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Sample records for rescues defects linked

  1. A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome.

    Science.gov (United States)

    Benjamin, Joel S; Pilarowski, Genay O; Carosso, Giovanni A; Zhang, Li; Huso, David L; Goff, Loyal A; Vernon, Hilary J; Hansen, Kasper D; Bjornsson, Hans T

    2017-01-03

    Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d +/βGeo ). Unlike a drug, a dietary intervention could be quickly transitioned to the clinic. Therefore, we have explored whether treatment with a ketogenic diet could lead to a similar rescue through increased amounts of beta-hydroxybutyrate, an endogenous HDACi. Here, we report that a ketogenic diet in Kmt2d +/βGeo mice modulates H3ac and H3K4me3 in the granule cell layer, with concomitant rescue of both the neurogenesis defect and hippocampal memory abnormalities seen in Kmt2d +/βGeo mice; similar effects on neurogenesis were observed on exogenous administration of beta-hydroxybutyrate. These data suggest that dietary modulation of epigenetic modifications through elevation of beta-hydroxybutyrate may provide a feasible strategy to treat the intellectual disability seen in Kabuki syndrome and related disorders.

  2. Evolutionary rescue: linking theory for conservation and medicine.

    Science.gov (United States)

    Alexander, Helen K; Martin, Guillaume; Martin, Oliver Y; Bonhoeffer, Sebastian

    2014-12-01

    Evolutionary responses that rescue populations from extinction when drastic environmental changes occur can be friend or foe. The field of conservation biology is concerned with the survival of species in deteriorating global habitats. In medicine, in contrast, infected patients are treated with chemotherapeutic interventions, but drug resistance can compromise eradication of pathogens. These contrasting biological systems and goals have created two quite separate research communities, despite addressing the same central question of whether populations will decline to extinction or be rescued through evolution. We argue that closer integration of the two fields, especially of theoretical understanding, would yield new insights and accelerate progress on these applied problems. Here, we overview and link mathematical modelling approaches in these fields, suggest specific areas with potential for fruitful exchange, and discuss common ideas and issues for empirical testing and prediction.

  3. L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.

    Science.gov (United States)

    Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E; Gerton, Jennifer L

    2015-03-15

    Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. © The Author 2014. Published by Oxford University Press.

  4. Turmeric Extract Rescues Ethanol-Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD).

    Science.gov (United States)

    Muralidharan, Pooja; Connors, Craig T; Mohammed, Arooj S; Sarmah, Swapnalee; Marrs, Kathleen; Marrs, James A; Chism, Grady W

    2017-09-01

    Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol-induced developmental defect using zebrafish as a model was determined. Ethanol-induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol-induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol-treated embryos. The mechanism underlying the rescue remains to be determined. © 2017 Institute of Food Technologists®.

  5. HEK293T cell lines defective for O-linked glycosylation.

    Directory of Open Access Journals (Sweden)

    James M Termini

    Full Text Available Here we describe derivatives of the HEK293T cell line that are defective in their ability to generate mucin-type O-linked glycosylation. Using CRISPR/Cas9 and a single-cell GFP-sorting procedure, the UDP-galactose-4-epimerase (GALE, galactokinase 1 (GALK1, and galactokinase 2 (GALK2 genes were knocked out individually and in combinations with greater than 90% of recovered clones having the desired mutations. Although HEK293T cells are tetraploid, we found this approach to be an efficient method to target and disrupt all 4 copies of the target gene. Deficient glycosylation in the GALE knockout cell line could be rescued by the addition of galactose and N-acetylgalactosamine (GalNAc to the cell culture media. However, when key enzymes of the galactose/GalNAc salvage pathways were disrupted in tandem (GALE+GALK1 or GALE+GALK2, O-glycosylation was eliminated and could not be rescued by the addition of either galactose plus GalNAc or UDP-galactose plus UDP-GalNAc. GALK1 and GALK2 are key enzymes of the galactose/GalNAc salvage pathways. Mass spectrometry was performed on whole cell lysate of the knockout cell lines to verify the glycosylation phenotype. As expected, the GALE knockout was almost completely devoid of all O-glycosylation, with minimal glycosylation as a result of functional salvage pathways. However, the GALE+GALK1 and GALE+GALK2 knockout lines were devoid of all O-glycans. Mass spectrometry analysis revealed that the disruption of GALE, GALK1, and GALE+GALK2 had little effect on the N-glycome. But when GALE was knocked out in tandem with GALK1, N-glycans were exclusively of the high mannose type. Due to the well-characterized nature of these five knockout cell lines, they will likely prove useful for a wide variety of applications.

  6. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A.

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    Fayçal Guedj

    Full Text Available Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG - a member of a natural polyphenols family, found in great amount in green tea leaves - is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice.

  7. The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutants.

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    Sven Vilain

    2012-01-01

    Full Text Available Pink1 is a mitochondrial kinase involved in Parkinson's disease, and loss of Pink1 function affects mitochondrial morphology via a pathway involving Parkin and components of the mitochondrial remodeling machinery. Pink1 loss also affects the enzymatic activity of isolated Complex I of the electron transport chain (ETC; however, the primary defect in pink1 mutants is unclear. We tested the hypothesis that ETC deficiency is upstream of other pink1-associated phenotypes. We expressed Saccaromyces cerevisiae Ndi1p, an enzyme that bypasses ETC Complex I, or sea squirt Ciona intestinalis AOX, an enzyme that bypasses ETC Complex III and IV, in pink1 mutant Drosophila and find that expression of Ndi1p, but not of AOX, rescues pink1-associated defects. Likewise, loss of function of subunits that encode for Complex I-associated proteins displays many of the pink1-associated phenotypes, and these defects are rescued by Ndi1p expression. Conversely, expression of Ndi1p fails to rescue any of the parkin mutant phenotypes. Additionally, unlike pink1 mutants, fly parkin mutants do not show reduced enzymatic activity of Complex I, indicating that Ndi1p acts downstream or parallel to Pink1, but upstream or independent of Parkin. Furthermore, while increasing mitochondrial fission or decreasing mitochondrial fusion rescues mitochondrial morphological defects in pink1 mutants, these manipulations fail to significantly rescue the reduced enzymatic activity of Complex I, indicating that functional defects observed at the level of Complex I enzymatic activity in pink1 mutant mitochondria do not arise from morphological defects. Our data indicate a central role for Complex I dysfunction in pink1-associated defects, and our genetic analyses with heterologous ETC enzymes suggest that Ndi1p-dependent NADH dehydrogenase activity largely acts downstream of, or in parallel to, Pink1 but upstream of Parkin and mitochondrial remodeling.

  8. Functional antigen binding by the defective B cells of CBA/N mice.

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    Snippe, H; Merchant, B; Lizzio, E F; Inman, J K

    1982-01-01

    CBA/N mice have an X-linked B cell defect which prevents them from responding to nonmitogenic thymic independent (TI-2) antigens such as dinitrophenylated DNP-Ficoll (1,2). The F1 male progeny of CBA/N female mice express the same defect. Spleen cell suspensions from such defective mice (CBA/N X C3H/HeN F1 males) could not respond to DNP-Ficoll following in vitro immunization and subsequent transfer into irradiated, syngeneic, F1 male recipients as expected. In contrast, normal CBA/N X C3H/HeN F1 female spleen cells could respond and effect a "rescue"; they mounted strong plaque-forming cell responses 7 days after in vitro exposure to DNP-Ficoll and subsequent transfer into irradiated F1 male recipients. Defective F1 male spleen cells, however, could bind significant quantities of 125I-DNP-Ficoll after in vitro exposure. Extensive washing of these spleen cells could not reverse this binding. Such DNP-Ficoll-exposed and washed F1 male spleen cells could, after transfer, aid normal untreated F1 female cells in their rescue function. The defective F1 male spleen cells could convey immunogenic quantities of DNP-Ficoll to the "rescuing" F1 female cells. Mitomycin treatment of F1 male cells did not interfere with their conveyor function. Goat anti-mouse mu serum impeded the passive antigen conveyor function of defective F1 male cells as did prior exposure to high concentrations of free DNP hapten. Our data support the view that the B cell defect of CBA/N X C3H/HeN F1 male mice does not relate to antigen binding, but rather to an inability to be effectively triggered by certain cell-bound polymeric antigens.

  9. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

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    ... Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Printable PDF Open All Close ... boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

  10. Transgenic Expression of Dspp Partially Rescued the Long Bone Defects of Dmp1-null Mice

    Science.gov (United States)

    Jani, Priyam H.; Gibson, Monica P.; Liu, Chao; Zhang, Hua; Wang, Xiaofang; Lu, Yongbo; Qin, Chunlin

    2016-01-01

    Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1−/−) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1−/− mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as “Dmp1−/−;Dspp-Tg mice”). We characterized the long bones of the Dmp1−/−;Dspp-Tg mice at different ages and compared them with those from Dmp1−/− and Dmp1+/− (normal control) mice. Our analyses showed that the long bones of Dmp1−/−;Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1−/− mice. The long bones of Dmp1−/−;Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1−/− mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1−/− mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that

  11. Near-infrared 808 nm light boosts complex IV-dependent respiration and rescues a Parkinson-related pink1 model.

    Directory of Open Access Journals (Sweden)

    Melissa Vos

    Full Text Available Mitochondrial electron transport chain (ETC defects are observed in Parkinson's disease (PD patients and in PD fly- and mouse-models; however it remains to be tested if acute improvement of ETC function alleviates PD-relevant defects. We tested the hypothesis that 808 nm infrared light that effectively penetrates tissues rescues pink1 mutants. We show that irradiating isolated fly or mouse mitochondria with 808 nm light that is absorbed by ETC-Complex IV acutely improves Complex IV-dependent oxygen consumption and ATP production, a feature that is wavelength-specific. Irradiating Drosophila pink1 mutants using a single dose of 808 nm light results in a rescue of major systemic and mitochondrial defects. Time-course experiments indicate mitochondrial membrane potential defects are rescued prior to mitochondrial morphological defects, also in dopaminergic neurons, suggesting mitochondrial functional defects precede mitochondrial swelling. Thus, our data indicate that improvement of mitochondrial function using infrared light stimulation is a viable strategy to alleviate pink1-related defects.

  12. Splitting, linking, knotting, and solitonic escape of topological defects in nematic drops with handles.

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    Tasinkevych, Mykola; Campbell, Michael G; Smalyukh, Ivan I

    2014-11-18

    Topologically nontrivial field excitations, including solitonic, linked, and knotted structures, play important roles in physical systems ranging from classical fluids and liquid crystals, to electromagnetism, classic, and quantum field theories. These excitations can appear spontaneously during symmetry-breaking phase transitions. For example, in cosmological theories, cosmic strings may have formed knotted configurations influencing the Early Universe development, whereas in liquid crystals transient tangled defect lines were observed during isotropic-nematic transitions, eventually relaxing to defect-free states. Knotted and solitonic fields and defects were also obtained using optical manipulation, complex-shaped colloids, and frustrated cholesterics. Here we use confinement of nematic liquid crystal by closed surfaces with varied genus and perpendicular boundary conditions for a robust control of appearance and stability of such field excitations. Theoretical modeling and experiments reveal structure of defect lines as a function of the surface topology and material and geometric parameters, establishing a robust means of controlling solitonic, knotted, linked, and other field excitations.

  13. Nickel sulfate induces numerous defects in Caenorhabditis elegans that can also be transferred to progeny

    International Nuclear Information System (INIS)

    Wang Dayong; Wang Yang

    2008-01-01

    Whether the multiple biological toxicities from nickel exposure could be transferred to progeny has not been clarified. In this report, we explored the Caenorhabditis elegans to analyze the multiple toxicities of nickel and their possibly transferable properties. The nickel toxicity caused multiple biological defects in a concentration-dependent manner. Moreover, most of these toxicities could be transferred and could be only partially rescued in progeny. Some specific phenotypes in progeny were also found to exhibit no obvious rescue phenotypes or to show even more severe defects than their parents. The defects caused by nickel exposure could be classified into four groups according to their transferring properties. That is, the defects caused by nickel exposure could be largely, or partially, or unable to be rescued, or became even more severe in progeny animals. Therefore, most of the nickel exposure-caused defects can be transferred from parents to their progeny to different degrees in C. elegans. - Nickel exposure can cause multi-biological toxicities and these defects can be transferred from parents to their progeny in C. elegans

  14. Nickel sulfate induces numerous defects in Caenorhabditis elegans that can also be transferred to progeny

    Energy Technology Data Exchange (ETDEWEB)

    Wang Dayong [Department of Genetics and Developmental Biology, Southeast University, Nanjing 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Ministry of Education (China)], E-mail: dayongw@seu.edu.cn; Wang Yang [Department of Genetics and Developmental Biology, Southeast University, Nanjing 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Ministry of Education (China)

    2008-02-15

    Whether the multiple biological toxicities from nickel exposure could be transferred to progeny has not been clarified. In this report, we explored the Caenorhabditis elegans to analyze the multiple toxicities of nickel and their possibly transferable properties. The nickel toxicity caused multiple biological defects in a concentration-dependent manner. Moreover, most of these toxicities could be transferred and could be only partially rescued in progeny. Some specific phenotypes in progeny were also found to exhibit no obvious rescue phenotypes or to show even more severe defects than their parents. The defects caused by nickel exposure could be classified into four groups according to their transferring properties. That is, the defects caused by nickel exposure could be largely, or partially, or unable to be rescued, or became even more severe in progeny animals. Therefore, most of the nickel exposure-caused defects can be transferred from parents to their progeny to different degrees in C. elegans. - Nickel exposure can cause multi-biological toxicities and these defects can be transferred from parents to their progeny in C. elegans.

  15. Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like clinical syndrome.

    Science.gov (United States)

    Garone, Caterina; D'Souza, Aaron R; Dallabona, Cristina; Lodi, Tiziana; Rebelo-Guiomar, Pedro; Rorbach, Joanna; Donati, Maria Alice; Procopio, Elena; Montomoli, Martino; Guerrini, Renzo; Zeviani, Massimo; Calvo, Sarah E; Mootha, Vamsi K; DiMauro, Salvatore; Ferrero, Ileana; Minczuk, Michal

    2017-11-01

    Defects in nuclear-encoded proteins of the mitochondrial translation machinery cause early-onset and tissue-specific deficiency of one or more OXPHOS complexes. Here, we report a 7-year-old Italian boy with childhood-onset rapidly progressive encephalomyopathy and stroke-like episodes. Multiple OXPHOS defects and decreased mtDNA copy number (40%) were detected in muscle homogenate. Clinical features combined with low level of plasma citrulline were highly suggestive of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, however, the common m.3243 A > G mutation was excluded. Targeted exome sequencing of genes encoding the mitochondrial proteome identified a damaging mutation, c.567 G > A, affecting a highly conserved amino acid residue (p.Gly189Arg) of the MRM2 protein. MRM2 has never before been linked to a human disease and encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA. We generated a knockout yeast model for the orthologous gene that showed a defect in respiration and the reduction of the 2'-O-methyl modification at the equivalent position (U2791) in the yeast mitochondrial 21S rRNA. Complementation with the mrm2 allele carrying the equivalent yeast mutation failed to rescue the respiratory phenotype, which was instead completely rescued by expressing the wild-type allele. Our findings establish that defective MRM2 causes a MELAS-like phenotype, and suggests the genetic screening of the MRM2 gene in patients with a m.3243 A > G negative MELAS-like presentation. © The Author 2017. Published by Oxford University Press.

  16. Space Rescue

    Science.gov (United States)

    Muratore, John F.

    2007-01-01

    Space Rescue has been a topic of speculation for a wide community of people for decades. Astronauts, aerospace engineers, diplomats, medical and rescue professionals, inventors and science fiction writers have all speculated on this problem. Martin Caidin's 1964 novel Marooned dealt with the problems of rescuing a crew stranded in low earth orbit. Legend at the Johnson Space Center says that Caidin's portrayal of a Russian attempt to save the American crew played a pivotal role in convincing the Russians to join the real joint Apollo-Soyuz mission. Space Rescue has been a staple in science fiction television and movies portrayed in programs such as Star Trek, Stargate-SG1 and Space 1999 and movies such as Mission To Mars and Red Planet. As dramatic and as difficult as rescue appears in fictional accounts, in the real world it has even greater drama and greater difficulty. Space rescue is still in its infancy as a discipline and the purpose of this chapter is to describe the issues associated with space rescue and the work done so far in this field. For the purposes of this chapter, the term space rescue will refer to any system which allows for rescue or escape of personnel from situations which endanger human life in a spaceflight operation. This will span the period from crew ingress prior to flight through crew egress postlanding. For the purposes of this chapter, the term primary system will refer to the spacecraft system that a crew is either attempting to escape from or from which an attempt is being made to rescue the crew.

  17. The emergence of the rescue effect from explicit within and between-patch dynamics in a metapopulation

    KAUST Repository

    Eriksson, Anders

    2014-02-12

    Immigration can rescue local populations from extinction, helping to stabilize a metapopulation. Local population dynamics is important for determining the strength of this rescue effect, but the mechanistic link between local demographic parameters and the rescue effect at the metapopulation level has received very little attention by modellers. We develop an analytical framework that allows us to describe the emergence of the rescue effect from interacting local stochastic dynamics. We show this framework to be applicable to a wide range of spatial scales, providing a powerful and convenient alternative to individual-based models for making predictions concerning the fate of metapopulations. We show that the rescue effect plays an important role in minimizing the increase in local extinction probability associated with high demographic stochasticity, but its role is more limited in the case of high local environmental stochasticity of recruitment or survival. While most models postulate the rescue effect, our framework provides an explicit mechanistic link between local dynamics and the emergence of the rescue effect, and more generally the stability of the whole metapopulation. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  18. The emergence of the rescue effect from explicit within and between-patch dynamics in a metapopulation

    KAUST Repository

    Eriksson, Anders; Elí as-Wolff, Federico; Mehlig, Bernhard; Manica, Andrea

    2014-01-01

    Immigration can rescue local populations from extinction, helping to stabilize a metapopulation. Local population dynamics is important for determining the strength of this rescue effect, but the mechanistic link between local demographic parameters and the rescue effect at the metapopulation level has received very little attention by modellers. We develop an analytical framework that allows us to describe the emergence of the rescue effect from interacting local stochastic dynamics. We show this framework to be applicable to a wide range of spatial scales, providing a powerful and convenient alternative to individual-based models for making predictions concerning the fate of metapopulations. We show that the rescue effect plays an important role in minimizing the increase in local extinction probability associated with high demographic stochasticity, but its role is more limited in the case of high local environmental stochasticity of recruitment or survival. While most models postulate the rescue effect, our framework provides an explicit mechanistic link between local dynamics and the emergence of the rescue effect, and more generally the stability of the whole metapopulation. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  19. REM sleep rescues learning from interference

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    McDevitt, Elizabeth A.; Duggan, Katherine A.; Mednick, Sara C.

    2015-01-01

    Classical human memory studies investigating the acquisition of temporally-linked events have found that the memories for two events will interfere with each other and cause forgetting (i.e., interference; Wixted, 2004). Importantly, sleep helps consolidate memories and protect them from subsequent interference (Ellenbogen, Hulbert, Stickgold, Dinges, & Thompson-Schill, 2006). We asked whether sleep can also repair memories that have already been damaged by interference. Using a perceptual learning paradigm, we induced interference either before or after a consolidation period. We varied brain states during consolidation by comparing active wake, quiet wake, and naps with either non-rapid eye movement sleep (NREM), or both NREM and REM sleep. When interference occurred after consolidation, sleep and wake both produced learning. However, interference prior to consolidation impaired memory, with retroactive interference showing more disruption than proactive interference. Sleep rescued learning damaged by interference. Critically, only naps that contained REM sleep were able to rescue learning that was highly disrupted by retroactive interference. Furthermore, the magnitude of rescued learning was correlated with the amount of REM sleep. We demonstrate the first evidence of a process by which the brain can rescue and consolidate memories damaged by interference, and that this process requires REM sleep. We explain these results within a theoretical model that considers how interference during encoding interacts with consolidation processes to predict which memories are retained or lost. PMID:25498222

  20. Rescuing mutant CFTR: a multi-task approach to a better outcome in treating cystic fibrosis.

    Science.gov (United States)

    Amaral, Margarida D; Farinha, Carlos M

    2013-01-01

    Correcting multiple defects of mutant CFTR with small molecule compounds has been the goal of an increasing number of recent Cystic Fibrosis (CF) drug discovery programmes. However, the mechanism of action (MoA) by which these molecules restore mutant CFTR is still poorly understood, in particular of CFTR correctors, i.e., compounds rescuing to the cells surface the most prevalent mutant in CF patients--F508del-CFTR. However, there is increasing evidence that to fully restore the multiple defects associated with F508del-CFTR, different small molecules with distinct corrective properties may be required. Towards this goal, a better insight into MoA of correctors is needed and several constraints should be addressed. The methodological approaches to achieve this include: 1) testing the combined effect of compounds with that of other (non-pharmacological) rescuing strategies (e.g., revertants or low temperature); 2) assessing effects in multiple cellular models (non-epithelial vs epithelial, non-human vs human, immortalized vs primary cultures, polarized vs non polarized, cells vs tissues); 3) assessing compound effects on isolated CFTR domains (e.g., compound binding by surface plasmon resonance, assessing effects on domain folding and aggregation); and finally 4) assessing compounds specificity in rescuing different CFTR mutants and other mutant proteins. These topics are reviewed and discussed here so as to provide a state-of-the art review on how to combine multiple ways of rescuing mutant CFTR to the ultimate benefit of CF patients.

  1. Novel Mutation of LRP6 Identified in Chinese Han Population Links Canonical WNT Signaling to Neural Tube Defects.

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    Shi, Zhiwen; Yang, Xueyan; Li, Bin-Bin; Chen, Shuxia; Yang, Luming; Cheng, Liangping; Zhang, Ting; Wang, Hongyan; Zheng, Yufang

    2018-01-15

    Neural tube defects (NTDs), the second most frequent cause of human congenital abnormalities, are debilitating birth defects due to failure of neural tube closure. It has been shown that noncanonical WNT/planar cell polarity (PCP) signaling is required for convergent extension (CE), the initiation step of neural tube closure (NTC). But the effect of canonical WNT//β-catenin signaling during NTC is still elusive. LRP6 (low density lipoprotein receptor related proteins 6) was identified as a co-receptor for WNT/β-catenin signaling, but recent studies showed that it also can mediate WNT/PCP signaling. In this study, we screened mutations in the LRP6 gene in 343 NTDs and 215 ethnically matched normal controls of Chinese Han population. Three rare missense mutations (c.1514A>G, p.Y505C); c.2984A>G, p.D995G; and c.4280C>A, p.P1427Q) of the LRP6 gene were identified in Chinese NTD patients. The Y505C mutation is a loss-of-function mutation on both WNT/β-catenin and PCP signaling. The D995G mutation only partially lost inhibition on PCP signaling without affecting WNT/β-catenin signaling. The P1427Q mutation dramatically increased WNT/β-catenin signaling but only mildly loss of inhibition on PCP signaling. All three mutations failed to rescue CE defects caused by lrp6 morpholino oligos knockdown in zebrafish. Of interest, when overexpressed, D995G did not induce any defects, but Y505C and P1427Q caused more severe CE defects in zebrafish. Our results suggested that over-active canonical WNT signaling induced by gain-of-function mutation in LRP6 could also contribute to human NTDs, and a balanced WNT/β-catenin and PCP signaling is probably required for proper neural tube development. Birth Defects Research 110:63-71, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Rescue Manual. Module 6.

    Science.gov (United States)

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The sixth of 10 modules contains 4 chapters: (1) industrial rescue; (2) rescue from a confined space; (3) extrication from heavy equipment; and (4) rescue operations involving elevators. Key points, an introduction, and conclusion accompany…

  3. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

    Science.gov (United States)

    Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

    2016-01-01

    Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

  4. Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias.

    Science.gov (United States)

    Denton, Kyle; Mou, Yongchao; Xu, Chong-Chong; Shah, Dhruvi; Chang, Jaerak; Blackstone, Craig; Li, Xue-Jun

    2018-05-02

    Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes. We analyzed mitochondrial morphology and noted a significant reduction in both mitochondrial length and their densities within axons of these HSP neurons. Mitochondrial membrane potential was also decreased, confirming functional mitochondrial defects. Notably, mdivi-1, an inhibitor of the mitochondrial fission GTPase DRP1, rescues mitochondrial morphology defects and suppresses the impairment in neurite outgrowth and late-onset apoptosis in HSP neurons. Furthermore, knockdown of these HSP genes causes similar axonal defects, also mitigated by treatment with mdivi-1. Finally, neurite outgrowth defects in SPG15 and SPG48 cortical neurons can be rescued by knocking down DRP1 directly. Thus, abnormal mitochondrial morphology caused by an imbalance of mitochondrial fission and fusion underlies specific axonal defects and serves as a potential therapeutic target for SPG15 and SPG48.

  5. Progranulin modulates zebrafish motoneuron development in vivo and rescues truncation defects associated with knockdown of Survival motor neuron 1

    Directory of Open Access Journals (Sweden)

    Bateman Andrew

    2010-10-01

    Full Text Available Abstract Background Progranulin (PGRN encoded by the GRN gene, is a secreted glycoprotein growth factor that has been implicated in many physiological and pathophysiological processes. PGRN haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to progressive neuronal atrophy in the form of frontotemporal lobar degeneration (FTLD. This form of the disease is associated with neuronal inclusions that bear the ubiquitinated TAR DNA Binding Protein-43 (TDP-43 molecular signature (FTLD-U. The neurotrophic properties of PGRN in vitro have recently been reported but the role of PGRN in neurons is not well understood. Here we document the neuronal expression and functions of PGRN in spinal cord motoneuron (MN maturation and branching in vivo using zebrafish, a well established model of vertebrate embryonic development. Results Whole-mount in situ hybridization and immunohistochemical analyses of zebrafish embryos revealed that zfPGRN-A is expressed within the peripheral and central nervous systems including the caudal primary (CaP MNs within the spinal cord. Knockdown of zfPGRN-A mRNA translation mediated by antisense morpholino oligonucleotides disrupted normal CaP MN development resulting in both truncated MNs and inappropriate early branching. Ectopic over-expression of zfPGRN-A mRNA resulted in increased MN branching and rescued the truncation defects brought about by knockdown of zfPGRN-A expression. The ability of PGRN to interact with established MN developmental pathways was tested. PGRN over-expression was found to reverse the truncation defect resulting from knockdown of Survival of motor neuron 1 (smn1. This is involved in small ribonucleoprotein biogenesis RNA processing, mutations of which cause Spinal Muscular Atrophy (SMA in humans. It did not reverse the MN defects caused by interfering with the neuronal guidance pathway by knockdown of expression of NRP-1, a semaphorin co-receptor. Conclusions Expression of

  6. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

    Science.gov (United States)

    Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

    2014-08-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

  7. Restoration of Motor Defects Caused by Loss of Drosophila TDP-43 by Expression of the Voltage-Gated Calcium Channel, Cacophony, in Central Neurons.

    Science.gov (United States)

    Lembke, Kayly M; Scudder, Charles; Morton, David B

    2017-09-27

    Defects in the RNA-binding protein, TDP-43, are known to cause a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar dementia. A variety of experimental systems have shown that neurons are sensitive to TDP-43 expression levels, yet the specific functional defects resulting from TDP-43 dysregulation have not been well described. Using the Drosophila TDP-43 ortholog TBPH, we previously showed that TBPH-null animals display locomotion defects as third instar larvae. Furthermore, loss of TBPH caused a reduction in cacophony , a Type II voltage-gated calcium channel, expression and that genetically restoring cacophony in motor neurons in TBPH mutant animals was sufficient to rescue the locomotion defects. In the present study, we examined the relative contributions of neuromuscular junction physiology and the motor program to the locomotion defects and identified subsets of neurons that require cacophony expression to rescue the defects. At the neuromuscular junction, we showed mEPP amplitudes and frequency require TBPH. Cacophony expression in motor neurons rescued mEPP frequency but not mEPP amplitude. We also showed that TBPH mutants displayed reduced motor neuron bursting and coordination during crawling and restoring cacophony selectively in two pairs of cells located in the brain, the AVM001b/2b neurons, also rescued the locomotion and motor defects, but not the defects in neuromuscular junction physiology. These results suggest that the behavioral defects associated with loss of TBPH throughout the nervous system can be associated with defects in a small number of genes in a limited number of central neurons, rather than peripheral defects. SIGNIFICANCE STATEMENT TDP-43 dysfunction is a common feature in neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal lobar dementia, and Alzheimer's disease. Loss- and gain-of-function models have shown that neurons are sensitive to TDP-43

  8. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress

    Science.gov (United States)

    Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S.

    2016-01-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  9. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Therese Wilhelm

    2016-05-01

    Full Text Available Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es. Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3% rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing, and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and

  10. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Science.gov (United States)

    Wilhelm, Therese; Ragu, Sandrine; Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S

    2016-05-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  11. Vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association with Mayer-Rokitansky-Küster-Hauser syndrome in co-occurrence

    DEFF Research Database (Denmark)

    Bjørsum-Meyer, Thomas; Herlin, Morten; Qvist, Niels

    2016-01-01

    Background: The vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome are rare conditions. We aimed to present two cases with the vertebral defect, anal atresia, cardiac...... defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser co-occurrence from our local surgical center and through a systematic literature search detect published cases. Furthermore, we aimed to collect existing knowledge...... in the embryopathogenesis and genetics in order to discuss a possible link between the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome. Case presentation: Our first case was a white girl...

  12. Link Between RI-ISI and Inspection Qualification: Relationship between Defect Detection Rate and Margin of Detection

    International Nuclear Information System (INIS)

    Shepherd, Barrie; Goujon, Sophie; Whittle, John

    2007-01-01

    Quantitative risk-informed in-service inspection (RI-ISI) requires a quantitative measurement of inspection effectiveness if the risk change associated with an inspection is to be determined. Knowing the probability of detection (POD) as a function of defect depth (through wall dimension) would provide ideal information. However the main in-service inspection method for nuclear plant is ultrasonics, for which defect detection capability depends on a wide variety of parameters besides defect depth, such as defect orientation, roughness, location, shape etc. In recognition of this the European approach to inspection qualification is generally based on some combination of technical justification, and practical trials on a relatively limited number of defects. This inspection qualification process involves demonstrating that defects of concern will generate responses in excess of the specified recording level or noise, depending on the inspection. It is not currently designed to quantify the probability with which defects will be detected. The work described in this report has been performed in order to help address the problem of how the information generated during inspection qualification can be used as an input for RI-ISI. The approach adopted has been to recognise that as the defect response increases above the recording or noise level, the probability of detecting defects is likely to increase. The work therefore involved an investigation of the relationship between POD (strictly speaking defect detection rate) and margin of detection. It involved blind manual and automated ultrasonic trials on artificial defects in test plates designed to generate a range of signal responses. The detection rate for defects which provided signals at a particular level above noise or above a recording level was then measured. A relationship between defect detection rate and margin of detection has been established based on these trials. In addition to establishing a stronger link

  13. Absence of Wip1 partially rescues Atm deficiency phenotypes in mice

    Science.gov (United States)

    Darlington, Yolanda; Nguyen, Thuy-Ai; Moon, Sung-Hwan; Herron, Alan; Rao, Pulivarthi; Zhu, Chengming; Lu, Xiongbin; Donehower, Lawrence A.

    2011-01-01

    Wildtype p53-Induced Phosphatase 1 (WIP1) is a serine/threonine phosphatase that dephosphorylates proteins in the ataxia telangiectasia mutated (ATM)-initiated DNA damage response pathway. WIP1 may play a homeostatic role in ATM signaling by returning the cell to a normal pre-stress state following completion of DNA repair. To better understand the effects of WIP1 on ATM signaling, we crossed Atm-deficient mice to Wip1-deficient mice and characterized phenotypes of the double knockout progeny. We hypothesized that the absence of Wip1 might rescue Atm deficiency phenotypes. Atm null mice, like ATM-deficient humans with the inherited syndrome ataxia telangiectasia, exhibit radiation sensitivity, fertility defects, and are T-cell lymphoma prone. Most double knockout mice were largely protected from lymphoma development and had a greatly extended lifespan compared to Atm null mice. Double knockout mice had increased p53 and H2AX phosphorylation and p21 expression compared to their Atm null counterparts, indicating enhanced p53 and DNA damage responses. Additionally, double knockout splenocytes displayed reduced chromosomal instability compared to Atm null mice. Finally, doubly null mice were partially rescued from infertility defects observed in Atm null mice. These results indicate that inhibition of WIP1 may represent a useful strategy for cancer treatment in general and A-T patients in particular. PMID:21765465

  14. Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging.

    Science.gov (United States)

    Sage, Peter T; Tan, Catherine L; Freeman, Gordon J; Haigis, Marcia; Sharpe, Arlene H

    2015-07-14

    Defective antibody production in aging is broadly attributed to immunosenescence. However, the precise immunological mechanisms remain unclear. Here, we demonstrate an increase in the ratio of inhibitory T follicular regulatory (TFR) cells to stimulatory T follicular helper (TFH) cells in aged mice. Aged TFH and TFR cells are phenotypically distinct from those in young mice, exhibiting increased programmed cell death protein-1 expression but decreased ICOS expression. Aged TFH cells exhibit defective antigen-specific responses, and programmed cell death protein-ligand 1 blockade can partially rescue TFH cell function. In contrast, young and aged TFR cells have similar suppressive capacity on a per-cell basis in vitro and in vivo. Together, these studies reveal mechanisms contributing to defective humoral immunity in aging: an increase in suppressive TFR cells combined with impaired function of aged TFH cells results in reduced T-cell-dependent antibody responses in aged mice. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Atrial septal defect in a Korean wild raccoon dog.

    Science.gov (United States)

    Yim, Soomi; Choi, Sooyoung; Kim, Jongtaek; Chung, Jin-Young; Park, Inchul

    2017-10-07

    An approximately two-year-old, male 6.1 kg body weight, Korean wild raccoon dog (Nyctereutes procyonoides koreensis) was captured by the wildlife medical rescue center of Kangwon National University. Upon physical examination, the heart rate was 87 beats per min and there were no clinical signs. The hematological, and blood biochemical profiles revealed no remarkable findings; however, thoracic radiographs showed cardiac enlargement, especially in the right atrium. On electrocardiogram, sinus node dysfunction and bradyarrhythmia were revealed. Echocardiography showed a left-to-right shunting atrial septal defect. Based on these findings, this Korean wild raccoon dog was diagnosed with atrial septal defect. This is the rare case report of atrial septal defect in wildlife.

  16. Rescuing--a universal phenomenon.

    Science.gov (United States)

    Little, John

    2014-12-01

    Rescuing, where the person is delivered from the immediacy of their conundrum by another, complicates management. The object of this paper is to understand the difficulty in relinquishing the rescuing role. Rescuing is a universal phenomenon in parenting, teaching and therapy that has developed over time through a variety of interwoven social, economic, psychological and clinical variables. © The Royal Australian and New Zealand College of Psychiatrists 2014.

  17. X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect.

    Science.gov (United States)

    Ravell, Juan; Chaigne-Delalande, Benjamin; Lenardo, Michael

    2014-12-01

    To describe the role of the magnesium transporter 1 (MAGT1) in the pathogenesis of 'X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia' (XMEN) disease and its clinical implications. The magnesium transporter protein MAGT1 participates in the intracellular magnesium ion (Mg) homeostasis and facilitates a transient Mg influx induced by the activation of the T-cell receptor. Loss-of-function mutations in MAGT1 cause an immunodeficiency named 'XMEN syndrome', characterized by CD4 lymphopenia, chronic EBV infection, and EBV-related lymphoproliferative disorders. Patients with XMEN disease have impaired T-cell activation and decreased cytolytic function of natural killer (NK) and CD8 T cells because of decreased expression of the NK stimulatory receptor 'natural-killer group 2, member D' (NKG2D). Patients may have defective specific antibody responses secondary to T cell dysfunction, but B cells have not been shown to be directly affected by mutations in MAGT1. XMEN disease has revealed a novel role for free intracellular magnesium in the immune system. Further understanding of the MAGT1 signaling pathway may lead to new diagnostic and therapeutic approaches.

  18. [Medical rescue of China National Earthquake Disaster Emergency Search and Rescue Team in Lushan earthquake].

    Science.gov (United States)

    Liu, Ya-hua; Yang, Hui-ning; Liu, Hui-liang; Wang, Fan; Hu, Li-bin; Zheng, Jing-chen

    2013-05-01

    To summarize and analyze the medical mission of China National Earthquake Disaster Emergency Search and Rescue Team (CNESAR) in Lushan earthquake, to promote the medical rescue effectiveness incorporated with search and rescue. Retrospective analysis of medical work data by CNESAR from April 21th, 2013 to April 27th during Lushan earthquake rescue, including the medical staff dispatch and the wounded case been treated. The reasonable medical corps was composed by 22 members, including 2 administrators, 11 doctors [covering emergency medicine, orthopedics (joints and limbs, spinal), obstetrics and gynecology, gastroenterology, cardiology, ophthalmology, anesthesiology, medical rescue, health epidemic prevention, clinical laboratory of 11 specialties], 1 ultrasound technician, 5 nurses, 1 pharmacist, 1 medical instrument engineer and 1 office worker for propaganda. There were two members having psychological consultants qualifications. The medical work were carried out in seven aspects, including medical care assurance for the CNESAR members, first aid cooperation with search and rescue on site, clinical work in refugees' camp, medical round service for scattered village people, evacuation for the wounded, mental intervention, and the sanitary and anti-epidemic work. The medical work covered 24 small towns, and medical staff established 3 medical clinics at Taiping Town, Shuangshi Town of Lushan County and Baoxing County. Medical rescue, mental intervention for the old and kids, and sanitary and anti-epidemic were performed at the above sites. The medical corps had successful evacuated 2 severe wounded patients and treated the wounded over thousands. Most of the wounded were soft tissue injuries, external injury, respiratory tract infections, diarrhea, and heat stroke. Compared with the rescue action in 2008 Wenchuan earthquake, the aggregation and departure of rescue team in Lushan earthquake, the traffic control order in disaster area, the self-aid and buddy aid

  19. Failure to Rescue, Rescue Surgery and Centralization of Postoperative Complications: A Challenge for General and Acute Care Surgeons.

    Science.gov (United States)

    Zago, Mauro; Bozzo, Samantha; Carrara, Giulia; Mariani, Diego

    2017-01-01

    To explore the current literature on the failure to rescue and rescue surgery concepts, to identify the key items for decreasing the failure to rescue rate and improve outcome, to verify if there is a rationale for centralization of patients suffering postoperative complications. There is a growing awareness about the need to assess and measure the failure to rescue rate, on institutional, regional and national basis. Many factors affect failure to rescue, and all should be individually analyzed and considered. Rescue surgery is one of these factors. Rescue surgery assumes an acute care surgery background. Measurement of failure to rescue rate should become a standard for quality improvement programs. Implementation of all clinical and organizational items involved is the key for better outcomes. Preparedness for rescue surgery is a main pillar in this process. Centralization of management, audit, and communication are important as much as patient centralization. Celsius.

  20. 46 CFR 133.135 - Rescue boats.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Rescue boats. 133.135 Section 133.135 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS LIFESAVING SYSTEMS Requirements for All OSVs § 133.135 Rescue boats. (a) Each OSV must carry at least one rescue boat. Each rescue...

  1. 46 CFR 199.262 - Rescue boats.

    Science.gov (United States)

    2010-10-01

    ... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST...

  2. A Novel Expression Cassette of Lyssavirus Shows that the Distantly Related Mokola Virus Can Rescue a Defective Rabies Virus Genome

    Science.gov (United States)

    Le Mercier, Philippe; Jacob, Yves; Tanner, Kyle; Tordo, Noël

    2002-01-01

    By comparing three expression vectors for the rabies virus (Rv) minigenome, we show that the characteristic of the Rv RNA is important for efficient rescue despite its not being crucial for replication. Moreover, we show that the coexpression of the viral proteins from helper Rv and Mokola virus could rescue the Rv minigenome while Rv-related European bat lyssavirus 1 could not, suggesting that the signals controlling transcription and replication are conserved in the distantly related Rv and Mokola virus. PMID:11799201

  3. Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice.

    Science.gov (United States)

    Li, C; Lan, Y; Krumlauf, R; Jiang, R

    2017-10-01

    Cleft palate is a common birth defect caused by disruption of palatogenesis during embryonic development. Although mutations disrupting components of the Wnt signaling pathway have been associated with cleft lip and palate in humans and mice, the mechanisms involving canonical Wnt signaling and its regulation in secondary palate development are not well understood. Here, we report that canonical Wnt signaling plays an important role in Pax9-mediated regulation of secondary palate development. We found that cleft palate pathogenesis in Pax9-deficient embryos is accompanied by significantly reduced expression of Axin2, an endogenous target of canonical Wnt signaling, in the developing palatal mesenchyme, particularly in the posterior regions of the palatal shelves. We found that expression of Dkk2, encoding a secreted Wnt antagonist, is significantly increased whereas the levels of active β-catenin protein, the essential transcriptional coactivator of canonical Wnt signaling, is significantly decreased in the posterior regions of the palatal shelves in embryonic day 13.5 Pax9-deficent embryos in comparison with control littermates. We show that small molecule-mediated inhibition of Dickkopf (DKK) activity in utero during palatal shelf morphogenesis partly rescued secondary palate development in Pax9-deficient embryos. Moreover, we found that genetic inactivation of Wise, which is expressed in the developing palatal shelves and encodes another secreted antagonist of canonical Wnt signaling, also rescued palate morphogenesis in Pax9-deficient mice. Furthermore, whereas Pax9 del/del embryos exhibit defects in palatal shelf elevation/reorientation and significant reduction in accumulation of hyaluronic acid-a high molecular extracellular matrix glycosaminoglycan implicated in playing an important role in palatal shelf elevation-80% of Pax9 del/del ;Wise -/- double-mutant mouse embryos exhibit rescued palatal shelf elevation/reorientation, accompanied by restored

  4. The problem with rescue medicine.

    Science.gov (United States)

    Jecker, Nancy S

    2013-02-01

    Is there a rational and ethical basis for efforts to rescue individuals in dire straits? When does rescue have ethical support, and when does it reflect an irrational impulse? This paper defines a Rule of Rescue and shows its intuitive appeal. It then proceeds to argue that this rule lacks support from standard principles of justice and from ethical principles more broadly, and should be rejected in many situations. I distinguish between agent-relative and agent-neutral reasons, and argue that the Rule of Rescue qualifies only in a narrow range of cases where agent-relative considerations apply. I conclude that it would be wise to set aside the Rule of Rescue in many cases, especially those involving public policies, where it has only weak normative justification. The broader implications of this analysis are noted.

  5. Rescue of a pathogenic mutant human glucagon receptor by pharmacological chaperones.

    Science.gov (United States)

    Yu, Run; Chen, Chun-Rong; Liu, Xiaohong; Kodra, János T

    2012-10-01

    We have previously demonstrated that a homozygous inactivating P86S mutation of the glucagon receptor (GCGR) causes a novel human disease of hyperglucagonemia, pancreatic α-cell hyperplasia, and pancreatic neuroendocrine tumors (Mahvash disease). The mechanisms for the decreased activity of the P86S mutant (P86S) are abnormal receptor localization to the endoplasmic reticulum (ER) and defective interaction with glucagon. To search for targeted therapies for Mahvash disease, we examined whether P86S can be trafficked to the plasma membrane by pharmacological chaperones and whether novel glucagon analogs restore effective receptor interaction. We used enhanced green fluorescent protein-tagged P86S stably expressed in HEK 293 cells to allow fluorescence imaging and western blotting and molecular modeling to design novel glucagon analogs in which alanine 19 was replaced with serine or asparagine. Incubation at 27 °C largely restored normal plasma membrane localization and normal processing of P86S but osmotic chaperones had no effects. The ER stressors thapsigargin and curcumin partially rescued P86S. The lipophilic GCGR antagonist L-168,049 also partially rescued P86S, so did Cpd 13 and 15 to a smaller degree. The rescued P86S led to more glucagon-stimulated cAMP production and was internalized by glucagon. Compared with the native glucagon, the novel glucagon analogs failed to stimulate more cAMP production by P86S. We conclude that the mutant GCGR is partially rescued by several pharmacological chaperones and our data provide proof-of-principle evidence that Mahvash disease can be potentially treated with pharmacological chaperones. The novel glucagon analogs, however, failed to interact with P86S more effectively.

  6. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction

    DEFF Research Database (Denmark)

    Fang, Evandro Fei; Scheibye-Knudsen, Morten; Brace, Lear E

    2014-01-01

    with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD(+)-SIRT1-PGC-1α axis triggered by hyperactivation of the DNA damage sensor PARP-1. This phenotype is rescued by PARP-1 inhibition...... or by supplementation with NAD(+) precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration...

  7. Rescue of avian leukosis subgroup-J-associated acutely transforming viruses carrying different lengths of the v-fps oncogene and analysis of their tumorigenicity.

    Science.gov (United States)

    Wang, Yixin; Fang, Lichun; Li, Jianliang; Li, Yang; Cui, Shuai; Sun, Xiaolong; Chang, Shuang; Zhao, Peng; Cui, Zhizhong

    2016-12-01

    In our previous study, six subgroup J strains of avian leukosis virus (ALV-J)-associated acutely transforming viruses carrying different lengths of the v-fps oncogene, designated as Fu-J and Fu-J1-5, were isolated and characterized from fibrosarcomas in ALV-J-infected chickens. In the present study, the oncogenic potential of Fu-J and Fu-J1-5 was investigated using a reverse genetics technique. Six replication-defective viruses, named rFu-J and rFu-J1-5, were rescued with the replication-competent rescued ALV-J strain rSDAU1005 as a helper virus by co-transfection of chicken embryo fibroblast monolayers with infectious clone plasmids. Experimental bird studies were performed, demonstrating that only the rescued rFu-J virus carrying the complete v-fps oncogene with rSDAU1005 as the helper virus could induce acute fibrosarcoma after inoculation in specific-pathogen-free (SPF) chickens. These results provide direct evidence that the replication-defective acutely transforming Fu-J virus, with the complete v-fps oncogene, was associated with acute fibrosarcoma in chickens infected with ALV-J in the field, as reported previously.

  8. Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

    International Nuclear Information System (INIS)

    Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.; Finnell, Richard H.

    2009-01-01

    Background: Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives: We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods: We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-α-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results: Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions: IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.

  9. Rescue from replication stress during mitosis.

    Science.gov (United States)

    Fragkos, Michalis; Naim, Valeria

    2017-04-03

    Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

  10. Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate.

    Science.gov (United States)

    Brookes, Steven J; Barron, Martin J; Boot-Handford, Ray; Kirkham, Jennifer; Dixon, Michael J

    2014-05-01

    Inherited diseases caused by genetic mutations can arise due to loss of protein function. Alternatively, mutated proteins may mis-fold, impairing endoplasmic reticulum (ER) trafficking, causing ER stress and triggering the unfolded protein response (UPR). The UPR attempts to restore proteostasis but if unsuccessful drives affected cells towards apoptosis. Previously, we reported that in mice, the p.Tyr64His mutation in the enamel extracellular matrix (EEM) protein amelogenin disrupts the secretory pathway in the enamel-forming ameloblasts, resulting in eruption of malformed tooth enamel that phenocopies human amelogenesis imperfecta (AI). Defective amelogenin post-secretory self-assembly and processing within the developing EEM has been suggested to underlie the pathogenesis of X chromosome-linked AI. Here, we challenge this concept by showing that AI pathogenesis associated with the p.Tyr64His amelogenin mutation involves ameloblast apoptosis induced by ER stress. Furthermore, we show that 4-phenylbutyrate can rescue the enamel phenotype in affected female mice by promoting cell survival over apoptosis such that they are able to complete enamel formation despite the presence of the mutation, offering a potential therapeutic option for patients with this form of AI and emphasizing the importance of ER stress in the pathogenesis of this inherited conformational disease.

  11. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    Energy Technology Data Exchange (ETDEWEB)

    Sakaidani, Yuta [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ichiyanagi, Naoki [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Saito, Chika; Nomura, Tomoko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ito, Makiko [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Nishio, Yosuke [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Nadano, Daita; Matsuda, Tsukasa [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Furukawa, Koichi [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Okajima, Tetsuya, E-mail: tokajima@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer We characterized A130022J15Rik (Eogt1)-a mouse gene homologous to Drosophila Eogt. Black-Right-Pointing-Pointer Eogt1 encodes EGF domain O-GlcNAc transferase. Black-Right-Pointing-Pointer Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. Black-Right-Pointing-Pointer O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-{beta}-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  12. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    International Nuclear Information System (INIS)

    Sakaidani, Yuta; Ichiyanagi, Naoki; Saito, Chika; Nomura, Tomoko; Ito, Makiko; Nishio, Yosuke; Nadano, Daita; Matsuda, Tsukasa; Furukawa, Koichi; Okajima, Tetsuya

    2012-01-01

    Highlights: ► We characterized A130022J15Rik (Eogt1)—a mouse gene homologous to Drosophila Eogt. ► Eogt1 encodes EGF domain O-GlcNAc transferase. ► Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. ► O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-β-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  13. 49 CFR 238.114 - Rescue access windows.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Rescue access windows. 238.114 Section 238.114... § 238.114 Rescue access windows. (a) Number and location. Except as provided in paragraph (a)(1)(ii) of... rescue access windows. At least one rescue access window shall be located in each side of the car...

  14. The future for the Global Sea Level Observing System (GLOSS) Sea Level Data Rescue

    Science.gov (United States)

    Bradshaw, Elizabeth; Matthews, Andrew; Rickards, Lesley; Aarup, Thorkild

    2016-04-01

    Historical sea level data are rare and unrepeatable measurements with a number of applications in climate studies (sea level rise), oceanography (ocean currents, tides, surges), geodesy (national datum), geophysics and geology (coastal land movements) and other disciplines. However, long-term time series are concentrated in the northern hemisphere and there are no records at the Permanent Service for Mean Sea Level (PSMSL) global data bank longer than 100 years in the Arctic, Africa, South America or Antarctica. Data archaeology activities will help fill in the gaps in the global dataset and improve global sea level reconstruction. The Global Sea Level Observing System (GLOSS) is an international programme conducted under the auspices of the WMO-IOC Joint Technical Commission for Oceanography and Marine Meteorology. It was set up in 1985 to collect long-term tide gauge observations and to develop systems and standards "for ocean monitoring and flood warning purposes". At the GLOSS-GE-XIV Meeting in 2015, GLOSS agreed on a number of action items to be developed in the next two years. These were: 1. To explore mareogram digitisation applications, including NUNIEAU (more information available at: http://www.mediterranee.cerema.fr/logiciel-de-numerisation-des-enregistrements-r57.html) and other recent developments in scanning/digitisation software, such as IEDRO's Weather Wizards program, to see if they could be used via a browser. 2. To publicise sea level data archaeology and rescue by: • maintaining and regularly updating the Sea Level Data Archaeology page on the GLOSS website • strengthening links to the GLOSS data centres and data rescue organisations e.g. linking to IEDRO, ACRE, RDA • restarting the sea level data rescue blog with monthly posts. 3. Investigate sources of funding for data archaeology and rescue projects. 4. Propose "Guidelines" for rescuing sea level data. These action items will aid the discovery, scanning, digitising and quality control

  15. 46 CFR 199.202 - Rescue boats.

    Science.gov (United States)

    2010-10-01

    ... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.202 Rescue boats... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boats. 199.202 Section 199.202 Shipping COAST... least one rescue boat approved under approval series 160.156 that is equipped as specified in table 199...

  16. 46 CFR 133.140 - Stowage of rescue boats.

    Science.gov (United States)

    2010-10-01

    ... SYSTEMS Requirements for All OSVs § 133.140 Stowage of rescue boats. (a) Rescue boats must be stowed as follows: (1) Each rescue boat must be ready for launching in not more than 5 minutes. (2) Each rescue boat... 46 Shipping 4 2010-10-01 2010-10-01 false Stowage of rescue boats. 133.140 Section 133.140...

  17. [Design and application of portable rescue vehicle].

    Science.gov (United States)

    Guo, Ying; Qi, Huaying; Wang, Shen

    2017-12-01

    The disease of critically ill patients was with rapid changes, and at any time faced the risk of emergency. The current commonly used rescue vehicles were larger and bulky implementation, which were not conducive to the operation, therefore the design of a portable rescue vehicle was needed. This new type of rescue vehicle is multi-layer folding structure, with small footprint, large storage space, so a variety of first aid things can be classified and put, easy to be cleaned and disinfected. In the rescue process, the portable rescue vehicles can be placed in the required position; box of various emergency items can be found at a glance with easy access; the height of the infusion stand can adjust freely according to the user height; the rescue vehicle handle can be easy to pull and adjust accord with human body mechanics principle. The portable rescue vehicle facilitates the operation of medical staff, and is worthy of clinical application.

  18. Self-Rescue Mask Training

    CERN Multimedia

    2013-01-01

    Nine new self-rescue mask instructors have been trained since early 2013, which provides CERN with a total of 26 self-rescue mask instructors to date. This will allow us to meet the increasing training needs caused by the Long Shut Down LS1.   The self-rescue mask instructors have trained 1650 persons in 2012 and about 500 persons since the beginning of the year on how to wear the masks properly. We thank all the instructors and all the persons that made this training possible. Please remember that the self-rescue masks training sessions are scheduled as follows: Basic course: Tuesday and Thursday mornings (2 sessions – 8.30 AM and 10.30 AM), duration:  1.30 hour, in French and English – registration via CERN online training catalogue – Course code 077Y00. Refresher training : Monday mornings (2 sessions – 8.30 AM and 10.30 AM), duration: 1.30 hour , in French and English – registration via CERN online training catalogue &...

  19. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment.

    Directory of Open Access Journals (Sweden)

    Palittiya Sintusek

    Full Text Available Gastrointestinal (GI defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA. Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome.

  20. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment

    Science.gov (United States)

    Sintusek, Palittiya; Catapano, Francesco; Angkathunkayul, Napat; Marrosu, Elena; Parson, Simon H.; Morgan, Jennifer E.; Muntoni, Francesco; Zhou, Haiyan

    2016-01-01

    Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome. PMID:27163330

  1. Chemosensitivity of primary human fibroblasts with defective unhooking of DNA interstrand cross-links

    International Nuclear Information System (INIS)

    Clingen, Peter H.; Arlett, Colin F.; Hartley, John A.; Parris, Christopher N.

    2007-01-01

    Xeroderma pigmentosum (XP) is characterised by defects in nucleotide excision repair, ultraviolet (UV) radiation sensitivity and increased skin carcinoma. Compared to other complementation groups, XP-F patients show relatively mild cutaneous symptoms. DNA interstrand cross-linking agents are a highly cytotoxic class of DNA damage induced by common cancer chemotherapeutics such as cisplatin and nitrogen mustards. Although the XPF-ERCC1 structure-specific endonuclease is required for the repair of ICLs cellular sensitivity of primary human XP-F cells has not been established. In clonogenic survival assays, primary fibroblasts from XP-F patients were moderately sensitive to both UVC and HN2 compared to normal cells (2- to 3-fold and 3- to 5-fold, respectively). XP-A fibroblasts were considerably more sensitive to UVC (10- to 12-fold) but not sensitive to HN2. The sensitivity of XP-F fibroblasts to HN2 correlated with the defective incision or 'unhooking' step of ICL repair. Using the comet assay, XP-F cells exhibited only 20% residual unhooking activity over 24 h. Over the same time, normal and XP-A cells unhooked greater than 95% and 62% of ICLs, respectively. After HN2 treatment, ICL-associated DNA double-strand breaks (DSBs) are detected by pulse field gel electrophoresis in dividing cells. Induction and repair of DNA DSBs was normal in XP-F fibroblasts. These findings demonstrate that in primary human fibroblasts, XPF is required for the unhooking of ICLs and not for the induction or repair of ICL-associated DNA DSBs induced by HN2. In terms of cancer chemotherapy, people with mild DNA repair defects affecting ICL repair may be more prevalent in the general population than expected. Since cellular sensitivity of primary human fibroblasts usually reflects clinical sensitivity such patients with cancer would be at risk of increased toxicity

  2. Factors influencing mine rescue team behaviors.

    Science.gov (United States)

    Jansky, Jacqueline H; Kowalski-Trakofler, K M; Brnich, M J; Vaught, C

    2016-01-01

    A focus group study of the first moments in an underground mine emergency response was conducted by the National Institute for Occupational Safety and Health (NIOSH), Office for Mine Safety and Health Research. Participants in the study included mine rescue team members, team trainers, mine officials, state mining personnel, and individual mine managers. A subset of the data consists of responses from participants with mine rescue backgrounds. These responses were noticeably different from those given by on-site emergency personnel who were at the mine and involved with decisions made during the first moments of an event. As a result, mine rescue team behavior data were separated in the analysis and are reported in this article. By considering the responses from mine rescue team members and trainers, it was possible to sort the data and identify seven key areas of importance to them. On the basis of the responses from the focus group participants with a mine rescue background, the authors concluded that accurate and complete information and a unity of purpose among all command center personnel are two of the key conditions needed for an effective mine rescue operation.

  3. Combat Rescue Helicopter (CRH)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-479 Combat Rescue Helicopter (CRH) As of FY 2017 President’s Budget Defense Acquisition...Name Combat Rescue Helicopter (CRH) DoD Component Air Force Responsible Office References SAR Baseline (Development Estimate) Defense Acquisition... Helicopter (CRH) system will provide Personnel Recovery (PR) forces with a vertical takeoff and landing aircraft that is quickly deployable and

  4. A new approach to road accident rescue.

    Science.gov (United States)

    Morales, Alejandro; González-Aguilera, Diego; López, Alfonso I; Gutiérrez, Miguel A

    2016-01-01

    This article develops and validates a new methodology and tool for rescue assistance in traffic accidents, with the aim of improving its efficiency and safety in the evacuation of people, reducing the number of victims in road accidents. Different tests supported by professionals and experts have been designed under different circumstances and with different categories of damaged vehicles coming from real accidents and simulated trapped victims in order to calibrate and refine the proposed methodology and tool. To validate this new approach, a tool called App_Rescue has been developed. This tool is based on the use of a computer system that allows an efficient access to the technical information of the vehicle and sanitary information of the common passengers. The time spent during rescue using the standard protocol and the proposed method was compared. This rescue assistance system allows us to make vital information accessible in posttrauma care services, improving the effectiveness of interventions by the emergency services, reducing the rescue time and therefore minimizing the consequences involved and the number of victims. This could often mean saving lives. In the different simulated rescue operations, the rescue time has been reduced an average of 14%.

  5. The Conserved ATM Kinase RAG2-S365 Phosphorylation Site Limits Cleavage Events in Individual Cells Independent of Any Repair Defect

    Directory of Open Access Journals (Sweden)

    Susannah L. Hewitt

    2017-10-01

    Full Text Available Many DNA lesions associated with lymphoid malignancies are linked to off-target cleavage by the RAG1/2 recombinase. However, off-target cleavage has mostly been analyzed in the context of DNA repair defects, confounding any mechanistic understanding of cleavage deregulation. We identified a conserved SQ phosphorylation site on RAG2 365 to 366 that is involved in feedback control of RAG cleavage. Mutation of serine 365 to a non-phosphorylatable alanine permits bi-allelic and bi-locus RAG-mediated breaks in the same cell, leading to reciprocal translocations. This phenomenon is analogous to the phenotype we described for ATM kinase inactivation. Here, we establish deregulated cleavage itself as a driver of chromosomal instability without the associated repair defect. Intriguingly, a RAG2-S365E phosphomimetic rescues the deregulated cleavage of ATM inactivation, reducing the incidence of reciprocal translocations. These data support a model in which feedback control of cleavage and maintenance of genome stability involves ATM-mediated phosphorylation of RAG2.

  6. Rope rescue in National fire-fighting and rescue system

    OpenAIRE

    SOCHACKI MARIAN

    2008-01-01

    Автор описывает организацию, функционирование и место системы спасения с высоты в Государственной спасательно-гасящей системе.The author describes organization, working and place of rope rescue in National Firefighting and Rescue System (KSRG).

