: 120-121, 1976. The serum used in cell culture media can be replaced by a mixture of hormones and some accesory blood factors. The pituitary cell line GH3 can be grown in a medium in which serum is replaced by triiodothyronine, transferrin, parathormone, tyrotrophin releasing hormone and somatomedins. Hela and BHK cell strains can also be grown in serum free medium supplemented with hormones. Each cell type appears to have different hormonal requirements yet it may found that some hormones are required for most cell types.

  20. Prospects for replacement of auditory neurons by stem cells.

    Science.gov (United States)

    Shi, Fuxin; Edge, Albert S B

    2013-03-01

    Sensorineural hearing loss is caused by degeneration of hair cells or auditory neurons. Spiral ganglion cells, the primary afferent neurons of the auditory system, are patterned during development and send out projections to hair cells and to the brainstem under the control of largely unknown guidance molecules. The neurons do not regenerate after loss and even damage to their projections tends to be permanent. The genesis of spiral ganglion neurons and their synapses forms a basis for regenerative approaches. In this review we critically present the current experimental findings on auditory neuron replacement. We discuss the latest advances with a focus on (a) exogenous stem cell transplantation into the cochlea for neural replacement, (b) expression of local guidance signals in the cochlea after loss of auditory neurons, (c) the possibility of neural replacement from an endogenous cell source, and (d) functional changes from cell engraftment. Copyright © 2013 Elsevier B.V. All rights reserved.