  7. Treatment of Inherited Eye Defects by Systemic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Rocca, Celine J; Kreymerman, Alexander; Ur, Sarah N; Frizzi, Katie E; Naphade, Swati; Lau, Athena; Tran, Tammy; Calcutt, Nigel A; Goldberg, Jeffrey L; Cherqui, Stephanie

    2015-11-01

    Cystinosis is caused by a deficiency in the lysosomal cystine transporter, cystinosin (CTNS gene), resulting in cystine crystal accumulation in tissues. In eyes, crystals accumulate in the cornea causing photophobia and eventually blindness. Hematopoietic stem progenitor cells (HSPCs) rescue the kidney in a mouse model of cystinosis. We investigated the potential for HSPC transplantation to treat corneal defects in cystinosis. We isolated HSPCs from transgenic DsRed mice and systemically transplanted irradiated Ctns-/- mice. A year posttransplantation, we investigated the fate and function of HSPCs by in vivo confocal and fluorescence microscopy (IVCM), quantitative RT-PCR (RT-qPCR), mass spectrometry, histology, and by measuring the IOP. To determine the mechanism by which HSPCs may rescue disease cells, we transplanted Ctns-/- mice with Ctns-/- DsRed HSPCs virally transduced to express functional CTNS-eGFP fusion protein. We found that a single systemic transplantation of wild-type HSPCs prevented ocular pathology in the Ctns-/- mice. Engraftment-derived HSPCs were detected within the cornea, and also in the sclera, ciliary body, retina, choroid, and lens. Transplantation of HSPC led to substantial decreases in corneal cystine crystals, restoration of normal corneal thickness, and lowered IOP in mice with high levels of donor-derived cell engraftment. Finally, we found that HSPC-derived progeny differentiated into macrophages, which displayed tunneling nanotubes capable of transferring cystinosin-bearing lysosomes to diseased cells. To our knowledge, this is the first demonstration that HSPCs can rescue hereditary corneal defects, and supports a new potential therapeutic strategy for treating ocular pathologies.

  8. Precision Rescue Behavior in North American Ants

    Directory of Open Access Journals (Sweden)

    Katherine Taylor

    2013-07-01

    Full Text Available Altruistic behavior, in which one individual provides aid to another at some cost to itself, is well documented. However, some species engage in a form of altruism, called rescue, that places the altruist in immediate danger. Here we investigate one such example, namely rescuing victims captured by predators. In a field experiment with two North American ant species, Tetramorium sp. E and Prenolepis imparis, individuals were held in artificial snares simulating capture. T. sp. E, but not P. imparis, exhibited digging, pulling, and snare biting, the latter precisely targeted to the object binding the victim. These results are the first to document precision rescue in a North American ant species; moreover, unlike rescue in other ants, T. sp. E rescues conspecifics from different colonies, mirroring their atypical social behavior, namely the lack of aggression between non-nestmate (heterocolonial conspecifics. In a second, observational study designed to demonstrate rescue from an actual predator, T. sp. E victims were dropped into an antlion's pit and the behavior of a single rescuer was observed. Results showed that T. sp. E not only attempted to release the victim, but also risked attacking the predator, suggesting that precision rescue may play an important role in this species' antipredator behavior.

  9. Joseph Conrad's tormented Rescue (fantasy).

    Science.gov (United States)

    Freedman, William

    2014-02-01

    Joseph Conrad was a notoriously tormented writer for whom the creative act was often a punishment severe enough to drive him into paralyzing depressions that delayed the completion of his novels, sometimes for years. By far the most agonizing of these projects was The Rescue, a novel he began in 1898, abandoned a year later, tried unsuccessfully to continue several times over the next two decades, but was only able to resume in 1918 and to complete, after another tortured two-year struggle, in 1920. An explanation for this incapacity, that is powerfully suggested by the novel's evocative title and perhaps unintentionally ironic subtitle (A Romance of the Shallows) has not yet been explored. Using Freud's 1910 essay on the rescue fantasy, "Contributions to the Psychology of Love: A Special Type of Choice of Object Made by Men," and Emanuel Berman's instructive revision and expansion of the concept in his 2003 American Imago essay, "Ferenczi, Rescue, and Utopia," I argue that a substantial explanation for Conrad's tormented history with The Rescue is ascribable to its quite remarkably faithful treatment of a rescue fantasy with deep and disabling resonance for its author. More specifically, the difficulty was compounded by the novel's dramatization of the soul-crushing conflict between two such fantasies: one in the service of the masculine ideal of unflinching dedication to a heroic purpose, the other promising satisfaction to the equally potent demands of emotional and sexual desire. Features of Conrad's narrative fit so tightly and consistently with the theory as Freud (and Abraham) proposed and as Berman elaborated it that The Rescue offers itself as one of those rare and reinforcing instances wherein the literary text seems to validate the psychoanalytic theory at least as persuasively as the theory "understands" the text.

  10. Links between environmental geochemistry and rate of birth defects: Shanxi Province, China

    Energy Technology Data Exchange (ETDEWEB)

    Yu Haiying [State Key Laboratory of Earth Surface Processes and Resource Ecology, School of Geography, Beijing Normal University, Beijing 100875 (China); College of Resources and Environmental Sciences, Sichuan Agricultural University, Ya' an, Sichuan 625014 (China); Zhang Keli, E-mail: keli@bnu.edu.cn [State Key Laboratory of Earth Surface Processes and Resource Ecology, School of Geography, Beijing Normal University, Beijing 100875 (China)

    2011-01-01

    The rate of birth defects in Shanxi Province is among the highest worldwide. In order to identify the impacts of geochemical and environmental factors on birth defect risk, samples of soil, water and food were collected from an area with an unusually high rate of birth defects (study area) and an area with a low rate of birth defects (control area) in Shanxi Province, China. Element contents were determined by ICP-OES, and the results were analyzed using a non-parametric test and stepwise regression. Differences in the level and distribution of 14 geochemical elements, namely arsenic (As), selenium (Se), molybdenum (Mo), zinc (Zn), strontium (Sr), iron (Fe), tin (Sn), magnesium (Mg), vanadium (V), calcium (Ca), copper (Cu), aluminum (Al), potassium (K) and sulfur (S) were thus compared between the study and control areas. The results reveal that the geochemical element contents in soil, water and food show a significant difference between the study area and control area, and suggest that the study area was characterized by higher S and lower Sr and Al contents. These findings, based on statistical analysis, may be useful in directing further epidemiological investigations identifying the leading causes of birth defects. - Research Highlights: {yields} Environmental geochemistry has an significant impact on birth defects in the regions with an unusually high rate of birth defects. {yields} An excess of S and deficiency of Sr and Al are the distinctive environmental features associated with the high rate of birth defects in the Shanxi Province of China. {yields} Geochemical anomalies is a non-medical basis for effective prevention and cure of birth defects.

  11. Links between environmental geochemistry and rate of birth defects: Shanxi Province, China

    International Nuclear Information System (INIS)

    Yu Haiying; Zhang Keli

    2011-01-01

    The rate of birth defects in Shanxi Province is among the highest worldwide. In order to identify the impacts of geochemical and environmental factors on birth defect risk, samples of soil, water and food were collected from an area with an unusually high rate of birth defects (study area) and an area with a low rate of birth defects (control area) in Shanxi Province, China. Element contents were determined by ICP-OES, and the results were analyzed using a non-parametric test and stepwise regression. Differences in the level and distribution of 14 geochemical elements, namely arsenic (As), selenium (Se), molybdenum (Mo), zinc (Zn), strontium (Sr), iron (Fe), tin (Sn), magnesium (Mg), vanadium (V), calcium (Ca), copper (Cu), aluminum (Al), potassium (K) and sulfur (S) were thus compared between the study and control areas. The results reveal that the geochemical element contents in soil, water and food show a significant difference between the study area and control area, and suggest that the study area was characterized by higher S and lower Sr and Al contents. These findings, based on statistical analysis, may be useful in directing further epidemiological investigations identifying the leading causes of birth defects. - Research Highlights: → Environmental geochemistry has an significant impact on birth defects in the regions with an unusually high rate of birth defects. → An excess of S and deficiency of Sr and Al are the distinctive environmental features associated with the high rate of birth defects in the Shanxi Province of China. → Geochemical anomalies is a non-medical basis for effective prevention and cure of birth defects.

  12. Impaired hair follicle morphogenesis and polarized keratinocyte movement upon conditional inactivation of integrin-linked kinase in the epidermis.

    Science.gov (United States)

    Nakrieko, Kerry-Ann; Welch, Ian; Dupuis, Holly; Bryce, Dawn; Pajak, Agnieszka; St Arnaud, René; Dedhar, Shoukat; D'Souza, Sudhir J A; Dagnino, Lina

    2008-04-01

    Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little is known about its role in epidermal development and homeostasis in vivo. We generated mice with conditional inactivation of the Ilk gene in squamous epithelia. These mice die perinatally and exhibit skin blistering and severe defects in hair follicle morphogenesis, including greatly reduced follicle numbers, failure to progress beyond very early developmental stages, and pronounced defects in follicular keratinocyte proliferation. ILK-deficient epidermis shows abnormalities in adhesion to the basement membrane and in differentiation. ILK-deficient cultured keratinocytes fail to attach and spread efficiently and exhibit multiple abnormalities in actin cytoskeletal organization. Ilk gene inactivation in cultured keratinocytes causes impaired ability to form stable lamellipodia, to directionally migrate, and to polarize. These defects are accompanied by abnormal distribution of active Cdc42 to cell protrusions, as well as reduced activation of Rac1 upon induction of cell migration in scraped keratinocyte monolayers. Significantly, alterations in cell spreading and forward movement in single cells can be rescued by expression of constitutively active Rac1 or RhoG. Our studies underscore a central and distinct role for ILK in hair follicle development and in polarized cell movements, two key aspects of epithelial morphogenesis and function.

  13. Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells.

    Science.gov (United States)

    Farioli-Vecchioli, Stefano; Mattera, Andrea; Micheli, Laura; Ceccarelli, Manuela; Leonardi, Luca; Saraulli, Daniele; Costanzi, Marco; Cestari, Vincenzo; Rouault, Jean-Pierre; Tirone, Felice

    2014-07-01

    Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wild-type mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis. © 2014 AlphaMed Press.

  14. Review and expectations of terror attack emergency rescue

    Directory of Open Access Journals (Sweden)

    De-wen WANG

    2012-03-01

    Full Text Available Ten years of anti-terror struggle since the 9/11 event has indicated adequately that terrorism is a global problem and international danger. Likewise, anti-terror emergency rescue is also an important task which will influence the safety and benefit of every country all over the world. This paper reviews the main progress and result of international anti-terror struggle in the last ten years, and also introduces the new characteristic of the international anti-terror activity. Besides that, this paper also brings forward the further consideration about the anti-terror emergency medical rescue and the researches remaining to be carried out. The latter includes: (1 to further perfect the high-efficient medical rescue command organization; (2 to further perfect the emergency medical rescue prearranged scheme; (3 to further perfect the construction of rescue system and rescue base after various types of terror attack; (4 to further promote the anti-terror consciousness in the public, and pay more attention to the prevention and investigation of the psychological disaster; (5 to further carry out the basic investigation on emergency medical rescue after various terror attack injuries (for example the types and characteristics of new injuries, pathophysiology and prevention and treatment of stress-psychological effect induced by terror attack, new high-efficient medical rescue measure and equipments, and so on.

  15. Geometrical size effect in high cycle fatigue strength of heavy-walled Ductile Cast Iron GJS400: Weakest link vs. defect-based approach

    Directory of Open Access Journals (Sweden)

    Cova Matteo

    2014-06-01

    Full Text Available Fatigue strength is known to decrease with increasing dimension of the component. This is due to a technological size effect, related to the production process, and to a geometrical size effect, due to a higher probability of finding a large defect. To investigate the latter, an heavy-walled component made of Ductile Cast Iron (DCI has been trepanned and a fatigue test plan has been carried out using 4 different specimen geometries. An attempt has been made to relate the resulting fatigue strength using a weakest-link approach based on the effective volumes and surfaces. This approach seems to work well only in cases of different specimen's lengths. Some of the fracture surfaces were analyzed by means of SEM and the initiating defects were identified and measured. An approach in which the defects population can be randomly distributed in the specimen has been tried. Virtual fatigue tests have been carried out by considering pure propagation of the worst defect. The resulting fatigue curves showed that this approach is promising but needs further description of the initiation phase.

  16. 30 CFR 49.17 - Physical requirements for mine rescue team.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.17 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a...

  17. Emergency rescue in accidents with HDR afterloading units

    International Nuclear Information System (INIS)

    Kaulich, T.W.; Nuesslin, F.; Becker, G.; Lamprecht, U.; Bamberg, M.

    1999-01-01

    Problem: HDR brachyradiotherapy has minimized the exposure to radiation of the personnel working in this field. Nonetheless there are periodically reported troubles with afterloading units concerning the retraction of sources that require immediate action for the limitation of possible damage. Legal Principles according to the German Regulation Concerning Protection against Radiation (Strahlenschutzverordnung=StrlSchV): If in afterloading brachyradiotherapy the radiation source remains extended through malfunction we deal with an emergency according to the StrlSchV. The rescue personnel should be chosen in accordance with Paragraph 50 StrlSchV. Organization of the Rescue of the Patient: The quickest possible rescue of a patient in an emergency demands an unequivocal definition of responsibilities. Our recommendations in this instance: The physicist is responsible for the organization of the emergency rescue. The radiation oncologist in charge informs himself about the necessary emergency measures before starting the treatment and carries out the emergency rescue. If the physicist diagnoses a failure in the retraction of the source he tries to remove the failure. If he doesn't succeed in retracting the source the radiation oncologist carries out the rescue of the patient. The organizational structure of the clinic allowing, the emergency physician should invariably be the physician who placed the applicator. In the emergency rescue the radiation oncologist should be protected by a lead barrier and use manipulators. Dose Assessment in Personnel and Patient: The radiation exposure of the rescue personnel is calculated from the photon-equivalence dose H x with the help of the dose-rate constant of 192 Ir. According to the same procedure there can be evaluated the local radiation exposure of the patient concerned. Conclusions: Generally speaking, all considerations regarding the topic of emergency rescue should always start out from a worst-case scenario. Of all the

  18. Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications.

    Science.gov (United States)

    Soheili, Tayebeh; Gicquel, Evelyne; Poupiot, Jérôme; N'Guyen, Luu; Le Roy, Florence; Bartoli, Marc; Richard, Isabelle

    2012-02-01

    Sarcoglycanopathies (SGP) are a group of autosomal recessive muscle disorders caused by primary mutations in one of the four sarcoglycan genes. The sarcoglycans (α-, β-, γ-, and δ-sarcoglycan) form a tetrameric complex at the muscle membrane that is part of the dystrophin-glycoprotein complex and plays an essential role for membrane integrity during muscle contractions. We previously showed that the most frequent missense mutation in α-sarcoglycan (p.R77C) leads to the absence of the protein at the cell membrane due to its blockade by the endoplasmic reticulum (ER) quality control. Moreover, we demonstrated that inhibition of the ER α-mannosidase I activity using kifunensine could rescue the mutant protein localization at the cell membrane. Here, we investigate 25 additional disease-causing missense mutations in the sarcoglycan genes with respect to intracellular fate and localization rescue of the mutated proteins by kifunensine. Our studies demonstrate that, similarly to p.R77C, 22 of 25 of the selected mutations lead to defective intracellular trafficking of the SGs proteins. Six of these were saved from ER retention upon kifunensine treatment. The trafficking of SGs mutants rescued by kifunensine was associated with mutations that have moderate structural impact on the protein. © 2011 Wiley Periodicals, Inc.

  19. Management of Anterior Skull Base Defect Depending on Its Size and Location

    Science.gov (United States)

    Bernal-Sprekelsen, Manuel; Rioja, Elena; Enseñat, Joaquim; Enriquez, Karla; Viscovich, Liza; Agredo-Lemos, Freddy Enrique; Alobid, Isam

    2014-01-01

    Introduction. We present our experience in the reconstruction of these leaks depending on their size and location. Material and Methods. Fifty-four patients who underwent advanced skull base surgery (large defects, >20 mm) and 62 patients with CSF leaks of different origin (small, 2–10 mm, and midsize, 11–20 mm, defects) were included in the retrospective study. Large defects were reconstructed with a nasoseptal pedicled flap positioned on fat and fascia lata. In small and midsized leaks. Fascia lata in an underlay position was used for its reconstruction covered with mucoperiosteum of either the middle or the inferior turbinate. Results. The most frequent etiology for small and midsized defects was spontaneous (48.4%), followed by trauma (24.2%), iatrogenic (5%). The success rate after the first surgical reconstruction was 91% and 98% in large skull base defects and small/midsized, respectively. Rescue surgery achieved 100%. Conclusions. Endoscopic surgery for any type of skull base defect is the gold standard. The size of the defects does not seem to play a significant role in the success rate. Fascia lata and mucoperiosteum of the turbinate allow a two-layer reconstruction of small and midsized defects. For larger skull base defects, a combination of fat, fascia lata, and nasoseptal pedicled flaps provides a successful reconstruction. PMID:24895567

  20. Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice.

    Science.gov (United States)

    Cabral-Costa, J V; Andreotti, D Z; Mello, N P; Scavone, C; Camandola, S; Kawamoto, E M

    2018-06-05

    Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.

  1. Rescuing Israeli travellers: effects of substance abuse, mental health, geographic region of rescue, gender and age of rescuees.

    Science.gov (United States)

    Bonny-Noach, Hagit; Sagiv-Alayoff, Moran

    2017-09-01

    Research conducted on young Israeli travellers has pointed to high substance usage rates. For some drug-using backpackers, actual extraction and rescue from their trip abroad is necessary. This study represents a first attempt to explore the influence of geographic region in which rescue occurs, cause for rescue and gender and age differences among Israeli rescuees. Sub-analysis of all logs of individual rescuees during a 5-year period from 2011 to 2016 ( N  = 86) included 66 men and 20 women, with an average age of 27.83 (SD = 7.86). The findings demonstrate that Israelis are most frequently rescued from South and Southeast Asia (57%) followed by Europe (22%), South America (17%), North America (2.3%) and Africa (1.2%). India was the country with the highest rate of rescue incidents ( N  = 36) followed by Thailand ( N  = 8) and the Netherlands ( N  = 5). The most common cause for rescue was substance abuse (87%). However, significant regional differences were found based on the variable of age ( F  = 3.21, df = 3,50, P  young travellers should be taken into consideration when thinking about induced acute psychosis caused by substance use. Policymakers need to consider prevention and harm reduction interventions relevant to this risk group. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  2. Teaching Holocaust Rescue: A Problematic Pedagogy

    Science.gov (United States)

    Lindquist, David H.

    2008-01-01

    Determining how to teach about rescue during the Holocaust presents many dilemmas to teachers as they plan Holocaust curricula. Rescue is often overemphasized, and faulty perspectives about rescuers and their actions may cause students to develop distorted views about this aspect of Holocaust history. This article explores several factors that…

  3. Advances in search and rescue at sea

    Science.gov (United States)

    Breivik, Øyvind; Allen, Arthur Addoms; Maisondieu, Christophe; Olagnon, Michel

    2013-01-01

    A topical collection on "Advances in Search and Rescue at Sea" has appeared in recent issues of Ocean Dynamics following the latest in a series of workshops on "Technologies for Search and Rescue and other Emergency Marine Operations" (2004, 2006, 2008, and 2011), hosted by IFREMER in Brest, France. Here, we give a brief overview of the history of search and rescue at sea before we summarize the main results of the papers that have appeared in the topical collection.

  4. Search and rescue in collapsed structures: engineering and social science aspects.

    Science.gov (United States)

    El-Tawil, Sherif; Aguirre, Benigno

    2010-10-01

    This paper discusses the social science and engineering dimensions of search and rescue (SAR) in collapsed buildings. First, existing information is presented on factors that influence the behaviour of trapped victims, particularly human, physical, socioeconomic and circumstantial factors. Trapped victims are most often discussed in the context of structural collapse and injuries sustained. Most studies in this area focus on earthquakes as the type of disaster that produces the most extensive structural damage. Second, information is set out on the engineering aspects of urban search and rescue (USAR) in the United States, including the role of structural engineers in USAR operations, training and certification of structural specialists, and safety and general procedures. The use of computational simulation to link the engineering and social science aspects of USAR is discussed. This could supplement training of local SAR groups and USAR teams, allowing them to understand better the collapse process and how voids form in a rubble pile. A preliminary simulation tool developed for this purpose is described. © 2010 The Author(s). Journal compilation © Overseas Development Institute, 2010.

  5. 46 CFR 199.175 - Survival craft and rescue boat equipment.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft and rescue boat equipment. 199.175....175 Survival craft and rescue boat equipment. (a) All lifeboat and rescue boat equipment— (1) Must be... craft or rescue boat; or (iii) Overload the launching appliance. (b) Each lifeboat, rigid liferaft, and...

  6. Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

    Directory of Open Access Journals (Sweden)

    Quan Yuan

    Full Text Available Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH, Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23(-/- and Klotho(-/- (Kl(-/- mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23(-/- mice ameliorated the phenotype in Fgf23(-/-/PTH(-/- mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23(-/- mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl(-/- (Kl(-/-/PTH(-/- or DKO mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl(-/-/PTH(-/- mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23(-/-/PTH(-/- mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl(-/-/PTH(-/- mice. Moreover, continuous PTH infusion of Kl(-/- mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl(-/-, but not of Fgf23(-/- mice, possibly by regulating Opn expression. These are significant new perceptions into

  7. Physical capacity of rescue personnel in the mining industry

    Directory of Open Access Journals (Sweden)

    Hunt Andrew P

    2008-10-01

    Full Text Available Abstract Background The mining industry has one of the highest occupational rates of serious injury and fatality. Mine staff involved with rescue operations are often required to respond to physically challenging situations. This paper describes the physical attributes of mining rescue personnel. Methods 91 rescue personnel (34 ± 8.6 yrs, 1.79 ± 0.07 m, 90 ± 15.0 kg participating in the Queensland Mines Rescue Challenge completed a series of health-related and rescue-related fitness tasks. Health-related tasks comprised measurements of aerobic capacity (VO2max, abdominal endurance, abdominal strength, flexibility, lower back strength, leg strength, elbow flexion strength, shoulder strength, lower back endurance, and leg endurance. Rescue-related tasks comprised an incremental carry (IC, coal shovel (CS, and a hose drag (HD, completed in this order. Results Cardiovascular (VO2max and muscular endurance was average or below average compared with the general population. Isometric strength did not decline with age. The rescue-related tasks were all extremely demanding with heart rate responses averaging greater than 88% of age predicted maximal heart rates. Heart rate recovery responses were more discriminating than heart rates recorded during the tasks, indicating the hose drag as the most physically demanding of the tasks. Conclusion Relying on actual rescues or mining related work to provide adequate training is generally insufficient to maintain, let alone increase, physical fitness. It is therefore recommended that standards of required physical fitness be developed and mines rescue personnel undergo regularly training (and assessment in order to maintain these standards.

  8. 30 CFR 49.7 - Physical requirements for mine rescue team.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.7 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a physician who shall certify that each person is...

  9. Organizations of food redistribution and rescue.

    Science.gov (United States)

    Mousa, T Y; Freeland-Graves, J H

    2017-11-01

    Food insecurity affects 13.4% of the USA population, despite the fact that 30-40% of all food is deposited in a landfill. Food rescue nutrition is the process of redistribution of surplus food to the impoverished. The aim of this study is to document the extent of involvement of organizations in food rescue nutrition. In this cross-sectional study, a survey about organizations involved in food rescue nutrition was developed, validated, and then tested. Directors of 100 organizations involved in food rescue nutrition from eight Southwestern States in the USA participated in this research. These organizations provided an average of 2 million kg of food to more than 40,000 clients each month. Food assistance programs had an average of eight workers and 3081 volunteers. In addition to food, these organizations provided other services such as clothing, clinical, and childcare. The agencies encountered several challenges, including lack of resources that resulted in reducing food portions and turning away clients. The extent of involvement of community-based programs in food rescue nutrition was strong in eight Southwestern states in the USA. Organizations involved in food redistribution helped alleviate food insecurity in their clients. Sustainability of these charitable networks was dependent on availability of resources and sufficient volunteers. Health professionals should encourage these organizations by providing support through donations of time, money, and/or food. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  10. Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia

    Directory of Open Access Journals (Sweden)

    Yongjun Fan

    2014-05-01

    Full Text Available Hereditary Spastic Paraplegia (HSP is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials.

  11. Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia

    Science.gov (United States)

    Fan, Yongjun; Wali, Gautam; Sutharsan, Ratneswary; Bellette, Bernadette; Crane, Denis I.; Sue, Carolyn M.; Mackay-Sim, Alan

    2014-01-01

    ABSTRACT Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine) that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials. PMID:24857849

  12. Modulation of NF-KB in rescued irradiated cells

    International Nuclear Information System (INIS)

    Lam, R.K.K.; Fung, Y.K.; Han, W.; Li, L.; Chiu, S.K.; Cheng, S.H.; Yu, K.N.

    2015-01-01

    Studies by different groups on the rescue effect, where unirradiated bystander cells mitigated the damages in the irradiated cells, since its discovery by the authors' group in 2011 were first reviewed. The properties of the rescue effect were then examined using a novel experimental set-up to physically separate the rescue signals from the bystander signals. The authors' results showed that the rescue effect was mediated through activation of the nuclear factor-KB (NF-KB) response pathway in the irradiated cells, and that the NF-KB activation inhibitor BAy -1 1-7082 did not affect the activation of this response pathway in the irradiated cells induced by direct irradiation. (authors)

  13. Clinical and economic analysis of rescue intracytoplasmic sperm injection cycles.

    Science.gov (United States)

    Shalom-paz, Einat; Alshalati, Jana; Shehata, Fady; Jimenez, Luis; Son, Weon-Young; Holzer, Hananel; Tan, Seang Lin; Almog, Benny

    2011-12-01

    To identify clinical and embryological factors that may predict success in rescue intracytoplasmic sperm injection (ICSI) cycles (after total fertilization failure has occurred) and to evaluate the cost effectiveness of rescue ICSI strategy. Additionally, follow-up of 20 rescue ICSI pregnancies is reported. Retrospective analysis of total fertilization failure cycles. University-based tertiary medical center. In total, 92 patients who had undergone conventional in-vitro fertilization (IVF) cycles with total fertilization failure were included. The patients were divided into two subgroups: those who conceived through rescue ICSI and those who did not. The pregnant members of the rescue ICSI subgroup were found to be significantly younger (32.9 ± 4.2 vs. 36.3 ± 4.5, respectively, p = 0.0035,) and to have better-quality embryos than those who did not conceive (cumulative embryo score: 38.3 ± 20.4 vs. 29.3 ± 14.7, p = 0.025). Cost effectiveness analysis showed 25% reduction in the cost per live birth when rescue ICSI is compared to cycle cancellation approach. The pregnancies follow-up did not show adverse perinatal outcome. Rescue ICSI is an option for salvaging IVF cycles complicated by total fertilization failure. Success in rescue ICSI was found to be associated with younger age and higher quality of embryos. Furthermore, the cost effectiveness of rescue ICSI in terms of total fertilization failure was found to be worthwhile.

  14. Rescue of placental phenotype in a mechanistic model of Beckwith-Wiedemann syndrome

    Directory of Open Access Journals (Sweden)

    Higgins Michael J

    2010-05-01

    fully rescuing LQ trans placental abnormalities that are caused by imprinting defects.

  15. Neurotrauma and the rule of rescue.

    Science.gov (United States)

    Honeybul, S; Gillett, G R; Ho, K M; Lind, C R P

    2011-12-01

    The rule of rescue describes the powerful human proclivity to rescue identified endangered lives, regardless of cost or risk. Deciding whether or not to perform a decompressive craniectomy as a life-saving or 'rescue' procedure for a young person with a severe traumatic brain injury provides a good example of the ethical tensions that occur in these situations. Unfortunately, there comes a point when the primary brain injury is so severe that if the patient survives they are likely to remain severely disabled and fully dependent. The health resource implications of this outcome are significant. By using a web-based outcome prediction model this study compares the long-term outcome and designation of two groups of patients. One group had a very severe injury as adjudged by the model and the other group a less severe injury. At 18 month follow-up there were significant differences in outcome and healthcare requirements. This raises important ethical issues when considering life-saving but non-restorative surgical intervention. The discussion about realistic outcome cannot be dichotomised into simply life or death so that the outcome for the patient must enter the equation. As in other 'rescue situations', the utility of the procedure cannot be rationalised on a mere cost-benefit analysis. A compromise has to be reached to determine at what point either the likely outcome would be unacceptable to the person on whom the procedure is being performed or the social utility gained from the rule of rescue intervention fails to justify the utilitarian value and justice of equitable resource allocation.

  16. Disruption of Mediator rescues the stunted growth of a lignin-deficient Arabidopsis mutant.

    Science.gov (United States)

    Bonawitz, Nicholas D; Kim, Jeong Im; Tobimatsu, Yuki; Ciesielski, Peter N; Anderson, Nickolas A; Ximenes, Eduardo; Maeda, Junko; Ralph, John; Donohoe, Bryon S; Ladisch, Michael; Chapple, Clint

    2014-05-15

    Lignin is a phenylpropanoid-derived heteropolymer important for the strength and rigidity of the plant secondary cell wall. Genetic disruption of lignin biosynthesis has been proposed as a means to improve forage and bioenergy crops, but frequently results in stunted growth and developmental abnormalities, the mechanisms of which are poorly understood. Here we show that the phenotype of a lignin-deficient Arabidopsis mutant is dependent on the transcriptional co-regulatory complex, Mediator. Disruption of the Mediator complex subunits MED5a (also known as REF4) and MED5b (also known as RFR1) rescues the stunted growth, lignin deficiency and widespread changes in gene expression seen in the phenylpropanoid pathway mutant ref8, without restoring the synthesis of guaiacyl and syringyl lignin subunits. Cell walls of rescued med5a/5b ref8 plants instead contain a novel lignin consisting almost exclusively of p-hydroxyphenyl lignin subunits, and moreover exhibit substantially facilitated polysaccharide saccharification. These results demonstrate that guaiacyl and syringyl lignin subunits are largely dispensable for normal growth and development, implicate Mediator in an active transcriptional process responsible for dwarfing and inhibition of lignin biosynthesis, and suggest that the transcription machinery and signalling pathways responding to cell wall defects may be important targets to include in efforts to reduce biomass recalcitrance.

  17. Tactical mobile robots for urban search and rescue

    Science.gov (United States)

    Blitch, John; Sidki, Nahid; Durkin, Tim

    2000-07-01

    Few disasters can inspire more compassion for victims and families than those involving structural collapse. Video clips of children's bodies pulled from earthquake stricken cities and bombing sties tend to invoke tremendous grief and sorrow because of the totally unpredictable nature of the crisis and lack of even the slightest degree of negligence (such as with those who choose to ignore storm warnings). Heartbreaking stories of people buried alive for days provide a visceral and horrific perspective of some of greatest fears ever to be imagined by human beings. Current trends toward urban sprawl and increasing human discord dictates that structural collapse disasters will continue to present themselves at an alarming rate. The proliferation of domestic terrorism, HAZMAT and biological contaminants further complicates the matter further and presents a daunting problem set for Urban Search and Rescue (USAR) organizations around the world. This paper amplifies the case for robot assisted search and rescue that was first presented during the KNOBSAR project initiated at the Colorado School of Mines in 1995. It anticipates increasing technical development in mobile robot technologies and promotes their use for a wide variety of humanitarian assistance missions. Focus is placed on development of advanced robotic systems that are employed in a complementary tool-like fashion as opposed to traditional robotic approaches that portend to replace humans in hazardous tasks. Operational challenges for USAR are presented first, followed by a brief history of mobiles robot development. The paper then presents conformal robotics as a new design paradigm with emphasis on variable geometry and volumes. A section on robot perception follows with an initial attempt to characterize sensing in a volumetric manner. Collaborative rescue is then briefly discussed with an emphasis on marsupial operations and linked mobility. The paper concludes with an emphasis on Human Robot Interface

  18. Development of a Mine Rescue Drilling System (MRDS)

    Energy Technology Data Exchange (ETDEWEB)

    Raymond, David W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gaither, Katherine N. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Polsky, Yarom [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Knudsen, Steven D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Broome, Scott Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Su, Jiann-Cherng [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Blankenship, Douglas A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Costin, Laurence S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-06-01

    Sandia National Laboratories (Sandia) has a long history in developing compact, mobile, very high-speed drilling systems and this technology could be applied to increasing the rate at which boreholes are drilled during a mine accident response. The present study reviews current technical approaches, primarily based on technology developed under other programs, analyzes mine rescue specific requirements to develop a conceptual mine rescue drilling approach, and finally, proposes development of a phased mine rescue drilling system (MRDS) that accomplishes (1) development of rapid drilling MRDS equipment; (2) structuring improved web communication through the Mine Safety & Health Administration (MSHA) web site; (3) development of an improved protocol for employment of existing drilling technology in emergencies; (4) deployment of advanced technologies to complement mine rescue drilling operations during emergency events; and (5) preliminary discussion of potential future technology development of specialized MRDS equipment. This phased approach allows for rapid fielding of a basic system for improved rescue drilling, with the ability to improve the system over time at a reasonable cost.

  19. UvA Rescue - Team Description Paper - Infrastructure competition - Rescue Simulation League RoboCup 2014 - João Pessoa - Brazil

    NARCIS (Netherlands)

    Visser, A.

    2014-01-01

    The UvA Rescue Team has several innovative ideas to further improve the infrastructure of the RoboCup Rescue Simulation League. Those ideas range from providing USARSim an interface compatible with the RoboCup@Home Simulation, to provide the possibility to specify robots in the URDF format, to

  20. X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene.

    Science.gov (United States)

    Lagresle-Peyrou, Chantal; Luce, Sonia; Ouchani, Farid; Soheili, Tayebeh Shabi; Sadek, Hanem; Chouteau, Myriam; Durand, Amandine; Pic, Isabelle; Majewski, Jacek; Brouzes, Chantal; Lambert, Nathalie; Bohineust, Armelle; Verhoeyen, Els; Cosset, François-Loïc; Magerus-Chatinet, Aude; Rieux-Laucat, Frédéric; Gandemer, Virginie; Monnier, Delphine; Heijmans, Catherine; van Gijn, Marielle; Dalm, Virgil A; Mahlaoui, Nizar; Stephan, Jean-Louis; Picard, Capucine; Durandy, Anne; Kracker, Sven; Hivroz, Claire; Jabado, Nada; de Saint Basile, Geneviève; Fischer, Alain; Cavazzana, Marina; André-Schmutz, Isabelle

    2016-12-01

    We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency. We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment. We observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8 + T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities. Our observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Constraints on decision making regarding post-commencement finance in Business rescue

    Directory of Open Access Journals (Sweden)

    Marius Pretorius

    2013-12-01

    Full Text Available Since its introduction, business rescue has become a critical consideration in business strategy decision making. One of the critical components of business rescue, which appears largely unsuccessful to date, involves securing post-commencement finance (PCF to restore the company’s financial health. Despite extensive theory in the literature on failure, there is a void regarding post-commencement finance. Specialist practitioners and financiers with extensive experience in rescue and turnaround were interviewed in this study. Findings showed that many critical factors and reasons for lack of interest are due to the newness of the South African Companies Act 71 of 2008 (introduced May 2011. These include business rescue filing being left too late; the poor financial state of the business that files for rescue; and the significant impact on the outcome by some of the key players (especially the financiers and business rescue practitioners. Better understanding of this aspect would be beneficial for creditors, rescue practitioners, shareholders, government regulators, court officials and educators alike. Key words: business rescue, post-commencement finance, turnaround, decision making

  2. Radioactive fallout and neural tube defects

    Directory of Open Access Journals (Sweden)

    Nejat Akar

    2015-10-01

    Full Text Available Possible link between radioactivity and the occurrence of neural tube defects is a long lasting debate since the Chernobyl nuclear fallout in 1986. A recent report on the incidence of neural defects in the west coast of USA, following Fukushima disaster, brought another evidence for effect of radioactive fallout on the occurrence of NTD’s. Here a literature review was performed focusing on this special subject.

  3. Burnout syndrome in nurses of prehospital rescue team

    Directory of Open Access Journals (Sweden)

    Rosemeire Pereira Bezerra

    2009-09-01

    Full Text Available Objective: To verify the presence and evaluate the levels of burnout syndrome in nurses of the prehospital rescue team. Methods: A cross-sectional study with a sample of 17 nurses from the prehospital rescue team, by application of the Maslach burnout Inventory and a questionnaire prepared by the authors. Rresults: In the group studied, 76% of the nurses of the prehospital rescue team were female. Ages varied from 30 to 49 years old. As to time already in the profession, 59% reported having worked from five to ten years in prehospital rescue. As to Maslach burnout Inventory subscale means, in the group analyzed of 17 prehospital rescue team nurses, low/moderate level (31.53 of reduced professional accomplishment, low/moderate level (18.41 of emotional exhaustion, and low/moderate level (8.88 of depersonalization were observed. As to dimensions of burnout levels, it was noted that 76.47% of the nurses displayed a low/moderate level of emotional exhaustion, depersonalization, and reduced professional accomplishment. Cconclusions: It was demonstrated that this sample showed no evidence of burnout syndrome, since its presence is proven only when there are high scores of emotional exhaustion, depersonalization, and reduced professional accomplishment.

  4. Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects

    Directory of Open Access Journals (Sweden)

    Vincent Runtuwene

    2011-05-01

    Noonan syndrome is a relatively common developmental disorder that is characterized by reduced growth, wide-set eyes and congenital heart defects. Noonan syndrome is associated with dysregulation of the Ras–mitogen-activated-protein-kinase (MAPK signaling pathway. Recently, two mutations in NRAS were reported to be associated with Noonan syndrome, T50I and G60E. Here, we report a mutation in NRAS, resulting in an I24N amino acid substitution, that we identified in an individual bearing typical Noonan syndrome features. The I24N mutation activates N-Ras, resulting in enhanced downstream signaling. Expression of N-Ras-I24N, N-Ras-G60E or the strongly activating mutant N-Ras-G12V, which we included as a positive control, results in developmental defects in zebrafish embryos, demonstrating that these activating N-Ras mutants are sufficient to induce developmental disorders. The defects in zebrafish embryos are reminiscent of symptoms in individuals with Noonan syndrome and phenocopy the defects that other Noonan-syndrome-associated genes induce in zebrafish embryos. MEK inhibition completely rescued the activated N-Ras-induced phenotypes, demonstrating that these defects are mediated exclusively by Ras-MAPK signaling. In conclusion, mutations in NRAS from individuals with Noonan syndrome activated N-Ras signaling and induced developmental defects in zebrafish embryos, indicating that activating mutations in NRAS cause Noonan syndrome.

  5. Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects

    Science.gov (United States)

    Runtuwene, Vincent; van Eekelen, Mark; Overvoorde, John; Rehmann, Holger; Yntema, Helger G.; Nillesen, Willy M.; van Haeringen, Arie; van der Burgt, Ineke; Burgering, Boudewijn; den Hertog, Jeroen

    2011-01-01

    SUMMARY Noonan syndrome is a relatively common developmental disorder that is characterized by reduced growth, wide-set eyes and congenital heart defects. Noonan syndrome is associated with dysregulation of the Ras–mitogen-activated-protein-kinase (MAPK) signaling pathway. Recently, two mutations in NRAS were reported to be associated with Noonan syndrome, T50I and G60E. Here, we report a mutation in NRAS, resulting in an I24N amino acid substitution, that we identified in an individual bearing typical Noonan syndrome features. The I24N mutation activates N-Ras, resulting in enhanced downstream signaling. Expression of N-Ras-I24N, N-Ras-G60E or the strongly activating mutant N-Ras-G12V, which we included as a positive control, results in developmental defects in zebrafish embryos, demonstrating that these activating N-Ras mutants are sufficient to induce developmental disorders. The defects in zebrafish embryos are reminiscent of symptoms in individuals with Noonan syndrome and phenocopy the defects that other Noonan-syndrome-associated genes induce in zebrafish embryos. MEK inhibition completely rescued the activated N-Ras-induced phenotypes, demonstrating that these defects are mediated exclusively by Ras-MAPK signaling. In conclusion, mutations in NRAS from individuals with Noonan syndrome activated N-Ras signaling and induced developmental defects in zebrafish embryos, indicating that activating mutations in NRAS cause Noonan syndrome. PMID:21263000

  6. Posture manipulation for rescue activity via small traction robots

    International Nuclear Information System (INIS)

    Iwano, Yuki; Osuka, Koichi; Amano, Hisanori

    2006-01-01

    We discuss a conceptual design of rescue robots against nuclear-power plant accidents. We claim that the rescue robots in nuclear-power plants should have the following properties. (1) The size is small. (2) The structure is simple. (3) The number of the robots is large. This paper studies the rescue robots to rescue people in an area polluted with radioactive leakage in nuclear power institutions. In particular, we propose a rescue system which consists of a group of small mobile robots. First, small traction robots set the posture of the fainted victims to carry easily, and carry them to the safety space with the mobile robots for the stretcher composition. In this paper, we describe the produced small traction robots. And, we confirm that the robots can manipulate a 40 kg dummy doll's posture. We also examine the optimal number of robots from a perspective of working efficiency in the assumption spot. (author)

  7. Early environmental therapy rescues brain development in a mouse model of Down syndrome.

    Science.gov (United States)

    Begenisic, Tatjana; Sansevero, Gabriele; Baroncelli, Laura; Cioni, Giovanni; Sale, Alessandro

    2015-10-01

    Down syndrome (DS), the most common genetic disorder associated with intellectual disabilities, is an untreatable condition characterized by a number of developmental defects and permanent deficits in the adulthood. Ts65Dn mice, the major animal model for DS, display severe cognitive and synaptic plasticity defects closely resembling the human phenotype. Here, we employed a multidisciplinary approach to investigate, for the first time in developing Ts65Dn mice, the effects elicited by early environmental enrichment (EE) on brain maturation and function. We report that exposure to EE resulted in a robust increase in maternal care levels displayed by Ts65Dn mothers and led to a normalization of declarative memory abilities and hippocampal plasticity in trisomic offspring. The positive effects of EE on Ts65Dn phenotype were not limited to the cognitive domain, but also included a rescue of visual system maturation. The beneficial EE effects were accompanied by increased BDNF and correction of over-expression of the GABA vesicular transporter vGAT. These findings highlight the beneficial impact of early environmental stimuli and their potential for application in the treatment of major functional deficits in children with DS. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

    Science.gov (United States)

    Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  9. Neurological disease mutations of α3 Na+,K+-ATPase: Structural and functional perspectives and rescue of compromised function.

    Science.gov (United States)

    Holm, Rikke; Toustrup-Jensen, Mads S; Einholm, Anja P; Schack, Vivien R; Andersen, Jens P; Vilsen, Bente

    2016-11-01

    Na + ,K + -ATPase creates transmembrane ion gradients crucial to the function of the central nervous system. The α-subunit of Na + ,K + -ATPase exists as four isoforms (α1-α4). Several neurological phenotypes derive from α3 mutations. The effects of some of these mutations on Na + ,K + -ATPase function have been studied in vitro. Here we discuss the α3 disease mutations as well as information derived from studies of corresponding mutations of α1 in the light of the high-resolution crystal structures of the Na + ,K + -ATPase. A high proportion of the α3 disease mutations occur in the transmembrane sector and nearby regions essential to Na + and K + binding. In several cases the compromised function can be traced to disturbance of the Na + specific binding site III. Recently, a secondary mutation was found to rescue the defective Na + binding caused by a disease mutation. A perspective is that it may be possible to develop an efficient pharmaceutical mimicking the rescuing effect. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Emergency Air Rescue System in Romania

    Directory of Open Access Journals (Sweden)

    Tranca Sebastian

    2018-03-01

    Full Text Available The helicopter, as a means of transport, has facilitated a significant decrease in intervention time at the site of request, increasing the chances of survival of the critical patient. Since 2003, SMURD has managed to form a fleet composed of nine helicopters and two airplanes. From an operational and strategic point of view, the SMURD intervention unit, set up seven Aeromedical Operational Bases (A.O.B. equipped with helicopters and materials necessary for their operation. There is a dynamic increase in the number of air rescue missions in Romania, with most missions being carried out by the air rescue bases in Târgu Mureş and Bucharest. Specialty literature has clearly demonstrated the positive impact on the survival of critical patients assisted by airborne crews, so it is necessary for the Romanian air rescue system to grow up. It is necessary to increase the number of air bases, purchase new helicopters and to continue the training programs of both pilots and medical personnel.

  11. Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

    Science.gov (United States)

    Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

    2008-01-01

    Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

  12. [Analysis on on-site rescue and traumatic features of victims involved in gas explosion accident in Hangzhou].

    Science.gov (United States)

    Wang, X G; Jin, R H; Liu, F P; Han, C M

    2017-10-20

    Objective: To investigate the situations of on-site rescue and traumatic features of victims involved in gas explosion accident in Hangzhou, so as to provide more data support for emergency medical rescues of the similar incidents of massive casualty. Methods: Two medical workers with a certain clinical experience were sent to Hangzhou 120 emergency medical centers to collect data of the on-site rescue on 21st July, 2017, including ambulance call-outs, on-site command and traffic conditions, and on-site triage and evacuation of the victims. They were then sent to the hospitals receiving the victims to investigate the situations of these victims including the general information (such as gender, age, admitted hospitals, and number of admission, discharge, and transferring in the first two weeks after the accident) and injury assessment [such as injury position and type, injury severity evaluation by New Injury Severity Scoring (NISS), and burn severity evaluation for victims with burns]. Results: (1) A total of 15 ambulances reached the accident site for rescue. The traffic and transportation were jammed and interrupted after this accident. On-site triage and distribution were disorderly conducted. (2) Clinical data of 53 victims were collected, including 24 males and 29 females, with the age of 8 to 70 (34±14) years old. They were sent into 6 hospitals in Hangzhou. Two victims died on the day of accident. Up to two weeks after this accident, 28 (52.8%) victims were discharged from the hospitals and received follow-up in outpatient department. Five victims with severe injuries were transferred to the other hospitals. (3) Based on the results of NISS, the injury severities were mild in 29 (54.7%) cases, moderate in 9 (17.0%) cases, serious in 3 (5.7%) cases, and severe in 12 (22.6%) cases. Those 2 dead victims were classified into the severe category due to the highest NISS score of 75. For all of the victims, skin and soft tissue defects were most common. Six (11

  13. A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome.

    Science.gov (United States)

    Cuykendall, Tawny N; Satyaki, P; Ji, Shuqing; Clay, Derek M; Edelman, Nathaniel B; Kimchy, Alexandra; Li, Ling-Hei; Nuzzo, Erin A; Parekh, Neil; Park, Suna; Barbash, Daniel A

    2014-10-27

    Hybrid sons between Drosophila melanogaster females and D. simulans males die as 3rd instar larvae. Two genes, D. melanogaster Hybrid male rescue (Hmr) on the X chromosome, and D. simulans Lethal hybrid rescue (Lhr) on chromosome II, interact to cause this lethality. Loss-of-function mutations in either gene suppress lethality, but several pieces of evidence suggest that additional factors are required for hybrid lethality. Here we screen the D. melanogaster autosomal genome by using the Bloomington Stock Center Deficiency kit to search for additional regions that can rescue hybrid male lethality. Our screen is designed to identify putative hybrid incompatibility (HI) genes similar to Hmr and Lhr which, when removed, are dominant suppressors of lethality. After screening 89% of the autosomal genome, we found no regions that rescue males to the adult stage. We did, however, identify several regions that rescue up to 13% of males to the pharate adult stage. This weak rescue suggests the presence of multiple minor-effect HI loci, but we were unable to map these loci to high resolution, presumably because weak rescue can be masked by genetic background effects. We attempted to test one candidate, the dosage compensation gene male specific lethal-3 (msl-3), by using RNA interference with short hairpin microRNA constructs targeted specifically against D. simulans msl-3 but failed to achieve knockdown, in part due to off-target effects. We conclude that the D. melanogaster autosomal genome likely does not contain additional major-effect HI loci. We also show that Hmr is insufficient to fully account for the lethality associated with the D. melanogaster X chromosome, suggesting that additional X-linked genes contribute to hybrid lethality. Copyright © 2014 Cuykendall et al.

  14. Expectations of a business rescue plan: international directives for ...

    African Journals Online (AJOL)

    Expectations of a business rescue plan: international directives for Chapter 6 implementation. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... Preliminary analysis of business rescue plans suggested that a significant ...

  15. In vitro embryo rescue and plant regeneration following self ...

    African Journals Online (AJOL)

    In vitro embryo rescue and plant regeneration following self-pollination with irradiated ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... shows that pollen irradiation coupled with self-pollination and embryo rescue ...

  16. Cooperative RNP assembly: Complementary rescue of structural defects by protein and RNA subunits of archaeal RNase P

    Science.gov (United States)

    Chen, Wen-Yi; Xu, Yiren; Cho, I-Ming; Oruganti, Sri Vidya; Foster, Mark P.; Gopalan, Venkat

    2011-01-01

    RNase P is a ribonucleoprotein (RNP) complex that utilizes a Mg2+-dependent RNA catalyst to cleave the 5′-leader of precursor tRNAs (pre-tRNAs) and generate mature tRNAs. The bacterial RNase P protein (RPP) aids RNase P RNA (RPR) catalysis by promoting substrate binding, Mg2+ coordination, and product release. Archaeal RNase P comprises an RPR and at least four RPPs, which have eukaryal homologs and function as two binary complexes (POP5•RPP30 and RPP21•RPP29). In this study, we employed a previously characterized substrate-enzyme conjugate [pre-tRNATyr-Methanocaldococcus jannaschii (Mja) RPR] to investigate the functional role of a universally conserved uridine in a bulge-helix structure in archaeal RPRs. Deletion of this bulged uridine resulted in an 80-fold decrease in the self-cleavage rate of pre-tRNATyr-MjaΔU RPR compared to the wildtype, and this defect was partially ameliorated upon addition of either RPP pair. The catalytic defect in the archaeal mutant RPR mirrors that reported in a bacterial RPR and highlights a parallel in their active sites. Furthermore, an N-terminal deletion mutant of Pyrococcus furiosus (Pfu) RPP29 that is defective in assembling with its binary partner RPP21, as assessed by isothermal titration calorimetry and NMR spectroscopy, is functional when reconstituted with the cognate Pfu RPR. Collectively, these results indicate that archaeal RPPs are able to compensate for structural defects in their cognate RPR and vice-versa, and provide striking examples of the cooperative subunit interactions critical for driving archaeal RNase P towards its functional conformation. (236 words) PMID:21683084

  17. Medical rescue of naval combat: challenges and future.

    Science.gov (United States)

    Jin, Hai; Hou, Li-Jun; Fu, Xiao-Bing

    2015-01-01

    There has been no large-scale naval combat in the last 30 years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Additionally, naval combat is facing unprecedented challenges. In this paper, we discuss the topic of medical rescue at sea: what challenges we face and what we could do. The contents discussed in this paper contain battlefield self-aid buddy care, clinical skills, organized health services, medical training and future medical research programs. We also discuss the characteristics of modern naval combat, medical rescue challenges, medical treatment highlights and future developments of medical rescue at sea.

  18. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boat embarkation, launching and recovery...) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must...

  19. Emotional Reactions of Rescue Workers Following a Tornado.

    Science.gov (United States)

    McCammon, Susan L.; And Others

    Rescue and medical workers may be at risk for negative emotional experience following intervention efforts in disaster situations. To examine this possibility, 120 rescue and hospital personnel responded to a survey of their emotional reactions and coping behaviors 3 months after a devastating tornado. Twenty-eight subjects had been involved in…

  20. F508del-CFTR rescue: a matter of cell stress response.

    Science.gov (United States)

    Nieddu, Erika; Pollarolo, Benedetta; Merello, Luisa; Schenone, Silvia; Mazzei, Mauro

    2013-01-01

    Cystic fibrosis (CF) is a common inherited fatal disease affecting 70,000 people worldwide, with a median predicted age of survival of approximately 38 years. The deletion of Phenylalanine in position 508 of the Cystic Fibrosis Transmembrane conductance Regulator (F508del-CFTR) is the most common mutation in CF patients: the deleted protein, not properly folded, is degraded. To date no commercial drugs are available. Low temperature, some osmolytes and conditions able to induce heat shock protein 70 (Hsp70) expression and heat shock cognate 70 (Hsc70) inhibition result in F508del-CFTR rescue, hence restoring its physiological function: this review sheds light on the correlation between these several evidences. Interestingly, all these approaches have a role in the cell stress response (CSR), a set of cell reactions to stress. In addition, unpredictably, F508del-CFTR rescue has to be considered in the frame of CSR: entities that induce - or are induced during - the CSR are, in general, also able to correct trafficking defect of CFTR. Specifically, the low temperature induces, by definition, a CSR; osmolytes, such as glycerol and trimethylamine N-oxide (TMAO), are products of the CSR; pharmacological correctors, such as Matrine and 4-phenylbutirric acid (4PBA), down-regulate the constitutive Hsc70 in favor of an up-regulation of the inducible chaperone Hsp70, another component of the CSR. The identification of a common mechanism of action for different types of correctors could drive the discovery of new active molecules in CF, overcoming methods clinically inapplicable, such as the low temperature.

  1. A versatile sensor network for urban search and rescue operations

    Science.gov (United States)

    Känsälä, Klaus; Korkalainen, Marko; Mäyrä, Aki

    2011-11-01

    The presentation is based in the research work carried out in EU funded project SGL for USaR (Second Generation Locator for Urban Search and Rescue Operations). The aim of this project is to develop wireless standalone communication system with embedded sensor network which can be globally used in rescue operations after accidents or terrorist attacks. The system should be able to operate without external support for several days: it should have autonomy with power supply and communication. The devices must be lightweight so that rescue team can easily carry them and finally they must be easy to install and use. The range of the wireless communication must cover an area of several square kilometers. The embedded sensor system must be able to detect sings of life but also detect hazards threatening the rescue operators thus preventing more accidents. It should also support positioning and digital mapping as well as the management of the search and rescue operation. This sensor network for urban search and rescue operations has been tested on a field conditions and it has proven to be robust and reliable and provides an energy efficient way of communication and positioning on harsh conditions.

  2. Rescue workers and trauma

    DEFF Research Database (Denmark)

    Romano, Eugenia; Elklit, Ask

    2017-01-01

    Introduction: This study investigates which factors had the biggest impact on developing distress in rescue workers who were involved in a firework factory explosion. Method: Four hundred sixty-five rescuers were assessed using items investigating demographic factors, organizational variables, so...

  3. Vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association with Mayer-Rokitansky-Küster-Hauser syndrome in co-occurrence: two case reports and a review of the literature.

    Science.gov (United States)

    Bjørsum-Meyer, Thomas; Herlin, Morten; Qvist, Niels; Petersen, Michael B

    2016-12-21

    The vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome are rare conditions. We aimed to present two cases with the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser co-occurrence from our local surgical center and through a systematic literature search detect published cases. Furthermore, we aimed to collect existing knowledge in the embryopathogenesis and genetics in order to discuss a possible link between the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome. Our first case was a white girl delivered by caesarean section at 37 weeks of gestation; our second case was a white girl born at a gestational age of 40 weeks. A co-occurrence of vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome was diagnosed in both cases. We performed a systematic literature search in PubMed ((VACTERL) OR (VATER)) AND ((MRKH) OR (Mayer-Rokitansky-Küster-Hauser) OR (mullerian agenesis) OR (mullerian aplasia) OR (MURCS)) without limitations. A similar search was performed in Embase and the Cochrane library. We added two cases from our local center. All cases (n = 9) presented with anal atresia and renal defect. Vertebral defects were present in eight patients. Rectovestibular fistula was confirmed in seven patients. Along with the uterovaginal agenesis, fallopian tube aplasia appeared in five of nine cases and in two cases ovarian involvement also existed. The co-occurrence of the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal

  4. 46 CFR 133.160 - Rescue boat embarkation, launching and recovery arrangements.

    Science.gov (United States)

    2010-10-01

    ...) OFFSHORE SUPPLY VESSELS LIFESAVING SYSTEMS Requirements for All OSVs § 133.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each davit for a rescue boat must be approved under approval series... 46 Shipping 4 2010-10-01 2010-10-01 false Rescue boat embarkation, launching and recovery...

  5. CO{sub 2} in underground openings and mine rescue training

    Energy Technology Data Exchange (ETDEWEB)

    Weyer, J. [Freiburg Univ. of Mining and Technology (Germany). Inst. of Mining Engineering and Special Civil Engineering

    2010-07-01

    Mine rescue training procedures related to dangerous gases in mines were discussed. Methods of detecting carbon dioxide (CO{sub 2}) in abandoned opening and old adits were presented. High concentrations of CO{sub 2} combine with hemoglobin and lead to a lack of oxygen supply to the inner organs. Nitric acid forms in the alveoli and can lead to injuries or death after a period of 4 to 12 hours. Exposure to very high concentrations of CO{sub 2} can cause people to immediately lose consciousness. CO{sub 2} concentrations in the blood can change pH blood values. Members of mine rescue teams should be equipped with breathing equipment and be between 18 and 40 years old. Training rescue operations should be conducted 4 times per year. While larger mines have their own rescue teams, smaller mines must ensure that guest rescue teams are familiar with their mines. Various mine training activities were reviewed. 5 refs.

  6. Radioactive fallout and neural tube defects | Akar | Egyptian Journal ...

    African Journals Online (AJOL)

    Possible link between radioactivity and the occurrence of neural tube defects is a long lasting debate since the Chernobyl nuclear fallout in 1986. A recent report on the incidence of neural defects in the west coast of USA, following Fukushima disaster, brought another evidence for effect of radioactive fallout on the ...

  7. Reliable Rescue Routing Optimization for Urban Emergency Logistics under Travel Time Uncertainty

    Directory of Open Access Journals (Sweden)

    Qiuping Li

    2018-02-01

    Full Text Available The reliability of rescue routes is critical for urban emergency logistics during disasters. However, studies on reliable rescue routing under stochastic networks are still rare. This paper proposes a multiobjective rescue routing model for urban emergency logistics under travel time reliability. A hybrid metaheuristic integrating ant colony optimization (ACO and tabu search (TS was designed to solve the model. An experiment optimizing rescue routing plans under a real urban storm event, was carried out to validate the proposed model. The experimental results showed how our approach can improve rescue efficiency with high travel time reliability.

  8. The rule of rescue.

    Science.gov (United States)

    McKie, John; Richardson, Jeff

    2003-06-01

    Jonsen coined the term "Rule of Rescue"(RR) to describe the imperative people feel to rescue identifiable individuals facing avoidable death. In this paper we attempt to draw a more detailed picture of the RR, identifying its conflict with cost-effectiveness analysis, the preference it entails for identifiable over statistical lives, the shock-horror response it elicits, the preference it entails for lifesaving over non-lifesaving measures, its extension to non-life-threatening conditions, and whether it is motivated by duty or sympathy. We also consider the measurement problems it raises, and argue that quantifying the RR would probably require a two-stage procedure. In the first stage the size of the individual utility gain from a health intervention would be assessed using a technique such as the Standard Gamble or the Time Trade-Off, and in the second the social benefits arising from the RR would be quantified employing the Person Trade-Off. We also consider the normative status of the RR. We argue that it can be defended from a utilitarian point of view, on the ground that rescues increase well-being by reinforcing people's belief that they live in a community that places great value upon life. However, utilitarianism has long been criticised for failing to take sufficient account of fairness, and the case is no different here: fairness requires that we do not discriminate between individuals on morally irrelevant grounds, whereas being "identifiable" does not seem to be a morally relevant ground for discrimination.

  9. Simulation Optimization of Search and Rescue in Disaster Relief Based on Distributed Auction Mechanism

    Directory of Open Access Journals (Sweden)

    Jian Tang

    2017-11-01

    Full Text Available In this paper, we optimize the search and rescue (SAR in disaster relief through agent-based simulation. We simulate rescue teams’ search behaviors with the improved Truncated Lévy walks. Then we propose a cooperative rescue plan based on a distributed auction mechanism, and illustrate it with the case of landslide disaster relief. The simulation is conducted in three scenarios, including “fatal”, “serious” and “normal”. Compared with the non-cooperative rescue plan, the proposed rescue plan in this paper would increase victims’ relative survival probability by 7–15%, increase the ratio of survivors getting rescued by 5.3–12.9%, and decrease the average elapsed time for one site getting rescued by 16.6–21.6%. The robustness analysis shows that search radius can affect the rescue efficiency significantly, while the scope of cooperation cannot. The sensitivity analysis shows that the two parameters, the time limit for completing rescue operations in one buried site and the maximum turning angle for next step, both have a great influence on rescue efficiency, and there exists optimal value for both of them in view of rescue efficiency.

  10. International Fund of Aral Sea rescue:prospects and new aims

    International Nuclear Information System (INIS)

    Aslov, S.M.

    2003-01-01

    In this chapter of book author suggest about aims and prospects of International Fund of Aral Sea rescue. The base aim of International Fund of Aral Sea rescue was the funds attraction of Central Asia governments and international community-donors for financing of Program of Aral Sea basin. Now the Executive Committee of International Fund of Aral Sea rescue develops the program of basin of Aral Sea for the period till 2010

  11. Embryo rescue of crosses between diploid and tetraploid grape ...

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... embryo rescue from interspecific hybridization between diploid and tetraploid grape species. Wakana et al. (2003) and Motosugi et al. (2003) studied the formation and developments of hybrid seeds from cross between diploid and tetraploid, and then obtained triploid progenies through embryo rescue.

  12. Microtubule catastrophe and rescue.

    Science.gov (United States)

    Gardner, Melissa K; Zanic, Marija; Howard, Jonathon

    2013-02-01

    Microtubules are long cylindrical polymers composed of tubulin subunits. In cells, microtubules play an essential role in architecture and motility. For example, microtubules give shape to cells, serve as intracellular transport tracks, and act as key elements in important cellular structures such as axonemes and mitotic spindles. To accomplish these varied functions, networks of microtubules in cells are very dynamic, continuously remodeling through stochastic length fluctuations at the ends of individual microtubules. The dynamic behavior at the end of an individual microtubule is termed 'dynamic instability'. This behavior manifests itself by periods of persistent microtubule growth interrupted by occasional switching to rapid shrinkage (called microtubule 'catastrophe'), and then by switching back from shrinkage to growth (called microtubule 'rescue'). In this review, we summarize recent findings which provide new insights into the mechanisms of microtubule catastrophe and rescue, and discuss the impact of these findings in regards to the role of microtubule dynamics inside of cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Who is going to rescue the rescuers? Post-traumatic stress disorder among rescue workers operating in Greece during the European refugee crisis.

    Science.gov (United States)

    Sifaki-Pistolla, Dimitra; Chatzea, Vasiliki-Eirini; Vlachaki, Sofia-Aikaterini; Melidoniotis, Evangelos; Pistolla, Georgia

    2017-01-01

    During the European refugee crisis, numerous Greek and international rescue workers are operating in Lesvos, offering search, rescue, and first aid services. Exposure to stressful life events while engaging in this rescue work can result in developing Post-Traumatic Stress Disorder (PTSD). The study aimed to assess the prevalence of PTSD and explore potential differences between different categories of rescuers. A cross-sectional study was conducted among 217 rescue workers. Participants were grouped according to affiliation: "Greek Professionals Rescuers/GPR", "International Professionals Rescuers/IPR" and "Volunteer Rescuers/VR". The PTSD Checklist-Civilian Version (PCL-C) was utilized. All tests were two-tailed (a = 0.05). Mann-Whitney, Kruskal-Wallis, and multivariate logistic regression were performed. Overall probable PTSD prevalence found was 17.1%. Rates varied significantly per rescuer's category; 23.1% in GPR, 11.8% in IPR, and 14.6% in VR (p = 0.02). GPR demonstrated the highest risk compared to IPR and VR (p hours, and handling dead refugees and dead children were also considered major risk factors. Rescue workers providing substantial aid to the refugees and migrants at Lesvos experience significant psychological distress. The present findings indicate the urgent need for targeted interventions. Further studies are needed to address long-term effects of the refugee crisis on rescuers, and explore effective measures to prevent PTSD.

  14. Guidance of Autonomous Amphibious Vehicles for Flood Rescue Support

    Directory of Open Access Journals (Sweden)

    Shankarachary Ragi

    2013-01-01

    Full Text Available We develop a path-planning algorithm to guide autonomous amphibious vehicles (AAVs for flood rescue support missions. Specifically, we develop an algorithm to control multiple AAVs to reach/rescue multiple victims (also called targets in a flood scenario in 2D, where the flood water flows across the scene and the targets move (drifted by the flood water along the flood stream. A target is said to be rescued if an AAV lies within a circular region of a certain radius around the target. The goal is to control the AAVs such that each target gets rescued while optimizing a certain performance objective. The algorithm design is based on the theory of partially observable Markov decision process (POMDP. In practice, POMDP problems are hard to solve exactly, so we use an approximation method called nominal belief-state optimization (NBO. We compare the performance of the NBO approach with a greedy approach.

  15. Intelligent Robot-assisted Humanitarian Search and Rescue System

    Directory of Open Access Journals (Sweden)

    Henry Y. K. Lau

    2009-11-01

    Full Text Available The unprecedented scale and number of natural and man-made disasters in the past decade has urged international emergency search and rescue communities to seek for novel technology to enhance operation efficiency. Tele-operated search and rescue robots that can navigate deep into rubble to search for victims and to transfer critical field data back to the control console has gained much interest among emergency response institutions. In response to this need, a low-cost autonomous mini robot equipped with thermal sensor, accelerometer, sonar, pin-hole camera, microphone, ultra-bright LED and wireless communication module is developed to study the control of a group of decentralized mini search and rescue robots. The robot can navigate autonomously between voids to look for living body heat and can send back audio and video information to allow the operator to determine if the found object is a living human. This paper introduces the design and control of a low-cost robotic search and rescue system based on an immuno control framework developed for controlling decentralized systems. Design and development of the physical prototype and the immunity-based control system are described in this paper.

  16. Intelligent Robot-Assisted Humanitarian Search and Rescue System

    Directory of Open Access Journals (Sweden)

    Albert W. Y. Ko

    2009-06-01

    Full Text Available The unprecedented scale and number of natural and man-made disasters in the past decade has urged international emergency search and rescue communities to seek for novel technology to enhance operation efficiency. Tele-operated search and rescue robots that can navigate deep into rubble to search for victims and to transfer critical field data back to the control console has gained much interest among emergency response institutions. In response to this need, a low-cost autonomous mini robot equipped with thermal sensor, accelerometer, sonar, pin-hole camera, microphone, ultra-bright LED and wireless communication module is developed to study the control of a group of decentralized mini search and rescue robots. The robot can navigate autonomously between voids to look for living body heat and can send back audio and video information to allow the operator to determine if the found object is a living human. This paper introduces the design and control of a low-cost robotic search and rescue system based on an immuno control framework developed for controlling decentralized systems. Design and development of the physical prototype and the immunity-based control system are described in this paper.

  17. Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

    Energy Technology Data Exchange (ETDEWEB)

    Mosier, D.E.; Mond, J.J.; Goldings, E.A.

    1977-12-01

    The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other.

  18. Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

    International Nuclear Information System (INIS)

    Mosier, D.E.; Mond, J.J.; Goldings, E.A.

    1977-01-01

    The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other

  19. Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice.

    Science.gov (United States)

    Liu, Karen J; Arron, Joseph R; Stankunas, Kryn; Crabtree, Gerald R; Longaker, Michael T

    2007-03-01

    Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interacts with many different pathways, its specific developmental roles remain unclear. We have discovered a genetic requirement for GSK-3beta in midline development. Homozygous null mice display cleft palate, incomplete fusion of the ribs at the midline and bifid sternum as well as delayed sternal ossification. Using a chemically regulated allele of GSK-3beta (ref. 6), we have defined requirements for GSK-3beta activity during discrete temporal windows in palatogenesis and skeletogenesis. The rapamycin-dependent allele of GSK-3beta produces GSK-3beta fused to a tag, FRB* (FKBP/rapamycin binding), resulting in a rapidly destabilized chimaeric protein. In the absence of drug, GSK-3beta(FRB)*(/FRB)* mutants appear phenotypically identical to GSK-3beta-/- mutants. In the presence of drug, GSK-3betaFRB* is rapidly stabilized, restoring protein levels and activity. Using this system, mutant phenotypes were rescued by restoring endogenous GSK-3beta activity during two distinct periods in gestation. This technology provides a powerful tool for defining windows of protein function during development.

  20. Endovascular rescue method for undesirably stretched coil.

    Science.gov (United States)

    Cho, Jae Hoon

    2014-10-01

    Undesirable detachment or stretching of coils within the parent artery during aneurysm embolization can be related with thrombus formation, which can be caused occlusion of parent artery or embolic event(s). To escape from this situation, several rescue methods have been reported. A case with undesirably stretched coil in which another rescue method was used, is presented. When the stretched coil is still located in the coil delivery microcatheter, the stretched coil can be removed safely using a snare and a handmade monorail microcatheter. After a snare is lodged in the handmade monorail microcatheter, the snare is introduced over the coil delivery micorcatheter and located in the distal part of the stretched coil. After then, the handmade monorail microcatheter captures the stretched coil and the snare as one unit. This technique using a handmade monorail microcatheter and a snare can be a good rescue modality for the undesirably stretched coil, still remained within the coil delivery microcatheter.

  1. Current insights into the role of PKA phosphorylation in CFTR channel activity and the pharmacological rescue of cystic fibrosis disease-causing mutants.

    Science.gov (United States)

    Chin, Stephanie; Hung, Maurita; Bear, Christine E

    2017-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) channel gating is predominantly regulated by protein kinase A (PKA)-dependent phosphorylation. In addition to regulating CFTR channel activity, PKA phosphorylation is also involved in enhancing CFTR trafficking and mediating conformational changes at the interdomain interfaces of the protein. The major cystic fibrosis (CF)-causing mutation is the deletion of phenylalanine at position 508 (F508del); it causes many defects that affect CFTR trafficking, stability, and gating at the cell surface. Due to the multiple roles of PKA phosphorylation, there is growing interest in targeting PKA-dependent signaling for rescuing the trafficking and functional defects of F508del-CFTR. This review will discuss the effects of PKA phosphorylation on wild-type CFTR, the consequences of CF mutations on PKA phosphorylation, and the development of therapies that target PKA-mediated signaling.

  2. Flash flood swift water rescues, Texas, 2005–2014

    Directory of Open Access Journals (Sweden)

    Vaidehi Shah

    2017-01-01

    Full Text Available Although rainfall patterns are complex and difficult to predict, climate models suggest precipitation in Texas will occur less frequently and with greater intensity in the future. In combination with rapid population growth and development, extreme rainfall events are likely to lead to flash floods and necessitate swift water rescues. Swift water rescues are used to retrieve person(s from swift water flowing at a rate of 1 knot or greater. Data were obtained from the Texas Fire Marshal’s Office and analyzed to describe spatial and temporal characteristics of rescues. Between 2005 and 2014, 3256 swift water rescues were reported from 136 of 254 (54% counties. Over half (54.6%, n = 1777 occurred in counties known as Flash Flood Alley, which includes Texas’ largest and fastest growing cities. Less than 1.0% (n = 18 were reported from 49 counties designated as completely rural, or with an urban population less than 2500. Increases in swift water rescues were seen between March and September and during major weather events such as tropical storms. Because county-level data was utilized and demographic data was missing in all but 2% (n = 47 of the incidents, our ability to identify populations at risk or target interventions in the future using this data is limited. Despite the frequency of flash flood events and swift water rescues in Texas, knowledge gaps persist that should be addressed through the conduct of interdisciplinary research by epidemiologists and climatologists and by disseminating evidence-based health education and safety programs, particularly in rapidly growing counties that make up Texas’ Flash Flood Alley.

  3. Rescue US energy innovation

    Science.gov (United States)

    Anadon, Laura Diaz; Gallagher, Kelly Sims; Holdren, John P.

    2017-10-01

    President Trump has proposed severe cuts to US government spending on energy research, development and demonstration, but Congress has the `power of the purse' and can rescue US energy innovation. If serious cuts are enacted, the pace of innovation will slow, harming the economy, energy security and global environmental quality.

  4. The RESCueH Programme

    DEFF Research Database (Denmark)

    Søgaard Nielsen, Anette; Nielsen, Bent; Andersen, Kjeld

    2016-01-01

    Excessive alcohol consumption is one of the most important lifestyle factors affecting the disease burden in the Western world. The results of treatment in daily practice are modest at best. The aim of the RESCueH programme is to develop and evaluate methods, which are as practice-near as possible...

  5. EPS insulated façade fires from a fire and rescue perspective

    Directory of Open Access Journals (Sweden)

    Kumm M.

    2013-11-01

    Full Text Available This paper highlights the challenges the fire and rescue services can meet at façade fires involving EPS insulation during construction and use of a building. The EPS characteristics are discussed in respect to the fire and rescue operation and results from orientating fire tests performed at a fire and rescue services training and test field are presented. Types of evacuation solutions, involving the fire and rescue services, where façade fires can delay or completely rule out the possibilities for safe evacuation, are presented. The restrictions in the Swedish building codes regarding use of combustible insulation are analysed and reflections over the practical problems with following the instructions to keep an EPS insulated façade safe through the building's whole lifespan are made. A number of occurred fires involving EPS are discussed and analysed from a fire and rescue perspective. Finally, recommendations are given for the fire and rescue services and future research fields are proposed.

  6. Shp2 knockdown and Noonan/LEOPARD mutant Shp2-induced gastrulation defects.

    Directory of Open Access Journals (Sweden)

    Chris Jopling

    2007-12-01

    Full Text Available Shp2 is a cytoplasmic protein-tyrosine phosphatase that is essential for normal development. Activating and inactivating mutations have been identified in humans to cause the related Noonan and LEOPARD syndromes, respectively. The cell biological cause of these syndromes remains to be determined. We have used the zebrafish to assess the role of Shp2 in early development. Here, we report that morpholino-mediated knockdown of Shp2 in zebrafish resulted in defects during gastrulation. Cell tracing experiments demonstrated that Shp2 knockdown induced defects in convergence and extension cell movements. In situ hybridization using a panel of markers indicated that cell fate was not affected by Shp2 knock down. The Shp2 knockdown-induced defects were rescued by active Fyn and Yes and by active RhoA. We generated mutants of Shp2 with mutations that were identified in human patients with Noonan or LEOPARD Syndrome and established that Noonan Shp2 was activated and LEOPARD Shp2 lacked catalytic protein-tyrosine phosphatase activity. Expression of Noonan or LEOPARD mutant Shp2 in zebrafish embryos induced convergence and extension cell movement defects without affecting cell fate. Moreover, these embryos displayed craniofacial and cardiac defects, reminiscent of human symptoms. Noonan and LEOPARD mutant Shp2s were not additive nor synergistic, consistent with the mutant Shp2s having activating and inactivating roles in the same signaling pathway. Our results demonstrate that Shp2 is required for normal convergence and extension cell movements during gastrulation and that Src family kinases and RhoA were downstream of Shp2. Expression of Noonan or LEOPARD Shp2 phenocopied the craniofacial and cardiac defects of human patients. The finding that defective Shp2 signaling induced cell movement defects as early as gastrulation may have implications for the monitoring and diagnosis of Noonan and LEOPARD syndrome.

  7. 46 CFR 111.75-16 - Lighting of survival craft and rescue boats.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Lighting of survival craft and rescue boats. 111.75-16... craft and rescue boats. (a) During preparation, launching, and recovery, each survival craft and rescue... of circuits must be such that the lighting for adjacent launching stations for survival craft or...

  8. Development of stretcher component robots for rescue against nuclear disaster

    International Nuclear Information System (INIS)

    Iwano, Yuki; Osuka, Koichi; Amano, Hisanori

    2006-01-01

    This paper studies the rescue robots to rescue people in an area polluted with radioactive leakage in nuclear power institutions. In particular, we propose the rescue system which consists of a group of small mobile robots. First, small traction robots set the posture of the fainted victims to carry easily, and carry them to the safety space with the mobile robots for the stretcher composition. In this paper, we confirm that the stretcher component robots could transport and convey a 40 [kg] dummy doll. And, we also show an application usage of stretcher robot. (author)

  9. GIS Support for Flood Rescue

    DEFF Research Database (Denmark)

    Liang, Gengsheng; Mioc, Darka; Anton, François

    2007-01-01

    Under flood events, the ground traffic is blocked in and around the flooded area due to damages to roads and bridges. The traditional transportation network may not always help people to make a right decision for evacuation. In order to provide dynamic road information needed for flood rescue, we...... to retrieve the shortest and safest route in Fredericton road network during flood event. It enables users to make a timely decision for flood rescue. We are using Oracle Spatial to deal with emergency situations that can be applied to other constrained network applications as well....... developed an adaptive web-based transportation network application using Oracle technology. Moreover, the geographic relationships between the road network and flood areas are taken into account. The overlay between the road network and flood polygons is computed on the fly. This application allows users...

  10. 29 CFR 553.215 - Ambulance and rescue service employees.

    Science.gov (United States)

    2010-07-01

    ... activities, the applicable standard is the one which applies to the activity in which the employee spends the majority of work time during the work period. (b) Ambulance and rescue service employees of public agencies... 29 Labor 3 2010-07-01 2010-07-01 false Ambulance and rescue service employees. 553.215 Section 553...

  11. Extrusion product defects: a statistical study

    International Nuclear Information System (INIS)

    Qamar, S.Z.; Arif, A.F.M.; Sheikh, A.K.

    2003-01-01

    In any manufacturing environment, defects resulting in rework or rejection are directly related to product cost and quality, and indirectly linked with process, tooling and product design. An analysis of product defects is therefore integral to any attempt at improving productivity, efficiency and quality. Commercial aluminum extrusion is generally a hot working process and consists of a series of different but integrated operations: billet preheating and sizing, die set and container preheating, billet loading and deformation, product sizing and stretching/roll-correction, age hardening, and painting/anodizing. Product defects can be traced back to problems in billet material and preparation, die and die set design and maintenance, process variable aberrations (ram speed, extrusion pressure, container temperature, etc), and post-extrusion treatment (age hardening, painting/anodizing, etc). The current paper attempts to analyze statistically the product defects commonly encountered in a commercial hot aluminum extrusion setup. Real-world rejection data, covering a period of nine years, has been researched and collected from a local structural aluminum extrusion facility. Rejection probabilities have been calculated for all the defects studied. The nine-year rejection data have been statistically analyzed on the basis of (i) an overall breakdown of defects, (ii) year-wise rejection behavior, (iii) breakdown of defects in each of three cost centers: press, anodizing, and painting. (author)

  12. Analysis of factors related to military training injury and the effect of self-rescue and buddy rescue on the final result of the injury in tank crew of the armored forces

    Directory of Open Access Journals (Sweden)

    Rong-bin ZHOU

    2011-09-01

    Full Text Available Objective To analyze the factors related to military training injury and the effect of self-rescue and buddy rescue on the result of the injury in the soldiers.Methods All data were statistically classified with cluster sampling according to the diagnosis standard of Chinese PLA for analysis.Investigation was conducted in 1028 soldiers of the armored forces with questionnaire,and non-condition logistic regression analysis was applied.Results The total incidence of military training injury was 40.2%.Of all the injured soldiers,36.80% of them served for one year only,and the incidence of injury was obviously higher than those who had served in armed forces for 2 or 3 years.Unconditioned regression analysis revealed that the main causes related to military training injury in the soldiers were as follows: the items of training,the terrain feature,motion sickness,self-rescue and buddy rescue training,and whether the action consistent with the standards.The rehabilitation rate within one month was significantly higher in those who underwent self-rescue or buddy rescue(93.8% and 94.2%,respectively than those who did not undergo self-rescue or buddy rescue(76.3%,76.7%,respectively,P < 0.001.Conclusions The incidence of military training injury in the armored forces is high.It should be emphysized that soldiers with one year of military service should be partioularly taken care to prevent from injuries.Many factors may influence the military training injury,and protective measures should be taken.Those who have the knowledge of self-rescue or undergo buddy rescue will have higher rehabilitation rate within one month.

  13. Defect mediated optical properties in ZnAl2O4 phosphor

    Science.gov (United States)

    Pathak, Nimai; Saxena, Suryansh; Kadam, R. M.

    2018-04-01

    The present work describes defect mediated optical properties in ZnAl2O4 phosphor material, synthesized through sol-gel combustion method, which has potential to be used both as a blue emitting phosphor material as well as white emitting, depending upon the annealing temperature during the synthesis procedure. Various defect centers such as anionic vacancy, cationic vacancy, antisite defects etc. create different electronic states inside the band gap, which are responsible for the multicolour emission. The interesting colour tunable emission characteristics can be linked with the various defect centers and their changes upon annealing.

  14. Electron Transport Chain Is Biochemically Linked to Pilus Assembly Required for Polymicrobial Interactions and Biofilm Formation in the Gram-Positive Actinobacterium Actinomyces oris

    Directory of Open Access Journals (Sweden)

    Belkys C. Sanchez

    2017-06-01

    Full Text Available The Gram-positive actinobacteria Actinomyces spp. are key colonizers in the development of oral biofilms due to the inherent ability of Actinomyces to adhere to receptor polysaccharides on the surface of oral streptococci and host cells. This receptor-dependent bacterial interaction, or coaggregation, requires a unique sortase-catalyzed pilus consisting of the pilus shaft FimA and the coaggregation factor CafA forming the pilus tip. While the essential role of the sortase machine SrtC2 in pilus assembly, biofilm formation, and coaggregation has been established, little is known about trans-acting factors contributing to these processes. We report here a large-scale Tn5 transposon screen for mutants defective in Actinomyces oris coaggregation with Streptococcus oralis. We obtained 33 independent clones, 13 of which completely failed to aggregate with S. oralis, and the remainder of which exhibited a range of phenotypes from severely to weakly defective coaggregation. The former had Tn5 insertions in fimA, cafA, or srtC2, as expected; the latter were mapped to genes coding for uncharacterized proteins and various nuo genes encoding the NADH dehydrogenase subunits. Electron microscopy and biochemical analyses of mutants with nonpolar deletions of nuo genes and ubiE, a menaquinone C-methyltransferase-encoding gene downstream of the nuo locus, confirmed the pilus and coaggregation defects. Both nuoA and ubiE mutants were defective in oxidation of MdbA, the major oxidoreductase required for oxidative folding of pilus proteins. Furthermore, supplementation of the ubiE mutant with exogenous menaquinone-4 rescued the cell growth and pilus defects. Altogether, we propose that the A. oris electron transport chain is biochemically linked to pilus assembly via oxidative protein folding.

  15. Knockdown of Pnpla6 protein results in motor neuron defects in zebrafish

    Directory of Open Access Journals (Sweden)

    Yang Song

    2013-03-01

    Mutations in patatin-like phospholipase domain containing 6 (PNPLA6, also known as neuropathy target esterase (NTE or SPG39, cause hereditary spastic paraplegia (HSP. Although studies on animal models, including mice and Drosophila, have extended our understanding of PNPLA6, its roles in neural development and in HSP are not clearly understood. Here, we describe the generation of a vertebrate model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio. Pnpla6 knockdown resulted in developmental abnormalities and motor neuron defects, including axon truncation and branching. The phenotypes in pnpla6 knockdown morphants were rescued by the introduction of wild-type, but not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP signaling in pnpla6 knockdown phenotypes. Taken together, these results demonstrate an important role of PNPLA6 in motor neuron development and implicate overexpression of BMP signaling as a possible mechanism underlying the developmental defects in pnpla6 morphants.

  16. Business rescue decision making through verifier determinants – ask the specialists

    Directory of Open Access Journals (Sweden)

    Marius Pretorius

    2013-11-01

    Full Text Available Orientation: Business rescue has become a critical part of business strategy decision making, especially during economic downturns and recessions. Past legislation has generally supported creditor-friendly regimes, and its mind-set still applies which increases the difficulty of such turnarounds. There are many questions and critical issues faced by those involved in rescue. Despite extensive theory in the literature on failure, there is a void regarding practical verifiers of the signs and causes of venture decline, as specialists are not forthcoming about what they regard as their “competitive advantage”. Research purpose: This article introduces the concept and role of “verifier determinants” of early warning signs, as a tool to confirm the causes of decline in order to direct rescue strategies and, most importantly, reduce time between the first observation and the implementation of the rescue. Motivation for the study: Knowing how specialist practitioners confirm causes of business decline could assist in deciding on strategies for the rescue earlier than can be done using traditional due diligence which is time consuming. Reducing time is a crucial element of a successful rescue. Research design and approach: The researchers interviewed specialist practitioners with extensive experience in rescue and turnaround. An experimental design was used to ensure the specialists evaluated the same real cases to extract their experiences and base their decisions on. Main findings: The specialists confirmed the use of verifier determinants and identified such determinants as they personally used them to confirm causes of decline. These verifier determinants were classified into five categories; namely, management, finance, strategic, banking and operations and marketing of the ventures under investigation. The verifier determinants and their use often depend heavily on subconscious (non-factual information based on previous experiences

  17. Field studies of safety security rescue technologies through training and response activities

    Science.gov (United States)

    Murphy, Robin R.; Stover, Sam

    2006-05-01

    This paper describes the field-oriented philosophy of the Institute for Safety Security Rescue Technology (iSSRT) and summarizes the activities and lessons learned during calendar year 2005 of its two centers: the Center for Robot-Assisted Search and Rescue and the NSF Safety Security Rescue industry/university cooperative research center. In 2005, iSSRT participated in four responses (La Conchita, CA, Mudslides, Hurricane Dennis, Hurricane Katrina, Hurricane Wilma) and conducted three field experiments (NJTF-1, Camp Hurricane, Richmond, MO). The lessons learned covered mobility, operator control units, wireless communications, and general reliability. The work has collectively identified six emerging issues for future work. Based on these studies, a 10-hour, 1 continuing education unit credit course on rescue robotics has been created and is available. Rescue robots and sensors are available for loan upon request.

  18. A Review of Mine Rescue Ensembles for Underground Coal Mining in the United States.

    Science.gov (United States)

    Kilinc, F Selcen; Monaghan, William D; Powell, Jeffrey B

    The mining industry is among the top ten industries nationwide with high occupational injury and fatality rates, and mine rescue response may be considered one of the most hazardous activities in mining operations. In the aftermath of an underground mine fire, explosion or water inundation, specially equipped and trained teams have been sent underground to fight fires, rescue entrapped miners, test atmospheric conditions, investigate the causes of the disaster, or recover the dead. Special personal protective ensembles are used by the team members to improve the protection of rescuers against the hazards of mine rescue and recovery. Personal protective ensembles used by mine rescue teams consist of helmet, cap lamp, hood, gloves, protective clothing, boots, kneepads, facemask, breathing apparatus, belt, and suspenders. While improved technology such as wireless warning and communication systems, lifeline pulleys, and lighted vests have been developed for mine rescuers over the last 100 years, recent research in this area of personal protective ensembles has been minimal due to the trending of reduced exposure of rescue workers. In recent years, the exposure of mine rescue teams to hazardous situations has been changing. However, it is vital that members of the teams have the capability and proper protection to immediately respond to a wide range of hazardous situations. Currently, there are no minimum requirements, best practice documents, or nationally recognized consensus standards for protective clothing used by mine rescue teams in the United States (U.S.). The following review provides a summary of potential issues that can be addressed by rescue teams and industry to improve potential exposures to rescue team members should a disaster situation occur. However, the continued trending in the mining industry toward non-exposure to potential hazards for rescue workers should continue to be the primary goal. To assist in continuing this trend, the mining industry

  19. The Data Rescue @ Home Project

    Science.gov (United States)

    Stickler, A.; Allan, R.; Valente, M. A.; Tinz, B.; Brönnimann, S.

    2012-04-01

    Climate science as a whole as well as reanalyses as a special case can significantly profit from the recovery, imaging and digitisation of historical observations. The importance of this fact is reflected in large, global data rescue projects and initiatives such as the Atmospheric Circulation Reconstructions over the Earth (ACRE, www.met-acre.org) or the EU FP7 ERA-CLIM project (www.era-clim.eu). From the time before 1957, there are still large amounts of surface data e.g. from former colonies and from overseas territories of European countries )e.g. Portugal, France and Germany) that need to be rescued. Also in case of the very early upper-air observations before the 1930s, even Europe and North America still hold an important quantity of data to be recovered in digital form. Here, we present the web platform "Data Rescue @ Home" (www.data-rescue-at-home.org), which has been developed at ETH Zurich and Oeschger Centre for Climate Change Research, and which has been designed to take advantage of the voluntary assistance of the thousands of people on the web who are interested in climate or old weather data. On the website, these volunteers can enter meteorological data shown on digital images into entry masks that resemble the original. By registering, the users get access to their personal digitisation statistics and help optimising the project. At the moment, 4 digitisation projects are online: One project is dealing with German upper-air data from the Second World War period. In a second project, station data from Tulagi (Solomon Islands) is being digitised. Finally, two collaborative projects have been included: One in cooperation with the Instituto Dom Luiz (Univ. Lisbon, Portugal), where Portuguese station data from Angra (Azores) is digitised, and a further one in cooperation with the German Meteorological Service (DWD), in which precipitation data from former German colonies is being digitised. On our poster, we will report on the status of the projects

  20. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

    Directory of Open Access Journals (Sweden)

    Andrew T Kempsell

    2015-09-01

    Full Text Available Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature versus advanced age Aplysia. Glutamate- (L-Glu- evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT in sensory neurons (SN isolated from mature but not aged animals. Activation of PKA and PKC signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems

  1. 78 FR 79010 - Criteria to Certify Coal Mine Rescue Teams

    Science.gov (United States)

    2013-12-27

    ... coal requires more heat to combust; (3) anthracite dust does not propagate an explosion; and (4) there... to Certify Coal Mine Rescue Teams AGENCY: Mine Safety and Health Administration, Labor. ACTION... updated the coal mine rescue team certification criteria. The Mine Improvement and New Emergency Response...

  2. 46 CFR 108.575 - Survival craft and rescue boat equipment.

    Science.gov (United States)

    2010-10-01

    ... Fishing kit 1 1 12 Flashlight 1 1 1 1 1 1 13 Hatchet 2 2 14 Heaving line 2 1 2 2 1 2 15 Instruction card 1... rigid/inflated rescue boats. 4 A hatchet counts toward this requirement in rigid rescue boats. 5 Oars...

  3. Thermodynamic Data Rescue and Informatics for Deep Carbon Science

    Science.gov (United States)

    Zhong, H.; Ma, X.; Prabhu, A.; Eleish, A.; Pan, F.; Parsons, M. A.; Ghiorso, M. S.; West, P.; Zednik, S.; Erickson, J. S.; Chen, Y.; Wang, H.; Fox, P. A.

    2017-12-01

    A large number of legacy datasets are contained in geoscience literature published between 1930 and 1980 and not expressed external to the publication text in digitized formats. Extracting, organizing, and reusing these "dark" datasets is highly valuable for many within the Earth and planetary science community. As a part of the Deep Carbon Observatory (DCO) data legacy missions, the DCO Data Science Team and Extreme Physics and Chemistry community identified thermodynamic datasets related to carbon, or more specifically datasets about the enthalpy and entropy of chemicals, as a proof of principle analysis. The data science team endeavored to develop a semi-automatic workflow, which includes identifying relevant publications, extracting contained datasets using OCR methods, collaborative reviewing, and registering the datasets via the DCO Data Portal where the 'Linked Data' feature of the data portal provides a mechanism for connecting rescued datasets beyond their individual data sources, to research domains, DCO Communities, and more, making data discovery and retrieval more effective.To date, the team has successfully rescued, deposited and registered additional datasets from publications with thermodynamic sources. These datasets contain 3 main types of data: (1) heat content or enthalpy data determined for a given compound as a function of temperature using high-temperature calorimetry, (2) heat content or enthalpy data determined for a given compound as a function of temperature using adiabatic calorimetry, and (3) direct determination of heat capacity of a compound as a function of temperature using differential scanning calorimetry. The data science team integrated these datasets and delivered a spectrum of data analytics including visualizations, which will lead to a comprehensive characterization of the thermodynamics of carbon and carbon-related materials.

  4. New refresher training in the use of self-rescue masks

    CERN Multimedia

    HSE Unit

    2012-01-01

    Photos of the training session for self-rescue mask instructors held on 21 March 2012 – 10 new instructors followed the coursePhotos of the training session for self-rescue mask instructors held on 21 March 2012 – 10 new instructors followed the course   A refresher course in the use of self-rescue masks has been added to the CERN training catalogue. Sign up! More than 3500 people have followed the course since it was introduced in 2009. Taking account of the forthcoming long shutdown, requests for follow-up training from course participants and recent changes in the course content, the HSE Unit has decided to place a three-year limit on the validity of the initial training and to introduce a refresher course. The new refresher course is open to all personnel having completed the initial course at least 2 years ago. The course, "Recyclage Formation masque auto-sauveteur » / "Refresher course Self-Rescue Mask Training", (code No. 077...

  5. Computational design of a PDZ domain peptide inhibitor that rescues CFTR activity.

    Directory of Open Access Journals (Sweden)

    Kyle E Roberts

    Full Text Available The cystic fibrosis transmembrane conductance regulator (CFTR is an epithelial chloride channel mutated in patients with cystic fibrosis (CF. The most prevalent CFTR mutation, ΔF508, blocks folding in the endoplasmic reticulum. Recent work has shown that some ΔF508-CFTR channel activity can be recovered by pharmaceutical modulators ("potentiators" and "correctors", but ΔF508-CFTR can still be rapidly degraded via a lysosomal pathway involving the CFTR-associated ligand (CAL, which binds CFTR via a PDZ interaction domain. We present a study that goes from theory, to new structure-based computational design algorithms, to computational predictions, to biochemical testing and ultimately to epithelial-cell validation of novel, effective CAL PDZ inhibitors (called "stabilizers" that rescue ΔF508-CFTR activity. To design the "stabilizers", we extended our structural ensemble-based computational protein redesign algorithm K* to encompass protein-protein and protein-peptide interactions. The computational predictions achieved high accuracy: all of the top-predicted peptide inhibitors bound well to CAL. Furthermore, when compared to state-of-the-art CAL inhibitors, our design methodology achieved higher affinity and increased binding efficiency. The designed inhibitor with the highest affinity for CAL (kCAL01 binds six-fold more tightly than the previous best hexamer (iCAL35, and 170-fold more tightly than the CFTR C-terminus. We show that kCAL01 has physiological activity and can rescue chloride efflux in CF patient-derived airway epithelial cells. Since stabilizers address a different cellular CF defect from potentiators and correctors, our inhibitors provide an additional therapeutic pathway that can be used in conjunction with current methods.

  6. 14 CFR 139.315 - Aircraft rescue and firefighting: Index determination.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Aircraft rescue and firefighting: Index... CERTIFICATION OF AIRPORTS Operations § 139.315 Aircraft rescue and firefighting: Index determination. (a) An index is required by paragraph (c) of this section for each certificate holder. The Index is determined...

  7. Elastic dipoles of point defects from atomistic simulations

    Science.gov (United States)

    Varvenne, Céline; Clouet, Emmanuel

    2017-12-01

    The interaction of point defects with an external stress field or with other structural defects is usually well described within continuum elasticity by the elastic dipole approximation. Extraction of the elastic dipoles from atomistic simulations is therefore a fundamental step to connect an atomistic description of the defect with continuum models. This can be done either by a fitting of the point-defect displacement field, by a summation of the Kanzaki forces, or by a linking equation to the residual stress. We perform here a detailed comparison of these different available methods to extract elastic dipoles, and show that they all lead to the same values when the supercell of the atomistic simulations is large enough and when the anharmonic region around the point defect is correctly handled. But, for small simulation cells compatible with ab initio calculations, only the definition through the residual stress appears tractable. The approach is illustrated by considering various point defects (vacancy, self-interstitial, and hydrogen solute atom) in zirconium, using both empirical potentials and ab initio calculations.

  8. X-linked NDUFA1 gene mutations associated with mitochondrial encephalomyopathy.

    NARCIS (Netherlands)

    Fernandez-Moreira, D.; Ugalde, C.; Smeets, R.; Rodenburg, R.J.T.; Lopez-Laso, E.; Ruiz-Falco, M.L.; Briones, P.; Martin, M.A.; Smeitink, J.A.M.; Arenas, J.

    2007-01-01

    OBJECTIVE: Mitochondrial complex I deficiency is the commonest diagnosed respiratory chain defect, being genetically heterogeneous. The male preponderance of previous patient cohorts suggested an X-linked underlying genetic defect. We investigated mutations in the X-chromosomal complex I structural

  9. Study of point defects in bismuth

    International Nuclear Information System (INIS)

    Bois, P.

    1987-03-01

    Single crystalline samples of bismuth, pure and n or p - doped by adding tellurium or tin, were electron irradiated at low temperature (4.2 K and 20 K). In the energy range 0.7 - 2.5 MeV, a displacement threshold energy of 13 eV and an athermal recombination volume of 150 atomic volumes were determined. Joint measurements of resistivity, magnetotransport and positron annihilation enabled to precised the nature of the annealing stages: 40-50 K, free migration of interstitials; 90-120 K long range migration of vacancy. Point defects have according to their nature a different effect on the electronic properties of bismuth: isolated Frenkel pairs are globally donnors with a charge of + 0.16 e- and the vacancy is donnor, which seems to attribute to it a negative formation volume. A simple model with non-deformating bands is no longer sufficient to explain the behaviour under irradiation: one has to take into account an acceptor level with a charge of - 0,27 e-, linked to the cascade-type defects and resonating with the valence band. It's position in the band overlap and it's width (8 meV) could be precised. In first approximation this coupling with less mobile carriers does not affect the simple additive rule which exists for relaxation times. Some yet obscure magnetic properties seem to be linked to this defect level [fr

  10. Functional phenotypic rescue of Caenorhabditis elegans neuroligin-deficient mutants by the human and rat NLGN1 genes.

    Directory of Open Access Journals (Sweden)

    Fernando Calahorro

    Full Text Available Neuroligins are cell adhesion proteins that interact with neurexins at the synapse. This interaction may contribute to differentiation, plasticity and specificity of synapses. In humans, single mutations in neuroligin encoding genes lead to autism spectrum disorder and/or mental retardation. Caenorhabditis elegans mutants deficient in nlg-1, an orthologue of human neuroligin genes, have defects in different behaviors. Here we show that the expression of human NLGN1 or rat Nlgn1 cDNAs in C. elegans nlg-1 mutants rescues the fructose osmotic strength avoidance and gentle touch response phenotypes. Two specific point mutations in NLGN3 and NLGN4 genes, involved in autistic spectrum disorder, were further characterized in this experimental system. The R451C allele described in NLGN3, was analyzed with both human NLGN1 (R453C and worm NLG-1 (R437C proteins, and both were not functional in rescuing the osmotic avoidance behavior and the gentle touch response phenotype. The D396X allele described in NLGN4, which produces a truncated protein, was studied with human NLGN1 (D432X and they did not rescue any of the behavioral phenotypes analyzed. In addition, RNAi feeding experiments measuring gentle touch response in wild type strain and worms expressing SID-1 in neurons (which increases the response to dsRNA, both fed with bacteria expressing dsRNA for nlg-1, provided evidence for a postsynaptic in vivo function of neuroligins both in muscle cells and neurons, equivalent to that proposed in mammals. This finding was further confirmed generating transgenic nlg-1 deficient mutants expressing NLG-1 under pan-neuronal (nrx-1 or pan-muscular (myo-3 specific promoters. All these results suggest that the nematode could be used as an in vivo model for studying particular synaptic mechanisms with proteins orthologues of humans involved in pervasive developmental disorders.

  11. Overexpression of Indian hedgehog partially rescues short stature homeobox 2-overexpression-associated congenital dysplasia of the temporomandibular joint in mice.

    Science.gov (United States)

    Li, Xihai; Liang, Wenna; Ye, Hongzhi; Weng, Xiaping; Liu, Fayuan; Lin, Pingdong; Liu, Xianxiang

    2015-09-01

    The role of short stature homeobox 2 (shox2) in the development and homeostasis of the temporomandibular joint (TMJ) has been well documented. Shox2 is known to be expressed in the progenitor cells and perichondrium of the developing condyle. A previous study by our group reported that overexpression of shox2 leads to congenital dysplasia of the TMJ via downregulation of the Indian hedgehog (Ihh) signaling pathway, which is essential for embryonic disc primordium formation and mandibular condylar growth. To determine whether overexpression of Ihh may rescue the overexpression of shox2 leading to congenital dysplasia of the TMJ, a mouse model in which Ihh and shox2 were overexpressed (Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice) was utilized to assess the consequences of this overexpression on TMJ development during post-natal life. The results showed that the developmental process and expression levels of runt-related transcription factor 2 and sex determining region Y-box 9 in the TMJ of the Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice were similar to those in wild‑type mice. Overexpression of Ihh rescued shox2 overexpression-associated reduction of extracellular matrix components. However, overexpression of Ihh did not inhibit the shox2 overexpression-associated increase of matrix metalloproteinases (MMPs) MMP9, MMP13 and apoptosis in the TMJ. These combinatory cellular and molecular defects appeared to account for the observed congenital dysplasia of TMJ, suggesting that overexpression of Ihh partially rescued shox2 overexpression‑associated congenital dysplasia of the TMJ in mice.

  12. Strategies to improve sleep during extended search and rescue operations.

    Science.gov (United States)

    Jenkins, Jennifer Lee; Fredericksen, Kim; Stone, Roger; Tang, Nelson

    2007-01-01

    This study investigated strategies to improve sleeping conditions during search and rescue operations during disaster response. Forty members of the Montgomery County (Maryland) Urban Search and Rescue Team were surveyed for individual sleep habits and sleeping aids used during extended deployments. Team members were also asked to suggest methods to improve sleep on future deployments. The average amount of sleep during field operations was 5.4 hours with a range of 4-8 hours. Eight percent surveyed would prefer another schedule besides the 12-hour work day, all of whom proposed three 8-hour shifts. Fifteen percent of participants were interested in a pharmacological sleeping aid. Fifty percent of search and rescue members interviewed would consider using nonpharmacological sleeping aids. Furthermore, 40% of participants stated they had successfully devised self-employed methods of sleep aids for previous deployments, such as ear plugs, massage, mental imagery, personal routines, music and headphones, reading, and blindfolds. This study suggests that availability of both pharmacological and nonpharmacological sleeping aids to search and rescue workers via the team cache could impact the quantity of sleep. Further investigation into methods of optimizing sleep during field missions could theoretically show enhanced performance through various aspects of missions including mitigation of errors, improved productivity, and improved overall physiological and emotional well-being of search and rescue personnel.

  13. Does modern helicopter construction reduce noise exposure in helicopter rescue operations?

    Science.gov (United States)

    Küpper, Thomas; Jansing, Paul; Schöffl, Volker; van Der Giet, Simone

    2013-01-01

    During helicopter rescue operations the medical personnel are at high risk for hearing damage by noise exposure. There are two important factors to be taken into account: first, the extreme variability, with some days involving no exposure but other days with extreme exposure; second, the extreme noise levels during work outside the helicopter, e.g. during winch operations. The benefit of modern, less noisier constructions and the consequences for noise protection are still unknown. We estimated the noise exposure of the personnel for different helicopter types used during rescue operations in the Alps and in other regions of the world with special regard to the advanced types like Eurocopter EC 135 to compare the benefit of modern constructions for noise protection with earlier ones. The rescue operations over 1 year of four rescue bases in the Alps (Raron and Zermatt in Switzerland; Landeck and Innsbruck in Austria, n = 2731) were analyzed for duration of rescue operations (noise exposure). Noise levels were measured during rescue operations at defined points inside and outside the different aircraft. The setting is according to the European standard (Richtlinie 2003/10/EG Amtsblatt) and to Class 1 DIN/IEC 651. With both data sets the equivalent noise level L(eq8h) was calculated. For comparison it was assumed that all rescue operations were performed with a specific type of helicopter. Then model calculations for noise exposure by different helicopter types, such as Alouette IIIb, Alouette II 'Lama', Ecureuil AS350, Bell UH1D, Eurocopter EC135, and others were performed. Depending on modern technologies the situation for the personnel has been improved significantly. Nevertheless noise prevention, which includes noise intermissions in spare time, is essential. Medical checks of the crews by occupational medicine (e.g. 'G20' in Germany) are still mandatory.

  14. Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus.

    Science.gov (United States)

    Sindhi, R; Webber, S; Venkataramanan, R; McGhee, W; Phillips, S; Smith, A; Baird, C; Iurlano, K; Mazariegos, G; Cooperstone, B; Holt, D W; Zeevi, A; Fung, J J; Reyes, J

    2001-09-15

    The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease. Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42 rescue patients, 3 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8+/-5.5 hr, n=21). SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.

  15. Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease

    International Nuclear Information System (INIS)

    Werner, Christian; Boehm, Michael; Friedrich, Erik B.

    2008-01-01

    Number and function of endothelial progenitor cells (EPCs) are down-regulated in patients with coronary artery disease (CAD). Integrin-linked kinase (ILK) is a signal and adaptor protein that regulates survival of mature endothelial cells and vascular development. Here we show that EPC dysfunction in patients with CAD is paralleled by down-regulation of ILK while restoration of ILK expression rescues the migratory defect of CAD-EPCs. Human EPCs transduced with dominant-negative ILK (DN-ILK) display significantly reduced expression of CD34 + /VEGFR-2 + , DiI-Ac-LDL uptake, and Ulex europaeus lectin binding. Mechanistically, DN-ILK-transfected EPCs are characterized by decreased proliferation, while proliferation is increased in wild-type ILK-transfected EPCs. These effects are paralleled by changes in cyclin D1 expression, colony forming units, and cytoskeletal rearrangement. Functionally, ILK is necessary and sufficient for SDF-1-triggered migration and adhesion in EPCs. These data extend current knowledge about the role of ILK in EPC biology and implicate ILK as a therapeutic target in CAD.

  16. Genetic Information, the Principle of Rescue, and Special Obligations.

    Science.gov (United States)

    Liao, S Matthew; Mackenzie, Jordan

    2018-05-01

    In "Genetic Privacy, Disease Prevention, and the Principle of Rescue," Madison Kilbride argues that patients have a duty to warn biological family members about clinically actionable adverse genetic findings. The duty does not stem from the special obligations that we may have to family members, she argues, but rather follows from the principle of rescue, which she understands as the idea that one ought to prevent, reduce, or mitigate the risk of harm to another person when the expected harm is serious and the cost or risk to oneself is sufficiently moderate. We doubt, however, whether the principle of rescue can ground a duty to warn in the cases Kilbride envisages, and we suggest that Kilbride may have underappreciated the role that special obligations could play in generating a duty to warn family members. © 2018 The Hastings Center.

  17. Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3.

    Science.gov (United States)

    Ting, Stephen B; Wilanowski, Tomasz; Auden, Alana; Hall, Mark; Voss, Anne K; Thomas, Tim; Parekh, Vishwas; Cunningham, John M; Jane, Stephen M

    2003-12-01

    The neural tube defects (NTDs) spina bifida and anencephaly are widely prevalent severe birth defects. The mouse mutant curly tail (ct/ct) has served as a model of NTDs for 50 years, even though the responsible genetic defect remained unrecognized. Here we show by gene targeting, mapping and genetic complementation studies that a mouse homolog of the Drosophila grainyhead (grh) gene, grainyhead-like-3 (Grhl3), is a compelling candidate for the gene underlying the curly tail phenotype. The NTDs in Grhl3-null mice are more severe than those in the curly tail strain, as the Grhl3 alleles in ct/ct mice are hypomorphic. Spina bifida in ct/ct mice is folate resistant, but its incidence can be markedly reduced by maternal inositol supplementation periconceptually. The NTDs in Grhl3-/- embryos are also folate resistant, but unlike those in ct/ct mice, they are resistant to inositol. These findings suggest that residual Grhl3 expression in ct/ct mice may be required for inositol rescue of folate-resistant NTDs.

  18. Rescue of failed filtering blebs with ab interno trephination.

    Science.gov (United States)

    Shihadeh, Wisam A; Ritch, Robert; Liebmann, Jeffrey M

    2006-06-01

    We evaluated the effectiveness of ab interno automated trephination as a technique for rescuing failed mature filtering blebs. A retrospective chart review of 40 failed blebs of 38 patients who had a posttrephination follow-up period of at least 3 months was done. With success defined as intraocular pressure (IOP) control with other modalities of management. Complications were few. We believe that ab interno trephination is an excellent option for rescuing selected failed filtering blebs.

  19. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica.

    Science.gov (United States)

    Kempsell, Andrew T; Fieber, Lynne A

    2015-01-01

    Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature vs. advanced age Aplysia californica (Aplysia). L-Glutamate- (L-Glu-) evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT) in sensory neurons (SN) isolated from mature but not aged animals. Activation of protein kinase A (PKA) and protein kinase C (PKC) signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems.

  20. A new resource for characterizing X-linked genes in Drosophila melanogaster: systematic coverage and subdivision of the X chromosome with nested, Y-linked duplications.

    Science.gov (United States)

    Cook, R Kimberley; Deal, Megan E; Deal, Jennifer A; Garton, Russell D; Brown, C Adam; Ward, Megan E; Andrade, Rachel S; Spana, Eric P; Kaufman, Thomas C; Cook, Kevin R

    2010-12-01

    Interchromosomal duplications are especially important for the study of X-linked genes. Males inheriting a mutation in a vital X-linked gene cannot survive unless there is a wild-type copy of the gene duplicated elsewhere in the genome. Rescuing the lethality of an X-linked mutation with a duplication allows the mutation to be used experimentally in complementation tests and other genetic crosses and it maps the mutated gene to a defined chromosomal region. Duplications can also be used to screen for dosage-dependent enhancers and suppressors of mutant phenotypes as a way to identify genes involved in the same biological process. We describe an ongoing project in Drosophila melanogaster to generate comprehensive coverage and extensive breakpoint subdivision of the X chromosome with megabase-scale X segments borne on Y chromosomes. The in vivo method involves the creation of X inversions on attached-XY chromosomes by FLP-FRT site-specific recombination technology followed by irradiation to induce large internal X deletions. The resulting chromosomes consist of the X tip, a medial X segment placed near the tip by an inversion, and a full Y. A nested set of medial duplicated segments is derived from each inversion precursor. We have constructed a set of inversions on attached-XY chromosomes that enable us to isolate nested duplicated segments from all X regions. To date, our screens have provided a minimum of 78% X coverage with duplication breakpoints spaced a median of nine genes apart. These duplication chromosomes will be valuable resources for rescuing and mapping X-linked mutations and identifying dosage-dependent modifiers of mutant phenotypes.

  1. 46 CFR 199.220 - Survival craft and rescue boat embarkation arrangements.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft and rescue boat embarkation arrangements... APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.220 Survival craft and rescue boat embarkation arrangements. (a) Survival craft...

  2. Promotion and Rescue of Intracellular Brucella neotomae Replication during Coinfection with Legionella pneumophila.

    Science.gov (United States)

    Kang, Yoon-Suk; Kirby, James E

    2017-05-01

    We established a new Brucella neotomae in vitro model system for study of type IV secretion system-dependent (T4SS) pathogenesis in the Brucella genus. Importantly, B. neotomae is a rodent pathogen, and unlike B. abortus , B. melitensis , and B. suis , B. neotomae has not been observed to infect humans. It therefore can be handled more facilely using biosafety level 2 practices. More particularly, using a series of novel fluorescent protein and lux operon reporter systems to differentially label pathogens and track intracellular replication, we confirmed T4SS-dependent intracellular growth of B. neotomae in macrophage cell lines. Furthermore, B. neotomae exhibited early endosomal (LAMP-1) and late endoplasmic reticulum (calreticulin)-associated phagosome maturation. These findings recapitulate prior observations for human-pathogenic Brucella spp. In addition, during coinfection experiments with Legionella pneumophila , we found that defective intracellular replication of a B. neotomae T4SS virB4 mutant was rescued and baseline levels of intracellular replication of wild-type B. neotomae were significantly stimulated by coinfection with wild-type but not T4SS mutant L. pneumophila Using confocal microscopy, it was determined that intracellular colocalization of B. neotomae and L. pneumophila was required for rescue and that colocalization came at a cost to L. pneumophila fitness. These findings were not completely expected based on known temporal and qualitative differences in the intracellular life cycles of these two pathogens. Taken together, we have developed a new system for studying in vitro Brucella pathogenesis and found a remarkable T4SS-dependent interplay between Brucella and Legionella during macrophage coinfection. Copyright © 2017 American Society for Microbiology.

  3. Pharmacologic Approach to Defective Protein Trafficking in the E637K-hERG Mutant with PD-118057 and Thapsigargin.

    Directory of Open Access Journals (Sweden)

    Haiyan Mao

    Full Text Available Treatment of LQT2 is inadequate. Many drugs which can pharmacologically rescue defective protein trafficking in LQT2 also result in potent blockade of HERG current, negating their therapeutic benefit. It is reported that PD-118057 and thapsigargin can rescue LQT2 without hERG channel blockade, but the precise mechanism of action is unknown. Furthermore, the effect of PD-118057 and thapsigargin on the dominant negative E637K-hERG mutant has not been previously investigated.IN THIS STUDY, WE INVESTIGATED: (a the effect of PD-118057 and thapsigargin on the current amplitudes of WT-hERG and WT/E637K-hERG channels; (b the effect of PD-118057 and thapsigargin on the biophysical properties of WT-hERG and WT/E637K-hERG channels; (c whether drug treatment can rescue channel processing and trafficking defects of the WT/E637K-hERG mutant.The whole-cell Patch-clamp technique was used to assess the effect of PD-118057 and thapsigargin on the electrophysiological characteristics of the rapidly activating delayed rectifier K(+ current (Ikr of the hERG protein channel. Western blot was done to investigate pharmacological rescue on hERG protein channel function.In our study, PD-118057 was shown to significantly enhance both the maximum current amplitude and tail current amplitude, but did not alter the gating and kinetic properties of the WT-hERG channel, with the exception of accelerating steady-state inactivation. Additionally, thapsigargin shows a similar result as PD-118057 for the WT-hERG channel, but with the exception of attenuating steady-state inactivation. However, for the WT/E637K-hERG channel, PD-118057 had no effect on either the current or on the gating and kinetic properties. Furthermore, thapsigargin treatment did not alter the current or the gating and kinetic properties of the WT/E637K-hERG channel, with the exception of opening at more positive voltages.Our findings illustrate that neither PD-118057 nor thapsigargin play a role in correcting

  4. Rescue US: Birth, Django, and the Violence of Racial Redemption

    Directory of Open Access Journals (Sweden)

    Joseph Winters

    2018-01-01

    Full Text Available In this article, I show how the relationship between race, violence, and redemption is articulated and visualized through film. By juxtaposing DW Griffith’s The Birth of a Nation and Quentin Tarantino’s Django Unchained, I contend that the latter inverts the logic of the former. While Birth sacrifices black bodies and explains away anti-black violence for the sake of restoring white sovereignty (or rescuing the nation from threatening forms of blackness, Django adopts a rescue narrative in order to show the excessive violence that structured slavery and the emergence of the nation-state. As an immanent break within the rescue narrative, Tarantino’s film works to “rescue” images and sounds of anguish from forgetful versions of history.

  5. Design and implementation of fishery rescue data mart system

    Science.gov (United States)

    Pan, Jun; Huang, Haiguang; Liu, Yousong

    A novel data mart based system for fishery rescue field was designed and implemented. The system runs ETL process to deal with original data from various databases and data warehouses, and then reorganized the data into the fishery rescue data mart. Next, online analytical processing (OLAP) are carried out and statistical reports are generated automatically. Particularly, quick configuration schemes are designed to configure query dimensions and OLAP data sets. The configuration file will be transformed into statistic interfaces automatically through a wizard-style process. The system provides various forms of reporting files, including crystal reports, flash graphical reports, and two-dimensional data grids. In addition, a wizard style interface was designed to guide users customizing inquiry processes, making it possible for nontechnical staffs to access customized reports. Characterized by quick configuration, safeness and flexibility, the system has been successfully applied in city fishery rescue department.

  6. CERN Fire Brigade rescue simulation

    CERN Multimedia

    Maximilien Brice

    2004-01-01

    The CERN Fire Brigade is made up of experienced firemen from all of the 20 Member States. In these images they are seen at a 'Discovery Monday' held at the Microcosm exhibition. Here visitors learn how the Fire Brigade deal with various situations, including a simulated cave rescue performed by the Hazardous Environments Response Team.

  7. Importance of teamwork, communication and culture on failure-to-rescue in the elderly.

    Science.gov (United States)

    Ghaferi, A A; Dimick, J B

    2016-01-01

    Surgical mortality increases significantly with age. Wide variations in mortality rates across hospitals suggest potential levers for improvement. Failure-to-rescue has been posited as a potential mechanism underlying these differences. A review was undertaken of the literature evaluating surgery, mortality, failure-to-rescue and the elderly. This was followed by a review of ongoing studies and unpublished work aiming to understand better the mechanisms underlying variations in surgical mortality in elderly patients. Multiple hospital macro-system factors, such as nurse staffing, available hospital technology and teaching status, are associated with differences in failure-to-rescue rates. There is emerging literature regarding important micro-system factors associated with failure-to-rescue. These are grouped into three broad categories: hospital resources, attitudes and behaviours. Ongoing work to produce interventions to reduce variations in failure-to-rescue rates include a focus on teamwork, communication and safety culture. Researchers are using novel mixed-methods approaches and theories adapted from organizational studies in high-reliability organizations in an effort to improve the care of elderly surgical patients. Although elderly surgical patients experience failure-to-rescue events at much higher rates than their younger counterparts, patient-level effects do not sufficiently explain these differences. Increased attention to the role of organizational dynamics in hospitals' ability to rescue these high-risk patients will establish high-yield interventions aimed at improving patient safety. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

  8. Dendrimer-based selective autophagy-induction rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Scott Mackenzie Brockman

    Full Text Available Cystic Fibrosis (CF is a genetic disorder caused by mutation(s in the CF-transmembrane conductance regulator (Cftr gene. The most common mutation, ΔF508, leads to accumulation of defective-CFTR protein in aggresome-bodies. Additionally, Pseudomonas aeruginosa (Pa, a common CF pathogen, exacerbates obstructive CF lung pathology. In the present study, we aimed to develop and test a novel strategy to improve the bioavailability and potentially achieve targeted drug delivery of cysteamine, a potent autophagy-inducing drug with anti-bacterial properties, by developing a dendrimer (PAMAM-DEN-based cysteamine analogue.We first evaluated the effect of dendrimer-based cysteamine analogue (PAMAM-DENCYS on the intrinsic autophagy response in IB3-1 cells and observed a significant reduction in Ub-RFP and LC3-GFP co-localization (aggresome-bodies by PAMAM-DENCYS treatment as compared to plain dendrimer (PAMAM-DEN control. Next, we observed that PAMAM-DENCYS treatment shows a modest rescue of ΔF508-CFTR as the C-form. Moreover, immunofluorescence microscopy of HEK-293 cells transfected with ΔF508-CFTR-GFP showed that PAMAM-DENCYS is able to rescue the misfolded-ΔF508-CFTR from aggresome-bodies by inducing its trafficking to the plasma membrane. We further verified these results by flow cytometry and observed significant (p<0.05; PAMAM-DEN vs. PAMAM-DENCYS rescue of membrane-ΔF508-CFTR with PAMAM-DENCYS treatment using non-permeabilized IB3-1 cells immunostained for CFTR. Finally, we assessed the autophagy-mediated bacterial clearance potential of PAMAM-DENCYS by treating IB3-1 cells infected with PA01-GFP, and observed a significant (p<0.01; PAMAM-DEN vs. PAMAM-DENCYS decrease in intracellular bacterial counts by immunofluorescence microscopy and flow cytometry. Also, PAMAM-DENCYS treatment significantly inhibits the growth of PA01-GFP bacteria and demonstrates potent mucolytic properties.We demonstrate here the efficacy of dendrimer-based autophagy

  9. Defects in Cu(In,Ga)Se{sub 2} chalcopyrite semiconductors: a comparative study of material properties, defect states, and photovoltaic performance

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Qing; Gunawan, Oki; Copel, Matthew; Reuter, Kathleen B; Chey, S Jay; Mitzi, David B [IBM T.J. Watson Research Center, Yorktown Heights, NY (United States); Deline, Vaughn R [IBM Almaden Resesarch Center, San Jose, CA (United States)

    2011-10-15

    Understanding defects in Cu(In,Ga)(Se,S){sub 2} (CIGS), especially correlating changes in the film formation process with differences in material properties, photovoltaic (PV) device performance, and defect levels extracted from admittance spectroscopy, is a critical but challenging undertaking due to the complex nature of this polycrystalline compound semiconductor. Here we present a systematic comparative study wherein varying defect density levels in CIGS films were intentionally induced by growing CIGS grains using different selenium activity levels. Material characterization results by techniques including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, secondary ion mass spectrometry, X-ray photoelectron spectroscopy, and medium energy ion scattering indicate that this process variation, although not significantly affecting CIGS grain structure, crystal orientation, or bulk composition, leads to enhanced formation of a defective chalcopyrite layer with high density of indium or gallium at copper antisite defects ((In, Ga){sub Cu}) near the CIGS surface, for CIGS films grown with insufficient selenium supply. This defective layer or the film growth conditions associated with it is further linked with observed current-voltage characteristics, including rollover and crossover behavior, and a defect state at around 110 meV (generally denoted as the N1 defect) commonly observed in admittance spectroscopy. The impact of the (In, Ga){sub Cu} defects on device PV performance is also established. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. Ontological Reasoning for Human-Robot Teaming in Search and Rescue Missions

    NARCIS (Netherlands)

    Bagosi, T.; Hindriks, k.V.; Neerincx, M.A.

    2016-01-01

    In search and rescue missions robots are used to help rescue workers in exploring the disaster site. Our research focuses on how multiple robots and rescuers act as a team, and build up situation awareness. We propose a multi-agent system where each agent supports one member, either human or robot.

  11. Final report 'Establishing bonds for the advancement of the Rescue League'

    NARCIS (Netherlands)

    Riaño, I.; Visser, A.

    2014-01-01

    The RoboCup Rescue Simulation League aims to benchmark the intelligence of software agents and robots on their capabilities to make autonomously the right decisions in a disaster response scenario. The UvA Rescue and Distribot team have come together to work co-operatively to support this aim in two

  12. Variation in Medicare Expenditures for Treating Perioperative Complications: The Cost of Rescue.

    Science.gov (United States)

    Pradarelli, Jason C; Healy, Mark A; Osborne, Nicholas H; Ghaferi, Amir A; Dimick, Justin B; Nathan, Hari

    2016-12-21

    Treating surgical complications presents a major challenge for hospitals striving to deliver high-quality care while reducing costs. Costs associated with rescuing patients from perioperative complications are poorly characterized. To evaluate differences across hospitals in the costs of care for patients surviving perioperative complications after major inpatient surgery. Retrospective cohort study using claims data from the Medicare Provider Analysis and Review files. We compared payments for patients who died vs patients who survived after perioperative complications occurred. Hospitals were stratified using average payments for patients who survived following complications, and payment components were analyzed across hospitals. Administrative claims database of surgical patients was analyzed at hospitals treating Medicare patients nationwide. This study included Medicare patients aged 65 to 100 years who underwent abdominal aortic aneurysm repair (n = 69 207), colectomy for cancer (n = 107 647), pulmonary resection (n = 91 758), and total hip replacement (n = 307 399) between 2009 and 2012. Data analysis took place between November 2015 and March 2016. Clinical outcome of surgery (eg, no complication, complication and death, or complication and survival) and the individual hospital where a patient received an operation. Risk-adjusted, price-standardized Medicare payments for an episode of surgery. Risk-adjusted perioperative outcomes were also assessed. The mean age for Medicare beneficiaries in this study ranged from 74.1 years (pulmonary resection) to 78.2 years (colectomy). The proportion of male patients ranged from 37% (total hip replacement) to 77% (abdominal aortic aneurysm repair), and most patients were white. Among patients who experienced complications, those who were rescued had higher price-standardized Medicare payments than did those who died for all 4 operations. Assessing variation across hospitals, payments for patients

  13. Overexpression of Indian hedgehog partially rescues short stature homeobox 2-overexpression-associated congenital dysplasia of the temporomandibular joint in mice

    Science.gov (United States)

    LI, XIHAI; LIANG, WENNA; YE, HONGZHI; WENG, XIAPING; LIU, FAYUAN; LIN, PINGDONG; LIU, XIANXIANG

    2015-01-01

    The role of short stature homeobox 2 (shox2) in the development and homeostasis of the temporomandibular joint (TMJ) has been well documented. Shox2 is known to be expressed in the progenitor cells and perichondrium of the developing condyle. A previous study by our group reported that overexpression of shox2 leads to congenital dysplasia of the TMJ via downregulation of the Indian hedgehog (Ihh) signaling pathway, which is essential for embryonic disc primordium formation and mandibular condylar growth. To determine whether overexpression of Ihh may rescue the overexpression of shox2 leading to congenital dysplasia of the TMJ, a mouse model in which Ihh and shox2 were overexpressed (Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice) was utilized to assess the consequences of this overexpression on TMJ development during post-natal life. The results showed that the developmental process and expression levels of runt-related transcription factor 2 and sex determining region Y-box 9 in the TMJ of the Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice were similar to those in wild-type mice. Overexpression of Ihh rescued shox2 overexpression-associated reduction of extracellular matrix components. However, overexpression of Ihh did not inhibit the shox2 overexpression-associated increase of matrix metalloproteinases (MMPs) MMP9, MMP13 and apoptosis in the TMJ. These combinatory cellular and molecular defects appeared to account for the observed congenital dysplasia of TMJ, suggesting that overexpression of Ihh partially rescued shox2 overexpression-associated congenital dysplasia of the TMJ in mice. PMID:26096903

  14. Rescue of mutant fitness defects using in vitro reconstituted designer transposons in Mycoplasma mycoides

    Directory of Open Access Journals (Sweden)

    Bogumil Jacek Karas

    2014-07-01

    Full Text Available With only hundreds of genes contained within their genomes, mycoplasmas have become model organisms for precise understanding of cellular processes, as well as platform organisms for predictable engineering of microbial functions for mission-critical applications. Despite the availability of whole genome writing in Mycoplasma mycoides, some traditional methods for genetic engineering are underdeveloped in mycoplasmas. Here we demonstrate two facile transposon-mediated approaches for introducing genes into the synthetic cell based on M. mycoides. The marker-less approach involves preparing a fragment containing only a small genomic region of interest with flanking transposase-binding sites, followed by in vitro transposase loading and introduction into the cells. The marker-driven approach involves cloning an open reading frame (ORF of interest into a vector containing a marker for mycoplasma transformation, as well as sites for transposase loading and random genomic integration. An innovative feature of this construct is to use a single promoter to express the transformation marker and the introduced ORF. The marker-driven approach can be conveniently applied to any exogenous or synthetic gene without any information on the effect of the gene on the strain, whereas the marker-less approach requires that the fragment has a recognizable effect. Using the marker-less method, we found that a region containing the nusG gene rescues a slow growth phenotype of a strain containing a larger deletion encompassing this gene. Using the marker-driven approach, we better defined this finding, thereby establishing that nusG is required for a normal growth rate in synthetic M. mycoides. These methods are suitable for complementation tests to identify genes responsible for assorted functions lacking in deletion mutants. These approaches are also expected to facilitate rapid testing of various natural and engineered genes or gene clusters from numerous sources in

  15. Ion-irradiation-induced defects in bundles of carbon nanotubes

    International Nuclear Information System (INIS)

    Salonen, E.; Krasheninnikov, A.V.; Nordlund, K.

    2002-01-01

    We study the structure and formation yields of atomic-scale defects produced by low-dose Ar ion irradiation in bundles of single-wall carbon nanotubes. For this, we employ empirical potential molecular dynamics and simulate ion impact events over an energy range of 100-1000 eV. We show that the most common defects produced at all energies are vacancies on nanotube walls, which at low temperatures are metastable but long-lived defects. We further calculate the spatial distribution of the defects, which proved to be highly non-uniform. We also show that ion irradiation gives rise to the formations of inter-tube covalent bonds mediated by carbon recoils and nanotube lattice distortions due to dangling bond saturation. The number of inter-tube links, as well as the overall damage, linearly grows with the energy of incident ions

  16. Business rescue: How can its success be evaluated at company level?

    African Journals Online (AJOL)

    The question of what constitutes a successful business rescue is a very topical and unanswered one. Reports on success are contradictory and seem to lack a set of standardised evaluation criteria. The purpose of this article is to investigate how business rescue success is evaluated internationally in order to develop a set ...

  17. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

    Directory of Open Access Journals (Sweden)

    Abisambra Jose F

    2010-11-01

    Full Text Available Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB, the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17: Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.

  18. More than a bystander: the contributions of intrinsic skeletal muscle defects in motor neuron diseases.

    Science.gov (United States)

    Boyer, Justin G; Ferrier, Andrew; Kothary, Rashmi

    2013-12-18

    Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and spinal-bulbar muscular atrophy (SBMA) are devastating diseases characterized by the degeneration of motor neurons. Although the molecular causes underlying these diseases differ, recent findings have highlighted the contribution of intrinsic skeletal muscle defects in motor neuron diseases. The use of cell culture and animal models has led to the important finding that muscle defects occur prior to and independently of motor neuron degeneration in motor neuron diseases. In SMA for instance, the muscle specific requirements of the SMA disease-causing gene have been demonstrated by a series of genetic rescue experiments in SMA models. Conditional ALS mouse models expressing a muscle specific mutant SOD1 gene develop atrophy and muscle degeneration in the absence of motor neuron pathology. Treating SBMA mice by over-expressing IGF-1 in a skeletal muscle-specific manner attenuates disease severity and improves motor neuron pathology. In the present review, we provide an in depth description of muscle intrinsic defects, and discuss how they impact muscle function in these diseases. Furthermore, we discuss muscle-specific therapeutic strategies used to treat animal models of SMA, ALS, and SBMA. The study of intrinsic skeletal muscle defects is crucial for the understanding of the pathophysiology of these diseases and will open new therapeutic options for the treatment of motor neuron diseases.

  19. Dispatching Plan Based on Route Optimization Model Considering Random Wind for Aviation Emergency Rescue

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    2016-01-01

    Full Text Available Aviation emergency rescue is an effective means of nature disaster relief that is widely used in many countries. The dispatching plan of aviation emergency rescue guarantees the efficient implementation of this relief measure. The conventional dispatching plan that does not consider random wind factors leads to a nonprecise quick-responsive scheme and serious safety issues. In this study, an aviation emergency rescue framework that considers the influence of random wind at flight trajectory is proposed. In this framework, the predicted wind information for a disaster area is updated by using unscented Kalman filtering technology. Then, considering the practical scheduling problem of aircraft emergency rescue at present, a multiobjective model is established in this study. An optimization model aimed at maximizing the relief supply satisfaction, rescue priority satisfaction, and minimizing total rescue flight distance is formulated. Finally, the transport times of aircraft with and without the influence of random wind are analyzed on the basis of the data of an earthquake disaster area. Results show that the proposed dispatching plan that considers the constraints of updated wind speed and direction is highly applicable in real operations.

  20. Modulation of mitochondrial morphology by bioenergetics defects in primary human fibroblasts

    DEFF Research Database (Denmark)

    Guillery, O.; Malka, F.; Frachon, P.

    2008-01-01

    induced partial but significant mitochondrial fragmentation, whereas dissipation of mitochondrial membrane potential (D Psi m) provoked complete fragmentation, and glycolysis inhibition had no effect. Oxidative phosphorylation defective fibroblasts had essentially normal filamentous mitochondria under...... basal conditions, although when challenged some of them presented with mild alteration of fission or fusion efficacy. Severely defective cells disclosed complete mitochondrial fragmentation under glycolysis inhibition. In conclusion, mitochondrial morphology is modulated by D Psi m but loosely linked...... to mitochondrial oxidative phosphorylation. Its alteration by glycolysis, inhibition points to a severe oxidative phosphorylation defect. (C) 2008 Elsevier B.V. All rights reserved Udgivelsesdato: 2008/4...

  1. Prenatal nitrate intake from drinking water and selected birth defects in offspring of participants in the national birth defects prevention study.

    Science.gov (United States)

    Brender, Jean D; Weyer, Peter J; Romitti, Paul A; Mohanty, Binayak P; Shinde, Mayura U; Vuong, Ann M; Sharkey, Joseph R; Dwivedi, Dipankar; Horel, Scott A; Kantamneni, Jiji; Huber, John C; Zheng, Qi; Werler, Martha M; Kelley, Katherine E; Griesenbeck, John S; Zhan, F Benjamin; Langlois, Peter H; Suarez, Lucina; Canfield, Mark A

    2013-09-01

    Previous studies of prenatal exposure to drinking-water nitrate and birth defects in offspring have not accounted for water consumption patterns or potential interaction with nitrosatable drugs. We examined the relation between prenatal exposure to drinking-water nitrate and selected birth defects, accounting for maternal water consumption patterns and nitrosatable drug exposure. With data from the National Birth Defects Prevention Study, we linked addresses of 3,300 case mothers and 1,121 control mothers from the Iowa and Texas sites to public water supplies and respective nitrate measurements. We assigned nitrate levels for bottled water from collection of representative samples and standard laboratory testing. Daily nitrate consumption was estimated from self-reported water consumption at home and work. With the lowest tertile of nitrate intake around conception as the referent group, mothers of babies with spina bifida were 2.0 times more likely (95% CI: 1.3, 3.2) to ingest ≥ 5 mg nitrate daily from drinking water (vs. nitrate daily (vs. water nitrate intake did not increase associations between prenatal nitrosatable drug use and birth defects. Higher water nitrate intake was associated with several birth defects in offspring, but did not strengthen associations between nitrosatable drugs and birth defects.

  2. The goal(s of corporate rescue in company law: A comparative analysis

    Directory of Open Access Journals (Sweden)

    Anthony O. Nwafor

    2017-09-01

    Full Text Available The concept of corporate rescue lays emphasis on corporate sustainability than liquidation. This trend in corporate legislation which featured in the United Kingdom Insolvency Act of 1986, Australian Corporations Act 2001, Indian Sick Industrial Companies (Special Provisions Act of 1985 (as replaced by Companies Act, 2013 and supplanted by the Insolvency and Bankruptcy Code, 2016 has been adopted in the South African Companies Act of 2008. The goal(s of corporate rescue in some of these jurisdictions are not clearly defined. The paper examines, through a comparative analysis, the relevant statutory provisions in the United Kingdom, India, Australia and South Africa and the attendant judicial interpretations of those provisions with a view to discovering the goal(s of corporate rescue in those jurisdictions. It is argued that while under the United Kingdom and Australian statutory provisions, the administrator could pursue alternative goals of either rescuing the company or achieving better results for the creditors; the South African and Indian statutory provisions do not provide such alternatives. The seeming ancillary purpose of crafting a fair deal for the stakeholders under the South African Companies Act’s provision is not sustainable if the company as an entity cannot be rescued

  3. Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

    Science.gov (United States)

    Siler, Ulrich; Paruzynski, Anna; Holtgreve-Grez, Heidi; Kuzmenko, Elena; Koehl, Ulrike; Renner, Eleonore D; Alhan, Canan; de Loosdrecht, Arjan A van; Schwäble, Joachim; Pfluger, Thomas; Tchinda, Joelle; Schmugge, Markus; Jauch, Anna; Naundorf, Sonja; Kühlcke, Klaus; Notheis, Gundula; Güngor, Tayfun; Kalle, Christof V; Schmidt, Manfred; Grez, Manuel; Seger, Reinhard; Reichenbach, Janine

    2015-01-01

    We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections. However, one child developed dual insertional activation of ecotropic viral integration site 1 (EVI1) and signal transducer and activator of transcription 3 (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite resistance to mismatched allo-HSCT with standard myeloablative conditioning, secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and disappearance of MDS. The other child did not develop MDS despite expansion of a clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and was cured by early standard allo-HSCT. The slowly developing dominance of clones harboring integrations in MDS1-EVI1 may guide clinical intervention strategies, i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential for both children to survive and to clear therapy-refractory infections, and future GT with safer lentiviral self-inactivated (SIN) vectors may offer a therapeutic alternative for X-CGD patients suffering from life-threatening infections and lacking HLA-identical HSC donors.

  4. Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.

    Science.gov (United States)

    Lund, Raymond D; Wang, Shaomei; Klimanskaya, Irina; Holmes, Toby; Ramos-Kelsey, Rebeca; Lu, Bin; Girman, Sergej; Bischoff, N; Sauvé, Yves; Lanza, Robert

    2006-01-01

    Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in which photoreceptor loss is caused by a defect in the adjacent retinal pigment epithelium. Improvement in visual performance was 100% over untreated controls (spatial acuity was approximately 70% that of normal nondystrophic rats) without evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT) and/or the creation of banks of reduced complexity human leucocyte antigen (HLA) hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols.

  5. 'Don't save her'- Sigmund Freud meets Project Pat: the rescue motif in hip-hop.

    Science.gov (United States)

    Fulmer, Richard H

    2008-08-01

    Freud originally explicated the dynamics of rescue wishes by describing men who fell in love with prostitutes. He saw this attempt at attachment as driven by the man's wish to repay his parents for giving him life. Many subsequent writers shift this emphasis, seeing rescue wishes as motivated by aggressive oedipal competition with the father. This article highlights the attachment aspects of Freud's original conception and traces how writers in the last three decades use the family romance rather than Oedipus as a model to view rescue wishes as having a more tender aspect. Rescue wishes are especially characteristic of the developmental stage of young adulthood. They at once attempt to repay the parental debt the young adult feels and serve as practice for the vicissitudes of the couple bond and the benign sacrifices of parenthood. Popular culture contains many vivid examples of Freud 's original description of the rescue-motif. A detailed examination of the rap song, Don't save her, demonstrates all the elements of Freud's original conception and the interpersonal risks of the rescue relationship. Three additional rap songs by other artists are briefly analyzed to show the extensive occurrence of the wish to rescue and its psychic and interpersonal dangers.

  6. Amphibious Search and Rescue: Shaping the Future

    National Research Council Canada - National Science Library

    Dowling, Michael

    2002-01-01

    The current Amphibious Search and Rescue (ASAR) mission is outdated, lacks integration with the mission/doctrine of the amphibious force and fails to exploit the multi-mission and tactical capabilities of the MH-60S helicopter...

  7. Persistent Epithelial Defects and Corneal Opacity After Collagen Cross-Linking With Substitution of Dextran (T-500) With Dextran Sulfate in Compounded Topical Riboflavin.

    Science.gov (United States)

    Höllhumer, Roland; Watson, Stephanie; Beckingsale, Peter

    2017-03-01

    Collagen cross-linking (CXL) is a commonly performed procedure to prevent the progression of keratoconus. Riboflavin is an essential part of the procedure, which facilitates both the cross-linking process and protection of intraocular structures. Dextran can be added to riboflavin to create an isotonic solution. This case report highlights the importance of compounding riboflavin with the correct dextran solution. A retrospective case series. Six eyes of 4 male patients with keratoconus aged from 20 to 38 years underwent CXL with substitution of 20% dextran (T-500) with 20% dextran sulfate in a compounded riboflavin 0.1% solution. Postoperatively, persistent corneal epithelial defects, stromal haze, and then scarring occurred. Corneal transplantation was performed for visual rehabilitation but was complicated by graft rejection followed by failure (n = 1 eye), dehiscence (n = 4), cataract (n = 2), post-laser ablation haze (n = 1), and steroid-induced glaucoma (n = 2). The visual outcome was dextran (T-500) with dextran sulfate in riboflavin solutions during CXL results in loss of vision from permanent corneal opacity. Residual host changes may compromise the results of corneal transplantation.

  8. TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity

    DEFF Research Database (Denmark)

    Decressac, Mickael; Mattsson, Bengt; Weikop, Pia

    2013-01-01

    that the PD-like neurodegenerative changes induced by excess cellular levels of α-synuclein in nigral dopamine neurons are closely linked to a progressive decline in markers of lysosome function, accompanied by cytoplasmic retention of transcription factor EB (TFEB), a major transcriptional regulator...... in both A9 and A10 dopamine neurons. Delayed activation of TFEB function through inhibition of mammalian target of rapamycin blocked α-synuclein induced neurodegeneration and further disease progression. The results provide a mechanistic link between α-synuclein toxicity and impaired TFEB function......The aggregation of α-synuclein plays a major role in Parkinson disease (PD) pathogenesis. Recent evidence suggests that defects in the autophagy-mediated clearance of α-synuclein contribute to the progressive loss of nigral dopamine neurons. Using an in vivo model of α-synuclein toxicity, we show...

  9. Dictyostelium discoideum: mutants in the biosynthesis of the lipid-linked precursor of N-linked oligosaccharides

    International Nuclear Information System (INIS)

    Freeze, H.; Willies, L.; Hamilton, S.

    1986-01-01

    The lysosomal enzymes of Dictyostelium discoideum share highly immunogenic oligosaccharides which contain multiple Man-6-SO 4 residues. Two mutant strains which lack the shared antigenic determinant were analyzed in an attempt to identify the primary defect in each. [ 3 H]Man labelled N-linked oligosaccharides of secreted glycoproteins were released by Endo/PNGaseF digestion and analyzed. Both of the mutant strains produced smaller, less sulfated oligosaccharides compared to the wild-type, yet both still contained considerable amounts of Man-6-SO 4 . The size of the precursor lipid-linked oligosaccharide from the wild-type is consistent with a Glc 3 Man 9 GlcNAc 2 structure, while those from both of the mutants have an oligosaccharide the size of Man 5 GlcNAc 2 . The authors conclude that both of the mutants are defective in the biosynthesis of the precursor oligosaccharide. Both oligosaccharides from the mutants contain a tri-mannosyl core and are not glucosylated. Two of the five Man residues are released by a 1,2 specific α mannosidase. Based on the size and mannosidase digestions the authors conclude that 4/5 of the Man residues on the α1,6 branch of the β-linked Man residues are missing. Thus, these residues must be required to define the shared antigenic determinant

  10. Boulder Food Rescue: An Innovative Approach to Reducing Food Waste and Increasing Food Security.

    Science.gov (United States)

    Sewald, Craig A; Kuo, Elena S; Dansky, Hana

    2018-05-01

    Food waste and food insecurity are both significant issues in communities throughout the U.S., including Boulder, Colorado. As much as 40% of the food produced in the U.S. goes uneaten and ends up in landfills. Nearly 13% of people in the Boulder region experience some level of food insecurity. Founded in 2011, Boulder Food Rescue supports community members to create their own food security through a participatory approach to an emergency food system. The organization uses a web-application "robot" to manage a schedule of volunteers. They coordinate with individuals at low-income senior housing sites, individual housing sites, family housing sites, after-school programs, and pre-schools to set up no-cost grocery programs stocked with food from local markets and grocers that would otherwise go to waste. Each site coordinator makes decisions about how, when, and where food delivery and distribution will occur. The program also conducts robust, real-time data collection and analysis. Boulder Food Rescue is a member and manager of the Food Rescue Alliance, and its model has been replicated and adapted by other cities, including Denver, Colorado Springs, Seattle, Jackson Hole, Minneapolis, Binghamton, and in the Philippines. Information for this special article was collected through key informant interviews with current and former Boulder Food Rescue staff and document review of Boulder Food Rescue materials. Boulder Food Rescue's open source software is available to other communities; to date, 40 cities have used the tool to start their own food rescue organizations. Boulder Food Rescue hopes to continue spreading this model to other cities that are considering ways to reduce food waste and increase food security. This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health. Copyright © 2018 American Journal of Preventive Medicine. Published by

  11. Rescue Medicine for Epilepsy: New Options for Education Settings.

    Science.gov (United States)

    Galemore, Cynthia A

    2016-11-01

    The American Academy of Pediatrics (AAP) recently published a clinical report recommending expanded options for seizure rescue medications in the school setting. School nurses rely on prescribing professionals for medical orders to manage children with epilepsy in the school setting. The report suggests additional medications beyond rectal diazepam gel along with discussing the purpose of the medications, the variations in prescribing practices for seizure rescue medications, inconsistencies in legislation based on jurisdictions, and the need for school medical orders for students with epilepsy. There are many issues faced by school personnel when caring for students with a diagnosis of epilepsy, chief among them the presence of licensed health professions for the school to be able to respond quickly and appropriately in the event of a seizure. School nurses can assist health care providers in determining the rescue medication most easily delivered and monitored in the variety of activities that are part of the school experience, including transportation to and from school, field trips, and before- and after-school activities, all beyond the regular classroom setting.

  12. Defects and defect processes in nonmetallic solids

    CERN Document Server

    Hayes, W

    2004-01-01

    This extensive survey covers defects in nonmetals, emphasizing point defects and point-defect processes. It encompasses electronic, vibrational, and optical properties of defective solids, plus dislocations and grain boundaries. 1985 edition.

  13. Defects in Amorphous Semiconductors: The Case of Amorphous Indium Gallium Zinc Oxide

    Science.gov (United States)

    de Jamblinne de Meux, A.; Pourtois, G.; Genoe, J.; Heremans, P.

    2018-05-01

    Based on a rational classification of defects in amorphous materials, we propose a simplified model to describe intrinsic defects and hydrogen impurities in amorphous indium gallium zinc oxide (a -IGZO). The proposed approach consists of organizing defects into two categories: point defects, generating structural anomalies such as metal—metal or oxygen—oxygen bonds, and defects emerging from changes in the material stoichiometry, such as vacancies and interstitial atoms. Based on first-principles simulations, it is argued that the defects originating from the second group always act as perfect donors or perfect acceptors. This classification simplifies and rationalizes the nature of defects in amorphous phases. In a -IGZO, the most important point defects are metal—metal bonds (or small metal clusters) and peroxides (O - O single bonds). Electrons are captured by metal—metal bonds and released by the formation of peroxides. The presence of hydrogen can lead to two additional types of defects: metal-hydrogen defects, acting as acceptors, and oxygen-hydrogen defects, acting as donors. The impact of these defects is linked to different instabilities observed in a -IGZO. Specifically, the diffusion of hydrogen and oxygen is connected to positive- and negative-bias stresses, while negative-bias illumination stress originates from the formation of peroxides.

  14. Gas Concentration Prediction Based on the Measured Data of a Coal Mine Rescue Robot

    Directory of Open Access Journals (Sweden)

    Xiliang Ma

    2016-01-01

    Full Text Available The coal mine environment is complex and dangerous after gas accident; then a timely and effective rescue and relief work is necessary. Hence prediction of gas concentration in front of coal mine rescue robot is an important significance to ensure that the coal mine rescue robot carries out the exploration and search and rescue mission. In this paper, a gray neural network is proposed to predict the gas concentration 10 meters in front of the coal mine rescue robot based on the gas concentration, temperature, and wind speed of the current position and 1 meter in front. Subsequently the quantum genetic algorithm optimization gray neural network parameters of the gas concentration prediction method are proposed to get more accurate prediction of the gas concentration in the roadway. Experimental results show that a gray neural network optimized by the quantum genetic algorithm is more accurate for predicting the gas concentration. The overall prediction error is 9.12%, and the largest forecasting error is 11.36%; compared with gray neural network, the gas concentration prediction error increases by 55.23%. This means that the proposed method can better allow the coal mine rescue robot to accurately predict the gas concentration in the coal mine roadway.

  15. Multi-agent cooperation rescue algorithm based on influence degree and state prediction

    Science.gov (United States)

    Zheng, Yanbin; Ma, Guangfu; Wang, Linlin; Xi, Pengxue

    2018-04-01

    Aiming at the multi-agent cooperative rescue in disaster, a multi-agent cooperative rescue algorithm based on impact degree and state prediction is proposed. Firstly, based on the influence of the information in the scene on the collaborative task, the influence degree function is used to filter the information. Secondly, using the selected information to predict the state of the system and Agent behavior. Finally, according to the result of the forecast, the cooperative behavior of Agent is guided and improved the efficiency of individual collaboration. The simulation results show that this algorithm can effectively solve the cooperative rescue problem of multi-agent and ensure the efficient completion of the task.

  16. A competency framework for the business rescue practitioner profession

    Directory of Open Access Journals (Sweden)

    Marius Pretorius

    2014-08-01

    Research purpose: Competencies required by business rescue practitioners (BRPs to navigate a distressed venture were investigated. What BRPs actually ‘do’ during a rescue guided the development of a competency framework to inform future qualification guidelines for BRP education and accreditation. Motivation for the study: To investigate the research question: ‘What are the competencies that underlie the activities of a business rescue practitioner?’. Research design, approach and method: A modified ‘interview to the double’ (ITTD process was used to elicit instructions that a BRP would give to an imaginary ‘double’. These instructions were analysed and rated for importance, transferability, knowledge requirement and skills requirement; in conclusion, these instructions were ranked and subjected to a content analysis. Main findings: Based on the main activities that were derived from the practices and praxis, one assignment and four supra (higher-level competencies were consequent to the analysis. A BRP able to successfully navigate a distressed venture towards normal operations should demonstrate a high level of competency in sense-making, decision making and integration, achieved through collaboration as the central competency. Practical implications: Firstly, the study addresses educators’ need for a framework of competencies to guide education. Secondly, it paves the way for the Regulator to develop a qualifications framework for accreditation. Contribution: The findings gave structure to the competencies underlying the activities of a BRP to navigate a rescue. Pre-business and financial acumen appears limited without these competencies containing insight, experience, intuition, heuristics, tacit knowledge, perceptive induction and more.

  17. Mid-Term report 'Establishing bonds for the advancement of the Rescue League'

    NARCIS (Netherlands)

    Riaño, I.; Visser, A.

    2014-01-01

    The RoboCup Rescue Simulation League aims to benchmark the intelligence of software agents and robots on their capabilities to make autonomously the right decisions in a disaster response scenario. The UvA Rescue and Distribot team have come together to work co-operatively to support this aim in two

  18. The role of "rescue saccades" in tracking objects through occlusions.

    Science.gov (United States)

    Zelinsky, Gregory J; Todor, Andrei

    2010-12-29

    We hypothesize that our ability to track objects through occlusions is mediated by timely assistance from gaze in the form of "rescue saccades"-eye movements to tracked objects that are in danger of being lost due to impending occlusion. Observers tracked 2-4 target sharks (out of 9) for 20 s as they swam through a rendered 3D underwater scene. Targets were either allowed to enter into occlusions (occlusion trials) or not (no occlusion trials). Tracking accuracy with 2-3 targets was ≥ 92% regardless of target occlusion but dropped to 74% on occlusion trials with four targets (no occlusion trials remained accurate; 83%). This pattern was mirrored in the frequency of rescue saccades. Rescue saccades accompanied approximatlely 50% of the Track 2-3 target occlusions, but only 34% of the Track 4 occlusions. Their frequency also decreased with increasing distance between a target and the nearest other object, suggesting that it is the potential for target confusion that summons a rescue saccade, not occlusion itself. These findings provide evidence for a tracking system that monitors for events that might cause track loss (e.g., occlusions) and requests help from the oculomotor system to resolve these momentary crises. As the number of crises increase with the number of targets, some requests for help go unsatisfied, resulting in degraded tracking.

  19. Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo.

    Science.gov (United States)

    Itani, Nozomi; Skeffington, Katie L; Beck, Christian; Niu, Youguo; Giussani, Dino A

    2016-01-01

    There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment commences following FGR diagnosis is also unknown. We isolated the effects of melatonin on the developing cardiovascular system of the chick embryo during hypoxic incubation. We tested the hypothesis that melatonin directly protects the fetal cardiovascular system in adverse development and that it can rescue dysfunction following FGR diagnosis. Chick embryos were incubated under normoxia or hypoxia (14% O2) from day 1 ± melatonin treatment (1 mg/kg/day) from day 13 of incubation (term ~21 days). Melatonin in hypoxic chick embryos rescued cardiac systolic dysfunction, impaired cardiac contractility and relaxability, increased cardiac sympathetic dominance, and endothelial dysfunction in peripheral circulations. The mechanisms involved included reduced oxidative stress, enhanced antioxidant capacity and restored vascular endothelial growth factor expression, and NO bioavailability. Melatonin treatment of the chick embryo starting at day 13 of incubation, equivalent to ca. 25 wk of gestation in human pregnancy, rescues early origins of cardiovascular dysfunction during hypoxic development. Melatonin may be a suitable antioxidant candidate for translation to human therapy to protect the fetal cardiovascular system in adverse pregnancy. © 2015 The Authors. Journal of Pineal Research. Published by John Wiley & Sons Ltd.

  20. Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo

    OpenAIRE

    Itani, Nozomi; Skeffington, Katie L.; Beck, Christian; Niu, Youguo; Giussani, Dino A.

    2015-01-01

    Abstract There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment comm...

  1. Human Detection and Classification of Landing Sites for Search and Rescue Drones

    NARCIS (Netherlands)

    N. Martins, Felipe; de Groot, Marc; Stokkel, Xeryus; Wiering, Marco

    2016-01-01

    Search and rescue is often time and labour intensive. We present a system to be used in drones to make search and rescue operations more effective. The system uses a drone downward facing camera to detect people and to evaluate potential sites as being safe or not for the drone to land. Histogram of

  2. An innovative strategy to clone positive modifier genes of defects caused by mtDNA mutations: MRPS18C as suppressor gene of m.3946G>A mutation in MT-ND1 gene.

    Science.gov (United States)

    Rodríguez-García, María Elena; Cotrina-Vinagre, Francisco Javier; Carnicero-Rodríguez, Patricia; Martínez-Azorín, Francisco

    2017-07-01

    We have developed a new functional complementation approach to clone modifier genes which overexpression is able to suppress the biochemical defects caused by mtDNA mutations (suppressor genes). This strategy consists in transferring human genes into respiratory chain-deficient fibroblasts, followed by a metabolic selection in a highly selective medium. We used a normalized expression cDNA library in an episomal vector (pREP4) to transfect the fibroblasts, and a medium with glutamine and devoid of any carbohydrate source to select metabolically. Growing the patient's fibroblasts in this selective medium, the deficient cells rapidly disappear unless they are rescued by the cDNA of a suppressor gene. The use of an episomal vector allows us to carry out several rounds of transfection/selection (cyclical phenotypic rescue) to enrich the rescue with true clones of suppressor genes. Using fibroblasts from a patient with epileptic encephalopathy with the m.3946G>A (p.E214K) mutation in the MT-ND1 gene, several candidate genes were identified and one of them was characterized functionally. Thus, overexpression of MRPS18C gene (that encode for bS18m protein) suppressed the molecular defects produced by this mtDNA mutation, recovering the complex I activity and reducing the ROS produced by this complex to normal levels. We suggest that modulation of bS18m expression may be an effective therapeutic strategy for the patients with this mutation.

  3. Effect of radiation-induced substrate defects on microstrip gas chamber gain behaviour

    International Nuclear Information System (INIS)

    Pallares, A.; Brom, J.M.; Bergdolt, A.M.; Coffin, J.; Eberle, H.; Sigward, M.H.; Fontaine, J.C.; Barthe, S.; Schunck, J.P.

    1998-01-01

    The aim of this work was to quantify the influence of radiation-induced substrate defects on microstrip gas chamber (MSGC) gain behaviour. The first part of this paper focuses on radiation effects on a typical MSGC substrate: Desag D263 glass. Defect generation was studied for Desag D263 with pure silica (Suprasil 1) as a reference. We studied the evolution of defect concentration with respect to accumulated doses up to 480 kGy. Annealing studies of defects in Desag D263 were also performed. In the second part, the radiation sensitivity of Desag D263 glass has been linked to the behaviour of the detector under irradiation. Comparative gain measurements were taken before and after substrate irradiation at 10 and 80 kGy the minimal dose received during LHC operation and the dose for which defect density is maximum (respectively). (orig.)

  4. RoboCup Rescue Robot and Simulation Leagues

    NARCIS (Netherlands)

    Akin, H.L.; Ito, N.; Jacoff, A.; Kleiner, A.; Pellenz, J.; Visser, A.

    2013-01-01

    The RoboCup Rescue Robot and Simulation competitions have been held since 2000. The experience gained during these competitions has increased the maturity level of the field, which allowed deploying robots after real disasters (for example, Fukushima Daiichi nuclear disaster). This article provides

  5. Gazing toward humans: a study on water rescue dogs using the impossible task paradigm.

    Science.gov (United States)

    D'Aniello, Biagio; Scandurra, Anna; Prato-Previde, Emanuela; Valsecchi, Paola

    2015-01-01

    Various studies have assessed the role of life experiences, including learning opportunities, living conditions and the quality of dog-human relationships, in the use of human cues and problem-solving ability. The current study investigates how and to what extent training affects the behaviour of dogs and the communication of dogs with humans by comparing dogs trained for a water rescue service and untrained pet dogs in the impossible task paradigm. Twenty-three certified water rescue dogs (the water rescue group) and 17 dogs with no training experience (the untrained group) were tested using a modified version of the impossible task described by Marshall-Pescini et al. in 2009. The results demonstrated that the water rescue dogs directed their first gaze significantly more often towards the owner and spent more time gazing toward two people compared to the untrained pet dogs. There was no difference between the dogs of the two groups as far as in the amount of time spent gazing at the owner or the stranger; neither in the interaction with the apparatus attempting to obtain food. The specific training regime, aimed at promoting cooperation during the performance of water rescue, could account for the longer gazing behaviour shown toward people by the water rescue dogs and the priority of gazing toward the owner. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. The Rescue and Rehabilitation of Koalas (Phascolarctos cinereus in Southeast Queensland

    Directory of Open Access Journals (Sweden)

    Emily Burton

    2016-09-01

    Full Text Available Koala populations in southeast Queensland are under threat from many factors, particularly habitat loss, dog attack, vehicle trauma and disease. Animals not killed from these impacts are often rescued and taken into care for rehabilitation, and eventual release back to the wild if deemed to be healthy. This study investigated current rescue, rehabilitation and release data for koalas admitted to the four major wildlife hospitals in southeast Queensland (Australia Zoo Wildlife Hospital (AZWH, Currumbin Wildlife Sanctuary Hospital (CWH, Moggill Koala Hospital (MKH and the Royal Society for the Prevention Against Cruelty to Animals Wildlife Hospital at Wacol (RSPCA, and suggests aspects of the practice that may be changed to improve its contribution to the preservation of the species. It concluded that: (a the main threats to koalas across southeast Queensland were related to urbanization (vehicle collisions, domestic animal attacks and the disease chlamydiosis; (b case outcomes varied amongst hospitals, including time spent in care, euthanasia and release rates; and (c the majority (66.5% of rescued koalas were either euthanized or died in care with only 27% released back to the wild. The results from this study have important implications for further research into koala rescue and rehabilitation to gain a better understanding of its effectiveness as a conservation strategy.

  7. The Rescue and Rehabilitation of Koalas (Phascolarctos cinereus) in Southeast Queensland.

    Science.gov (United States)

    Burton, Emily; Tribe, Andrew

    2016-09-15

    Koala populations in southeast Queensland are under threat from many factors, particularly habitat loss, dog attack, vehicle trauma and disease. Animals not killed from these impacts are often rescued and taken into care for rehabilitation, and eventual release back to the wild if deemed to be healthy. This study investigated current rescue, rehabilitation and release data for koalas admitted to the four major wildlife hospitals in southeast Queensland (Australia Zoo Wildlife Hospital (AZWH), Currumbin Wildlife Sanctuary Hospital (CWH), Moggill Koala Hospital (MKH) and the Royal Society for the Prevention Against Cruelty to Animals Wildlife Hospital at Wacol (RSPCA)), and suggests aspects of the practice that may be changed to improve its contribution to the preservation of the species. It concluded that: (a) the main threats to koalas across southeast Queensland were related to urbanization (vehicle collisions, domestic animal attacks and the disease chlamydiosis); (b) case outcomes varied amongst hospitals, including time spent in care, euthanasia and release rates; and (c) the majority (66.5%) of rescued koalas were either euthanized or died in care with only 27% released back to the wild. The results from this study have important implications for further research into koala rescue and rehabilitation to gain a better understanding of its effectiveness as a conservation strategy.

  8. Motivations for volunteers in food rescue nutrition.

    Science.gov (United States)

    Mousa, T Y; Freeland-Graves, J H

    2017-08-01

    A variety of organizations redistribute surplus food to low-income populations through food rescue nutrition. Why volunteers participate in these charitable organizations is unclear. The aim of this study is to document the participation and motivations of volunteers who are involved specifically in food rescue nutrition. A cross-sectional study was conducted in two phases. In phase 1, a new instrument, Motivations to Volunteer Scale, was developed and validated in 40 participants (aged ≥18 years). In phase 2, the new scale and a demographics questionnaire were administered to 300 participants who were volunteering in food pantries and churches. The pilot study showed that Motivations to Volunteer Scale exhibited an internal consistency of Cronbach's α of 0.73 (P  0.05). The scale was validated also by comparison to the Volunteer Function Inventory (r = 0.86, P social life, and altruism. The mean motivation score of the 300 volunteers was 9.15 ± 0.17. Greater motivations were observed among participants who were aged >45 years, women, Hispanics, college/university graduates, physically inactive, non-smokers, and had an income ≥ $48,000. The Motivations to Volunteer Scale is a valid tool to assess why individuals volunteer in food rescue nutrition. The extent of motivations of participants was relatively high, and the primary reason for volunteering was altruism. Health professionals should be encouraged to participate in food redistribution. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  9. Saving the injured: Rescue behavior in the termite-hunting ant Megaponera analis.

    Science.gov (United States)

    Frank, Erik Thomas; Schmitt, Thomas; Hovestadt, Thomas; Mitesser, Oliver; Stiegler, Jonas; Linsenmair, Karl Eduard

    2017-04-01

    Predators of highly defensive prey likely develop cost-reducing adaptations. The ant Megaponera analis is a specialized termite predator, solely raiding termites of the subfamily Macrotermitinae (in this study, mostly colonies of Pseudocanthotermes sp.) at their foraging sites. The evolutionary arms race between termites and ants led to various defensive mechanisms in termites (for example, a caste specialized in fighting predators). Because M. analis incurs high injury/mortality risks when preying on termites, some risk-mitigating adaptations seem likely to have evolved. We show that a unique rescue behavior in M. analis , consisting of injured nestmates being carried back to the nest, reduces combat mortality. After a fight, injured ants are carried back by their nestmates; these ants have usually lost an extremity or have termites clinging to them and are able to recover within the nest. Injured ants that are forced experimentally to return without help, die in 32% of the cases. Behavioral experiments show that two compounds, dimethyl disulfide and dimethyl trisulfide, present in the mandibular gland reservoirs, trigger the rescue behavior. A model accounting for this rescue behavior identifies the drivers favoring its evolution and estimates that rescuing enables maintenance of a 28.7% larger colony size. Our results are the first to explore experimentally the adaptive value of this form of rescue behavior focused on injured nestmates in social insects and help us to identify evolutionary drivers responsible for this type of behavior to evolve in animals.

  10. Emergency Medical Rescue in a Radiation Environment

    International Nuclear Information System (INIS)

    Briesmeister, L.; Ellington, Y.; Hollis, R.; Kunzman, J.; McNaughton, M.; Ramsey, G.; Somers, B.; Turner, A.; Finn, J.

    1999-01-01

    Previous experience with emergency medical rescues in the presence of radiation or contamination indicates that the training provided to emergency responders is not always appropriate. A new course developed at Los Alamos includes specific procedures for emergency response in a variety of radiological conditions

  11. Work engagement among rescue workers: psychometric properties of the portuguese UWES

    OpenAIRE

    Jorge Sinval; Alexandra Marques-Pinto; Cristina Queirós; João Marôco

    2018-01-01

    Rescue workers have a stressful and risky occupation where being engaged is crucial to face physical and emotional risks in order to help other persons. This study aims to estimate work engagement levels of rescue workers (namely comparing nurses, firefighters, and police officers) and to assess the validity evidence related to the internal structure of the Portuguese versions of the UWES-17 and UWES-9, namely, dimensionality, measurement invariance between occupational groups, and reliabilit...

  12. Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma

    OpenAIRE

    Chen, Xue; Zhang, Yang; Wang, Fang; Wang, Mangju; Teng, Wen; Lin, Yuehui; Han, Xiangping; Jin, Fangyuan; Xu, Yuanli; Cao, Panxiang; Fang, Jiancheng; Zhu, Ping; Tong, Chunrong; Liu, Hongxing

    2017-01-01

    Certain patients with lymphoma may harbor mutations in perforin 1 (PRF1), unc-13 homolog D (UNC13D), syntaxin 11 (STX11), STXBP2 (syntaxin binding protein 2) or SH2 domain containing 1A (SH2D1A), which causes functional defects of cytotoxic lymphocytes. Data regarding the association between genetic defects and the development of lymphoma in Chinese patients are limited to date. In the present study, 90 patients with lymphoma were analyzed for UNC13D, PRF1, STXBP2, STX11, SH2D1A and X-linked ...

  13. Precise design-based defect characterization and root cause analysis

    Science.gov (United States)

    Xie, Qian; Venkatachalam, Panneerselvam; Lee, Julie; Chen, Zhijin; Zafar, Khurram

    2017-03-01

    As semiconductor manufacturing continues its march towards more advanced technology nodes, it becomes increasingly important to identify and characterize design weak points, which is typically done using a combination of inline inspection data and the physical layout (or design). However, the employed methodologies have been somewhat imprecise, relying greatly on statistical techniques to signal excursions. For example, defect location error that is inherent to inspection tools prevents them from reporting the true locations of defects. Therefore, common operations such as background-based binning that are designed to identify frequently failing patterns cannot reliably identify specific weak patterns. They can only identify an approximate set of possible weak patterns, but within these sets there are many perfectly good patterns. Additionally, characterizing the failure rate of a known weak pattern based on inline inspection data also has a lot of fuzziness due to coordinate uncertainty. SEM (Scanning Electron Microscope) Review attempts to come to the rescue by capturing high resolution images of the regions surrounding the reported defect locations, but SEM images are reviewed by human operators and the weak patterns revealed in those images must be manually identified and classified. Compounding the problem is the fact that a single Review SEM image may contain multiple defective patterns and several of those patterns might not appear defective to the human eye. In this paper we describe a significantly improved methodology that brings advanced computer image processing and design-overlay techniques to better address the challenges posed by today's leading technology nodes. Specifically, new software techniques allow the computer to analyze Review SEM images in detail, to overlay those images with reference design to detect every defect that might be present in all regions of interest within the overlaid reference design (including several classes of defects

  14. Chemical Rescue of Enzymes: Proton Transfer in Mutants of Human Carbonic Anhydrase II

    Science.gov (United States)

    Maupin, C. Mark; Castillo, Norberto; Taraphder, Srabani; Tu, Chingkuang; McKenna, Robert; Silverman, David N.; Voth, Gregory A.

    2011-01-01

    In human carbonic anhydrase II (HCA II) the mutation of position 64 from histidine to alanine (H64A) disrupts the rate limiting proton transfer (PT) event, resulting in a reduction of the catalytic activity of the enzyme as compared to the wild-type. Potential of mean force (PMF) calculations utilizing the multistate empirical valence bond (MS-EVB) methodology for H64A HCA II give a PT free energy barrier significantly higher than that found in the wild-type enzyme. This high barrier, determined in the absence of exogenous buffer and assuming no additional ionizable residues in the PT pathway, indicates the likelihood of alternate enzyme pathways that utilize either ionizable enzyme residues (self-rescue) and/or exogenous buffers (chemical rescue). It has been shown experimentally that the catalytic activity of H64A HCA II can be chemically rescued to near wild type levels by the addition of the exogenous buffer 4-methylimidazole (4MI). Crystallographic studies have identified two 4MI binding sites, yet site specific mutations intended to disrupt 4MI binding have demonstrated these sites to be non-productive. In the present work MS-EVB simulations show that binding of 4MI near Thr199 in the H64A HCA II mutant, a binding site determined by NMR spectroscopy, results in a viable chemical rescue pathway. Additional viable rescue pathways are also identified where 4MI acts as a proton transport intermediary from the active site to ionizable residues on the rim of the active site, revealing a probable mode of action for the chemical rescue pathway PMID:21452838

  15. Rescuing Dogs in the Frederick Community | Poster

    Science.gov (United States)

    Many Frederick National Lab employees have a favorite cause to which they volunteer a significant amount of time. For Dianna Kelly, IT program manager/scientific program analyst, Office of Scientific Operations, and Courtney Kennedy, associate technical project manager, Business Enterprise Systems, that cause is dog rescue.

  16. Glycoprotein cytoplasmic domain sequences required for rescue of a vesicular stomatitis virus glycoprotein mutant

    International Nuclear Information System (INIS)

    Whitt, M.A.; Chong, L.; Rose, J.K.

    1989-01-01

    The authors have used transient expression of the wild-type vesicular stomatitis virus (VSV) glycoprotein (G protein) from cloned cDNA to rescue a temperature-sensitive G protein mutant of VSV in cells at the nonpermissive temperature. Using cDNAs encoding G proteins with deletions in the normal 29-amino-acid cytoplasmic domain, they determined that the presence of either the membrane-proximal 9 amino acids or the membrane-distal 12 amino acids was sufficient for rescue of the temperature-sensitive mutant. G proteins with cytoplasmic domains derived from other cellular or viral G proteins did not rescue the mutant, nor did G proteins with one or three amino acids of the normal cytoplasmic domain. Rescue correlated directly with the ability of the G proteins to be incorporated into virus particles. This was shown by analysis of radiolabeled particles separated on sucrose gradients as well as by electron microscopy of rescued virus after immunogold labeling. Quantitation of surface expression showed that all of the mutated G proteins were expressed less efficiently on the cell surface than was wild-type G protein. However, they were able to correct for differences in rescue efficiency resulting from differences in the level of surface expression by reducing wild-type G protein expression to levels equivalent to those observed for the mutated G proteins. The results provide evidence that at least a portion of the cytoplasmic domain is required for efficient assembly of the VSV G protein into virions during virus budding

  17. Effect of radiation-induced substrate defects on microstrip gas chamber gain behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Pallares, A.; Brom, J.M.; Bergdolt, A.M.; Coffin, J.; Eberle, H.; Sigward, M.H. [Institute de Recherches Subatomiques, 67 - Strasbourg (France); Fontaine, J.C. [Universite de Haute Alsace, GRPHE, 61 rue Albert Camus, 68093 Mulhouse Cedex (France); Barthe, S.; Schunck, J.P. [Laboratoire PHASE (UPR 292 du CNRS), 23 rue du Loess, BP 28, 67037 Strasbourg Cedex 2 (France)

    1998-08-01

    The aim of this work was to quantify the influence of radiation-induced substrate defects on microstrip gas chamber (MSGC) gain behaviour. The first part of this paper focuses on radiation effects on a typical MSGC substrate: Desag D263 glass. Defect generation was studied for Desag D263 with pure silica (Suprasil 1) as a reference. We studied the evolution of defect concentration with respect to accumulated doses up to 480 kGy. Annealing studies of defects in Desag D263 were also performed. In the second part, the radiation sensitivity of Desag D263 glass has been linked to the behaviour of the detector under irradiation. Comparative gain measurements were taken before and after substrate irradiation at 10 and 80 kGy the minimal dose received during LHC operation and the dose for which defect density is maximum (respectively). (orig.) 26 refs.

  18. PSO-Based Robot Path Planning for Multisurvivor Rescue in Limited Survival Time

    Directory of Open Access Journals (Sweden)

    N. Geng

    2014-01-01

    Full Text Available Since the strength of a trapped person often declines with time in urgent and dangerous circumstances, adopting a robot to rescue as many survivors as possible in limited time is of considerable significance. However, as one key issue in robot navigation, how to plan an optimal rescue path of a robot has not yet been fully solved. This paper studies robot path planning for multisurvivor rescue in limited survival time using a representative heuristic, particle swarm optimization (PSO. First, the robot path planning problem including multiple survivors is formulated as a discrete optimization one with high constraint, where the number of rescued persons is taken as the unique objective function, and the strength of a trapped person is used to constrain the feasibility of a path. Then, a new integer PSO algorithm is presented to solve the mathematical model, and several new operations, such as the update of a particle, the insertion and inversion operators, and the rapidly local search method, are incorporated into the proposed algorithm to improve its effectiveness. Finally, the simulation results demonstrate the capacity of our method in generating optimal paths with high quality.

  19. Autonomous and Non-autonomous Defects Underlie Hypertrophic Cardiomyopathy in BRAF-Mutant hiPSC-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Rebecca Josowitz

    2016-09-01

    Full Text Available Germline mutations in BRAF cause cardio-facio-cutaneous syndrome (CFCS, whereby 40% of patients develop hypertrophic cardiomyopathy (HCM. As the role of the RAS/MAPK pathway in HCM pathogenesis is unclear, we generated a human induced pluripotent stem cell (hiPSC model for CFCS from three patients with activating BRAF mutations. By cell sorting for SIRPα and CD90, we generated a method to examine hiPSC-derived cell type-specific phenotypes and cellular interactions underpinning HCM. BRAF-mutant SIRPα+/CD90− cardiomyocytes displayed cellular hypertrophy, pro-hypertrophic gene expression, and intrinsic calcium-handling defects. BRAF-mutant SIRPα−/CD90+ cells, which were fibroblast-like, exhibited a pro-fibrotic phenotype and partially modulated cardiomyocyte hypertrophy through transforming growth factor β (TGFβ paracrine signaling. Inhibition of TGFβ or RAS/MAPK signaling rescued the hypertrophic phenotype. Thus, cell autonomous and non-autonomous defects underlie HCM due to BRAF mutations. TGFβ inhibition may be a useful therapeutic option for patients with HCM due to RASopathies or other etiologies.

  20. Design and rescue scenario of common repair equipment for in-vessel components in ITER hot cell

    International Nuclear Information System (INIS)

    Kakudate, Satoshi; Takeda, Nobukazu; Nakahira, Masataka; Shibanuma, Kiyoshi

    2006-06-01

    Transportation of the in-vessel components to be repaired in the ITER hot cell is carried by two kinds of transporters, i.e., overhead cranes and floor vehicles. The access area for repair operations in the hot cell is duplicated by these transporters. Clear sharing of the respective roles of these transporters with the minimum duplication is therefore useful for rationalization. The overhead cranes, which are independently installed in the respective cells in the hot sell, cannot pass through the components to be repaired between cells, i.e., receiving cell and refurbishment cell as an example. If the floor vehicle with simple mechanisms can cover the inaccessible area for the overhead cranes, a global transporter system in the hot cell will be simplified and the reliability will be increased. Based on this strategy, the overhead crane and floor vehicle concepts are newly proposed. The overhead crane has an adapter for change of the end-effectors, which can be easily changed, to grasp many kinds of components to be repaired. The floor vehicle, which is equipped with wheel mechanisms for transportation, is just to pass through the components between cells with only straight (linear) motion on the floor. The simple wheel mechanism can solve the spread of the dust, which is the critical issue of the original air bearing mechanism for traveling in the 2001 FDR design. Rescue scenarios and procedures in the hot cell are also studied in this report. The proposed rescue crane has major two functions for rescue operations of the hot cell facility, i.e., one for the overhead crane and the other for refurbishment equipment such as workstation for divertor repair. The rescue of the faulty overhead crane is carried out using the rescue tool installed on the rescue crane or directly traveled by pushing/pulling by the rescue crane after docking on the faulty overhead crane. For the rescue of the workstation, the rescue crane consists of a telescopic manipulator (maximum length

  1. New simulated gas detector offers realistic training for mine rescue teams

    Energy Technology Data Exchange (ETDEWEB)

    Bealko, S.B.; Alexander, D.; Chasko, L.L. [National Inst. for Occupational Safety and Health, Pittsburgh, PA (United States). Office of Mine Safety and Health Research; Holtan, J. [LightsOn Safety Solutions, Spring, TX (United States)

    2010-07-01

    The National Institute for Occupational Safety and Health, together with LightsOn Safety Solutions, evaluated 2 versions of a multi-gas simulated gas monitor system (GMS) in separate field trials with mine rescue teams. This paper described the GMS wireless simulation tool along with its development and testing. It also described the GMS functions for the initial phase of testing as well as plans for the next phase of research which may introduce tracking and automation features. The GMS requires a personal computer and uses a wireless local area network. The GMS teaches mine rescue members about gas detection and helps them understand the importance of gas concentrations. In addition, it promotes decision-making actions by team members and offers a more realistic method of receiving gas concentration readings using a simulated hand-held gas detector. The purpose of the evaluation was to determine if the electronic placard in the GMS could be used by mine rescue teams instead of the currently used cardboard placards, and if the functionality of the device was suitable, reliable and practical. Results from the second field trial demonstrated improvements with the GMS over the original prototype technology, particularly with regards to wireless and connectivity issues. The GMS was successfully incorporated into the mine rescue exercises as planned, with very few problems encountered. 4 refs., 2 figs.

  2. New simulated gas detector offers realistic training for mine rescue teams

    International Nuclear Information System (INIS)

    Bealko, S.B.; Alexander, D.; Chasko, L.L.

    2010-01-01

    The National Institute for Occupational Safety and Health, together with LightsOn Safety Solutions, evaluated 2 versions of a multi-gas simulated gas monitor system (GMS) in separate field trials with mine rescue teams. This paper described the GMS wireless simulation tool along with its development and testing. It also described the GMS functions for the initial phase of testing as well as plans for the next phase of research which may introduce tracking and automation features. The GMS requires a personal computer and uses a wireless local area network. The GMS teaches mine rescue members about gas detection and helps them understand the importance of gas concentrations. In addition, it promotes decision-making actions by team members and offers a more realistic method of receiving gas concentration readings using a simulated hand-held gas detector. The purpose of the evaluation was to determine if the electronic placard in the GMS could be used by mine rescue teams instead of the currently used cardboard placards, and if the functionality of the device was suitable, reliable and practical. Results from the second field trial demonstrated improvements with the GMS over the original prototype technology, particularly with regards to wireless and connectivity issues. The GMS was successfully incorporated into the mine rescue exercises as planned, with very few problems encountered. 4 refs., 2 figs.

  3. Achievements in emergency medical rescue service, North-West ...

    African Journals Online (AJOL)

    2006-08-28

    Aug 28, 2006 ... In North-West province this process of provincialisation took place in ... Emergency Medical Rescue Service, Department of Health, North-West. Victor R .... recovery after CPR treatment should be started as soon as possible ...

  4. The Chemical Chaperone Phenylbutyrate Rescues MCT8 Mutations Associated With Milder Phenotypes in Patients With Allan-Herndon-Dudley Syndrome.

    Science.gov (United States)

    Braun, Doreen; Schweizer, Ulrich

    2017-03-01

    Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) prevent appropriate entry of thyroid hormones into brain cells during development and cause severe mental retardation in affected patients. The current treatment options are thyromimetic compounds that enter the brain independently of MCT8. Some MCT8-deficient patients (e.g., those carrying MCT8delF501) will not be as severely affected as most others. We have shown that the MCT8delF501 protein has decreased protein stability but important residual function once it reaches the plasma membrane. We were able to rescue protein expression and the function of MCT8delF501 in a Madin-Darby canine kidney cell model by application of the chemical chaperone sodium phenylbutyrate (NaPB), a drug that has been used to treat patients with cystic fibrosis and urea cycle defects for extended periods of time. In the present study, we have extended our previous study and report on the NaPB-dependent rescue of a series of other pathogenic MCT8 mutants associated with milder patient phenotypes. We show that NaPB can functionally rescue the expression and activities of Ser194Phe, Ser290Phe, Leu434Trp, Arg445Cys, Leu492Pro, and Leu568Pro mutations in MCT8 in a dose-dependent manner. The soy isoflavone genistein, a dietary supplement, which was effective in MCT8delF501, was also effective in increasing the expression and transport of these MCT8 mutants; however, the effect size differed among mutants. Kinetic analyses revealed that the Michaelis constants of the mutants toward the primary substrate 3,3',5-triiodothyronine were not much different from the wild-type value, suggesting that these mutants are not impaired in their interaction with substrate but rather destabilized by the mutation and degraded. Copyright © 2017 by the Endocrine Society.

  5. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  6. Functional Rescue of a Misfolded Drosophila melanogaster Dopamine Transporter Mutant Associated with a Sleepless Phenotype by Pharmacological Chaperones.

    Science.gov (United States)

    Kasture, Ameya; El-Kasaby, Ali; Szöllősi, Daniel; Asjad, H M Mazhar; Grimm, Alexandra; Stockner, Thomas; Hummel, Thomas; Freissmuth, Michael; Sucic, Sonja

    2016-09-30

    Folding-defective mutants of the human dopamine transporter (DAT) cause a syndrome of infantile dystonia/parkinsonism. Here, we provide a proof-of-principle that the folding deficit is amenable to correction in vivo by two means, the cognate DAT ligand noribogaine and the HSP70 inhibitor, pifithrin-μ. We examined the Drosophila melanogaster (d) mutant dDAT-G108Q, which leads to a sleepless phenotype in flies harboring this mutation. Molecular dynamics simulations suggested an unstable structure of dDAT-G108Q consistent with a folding defect. This conjecture was verified; heterologously expressed dDAT-G108Q and the human (h) equivalent hDAT-G140Q were retained in the endoplasmic reticulum in a complex with endogenous folding sensors (calnexin and HSP70-1A). Incubation of the cells with noribogaine (a DAT ligand selective for the inward-facing state) and/or pifithrin-μ (an HSP70 inhibitor) restored folding of, and hence dopamine transport by, dDAT-G108Q and hDAT-G140Q. The mutated versions of DAT were confined to the cell bodies of the dopaminergic neurons in the fly brain and failed to reach the axonal compartments. Axonal delivery was restored, and sleep time was increased to normal length (from 300 to 1000 min/day) if the dDAT-G108Q-expressing flies were treated with noribogaine and/or pifithrin-μ. Rescuing misfolded versions of DAT by pharmacochaperoning is of therapeutic interest; it may provide opportunities to remedy disorders arising from folding-defective mutants of human DAT and of other related SLC6 transporters. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Effect of late-stage therapy on disease progression in AAV-mediated rescue of photoreceptor cells in the retinoschisin-deficient mouse.

    Science.gov (United States)

    Janssen, Andreas; Min, Seok H; Molday, Laurie L; Tanimoto, Naoyuki; Seeliger, Mathias W; Hauswirth, William W; Molday, Robert S; Weber, Bernhard H F

    2008-06-01

    Proof-of-concept for a successful adeno-associated virus serotype 5 (AAV5)-mediated gene therapy in X-linked juvenile retinoschisis (XLRS) has been demonstrated in an established mouse model for this condition. The initial studies concentrated on early time-points of treatment. In this study, we aimed to explore the consequences of single subretinal injections administered at various stages of more advanced disease. By electroretinogram (ERG), functional improvement in treated versus untreated eyes is found to be significant in retinoschisin-deficient mice injected at the time-points of 15 days (P15), 1 month (PM1), and 2 months (PM2) after birth. In mice treated at 7 months after birth (PM7), an age previously shown to exhibit advanced retinal disease, ERG responses reveal no beneficial effects of vector treatment. Generally, functional rescue is paralleled by sustained retinoschisin expression and significant photoreceptor survival relative to untreated eyes. Quantitative measures of photoreceptors and peanut agglutinin-labeled ribbon synapses demonstrate rescue effects even in mice injected as late as PM7. Taken together, AAV5-mediated gene replacement is beneficial in slowing disease progression in murine XLRS. In addition, we show the effectiveness of rescue efforts even if treatment is delayed until advanced signs of disease have developed. Human XLRS patients might benefit from these findings, which suggest that the effectiveness of treatment appears not to be restricted to the early stages of the disease, and that treatment may prove to be valuable even when administered at more advanced stages.

  8. Post-traumatic stress disorder status in a rescue group after the Wenchuan earthquake relief.

    Science.gov (United States)

    Huang, Junhua; Liu, Qunying; Li, Jinliang; Li, Xuejiang; You, Jin; Zhang, Liang; Tian, Changfu; Luan, Rongsheng

    2013-07-15

    Previous studies have suggested that the incidence of post-traumatic stress disorder in earthquake rescue workers is relatively high. Risk factors for this disorder include demographic characteristics, earthquake-related high-risk factors, risk factors in the rescue process, personality, social support and coping style. This study examined the current status of a unit of 1 040 rescue workers who participated in earthquake relief for the Wenchuan earthquake that occurred on May 12(th), 2008. Post-traumatic stress disorder was diagnosed primarily using the Clinician-Administered Post-traumatic Stress Disorder Scale during structured interviews. Univariate and multivariate statistical analyses were used to examine major risk factors that contributed to the incidence of post-traumatic stress disorder. Results revealed that the incidence of this disorder in the rescue group was 5.96%. The impact factors in univariate analysis included death of family members, contact with corpses or witnessing of the deceased or seriously injured, near-death experience, severe injury or mental trauma in the rescue process and working at the epicenter of the earthquake. Correlation analysis suggested that post-traumatic stress disorder was positively correlated with psychotic and neurotic personalities, negative coping and low social support. Impact factors in multivariate logistic regression analysis included near-death experience, severe injury or mental trauma, working in the epicenter of the rescue, neurotic personality, negative coping and low social support, among which low social support had the largest odds ratio of 20.42. Findings showed that the occurrence of post-traumatic stress disorder was the result of the interaction of multiple factors.

  9. Post-traumatic stress disorder status in a rescue group after the Wenchuan earthquake relief

    Science.gov (United States)

    Huang, Junhua; Liu, Qunying; Li, Jinliang; Li, Xuejiang; You, Jin; Zhang, Liang; Tian, Changfu; Luan, Rongsheng

    2013-01-01

    Previous studies have suggested that the incidence of post-traumatic stress disorder in earthquake rescue workers is relatively high. Risk factors for this disorder include demographic characteristics, earthquake-related high-risk factors, risk factors in the rescue process, personality, social support and coping style. This study examined the current status of a unit of 1 040 rescue workers who participated in earthquake relief for the Wenchuan earthquake that occurred on May 12th, 2008. Post-traumatic stress disorder was diagnosed primarily using the Clinician-Administered Post-traumatic Stress Disorder Scale during structured interviews. Univariate and multivariate statistical analyses were used to examine major risk factors that contributed to the incidence of post-traumatic stress disorder. Results revealed that the incidence of this disorder in the rescue group was 5.96%. The impact factors in univariate analysis included death of family members, contact with corpses or witnessing of the deceased or seriously injured, near-death experience, severe injury or mental trauma in the rescue process and working at the epicenter of the earthquake. Correlation analysis suggested that post-traumatic stress disorder was positively correlated with psychotic and neurotic personalities, negative coping and low social support. Impact factors in multivariate logistic regression analysis included near-death experience, severe injury or mental trauma, working in the epicenter of the rescue, neurotic personality, negative coping and low social support, among which low social support had the largest odds ratio of 20.42. Findings showed that the occurrence of post-traumatic stress disorder was the result of the interaction of multiple factors. PMID:25206499

  10. Maternal Residential Exposure to Agricultural Pesticides and Birth Defects in a 2003 to 2005 North Carolina Birth Cohort

    Science.gov (United States)

    Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. We conducted a case-control study to estimate the associations between a residence-based metric of agr...

  11. UvA Rescue - Team Description Paper - Agent competition - Rescue Simulation League RoboCup 2014 - João Pessoa - Brazil

    NARCIS (Netherlands)

    Traichioiu, M.; Visser, A.

    2014-01-01

    This year's contribution of the UvA Rescue Team is twofold. On one hand a theoretical contribution is made by describing the planning and coordination problem formally as an POMDP problem, which will allow to apply POMDP-solution methods in this application area. On the other hand the impact of the

  12. A critical review of the Mediterranean sea turtle rescue network: a web looking for a weaver

    Directory of Open Access Journals (Sweden)

    Judith Ullmann

    2015-06-01

    Full Text Available A key issue in conservation biology is recognizing and bridging the gap between scientific results and specific action. We examine sea turtles—charismatic yet endangered flagship species—in the Mediterranean, a sea with historically high levels of exploitation and 22 coastal nations. We take sea turtle rescue facilities as a visible measure for implemented conservation action. Our study yielded 34 confirmed sea turtle rescue centers, 8 first-aid stations, and 7 informal rescue institutions currently in operation. Juxtaposing these facilities to known sea turtle distribution and threat hotspots reveals a clear disconnect. Only 14 of the 22 coastal countries had centers, with clear gaps in the Middle East and Africa. Moreover, the information flow between centers is apparently limited. The populations of the two species nesting in the Mediterranean, the loggerhead Caretta caretta and the green turtle Chelonia mydas, are far below historical levels and face a range of anthropogenic threats at sea and on land. Sea turtle rescue centers are acknowledged to reduce mortality in bycatch hotspots, provide a wealth of scientific data, and raise public awareness. The proposal for a Mediterranean-wide rescue network as published by the Regional Activity Centre for Specially Protected Areas a decade ago has not materialized in its envisioned scope. We discuss the efficiency, gaps, and needs for a rescue network and call for establishing additional rescue centers and an accompanying common online database to connect existing centers. This would provide better information on the number and types of rescue facilities on a Mediterranean scale, improve communication between these facilities, enhance standardization of procedures, yield large-scale data on the number of treated turtles and their injuries, and thus provide valuable input for targeted conservation measures.

  13. Rescuing Rover: A First Aid and Disaster Guide for Dog Owners

    OpenAIRE

    Heath, Sebastian E.

    1998-01-01

    Whether you're hiking with your canine friend in a remote area or work with a dog on a search-and-rescue team or police force, you need to be prepared for emergencies when veterinary service is not available. Rescuing Rover: A First Aid and Disaster Guide for Dog Owners provides dog owners, handlers, and emergency physicians with an understandable guide for safe treatment until the dog can be transported to a veterinarian. Although a number of books describe some techniques for the emergency ...

  14. Autonomous underwater vehicle for research and rescue operations

    CSIR Research Space (South Africa)

    Holtzhausen S

    2008-11-01

    Full Text Available Autonomous under water vehicles are ideal platforms for search and rescue operations. They can also be used for inspection of underwater terrains. These vehicles need to be autonomous and robust to cope with unpredictable current and high pressures...

  15. Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects

    Directory of Open Access Journals (Sweden)

    Swapnalee Sarmah

    2013-08-01

    Fetal alcohol spectrum disorder (FASD occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell, prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented that characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression was not affected by ethanol exposure, but E-cadherin distribution, which controls epiboly and gastrulation, was changed. E-cadherin was redistributed into cytoplasmic aggregates in blastomeres and dramatically redistributed in the extraembryonic yolk cell. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a, which controls epiboly, was significantly reduced in ethanol exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.

  16. Conservation and the 4 Rs, which are rescue, rehabilitation, release, and research.

    Science.gov (United States)

    Pyke, Graham H; Szabo, Judit K

    2018-02-01

    Vertebrate animals can be injured or threatened with injury through human activities, thus warranting their "rescue." Details of wildlife rescue, rehabilitation, release, and associated research (our 4 Rs) are often recorded in large databases, resulting in a wealth of available information. This information has huge research potential and can contribute to understanding of animal biology, anthropogenic impacts on wildlife, and species conservation. However, such databases have been little used, few studies have evaluated factors influencing success of rehabilitation and/or release, recommended actions to conserve threatened species have rarely arisen, and direct benefits for species conservation are yet to be demonstrated. We therefore recommend that additional research be based on data from rescue, rehabilitation, and release of animals that is broader in scope than previous research and would have community support. © 2017 Society for Conservation Biology.

  17. Transmission of feline immunodeficiency virus (FIV) among cohabiting cats in two cat rescue shelters.

    Science.gov (United States)

    Litster, Annette L

    2014-08-01

    Conflicting accounts have been published in the veterinary literature regarding transmission of feline immunodeficiency virus (FIV) between cohabiting cats in mixed households, and the mechanics of possible casual transmission, if it occurs, are poorly understood. Similarly, there are conflicting reports of vertical transmission of FIV. The aim of the present study was to document the FIV serological status of cats taken into two rescue shelters. At rescue shelter 1 (Rescue 1), cats cohabited in a multi-cat household of FIV-negative and naturally-infected, FIV-positive cats. A study was performed that combined a retrospective review of records of FIV serological status at intake (Test 1) and prospective FIV serological testing (Tests 2 and 3). Retrospective records were analyzed at rescue shelter 2 (Rescue 2), where FIV-positive queens with litters of nursing kittens were taken into the shelter, before being rehomed. FIV serology was performed on all kittens after weaning. Initial test results (Test 1) for 138 cohabiting cats from Rescue 1 showed that there were 130 FIV-negative cats and eight FIV-positive cats (six male neutered and two female spayed). A second test (Test 2), performed in 45 of the FIV-negative and five of the FIV-positive cats at median 28 months after Test 1 (range, 1 month to 8.8 years) showed that results were unchanged. Similarly, a third test (Test 3), performed in four of the original FeLV-negative cats and one remaining FIV-positive cat at median 38 months after Test 1 (range, 4 months to 4 years), also showed that results were unchanged. These results show a lack of evidence of FIV transmission, despite years of exposure to naturally-infected, FIV-positive cats in a mixed household. At Rescue 2, records were available from five FIV-positive queens with 19 kittens. All 19 kittens tested FIV-negative, suggesting that vertical transmission had not occurred. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Defect States Emerging from a Non-Hermitian Flatband of Photonic Zero Modes

    Science.gov (United States)

    Qi, Bingkun; Zhang, Lingxuan; Ge, Li

    2018-03-01

    We show the existence of a flatband consisting of photonic zero modes in a gain and loss modulated lattice system as a result of the underlying non-Hermitian particle-hole symmetry. This general finding explains the previous observation in parity-time symmetric systems where non-Hermitian particle-hole symmetry is hidden. We further discuss the defect states in these systems, whose emergence can be viewed as an unconventional alignment of a pseudospin under the influence of a complex-valued pseudomagnetic field. These defect states also behave as a chain with two types of links, one rigid in a unit cell and one soft between unit cells, as the defect states become increasingly localized with the gain and loss strength.

  19. The Cognitive Dissonance between Child Rescue and Child Protection

    NARCIS (Netherlands)

    K.E. Cheney (Kristen)

    2015-01-01

    textabstract‘Saving orphans’ has become an industry that irrevocably harms children and undermines the development of child welfare systems. We must replace the drive to rescue with the desire to protect.

  20. A space-based public service platform for terrestrial rescue operations

    Science.gov (United States)

    Fleisig, R.; Bernstein, J.; Cramblit, D. C.

    1977-01-01

    The space-based Public Service Platform (PSP) is a multibeam, high-gain communications relay satellite that can provide a variety of functions for a large number of people on earth equipped with extremely small, very low cost transceivers. This paper describes the PSP concept, the rationale used to derive the concept, the criteria for selecting specific communication functions to be performed, and the advantages of performing such functions via satellite. The discussion focuses on the benefits of using a PSP for natural disaster warning; control of attendant rescue/assistance operations; and rescue of people in downed aircraft, aboard sinking ships, lost or injured on land.

  1. Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-κB pathway in irradiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Lam, R.K.K. [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); Han, Wei [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong (Hong Kong)

    2015-12-15

    Highlights: • Rescue effect was observed in both irradiated and HeLa and NIH/3T3 cells. • Novel setup and procedures to separate the rescue signals and the bystander signals. • Confirmed activation of NF-κB pathway in rescue effect using activation inhibitor. • Confirmed activation of NF-κB pathway in rescue effect using anti-NF-κB p65 antibody. - Abstract: We studied the involvement of NF-κB pathway activation in the rescue effect in HeLa and NIH/3T3 cells irradiated by α particles. Firstly, upon irradiation by 5 cGy of α particles, for both cell lines, the numbers of 53BP1 foci/cell at 12 h post-irradiation were significantly smaller when only 2.5% of the cell population was irradiated as compared to 100% irradiation, which demonstrated the rescue effect. Secondly, we studied the effect of NF-κB on the rescue effect through the use of the NF-κB activation inhibitor BAY-11-7082. Novel experimental setup and procedures were designed to prepare the medium (CM) which had conditioned the bystander cells previously partnered with irradiated cells, to ensure physical separation between rescue and bystander signals. BAY-11-7082 itself did not inflict DNA damages in the cells or have effects on activation of the NF-κB response pathway in the irradiated cells through direct irradiation. The rescue effect was induced in both cell lines by the CM, which was abrogated if BAY-11-7082 was added to the CM. Thirdly, we studied the effect of NF-κB on the rescue effect through staining for phosphorylated NF-κB (p-NF-κB) expression using the anti-NF-κB p65 (phospho S536) antibody. When the fraction of irradiated cells dropped from 100% to 2.5%, the p-NF-κB expression in the cell nuclei of irradiated NIH/3T3 cells increased significantly, while that in the cell nuclei of irradiated HeLa cells also increased although not significantly. Moreover, the p-NF-κB expression in the cell nuclei of irradiated HeLa cells and NIH/3T3 cells treated with CM also increased

  2. Birth Defects

    Science.gov (United States)

    A birth defect is a problem that happens while a baby is developing in the mother's body. Most birth defects happen during the first 3 months of ... in the United States is born with a birth defect. A birth defect may affect how the ...

  3. The Algorithm of Link Prediction on Social Network

    Directory of Open Access Journals (Sweden)

    Liyan Dong

    2013-01-01

    Full Text Available At present, most link prediction algorithms are based on the similarity between two entities. Social network topology information is one of the main sources to design the similarity function between entities. But the existing link prediction algorithms do not apply the network topology information sufficiently. For lack of traditional link prediction algorithms, we propose two improved algorithms: CNGF algorithm based on local information and KatzGF algorithm based on global information network. For the defect of the stationary of social network, we also provide the link prediction algorithm based on nodes multiple attributes information. Finally, we verified these algorithms on DBLP data set, and the experimental results show that the performance of the improved algorithm is superior to that of the traditional link prediction algorithm.

  4. Rescuing Downed Aircrews: The Value of Time

    Science.gov (United States)

    2015-01-01

    Make a tax -deductible charitable contribution at www.rand.org/giving/contribute www.rand.org Library of Congress Control Number: 2015955037 ISBN...Predictors of Survival and Evasion ............................................................ 40   Table 5.2. Regression Predictors...a damaged aircraft, and the ability to avoid immediate capture. Combat rescue records and anecdotal evidence show that if the pilot were able to

  5. The goal(s) of corporate rescue in company law: A comparative analysis

    OpenAIRE

    Anthony O. Nwafor

    2017-01-01

    The concept of corporate rescue lays emphasis on corporate sustainability than liquidation. This trend in corporate legislation which featured in the United Kingdom Insolvency Act of 1986, Australian Corporations Act 2001, Indian Sick Industrial Companies (Special Provisions) Act of 1985 (as replaced by Companies Act, 2013 and supplanted by the Insolvency and Bankruptcy Code, 2016) has been adopted in the South African Companies Act of 2008. The goal(s) of corporate rescue in some of these ju...

  6. Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome.

    Directory of Open Access Journals (Sweden)

    Jennifer L Daily

    Full Text Available Angelman syndrome (AS, a genetic disorder occurring in approximately one in every 15,000 births, is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. However, we have determined that abnormal calcium/calmodulin-dependent protein kinase II (CaMKII regulation is seen in the maternal UBE3A deletion AS mouse model and is responsible for the major phenotypes. Specifically, there is an increased αCaMKII phosphorylation at the autophosphorylation sites Thr(286 and Thr(305/306, resulting in an overall decrease in CaMKII activity. CaMKII is not produced until after birth, indicating that the deficits associated with AS are not the result of developmental abnormalities. The present studies are focused on exploring the potential to rescue the learning and memory deficits in the adult AS mouse model through the use of an adeno-associated virus (AAV vector to increase neuronal UBE3A expression. These studies show that increasing the levels of E6-AP in the brain using an exogenous vector can improve the cognitive deficits associated with AS. Specifically, the associative learning deficit was ameliorated in the treated AS mice compared to the control AS mice, indicating that therapeutic intervention may be possible in older AS patients.

  7. Rescue of Long-Tail Data from the Ocean Bottom to the Moon

    Science.gov (United States)

    Hsu, L.; Lehnert, K. A.; Carbotte, S. M.; Ferrini, V.; Delano, J. W.; Gill, J. B.; Tivey, M.

    2013-12-01

    IEDA (Integrated Earth Data Applications, www.iedadata.org), the NSF facility that operates EarthChem, the Marine Geoscience Data System, and the System for Earth Sample Registration, launched a Data Rescue Initiative in 2013 to advance preservation and re-use of valuable legacy datasets that are in danger of being lost. As part of this initiative, IEDA established a competition for Data Rescue Mini-Awards that provide modest funds to investigators to properly compile, document, and transfer legacy data sets to IEDA. Applications from late-career and near-retirement investigators were specifically encouraged. Awardees were given approximately six months to complete their data rescue activities. Three projects were awarded in 2013: (1) Geochemistry of Lunar Glasses: assembly of major element, trace element, volatile element, and isotope ratio data for lunar volcanic glasses and lunar impact glasses, (2) Geochemical and Geochronological data from Fiji, Izu-Bonin-Marianas, and Endeavor segment: assembly of published and unpublished data and metadata from large rock sample collections, and (3) Near-bottom Magnetic Data: curation and archival of 35 years of high-resolution, near-bottom magnetic field data from deeptowed platforms, submersibles, and ROVs. IEDA is working closely with the awardees to guide and support the data rescue effort and to assist with specific challenges related to outdated storage media or technology, diversity of platforms over decades of research, and the lack of established standards for data documentation. In this contribution we describe procedures and tools used for each project, summarize lessons learned and best practices, and present the final output of each data rescue project. Depending on the experiences of this first year and the availability of funds, we plan to continue the competition in future years.

  8. 50 CFR 23.79 - How may I participate in the Plant Rescue Center Program?

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false How may I participate in the Plant Rescue Center Program? 23.79 Section 23.79 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE... may I participate in the Plant Rescue Center Program? (a) Purpose. We have established the Plant...

  9. Rescuing Quadratic Inflation

    CERN Document Server

    Ellis, John; Sueiro, Maria

    2014-01-01

    Inflationary models based on a single scalar field $\\phi$ with a quadratic potential $V = \\frac{1}{2} m^2 \\phi^2$ are disfavoured by the recent Planck constraints on the scalar index, $n_s$, and the tensor-to-scalar ratio for cosmological density perturbations, $r_T$. In this paper we study how such a quadratic inflationary model can be rescued by postulating additional fields with quadratic potentials, such as might occur in sneutrino models, which might serve as either curvatons or supplementary inflatons. Introducing a second scalar field reduces but does not remove the pressure on quadratic inflation, but we find a sample of three-field models that are highly compatible with the Planck data on $n_s$ and $r_T$. We exhibit a specific three-sneutrino example that is also compatible with the data on neutrino mass difference and mixing angles.

  10. That Others May Live: USAF Air Rescue in Korea

    National Research Council Canada - National Science Library

    Marion, Forrest L

    2004-01-01

    When the Korean War began in June 1950, the United States Air Force's Air Rescue Service was a fledgling organization possessing a variety of aircraft types, most having seen service during World War II...

  11. Water Supply Systems For Aircraft Fire And Rescue Protection

    Science.gov (United States)

    1995-01-01

    This Advisory Circular (AC) provides guidance for the selection : of a water source and standards for the design of a distribution system to : support aircraft rescue and fire fighting (ARFF) service operations on : airports.

  12. Human cathepsin L rescues the neurodegeneration and lethality incathepsin B/L double deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Sevenich, Lisa; Pennacchio, Len A.; Peters, Christoph; Reinheckel, Thomas

    2006-01-09

    Cathepsin B (CTSB) and cathepsin L (CTSL) are two widelyexpressed cysteine proteases thought to predominantly reside withinlysosomes. Functional analysis of CTSL in humans is complicated by theexistence of two CTSL-like homologues (CTSL and CTSL2), in contrast tomice which contain only one CTSL enzyme. Thus transgenic expression ofhuman CTSL in CTSL deficient mice provides an opportunity to study the invivo functions of this human protease without interference by its highlyrelated homologue. While mice with single gene deficiencies for murineCTSB or CTSL survive without apparent neuromuscular impairment, murineCTSB/CTSL double deficient mice display degeneration of cerebellarPurkinje cells and neurons of the cerebral cortex, resulting in severehypotrophy, motility defects, and lethality during their third to fourthweek of life. Here we show that expression of human CTSL through agenomic transgene results in widespread expression of human CTSL in themouse which is capable of rescuing the lethality found in CTSB/CTSLdouble-deficient animals. Human CTSL is expressed in the brain of thesecompound mutants predominantly in neurons of the cerebral cortex and inPurkinje cells of the cerebellum, where it appears to prevent neuronalcell death.

  13. A portable continuous blood purification machine for emergency rescue in disasters.

    Science.gov (United States)

    He, Ping; Zhou, Chunhua; Li, Hongyan; Yu, Yongwu; Dong, Zhen; Wen, Yuanyuan; Li, Ping; Tang, Wenhong; Wang, Xue

    2012-01-01

    Continuous renal replacement therapy plays an important role in emergency rescue. Currently, no continuous renal replacement therapy machine can be used under unstable conditions as the fluid flow of these machines is controlled electronically. A novel machine that can provide emergency continuous renal replacement therapy in disaster rescue is therefore needed. Based on a volumetric metering method, a prototype portable continuous blood purifier based on a volumetric metering method was developed. Basic performance tests, special environmental tests, animal experiments and clinical use of the novel machine were completed to test and verify its performance under unstable conditions. All tests completed showed that the machine met the requirements of the national industry standards with a size reduced to approximately one half of the Baxter Aquarius machine. The clearance of harmful substances by the machine described here was equal to that of the Baxter Aquarius machine and was adequate for clinical purposes. The novel prototype performed well in all situations tested and can aid rescue work on disaster sites. Copyright © 2012 S. Karger AG, Basel.

  14. Emergency Preparedness and Role Clarity among Rescue Workers during the Terror Attacks in Norway July 22, 2011.

    Directory of Open Access Journals (Sweden)

    May Janne Botha Pedersen

    Full Text Available Few studies address preparedness and role clarity in rescue workers after a disaster. On July 22, 2011, Norway was struck by two terror attacks; 77 people were killed and many injured. Healthcare providers, police officers and firefighters worked under demanding conditions. The aims of this study were to examine the level of preparedness, exposure and role clarity. In addition, the relationship between demographic variables, preparedness and exposure and a role clarity during the rescue operations and; b achieved mastering for future disaster operations.In this cross-sectional study, healthcare providers (n = 859, police officers (n = 252 and firefighters (n = 102 returned a questionnaire approximately 10 months after the terror attacks.The rescue personnel were trained and experienced, and the majority knew their professional role (healthcare providers M = 4.1 vs. police officers: M = 3.9 vs. firefighters: M = 4.2, p 5 fatalities (OR 1.6, p < .05 were all associated with role clarity, together with a feeling of control, not being obstructed in work and perceiving the rescue work as a success. Moreover, independent predictors of being more prepared for future operations were arousal during the operation (OR 2.0, p < .001 and perceiving the rescue work as a success (OR 1.5, p < .001.Most of the rescue workers were experienced and knew their professional role. Training and everyday-work-experience must be a focal point when preparing rescue workers for disaster.

  15. UvA Rescue Technical Report: a description of the methods and algorithms implemented in the UvA Rescue code release

    NARCIS (Netherlands)

    Visser, A.

    2012-01-01

    This technical report gives the background documentation behind the competition code of the UvA Rescue Team, who participates in the RoboCup Simulation League. The described code is used in the Virtual Robot competition, where a team of robots, guided by a single operator, has to find as many

  16. Expectations of a business rescue plan: international directives for ...

    African Journals Online (AJOL)

    Kirstam

    2014-09-01

    Sep 1, 2014 ... 10Key words: business rescue, South African Companies Act, business ... countries such as Germany, Australia, the United Kingdom (UK) and ...... operating statistics and detailed cash flow projections is needed for sound risk.

  17. Congenital Heart Defects and Receipt of Special Education Services.

    Science.gov (United States)

    Riehle-Colarusso, Tiffany; Autry, Andrew; Razzaghi, Hilda; Boyle, Coleen A; Mahle, William T; Van Naarden Braun, Kim; Correa, Adolfo

    2015-09-01

    We investigated the prevalence of receipt of special education services among children with congenital heart defects (CHDs) compared with children without birth defects. Children born from 1982 to 2004 in metropolitan Atlanta with CHDs (n = 3744) were identified from a population-based birth defect surveillance program; children without birth defects (n = 860 715) were identified from birth certificates. Cohorts were linked to special education files for the 1992-2012 school years to identify special education services. Children with noncardiac defects or genetic syndromes were excluded; children with CHDs were classified by presence or absence of critical CHDs (ie, CHDs requiring intervention by age one year). We evaluated the prevalence of receipt of special education services and prevalence rate ratios using children without birth defects as a reference. Compared with children without birth defects, children with CHDs were 50% more likely to receive special education services overall (adjusted prevalence rate ratio [aPRR] = 1.5; 95% confidence interval [CI]: 1.4-1.7). Specifically, they had higher prevalence of several special education categories including: intellectual disability (aPRR = 3.8; 95% CI: 2.8-5.1), sensory impairment (aPRR = 3.0; 95% CI: 1.8-5.0), other health impairment (aPRR = 2.8; 95% CI: 2.2-3.5), significant developmental delay (aPRR = 1.9; 95% CI: 1.3-2.8), and specific learning disability (aPRR = 1.4; 95% CI: 1.1-1.7). For most special education services, the excess prevalence did not vary by presence of critical CHDs. Children with CHDs received special education services more often than children without birth defects. These findings highlight the need for special education services and the importance of developmental screening for all children with CHDs. Copyright © 2015 by the American Academy of Pediatrics.

  18. Analgesic effect of bupivacaine eluting porcine small intestinal submucosa (SIS) in ferrets undergoing acute abdominal hernia defect surgery.

    Science.gov (United States)

    Johnson, Brenda M; Ko, Jeff C; Hall, Paul J; Saunders, Alan T; Lantz, Gary C

    2011-05-15

    Porcine small intestinal submucosa (SIS) is used as a biological implant for abdominal wall hernia repair to facilitate wound healing and augment local tissue strength. This prospective, randomized, blinded study evaluated local pain control provided by bupivacaine adsorbed to SIS for repair of acutely created abdominal wall full thickness muscle/fascial defects in ferrets. Eighteen healthy ferrets were randomly and equally assigned to three groups: (1) SIS with bupivacaine subjected to surgery, (2) SIS with no bupivacaine subjected to surgery, and (3) anesthesia only control group. Ferrets in groups 1 and 2 were anesthetized with butorphanol and sevoflurane for the surgery. Control ferrets were anesthetized in the same fashion for the same duration without surgery. Behavior and pain were evaluated in all ferrets by behavioral observation, algometer, and palpometer measurements, and heart and respiratory rates each obtained before surgery and at various intervals for 96 h after surgery. When pain reached a predetermined threshold, buprenorphine was used as a rescue analgesic. The serum and combined tissue concentrations of bupivacaine were analyzed. Overall, the palpometer testing was better tolerated in the bupivacaine treated SIS group than by the untreated SIS group (P = 0.04). There was an observed physiologically significant difference in algometer and other palpometer readings as well as heart and respiratory rates. All ferrets in the untreated SIS group were rescued while 33% of the SIS-bupivacaine groups were rescued (P pain relief over 2-4 days with no clinical adverse effects observed in the ferrets. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Intelligent systems for urban search and rescue: challenges and lessons learned

    Science.gov (United States)

    Jacoff, Adam; Messina, Elena; Weiss, Brian A.

    2003-09-01

    Urban search and rescue (USAR) is one of the most dangerous and time-critical non-wartime activities. Researchers have been developing hardware and software to enable robots to perform some search and rescue functions so as to minimize the exposure of human rescue personnel to danger and maximize the survival of victims. Significant progress has been achieved, but much work remains. USAR demands a blending of numerous specialized technologies. An effective USAR robot must be endowed with key competencies, such as being able to negotiate collapsed structures, find victims and assess their condition, identify potential hazards, generate maps of the structure and victim locations, and communicate with rescue personnel. These competencies bring to bear work in numerous sub-disciplines of intelligent systems (or artificial intelligence) such as sensory processing, world modeling, behavior generation, path planning, and human-robot interaction, in addition to work in communications, mechanism design and advanced sensors. In an attempt to stimulate progress in the field, reference USAR challenges are being developed and propagated worldwide. In order to make efficient use of finite research resources, the robotic USAR community must share a common understanding of what is required, technologically, to attain each competency, and have a rigorous measure of the current level of effectiveness of various technologies. NIST is working with partner organizations to measure the performance of robotic USAR competencies and technologies. In this paper, we describe the reference test arenas for USAR robots, assess the current challenges within the field, and discuss experiences thus far in the testing effort.

  20. CDKL5 protein substitution therapy rescues neurological phenotypes of a mouse model of CDKL5 disorder.

    Science.gov (United States)

    Trazzi, Stefania; De Franceschi, Marianna; Fuchs, Claudia; Bastianini, Stefano; Viggiano, Rocchina; Lupori, Leonardo; Mazziotti, Raffaele; Medici, Giorgio; Lo Martire, Viviana; Ren, Elisa; Rimondini, Roberto; Zoccoli, Giovanna; Bartesaghi, Renata; Pizzorusso, Tommaso; Ciani, Elisabetta

    2018-05-01

    Cyclin-dependent kinase like-5 (CDKL5) disorder is a rare neurodevelopmental disease caused by mutations in the CDKL5 gene. The consequent misexpression of the CDKL5 protein in the nervous system leads to a severe phenotype characterized by intellectual disability, motor impairment, visual deficits and early-onset epilepsy. No therapy is available for CDKL5 disorder. It has been reported that a protein transduction domain (TAT) is able to deliver macromolecules into cells and even into the brain when fused to a given protein. We demonstrate that TAT-CDKL5 fusion protein is efficiently internalized by target cells and retains CDKL5 activity. Intracerebroventricular infusion of TAT-CDKL5 restored hippocampal development, hippocampus-dependent memory and breathing pattern in Cdkl5-null mice. Notably, systemically administered TAT-CDKL5 protein passed the blood-brain-barrier, reached the CNS, and rescued various neuroanatomical and behavioral defects, including breathing pattern and visual responses. Our results suggest that CDKL5 protein therapy may be an effective clinical tool for the treatment of CDKL5 disorder.

  1. Influencing factors of embryo rescue in seedless grape

    International Nuclear Information System (INIS)

    Guo, X.; Chen, W.; Liu, Z.; Li, K.

    2015-01-01

    In this study, we investigated the impact of inoculating stage, medium type and concentration of plant growth regulators on embryo rescue effectiveness by L25(5)6 orthogonal design using selfed ovules of Venus Seedless as the testing material. The main results were as follows. The most important factor influencing ovule germination was inoculating stage. Ovule germinating rate gradually increased as inoculating being postponed. The highest germinating rate appeared when inoculation was done 55d after flowering. Other influencing factors were IBA concentration, exogenous amino acid, 6-BA concentration, GA3 concentration and medium type in descending order. The best embryo rescue result was based on Nitsch medium including 1.0 mg/L IBA, 0.1 mg/L GA3, 0.7 mg /L 6-BA and 2.0 mmol/L glutamine using ovules inoculated 55d after flowering. The highest germinating rate reached 41.25%, and a batch of seedlings was also obtained. (author)

  2. Risk assessment for pipelines with active defects based on artificial intelligence methods

    Energy Technology Data Exchange (ETDEWEB)

    Anghel, Calin I. [Department of Chemical Engineering, Faculty of Chemistry and Chemical Engineering, University ' Babes-Bolyai' , Cluj-Napoca (Romania)], E-mail: canghel@chem.ubbcluj.ro

    2009-07-15

    The paper provides another insight into the pipeline risk assessment for in-service pressure piping containing defects. Beside of the traditional analytical approximation methods or sampling-based methods safety index and failure probability of pressure piping containing defects will be obtained based on a novel type of support vector machine developed in a minimax manner. The safety index or failure probability is carried out based on a binary classification approach. The procedure named classification reliability procedure, involving a link between artificial intelligence and reliability methods was developed as a user-friendly computer program in MATLAB language. To reveal the capacity of the proposed procedure two comparative numerical examples replicating a previous related work and predicting the failure probabilities of pressured pipeline with defects were presented.

  3. Risk assessment for pipelines with active defects based on artificial intelligence methods

    International Nuclear Information System (INIS)

    Anghel, Calin I.

    2009-01-01

    The paper provides another insight into the pipeline risk assessment for in-service pressure piping containing defects. Beside of the traditional analytical approximation methods or sampling-based methods safety index and failure probability of pressure piping containing defects will be obtained based on a novel type of support vector machine developed in a minimax manner. The safety index or failure probability is carried out based on a binary classification approach. The procedure named classification reliability procedure, involving a link between artificial intelligence and reliability methods was developed as a user-friendly computer program in MATLAB language. To reveal the capacity of the proposed procedure two comparative numerical examples replicating a previous related work and predicting the failure probabilities of pressured pipeline with defects were presented.

  4. A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects.

    Directory of Open Access Journals (Sweden)

    Katherine Stewart

    2016-02-01

    Full Text Available Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase-activating proteins (GAPs, including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease.

  5. Neutral sphingomyelinase (SMPD3) deficiency causes a novel form of chondrodysplasia and dwarfism that is rescued by Col2A1-driven smpd3 transgene expression.

    Science.gov (United States)

    Stoffel, Wilhelm; Jenke, Britta; Holz, Barbara; Binczek, Erika; Günter, Robert Heinz; Knifka, Jutta; Koebke, Jürgen; Niehoff, Anja

    2007-07-01

    Neutral sphingomyelinase SMPD3 (nSMase2), a sphingomyelin phosphodiesterase, resides in the Golgi apparatus and is ubiquitously expressed. Gene ablation of smpd3 causes a generalized prolongation of the cell cycle that leads to late embryonic and juvenile hypoplasia because of the SMPD3 deficiency in hypothalamic neurosecretory neurons. We show here that this novel form of combined pituitary hormone deficiency is characterized by the perturbation of the hypothalamus-pituitary growth axis, associated with retarded chondrocyte development and enchondral ossification in the epiphyseal growth plate. To study the contribution by combined pituitary hormone deficiency and by the local SMPD3 deficiency in the epiphyseal growth plate to the skeletal phenotype, we introduced the full-length smpd3 cDNA transgene under the control of the chondrocyte-specific promoter Col2a1. A complete rescue of the smpd3(-/-) mouse from severe short-limbed skeletal dysplasia was achieved. The smpd3(-/-) mouse shares its dwarf and chondrodysplasia phenotype with the most common form of human achondrodysplasia, linked to the fibroblast-growth-factor receptor 3 locus, not linked to deficits in the hypothalamic-pituitary epiphyseal growth plate axis. The rescue of smpd3 in vivo has implications for future research into dwarfism and, particularly, growth and development of the skeletal system and for current screening and future treatment of combined dwarfism and chondrodysplasia.

  6. Neutral Sphingomyelinase (SMPD3) Deficiency Causes a Novel Form of Chondrodysplasia and Dwarfism That Is Rescued by Col2A1-Driven smpd3 Transgene Expression

    Science.gov (United States)

    Stoffel, Wilhelm; Jenke, Britta; Holz, Barbara; Binczek, Erika; Günter, Robert Heinz; Knifka, Jutta; Koebke, Jürgen; Niehoff, Anja

    2007-01-01

    Neutral sphingomyelinase SMPD3 (nSMase2), a sphingomyelin phosphodiesterase, resides in the Golgi apparatus and is ubiquitously expressed. Gene ablation of smpd3 causes a generalized prolongation of the cell cycle that leads to late embryonic and juvenile hypoplasia because of the SMPD3 deficiency in hypothalamic neurosecretory neurons. We show here that this novel form of combined pituitary hormone deficiency is characterized by the perturbation of the hypothalamus-pituitary growth axis, associated with retarded chondrocyte development and enchondral ossification in the epiphyseal growth plate. To study the contribution by combined pituitary hormone deficiency and by the local SMPD3 deficiency in the epiphyseal growth plate to the skeletal phenotype, we introduced the full-length smpd3 cDNA transgene under the control of the chondrocyte-specific promoter Col2a1. A complete rescue of the smpd3−/− mouse from severe short-limbed skeletal dysplasia was achieved. The smpd3−/− mouse shares its dwarf and chondrodysplasia phenotype with the most common form of human achondrodysplasia, linked to the fibroblast-growth-factor receptor 3 locus, not linked to deficits in the hypothalamic-pituitary epiphyseal growth plate axis. The rescue of smpd3 in vivo has implications for future research into dwarfism and, particularly, growth and development of the skeletal system and for current screening and future treatment of combined dwarfism and chondrodysplasia. PMID:17591962

  7. Evolutionary rescue of a parasite population by mutation rate evolution.

    Science.gov (United States)

    Greenspoon, Philip B; Mideo, Nicole

    2017-10-01

    The risk of antibiotic resistance evolution in parasites is a major problem for public health. Identifying factors which promote antibiotic resistance evolution is thus a priority in evolutionary medicine. The rate at which new mutations enter the parasite population is one important predictor; however, mutation rate is not necessarily a fixed quantity, as is often assumed, but can itself evolve. Here we explore the possible impacts of mutation rate evolution on the fate of a disease circulating in a host population, which is being treated with drugs, the use of which varies over time. Using an evolutionary rescue framework, we find that mutation rate evolution provides a dramatic increase in the probability that a parasite population survives treatment in only a limited region, while providing little or no advantage in other regions. Both epidemiological features, such as the virulence of infection, and population genetic parameters, such as recombination rate, play important roles in determining the probability of evolutionary rescue and whether mutation rate evolution enhances the probability of evolutionary rescue or not. While efforts to curtail mutation rate evolution in parasites may be worthwhile under some circumstances, our results suggest that this need not always be the case. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Parental mental illness and fatal birth defects in a national birth cohort

    DEFF Research Database (Denmark)

    Webb, Roger; Pickles, A.R.; King-Hele, Sarah

    2007-01-01

    BACKGROUND: Few large studies describe links between maternal mental illness and risk of major birth defect in offspring. Evidence is sparser still for how effects vary between maternal diagnoses and no previous study has assessed risk with paternal illnesses.MethodA population-based birth cohort...... genetic effects directly linked with maternal illness, lifestyle factors (diet, smoking, alcohol and drugs), poor antenatal care, psychotropic medication toxicity, and gene-environment interactions. Further research is needed to elucidate the causal mechanisms...

  9. Ensemble-based computational approach discriminates functional activity of p53 cancer and rescue mutants.

    Directory of Open Access Journals (Sweden)

    Özlem Demir

    2011-10-01

    Full Text Available The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain ("cancer mutants". Activity can be restored by second-site suppressor mutations ("rescue mutants". This paper relates the functional activity of p53 cancer and rescue mutants to their overall molecular dynamics (MD, without focusing on local structural details. A novel global measure of protein flexibility for the p53 core DNA-binding domain, the number of clusters at a certain RMSD cutoff, was computed by clustering over 0.7 µs of explicitly solvated all-atom MD simulations. For wild-type p53 and a sample of p53 cancer or rescue mutants, the number of clusters was a good predictor of in vivo p53 functional activity in cell-based assays. This number-of-clusters (NOC metric was strongly correlated (r(2 = 0.77 with reported values of experimentally measured ΔΔG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i p53 cancer mutants were more flexible than wild-type protein, (ii second-site rescue mutations decreased the flexibility of cancer mutants, and (iii negative controls of non-rescue second-site mutants did not. This new method reflects the overall stability of the p53 core domain and can discriminate which second-site mutations restore activity to p53 cancer mutants.

  10. NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

    Science.gov (United States)

    Sequerra, Eduardo B; Goyal, Raman; Castro, Patricio A; Levin, Jacqueline B; Borodinsky, Laura N

    2018-05-16

    Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy. Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.

  11. A concept for optimizing avalanche rescue strategies using a Monte Carlo simulation approach.

    Directory of Open Access Journals (Sweden)

    Ingrid Reiweger

    Full Text Available Recent technical and strategical developments have increased the survival chances for avalanche victims. Still hundreds of people, primarily recreationists, get caught and buried by snow avalanches every year. About 100 die each year in the European Alps-and many more worldwide. Refining concepts for avalanche rescue means to optimize the procedures such that the survival chances are maximized in order to save the greatest possible number of lives. Avalanche rescue includes several parameters related to terrain, natural hazards, the people affected by the event, the rescuers, and the applied search and rescue equipment. The numerous parameters and their complex interaction make it unrealistic for a rescuer to take, in the urgency of the situation, the best possible decisions without clearly structured, easily applicable decision support systems. In order to analyse which measures lead to the best possible survival outcome in the complex environment of an avalanche accident, we present a numerical approach, namely a Monte Carlo simulation. We demonstrate the application of Monte Carlo simulations for two typical, yet tricky questions in avalanche rescue: (1 calculating how deep one should probe in the first passage of a probe line depending on search area, and (2 determining for how long resuscitation should be performed on a specific patient while others are still buried. In both cases, we demonstrate that optimized strategies can be calculated with the Monte Carlo method, provided that the necessary input data are available. Our Monte Carlo simulations also suggest that with a strict focus on the "greatest good for the greatest number", today's rescue strategies can be further optimized in the best interest of patients involved in an avalanche accident.

  12. Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis.

    Science.gov (United States)

    Esposito, Speranza; Tosco, Antonella; Villella, Valeria R; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

    2016-12-01

    Cystic fibrosis (CF) is a lethal monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that entails the (diagnostic) increase in sweat electrolyte concentrations, progressive lung disease with chronic inflammation and recurrent bacterial infections, pancreatic insufficiency, and male infertility. Therapies aimed at restoring the CFTR defect have emerged. Thus, a small molecule which facilitates chloride channel opening, the potentiator Ivacaftor, has been approved for the treatment of CF patients bearing a particular class of rare CFTR mutations. However, small molecules that directly target the most common misfolded CFTR mutant, F508del, and improve its intracellular trafficking in vitro, have been less effective than expected when tested in CF patients, even in combination with Ivacaftor. Thus, new strategies are required to circumvent the F508del-CFTR defect. Airway and intestinal epithelial cells from CF patients bearing the F508del-CFTR mutation exhibit an impressive derangement of cellular proteostasis, with oxidative stress, overactivation of the tissue transglutaminase (TG2), and disabled autophagy. Proteostasis regulators such as cysteamine can rescue and stabilize a functional F508del-CFTR protein through suppressing TG2 activation and restoring autophagy in vivo in F508del-CFTR homozygous mice, in vitro in CF patient-derived cell lines, ex vivo in freshly collected primary patient's nasal cells, as well as in a pilot clinical trial involving homozygous F508del-CFTR patients. Here, we discuss how the therapeutic normalization of defective proteostasis can be harnessed for the treatment of CF patients with the F508del-CFTR mutation.

  13. Late Maternal Folate Supplementation Rescues from Methyl Donor Deficiency-Associated Brain Defects by Restoring Let-7 and miR-34 Pathways.

    Science.gov (United States)

    Geoffroy, Andréa; Kerek, Racha; Pourié, Grégory; Helle, Déborah; Guéant, Jean-Louis; Daval, Jean-Luc; Bossenmeyer-Pourié, Carine

    2017-09-01

    The micronutrients folate and vitamin B12 are essential for the proper development of the central nervous system, and their deficiency during pregnancy has been associated with a wide range of disorders. They act as methyl donors in the one-carbon metabolism which critically influences epigenetic mechanisms. In order to depict further underlying mechanisms, we investigated the role of let-7 and miR-34, two microRNAs regulated by methylation, on a rat model of maternal deficiency. In several countries, public health policies recommend periconceptional supplementation with folic acid. However, the question about the duration and periodicity of supplementation remains. We therefore tested maternal supply (3 mg/kg/day) during the last third of gestation from embryonic days (E) 13 to 20. Methyl donor deficiency-related developmental disorders at E20, including cerebellar and interhemispheric suture defects and atrophy of selective cerebral layers, were associated with increased brain expression (by 2.5-fold) of let-7a and miR-34a, with subsequent downregulation of their regulatory targets such as Trim71 and Notch signaling partners, respectively. These processes could be reversed by siRNA strategy in differentiating neuroprogenitors lacking folate, with improvement of their morphological characteristics. While folic acid supplementation helped restoring the levels of let-7a and miR-34a and their downstream targets, it led to a reduction of structural and functional defects taking place during the perinatal period. Our data outline the potential role of let-7 and miR-34 and their related signaling pathways in the developmental defects following gestational methyl donor deficiency and support the likely usefulness of late folate supplementation in at risk women.

  14. Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort.

    Science.gov (United States)

    Rappazzo, Kristen M; Warren, Joshua L; Meyer, Robert E; Herring, Amy H; Sanders, Alison P; Brownstein, Naomi C; Luben, Thomas J

    2016-04-01

    Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240-249, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Assessment of exposure to carbon monoxide group of firefighters from fire fighting and rescue units

    Directory of Open Access Journals (Sweden)

    Jadwiga Lembas-Bogaczyk

    2011-03-01

    Full Text Available Firemen threat during fire burning of chemical substances indicated presence of carbon monoxide (CO in all cases. Carbon monoxide causes death of fire. Inhaled through respiratory system, links with hemoglobin, thus blocking transport and distribution of oxygen in the body. This leads to tissue anoxia, which is a direct threat to firefighters’ life. The purpose of this study was to assess the exposure to carbon monoxide of participating firefighters extinguishing fire. Estimation of carbon monoxide quantity absorbed by firefighters was isolated in a group of 40 firefighters from Fire Extinguishing and Rescue Unit of State Fire in Nysa. The study was conducted by measuring carbon monoxide in exhaled air. For measurement of carbon monoxide concentration in exhaled air Micro CO meter was used. Results were demonstrated separately for nonsmokers (n425 and smokers (n415. Mean COHb[%] levels in nonsmokers, measured prior the rescue action was 0,3950,3% and increased statistically significant after the action to 0,6150,34%, while in the group smokers, this level was 2,1750,64% before the action and increased insignificantly after the action to 2,3350,63%. The average COHb level in the same groups before and after exercise, was respectively: for nonsmokers prior to exercise was 0,4850,28% and after exercise decreased statistically significant to 0,3050,27%. In the group of smokers before exercise was 2,2350,61% and decreased statistically significant up to 1,5450,71%. It was no difference between the group of age and time of employment.

  16. Mine rescue robots requirements: Outcomes from an industry workshop

    CSIR Research Space (South Africa)

    Green, J

    2013-10-01

    Full Text Available and internationally. The paper identifies three definite robot deployments in South Africa as a) box hole deployment (vertical tunnels), b) flying drone reconnaissance and c) proto (rescue) team assistance. These represent applications where there is a market need...

  17. Maternal and perinatal aspects of birth defects: a case-control study

    Directory of Open Access Journals (Sweden)

    Geiza Cesar Nhoncanse

    2014-03-01

    Full Text Available Objective: To assess the prevalence of congenital defects and to investigate their maternal and perinatal associated aspects by reviewing Birth Certificates. Methods: Among all born alive infants from January 2003 to December 2007 in Maternidade da Santa Casa de Misericórdia of São Carlos, Southeast Brazil (12,199 infants, cases were identified as the newborns whose Birth Certificates registered any congenital defect. The same sex neonate born immediately after the case was chosen as a control. In total, 13 variables were analyzed: six were maternal related, three represented labor and delivery conditions and four were linked to fetal status. The chi-square and Fisher's exact tests were used to compare the variables, being significant p<0.05. Results: The prevalence of congenital defects was 0.38% and the association of two or more defects represented 32% of all cases. The number of mothers whose education level was equal or less than eight years was significantly higher among the group with birth defects (p=0.047. A higher frequency of prematurity (p<0.001 and cesarean delivery (p=0.004 was observed among children with birth defects. This group also showed lower birth weight and Apgar scores in the 1st and the 5th minute (p<0.001. Conclusions: The prevalence of congenital defect of 0.38% is possibly due to underreporting. The defects notified in the Birth Certificates were only the most visible ones, regardless of their severity. There is a need of adequate epidemiological monitoring of birth defects in order to create and expand prevention and treatment programs.

  18. Exploring the Interplay between Rescue Drugs, Data Imputation, and Study Outcomes: Conceptual Review and Qualitative Analysis of an Acute Pain Data Set.

    Science.gov (United States)

    Singla, Neil K; Meske, Diana S; Desjardins, Paul J

    2017-12-01

    In placebo-controlled acute surgical pain studies, provisions must be made for study subjects to receive adequate analgesic therapy. As such, most protocols allow study subjects to receive a pre-specified regimen of open-label analgesic drugs (rescue drugs) as needed. The selection of an appropriate rescue regimen is a critical experimental design choice. We hypothesized that a rescue regimen that is too liberal could lead to all study arms receiving similar levels of pain relief (thereby confounding experimental results), while a regimen that is too stringent could lead to a high subject dropout rate (giving rise to a preponderance of missing data). Despite the importance of rescue regimen as a study design feature, there exist no published review articles or meta-analysis focusing on the impact of rescue therapy on experimental outcomes. Therefore, when selecting a rescue regimen, researchers must rely on clinical factors (what analgesics do patients usually receive in similar surgical scenarios) and/or anecdotal evidence. In the following article, we attempt to bridge this gap by reviewing and discussing the experimental impacts of rescue therapy on a common acute surgical pain population: first metatarsal bunionectomy. The function of this analysis is to (1) create a framework for discussion and future exploration of rescue as a methodological study design feature, (2) discuss the interplay between data imputation techniques and rescue drugs, and (3) inform the readership regarding the impact of data imputation techniques on the validity of study conclusions. Our findings indicate that liberal rescue may degrade assay sensitivity, while stringent rescue may lead to unacceptably high dropout rates.

  19. EMERGENCY VICTIM CARE AND RESCUE, TEXTBOOK FOR SQUADMEN.

    Science.gov (United States)

    Ohio State Dept. of Education, Columbus. Trade and Industrial Education Service.

    DESIGNED FOR TRAINING EMERGENCY SQUAD PERSONNEL IN RESCUE PROCEDURES AND VICTIM CARE BEYOND BASIC FIRST AID, THIS TEXTBOOK WAS DEVELOPED BY A COMMITTEE OF SQUADMEN, DOCTORS, NURSES, FIREMEN, AND STATE TRADE AND INDUSTRIAL PERSONNEL TO BE USED IN ADULT TRAINING CLASSES OF FULL-TIME OR VOLUNTEER SQUADMEN. THE INSTRUCTIONAL MATERIAL INCLUDES 26…

  20. Nonhomologous recombination between defective poliovirus and coxsackievirus genomes suggests a new model of genetic plasticity for picornaviruses.

    Science.gov (United States)

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line; Delpeyroux, Francis

    2014-08-05

    Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3' end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. Importance: The multiplication of circulating vaccine-derived polioviruses (cVDPVs) in poorly immunized human populations can render these viruses pathogenic, causing poliomyelitis outbreaks. Most cVDPVs are intertypic recombinants between a poliovirus (PV) strain and another human enterovirus, such as type 17 coxsackie A viruses (CA17). For further studies of the genetic exchanges

  1. Launch-Off-Need Shuttle Hubble Rescue Mission: Medical Issues

    Science.gov (United States)

    Hamilton, Douglas; Gillis, David; Ilcus, Linda; Perchonok, Michele; Polk, James; Brandt, Keith; Powers, Edward; Stepaniak, Phillip

    2008-01-01

    The Space Shuttle Hubble repair mission (STS-125) is unique in that a rescue mission (STS-400) has to be ready to launch before STS-125 life support runs out should the vehicle become stranded. The shuttle uses electrical power derived from fuel cells that use cryogenic oxygen and hydrogen (CRYO) to run all subsystems including the Environmental Control System. If the STS-125 crew cannot return to Earth due to failure of a critical subsystem, they must power down all nonessential systems and wait to be rescued by STS-400. This power down will cause the cabin temperature to be 60 F or less and freeze the rest of the vehicle, preventing it from attempting a reentry. After an emergency has been declared, STS-125 must wait at least 7 days to power down since that is the earliest that STS-400 can be launched. Problem The delayed power down of STS-125 causes CYRO to be consumed at high rates and limits the survival time after STS-400 launches to 10 days or less. CRYO will run out sooner every day that the STS-400 launch is delayed (weather at launch, technical issues etc.). To preserve CRYO and lithium hydroxide (LiOH - carbon dioxide removal) the crew will perform no exercise to reduce their metabolic rates, yet each deconditioned STS-125 crewmember must perform an EVA to rescue himself. The cabin may be cold for 10 days, which may cause shivering, increasing the metabolic rate of the STS-125 crew. Solution To preserve LiOH, the STS-125 manifest includes nutrition bars with low carbohydrate content to maintain crew respiratory quotient (RQ) below 0.85 as opposed to the usual shuttle galley food which is rich in carbohydrates and keeps the RQ at approximately 0.95. To keep the crew more comfortable in the cold vehicle warm clothing also has been included. However, with no exercise and limited diet, the deconditioned STS-125 crew returning on STS-400 may not be able to egress the vehicle autonomously requiring a supplemented crash-and-rescue capability.

  2. Defective balancing ability and hyperactivity in the CLX (circling behavior linked to the X-chromosome) mutant rat.

    Science.gov (United States)

    Fuji, Jun-ichiro; Tanabe, Hiroyuki; Fukuda, Ryo; Ooshima, Yojiro

    2003-12-01

    We have reported that the recently described circling behavior rat (CLX) is a hereditary mutant controlled by a single sex-linked recessive gene (gene symbol: clx). This mutant shows intermittent circle walking and/or running and head tossing with the neck twisted. The abnormal behavior begins to appear around weaning and continues throughout life. In the present study, behavioral tests were performed during the suckling and post-weaning periods and when the rats reached maturity, and the following peculiar abnormalities were revealed: (1) in the righting reflex test, the CLX young show a tendency to take a longer time to revert to normal posture; (2) in the negative geotaxis test, they had difficulty moving upward at 12 days of age; (3) in the air righting reflex test, they frequently fell on their backs or shoulders even after weaning; (4) almost none of the CLX rats showed nystagmus, which is invariably observed in normal rats after rotating stimulation, at 20 weeks of age; and (5) they showed hyperactivity in the open field test at the age of 5 or 6 weeks and a higher degree of locomotor activity in the home cage at the age of 7 and 15 weeks. These results suggest that CLX mutant rats may have some defect in vestibular function (balance sense) or abnormalities in an area of the central nervous system responsible for posture control, e.g., in the dopaminergic or GABAergic neurons.

  3. In vitro embryo rescue and plant regeneration following self ...

    African Journals Online (AJOL)

    EJIRO

    2015-07-08

    Jul 8, 2015 ... 2Department of Biological Sciences, College of Natural Sciences, Makerere ... Key words: Cassava, doubled haploids, embryo rescue, plant regeneration, pollen germination, pollen ... breeding as inbred lines are readily tested and used within a ... dominance, allowing the separation of homozygotes from.

  4. Protecting front-line survey and rescue teams during emergencies

    International Nuclear Information System (INIS)

    Tresise, H.

    1980-01-01

    Means of protecting front-line survey and rescue teams during emergencies are described. The team composition, their apparatus, the selection of the incident control point, the use of guidelines and breathing apparatus and control point trolley and equipment are discussed. (H.K.)

  5. Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

    International Nuclear Information System (INIS)

    McMahon, Laura W.; Zhang Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

    2009-01-01

    Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellular hypersensitivity to DNA interstrand cross-linking agents. An increased number of chromosomal aberrations were observed and, following treatment with a DNA interstrand cross-linking agent, mitomycin C, cells showed decreased cell growth and survival and decreased formation of damage-induced αIISp and XPF nuclear foci. Thus depletion of αIISp in normal cells leads to a number of defects observed in FA cells, such as chromosome instability and a deficiency in cross-link repair.

  6. Immobile defects in ferroelastic walls: Wall nucleation at defect sites

    Science.gov (United States)

    He, X.; Salje, E. K. H.; Ding, X.; Sun, J.

    2018-02-01

    Randomly distributed, static defects are enriched in ferroelastic domain walls. The relative concentration of defects in walls, Nd, follows a power law distribution as a function of the total defect concentration C: N d ˜ C α with α = 0.4 . The enrichment Nd/C ranges from ˜50 times when C = 10 ppm to ˜3 times when C = 1000 ppm. The resulting enrichment is due to nucleation at defect sites as observed in large scale MD simulations. The dynamics of domain nucleation and switching is dependent on the defect concentration. Their energy distribution follows the power law with exponents during yield between ɛ ˜ 1.82 and 2.0 when the defect concentration increases. The power law exponent is ɛ ≈ 2.7 in the plastic regime, independent of the defect concentration.

  7. Rescue behaviour in a social bird : removal of sticky 'bird-catcher tree' seeds by group members

    NARCIS (Netherlands)

    Hammers, Martijn; Brouwer, Lyanne

    2017-01-01

    Rescue behaviour is a special form of cooperation in which a rescuer exhibits behaviours directed towards averting a threat to an endangered individual, thereby potentially putting itself at risk. Although rescue behaviour has been well-documented in experimental studies on rats and ants, published

  8. Deletion of the cardiolipin-specific phospholipase Cld1 rescues growth and life span defects in the tafazzin mutant: implications for Barth syndrome

    NARCIS (Netherlands)

    Ye, Cunqi; Lou, Wenjia; Li, Yiran; Chatzispyrou, Iliana A.; Hüttemann, Maik; Lee, Icksoo; Houtkooper, Riekelt H.; Vaz, Frédéric M.; Chen, Shuliang; Greenberg, Miriam L.

    2014-01-01

    Cardiolipin (CL) that is synthesized de novo is deacylated to monolysocardiolipin (MLCL), which is reacylated by tafazzin. Remodeled CL contains mostly unsaturated fatty acids. In eukaryotes, loss of tafazzin leads to growth and respiration defects, and in humans, this results in the

  9. Retrospective on the construction and practice of a state-level emergency medical rescue team.

    Science.gov (United States)

    Lei, Zhang; Haitao, Guo; Xin, Wang; Yundou, Wang

    2014-10-01

    For the past few years, disasters like earthquakes, landslides, mudslides, tsunamis, and traffic accidents have occurred with an ever-growing frequency, coverage, and intensity greatly beyond the expectation of the public. In order to respond effectively to disasters and to reduce casualties and property damage, countries around the world have invested more efforts in the theoretical study of emergency medicine and the construction of emergency medical rescue forces. Consequently, emergency medical rescue teams of all scales and types have come into being and have played significant roles in disaster response work. As the only state-level emergency medical rescue force from the Chinese People's Armed Police Forces, the force described here has developed, through continuous learning and practice, a characteristic mode in terms of grouping methods, equipment system construction, and training.

  10. Job task characteristics of Australian emergency services volunteers during search and rescue operations.

    Science.gov (United States)

    Silk, Aaron; Lenton, Gavin; Savage, Robbie; Aisbett, Brad

    2018-02-01

    Search and rescue operations are necessary in locating, assisting and recovering individuals lost or in distress. In Australia, land-based search and rescue roles require a range of physically demanding tasks undertaken in dynamic and challenging environments. The aim of the current research was to identify and characterise the physically demanding tasks inherent to search and rescue operation personnel within Australia. These aims were met through a subjective job task analysis approach. In total, 11 criterion tasks were identified by personnel. These tasks were the most physically demanding, frequently occurring and operationally important tasks to these specialist roles. Muscular strength was the dominant fitness component for 7 of the 11 tasks. In addition to the discrete criterion tasks, an operational scenario was established. With the tasks and operational scenario identified, objective task analysis procedures can be undertaken so that practitioners can implement evidence-based strategies, such as physical selection procedures and task-based physical training programs, commensurate with the physical demands of search and rescue job roles. Practitioner Summary: The identification of physically demanding tasks amongst specialist emergency service roles predicates health and safety strategies which can be incorporated into organisations. Knowledge of physical task parameters allows employers to mitigate injury risk through the implementation of strategies modelled on the precise physical demands of the role.

  11. Drone configuration for seaside rescue missions

    OpenAIRE

    Garro Fernandez, Jose Miguel

    2017-01-01

    The project is based on creating a first aid tool to perform a coastline rescue with an unmanned. The System is formed by a ground segment, where the ground station will be placed and an air segment, where the unmanned vehicle, equipped with all the necessary extra devices to perform the mission will be found. For notices of possible drownings, the ground station will receive notifications that users will publish using a Mobile application. This app will allow users to capture images of the v...

  12. A ground moving target emergency tracking method for catastrophe rescue

    Science.gov (United States)

    Zhou, X.; Li, D.; Li, G.

    2014-11-01

    In recent years, great disasters happen now and then. Disaster management test the emergency operation ability of the government and society all over the world. Immediately after the occurrence of a great disaster (e.g., earthquake), a massive nationwide rescue and relief operation need to be kicked off instantly. In order to improve the organizations efficiency of the emergency rescue, the organizers need to take charge of the information of the rescuer teams, including the real time location, the equipment with the team, the technical skills of the rescuers, and so on. One of the key factors for the success of emergency operations is the real time location of the rescuers dynamically. Real time tracking methods are used to track the professional rescuer teams now. But volunteers' participation play more and more important roles in great disasters. However, real time tracking of the volunteers will cause many problems, e.g., privacy leakage, expensive data consumption, etc. These problems may reduce the enthusiasm of volunteers' participation for catastrophe rescue. In fact, the great disaster is just small probability event, it is not necessary to track the volunteers (even rescuer teams) every time every day. In order to solve this problem, a ground moving target emergency tracking method for catastrophe rescue is presented in this paper. In this method, the handheld devices using GPS technology to provide the location of the users, e.g., smart phone, is used as the positioning equipment; an emergency tracking information database including the ID of the ground moving target (including the rescuer teams and volunteers), the communication number of the handheld devices with the moving target, and the usually living region, etc., is built in advance by registration; when catastrophe happens, the ground moving targets that living close to the disaster area will be filtered by the usually living region; then the activation short message will be sent to the selected

  13. Rip current related drowning deaths and rescues in Australia 2004-2011

    Science.gov (United States)

    Brighton, B.; Sherker, S.; Brander, R.; Thompson, M.; Bradstreet, A.

    2013-04-01

    Rip currents are a common hazard to beachgoers found on many beaches around the world, but it has proven difficult to accurately quantify the actual number of rip current related drowning deaths in many regions and countries. Consequently, reported estimates of rip current drowning can fluctuate considerably and are often based on anecdotal evidence. This study aims to quantify the incidence of rip current related drowning deaths and rescues in Australia from 2004 to 2011. A retrospective search was undertaken for fatal and non-fatal rip-related drowning incidents from Australia's National Coronial Information System (NCIS), Surf Life Saving Australia's (SLSA, 2005-2011) SurfGuard Incident Report Database (IRD), and Media Monitors for the period 1 July 2004 to 30 June 2011. In this time, rip currents were recorded as a factor in 142 fatalities of a total of 613 coastal drowning deaths (23.2%), an average of 21 per year. Rip currents were related to 44% of all beach-related drowning deaths and were involved in 57.4% of reported major rescues in Australian locations where rips occur. A comparison with international operational statistics over the same time period describes rip-related rescues as 53.7% of the total rescues in the US, 57.9% in the UK and 49.4% in New Zealand. The range 49-58% is much lower than 80-89% traditionally cited. The results reported are likely to underestimate the size of the rip current hazard, because we are limited by the completeness of data on rip-related events; however this is the most comprehensive estimate to date. Beach safety practitioners need improved data collection and standardized definitions across organisations. The collection of drowning data using consistent categories and the routine collection of rip current information will allow for more accurate global comparisons.

  14. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet

    OpenAIRE

    Vanderperre, Beno?t; Herzig, S?bastien; Krznar, Petra; H?rl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

    2016-01-01

    Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic p...

  15. Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment.

    Science.gov (United States)

    Ponnath, Abhilash; Depreux, Frederic F; Jodelka, Francine M; Rigo, Frank; Farris, Hamilton E; Hastings, Michelle L; Lentz, Jennifer J

    2018-02-01

    The absence of functional outer hair cells is a component of several forms of hereditary hearing impairment, including Usher syndrome, the most common cause of concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of mice with the human Usher mutation, Ush1c c.216G>A, corrects gene expression and significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle morphology. However, it is not clear whether the improvement in hearing achieved by ASO treatment involves the functional rescue of outer hair cells. Here, we show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and high-frequency tone pairs. This OHC deficit is rescued by treatment with an ASO that corrects expression of Ush1c c.216G>A. Interestingly, although rescue of inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7 days after birth, rescue of outer hair cells, measured by DPOAE, requires treatment before post-natal day 5. These results suggest that ASO-mediated rescue of both IHC and OHC function is age dependent and that the treatment window is different for the different cell types. The timing of treatment for congenital hearing disorders is of critical importance for the development of drugs such ASO-29 for hearing rescue.

  16. Sex, Deportation and Rescue

    DEFF Research Database (Denmark)

    Plambech, Sine

    2017-01-01

    recirculating the claim that human trafficking is the “third largest” criminal economy after drugs and weapons. Based on ethnographic fieldwork among Nigerian sex worker migrants conducted in Benin City, Nigeria, in 2011 and 2012, this study brings together four otherwise isolated migration economies......This contribution explores the economies interlinked by the migration of Nigerian women sex workers. The literature and politics of sex work migration and human trafficking economies are commonly relegated to the realm that focuses on profits for criminal networks and pimps, in particular...... – facilitation, remittances, deportation, and rescue – and suggests that we have to examine multiple sites and relink these in order to more fully understand the complexity of sex work migration. Drawing upon literature within transnational feminist analysis, critical human trafficking studies, and migration...

  17. Primary biochemical defect in copper metabolism in mice with a recessive X-linked mutation analogous to Menkes' disease in man

    International Nuclear Information System (INIS)

    Prins, H.W.; Hamer, C.J.A. van den.

    1979-01-01

    The defect in Menkes' disease in man is identical to that in Brindled mice. The defect manifests itself in a accumulation of copper in some tissues, such as renal, intestinal (mucosa and muscle), pancreatic, osseous, muscular, and dermal. Hence a fatal copper deficiency results in other tissues (e.g., hepatic). The copper transport through the intestine is impaired and copper, which circumvents the block in the copper resorption, is irreversibly trapped in the above-mentioned, copper accumulating tissues where it is bound to a cytoplasmatic protein with molecular weight 10,000 daltons, probably the primary cytoplasmatic copper transporting protein. This protein shows a Cu-S absorption band at 250 nm, and the copper:protein ratio is increased. Such copper rich protein was found neither in the kidneys of the unaffected mica nor in the liver of the mice that do have the defect. Three models of the primary defect in Menkes' disease are proposed

  18. Spontaneous neural tube defects in splotch mice supplemented with selected micronutrients

    International Nuclear Information System (INIS)

    Wlodarczyk, Bogdan J.; Tang, Louisa S.; Triplett, Aleata; Aleman, Frank; Finnell, Richard H.

    2006-01-01

    Splotch (Sp/Sp) mice homozygous for a mutation in the Pax3 gene inevitably present with neural tube defects (NTDs), along with other associated congenital anomalies. The affected mutant embryos usually die by gestation days (E) 12-13. In the present study, the effect of modifier genes from a new genetic background (CXL-Sp) and periconceptional supplementation with selected micronutrients (folic acid, 5-formyltetrahydrofolate, 5-methyltetrahydrofolate, methionine, myoinositol, thiamine, thymidine, and α-tocopherol) was determined with respect to the incidence of NTDs. In order to explore how different exposure parameters (time, dose, and route of compound administration) modulate the beneficial effects of micronutrient supplementation, female mice received either short- or long-term nutrient supplements via enteral or parenteral routes. Embryos were collected on E12.5 and examined for the presence of anterior or posterior NTDs. Additionally, whole mount in situ hybridization studies were conducted in order to reveal/confirm normal expression patterns of the Pax3 gene during neurulation in the wild-type and Sp/Sp homozygous mutant mouse embryos utilized in this study. A strong Pax3 signal was demonstrated in CXL-Sp embryos during neural tube closure (E9.5 to E10.5). The intensity and spatial pattern of expression were similar to other Splotch mutant mice. Of all the micronutrients tested, only supplementation with folic acid or 5-methyltetrahydrofolate rescued the normal phenotype in Sp/Sp embryos. When the folate supplementation dose was increased to 200 mg/kg in the diet, the incidence of rescued splotch homozygotes reached 30%; however, this was accompanied by six-fold increased resorption rate

  19. Studies of defects and defect agglomerates by positron annihilation spectroscopy

    DEFF Research Database (Denmark)

    Eldrup, Morten Mostgaard; Singh, B.N.

    1997-01-01

    A brief introduction to positron annihilation spectroscopy (PAS), and in particular lo its use for defect studies in metals is given. Positrons injected into a metal may become trapped in defects such as vacancies, vacancy clusters, voids, bubbles and dislocations and subsequently annihilate from...... the trapped state iri the defect. The annihilation characteristics (e.g., the lifetime of the positron) can be measured and provide information about the nature of the defect (e.g., size, density, morphology). The technique is sensitive to both defect size (in the range from monovacancies up to cavities...

  20. Stress of Rescue Team Members Working in Confined Spaces During a Disaster : Effectiveness of Individual Wireless Communication Devices

    OpenAIRE

    Kitabayashi, Tsukasa; Kudo, Seiko; Kitajima, Maiko; Takamaki, Shizuka; Chiba, Tomohiro; Tachioka, Nobuaki; Kudo, Shungetsu; Kudo, Hiromi

    2016-01-01

    This study evaluated stress experienced by rescue team members during a simulated search and rescue operation in a confined space and determine if wireless communication reduces stress. A total of 57 rescue team members of X prefecture participated. The stress visualization indices were ptyalin (i.e., salivary amylase), salivary cortisol, autonomic nervous system response, visual analog scale, and a short version of the profile of mood states. The subjects were randomized to perform a simulat...

  1. Targeting the intracellular environment in cystic fibrosis: restoring autophagy as a novel strategy to circumvent the CFTR defect

    Directory of Open Access Journals (Sweden)

    Valeria Rachela Villella

    2013-01-01

    Full Text Available Cystic fibrosis (CF patients harboring the most common deletion mutation of the cystic fibrosis transmembrane conductance regulator (CFTR, F508del, are poor responders to potentiators of CFTR channel activity which can be used to treat a small subset of CF patients who genetically carry plasma membrane-resident CFTR mutants. The misfolded F508del-CFTR protein is unstable in the plasma membrane even if rescued by pharmacological agents that prevent its intracellular retention and degradation. CF is a conformational disease in which defective CFTR induces an impressive derangement of general proteostasis resulting from disabled autophagy. In this review, we discuss how rescuing Beclin 1 (BECN1, a major player of autophagosome formation, either by means of direct gene transfer or indirectly by administration of proteostasis regulators, could stabilize F508del-CFTR at the plasma membrane. We focus on the relationship between the improvement of peripheral proteostasis and CFTR plasma membrane stability in F508del-CFTR homozygous bronchial epithelia or mouse lungs. Moreover, this article reviews recent preclinical evidence indicating that targeting the intracellular environment surrounding the misfolded mutant CFTR instead of protein itself could constitute an attractive therapeutic option to sensitize patients carrying the F508del-CFTR mutation to the beneficial action of CFTR potentiators on lung inflammation.

  2. Targeting the Intracellular Environment in Cystic Fibrosis: Restoring Autophagy as a Novel Strategy to Circumvent the CFTR Defect

    Science.gov (United States)

    Villella, Valeria Rachela; Esposito, Speranza; Bruscia, Emanuela M.; Maiuri, Maria Chiara; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

    2013-01-01

    Cystic fibrosis (CF) patients harboring the most common deletion mutation of the CF transmembrane conductance regulator (CFTR), F508del, are poor responders to potentiators of CFTR channel activity which can be used to treat a small subset of CF patients who genetically carry plasma membrane (PM)-resident CFTR mutants. The misfolded F508del-CFTR protein is unstable in the PM even if rescued by pharmacological agents that prevent its intracellular retention and degradation. CF is a conformational disease in which defective CFTR induces an impressive derangement of general proteostasis resulting from disabled autophagy. In this review, we discuss how rescuing Beclin 1 (BECN1), a major player of autophagosome formation, either by means of direct gene transfer or indirectly by administration of proteostasis regulators, could stabilize F508del-CFTR at the PM. We focus on the relationship between the improvement of peripheral proteostasis and CFTR PM stability in F508del-CFTR homozygous bronchial epithelia or mouse lungs. Moreover, this article reviews recent pre-clinical evidence indicating that targeting the intracellular environment surrounding the misfolded mutant CFTR instead of protein itself could constitute an attractive therapeutic option to sensitize patients carrying the F508del-CFTR mutation to the beneficial action of CFTR potentiators on lung inflammation. PMID:23346057

  3. Inactivation of TGF-β signaling in lung cancer results in increased CDK4 activity that can be rescued by ELF

    International Nuclear Information System (INIS)

    Baek, Hye Jung; Kim, Sang Soo; Silva, Fabio May da; Volpe, Eugene A.; Evans, Stephen; Mishra, Bibhuti; Mishra, Lopa; Blair Marshall, M.

    2006-01-01

    Escape from TGF-β inhibition of proliferation is a hallmark of multiple cancers including lung cancer. We explored the role of ELF, crucial TGF-β adaptor protein identified from endodermal progenitor cells, in lung carcinogenesis and cell-cycle regulation. Interestingly, elf -/- mice develop multiple defects that include lung, liver, and cardiac abnormalities. Four out of 6 lung cancer and mesothelioma cell lines displayed deficiency of ELF expression with increased CDK4 expression. Immunohistochemistry and Western blot analysis of primary human lung cancers also showed decreased ELF expression and overexpression of CDK4. Moreover, rescue of ELF in ELF-deficient cell lines decreased the expression of CDK4 and resulted in accumulation of G1/S checkpoint arrested cells. These results suggest that disruption in TGF-β signaling mediated by loss of ELF in lung cancer leads to cell-cycle deregulation by modulating CDK4 and ELF highlights a key role of TGF-β adaptor protein in suppressing early lung cancer

  4. A Case of “en bloc” Excision of a Chest Wall Leiomyosarcoma and Closure of the Defect with Non-Cross-Linked Collagen Matrix (Egis®

    Directory of Open Access Journals (Sweden)

    Marco Rastrelli

    2016-10-01

    Full Text Available Sarcomas arising from the chest wall account for less than 20% of all soft tissue sarcomas, and at this site, primitive tumors are the most frequent to occur. Leiomyosarcoma is a malignant smooth muscle tumor and the best outcomes are achieved with wide surgical excision. Although advancements have been made in treatment protocols, leiomyosarcoma remains one of the more difficult soft tissue sarcoma to treat. Currently, general local control is obtained with surgical treatment with wide negative margins. We describe the case of a 50-year-old man who underwent a chest wall resection involving a wide portion of the pectoralis major and minor muscle, the serratus and part of the second, third and fourth ribs of the left side. The full-thickness chest wall defect of 10 × 8 cm was closed using a non-cross-linked acellular dermal matrix (Egis® placed in two layers, beneath the rib plane and over it. A successful repair was achieved with no incisional herniation and with complete tissue regeneration, allowing natural respiratory movements. No complications were observed in the postoperative course. Biological non-cross-linked matrix, derived from porcine dermis, behaves like a scaffold supporting tissue regeneration; it can be successfully used as an alternative to synthetic mesh for chest wall reconstruction.

  5. A Case of “en bloc” Excision of a Chest Wall Leiomyosarcoma and Closure of the Defect with Non-Cross-Linked Collagen Matrix (Egis®)

    Science.gov (United States)

    Rastrelli, Marco; Tropea, Saveria; Spina, Romina; Costa, Alessandra; Stramare, Roberto; Mocellin, Simone; Bonavina, Maria Giuseppina; Rossi, Carlo Riccardo

    2016-01-01

    Sarcomas arising from the chest wall account for less than 20% of all soft tissue sarcomas, and at this site, primitive tumors are the most frequent to occur. Leiomyosarcoma is a malignant smooth muscle tumor and the best outcomes are achieved with wide surgical excision. Although advancements have been made in treatment protocols, leiomyosarcoma remains one of the more difficult soft tissue sarcoma to treat. Currently, general local control is obtained with surgical treatment with wide negative margins. We describe the case of a 50-year-old man who underwent a chest wall resection involving a wide portion of the pectoralis major and minor muscle, the serratus and part of the second, third and fourth ribs of the left side. The full-thickness chest wall defect of 10 × 8 cm was closed using a non-cross-linked acellular dermal matrix (Egis®) placed in two layers, beneath the rib plane and over it. A successful repair was achieved with no incisional herniation and with complete tissue regeneration, allowing natural respiratory movements. No complications were observed in the postoperative course. Biological non-cross-linked matrix, derived from porcine dermis, behaves like a scaffold supporting tissue regeneration; it can be successfully used as an alternative to synthetic mesh for chest wall reconstruction. PMID:27920698

  6. Work Engagement among Rescue Workers: Psychometric Properties of the Portuguese UWES.

    Science.gov (United States)

    Sinval, Jorge; Marques-Pinto, Alexandra; Queirós, Cristina; Marôco, João

    2017-01-01

    Rescue workers have a stressful and risky occupation where being engaged is crucial to face physical and emotional risks in order to help other persons. This study aims to estimate work engagement levels of rescue workers (namely comparing nurses, firefighters, and police officers) and to assess the validity evidence related to the internal structure of the Portuguese versions of the UWES-17 and UWES-9, namely, dimensionality, measurement invariance between occupational groups, and reliability of the scores. To evaluate the dimensionality, we compared the fit of the three-factor model with the fit of a second-order model. A Portuguese version of the instrument was applied to a convenience sample of 3,887 rescue workers (50% nurses, 39% firefighters, and 11% police officers). Work engagement levels were moderate to high, with firefighters being the highest and nurses being the lowest engaged. Psychometric properties were evaluated in the three-factor original structure revealing acceptable fit to the data in the UWES-17, although the UWES-9 had better psychometric properties. Given the observed statistically significant correlations between the three original factors, we proposed a 2 nd hierarchal structure that we named work engagement. The UWES-9 first-order model obtained full uniqueness measurement invariance, and the second-order model obtained partial (metric) second-order invariance.

  7. Defect modelling

    International Nuclear Information System (INIS)

    Norgett, M.J.

    1980-01-01

    Calculations, drawing principally on developments at AERE Harwell, of the relaxation about lattice defects are reviewed with emphasis on the techniques required for such calculations. The principles of defect modelling are outlined and various programs developed for defect simulations are discussed. Particular calculations for metals, ionic crystals and oxides, are considered. (UK)

  8. Bone tissue ultrastructural defects in a mouse model for osteogenesis imperfecta: a Raman spectroscopy study

    Science.gov (United States)

    Chen, Tsoching; Kozloff, Kenneth M.; Goldstein, Steven A.; Morris, Michael D.

    2004-07-01

    Osteogenesis imperfecta (OI) is genetic defect in which the genes that code for the α1(I) or α2(I) chains of type I collagen are defective. The defects often result in substitution of a bulky amino acid for glycine, causing formation of collagen that can not form the normal triple helix. Depending on the details of the defects, the outcomes range from controllable to lethal. This study focuses on OI type IV, a more common and moderately severe form of the disease. People with the disease have a substantial increase in the risk and rate of fracture. We examine the spectroscopic consequences of these defects, using a mouse model (BRTL) that mimics OI type IV. We compare Raman images from tibial cortical tissue of wild-type mice and BRTL mice with single copy of mutation and show that both mineral to matrix ratios and collagen inter-fibril cross-links are different in wild-type and mutant mice.

  9. Mountain Search and Rescue with Remotely Piloted Aircraft Systems

    Science.gov (United States)

    Silvagni, Mario; Tonoli, Andrea; Zenerino, Enrico; Chiaberge, Marcello

    2016-04-01

    Remotely Piloted Aircraft Systems (RPAS) also known as Unmanned Aerial Systems (UAS) are nowadays becoming more and more popular in several applications. Even though a complete regulation is not yet available all over the world, researches, tests and some real case applications are wide spreading. These technologies can bring many benefits also to the mountain operations especially in emergencies and harsh environmental conditions, such as Search and Rescue (SAR) and avalanche rescue missions. In fact, during last decade, the number of people practicing winter sports in backcountry environment is increased and one of the greatest hazards for recreationists and professionals are avalanches. Often these accidents have severe consequences leading, mostly, to asphyxia-related death, which is confirmed by the hard drop of survival probability after ten minutes from the burying. Therefore, it is essential to minimize the time of burial. Modern avalanche beacon (ARTVA) interface guides the rescuer during the search phase reducing its time. Even if modern avalanche beacons are valid and reliable, the seeking range influences the rescue time. Furthermore, the environment and morphologic conditions of avalanches usually complicates the rescues. The recursive methodology of this kind of searching offers the opportunity to use automatic device like drones (RPAS). These systems allow performing all the required tasks autonomously, with high accuracy and without exposing the rescuers to additional risks due to secondary avalanches. The availability of highly integrated electronics and subsystems specifically meant for the applications, better batteries, miniaturized payload and, in general, affordable prices, has led to the availability of small RPAS with very good performances that can give interesting application opportunities in unconventional environments. The present work is one of the outcome from the experience made by the authors in RPAS fields and in Mechatronics

  10. Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

    Science.gov (United States)

    Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

    2005-04-01

    Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

  11. Sporulation-specific cell division defects in ylmE mutants of Streptomyces coelicolor are rescued by additional deletion of ylmD.

    Science.gov (United States)

    Zhang, Le; Willemse, Joost; Hoskisson, Paul A; van Wezel, Gilles P

    2018-05-09

    Cell division during the reproductive phase of the Streptomyces life-cycle requires tight coordination between synchronous formation of multiple septa and DNA segregation. One remarkable difference with most other bacterial systems is that cell division in Streptomyces is positively controlled by the recruitment of FtsZ by SsgB. Here we show that deletion of ylmD (SCO2081) or ylmE (SCO2080), which lie in operon with ftsZ in the dcw cluster of actinomycetes, has major consequences for sporulation-specific cell division in Streptomyces coelicolor. Electron and fluorescence microscopy demonstrated that ylmE mutants have a highly aberrant phenotype with defective septum synthesis, and produce very few spores with low viability and high heat sensitivity. FtsZ-ring formation was also highly disturbed in ylmE mutants. Deletion of ylmD had a far less severe effect on sporulation. Interestingly, the additional deletion of ylmD restored sporulation to the ylmE null mutant. YlmD and YlmE are not part of the divisome, but instead localize diffusely in aerial hyphae, with differential intensity throughout the sporogenic part of the hyphae. Taken together, our work reveals a function for YlmD and YlmE in the control of sporulation-specific cell division in S. coelicolor, whereby the presence of YlmD alone results in major developmental defects.

  12. Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental defects in rats.

    Science.gov (United States)

    Kumar, Praveen; Mohan, Vishwa; Sinha, Rohit Anthony; Chagtoo, Megha; Godbole, Madan M

    2015-11-01

    Thyroid hormone (TH) through its receptor (TRα/β) influences spatio-temporal regulation of its target gene repertoire during brain development. Though hypothyroidism in WT rodent models of perinatal hypothyroidism severely impairs neurodevelopment, its effect on TRα/β knockout mice is less severe. An explanation to this paradox is attributed to a possible repressive action of unliganded TRs during development. Since unliganded TRs suppress gene expression through the recruitment of histone deacetylase (HDACs) via co-repressor complexes, we tested whether pharmacological inhibition of HDACs may prevent the effects of hypothyroidism on brain development. Using valproate, an HDAC inhibitor, we show that HDAC inhibition significantly blocks the deleterious effects of hypothyroidism on rat cerebellum, evident by recovery of TH target genes like Bdnf, Pcp2 and Mbp as well as improved dendritic structure of cerebellar Purkinje neurons. Together with this, HDAC inhibition also rescues hypothyroidism-induced motor and cognitive defects. This study therefore provides an insight into the role of HDACs in TH insufficiency during neurodevelopment and their inhibition as a possible therapeutics for treatment. © 2015 Society for Endocrinology.

  13. Vulture rescue and rehabilitation in South Africa: An urban perspective

    Directory of Open Access Journals (Sweden)

    V. Naidoo

    2011-04-01

    Full Text Available SouthAfrica is home to 9 vulture species, of which 7 are endangered. While the cause of the population declines remains largely speculative, a vast amount of effort has been dedicated towards the protection of populations by ensuring sustainable and safe food sources for the various colonies. Limited focus was placed in the past on efforts related to the rescue and/or rehabilitation (R&R of injured birds and the release of these birds back into the wild. This paper provides an overview of the causes, the impact and success of 3 organisations involved in R&R efforts of vultures in the Magaliesberg mountain range and surrounding areas over a period of 10 years. Study material included 162 Cape griffon (CGV and 38 African white-backed (AWBV vultures. Datasets include the number, sex and age of birds received, the reason the vultures were brought in for R&R, surgical interventions performed and outcomes of rescue efforts. The CGV dominated the rehabilitation attempts. Results further show that a large number of apparently healthy birds were presented for veterinary treatment. The R&R data clearly indicate that the major cause of injuries was birds colliding with overhead pylons, as a high number of soft tissue and skeletal injuries were observed. The study also shows that successful releases of rescued birds are possible. It is concluded that urbanisation has had a major negative impact on vultures around the Magaliesberg mountain range.

  14. Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: the GnRH receptor.

    Science.gov (United States)

    Janovick, Jo Ann; Patny, Akshay; Mosley, Ralph; Goulet, Mark T; Altman, Michael D; Rush, Thomas S; Cornea, Anda; Conn, P Michael

    2009-02-01

    The human GnRH receptor (hGnRHR), a G protein-coupled receptor, is a useful model for studying pharmacological chaperones (pharmacoperones), drugs that rescue misfolded and misrouted protein mutants and restore them to function. This technique forms the basis of a therapeutic approach of rescuing mutants associated with human disease and restoring them to function. The present study relies on computational modeling, followed by site-directed mutagenesis, assessment of ligand binding, effector activation, and confocal microscopy. Our results show that two different chemical classes of pharmacoperones act to stabilize hGnRHR mutants by bridging residues D(98) and K(121). This ligand-mediated bridge serves as a surrogate for a naturally occurring and highly conserved salt bridge (E(90)-K(121)) that stabilizes the relation between transmembranes 2 and 3, which is required for passage of the receptor through the cellular quality control system and to the plasma membrane. Our model was used to reveal important pharmacophoric features, and then identify a novel chemical ligand, which was able to rescue a D(98) mutant of the hGnRHR that could not be rescued as effectively by previously known pharmacoperones.

  15. Rescue behaviour in a social bird: removal of sticky ‘bird-catcher tree’ seeds by group members

    NARCIS (Netherlands)

    Hammers, Martijn; Brouwer, Lyanne

    2017-01-01

    Rescue behaviour is a special form of cooperation in which a rescuer exhibits behaviours directed towards averting a threat to an endangered individual, thereby potentially putting itself at risk. Although rescue behaviour has been well-documented in experimental studies on rats and ants, published

  16. 33 CFR 150.504 - When must the operator service and examine lifeboat and rescue boat launching appliances?

    Science.gov (United States)

    2010-07-01

    ... and examine lifeboat and rescue boat launching appliances? 150.504 Section 150.504 Navigation and...: OPERATIONS Emergency and Specialty Equipment Launching Appliances § 150.504 When must the operator service and examine lifeboat and rescue boat launching appliances? (a) The operator must service launching...

  17. Effects of in-cascade defect clustering on near-term defect evolution

    Energy Technology Data Exchange (ETDEWEB)

    Heinisch, H.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-08-01

    The effects of in-cascade defect clustering on the nature of the subsequent defect population are being studied using stochastic annealing simulations applied to cascades generated in molecular dynamics (MD) simulations. The results of the simulations illustrates the strong influence of the defect configuration existing in the primary damage state on subsequent defect evolution. The large differences in mobility and stability of vacancy and interstitial defects and the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades have been shown to be significant factors affecting the evolution of the defect distribution. In recent work, the effects of initial cluster sizes appear to be extremely important.

  18. Combat Search and Rescue in Desert Storm

    Science.gov (United States)

    2006-09-01

    in the United States also sup- ported civil SAR. Almost daily, the veterans of Southeast Asia were called upon to rescue lost hikers and foundering ...Ridge in the Persian Gulf. Under the NRCC, Combined Task Force (CTF) 151 served as the regional SAR controller for Battle Force Zulu in the Persian...was ZULU + 3 [i.e., Greenwich Mean Time plus three hours]. Saudi Arabia local time was ZULU + 3:30. All times in the log extracts that follow are

  19. Genes Sufficient for Synthesizing Peptidoglycan are Retained in Gymnosperm Genomes, and MurE from Larix gmelinii can Rescue the Albino Phenotype of Arabidopsis MurE Mutation.

    Science.gov (United States)

    Lin, Xiaofei; Li, Ningning; Kudo, Hiromi; Zhang, Zhe; Li, Jinyu; Wang, Li; Zhang, Wenbo; Takechi, Katsuaki; Takano, Hiroyoshi

    2017-03-01

    The endosymbiotic theory states that plastids are derived from a single cyanobacterial ancestor that possessed a cell wall. Peptidoglycan (PG), the main component of the bacteria cell wall, gradually degraded during plastid evolution. PG-synthesizing Mur genes have been found to be retained in the genomes of basal streptophyte plants, although many of them have been lost from the genomes of angiosperms. The enzyme encoded by bacterial MurE genes catalyzes the formation of the UDP-N-acetylmuramic acid (UDP-MurNAc) tripeptide in bacterial PG biosynthesis. Knockout of the MurE gene in the moss Physcomitrella patens resulted in defects of chloroplast division, whereas T-DNA-tagged mutants of Arabidopsis thaliana for MurE revealed inhibition of chloroplast development but not of plastid division, suggesting that AtMurE is functionally divergent from the bacterial and moss MurE proteins. Here, we could identify 10 homologs of bacterial Mur genes, including MurE, in the recently sequenced genomes of Picea abies and Pinus taeda, suggesting the retention of the plastid PG system in gymnosperms. To investigate the function of gymnosperm MurE, we isolated an ortholog of MurE from the larch, Larix gmelinii (LgMurE) and confirmed its presence as a single copy per genome, as well as its abundant expression in the leaves of larch seedlings. Analysis with a fusion protein combining green fluorescent protein and LgMurE suggested that it localizes in chloroplasts. Cross-species complementation assay with MurE mutants of A. thaliana and P. patens showed that the expression of LgMurE cDNA completely rescued the albefaction defects in A. thaliana but did not rescue the macrochloroplast phenotype in P. patens. The evolution of plastid PG and the mechanism behind the functional divergence of MurE genes are discussed in the context of information about plant genomes at different evolutionary stages. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of

  20. Native flora rescue program: GASENE project case study

    Energy Technology Data Exchange (ETDEWEB)

    Serricchio, Claudio; Caldas, Flaviana V [PETROBRAS, Rio de Janeiro, RJ (Brazil); Akahori, Lisa [Telsan, Rio de Janeiro, RJ (Brazil); Jacomelli, Junior, Jose Almir [AGF Engenharia, Araucaria, PR (Brazil)

    2009-07-01

    Concerning the surrounding flora, the implementation of pipelines may cause fragmentation and isolation of the remaining natural vegetation, possibly changing the forest structure; thus raising the border effect; modifying the ratio of species and life forms, decreasing the vegetal diversity and/or causing a lack of connectivity among the remaining indigenous forest resources. In the case of pipelines, the most important environmental measure intended to mitigate the damage caused to the flora is the adoption of Indigenous Flora Rescue Programs. This paper is aimed at analyzing the programs currently applied during the implementation of the GASENE project, by conducting a case study. The main targets of such program are obtaining seeds and fruits with a view to subsidize the potential production of sapling to be further employed in the recovery of areas impacted by the pipeline works; and then relocate the most significant samples of species rescued from the suppressed areas in order to comprise forest areas adjacent to the pipeline's right-of-way. The programs had little differences in their methodology while being implemented, however, we consider that up to the present moment the results obtained in the preservation of species of native flora have been satisfactory. (author)

  1. The lived experience of rescuing people who have driven into floodwater: Understanding challenges and identifying areas for providing support.

    Science.gov (United States)

    Keech, Jacob J; Smith, Stephanie R; Peden, Amy E; Hagger, Martin S; Hamilton, Kyra

    2018-06-11

    Drowning is a major public health issue, with risk increasing during times of flood. Driving though floodwater is a major risk factor for flood-related drowning and injury, and despite widespread public health campaigns, many people continue to undertake this risky behaviour and require rescue. We aimed to identify key challenges faced by emergency services personnel when rescuing those who have driven into floodwater, and to identify strategies for supporting rescuers in this important role. Australian flood rescue operators (N=8) who had previously rescued a driver who had driven through floodwater, participated in semi-structured interviews. Data were analysed using thematic analysis. Four challenges emerged from their experiences: Involvement of untrained personnel, varying information provided by emergency telephone operators, behaviour of drivers complicating the rescue, people sightseeing floods or flood rescues, or ignoring closed roads providing sources of distraction and frustration. We propose five strategies for translating these results into practice, including: training and protocol development for (1) emergency personnel and (2) telephone operators, (3) training for rescuers regarding non-compliant rescuees, (4) educating the public, and (5) increasing compliance with closed roads. Current findings provide valuable insights into how rescuers can be supported in performing their roles, and implementation of these strategies has the potential to reduce fatalities occurring due to driving through floodwater. SO WHAT?: The strategies presented have the potential to reduce the frequency and improve the outcomes of floodwater rescues, aiding in the prevention of injury and death. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Periodontal Defects in the A116T Knock-in Murine Model of Odontohypophosphatasia.

    Science.gov (United States)

    Foster, B L; Sheen, C R; Hatch, N E; Liu, J; Cory, E; Narisawa, S; Kiffer-Moreira, T; Sah, R L; Whyte, M P; Somerman, M J; Millán, J L

    2015-05-01

    Mutations in ALPL result in hypophosphatasia (HPP), a disease causing defective skeletal mineralization. ALPL encodes tissue nonspecific alkaline phosphatase (ALP), an enzyme that promotes mineralization by reducing inorganic pyrophosphate, a mineralization inhibitor. In addition to skeletal defects, HPP causes dental defects, and a mild clinical form of HPP, odontohypophosphatasia, features only a dental phenotype. The Alpl knockout (Alpl (-/-)) mouse phenocopies severe infantile HPP, including profound skeletal and dental defects. However, the severity of disease in Alpl (-/-) mice prevents analysis at advanced ages, including studies to target rescue of dental tissues. We aimed to generate a knock-in mouse model of odontohypophosphatasia with a primarily dental phenotype, based on a mutation (c.346G>A) identified in a human kindred with autosomal dominant odontohypophosphatasia. Biochemical, skeletal, and dental analyses were performed on the resulting Alpl(+/A116T) mice to validate this model. Alpl(+/A116T) mice featured 50% reduction in plasma ALP activity compared with wild-type controls. No differences in litter size, survival, or body weight were observed in Alpl(+/A116T) versus wild-type mice. The postcranial skeleton of Alpl(+/A116T) mice was normal by radiography, with no differences in femur length, cortical/trabecular structure or mineral density, or mechanical properties. Parietal bone trabecular compartment was mildly altered. Alpl(+/A116T) mice featured alterations in the alveolar bone, including radiolucencies and resorptive lesions, osteoid accumulation on the alveolar bone crest, and significant differences in several bone properties measured by micro-computed tomography. Nonsignificant changes in acellular cementum did not appear to affect periodontal attachment or function, although circulating ALP activity was correlated significantly with incisor cementum thickness. The Alpl(+/A116T) mouse is the first model of odontohypophosphatasia

  3. Dirichlet topological defects

    International Nuclear Information System (INIS)

    Carroll, S.M.; Trodden, M.

    1998-01-01

    We propose a class of field theories featuring solitonic solutions in which topological defects can end when they intersect other defects of equal or higher dimensionality. Such configurations may be termed open-quotes Dirichlet topological defects,close quotes in analogy with the D-branes of string theory. Our discussion focuses on defects in scalar field theories with either gauge or global symmetries, in 3+1 dimensions; the types of defects considered include walls ending on walls, strings on walls, and strings on strings. copyright 1998 The American Physical Society

  4. Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome

    DEFF Research Database (Denmark)

    Jensen, Uffe Birk; Sunde, Lone; Timshel, Susanne

    2010-01-01

    of MLH1, MSH2 or MSH6 corresponding to the mutations identified in 7 of the 16 cases investigated, and these tumors were diagnosed at mean 50 (33-66) years of age. The demonstration of defective MMR in a substantial proportion of the breast cancers studied links yet another tumor type to HNPCC. Though...

  5. A change of attitude: From rescue to prevention

    International Nuclear Information System (INIS)

    Covalschi, Valentina

    2002-01-01

    The qualitative and quantitative leap recorded by economical companies after the Romanian Revolution occurred in 1989, has positively influenced the functioning of the workplaces and working environment by increasing the employees' occupational safety, well being, health and results of their activities. In fact it has determined a new approach of safety culture. This has resulted in a change of attitude: from rescue to prevention. (author)

  6. Probability of defect detection of Posiva's electron beam weld

    International Nuclear Information System (INIS)

    Kanzler, D.; Mueller, C.; Pitkaenen, J.

    2013-12-01

    The report 'Probability of Defect Detection of Posiva's electron beam weld' describes POD curves of four NDT methods radiographic testing, ultrasonic testing, eddy current testing and visual testing. POD-curves are based on the artificial defects in reference blocks. The results are devoted to the demonstration of suitability of the methods for EB weld testing. Report describes methodology and procedure applied by BAM. Report creates a link from the assessment of the reliability and inspection performance to the risk assessment process of the canister final disposal project. Report ensures the confirmation of the basic quality of the NDT methods and their capability to describe the quality of the EB-weld. The probability of detection curves are determined based on the MIL-1823 standard and it's reliability guidelines. The MIL-1823 standard was developed for the determination of integrity of gas turbine engines for the US military. In the POD-process there are determined as a key parameter for the defect detectability the a90/95 magnitudes, i.e. the size measure a of the defect, for which the lower 95 % confidence band crosses the 90 % POD level. By this way can be confirmed that defects with a size of a90/95 will be detected with 90 % probability. In case the experiment will be repeated 5 % might fall outside this confidence limit. (orig.)

  7. Prevalence of congenital color vision defects in Saudi females of Arab origin.

    Science.gov (United States)

    Alabdelmoneam, Mussaed

    2011-09-01

    Inherited color vision deficiencies (CVD) vary in prevalence by population and by sex. The most common CVD is X chromosome-linked anomalous trichromacy. Prevalence varies significantly by sex and race. The frequency of color vision defects in Saudi females has not been studied previously. This study surveyed the prevalence of congenital color vision defects in Saudi females of Arab origin. Seven thousand four hundred sixty-seven female subjects (N = 7,467) from the Kingdom of Saudi Arabia were screened using both Ishihara pseudoisochromatic plates and the Farnsworth Dichotomous test (D-15). CVD subjects were tested further with the Farnsworth-Munsell 100 Hue test. Of 7,467 female subjects tested, 26 subjects were found to have defective color vision, for a prevalence of 0.35%. Sixteen subjects had a deutan defect, and 10 had a protan defect. Arab females have significantly lower prevalence of CVD when compared with published data from females of other races. Analysis of the 5 regions of Saudi Arabia showed no significant difference between the regions. Prevalence of CVD among Saudi females of Arab origin is 0.35% and is among the lowest of all published data. Copyright © 2011 American Optometric Association. Published by Elsevier Inc. All rights reserved.

  8. Embryo rescue of crosses between diploid and tetraploid grape ...

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... Five cross combinations Jumeigui×Xinghua No.1, 87-1×Kyoho, Kyoho×Muscat Hamburg, Jumeigui×. Hongqitezao and Red globle×Kyoho were used as the testing materials. Factors that affect embryo rescue from crossed seeds between diploid and tetraploid grape were studied applying L25(55).

  9. Embryo rescue of crosses between diploid and tetraploid grape ...

    African Journals Online (AJOL)

    Five cross combinations Jumeigui×Xinghua No.1, 87-1×Kyoho, Kyoho×Muscat Hamburg, Jumeigui× Hongqitezao and Red globle×Kyoho were used as the testing materials. Factors that affect embryo rescue from crossed seeds between diploid and tetraploid grape were studied applying L25(55) orthogonal experiment ...

  10. Work Engagement among Rescue Workers: Psychometric Properties of the Portuguese UWES

    Science.gov (United States)

    Sinval, Jorge; Marques-Pinto, Alexandra; Queirós, Cristina; Marôco, João

    2018-01-01

    Rescue workers have a stressful and risky occupation where being engaged is crucial to face physical and emotional risks in order to help other persons. This study aims to estimate work engagement levels of rescue workers (namely comparing nurses, firefighters, and police officers) and to assess the validity evidence related to the internal structure of the Portuguese versions of the UWES-17 and UWES-9, namely, dimensionality, measurement invariance between occupational groups, and reliability of the scores. To evaluate the dimensionality, we compared the fit of the three-factor model with the fit of a second-order model. A Portuguese version of the instrument was applied to a convenience sample of 3,887 rescue workers (50% nurses, 39% firefighters, and 11% police officers). Work engagement levels were moderate to high, with firefighters being the highest and nurses being the lowest engaged. Psychometric properties were evaluated in the three-factor original structure revealing acceptable fit to the data in the UWES-17, although the UWES-9 had better psychometric properties. Given the observed statistically significant correlations between the three original factors, we proposed a 2nd hierarchal structure that we named work engagement. The UWES-9 first-order model obtained full uniqueness measurement invariance, and the second-order model obtained partial (metric) second-order invariance. PMID:29403403

  11. Work Engagement among Rescue Workers: Psychometric Properties of the Portuguese UWES

    Directory of Open Access Journals (Sweden)

    Jorge Sinval

    2018-01-01

    Full Text Available Rescue workers have a stressful and risky occupation where being engaged is crucial to face physical and emotional risks in order to help other persons. This study aims to estimate work engagement levels of rescue workers (namely comparing nurses, firefighters, and police officers and to assess the validity evidence related to the internal structure of the Portuguese versions of the UWES-17 and UWES-9, namely, dimensionality, measurement invariance between occupational groups, and reliability of the scores. To evaluate the dimensionality, we compared the fit of the three-factor model with the fit of a second-order model. A Portuguese version of the instrument was applied to a convenience sample of 3,887 rescue workers (50% nurses, 39% firefighters, and 11% police officers. Work engagement levels were moderate to high, with firefighters being the highest and nurses being the lowest engaged. Psychometric properties were evaluated in the three-factor original structure revealing acceptable fit to the data in the UWES-17, although the UWES-9 had better psychometric properties. Given the observed statistically significant correlations between the three original factors, we proposed a 2nd hierarchal structure that we named work engagement. The UWES-9 first-order model obtained full uniqueness measurement invariance, and the second-order model obtained partial (metric second-order invariance.

  12. Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity

    Science.gov (United States)

    Cai, Chenxu; Liu, Guangao; Wang, Yuande; Du, Juan; Lin, Xin; Yang, Meixiang

    2017-01-01

    Signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (TFH) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in TFH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient TFH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP. PMID:28049627

  13. Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity.

    Science.gov (United States)

    Chen, Shasha; Cai, Chenxu; Li, Zehua; Liu, Guangao; Wang, Yuande; Blonska, Marzenna; Li, Dan; Du, Juan; Lin, Xin; Yang, Meixiang; Dong, Zhongjun

    2017-02-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (T FH ) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in T FH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient T FH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP. © 2017 Chen et al.

  14. Defect forces, defect couples and path integrals in fracture mechanics

    International Nuclear Information System (INIS)

    Roche, R.L.

    1979-07-01

    In this work, it is shown that the path integrals can be introduced without any reference to the material behavior. The method is based on the definition in a continuous medium of a set of vectors and couples having the dimension of a force or a moment. More precisely, definitions are given of volume defect forces, surface defect forces, volume defect couples, and surface defect couples. This is done with the help of the stress working variation of a particule moving through the solid. The most important result is: the resultant of all the defect forces included in a volume V is the J integral on the surface surrounding V and the moment resultant is the L integral. So these integrals are defined without any assumption on the material constitutive equation. Another result is the material form of the virtual work principle - defect forces are acting like conventional forces in the conventional principles of virtual work. This lead to the introduction of the energy momentum tensor and of the associated couple stress. Application of this method is made to fracture mechanics in studying the defect forces distribution around a crack [fr

  15. X-Linked Creatine Transporter Deficiency Presenting as a Mitochondrial Disorder

    NARCIS (Netherlands)

    Hathaway, S.C.; Friez, M.; Limbo, K.; Parker, C.; Salomons, G.S.; Vockley, J.; Wood, T.; Abdul-Rahman, O.A.

    2010-01-01

    X-linked creatine transporter defect is caused by mutations in SLC6A8 at Xq28, which encodes the sodium-dependent creatine transporter. Reduction in creatine uptake results in elevated urine creatine and CSF creatine deficiency, which can be detected on magnetic resonance spectroscopy. We report a

  16. Neural Tube Defects

    Science.gov (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  17. Tethered Balloon Technology in Design Solutions for Rescue and Relief Team Emergency Communication Services.

    Science.gov (United States)

    Alsamhi, Saeed Hamood; Ansari, Mohd Samar; Ma, Ou; Almalki, Faris; Gupta, Sachin Kumar

    2018-05-23

    The actions taken at the initial times of a disaster are critical. Catastrophe occurs because of terrorist acts or natural hazards which have the potential to disrupt the infrastructure of wireless communication networks. Therefore, essential emergency functions such as search, rescue, and recovery operations during a catastrophic event will be disabled. We propose tethered balloon technology to provide efficient emergency communication services and reduce casualty mortality and morbidity for disaster recovery. The tethered balloon is an actively developed research area and a simple solution to support the performance, facilities, and services of emergency medical communication. The most critical requirement for rescue and relief teams is having a higher quality of communication services which enables them to save people's lives. Using our proposed technology, it has been reported that the performance of rescue and relief teams significantly improved. OPNET Modeler 14.5 is used for a network simulated with the help of ad hoc tools (Disaster Med Public Health Preparedness. 2018;page 1 of 8).

  18. Prospects of using medium-wave band for radio communication with rescue mobile teams of EMERCOM of Russia

    Science.gov (United States)

    Bazhukov, I. F.; Dulkejt, I. V.; Zavyalov, S. A.; Lvova, Yu V.; Lyashuk, A. N.; Puzyrev, P. I.; Rekunov, S. G.; Chaschin, E. A.; Sharapov, S. V.

    2018-01-01

    The results of tests in-situ of the prototype of medium-wave mobile radio station «Noema-SV» in Western Siberia, Omsk region and Vorkuta Arctic Integrated Emergency and Rescue Center of EMERCOM of Russia are presented. Radio paths tests in-situ in the Far North show the possibility of radio communication with rescue mobile teams of EMERCOM of Russia in the medium-wave band within distances of several tens of kilometers of rugged topography. The radio range on a flat terrain increases to several hundreds of kilometers. Shortened medium-wave band antennas developed at OmSTU and employed by rescue mobile teams of EMERCOM of Russia were used in.

  19. The Drosophila Neurally Altered Carbohydrate Mutant Has a Defective Golgi GDP-fucose Transporter*

    Science.gov (United States)

    Geisler, Christoph; Kotu, Varshika; Sharrow, Mary; Rendić, Dubravko; Pöltl, Gerald; Tiemeyer, Michael; Wilson, Iain B. H.; Jarvis, Donald L.

    2012-01-01

    Studying genetic disorders in model organisms can provide insights into heritable human diseases. The Drosophila neurally altered carbohydrate (nac) mutant is deficient for neural expression of the HRP epitope, which consists of N-glycans with core α1,3-linked fucose residues. Here, we show that a conserved serine residue in the Golgi GDP-fucose transporter (GFR) is substituted by leucine in nac1 flies, which abolishes GDP-fucose transport in vivo and in vitro. This loss of function is due to a biochemical defect, not to destabilization or mistargeting of the mutant GFR protein. Mass spectrometry and HPLC analysis showed that nac1 mutants lack not only core α1,3-linked, but also core α1,6-linked fucose residues on their N-glycans. Thus, the nac1 Gfr mutation produces a previously unrecognized general defect in N-glycan core fucosylation. Transgenic expression of a wild-type Gfr gene restored the HRP epitope in neural tissues, directly demonstrating that the Gfr mutation is solely responsible for the neural HRP epitope deficiency in the nac1 mutant. These results validate the Drosophila nac1 mutant as a model for the human congenital disorder of glycosylation, CDG-IIc (also known as LAD-II), which is also the result of a GFR deficiency. PMID:22745127

  20. Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect.

    Directory of Open Access Journals (Sweden)

    Guido Veit

    2016-05-01

    Full Text Available The most common cystic fibrosis (CF causing mutation, deletion of phenylalanine 508 (ΔF508 or Phe508del, results in functional expression defect of the CF transmembrane conductance regulator (CFTR at the apical plasma membrane (PM of secretory epithelia, which is attributed to the degradation of the misfolded channel at the endoplasmic reticulum (ER. Deletion of phenylalanine 670 (ΔF670 in the yeast oligomycin resistance 1 gene (YOR1, an ABC transporter of Saccharomyces cerevisiae phenocopies the ΔF508-CFTR folding and trafficking defects. Genome-wide phenotypic (phenomic analysis of the Yor1-ΔF670 biogenesis identified several modifier genes of mRNA processing and translation, which conferred oligomycin resistance to yeast. Silencing of orthologues of these candidate genes enhanced the ΔF508-CFTR functional expression at the apical PM in human CF bronchial epithelia. Although knockdown of RPL12, a component of the ribosomal stalk, attenuated the translational elongation rate, it increased the folding efficiency as well as the conformational stability of the ΔF508-CFTR, manifesting in 3-fold augmented PM density and function of the mutant. Combination of RPL12 knockdown with the corrector drug, VX-809 (lumacaftor restored the mutant function to ~50% of the wild-type channel in primary CFTRΔF508/ΔF508 human bronchial epithelia. These results and the observation that silencing of other ribosomal stalk proteins partially rescue the loss-of-function phenotype of ΔF508-CFTR suggest that the ribosomal stalk modulates the folding efficiency of the mutant and is a potential therapeutic target for correction of the ΔF508-CFTR folding defect.

  1. Space rescue system definition (system performance analysis and trades)

    Science.gov (United States)

    Housten, Sam; Elsner, Tim; Redler, Ken; Svendsen, Hal; Wenzel, Sheri

    This paper addresses key technical issues involved in the system definition of the Assured Crew Return Vehicle (ACRV). The perspective on these issues is that of a prospective ACRV contractor, performing system analysis and trade studies. The objective of these analyses and trade studies is to develop the recovery vehicle system concept and top level requirements. The starting point for this work is the definition of the set of design missions for the ACRV. This set of missions encompasses three classes of contingency/emergency (crew illness/injury, space station catastrophe/failure, transportation element catastrophe/failure). The need is to provide a system to return Space Station crew to Earth quickly (less than 24 hours) in response to randomly occurring contingency events over an extended period of time (30 years of planned Space Station life). The main topics addressed and characterized in this paper include the following: Key Recovery (Rescue) Site Access Considerations; Rescue Site Locations and Distribution; Vehicle Cross Range vs Site Access; On-orbit Loiter Capability and Vehicle Design; and Water vs. Land Recovery.

  2. 46 CFR 133.175 - Survival craft and rescue boat equipment.

    Science.gov (United States)

    2010-10-01

    ... line 1 2 1 2 15 Instruction card 1 1 17 Knife 1,3 1 1 1 1 18 Ladder 1 1 19 Mirror, signalling 1 1 20... Not required for inflated or rigid-inflated rescue boats. 3 A hatchet counts towards this requirement...

  3. Poly(lactic-co-glycolide) polymer constructs cross-linked with human BMP-6 and VEGF protein significantly enhance rat mandible defect repair.

    Science.gov (United States)

    Das, Anusuya; Fishero, Brian A; Christophel, J Jared; Li, Ching-Ju; Kohli, Nikita; Lin, Yong; Dighe, Abhijit S; Cui, Quanjun

    2016-04-01

    We have previously shown that the combined delivery of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 6 (BMP-6) induces significantly more bone formation than that induced by the delivery of any single factor or a combination of any two factors. We now determine whether the exogenous addition of VEGF and BMP-6 is sufficient for bone healing when MSCs are not provided. Poly(lactic-co-glycolic acid) (PLAGA) microsphere-based three-dimensional scaffolds (P) were fabricated by thermal sintering of PLAGA microspheres. The scaffolds were chemically cross-linked with 200 ng recombinant human VEGF (P(VEGF)) or BMP-6 (P(BMP-6)) or both (P(VEGF+BMP-6)) by the EDC-NHS-MES method. Release of the proteins from the scaffolds was detected for 21 days in vitro which confirmed their comparable potential to supply the proteins in vivo. The scaffolds were delivered to a critical-sized mandibular defect created in 32 Sprague Dawley rats. Significant bone regeneration was observed only in rats with P(VEGF+BMP-6) scaffolds at weeks 2, 8 and 12 as revealed by micro-computer tomography. Vascular ingrowth was higher in the P(VEGF+BMP-6) group as seen by microfil imaging than in other groups. Trichrome staining revealed that a soft callus formed in P(VEGF), P(BMP-6) and P(VEGF+BMP-6) but not in P. MSCs isolated from rat femurs displayed expression of the bone-specific marker osteocalcin when cultured with P(VEGF), P(BMP-6), or P(VEGF+BMP-6) but not with P. Robust mineralization and increased alkaline phosphatase gene expression were seen in rat MSCs when cultured on P(VEGF+BMP-6) but not on P, P(VEGF), or P(BMP-6). Thus, unlike the delivery of VEGF or BMP-6 alone, the combined delivery of VEGF and BMP-6 to the bone defect significantly enhanced bone repair through the enhancement of angiogenesis and the differentiation of endogenously recruited MSCs into the bone repair site.

  4. Volunteers Oriented Interface Design for the Remote Navigation of Rescue Robots at Large-Scale Disaster Sites

    Science.gov (United States)

    Yang, Zhixiao; Ito, Kazuyuki; Saijo, Kazuhiko; Hirotsune, Kazuyuki; Gofuku, Akio; Matsuno, Fumitoshi

    This paper aims at constructing an efficient interface being similar to those widely used in human daily life, to fulfill the need of many volunteer rescuers operating rescue robots at large-scale disaster sites. The developed system includes a force feedback steering wheel interface and an artificial neural network (ANN) based mouse-screen interface. The former consists of a force feedback steering control and a six monitors’ wall. It provides a manual operation like driving cars to navigate a rescue robot. The latter consists of a mouse and a camera’s view displayed in a monitor. It provides a semi-autonomous operation by mouse clicking to navigate a rescue robot. Results of experiments show that a novice volunteer can skillfully navigate a tank rescue robot through both interfaces after 20 to 30 minutes of learning their operation respectively. The steering wheel interface has high navigating speed in open areas, without restriction of terrains and surface conditions of a disaster site. The mouse-screen interface is good at exact navigation in complex structures, while bringing little tension to operators. The two interfaces are designed to switch into each other at any time to provide a combined efficient navigation method.

  5. The potential use of unmanned aircraft systems (drones) in mountain search and rescue operations.

    Science.gov (United States)

    Karaca, Yunus; Cicek, Mustafa; Tatli, Ozgur; Sahin, Aynur; Pasli, Sinan; Beser, Muhammed Fatih; Turedi, Suleyman

    2018-04-01

    This study explores the potential use of drones in searching for and locating victims and of motorized transportation of search and rescue providers in a mountain environment using a simulation model. This prospective randomized simulation study was performed in order to compare two different search and rescue techniques in searching for an unconscious victim on snow-covered ground. In the control arm, the Classical Line Search Technique (CLT) was used, in which the search is performed on foot and the victim is reached on foot. In the intervention arm, the Drone-snowmobile Technique (DST) was used, the search being performed by drone and the victim reached by snowmobile. The primary outcome of the study was the comparison of the two search and rescue techniques in terms of first human contact time. Twenty search and rescue operations were conducted in this study. Median time to arrival at the mannequin was 57.3min for CLT, compared to 8.9min for DST. The median value of the total searched area was 88,322.0m 2 for CLT and 228,613.0m 2 for DST. The median area searched per minute was 1489.6m 2 for CLT and 32,979.9m 2 for DST (pdrone using DST compared to the classical technique, and the victim can be located faster and reached earlier with rescuers transported by snowmobile. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

    Science.gov (United States)

    Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

    2005-12-15

    Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

  7. Native flora rescue program: GASENE project case study

    Energy Technology Data Exchange (ETDEWEB)

    Serricchio, Claudio; Caldas, Flaviana V. [PETROBRAS, Rio de Janeiro, RJ (Brazil); Akahori, Lisa [Telsan, Rio de Janeiro, RJ (Brazil); Jacomelli Junior, Jose Almir [AGF Engenharia, Araucaria, PR (Brazil)

    2009-07-01

    Concerning the surrounding flora, the implementation of pipelines may cause fragmentation and isolation of the remaining natural vegetation, possibly changing the forest structure; thus raising the border effect; modifying the ratio of species and life forms, decreasing the vegetal diversity and/or causing a lack of connectivity among the remaining indigenous forest resources. In the case of pipelines, the most important environmental measure intended to mitigate the damage caused to the flora is the adoption of Indigenous Flora Rescue Programs. This paper is aimed at analyzing the programs currently applied during the implementation of the GASENE project, by conducting a case study. The main targets of such program are obtaining seeds and fruits with a view to subsidize the potential production of sapling to be further employed in the recovery of areas impacted by the pipeline works; and then relocate the most significant samples of species rescued from the suppressed areas in order to comprise forest areas adjacent to the pipeline's right-of-way. The programs had little differences in their methodology while being implemented, however, we consider that up to the present moment the results obtained in the preservation of species of native flora have been satisfactory. (author)

  8. On holographic defect entropy

    International Nuclear Information System (INIS)

    Estes, John; Jensen, Kristan; O’Bannon, Andy; Tsatis, Efstratios; Wrase, Timm

    2014-01-01

    We study a number of (3+1)- and (2+1)-dimensional defect and boundary conformal field theories holographically dual to supergravity theories. In all cases the defects or boundaries are planar, and the defects are codimension-one. Using holography, we compute the entanglement entropy of a (hemi-)spherical region centered on the defect (boundary). We define defect and boundary entropies from the entanglement entropy by an appropriate background subtraction. For some (3+1)-dimensional theories we find evidence that the defect/boundary entropy changes monotonically under certain renormalization group flows triggered by operators localized at the defect or boundary. This provides evidence that the g-theorem of (1+1)-dimensional field theories generalizes to higher dimensions

  9. Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents

    International Nuclear Information System (INIS)

    Hoy, C.A.; Thompson, L.H.; Mooney, C.L.; Salazar, E.P.

    1985-01-01

    DNA repair-deficient mutants from five genetic complementation groups isolated previously from Chinese hamster cells were assayed for survival after exposure to the bifunctional alkylating agents mitomycin C or diepoxybutane. Groups 1, 3, and 5 exhibited 1.6- to 3-fold hypersensitivity compared to the wild-type cells, whereas Groups 2 and 4 exhibited extraordinary hypersensitivity. Mutants from Groups 1 and 2 were exposed to 22 other bifunctional alkylating agents in a rapid assay that compared cytotoxicity of the mutants to the wild-type parental strain, AA8. With all but two of the compounds, the Group 2 mutant (UV4) was 15- to 60-fold more sensitive than AA8 or the Group 1 mutant (UV5). UV4 showed only 6-fold hypersensitivity to quinacrine mustard. Alkaline elution measurements showed that this compound produced few DNA interstrand cross-links but numerous strand breaks. Therefore, the extreme hypersensitivity of mutants from Groups 2 and 4 appeared specific for compounds the main cytotoxic lesions of which were DNA cross-links. Mutant UV5 was only 1- to 4-fold hypersensitive to all the compounds. Although the initial number of cross-links was similar for the three cell lines, the efficiency of removal of cross-links was lowest in UV4 and intermediate in UV5. These results suggest that the different levels of sensitivity are specifically related to different efficiencies of DNA cross-link removal. The phenotype of hypersensitivity to both UV radiation and cross-link damage exhibited by the mutants in Groups 2 and 4 appears to differ from those of the known human DNA repair syndromes

  10. Single-step generation of gene knockout-rescue system in pluripotent stem cells by promoter insertion with CRISPR/Cas9.

    Science.gov (United States)

    Matsunaga, Taichi; Yamashita, Jun K

    2014-02-07

    Specific gene knockout and rescue experiments are powerful tools in developmental and stem cell biology. Nevertheless, the experiments require multiple steps of molecular manipulation for gene knockout and subsequent rescue procedures. Here we report an efficient and single step strategy to generate gene knockout-rescue system in pluripotent stem cells by promoter insertion with CRISPR/Cas9 genome editing technology. We inserted a tetracycline-regulated inducible gene promoter (tet-OFF/TRE-CMV) upstream of the endogenous promoter region of vascular endothelial growth factor receptor 2 (VEGFR2/Flk1) gene, an essential gene for endothelial cell (EC) differentiation, in mouse embryonic stem cells (ESCs) with homologous recombination. Both homo- and hetero-inserted clones were efficiently obtained through a simple selection with a drug-resistant gene. The insertion of TRE-CMV promoter disrupted endogenous Flk1 expression, resulting in null mutation in homo-inserted clones. When the inserted TRE-CMV promoter was activated with doxycycline (Dox) depletion, Flk1 expression was sufficiently recovered from the downstream genomic Flk1 gene. Whereas EC differentiation was almost completely perturbed in homo-inserted clones, Flk1 rescue with TRE-CMV promoter activation restored EC appearance, indicating that phenotypic changes in EC differentiation can be successfully reproduced with this knockout-rescue system. Thus, this promoter insertion strategy with CRISPR/Cas9 would be a novel attractive method for knockout-rescue experiments. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Reduced prostasin (CAP1/PRSS8 activity eliminates HAI-1 and HAI-2 deficiency-associated developmental defects by preventing matriptase activation.

    Directory of Open Access Journals (Sweden)

    Roman Szabo

    Full Text Available Loss of either hepatocyte growth factor activator inhibitor (HAI-1 or -2 is associated with embryonic lethality in mice, which can be rescued by the simultaneous inactivation of the membrane-anchored serine protease, matriptase, thereby demonstrating that a matriptase-dependent proteolytic pathway is a critical developmental target for both protease inhibitors. Here, we performed a genetic epistasis analysis to identify additional components of this pathway by generating mice with combined deficiency in either HAI-1 or HAI-2, along with genes encoding developmentally co-expressed candidate matriptase targets, and screening for the rescue of embryonic development. Hypomorphic mutations in Prss8, encoding the GPI-anchored serine protease, prostasin (CAP1, PRSS8, restored placentation and normal development of HAI-1-deficient embryos and prevented early embryonic lethality, mid-gestation lethality due to placental labyrinth failure, and neural tube defects in HAI-2-deficient embryos. Inactivation of genes encoding c-Met, protease-activated receptor-2 (PAR-2, or the epithelial sodium channel (ENaC alpha subunit all failed to rescue embryonic lethality, suggesting that deregulated matriptase-prostasin activity causes developmental failure independent of aberrant c-Met and PAR-2 signaling or impaired epithelial sodium transport. Furthermore, phenotypic analysis of PAR-1 and matriptase double-deficient embryos suggests that the protease may not be critical for focal proteolytic activation of PAR-2 during neural tube closure. Paradoxically, although matriptase auto-activates and is a well-established upstream epidermal activator of prostasin, biochemical analysis of matriptase- and prostasin-deficient placental tissues revealed a requirement of prostasin for conversion of the matriptase zymogen to active matriptase, whereas prostasin zymogen activation was matriptase-independent.

  12. Exploring the ethical landscape of robot-assisted Search and Rescue

    NARCIS (Netherlands)

    Harbers, M.; Greeff, J. de; Kruijff-Korbayová, I.; Neerincx, M.A.; Hindriks, K.V.

    2017-01-01

    As robots are increasingly used in Search and Rescue (SAR) missions, it becomes highly relevant to study how SAR robots can be developed and deployed in a responsible way. In contrast to some other robot application domains, e.g. military and healthcare, the ethics of robot-assisted SAR are

  13. Rescue apparatus for a high working oil derrick

    Energy Technology Data Exchange (ETDEWEB)

    Prokopov, O.P.; Yagudin, S.Z.

    1980-05-18

    In order to improve reliability of the rescue apparatus a device for lowering a basket is made in the form of a collapsible forked support installed in the vertical plane inclined away from the tower. Its lower ends are attached by hinges to the base of the derrick. The upper end is connected to the derrick by means of a fastener. The apparatus has brakes with shock straps for receiving forked support.

  14. Defects in semiconductors

    CERN Document Server

    Romano, Lucia; Jagadish, Chennupati

    2015-01-01

    This volume, number 91 in the Semiconductor and Semimetals series, focuses on defects in semiconductors. Defects in semiconductors help to explain several phenomena, from diffusion to getter, and to draw theories on materials' behavior in response to electrical or mechanical fields. The volume includes chapters focusing specifically on electron and proton irradiation of silicon, point defects in zinc oxide and gallium nitride, ion implantation defects and shallow junctions in silicon and germanium, and much more. It will help support students and scientists in their experimental and theoret

  15. Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice

    Directory of Open Access Journals (Sweden)

    Coralie Fassier

    2013-01-01

    Mutations in SPG4, encoding the microtubule-severing protein spastin, are responsible for the most frequent form of hereditary spastic paraplegia (HSP, a heterogeneous group of genetic diseases characterized by degeneration of the corticospinal tracts. We previously reported that mice harboring a deletion in Spg4, generating a premature stop codon, develop progressive axonal degeneration characterized by focal axonal swellings associated with impaired axonal transport. To further characterize the molecular and cellular mechanisms underlying this mutant phenotype, we have assessed microtubule dynamics and axonal transport in primary cultures of cortical neurons from spastin-mutant mice. We show an early and marked impairment of microtubule dynamics all along the axons of spastin-deficient cortical neurons, which is likely to be responsible for the occurrence of axonal swellings and cargo stalling. Our analysis also reveals that a modulation of microtubule dynamics by microtubule-targeting drugs rescues the mutant phenotype of cortical neurons. Together, these results contribute to a better understanding of the pathogenesis of SPG4-linked HSP and ascertain the influence of microtubule-targeted drugs on the early axonal phenotype in a mouse model of the disease.

  16. CMSMAP : oil, chemical, search and rescue, and marine emergency response crisis management system

    International Nuclear Information System (INIS)

    Anderson, E.L.; Howlett, E.; Galagan, C.; Giguere, T.; Wee, F.; Chong, J.

    2002-01-01

    This paper describes a newly developed Crisis Management System (CMS) which makes it possible to view oil and chemical spills on the seafloor. The CMS is designed to run in a network environment, so that multiple stations can be used cooperatively to respond to a spill incident. It was developed by the Maritime and Port Authority in Singapore and represents a singular integration of a ship's bridge simulator hardware and software. It incorporates numerical models and emergency response software. The CMS is installed in a specifically designed building at the Singapore Polytechnic University, and is integrated with two shipping bridge simulators. One user interface has access to models dealing with oil spills, chemical spills, search and rescues, marine emergencies, and nuclear disasters. The interface is linked to a response management system. The entire system is used to train response personnel to marine emergencies. The histories and costs of planned response activities are described and logged for reference purposes. Estimates of damages associated with spills can be obtained. Alternative response plans can also be determined. Further research in 2002 will focus on developing real time response. 3 refs., 6 figs

  17. Review of the rescue, rehabilitation and restoration of oiled seabirds ...

    African Journals Online (AJOL)

    Review of the rescue, rehabilitation and restoration of oiled seabirds in South Africa, especially African penguins Spheniscus demersus and Cape gannets Morus capensis , 1983–2005. ... In addition, oiling has a long-term negative impact on the breeding productivity and cost of reproduction in de-oiled birds. The primary ...

  18. Developmental Defects of Caenorhabditis elegans Lacking Branched-chain α-Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency.

    Science.gov (United States)

    Jia, Fan; Cui, Mingxue; Than, Minh T; Han, Min

    2016-02-05

    Branched-chain α-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue-specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Percutaneous transhepatic recanalization of malignant hilarobstruction: A possible rescue for early failure of endoscopic y-stenting

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hoon; Kim, Chang Won; Lee, Tae Hong; Kim, Dong Uk [Pusan National University School of Medicine, Pusan National University Hospital, Busan (Korea, Republic of); Jeon, Ung Bae; Kang, Dae Hwan [Pusan National University School of Medicine, Yangsan Pusan National University Hospital, Yangsan (Korea, Republic of)

    2013-11-15

    Endoscopic biliary stenting is well known as an optimal method of management of malignant hilar obstruction, but sometimes the result is not satisfactory, with early stent failure. Percutaneous transhepatic biliary drainage (PTBD) has a distinct advantage over endoscopic retrograde cholangiopancreatoscopy in that with ultrasound guidance one or more appropriate segments for drainage can be chosen. We evaluated the effectiveness of percutaneous transhepatic stenting as a rescue of early failure of endoscopic stenting. Ten patients (4 men, 6 women; age range, 52-78 years; mean age, 69 years) with inoperable biliary obstruction (2 patients with gall bladder cancer and hilar invasion, and 8 patients with Klatskin tumor) and with early endoscopic stent failure were included in our study. All of the patients underwent PTBD and percutaneous transhepatic biliary stenting. Metallic stents were placed in all patients for internal drainage. Percutaneous rescue stenting was successful in all the patients technically and clinically. Mean time for the development of biliary obstruction was 13.5 days after endoscopic stenting. The mean patency of the rescue stenting was 122 days. The mean survival time for percutaneous transhepatic rescue stenting was 226.3 days. In early failure of endoscopic biliary stenting, percutaneous transhepatic recanalization can be a possible solution.

  20. Validation of the Athens Insomnia Scale for screening insomnia in South Korean firefighters and rescue workers.

    Science.gov (United States)

    Jeong, Hyeonseok S; Jeon, Yujin; Ma, Jiyoung; Choi, Yera; Ban, Soonhyun; Lee, Sooyeon; Lee, Bora; Im, Jooyeon Jamie; Yoon, Sujung; Kim, Jieun E; Lim, Jae-Ho; Lyoo, In Kyoon

    2015-10-01

    Sleep problems are a major cause of occupational stress in firefighters and rescue workers. We evaluated the psychometric properties of the Athens Insomnia Scale (AIS) among South Korean firefighters and rescue workers. Structured clinical interviews and self-report questionnaires were administered to 221 firefighters and rescue workers. The Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Short-Form 36-item Health Survey (SF36), and Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) were used to examine convergent and divergent validity. Test-retest reliability was calculated from a subsample (n = 24). Analysis of internal consistency, factor analysis, and receiver operator characteristic curve analysis were conducted. Cronbach's alpha was 0.88. The mean item-total correlation coefficient was 0.73. The test-retest reliability was excellent (ICC = 0.94). Significant correlations of the AIS with the PSQI, ISI, ESS, and SF36 confirmed convergent validity. Nonsignificant associations of the AIS with the AUDIT-C and socioeconomic status showed divergent validity. Factor analysis revealed a one-factor structure. For groups with different symptom severity, group-specific cutoff scores which may improve positive predictive values were suggested. The AIS may be a useful tool with good reliability and validity for screening insomnia symptoms in firefighters and rescue workers.

  1. Percutaneous transhepatic recanalization of malignant hilarobstruction: A possible rescue for early failure of endoscopic y-stenting

    International Nuclear Information System (INIS)

    Kwon, Hoon; Kim, Chang Won; Lee, Tae Hong; Kim, Dong Uk; Jeon, Ung Bae; Kang, Dae Hwan

    2013-01-01

    Endoscopic biliary stenting is well known as an optimal method of management of malignant hilar obstruction, but sometimes the result is not satisfactory, with early stent failure. Percutaneous transhepatic biliary drainage (PTBD) has a distinct advantage over endoscopic retrograde cholangiopancreatoscopy in that with ultrasound guidance one or more appropriate segments for drainage can be chosen. We evaluated the effectiveness of percutaneous transhepatic stenting as a rescue of early failure of endoscopic stenting. Ten patients (4 men, 6 women; age range, 52-78 years; mean age, 69 years) with inoperable biliary obstruction (2 patients with gall bladder cancer and hilar invasion, and 8 patients with Klatskin tumor) and with early endoscopic stent failure were included in our study. All of the patients underwent PTBD and percutaneous transhepatic biliary stenting. Metallic stents were placed in all patients for internal drainage. Percutaneous rescue stenting was successful in all the patients technically and clinically. Mean time for the development of biliary obstruction was 13.5 days after endoscopic stenting. The mean patency of the rescue stenting was 122 days. The mean survival time for percutaneous transhepatic rescue stenting was 226.3 days. In early failure of endoscopic biliary stenting, percutaneous transhepatic recanalization can be a possible solution.

  2. Transfection of embryonated Muscovy duck eggs with a recombinant plasmid is suitable for rescue of infectious Muscovy duck parvovirus.

    Science.gov (United States)

    Wang, Jianye; Huang, Yu; Ling, Jueyi; Wang, Zhixiang; Zhu, Guoqiang

    2017-12-01

    For members of the family Parvoviridae, rescue of infectious virus from recombinant plasmid is usually done in cultured cells. In this study, the whole genome of the pathogenic Muscovy duck parvovirus (MDPV) strain YY was cloned into the pBluescript II (SK) vector, generating recombinant plasmid pYY. With the aid of a transfection reagent, pYY plasmid was inoculated into 11-day-old embryonated Muscovy duck eggs via the chorioallantoic membrane route, resulting in the successful rescue of infectious virus and death of the embryos. The rescued virus exhibited pathogenicity in Muscovy ducklings similar to that of its parental strain, as evaluated based on the mortality rate. The results demonstrate that plasmid transfection in embryonated Muscovy duck eggs is a convenient and efficacious method for rescue of infectious MDPV in comparison to transfection of primary cells, which is somewhat time-consuming and laborious.

  3. Fibrous metaphyseal defects

    International Nuclear Information System (INIS)

    Ritschl, P.; Hajek, P.C.; Pechmann, U.

    1989-01-01

    Sixteen patients with fibrous metaphyseal defects were examined with both plain radiography and magnetic resonance (MR) imaging. Depending on the age of the fibrous metaphyseal defects, characteristic radiomorphologic changes were found which correlated well with MR images. Following intravenous Gadolinium-DTPA injection, fibrous metaphyseal defects invariably exhibited a hyperintense border and signal enhancement. (orig./GDG)

  4. Evolutionary developmental pathology and anthropology: A new field linking development, comparative anatomy, human evolution, morphological variations and defects, and medicine.

    Science.gov (United States)

    Diogo, Rui; Smith, Christopher M; Ziermann, Janine M

    2015-11-01

    We introduce a new subfield of the recently created field of Evolutionary-Developmental-Anthropology (Evo-Devo-Anth): Evolutionary-Developmental-Pathology-and-Anthropology (Evo-Devo-P'Anth). This subfield combines experimental and developmental studies of nonhuman model organisms, biological anthropology, chordate comparative anatomy and evolution, and the study of normal and pathological human development. Instead of focusing on other organisms to try to better understand human development, evolution, anatomy, and pathology, it places humans as the central case study, i.e., as truly model organism themselves. We summarize the results of our recent Evo-Devo-P'Anth studies and discuss long-standing questions in each of the broader biological fields combined in this subfield, paying special attention to the links between: (1) Human anomalies and variations, nonpentadactyly, homeotic transformations, and "nearest neighbor" vs. "find and seek" muscle-skeleton associations in limb+facial muscles vs. other head muscles; (2) Developmental constraints, the notion of "phylotypic stage," internalism vs. externalism, and the "logic of monsters" vs. "lack of homeostasis" views about human birth defects; (3) Human evolution, reversions, atavisms, paedomorphosis, and peromorphosis; (4) Scala naturae, Haeckelian recapitulation, von Baer's laws, and parallelism between phylogeny and development, here formally defined as "Phylo-Devo parallelism"; and (5) Patau, Edwards, and Down syndrome (trisomies 13, 18, 21), atavisms, apoptosis, heart malformations, and medical implications. © 2015 Wiley Periodicals, Inc.

  5. Enhanced endotoxin sensitivity in fps/fes-null mice with minimal defects in hematopoietic homeostasis.

    Science.gov (United States)

    Zirngibl, Ralph A; Senis, Yotis; Greer, Peter A

    2002-04-01

    The fps/fes proto-oncogene encodes a cytoplasmic protein tyrosine kinase implicated in growth factor and cytokine receptor signaling and thought to be essential for the survival and terminal differentiation of myeloid progenitors. Fps/Fes-null mice were healthy and fertile, displayed slightly reduced numbers of bone marrow myeloid progenitors and circulating mature myeloid cells, and were more sensitive to lipopolysaccharide (LPS). These phenotypes were rescued using a fps/fes transgene. This confirmed that Fps/Fes is involved in, but not required for, myelopoiesis and that it plays a role in regulating the innate immune response. Bone marrow-derived Fps/Fes-null macrophages showed no defects in granulocyte-macrophage colony-stimulating factor-, interleukin 6 (IL-6)-, or IL-3-induced activation of signal transducer and activator of transcription 3 (Stat3) and Stat5A or LPS-induced degradation of I kappa B or activation of p38, Jnk, Erk, or Akt.

  6. Management of Multi-Casualty Incidents in Mountain Rescue: Evidence-Based Guidelines of the International Commission for Mountain Emergency Medicine (ICAR MEDCOM).

    Science.gov (United States)

    Blancher, Marc; Albasini, François; Elsensohn, Fidel; Zafren, Ken; Hölzl, Natalie; McLaughlin, Kyle; Wheeler, Albert R; Roy, Steven; Brugger, Hermann; Greene, Mike; Paal, Peter

    2018-02-15

    Blancher, Marc, François Albasini, Fidel Elsensohn, Ken Zafren, Natalie Hölzl, Kyle McLaughlin, Albert R. Wheeler III, Steven Roy, Hermann Brugger, Mike Greene, and Peter Paal. Management of multi-casualty incidents in mountain rescue. High Alt Med Biol. 00:000-000, 2018. Multi-Casualty Incidents (MCI) occur in mountain areas. Little is known about the incidence and character of such events, and the kind of rescue response. Therefore, the International Commission for Mountain Emergency Medicine (ICAR MEDCOM) set out to provide recommendations for the management of MCI in mountain areas. Details of MCI occurring in mountain areas related to mountaineering activities and involving organized mountain rescue were collected. A literature search using (1) PubMed, (2) national mountain rescue registries, and (3) lay press articles on the internet was performed. The results were analyzed with respect to specific aspects of mountain rescue. We identified 198 MCIs that have occurred in mountain areas since 1956: 137 avalanches, 38 ski lift accidents, and 23 other events, including lightning injuries, landslides, volcanic eruptions, lost groups of people, and water-related accidents. General knowledge on MCI management is required. Due to specific aspects of triage and management, the approach to MCIs may differ between those in mountain areas and those in urban settings. Mountain rescue teams should be prepared to manage MCIs. Knowledge should be reviewed and training performed regularly. Cooperation between terrestrial rescue services, avalanche safety authorities, and helicopter crews is critical to successful management of MCIs in mountain areas.

  7. A change of attitude: from rescue to prevention

    International Nuclear Information System (INIS)

    Covalschi, Valentina I.

    2003-01-01

    The qualitative and quantitative leap recorded by economical companies after the Romanian Revolution occurred in 1989, has positively influenced the functioning of the workplaces and working environment by increasing the employees' occupational safety, well being, health and results of their activities. In fact it has determined a new approach of safety culture. This has resulted in a change of attitude: from rescue to prevention. The paper is addressing the steps in which this change has been occurred. (author)

  8. Medical rescue of naval combat: challenges and future

    OpenAIRE

    Jin, Hai; Hou, Li-Jun; Fu, Xiao-Bing

    2015-01-01

    There has been no large-scale naval combat in the last 30?years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Additionally, naval combat is facing unprecedented challenges. In this paper, we discuss the topic of medical rescue at sea: what challenges we face and what we could do. The contents discussed in this paper contain battlefield self-aid buddy care, clinical skills, organized health servi...

  9. ILT based defect simulation of inspection images accurately predicts mask defect printability on wafer

    Science.gov (United States)

    Deep, Prakash; Paninjath, Sankaranarayanan; Pereira, Mark; Buck, Peter

    2016-05-01

    At advanced technology nodes mask complexity has been increased because of large-scale use of resolution enhancement technologies (RET) which includes Optical Proximity Correction (OPC), Inverse Lithography Technology (ILT) and Source Mask Optimization (SMO). The number of defects detected during inspection of such mask increased drastically and differentiation of critical and non-critical defects are more challenging, complex and time consuming. Because of significant defectivity of EUVL masks and non-availability of actinic inspection, it is important and also challenging to predict the criticality of defects for printability on wafer. This is one of the significant barriers for the adoption of EUVL for semiconductor manufacturing. Techniques to decide criticality of defects from images captured using non actinic inspection images is desired till actinic inspection is not available. High resolution inspection of photomask images detects many defects which are used for process and mask qualification. Repairing all defects is not practical and probably not required, however it's imperative to know which defects are severe enough to impact wafer before repair. Additionally, wafer printability check is always desired after repairing a defect. AIMSTM review is the industry standard for this, however doing AIMSTM review for all defects is expensive and very time consuming. Fast, accurate and an economical mechanism is desired which can predict defect printability on wafer accurately and quickly from images captured using high resolution inspection machine. Predicting defect printability from such images is challenging due to the fact that the high resolution images do not correlate with actual mask contours. The challenge is increased due to use of different optical condition during inspection other than actual scanner condition, and defects found in such images do not have correlation with actual impact on wafer. Our automated defect simulation tool predicts

  10. A Disulfide Bond-forming Machine Is Linked to the Sortase-mediated Pilus Assembly Pathway in the Gram-positive Bacterium Actinomyces oris*

    Science.gov (United States)

    Reardon-Robinson, Melissa E.; Osipiuk, Jerzy; Chang, Chungyu; Wu, Chenggang; Jooya, Neda; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2015-01-01

    Export of cell surface pilins in Gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. Here, we present physiological studies to demonstrate that the FimA pilin of Actinomyces oris contains two disulfide bonds. Alanine substitution of cysteine residues forming the C-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial interaction. Transposon mutagenesis of A. oris yielded a mutant defective in adherence to Streptococcus oralis, and revealed the essential role of a vitamin K epoxide reductase (VKOR) gene in pilus assembly. Targeted deletion of vkor results in the same defects, which are rescued by ectopic expression of VKOR, but not a mutant containing an alanine substitution in its conserved CXXC motif. Depletion of mdbA, which encodes a membrane-bound thiol-disulfide oxidoreductase, abrogates pilus assembly and alters cell morphology. Remarkably, overexpression of MdbA or a counterpart from Corynebacterium diphtheriae, rescues the Δvkor mutant. By alkylation assays, we demonstrate that VKOR is required for MdbA reoxidation. Furthermore, crystallographic studies reveal that A. oris MdbA harbors a thioredoxin-like fold with the conserved CXXC active site. Consistently, each MdbA enzyme catalyzes proper disulfide bond formation within FimA in vitro that requires the catalytic CXXC motif. Because the majority of signal peptide-containing proteins encoded by A. oris possess multiple Cys residues, we propose that MdbA and VKOR constitute a major folding machine for the secretome of this organism. This oxidative protein folding pathway may be a common feature in Actinobacteria. PMID:26170452

  11. A Disulfide Bond-forming Machine Is Linked to the Sortase-mediated Pilus Assembly Pathway in the Gram-positive Bacterium Actinomyces oris.

    Science.gov (United States)

    Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Chang, Chungyu; Wu, Chenggang; Jooya, Neda; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2015-08-28

    Export of cell surface pilins in Gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. Here, we present physiological studies to demonstrate that the FimA pilin of Actinomyces oris contains two disulfide bonds. Alanine substitution of cysteine residues forming the C-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial interaction. Transposon mutagenesis of A. oris yielded a mutant defective in adherence to Streptococcus oralis, and revealed the essential role of a vitamin K epoxide reductase (VKOR) gene in pilus assembly. Targeted deletion of vkor results in the same defects, which are rescued by ectopic expression of VKOR, but not a mutant containing an alanine substitution in its conserved CXXC motif. Depletion of mdbA, which encodes a membrane-bound thiol-disulfide oxidoreductase, abrogates pilus assembly and alters cell morphology. Remarkably, overexpression of MdbA or a counterpart from Corynebacterium diphtheriae, rescues the Δvkor mutant. By alkylation assays, we demonstrate that VKOR is required for MdbA reoxidation. Furthermore, crystallographic studies reveal that A. oris MdbA harbors a thioredoxin-like fold with the conserved CXXC active site. Consistently, each MdbA enzyme catalyzes proper disulfide bond formation within FimA in vitro that requires the catalytic CXXC motif. Because the majority of signal peptide-containing proteins encoded by A. oris possess multiple Cys residues, we propose that MdbA and VKOR constitute a major folding machine for the secretome of this organism. This oxidative protein folding pathway may be a common feature in Actinobacteria. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in Swine.

    Science.gov (United States)

    Forbes, Angela S; Regis, David P; Hall, Aaron A; Mahon, Richard T; Cronin, William A

    2017-04-01

    Disabled submarine (DISSUB) survivors may face elevated CO2 levels and inert gas saturation, putting them at risk for CO2 toxicity and decompression sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB rescue to study the effect of propranolol on DCS incidence and mortality with and without an OPB. In Experiment 1, male Yorkshire Swine (70 kg) were pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg · kg-1 (IV) was administered at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS type, onset time, and mortality. Experimental animals (N = 21; 69 ± 4.1 kg), PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 ± 2.8 kg) with the same dive profile, except for a 45 min OPB prior to decompression. In Experiment 2, the same methodology was used with the following changes: swine pressurized to 2.8 ATA for 28 h; experimental group (N = 25; 67 ± 3.3 kg), PROP0.5 bis, propranolol 0.5 mg · kg-1 bis (twice) (IV) was administered at 22 h and 26 h. Control animals (N = 25; 67 ± 3.9 kg) received normal saline. OPB reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis had increased mortality compared to CONTROL (60-% vs. 4%). Administration of beta blockers prior to saturation decompression appears to increase DCS and worsen mortality in a swine model; however, their effects in bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA. Propranolol effects on decompression sickness in a simulated DISSUB rescue in swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.

  13. Defect detection based on extreme edge of defective region histogram

    Directory of Open Access Journals (Sweden)

    Zouhir Wakaf

    2018-01-01

    Full Text Available Automatic thresholding has been used by many applications in image processing and pattern recognition systems. Specific attention was given during inspection for quality control purposes in various industries like steel processing and textile manufacturing. Automatic thresholding problem has been addressed well by the commonly used Otsu method, which provides suitable results for thresholding images based on a histogram of bimodal distribution. However, the Otsu method fails when the histogram is unimodal or close to unimodal. Defects have different shapes and sizes, ranging from very small to large. The gray-level distributions of the image histogram can vary between unimodal and multimodal. Furthermore, Otsu-revised methods, like the valley-emphasis method and the background histogram mode extents, which overcome the drawbacks of the Otsu method, require preprocessing steps and fail to use the general threshold for multimodal defects. This study proposes a new automatic thresholding algorithm based on the acquisition of the defective region histogram and the selection of its extreme edge as the threshold value to segment all defective objects in the foreground from the image background. To evaluate the proposed defect-detection method, common standard images for experimentation were used. Experimental results of the proposed method show that the proposed method outperforms the current methods in terms of defect detection.

  14. 33 CFR 149.303 - What survival craft and rescue boats may be used on a manned deepwater port?

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false What survival craft and rescue boats may be used on a manned deepwater port? 149.303 Section 149.303 Navigation and Navigable Waters... craft and rescue boats may be used on a manned deepwater port? (a) Each survival craft on a manned...

  15. Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria.

    Directory of Open Access Journals (Sweden)

    Parmida Ranji

    Full Text Available HMG-CoA reductase is the rate-limiting enzyme in the mevalonate pathway and the target of cholesterol-lowering statins. We characterized the C. elegans hmgr-1(tm4368 mutant, which lacks HMG-CoA reductase, and show that its phenotypes recapitulate that of statin treatment, though in a more severe form. Specifically, the hmgr-1(tm4368 mutant has defects in growth, reproduction and protein prenylation, is rescued by exogenous mevalonate, exhibits constitutive activation of the UPRer and requires less mevalonate to be healthy when the UPRmt is activated by a constitutively active form of ATFS-1. We also show that different amounts of mevalonate are required for different physiological processes, with reproduction requiring the highest levels. Finally, we provide evidence that the mevalonate pathway is required for the activation of the UPRmt.

  16. Uncertainty, Alert and Distress: The Precarious Position of NGO Search and Rescue Operations in the Central Mediterranean

    OpenAIRE

    Smith, Adam

    2017-01-01

    The international framework for maritime search and rescue relies on state actors establishing regions of responsibility supported by private shipmasters acting in compliance with traditional duties to rescue persons in distress at sea. Despite revisions to the framework’s foundational treaty, questions persist about the extent of state responsibilities and the interaction between those responsibilities and international human rights law. Over the past three years, non-governmenta...

  17. A Standardized "Rescue" Exercise Program for Symptomatic Flare-up of Knee Osteoarthritis

    DEFF Research Database (Denmark)

    Bartholdy, Cecilie; Klokker, Louise; Bandak, Elisabeth

    2016-01-01

    the implementation of standardized rescue exercises for patients with pain exacerbations and to assess whether performing these benefit or further worsen symptoms in patients with exacerbated symptoms of knee OA. Methods The data from 2 randomized controlled studies of exercise in patients with knee OA were used......Study Design Secondary analysis of clinical trial data. Background Knee osteoarthritis (OA) management has changed significantly over recent decades toward nonpharmacological treatments, particularly exercise. However, the optimal exercise program remains to be established. Objective To describe....... A supervised, standard exercise program that included standardized "rescue" exercises to be performed in the event of symptomatic exacerbation, defined as knee pain of greater than 5 on a 0-to-10 numeric pain-rating scale, was conducted for 12 weeks at 3 sessions per week. Pain ratings were obtained before...

  18. Patterning and gastrulation defects caused by the tw18 lethal are due to loss of Ppp2r1a

    Directory of Open Access Journals (Sweden)

    Lisette Lange

    2017-06-01

    Full Text Available The mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors 16 embryonic control genes identified by recessive lethal mutations isolated from wild mouse populations. Due to technical constraints so far only one of these, the tw5 lethal, has been cloned and molecularly characterized. Here we report the molecular isolation of the tw18 lethal. Embryos carrying the tw18 lethal die from major gastrulation defects commencing with primitive streak formation at E6.5. We have used transcriptome and marker gene analyses to describe the molecular etiology of the tw18 phenotype. We show that both WNT and Nodal signal transduction are impaired in the mutant epiblast, causing embryonic patterning defects and failure of primitive streak and mesoderm formation. By using a candidate gene approach, gene knockout by homologous recombination and genetic rescue, we have identified the gene causing the tw18 phenotype as Ppp2r1a, encoding the PP2A scaffolding subunit PR65alpha. Our work highlights the importance of phosphatase 2A in embryonic patterning, primitive streak formation, gastrulation, and mesoderm formation downstream of WNT and Nodal signaling.

  19. ADMINISTRATIVE CIRCULAR No. 25 (REV. 3) - Special provisions for the fire and rescue service governing working and rest time

    CERN Multimedia

    2012-01-01

    Administrative Circular No. 25 (Rev. 3) entitled “Special provisions for the Fire and Rescue Service governing working and rest time”, approved by the Director-General following discussion at the Standing Concertation Committee meeting of 28 September 2012 and entering into force in October 2012, is available on the intranet site of the Human Resources Department: http://cern.ch/hr-docs/admincirc/admincirc.asp This Circular is applicable to staff members of the Fire and Rescue Service It cancels and replaces Administrative Circular No. 25 (Rev. 2) entitled “Shift work – Special provisions for the Fire and Rescue Service” of April 2003. This new version takes into account the new organisation of the Fire and Rescue Service, members of which will henceforth not exclusively perform their functions in the context of shift work, but also during reference working hours and during stand-by duty. Additionally, applicable limits regarding working and rest times an...

  20. Primary defects in lipolysis and insulin action in skeletal muscle cells from type 2 diabetic individuals

    DEFF Research Database (Denmark)

    Kase, E. T.; Feng, Y. Z.; Badin, P. M.

    2015-01-01

    A decrease in skeletal muscle lipolysis and hormone sensitive-lipase (HSL) expression has been linked to insulin resistance in obesity. The purpose of this study was to identify potential intrinsic defects in lipid turnover and lipolysis in myotubes established from obese and type 2 diabetic...

  1. Synthetic Defects for Vibrothermography

    Science.gov (United States)

    Renshaw, Jeremy; Holland, Stephen D.; Thompson, R. Bruce; Eisenmann, David J.

    2010-02-01

    Synthetic defects are an important tool used for characterizing the performance of nondestructive evaluation techniques. Viscous material-filled synthetic defects were developed for use in vibrothermography (also known as sonic IR) as a tool to improve inspection accuracy and reliability. This paper describes how the heat-generation response of these VMF synthetic defects is similar to the response of real defects. It also shows how VMF defects can be applied to improve inspection accuracy for complex industrial parts and presents a study of their application in an aircraft engine stator vane.

  2. Distributed geo-services based on Wireless GIS- a case study for post-quake rescue information system

    OpenAIRE

    Liu, Yimei

    2014-01-01

    A useful application of Wireless GIS is the handling of natural disasters such as earthquakes. This thesis is dedicated to the construction and implementation of a post-quake rescue information system based on open source data and software programs. The emphasis is laid on the assessment of losses in the disaster area, estimation of collapsing buildings and trapped population, and efficient transmission of all the rescue-relevant information. The realized workflow of using open source data an...

  3. Paranormal experience in a medico-swimming rescue: a case study.

    Science.gov (United States)

    Avramidis, Stathis

    2013-06-01

    This study looks at the case of a 20-year-old fisherman, who was speared in the head, the spear entering at his jaw and protruding from the top of his scull, while he was swimming unaccompanied; he was rescued, admitted to the intensive care unit for an operation, remained in a coma for a few days and then had a full recovery. About 10 days before the rescue, he had visited a monk who, intuited and functioning as channel of the divine spirit, had told him that he 'should not be afraid of anything', rubbing the top of his scull and his jaw exactly at the points through which the 40-inch spear passed. After the incident, the monk prescience again the exact day on which he would recover from the coma. It is concluded that the survival of the fisherman can be attributed to a paranormal event. The monk's prescience permit the assumption that a divine spirit was pervasive throughout the universe and present in this life-threatening situation, endeavouring to assist the lifeguard, the neurosurgeons and the young fisherman.

  4. Computer aid in rescue organisation on site in case of catastrophic situation on nuclear plant

    International Nuclear Information System (INIS)

    Teissier, M.

    1992-01-01

    The rescue organisation in case of catastrophic situation is based on known principles: creation of medical buffer structures between hazard spot where injured people are being collected and rear hospitals, triage of victims as urgent casualties. We will propose computer aid in order to value the time used to prepare and evacuate all the victims from the site, knowing inventory of available means, waiting periods and lengths of intervention, types and number of victims. Thus, it is possible to optimize the former organisation, qualitatively and quantitatively to improve efficiency in rescuing operations. (author)

  5. Genetic and Chemical Correction of Cholesterol Accumulation and Impaired Autophagy in Hepatic and Neural Cells Derived from Niemann-Pick Type C Patient-Specific iPS Cells

    Directory of Open Access Journals (Sweden)

    Dorothea Maetzel

    2014-06-01

    Full Text Available Niemann-Pick type C (NPC disease is a fatal inherited lipid storage disorder causing severe neurodegeneration and liver dysfunction with only limited treatment options for patients. Loss of NPC1 function causes defects in cholesterol metabolism and has recently been implicated in deregulation of autophagy. Here, we report the generation of isogenic pairs of NPC patient-specific induced pluripotent stem cells (iPSCs using transcription activator-like effector nucleases (TALENs. We observed decreased cell viability, cholesterol accumulation, and dysfunctional autophagic flux in NPC1-deficient human hepatic and neural cells. Genetic correction of a disease-causing mutation rescued these defects and directly linked NPC1 protein function to impaired cholesterol metabolism and autophagy. Screening for autophagy-inducing compounds in disease-affected human cells showed cell type specificity. Carbamazepine was found to be cytoprotective and effective in restoring the autophagy defects in both NPC1-deficient hepatic and neuronal cells and therefore may be a promising treatment option with overall benefit for NPC disease.

  6. Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Susann Lehmann

    2017-02-01

    Full Text Available Familial forms of Parkinson's disease (PD caused by mutations in PINK1 are linked to mitochondrial impairment. Defective mitochondria are also found in Drosophila models of PD with pink1 mutations. The co-enzyme nicotinamide adenine dinucleotide (NAD+ is essential for both generating energy in mitochondria and nuclear DNA repair through NAD+-consuming poly(ADP-ribose polymerases (PARPs. We found alterations in NAD+ salvage metabolism in Drosophila pink1 mutants and showed that a diet supplemented with the NAD+ precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration. Additionally, a mutation of Parp improved mitochondrial function and was neuroprotective in the pink1 mutants. We conclude that enhancing the availability of NAD+ by either the use of a diet supplemented with NAD+ precursors or the inhibition of NAD+-dependent enzymes, such as PARPs, which compete with mitochondria for NAD+, is a viable approach to preventing neurotoxicity associated with mitochondrial defects.

  7. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet

    Science.gov (United States)

    Krznar, Petra; Hörl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

    2016-01-01

    Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic profiles, and both defects could be restored by reexpression of MPC1. Labeling experiments using 13C-labeled glucose and glutamine demonstrated that MPC deficiency causes increased glutaminolysis and reduced contribution of glucose-derived pyruvate to the TCA cycle. Morphological defects were observed in mutant embryonic brains, together with major alterations of their metabolome including lactic acidosis, diminished TCA cycle intermediates, energy deficit and a perturbed balance of neurotransmitters. Strikingly, these changes were reversed when the pregnant dams were fed a ketogenic diet, which provides acetyl-CoA directly to the TCA cycle and bypasses the need for a functional MPC. This allowed the normal gestation and development of MPC deficient pups, even though they all died within a few minutes post-delivery. This study establishes the MPC as a key player in regulating the metabolic state necessary for embryonic development, neurotransmitter balance and post-natal survival. PMID:27176894

  8. Mechanism of As2O3-Induced Action Potential Prolongation and Using hiPS-CMs to Evaluate the Rescue Efficacy of Drugs With Different Rescue Mechanism.

    Science.gov (United States)

    Yan, Meng; Feng, Lifang; Shi, Yanhui; Wang, Junnan; Liu, Yan; Li, Fengmei; Li, Baoxin

    2017-08-01

    Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking. Then we explored pharmacological rescue strategies on As2O3-induced LQTS, and found that 4 therapeutic agents exert rescue efficacy via 3 different pathways: fexofenadine and astemizole facilitate hERG trafficking via promotion of channel-chaperone formation after As2O3 incubation; ranolazine slows hERG degradation in the presence of As2O3; and resveratrol shows significant attenuation on calcium current increase triggered by As2O3. Moreover, we used human-induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) to evaluate the rescue effects of the above agents on As2O3-induced prolongation of action potential duration (APD) and demonstrated that fexofenadine and resveratrol significantly ameliorate the prolonged APD. These observations suggested that pharmacological chaperone like fexofenadine and resveratrol might have the potential to protect against the cardiotoxicity of As2O3. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Identification of photoluminescence P line in indium doped silicon as In{sub Si}-Si{sub i} defect

    Energy Technology Data Exchange (ETDEWEB)

    Lauer, Kevin, E-mail: klauer@cismst.de; Möller, Christian [CiS Forschungsinstitut für Mikrosensorik und Photovoltaik GmbH, Konrad-Zuse-Str. 14, 99099 Erfurt (Germany); Schulze, Dirk [TU Ilmenau, Institut für Physik, Weimarer Str. 32, 98693 Ilmenau (Germany); Ahrens, Carsten [Infineon Technologies AG, Am Campeon 1-12, 85579 Neubiberg (Germany)

    2015-01-15

    Indium and carbon co-implanted silicon was investigated by low-temperature photoluminescence spectroscopy. A photoluminescence peak in indium doped silicon (P line) was found to depend on the position of a silicon interstitial rich region, the existence of a SiN{sub x}:H/SiO{sub x} stack and on characteristic illumination and annealing steps. These results led to the conclusion that silicon interstitials are involved in the defect and that hydrogen impacts the defect responsible for the P line. By applying an unique illumination and annealing cycle we were able to link the P line defect with a defect responsible for degradation of charge carrier lifetime in indium as well as boron doped silicon. We deduced a defect model consisting of one acceptor and one silicon interstitial atom denoted by A{sub Si}-Si{sub i}, which is able to explain the experimental data of the P line as well as the light-induced degradation in indium and boron doped silicon. Using this model we identified the defect responsible for the P line as In{sub Si}-Si{sub i} in neutral charge state and C{sub 2v} configuration.

  10. Liver-specific rescuing of CEACAM1 reverses endothelial and cardiovascular abnormalities in male mice with null deletion of Ceacam1 gene

    Directory of Open Access Journals (Sweden)

    Lucia Russo

    2018-03-01

    Full Text Available Objective: Mice with global null mutation of Ceacam1 (Cc1−/−, display impairment of insulin clearance that causes hyperinsulinemia followed by insulin resistance, elevated hepatic de novo lipogenesis, and visceral obesity. In addition, they manifest abnormal vascular permeability and elevated blood pressure. Liver-specific rescuing of Ceacam1 reversed all of the metabolic abnormalities in Cc1−/−liver+ mice. The current study examined whether Cc1−/− male mice develop endothelial and cardiac dysfunction and whether this relates to the metabolic abnormalities caused by defective insulin extraction. Methods and results: Myography studies showed reduction of agonist-stimulated nitric oxide production in resistance arterioles in Cc1−/−, but not Cc1−/−liver+ mice. Liver-based rescuing of CEACAM1 also attenuated the abnormal endothelial adhesiveness to circulating leukocytes in parallel to reducing plasma endothelin-1 and recovering plasma nitric oxide levels. Echocardiography studies revealed increased septal wall thickness, cardiac hypertrophy and reduced cardiac performance in Cc1−/−, but not Cc1−/−xliver+ mice. Insulin signaling experiments indicated compromised IRS1/Akt/eNOS pathway leading to lower nitric oxide level, and activated Shc/MAPK pathway leading to more endothelin-1 production in the aortae and hearts of Cc1−/−, but not Cc1−/−xliver+ mice. The increase in the ratio of endothelin-1 receptor A/B indicated an imbalance in the vasomotor activity of Cc1−/− mice, which was normalized in Cc1−/−xliver+ mice. Conclusions: The data underscore a critical role for impaired CEACAM1-dependent hepatic insulin clearance pathways and resulting hyperinsulinemia and lipid accumulation in aortae and heart in regulating the cardiovascular function. Keywords: Insulin clearance, Hyperinsulinemia, Insulin resistance, Endothelial function, Cardiomyopathy

  11. Human-Based Human Milk Fortifier as Rescue Therapy in Very Low Birth Weight Infants Demonstrating Intolerance to Bovine-Based Human Milk Fortifier.

    Science.gov (United States)

    Sandhu, Amanjot; Fast, Sharla; Bonnar, Kari; Baier, Ronald John; Narvey, Michael

    2017-11-01

    To describe the results of utilizing a human milk-based human milk fortifier (HMHMF) as rescue therapy to meet nutritional requirements in very low birth weight and preterm infants demonstrating feeding intolerance to bovine-based human milk fortifier (BHMF) in the Canadian Neonatal Intensive Care Unit (NICU) setting. At two Level III NICUs in Winnipeg, MB, Canada, a rescue protocol was implemented to provide HMHMF for infants demonstrating intolerance to BHMF. To qualify for rescue, infants were required to experience two episodes of significant gastrointestinal (GI) symptoms associated with fortification with BHMF. A case series report was conducted retrospectively examining the success of rescue therapy, growth rates, protein, and calorie intakes before and after initiation of HMHMF in seven infants. Seven infants (birth weight 723 ± 247 g, gestation 25.3 ± 3.4 weeks) were treated with rescue fortification with HMHMF. All infants were transitioned off parenteral nutrition (PN) without relapse of GI symptoms. Growth rate, protein, and calorie intakes improved with the use of HMHMF. Very low birth weight and preterm infants with GI intolerance to BHMF were successfully rescued with use of HMHMF. Improvements in growth were achieved without need for supplementation with PN through achievement of sufficient enteral calorie and protein intakes.

  12. Rescue dose orders as an alternative to range orders: an evidence-based practice project.

    Science.gov (United States)

    Yi, Cassia

    2015-06-01

    Relief of pain is a fundamental aspect of optimal patient care. However, pain management in the inpatient setting is often constrained by concerns related to regulatory oversight, particularly with regard to the use of opioid dose range orders. These concerns can inadvertently result in the development of policies and practices that can negatively impact the health care team's ability to deliver optimal and individualized pain management. An evidence-based practice project was undertaken to address concerns about regulatory oversight of pain management processes by changing the way pain was managed in a large academic hospital setting. A novel pain management approach using rescue dose medications was established as an alternative to opioid dose range orders. The use of the rescue dose protocol was successfully implemented. Outcomes included an overall reduction in the administration of inappropriate intravenous opioids and opioid-acetaminophen combination medications, with a subsequent increase in single-entity first-line opioid analgesics. Rescue dose protocols may offer an alternative to opioid dose range orders as a means of effectively managing pain. Copyright © 2015 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  13. Blueprint for Implementing New Processes in Acute Care: Rescuing Adult Patients With Intraosseous Access.

    Science.gov (United States)

    Chreiman, Kristen M; Kim, Patrick K; Garbovsky, Lyudmila A; Schweickert, William D

    2015-01-01

    The intraosseous (IO) access initiative at an urban university adult level 1 trauma center began from the need for a more expeditious vascular access route to rescue patients in extremis. The goal of this project was a multidisciplinary approach to problem solving to increase access of IO catheters to rescue patients in all care areas. The initiative became a collaborative effort between nursing, physicians, and pharmacy to embark on an acute care endeavor to standardize IO access. This is a descriptive analysis of processes to effectively develop collaborative strategies to navigate hospital systems and successfully implement multilayered initiatives. Administration should empower nurse to advance their practice to include IO for patient rescue. Intraosseous access may expedite resuscitative efforts in patients in extremis who lack venous access or where additional venous access is required for life-saving therapies. Limiting IO dwell time may facilitate timely definitive venous access. Continued education and training by offering IO skill laboratory refreshers and annual e-learning didactic is optimal for maintaining proficiency and knowledge. More research opportunities exist to determine medication safety and efficacy in adult patients in the acute care setting.

  14. Desipramine rescues age-related phenotypes in depression-like rats induced by chronic mild stress.

    Science.gov (United States)

    Xie, Xiaoxian; Chen, Yangyang; Wang, Qi; Shen, Qichen; Ma, Lingyan; Huang, Liangfeng; Wu, Tao; Fu, Zhengwei

    2017-11-01

    Our previous finding demonstrates that major depressive disorder can mediate accelerated aging in rats. Desipramine is a typical tricyclic antidepressant, and can provide neuroprotection and counteract depression-like behaviors. However, whether desipramine can rescue age-related phenotypes in depressed individuals is not understood. In the present study, we investigated the physiological function of desipramine on rescuing the age-related phenotypes in these animals. The rats were induced by chronic mild stress paradigm, and the depression-like behaviors of rats were detected by sucrose intake test, open field test (OFT) and forced swimming test (FST). Then the depressed rats were treated by desipramine. Desipramine administration was effective in counteracting depression-like behaviors by increasing the sucrose solution intake, reducing the immobility time in the FST, and increasing total distance travelled and numbers of grid line crossed in the OFT. Moreover, desipramine treatment was able to reduce the oxidative damage to rat liver, and to increase the expression of telomerase reverse transcriptase (TERT), leading to correspondingly restored telomerase activity. Our findings identify that one function of desipramine may partly be to rescue age-related phenotypes in depressed individuals induced by chronic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Comparison of Temporal Parameters of Swimming Rescue Elements When Performed Using Dolphin and Flutter Kick with Fins - Didactical Approach

    Science.gov (United States)

    Rejman, Marek; Wiesner, Wojciech; Silakiewicz, Piotr; Klarowicz, Andrzej; Abraldes, J. Arturo

    2012-01-01

    The aim of this study was an analysis of the time required to swim to a victim and tow them back to shore, while perfoming the flutter-kick and the dolphin-kick using fins. It has been hypothesized that using fins while using the dolphin-kick when swimming leads to reduced rescue time. Sixteen lifeguards took part in the study. The main tasks performed by them, were to approach and tow (double armpit) a dummy a distance of 50m while applying either the flutter-kick, or the dolphin-kick with fins. The analysis of the temporal parameters of both techniques of kicking demonstrates that, during the approach to the victim, neither the dolphin (tmean = 32.9s) or the flutter kick (tmean = 33.0s) were significantly faster than the other. However, when used for towing a victim the flutter kick (tmean = 47.1s) was significantly faster when compared to the dolphin-kick (tmean = 52.8s). An assessment of the level of technical skills in competitive swimming, and in approaching and towing the victim, were also conducted. Towing time was significantly correlated with the parameter that linked the temporal and technical dimensions of towing and swimming (difference between flutter kick towing time and dolphin-kick towing time, 100m medley time and the four swimming strokes evaluation). No similar interdependency has been discovered in flutter kick towing time. These findings suggest that the dolphin-kick is a more difficult skill to perform when towing the victim than the flutter-kick. Since the hypothesis stated was not confirmed, postulates were formulated on how to improve dolphin-kick technique with fins, in order to reduce swimming rescue time. Key points The source of reduction of swimming rescue time was researched. Time required to approach and to tow the victim while doing the flutter kick and the dolphin-kick with fins was analyzed. The propulsion generated by dolphin-kick did not make the approach and tow faster than the flutter kick. More difficult skill to realize of

  16. Disparate peroxisome-related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization.

    Science.gov (United States)

    Gonzalez, Kim L; Fleming, Wendell A; Kao, Yun-Ting; Wright, Zachary J; Venkova, Savina V; Ventura, Meredith J; Bartel, Bonnie

    2017-10-01

    Catabolism of fatty acids stored in oil bodies is essential for seed germination and seedling development in Arabidopsis. This fatty acid breakdown occurs in peroxisomes, organelles that sequester oxidative reactions. Import of peroxisomal enzymes is facilitated by peroxins including PEX5, a receptor that delivers cargo proteins from the cytosol to the peroxisomal matrix. After cargo delivery, a complex of the PEX1 and PEX6 ATPases and the PEX26 tail-anchored membrane protein removes ubiquitinated PEX5 from the peroxisomal membrane. We identified Arabidopsis pex6 and pex26 mutants by screening for inefficient seedling β-oxidation phenotypes. The mutants displayed distinct defects in growth, response to a peroxisomally metabolized auxin precursor, and peroxisomal protein import. The low PEX5 levels in these mutants were increased by treatment with a proteasome inhibitor or by combining pex26 with peroxisome-associated ubiquitination machinery mutants, suggesting that ubiquitinated PEX5 is degraded by the proteasome when the function of PEX6 or PEX26 is reduced. Combining pex26 with mutations that increase PEX5 levels either worsened or improved pex26 physiological and molecular defects, depending on the introduced lesion. Moreover, elevating PEX5 levels via a 35S:PEX5 transgene exacerbated pex26 defects and ameliorated the defects of only a subset of pex6 alleles, implying that decreased PEX5 is not the sole molecular deficiency in these mutants. We found peroxisomes clustered around persisting oil bodies in pex6 and pex26 seedlings, suggesting a role for peroxisomal retrotranslocation machinery in oil body utilization. The disparate phenotypes of these pex alleles may reflect unanticipated functions of the peroxisomal ATPase complex. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  17. Facts about Birth Defects

    Science.gov (United States)

    ... label> Information For… Media Policy Makers Facts about Birth Defects Language: English (US) Español (Spanish) Recommend on ... having a baby born without a birth defect. Birth Defects Are Common Every 4 ½ minutes, a ...

  18. A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR-mediated non-canonical steroid action to cAMP signaling in the adult brain.

    Science.gov (United States)

    Ishimoto, Hiroshi; Wang, Zhe; Rao, Yi; Wu, Chun-Fang; Kitamoto, Toshihiro

    2013-01-01

    The biological actions of steroid hormones are mediated primarily by their cognate nuclear receptors, which serve as steroid-dependent transcription factors. However, steroids can also execute their functions by modulating intracellular signaling cascades rapidly and independently of transcriptional regulation. Despite the potential significance of such "non-genomic" steroid actions, their biological roles and the underlying molecular mechanisms are not well understood, particularly with regard to their effects on behavioral regulation. The major steroid hormone in the fruit fly Drosophila is 20-hydroxy-ecdysone (20E), which plays a variety of pivotal roles during development via the nuclear ecdysone receptors. Here we report that DopEcR, a G-protein coupled receptor for ecdysteroids, is involved in activity- and experience-dependent plasticity of the adult central nervous system. Remarkably, a courtship memory defect in rutabaga (Ca²⁺/calmodulin-responsive adenylate cyclase) mutants was rescued by DopEcR overexpression or acute 20E feeding, whereas a memory defect in dunce (cAMP-specific phosphodiestrase) mutants was counteracted when a loss-of-function DopEcR mutation was introduced. A memory defect caused by suppressing dopamine synthesis was also restored through enhanced DopEcR-mediated ecdysone signaling, and rescue and phenocopy experiments revealed that the mushroom body (MB)--a brain region central to learning and memory in Drosophila--is critical for the DopEcR-dependent processing of courtship memory. Consistent with this finding, acute 20E feeding induced a rapid, DopEcR-dependent increase in cAMP levels in the MB. Our multidisciplinary approach demonstrates that DopEcR mediates the non-canonical actions of 20E and rapidly modulates adult conditioned behavior through cAMP signaling, which is universally important for neural plasticity. This study provides novel insights into non-genomic actions of steroids, and opens a new avenue for genetic

  19. A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR-mediated non-canonical steroid action to cAMP signaling in the adult brain.

    Directory of Open Access Journals (Sweden)

    Hiroshi Ishimoto

    Full Text Available The biological actions of steroid hormones are mediated primarily by their cognate nuclear receptors, which serve as steroid-dependent transcription factors. However, steroids can also execute their functions by modulating intracellular signaling cascades rapidly and independently of transcriptional regulation. Despite the potential significance of such "non-genomic" steroid actions, their biological roles and the underlying molecular mechanisms are not well understood, particularly with regard to their effects on behavioral regulation. The major steroid hormone in the fruit fly Drosophila is 20-hydroxy-ecdysone (20E, which plays a variety of pivotal roles during development via the nuclear ecdysone receptors. Here we report that DopEcR, a G-protein coupled receptor for ecdysteroids, is involved in activity- and experience-dependent plasticity of the adult central nervous system. Remarkably, a courtship memory defect in rutabaga (Ca²⁺/calmodulin-responsive adenylate cyclase mutants was rescued by DopEcR overexpression or acute 20E feeding, whereas a memory defect in dunce (cAMP-specific phosphodiestrase mutants was counteracted when a loss-of-function DopEcR mutation was introduced. A memory defect caused by suppressing dopamine synthesis was also restored through enhanced DopEcR-mediated ecdysone signaling, and rescue and phenocopy experiments revealed that the mushroom body (MB--a brain region central to learning and memory in Drosophila--is critical for the DopEcR-dependent processing of courtship memory. Consistent with this finding, acute 20E feeding induced a rapid, DopEcR-dependent increase in cAMP levels in the MB. Our multidisciplinary approach demonstrates that DopEcR mediates the non-canonical actions of 20E and rapidly modulates adult conditioned behavior through cAMP signaling, which is universally important for neural plasticity. This study provides novel insights into non-genomic actions of steroids, and opens a new avenue for

  20. Rescue of foot-and-mouth disease viruses that are pathogenic for cattle from preserved viral RNA samples.

    Directory of Open Access Journals (Sweden)

    Graham J Belsham

    Full Text Available BACKGROUND: Foot and mouth disease is an economically important disease of cloven-hoofed animals including cattle, sheep and pigs. It is caused by a picornavirus, foot-and-mouth disease virus (FMDV, which has a positive sense RNA genome which, when introduced into cells, can initiate virus replication. PRINCIPAL FINDINGS: A system has been developed to rescue infectious FMDV from RNA preparations generated from clinical samples obtained under experimental conditions and then applied to samples collected in the "field". Clinical samples from suspect cases of foot-and-mouth disease (FMD were obtained from within Pakistan and Afghanistan. The samples were treated to preserve the RNA and then transported to National Veterinary Institute, Lindholm, Denmark. Following RNA extraction, FMDV RNA was quantified by real-time RT-PCR and samples containing significant levels of FMDV RNA were introduced into susceptible cells using electroporation. Progeny viruses were amplified in primary bovine thyroid cells and characterized using antigen ELISA and also by RT-PCR plus sequencing. FMD viruses of three different serotypes and multiple lineages have been successfully rescued from the RNA samples. Two of the rescued viruses (of serotype O and Asia 1 were inoculated into bull calves under high containment conditions. Acute clinical disease was observed in each case which spread rapidly from the inoculated calves to in-contact animals. Thus the rescued viruses were highly pathogenic. The availability of the rescued viruses enabled serotyping by antigen ELISA and facilitated genome sequencing. CONCLUSIONS: The procedure described here should improve the characterization of FMDVs circulating in countries where the disease is endemic and thus enhance disease control globally.

  1. First Report of Using Portable Unmanned Aircraft Systems (Drones) for Search and Rescue.

    Science.gov (United States)

    Van Tilburg, Christopher

    2017-06-01

    Unmanned aircraft systems (UAS), colloquially called drones, are used commonly for military, government, and civilian purposes, including both commercial and consumer applications. During a search and rescue mission in Oregon, a UAS was used to confirm a fatality in a slot canyon; this eliminated the need for a dangerous rappel at night by rescue personnel. A second search mission in Oregon used several UAS to clear terrain. This allowed search of areas that were not accessible or were difficult to clear by ground personnel. UAS with cameras may be useful for searching, observing, and documenting missions. It is possible that UAS might be useful for delivering equipment in difficult areas and in communication. Copyright © 2017. Published by Elsevier Inc.

  2. Defect production in ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J. [Oak Ridge National Lab., TN (United States); Kinoshita, C. [Kyushu Univ. (Japan)

    1997-08-01

    A review is given of several important defect production and accumulation parameters for irradiated ceramics. Materials covered in this review include alumina, magnesia, spinel silicon carbide, silicon nitride, aluminum nitride and diamond. Whereas threshold displacement energies for many ceramics are known within a reasonable level of uncertainty (with notable exceptions being AIN and Si{sub 3}N{sub 4}), relatively little information exists on the equally important parameters of surviving defect fraction (defect production efficiency) and point defect migration energies for most ceramics. Very little fundamental displacement damage information is available for nitride ceramics. The role of subthreshold irradiation on defect migration and microstructural evolution is also briefly discussed.

  3. Defects in dilute nitrides

    International Nuclear Information System (INIS)

    Chen, W.M.; Buyanova, I.A.; Tu, C.W.; Yonezu, H.

    2005-01-01

    We provide a brief review our recent results from optically detected magnetic resonance studies of grown-in non-radiative defects in dilute nitrides, i.e. Ga(In)NAs and Ga(Al,In)NP. Defect complexes involving intrinsic defects such as As Ga antisites and Ga i self interstitials were positively identified.Effects of growth conditions, chemical compositions and post-growth treatments on formation of the defects are closely examined. These grown-in defects are shown to play an important role in non-radiative carrier recombination and thus in degrading optical quality of the alloys, harmful to performance of potential optoelectronic and photonic devices based on these dilute nitrides. (author)

  4. Clinical emergency treatment of 68 critical patients with severe organophosphorus poisoning and prognosis analysis after rescue.

    Science.gov (United States)

    Dong, Hui; Weng, Yi-Bing; Zhen, Gen-Shen; Li, Feng-Jie; Jin, Ai-Chun; Liu, Jie

    2017-06-01

    This study reports the clinical emergency treatment of 68 critical patients with severe organophosphorus poisoning, and analyzes the prognosis after rescue.The general data of 68 patients with severe organophosphorus poisoning treated in our hospital were retrospectively analyzed. These patients were divided into 2 groups: treatment group, and control group. Patients in the control group received routine emergency treatment, while patients in the treatment group additionally received hemoperfusion plus hemodialysis on the basis of routine emergency treatment. The curative effects in these 2 groups and the prognosis after rescue were compared.Compared with the control group, atropinization time, recovery time of cholinesterase activity, recovery time of consciousness, extubation time, and length of hospital stay were shorter (P poisoning rebound rate was significantly lower (P treatment group.Hemoperfusion and hemodialysis on the basis of routine emergency treatment for critical patients with organophosphorus poisoning can improve rescue outcomes and improve the prognosis of patients, which should be popularized.

  5. Genital and Urinary Tract Defects

    Science.gov (United States)

    ... conditions > Genital and urinary tract defects Genital and urinary tract defects E-mail to a friend Please fill ... and extra fluids. What problems can genital and urinary tract defects cause? Genital and urinary tract defects affect ...

  6. Biparental chloroplast inheritance leads to rescue from cytonuclear incompatibility.

    Science.gov (United States)

    Barnard-Kubow, Karen B; McCoy, Morgan A; Galloway, Laura F

    2017-02-01

    Although organelle inheritance is predominantly maternal across animals and plants, biparental chloroplast inheritance has arisen multiple times in the angiosperms. Biparental inheritance has the potential to impact the evolutionary dynamics of cytonuclear incompatibility, interactions between nuclear and organelle genomes that are proposed to be among the earliest types of genetic incompatibility to arise in speciation. We examine the interplay between biparental inheritance and cytonuclear incompatibility in Campanulastrum americanum, a plant species exhibiting both traits. We first determine patterns of chloroplast inheritance in genetically similar and divergent crosses, and then associate inheritance with hybrid survival across multiple generations. There is substantial biparental inheritance in C. americanum. The frequency of biparental inheritance is greater in divergent crosses and in the presence of cytonuclear incompatibility. Biparental inheritance helps to mitigate cytonuclear incompatibility, leading to increased fitness of F 1 hybrids and recovery in the F 2 generation. This study demonstrates the potential for biparental chloroplast inheritance to rescue cytonuclear compatibility, reducing cytonuclear incompatibility's contribution to reproductive isolation and potentially slowing speciation. The efficacy of rescue depended upon the strength of incompatibility, with a greater persistence of weak incompatibilities in later generations. These findings suggest that incompatible plastids may lead to selection for biparental inheritance. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  7. The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds

    Directory of Open Access Journals (Sweden)

    Arati A. Inamdar

    2012-01-01

    Full Text Available Epidemiological studies link the herbicide paraquat to increased incidence of Parkinson's disease (PD. We previously reported that Drosophila exposed to paraquat recapitulate PD symptoms, including region-specific degeneration of dopaminergic neurons. Minocycline, a tetracycline derivative, exerts ameliorative effects in neurodegenerative disease models, including Drosophila. We investigated whether our environmental toxin-based PD model could contribute to an understanding of cellular and genetic mechanisms of minocycline action and whether we could assess potential interference with these drug effects in altered genetic backgrounds. Cofeeding of minocycline with paraquat prolonged survival, rescued mobility defects, blocked generation of reactive oxygen species, and extended dopaminergic neuron survival, as has been reported previously for a genetic model of PD in Drosophila. We then extended this study to identify potential interactions of minocycline with genes regulating dopamine homeostasis that might modify protection against paraquat and found that deficits in GTP cyclohydrolase adversely affect minocycline rescue. We further performed genetic studies to identify signaling pathways that are necessary for minocycline protection against paraquat toxicity and found that mutations in the Drosophila genes that encode c-Jun N-terminal kinase (JNK and Akt/Protein kinase B block minocycline rescue.

  8. Notes from the Field: Zika Virus-Associated Neonatal Birth Defects Surveillance - Texas, January 2016-July 2017.

    Science.gov (United States)

    Hall, Noemi Borsay; Broussard, Kelly; Evert, Nicole; Canfield, Mark

    2017-08-11

    On November 28, 2016, the Texas Department of State Health Services (Texas DSHS) reported its first confirmed case of local mosquitoborne Zika virus transmission in the city of Brownsville, located in south Texas along the U.S.-Mexico border. Zika virus infection during pregnancy has been linked to adverse congenital outcomes including microcephaly, neural tube defects, early brain malformations, structural eye abnormalities, congenital deafness, and limb contractures (1). On January 1, 2016, Texas DSHS established enhanced surveillance to identify women with laboratory evidence of possible Zika virus infection during pregnancy and suspected cases of Zika virus-associated birth defects among completed pregnancies.

  9. Intraoperative use of a reflective blanket (Sirius rescue sheet) for temperature management in dogs less than 10 kg.

    Science.gov (United States)

    Tünsmeyer, J; Bojarski, I; Nolte, I; Kramer, S

    2009-07-01

    To compare the effects of the Sirius rescue sheet with gel pads versus gel pads alone on intraoperative body temperature in dogs less than 10 kg. Forty small breed dogs undergoing elective surgical procedures were randomly assigned to two groups. One group was intraoperatively laid on warmed gel pads, and the other group was additionally wrapped in a Sirius rescue sheet. Oesophageal body temperature was determined every 10 minutes and compared between groups. Temperature of gel pads was measured preoperatively and postoperatively to compare heat loss of the gel pads between groups. The body temperature of dogs wrapped with the Sirius rescue sheet increased intraoperatively. In dogs just lying on warmed gel pads, a decrease in mean body temperature was revealed and mean body temperatures differed between groups after 40 minutes. Extent of heat loss from the gel pads did not differ between the groups. The Sirius rescue sheet, used in addition to warmed gel pads, led to higher intraoperative body temperatures in small breed dogs undergoing surgical procedures to the extremities and the head. The cost-effectiveness and ease of handling make this a useful addition to clinical practice.

  10. Effect of rescue breathing by lay rescuers for out-of-hospital cardiac arrest caused by respiratory disease: a nationwide, population-based, propensity score-matched study.

    Science.gov (United States)

    Fukuda, Tatsuma; Ohashi-Fukuda, Naoko; Kondo, Yutaka; Sera, Toshiki; Yahagi, Naoki

    2017-06-01

    The importance of respiratory care in cardiopulmonary resuscitation may vary depending on the cause of cardiac arrest. No previous study has investigated the effects of rescue breathing performed by a lay rescuer on the outcomes of patients with out-of-hospital cardiac arrest (OHCA) caused by intrinsic respiratory diseases. The aim of this study was to investigate whether rescue breathing performed by a lay rescuer is associated with outcomes after respiratory disease-related OHCA. In a nationwide, population-based, propensity score-matched study in Japan, among adult patients with OHCA caused by respiratory disease who received bystander cardiopulmonary resuscitation from January 1, 2005 to December 31, 2010, we compared patients with rescue breathing to those without rescue breathing. The primary outcome was neurologically favorable survival 1 month after OHCA. Of the eligible 14,781 patients, 4970 received rescue breathing from a lay rescuer and 9811 did not receive rescue breathing. In a propensity score-matched cohort (4897 vs. 4897 patients), the neurologically favorable survival rate was similar between patients with and without rescue breathing from a lay rescuer [0.9 vs. 0.7 %; OR 1.23 (95 % CI 0.79-1.93)]. Additionally, in subgroup analyses, rescue breathing was not associated with neurological outcome regardless of the type of rescuer [family member: adjusted OR 0.83 (95 % CI 0.39-1.70); or non-family member: adjusted OR 1.91 (95 % CI 0.79-5.35)]. Even among patients with OHCA caused by respiratory disease, rescue breathing performed by a lay rescuer was not associated with neurological outcomes, regardless of the type of lay rescuer.

  11. Aspects of defects in 3d-3d correspondence

    International Nuclear Information System (INIS)

    Gang, Dongmin; Kim, Nakwoo; Romo, Mauricio; Yamazaki, Masahito

    2016-01-01

    In this paper we study supersymmetric co-dimension 2 and 4 defects in the compactification of the 6d (2,0) theory of type A_N_−_1 on a 3-manifold M. The so-called 3d-3d correspondence is a relation between complexified Chern-Simons theory (with gauge group SL(N,ℂ)) on M and a 3d N=2 theory T_N[M]. We study this correspondence in the presence of supersymmetric defects, which are knots/links inside the 3-manifold. Our study employs a number of different methods: state-integral models for complex Chern-Simons theory, cluster algebra techniques, domain wall theory T[SU(N)], 5d N=2 SYM, and also supergravity analysis through holography. These methods are complementary and we find agreement between them. In some cases the results lead to highly non-trivial predictions on the partition function. Our discussion includes a general expression for the cluster partition function, which can be used to compute in the presence of maximal and certain class of non-maximal punctures when N>2. We also highlight the non-Abelian description of the 3d N=2T_N[M] theory with defect included, when such a description is available. This paper is a companion to our shorter paper http://dx.doi.org/10.1088/1751-8113/49/30/30LT02, which summarizes our main results.

  12. Point defects and defect clusters examined on the basis of some fundamental experiments

    International Nuclear Information System (INIS)

    Zuppiroli, L.

    1975-01-01

    On progressing from the centre of the defect to the surface the theoretical approach to a point defect passes from electronic theories to elastic theory. Experiments by which the point defect can be observed fall into two categories. Those which detect long-range effects: measurement of dimensional variations in the sample; measurement of the mean crystal parameter variation; elastic X-ray scattering near the nodes of the reciprocal lattice (Huang scattering). Those which detect more local effects: low-temperature resistivity measurement; positron capture and annihilation; local scattering far from the reciprocal lattice nodes. Experiments involving both short and long-range effects can always be found. This is the case for example with the dechanneling of α particles by defects. Certain of the experimental methods quoted above apply also to the study of point defect clusters. These methods are illustrated by some of their most striking results which over the last twenty years have refined our knowledge of point defects and defect clusters: length and crystal parameter measurements; diffuse X-ray scattering; low-temperature resistivity measurements; ion emission microscopy; electron microscopy; elastoresistivity [fr

  13. Birth Defects (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Birth Defects KidsHealth / For Parents / Birth Defects What's in ... Prevented? Print en español Anomalías congénitas What Are Birth Defects? While still in the womb, some babies ...

  14. Defect of the Eyelids.

    Science.gov (United States)

    Lu, Guanning Nina; Pelton, Ron W; Humphrey, Clinton D; Kriet, John David

    2017-08-01

    Eyelid defects disrupt the complex natural form and function of the eyelids and present a surgical challenge. Detailed knowledge of eyelid anatomy is essential in evaluating a defect and composing a reconstructive plan. Numerous reconstructive techniques have been described, including primary closure, grafting, and a variety of local flaps. This article describes an updated reconstructive ladder for eyelid defects that can be used in various permutations to solve most eyelid defects. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. [Impact of sperm DNA and acrosome integrity and acrosome reaction rate on outcomes of rescue intracytoplasmic sperm injection].

    Science.gov (United States)

    He, Yongzhi; Li, Dawen; Cheng, Junping; Huo, Zhongchao; Huang, Hongyi; Xiao, Xin

    2016-01-01

    Objective To explore the effects of sperm DNA integrity rate, acrosome integrity rate and acrosome reaction rate on the outcomes of rescue intracytoplasmic sperm injection (ICSI). This retrospective analysis was conducted among 97 infertile couples receiving rescue ICSI due to failure of in vitro fertilization procedures in our Reproductive Medicine Center. Of these 97 women, 41 had clinical pregnancy and 56 did not, and the effects of sperm DNA integrity rate (estimated by DNA fragmentation index, DFI), acrosome integrity rate and acrosome reaction rate on rescue ICSI outcomes were analyzed. No significant difference was found in paternal age, testosterone value, testicular volume, FSH, female patient' age or the number of eggs retrieved between the two groups (P>0.05), but the infertility years was significantly shorter in the pregnancy group than in the non-pregnancy group (Prate and cleavage rate were similar between the two groups (P>0.05), but the good embryo rate was significantly higher in the pregnancy group (Preaction rate did not differ significantly between the two groups (P>0.05), but the acrosome integrity rate was significantly higher in the pregnancy group (Prate, acrosome integrity or acrosome reaction rate were not correlated with the fertilization rate, cleavage rate or good embryo rate (P>0.05). The pregnancy rate, twin and single fetus rates were 42.3%, 10.3% and 32.0% in this cohort after recue ICSI, respectively. Rescue ICSI is an effective treatment after failed in vitro fertilization procedure, and sperm acrosome integrity rate is associated with the outcome of rescue ICSI.

  16. Defects in mitochondrial fission protein dynamin-related protein 1 are linked to apoptotic resistance and autophagy in a lung cancer model.

    Directory of Open Access Journals (Sweden)

    Kelly Jean Thomas

    Full Text Available Evasion of apoptosis is implicated in almost all aspects of cancer progression, as well as treatment resistance. In this study, resistance to apoptosis was identified in tumorigenic lung epithelial (A549 cells as a consequence of defects in mitochondrial and autophagic function. Mitochondrial function is determined in part by mitochondrial morphology, a process regulated by mitochondrial dynamics whereby the joining of two mitochondria, fusion, inhibits apoptosis while fission, the division of a mitochondrion, initiates apoptosis. Mitochondrial morphology of A549 cells displayed an elongated phenotype-mimicking cells deficient in mitochondrial fission protein, Dynamin-related protein 1 (Drp1. A549 cells had impaired Drp1 mitochondrial recruitment and decreased Drp1-dependent fission. Cytochrome c release and caspase-3 and PARP cleavage were impaired both basally and with apoptotic stimuli in A549 cells. Increased mitochondrial mass was observed in A549 cells, suggesting defects in mitophagy (mitochondrial selective autophagy. A549 cells had decreased LC3-II lipidation and lysosomal inhibition suggesting defects in autophagy occur upstream of lysosomal degradation. Immunostaining indicated mitochondrial localized LC3 punctae in A549 cells increased after mitochondrial uncoupling or with a combination of mitochondrial depolarization and ectopic Drp1 expression. Increased inhibition of apoptosis in A549 cells is correlated with impeded mitochondrial fission and mitophagy. We suggest mitochondrial fission defects contribute to apoptotic resistance in A549 cells.

  17. Direct observation of cascade defect formation at low temperatures in ion-irradiated metals

    International Nuclear Information System (INIS)

    Muroga, T.; Hirooka, K.; Ishino, S.

    1984-01-01

    Direct transmission electron microscopy observations of cascade defect formation have been carried out in gold, Type 316 stainless steel, and aluminum irradiated by Al + , Ar - , and Xe + ions with energies between 80 and 400 keV. By utilizing a link of an ion accelerator to an electron microscope, in situ observations at low temperature (-150 0 C) have become possible. In gold, subcascade structures are clearly observed in all cases. Obvious dependence on projectile mass and energy is observed for cascade structure and vacancy clustering efficiency in gold and for defect visibility in aluminum and Type 316 stainless steel. A computer simulation calculation using MARLOWE shows subcascade distributions a little smaller in size and larger in number than the present observation

  18. Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation.

    NARCIS (Netherlands)

    Kalscheuer, V.M.M.; Freude, K.; Musante, L.; Jensen, L.R.; Yntema, H.G.; Gecz, J.; Sefiani, A.; Hoffmann, K.; Moser, B.; Haas, S.; Gurok, U.; Haesler, S.; Aranda, B.; Nshedjan, A.; Tzschach, A.; Hartmann, N.; Roloff, T.C.; Shoichet, S.; Hagens, O.; Tao, J.; Bokhoven, J.H.L.M. van; Turner, G.; Chelly, J.; Moraine, C.; Fryns, J.P.; Nuber, U.; Hoeltzenbein, M.; Scharff, C.; Scherthan, H.; Lenzner, S.; Hamel, B.C.J.; Schweiger, S.; Ropers, H.H.

    2003-01-01

    We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously

  19. Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

    DEFF Research Database (Denmark)

    Kalscheuer, Vera M; Freude, Kristine; Musante, Luciana

    2003-01-01

    We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previou...

  20. Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

    NARCIS (Netherlands)

    Kalscheuer, VM; Freude, K; Musante, L; Jensen, LR; Yntema, HG; Gecz, J; Sefiani, A; Hoffmann, K; Moser, B; Haas, S; Gurok, U; Haesler, S; Aranda, B; Nshedjan, A; Tzschach, A; Hartmann, N; Roloff, TC; Shoichet, S; Hagens, O; Tao, J; van Bokhoven, H; Turner, G; Chelly, J; Moraine, C; Fryns, JP; Nuber, U; Hoeltzenbein, M; Scharff, C; Scherthan, H; Lenzner, S; Hamel, BCJ; Schweiger, S; Ropers, Hans-Hilger

    2003-01-01

    We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previously

  1. Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

    OpenAIRE

    McMahon, Laura W.; Zhang, Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

    2009-01-01

    Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellu...

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

    Science.gov (United States)

    Shibui, Tatsuro; Hara, Hiroyoshi

    2017-09-01

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

  3. Formation of topological defects

    International Nuclear Information System (INIS)

    Vachaspati, T.

    1991-01-01

    We consider the formation of point and line topological defects (monopoles and strings) from a general point of view by allowing the probability of formation of a defect to vary. To investigate the statistical properties of the defects at formation we give qualitative arguments that are independent of any particular model in which such defects occur. These arguments are substantiated by numerical results in the case of strings and for monopoles in two dimensions. We find that the network of strings at formation undergoes a transition at a certain critical density below which there are no infinite strings and the closed-string (loop) distribution is exponentially suppressed at large lengths. The results are contrasted with the results of statistical arguments applied to a box of strings in dynamical equilibrium. We argue that if point defects were to form with smaller probability, the distance between monopoles and antimonopoles would decrease while the monopole-to-monopole distance would increase. We find that monopoles are always paired with antimonopoles but the pairing becomes clean only when the number density of defects is small. A similar reasoning would also apply to other defects

  4. Photographic guide of selected external defect indicators and associated internal defects in sugar maple

    Science.gov (United States)

    Everette D. Rast; John A. Beaton; David L. Sonderman

    1991-01-01

    To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for sugar maple. Eleven types of external...

  5. Photographic guide of selected external defect indicators and associated internal defects in yellow-poplar

    Science.gov (United States)

    Everette D. Rast; John A. Beaton; David L. Sonderman

    1991-01-01

    To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow-poplar. Twelve types of external...

  6. Photographic guide of selected external defect indicators and associated internal defects in yellow birch

    Science.gov (United States)

    Everette D. Rast; John A. Beaton; David L. Sonderman

    1991-01-01

    To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow birch. Eleven types of external...

  7. Distribution of defects in wind turbine blades and reliability assessment of blades containing defects

    DEFF Research Database (Denmark)

    Stensgaard Toft, Henrik; Branner, Kim; Berring, Peter

    2009-01-01

    on the assumption that one error in the production process tends to trigger several defects. For both models additional information about number, type and size of the defects is included as stochastic variables. The probability of failure for a wind turbine blade will not only depend on variations in the material......In the present paper two stochastic models for the distribution of defects in wind turbine blades are proposed. The first model assumes that the individual defects are completely randomly distributed in the blade. The second model assumes that the defects occur in clusters of different size based...... properties and the load but also on potential defects in the blades. As a numerical example the probability of failure is calculated for the main spar both with and without defects in terms of delaminations. The delaminations increase the probability of failure compared to a perfect blade, but by applying...

  8. A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype

    Science.gov (United States)

    Slee, R.; Grimes, B.; Speed, R. M.; Taggart, M.; Maguire, S. M.; Ross, A.; McGill, N. I.; Saunders, P. T. K.; Cooke, H. J.

    1999-01-01

    In a subset of infertile men, a spectrum of spermatogenic defects ranging from a complete absence of germ cells (sertoli cell only) to oligozoospermia is associated with microdeletions of the DAZ (deleted in azoospermia) gene cluster on human distal Yq. DAZ encodes a testis-specific protein with RNA-binding potential recently derived from a single-copy gene DAZL1 (DAZ-like) on chromosome 3. Y chromosomal DAZ homologues are confined to humans and higher primates. It remains unclear which function unique to higher primate spermatogenesis DAZ may serve, and the functional status of the gene recently has been questioned. To assess the extent of functional conservation we have tested the capacity of a human DAZ gene contained in a 225-kb yeast artificial chromosome to complement the sterile phenotype of the Dazl null mouse (Dazl−/−), which is characterized by severe germ-cell depletion and meiotic failure. Although Dazl−/− mice remained infertile when the DAZ transgene was introduced, histological examination revealed a partial and variable rescue of the mutant phenotype, manifest as a pronounced increase in the germ cell population of the seminiferous tubules and survival to the pachytene stage of meiosis. As well as constituting definitive proof of the spermatogenic role of the DAZ gene product, these findings confirm the high degree of functional conservation between the DAZ and DAZL1 genes, suggesting they may constitute a single target for contraceptive intervention and raising the possibility of therapeutic up-regulation of the DAZL1 gene in infertile men. PMID:10393944

  9. Cell-permeable intrinsic cellular inhibitors of apoptosis protect and rescue intestinal epithelial cells from radiation-induced cell death

    International Nuclear Information System (INIS)

    Matsuzaki-Horibuchi, Shiori; Yasuda, Takeshi; Sakaguchi, Nagako; Yamaguchi, Yoshihiro; Akashi, Makoto

    2015-01-01

    One of the important mechanisms for gastrointestinal (GI) injury following high-dose radiation exposure is apoptosis of epithelial cells. X-linked inhibitor of apoptosis (XIAP) and cellular IAP2 (cIAP2) are intrinsic cellular inhibitors of apoptosis. In order to study the effects of exogenously added IAPs on apoptosis in intestinal epithelial cells, we constructed bacterial expression plasmids containing genes of XIAP (full-length, BIR2 domain and BIR3-RING domain with and without mutations of auto-ubiquitylation sites) and cIAP2 proteins fused to a protein-transduction domain (PTD) derived from HIV-1 Tat protein (TAT) and purified these cell-permeable recombinant proteins. When the TAT-conjugated IAPs were added to rat intestinal epithelial cells IEC6, these proteins were effectively delivered into the cells and inhibited apoptosis, even when added after irradiation. Our results suggest that PTD-mediated delivery of IAPs may have clinical potential, not only for radioprotection but also for rescuing the GI system from radiation injuries. (author)

  10. Entanglement entropy in integrable field theories with line defects II. Non-topological defect

    Science.gov (United States)

    Jiang, Yunfeng

    2017-08-01

    This is the second part of two papers where we study the effect of integrable line defects on bipartite entanglement entropy in integrable field theories. In this paper, we consider non-topological line defects in Ising field theory. We derive an infinite series expression for the entanglement entropy and show that both the UV and IR limits of the bulk entanglement entropy are modified by the line defect. In the UV limit, we give an infinite series expression for the coefficient in front of the logarithmic divergence and the exact defect g-function. By tuning the defect to be purely transmissive and reflective, we recover correctly the entanglement entropy of the bulk and with integrable boundary respectively.

  11. GIS plays key role in NYC Rescue and Relief Operation

    Science.gov (United States)

    Showstack, Randy

    New York City, Sept. 17—The posters of missing loved ones are pasted onto New York City walls and street signs six days after 2 hijacked commercial airlines destroyed the World Trade Center in lower Manhattan on September 11. Several miles uptown from “ground zero,” heightened security hovers around the city's Office of Emergency Management rescue and relief command center, an around-the-clock operation. Police, firefighters, military, officials with the Federal Emergency Management Agency, communications technicians, and a beehive of others work in controlled chaos in this cavernous, convention center-sized hall, lined with computers and adorned with several American flags.After the original command center at 7 World Trade Center collapsed to rubble as an after-effect of the plane strikes, city officials scrambled to recreate it. Alan Leidner, director of New York's citywide geographic information systems (GIS), and who is with the Department of Information Technology and Telecommunications, knew that maps would be an integral component of the rescue and relief efforts. Maps provide emergency workers and others with accurate and detailed scientific data in the form of visual aids upon which they can make informed decisions.

  12. Ten years of helicopter emergency medical services in Germany: do we still need the helicopter rescue in multiple traumatised patients?

    Science.gov (United States)

    Andruszkow, Hagen; Hildebrand, Frank; Lefering, Rolf; Pape, Hans-Christoph; Hoffmann, Reinhard; Schweigkofler, Uwe

    2014-10-01

    Helicopter emergency medical service (HEMS) has been established in the preclinical treatment of multiple traumatised patients despite an ongoing controversy towards the potential benefit. Celebrating the 20th anniversary of TraumaRegister DGU(®) of the German Trauma Society (DGU) the presented study intended to provide an overview of HEMS rescue in Germany over the last 10 years analysing the potential beneficial impact of a nationwide helicopter rescue in multiple traumatised patients. We analysed TraumaRegister DGU(®) including multiple traumatised patients (ISS ≥ 16) between 2002 and 2012. In-hospital mortality was defined as main outcome. An adjusted, multivariate regression with 13 confounders was performed to evaluate the potential survival benefit. 42,788 patients were included in the present study. 14,275 (33.4%) patients were rescued by HEMS and 28,513 (66.6%) by GEMS. Overall, 66.8% (n=28,569) patients were transported to a level I trauma centre and 28.2% (n=12,052) to a level II trauma centre. Patients rescued by HEMS sustained a higher injury severity compared to GEMS (ISS HEMS: 29.5 ± 12.6 vs. 27.5 ± 11.8). Helicopter rescue teams performed more on-scene interventions, and mission times were increased in HEMS rescue (HEMS: 77.2 ± 28.7 min. vs. GEMS: 60.9 ± 26.9 min.). Linear regression analysis revealed that the frequency of HEMS rescue has decreased significantly between 2002 and 2012. In case of transportation to level I trauma centres a decrease of 1.7% per year was noted (p<0.001) while a decline of 1.6% per year (p<0.001) was measured for level II trauma centre admissions. According to multivariate logistic regression HEMS was proven a positive independent survival predictor between 2002 and 2012 (OR 0.863; 95%-CI 0.800-0.930; Nagelkerkes-R(2) 0.539) with only little differences between each year. This study was able to prove an independent survival benefit of HEMS in multiple traumatised patients during the last 10 years. Despite this

  13. Dental enamel defects predict adolescent health indicators: A cohort study among the Tsimane' of Bolivia.

    Science.gov (United States)

    Masterson, Erin E; Fitzpatrick, Annette L; Enquobahrie, Daniel A; Mancl, Lloyd A; Eisenberg, Dan T A; Conde, Esther; Hujoel, Philippe P

    2018-05-01

    Bioarchaeological findings have linked defective enamel formation in preadulthood with adult mortality. We investigated how defective enamel formation in infancy and childhood is associated with risk factors for adult morbidity and mortality in adolescents. This cohort study of 349 Amerindian adolescents (10-17 years of age) related extent of enamel defects on the central maxillary incisors (none, less than 1/3, 1/3 to 2/3, more than 2/3) to adolescent anthropometrics (height, weight) and biomarkers (hemoglobin, glycated hemoglobin, white blood cell count, and blood pressure). Risk differences and 95% confidence intervals were estimated using multiple linear regression. Enamel defects and stunted growth were compared in their ability to predict adolescent health indicators using log-binomial regression and receiver operating characteristics (ROCs). Greater extent of defective enamel formation on the tooth surface was associated with shorter height (-1.35 cm, 95% CI: -2.17, -0.53), lower weight (-0.98 kg, 95% CI: -1.70, -0.26), lower hemoglobin (-0.36 g/dL, 95% CI: -0.59, -0.13), lower glycated hemoglobin (-0.04 %A 1c , 95% CI: -0.08, -0.00008), and higher white blood cell count (0.74 10 9 /L, 95% CI: 0.35, 1.14) in adolescence. Extent of enamel defects and stunted growth independently performed similarly as risk factors for adverse adolescent outcomes, including anemia, prediabetes/type II diabetes, elevated WBC count, prehypertension/hypertension, and metabolic health. Defective enamel formation in infancy and childhood predicted adolescent health outcomes and may be primarily associated with infection. Extent of enamel defects and stunted growth may be equally predictive of adverse adolescent health outcomes. © 2018 Wiley Periodicals, Inc.

  14. Natural defects and defects created by ionic implantation in zinc tellurium

    International Nuclear Information System (INIS)

    Roche, J.P.; Dupuy, M.; Pfister, J.C.

    1977-01-01

    Various defects have been studied in ZnTe crystals by transmission electron microscope and by scanning electron microscope in cathodo-luminescence mode: grain boundaries, sub-grain boundaries, twins. Ionic implants of boron (100 keV - 2x10 14 and 10 15 ions cm -2 ) were made on these crystals followed by isochrone annealing (30 minutes) of zinc under partial pressure at 550, 650 and 750 0 C. The nature of the defects was determined by transmission electron microscope: these are interstitial loops (b=1/3 ) the size of which varies between 20 A (non-annealed sample) and 180A (annealed at 750 0 C). The transmission electron microscope was also used to make concentration profiles of defects depending on depth. It is found that for the same implant (2x10 14 ions.cm -2 ), the defect peak moves towards the exterior of the crystal as the annealing temperature rises (400 - 1000 and 7000 A for the three annealings). These results are explained from a model which allows for the coalescence of defects and considers the surface of the sample as being the principal source of vacancies. During the annealings, the migration of vacancies brings about the gradual annihilation of the implant defects. The adjustment of certain calculation parameters on the computer result in giving 2 eV as energy value for the formation of vacancies [fr

  15. Modeling the relationships among internal defect features and external Appalachian hardwood log defect indicators

    Science.gov (United States)

    R. Edward. Thomas

    2009-01-01

    As a hardwood tree grows and develops, surface defects such as branch stubs and wounds are overgrown. Evidence of these defects remain on the log surface for decades and in many instances for the life of the tree. As the tree grows the defect is encapsulated or grown over by new wood. During this process the appearance of the defect in the tree's bark changes. The...

  16. 49 CFR Figure 1a to Subpart B of... - Example of Location of Rescue Access Windows-§ 238.114

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Example of Location of Rescue Access Windows-§ 238.114 1A Figure 1A to Subpart B of Part 238 Transportation Other Regulations Relating to... B of Part 238—Example of Location of Rescue Access Windows—§ 238.114 ER01FE08.002 [73 FR 6403, Feb...

  17. Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure

    Science.gov (United States)

    Konkalmatt, Prasad R.; Asico, Laureano D.; Zhang, Yanrong; Yang, Yu; Drachenberg, Cinthia; Zheng, Xiaoxu; Han, Fei; Jose, Pedro A.; Armando, Ines

    2016-01-01

    Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector with DRD2. Renal Drd2 siRNA treatment decreased the renal expression of DRD2 protein by 55%, and DRD2 AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selective DRD2 rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selective Drd2 silencing on renal function and blood pressure were rescued by renal-selective overexpression of DRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion of DRD2 AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused with DRD2 AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure. PMID:27358912

  18. Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade.

    Science.gov (United States)

    Huffaker, Thomas B; Lee, Soh-Hyun; Tang, William W; Wallace, Jared A; Alexander, Margaret; Runtsch, Marah C; Larsen, Dane K; Thompson, Jacob; Ramstead, Andrew G; Voth, Warren P; Hu, Ruozhen; Round, June L; Williams, Matthew A; O'Connell, Ryan M

    2017-11-10

    MicroRNA-155 (miR-155) regulates antitumor immune responses. However, its specific functions within distinct immune cell types have not been delineated in conditional KO mouse models. In this study, we investigated the role of miR-155 specifically within T cells during the immune response to syngeneic tumors. We found that miR-155 expression within T cells is required to limit syngeneic tumor growth and promote IFNγ production by T cells within the tumor microenvironment. Consequently, we found that miR-155 expression by T cells is necessary for proper tumor-associated macrophage expression of IFNγ-inducible genes. We also found that immune checkpoint-blocking (ICB) antibodies against programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) restored antitumor immunity in miR-155 T cell-conditional KO mice. We noted that these ICB antibodies rescued the levels of IFNγ-expressing T cells, expression of multiple activation and effector genes expressed by tumor-infiltrating CD8 + and CD4 + T cells, and tumor-associated macrophage activation. Moreover, the ICB approach partially restored expression of several derepressed miR-155 targets in tumor-infiltrating, miR-155-deficient CD8 + T cells, suggesting that miR-155 and ICB regulate overlapping pathways to promote antitumor immunity. Taken together, our findings highlight the multifaceted role of miR-155 in T cells, in which it promotes antitumor immunity. These results suggest that the augmentation of miR-155 expression could be used to improve anticancer immunotherapies. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Automatic classification of blank substrate defects

    Science.gov (United States)

    Boettiger, Tom; Buck, Peter; Paninjath, Sankaranarayanan; Pereira, Mark; Ronald, Rob; Rost, Dan; Samir, Bhamidipati

    2014-10-01

    Mask preparation stages are crucial in mask manufacturing, since this mask is to later act as a template for considerable number of dies on wafer. Defects on the initial blank substrate, and subsequent cleaned and coated substrates, can have a profound impact on the usability of the finished mask. This emphasizes the need for early and accurate identification of blank substrate defects and the risk they pose to the patterned reticle. While Automatic Defect Classification (ADC) is a well-developed technology for inspection and analysis of defects on patterned wafers and masks in the semiconductors industry, ADC for mask blanks is still in the early stages of adoption and development. Calibre ADC is a powerful analysis tool for fast, accurate, consistent and automatic classification of defects on mask blanks. Accurate, automated classification of mask blanks leads to better usability of blanks by enabling defect avoidance technologies during mask writing. Detailed information on blank defects can help to select appropriate job-decks to be written on the mask by defect avoidance tools [1][4][5]. Smart algorithms separate critical defects from the potentially large number of non-critical defects or false defects detected at various stages during mask blank preparation. Mechanisms used by Calibre ADC to identify and characterize defects include defect location and size, signal polarity (dark, bright) in both transmitted and reflected review images, distinguishing defect signals from background noise in defect images. The Calibre ADC engine then uses a decision tree to translate this information into a defect classification code. Using this automated process improves classification accuracy, repeatability and speed, while avoiding the subjectivity of human judgment compared to the alternative of manual defect classification by trained personnel [2]. This paper focuses on the results from the evaluation of Automatic Defect Classification (ADC) product at MP Mask

  20. Linking advanced fracture models to structural analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chiesa, Matteo

    2001-07-01

    Shell structures with defects occur in many situations. The defects are usually introduced during the welding process necessary for joining different parts of the structure. Higher utilization of structural materials leads to a need for accurate numerical tools for reliable prediction of structural response. The direct discretization of the cracked shell structure with solid finite elements in order to perform an integrity assessment of the structure in question leads to large size problems, and makes such analysis infeasible in structural application. In this study a link between local material models and structural analysis is outlined. An ''ad hoc'' element formulation is used in order to connect complex material models to the finite element framework used for structural analysis. An improved elasto-plastic line spring finite element formulation, used in order to take cracks into account, is linked to shell elements which are further linked to beam elements. In this way one obtain a global model of the shell structure that also accounts for local flexibilities and fractures due to defects. An important advantage with such an approach is a direct fracture mechanics assessment e.g. via computed J-integral or CTOD. A recent development in this approach is the notion of two-parameter fracture assessment. This means that the crack tip stress tri-axiality (constraint) is employed in determining the corresponding fracture toughness, giving a much more realistic capacity of cracked structures. The present thesis is organized in six research articles and an introductory chapter that reviews important background literature related to this work. Paper I and II address the performance of shell and line spring finite elements as a cost effective tool for performing the numerical calculation needed to perform a fracture assessment. In Paper II a failure assessment, based on the testing of a constraint-corrected fracture mechanics specimen under tension, is

  1. Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus.

    Science.gov (United States)

    Zhang, Ying; Cao, Shu-Xia; Sun, Peng; He, Hai-Yang; Yang, Ci-Hang; Chen, Xiao-Juan; Shen, Chen-Jie; Wang, Xiao-Dong; Chen, Zhong; Berg, Darwin K; Duan, Shumin; Li, Xiao-Ming

    2016-06-01

    Mutations in the X-linked MECP2 gene cause Rett syndrome (RTT), an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain (BF) cholinergic neurons rather than in the caudate putamen of conditional knockout (Chat-Mecp2(-/y)) mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2(-/y) mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2(-/y) mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.

  2. Holographic Chern-Simons defects

    International Nuclear Information System (INIS)

    Fujita, Mitsutoshi; Melby-Thompson, Charles M.; Meyer, René; Sugimoto, Shigeki

    2016-01-01

    We study SU(N) Yang-Mills-Chern-Simons theory in the presence of defects that shift the Chern-Simons level from a holographic point of view by embedding the system in string theory. The model is a D3-D7 system in Type IIB string theory, whose gravity dual is given by the AdS soliton background with probe D7 branes attaching to the AdS boundary along the defects. We holographically renormalize the free energy of the defect system with sources, from which we obtain the correlation functions for certain operators naturally associated to these defects. We find interesting phase transitions when the separation of the defects as well as the temperature are varied. We also discuss some implications for the Fractional Quantum Hall Effect and for 2-dimensional QCD.

  3. A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model.

    Science.gov (United States)

    Wang, Fang; Travins, Jeremy; Lin, Zhizhong; Si, Yaguang; Chen, Yue; Powe, Josh; Murray, Stuart; Zhu, Dongwei; Artin, Erin; Gross, Stefan; Santiago, Stephanie; Steadman, Mya; Kernytsky, Andrew; Straley, Kimberly; Lu, Chenming; Pop, Ana; Struys, Eduard A; Jansen, Erwin E W; Salomons, Gajja S; David, Muriel D; Quivoron, Cyril; Penard-Lacronique, Virginie; Regan, Karen S; Liu, Wei; Dang, Lenny; Yang, Hua; Silverman, Lee; Agresta, Samuel; Dorsch, Marion; Biller, Scott; Yen, Katharine; Cang, Yong; Su, Shin-San Michael; Jin, Shengfang

    2016-11-01

    D-2-hydroxyglutaric aciduria (D2HGA) type II is a rare neurometabolic disorder caused by germline gain-of-function mutations in isocitrate dehydrogenase 2 (IDH2), resulting in accumulation of D-2-hydroxyglutarate (D2HG). Patients exhibit a wide spectrum of symptoms including cardiomyopathy, epilepsy, developmental delay and limited life span. Currently, there are no effective therapeutic interventions. We generated a D2HGA type II mouse model by introducing the Idh2R140Q mutation at the native chromosomal locus. Idh2R140Q mice displayed significantly elevated 2HG levels and recapitulated multiple defects seen in patients. AGI-026, a potent, selective inhibitor of the human IDH2R140Q-mutant enzyme, suppressed 2HG production, rescued cardiomyopathy, and provided a survival benefit in Idh2R140Q mice; treatment withdrawal resulted in deterioration of cardiac function. We observed differential expression of multiple genes and metabolites that are associated with cardiomyopathy, which were largely reversed by AGI-026. These findings demonstrate the potential therapeutic benefit of an IDH2R140Q inhibitor in patients with D2HGA type II.

  4. Survival and differentiation defects contribute to neutropenia in glucose-6-phosphatase-β (G6PC3) deficiency in a model of mouse neutrophil granulocyte differentiation.

    Science.gov (United States)

    Gautam, S; Kirschnek, S; Gentle, I E; Kopiniok, C; Henneke, P; Häcker, H; Malleret, L; Belaaouaj, A; Häcker, G

    2013-08-01

    Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3(-/-) mice. Progenitor lines were established and differentiated into neutrophils when Hoxb8 was turned off. G6PC3(-/-) progenitor cells underwent substantial apoptosis when differentiation was started. Transgenic expression of Bcl-XL rescued survival; however, Bcl-XL-protected differentiated cells showed reduced proliferation, immaturity and functional deficiency such as altered MAP kinase signaling and reduced cytokine secretion. Impaired glucose utilization was found and was associated with ER stress and apoptosis, associated with the upregulation of Bim and Bax; downregulation of Bim protected against apoptosis during differentiation. ER-stress further caused a profound loss of expression and secretion of the main neutrophil product neutrophil elastase during differentiation. Transplantation of wild-type Hoxb8-progenitor cells into irradiated mice allowed differentiation into neutrophils in the bone marrow in vivo. Transplantation of G6PC3(-/-) cells yielded few mature neutrophils in bone marrow and peripheral blood. Transgenic Bcl-XL permitted differentiation of G6PC3(-/-) cells in vivo. However, functional deficiencies and differentiation abnormalities remained. Differentiation of macrophages from Hoxb8-dependent progenitors was only slightly disturbed. A combination of defects in differentiation

  5. Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase

    Directory of Open Access Journals (Sweden)

    Saul S. Siller

    2011-09-01

    Fragile X syndrome (FXS, caused by loss of the fragile X mental retardation 1 (FMR1 product (FMRP, is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess the effects of minocycline treatment on multiple neural circuit morphological defects and to investigate the MMP hypothesis. We first treat Drosophila Fmr1 (dfmr1 null animals with minocycline to assay the effects on mutant synaptic architecture in three disparate locations: the neuromuscular junction (NMJ, clock neurons in the circadian activity circuit and Kenyon cells in the mushroom body learning and memory center. We find that minocycline effectively restores normal synaptic structure in all three circuits, promising therapeutic potential for FXS treatment. We next tested the MMP hypothesis by assaying the effects of overexpressing the sole Drosophila tissue inhibitor of MMP (TIMP in dfmr1 null mutants. We find that TIMP overexpression effectively prevents defects in the NMJ synaptic architecture in dfmr1 mutants. Moreover, co-removal of dfmr1 similarly rescues TIMP overexpression phenotypes, including cellular tracheal defects and lethality. To further test the MMP hypothesis, we generated dfmr1;mmp1 double null mutants. Null mmp1 mutants are 100% lethal and display cellular tracheal defects, but co-removal of dfmr1 allows adult viability and prevents tracheal defects. Conversely, co-removal of mmp1 ameliorates the NMJ synaptic architecture defects in dfmr1 null mutants, despite the lack of detectable difference in MMP1 expression or gelatinase activity between the single

  6. A Novel Design of Rescue Capsule considering the Pressure Characteristics and Thermal Dynamic Response with Thermomechanical Coupling Action Subjected to Gas Explosion Load

    Directory of Open Access Journals (Sweden)

    Xiaowei Zhai

    2017-01-01

    Full Text Available To ensure the structural safety and reliability of coal mine rescue capsule in disastrous surroundings after gas explosion, in this paper, the thermomechanical coupling effect on a certain structure subjected to gas explosion was analyzed, and then a novel rescue capsule with a combination of radius and square features was designed according to the underground surroundings and relevant regulations on mine rescue devices. Foremost, the coupling mechanism of thermal-fluid-solid interaction between gas explosion shock wave and rescue capsule and the thermal dynamic response of the capsule subjected to explosion load of gas/air mixture was investigated and revealed by employing LS-DYNA. The variation laws and characteristics of stress field, displacement field, and temperature field of the capsule were analyzed based on the simulation results. Results show that the structural safety, tightness, and reliability of the capsule meet the requirements of the national safety regulations. The design method presented in this work provides a new thought for design of coal mine rescue capsule.

  7. Role of rescue IVF-ET treatment in the management of high response in stimulated IUI cycles.

    Science.gov (United States)

    Olufowobi, O; Sharif, K; Papaioannou, S; Mohamed, H; Neelakantan, D; Afnan, M

    2005-02-01

    Rescue in-vitro fertilisation and embryo transfer (IVF-ET) has been used in high response gonadotrophin intrauterine insemination (IUI) cycles to minimise the risks of ovarian hyperstimulation and multiple gestation. Such unplanned IVF treatment increases the cost of treatment. But can this added cost and the risks associated with IVF be justified? We present our experience with this treatment using clinical pregnancy and live birth rates as the primary outcomes. Between 1998 to 2001, 40 women undergoing IUI cycles who over responded (>3 follicles measuring >15 mm in diameter on the planned day of hCG administration) to gonadotrophin were offered the choice of conversion to IVF-ET or cancel the cycle. 17/40 declined rescue IVF/ET and had their cycles cancelled. 23/40 converted to IVF/ET and underwent transvaginal oocyte retrieval. 21/23 had embryo transferred. The clinical pregnancy and live birth rates were 52% and 48%, respectively. Rescue IVF-ET offers excellent clinical pregnancy and live birth rates in high responders. However, affordability can be an obstacle in the utilization of this treatment option.

  8. Monitoring and Information Fusion for Search and Rescue Operations in Large-Scale Disasters

    National Research Council Canada - National Science Library

    Nardi, Daniele

    2002-01-01

    ... for information fusion with application to search-and-rescue and large scale disaster relief. The objective is to develop and to deploy tools to support the monitoring activities in an intervention caused by a large-scale disaster...

  9. 33 CFR 149.304 - What type and how many survival craft and rescue boats must a manned deepwater port have?

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false What type and how many survival craft and rescue boats must a manned deepwater port have? 149.304 Section 149.304 Navigation and... What type and how many survival craft and rescue boats must a manned deepwater port have? (a) Except as...

  10. Point defects in solids

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The principal properties of point defects are studied: thermodynamics, electronic structure, interactions with etended defects, production by irradiation. Some measuring methods are presented: atomic diffusion, spectroscopic methods, diffuse scattering of neutron and X rays, positron annihilation, molecular dynamics. Then points defects in various materials are investigated: ionic crystals, oxides, semiconductor materials, metals, intermetallic compounds, carbides, nitrides [fr

  11. Complex Interaction Mechanisms between Dislocations and Point Defects Studied in Pure Aluminium by a Two-Wave Acoustic Coupling Technique

    Science.gov (United States)

    Bremnes, O.; Progin, O.; Gremaud, G.; Benoit, W.

    1997-04-01

    Ultrasonic experiments using a two-wave coupling technique were performed on 99.999% pure Al in order to study the interaction mechanisms occurring between dislocations and point defects. The coupling technique consists in measuring the attenuation of ultrasonic waves during low-frequency stress cycles (t). One obtains closed curves () called signatures whose shape and evolution are characteristic of the interaction mechanism controlling the low-frequency dislocation motion. The signatures observed were attributed to the interaction of the dislocations with extrinsic point defects. A new interpretation of the evolution of the signatures measured below 200 K with respect to temperature and stress frequency had to be established: they are linked to depinning of immobile point defects, whereas a thermally activated depinning mechanism does not fit the observations. The signatures measured between 200 and 370 K were interpreted as dragging and depinning of extrinsic point defects which are increasingly mobile with temperature.

  12. Defect detection using transient thermography

    International Nuclear Information System (INIS)

    Mohd Zaki Umar; Ibrahim Ahmad; Ab Razak Hamzah; Wan Saffiey Wan Abdullah

    2008-08-01

    An experimental research had been carried out to study the potential of transient thermography in detecting sub-surface defect of non-metal material. In this research, eight pieces of bakelite material were used as samples. Each samples had a sub-surface defect in the circular shape with different diameters and depths. Experiment was conducted using one-sided Pulsed Thermal technique. Heating of samples were done using 30 kWatt adjustable quartz lamp while infra red (IR) images of samples were recorded using THV 550 IR camera. These IR images were then analysed with ThermofitTMPro software to obtain the Maximum Absolute Differential Temperature Signal value, ΔΤ m ax and the time of its appearance, τ m ax (ΔΤ). Result showed that all defects were able to be detected even for the smallest and deepest defect (diameter = 5 mm and depth = 4 mm). However the highest value of Differential Temperature Signal (ΔΤ m ax), were obtained at defect with the largest diameter, 20 mm and at the shallowest depth, 1 mm. As a conclusion, the sensitivity of the pulsed thermography technique to detect sub-surface defects of bakelite material is proportionately related with the size of defect diameter if the defects are at the same depth. On the contrary, the sensitivity of the pulsed thermography technique inversely related with the depth of defect if the defects have similar diameter size. (Author)

  13. Data Rescue Case Studies from the Cryosphere

    Science.gov (United States)

    Fetterer, F. M.

    2017-12-01

    A simple definition of the cryosphere is "where the world is frozen", or where water takes the form of snow and ice. The cryosphere is shrinking as the Earth warms. Data, particularly old data, document this in often eye-opening fashion. A photograph of Alaska's Muir Glacier taken in 1902 next to one taken in 2005 has impact that a line graph of air temperature anomalies from a weather station can't match, even though temperature data are fundamental to climate research and to understanding the glacier retreat captured in the photographs. Whaling logbooks from the late 1800s, maps of sea ice shared internationally in the 1930s, and satellite images of the polar oceans from the 1960s are not as immediately thought-provoking as are glacier photographs, but when preserved and documented they provide a record of sea ice coverage that is more than 100 years long. We developed a data product from these and other sources that is used in meteorological reanalysis and to answer questions about ice in the Arctic prior to 1978, when commonly used satellite-data-derived sea ice records begin. Preserving glacier photographs and making them available online, and publishing a gridded sea ice data product that builds on the preservation work of others are examples of data rescue projects that benefit scientific research and mobilize knowledge. These and other case studies suggest that even absent secure funding and an organizational setting that supports data rescue, important data make the transition from someone's office to archived and online with metadata because scientists are impassioned about the data they collect and want others to be able to use these data. In these cases from the cryosphere, student interns, collaborations with librarians, and cooperation with colleagues in other data centers have made it possible to preserve data at low cost.

  14. Civilian Helicopter Search and Rescue Accidents in the United States: 1980 Through 2013.

    Science.gov (United States)

    Worley, Gordon H

    2015-12-01

    Helicopters are commonly used in search and rescue operations, and accidents have occurred during helicopter search and rescue (HSAR) missions. The purposes of this study were to investigate whether the HSAR accident rate in the United States could be determined and whether any common contributing factors or trends could be identified. Searches were conducted of the National Transportation Safety Board aviation accident database, the records of the major search and rescue and air medical organizations, and the medical and professional literature for reports of HSAR accidents. A total of 47 civilian HSAR accidents were identified during the study. Of these, 43% involved fatal injuries, compared with a 19% fatality rate for US helicopter general aviation accidents during the same time period and a 40% rate for helicopter emergency medical services. The HSAR accidents carried a significantly higher risk of fatal outcomes when compared with helicopter general aviation accidents (2-tailed Fisher's exact test, P .05). The number of HSAR missions conducted annually could not be established, so an overall accident rate could not be calculated. Although the overall number of HSAR accidents is small, the percentage of fatal outcomes from HSAR accidents is significantly higher than that from general helicopter aviation accidents and is comparable to that seen for helicopter emergency medical services operations. Further study could help to improve the safety of HSAR flights. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  15. Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy.

    Science.gov (United States)

    Gisbert, Javier P; Barrio, Jesús; Modolell, Inés; Molina-Infante, Javier; Aisa, Angeles Perez; Castro-Fernández, Manuel; Rodrigo, Luis; Cosme, Angel; Gisbert, Jose Luis; Fernández-Bermejo, Miguel; Marcos, Santiago; Marín, Alicia C; McNicholl, Adrián G

    2015-02-01

    Helicobacter pylori eradication is a challenge in penicillin allergy. To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.

  16. 46 CFR 160.056-4 - Approval tests of prototype rescue boat.

    Science.gov (United States)

    2010-10-01

    ... placed nine inches from the side in way of and about the level of the middle thwart. (c) Rescue boarding... third man balanced on the transom, the minimum freeboard of the transom shall be five inches. The men... boat crew. (d) Rowing test. Three men, averaging 165 pounds each, shall be seated on the centerline of...

  17. Quantitative estimation of defects from measurement obtained by remote field eddy current inspection

    International Nuclear Information System (INIS)

    Davoust, M.E.; Fleury, G.

    1999-01-01

    Remote field eddy current technique is used for dimensioning grooves that may occurs in ferromagnetic pipes. This paper proposes a method to estimate the depth and the length of corrosion grooves from measurement of a pick-up coil signal phase at different positions close to the defect. Grooves dimensioning needs the knowledge of the physical relation between measurements and defect dimensions. So, finite element calculations are performed to obtain a parametric algebraic function of the physical phenomena. By means of this model and a previously defined general approach, an estimate of groove size may be given. In this approach, algebraic function parameters and groove dimensions are linked through a polynomial function. In order to validate this estimation procedure, a statistical study has been performed. The approach is proved to be suitable for real measurements. (authors)

  18. ATM loss leads to synthetic lethality in BRCA1 BRCT mutant mice associated with exacerbated defects in homology-directed repair.

    Science.gov (United States)

    Chen, Chun-Chin; Kass, Elizabeth M; Yen, Wei-Feng; Ludwig, Thomas; Moynahan, Mary Ellen; Chaudhuri, Jayanta; Jasin, Maria

    2017-07-18

    BRCA1 is essential for homology-directed repair (HDR) of DNA double-strand breaks in part through antagonism of the nonhomologous end-joining factor 53BP1. The ATM kinase is involved in various aspects of DNA damage signaling and repair, but how ATM participates in HDR and genetically interacts with BRCA1 in this process is unclear. To investigate this question, we used the Brca1 S1598F mouse model carrying a mutation in the BRCA1 C-terminal domain of BRCA1. Whereas ATM loss leads to a mild HDR defect in adult somatic cells, we find that ATM inhibition leads to severely reduced HDR in Brca1 S1598F cells. Consistent with a critical role for ATM in HDR in this background, loss of ATM leads to synthetic lethality of Brca1 S1598F mice. Whereas both ATM and BRCA1 promote end resection, which can be regulated by 53BP1, 53bp1 deletion does not rescue the HDR defects of Atm mutant cells, in contrast to Brca1 mutant cells. These results demonstrate that ATM has a role in HDR independent of the BRCA1-53BP1 antagonism and that its HDR function can become critical in certain contexts.

  19. Defective splicing, disease and therapy: searching for master checkpoints in exon definition.

    Science.gov (United States)

    Buratti, Emanuele; Baralle, Marco; Baralle, Francisco E

    2006-01-01

    The number of aberrant splicing processes causing human disease is growing exponentially and many recent studies have uncovered some aspects of the unexpectedly complex network of interactions involved in these dysfunctions. As a consequence, our knowledge of the various cis- and trans-acting factors playing a role on both normal and aberrant splicing pathways has been enhanced greatly. However, the resulting information explosion has also uncovered the fact that many splicing systems are not easy to model. In fact we are still unable, with certainty, to predict the outcome of a given genomic variation. Nonetheless, in the midst of all this complexity some hard won lessons have been learned and in this survey we will focus on the importance of the wide sequence context when trying to understand why apparently similar mutations can give rise to different effects. The examples discussed in this summary will highlight the fine 'balance of power' that is often present between all the various regulatory elements that define exon boundaries. In the final part, we shall then discuss possible therapeutic targets and strategies to rescue genetic defects of complex splicing systems.

  20. Medical rescue for nuclear or radiologic emergencies

    International Nuclear Information System (INIS)

    Chen Xiaohua; Nie Suifeng

    2011-01-01

    Nuclear or radiologic emergencies are defined as incidents that are caused by radioactive substance or by other sources of radiation and can pose a serious hazard to public health. In case of nuclear or radiologic emergencies, radioactive rays will damage the human body and bring about psychological and mental stress, resulting in a series of social psychological effects. The key to medical rescue for nuclear or radiologic emergencies is to take effective measures which can minimize the body harm resulting from nuclear or radiologic emergencies and maintain social stability. This article reviews the personnel protection, on-the-spot salvage, treatments of various harm, and prevention of public psychological effect following nuclear or radiologic emergencies. (authors)

  1. Functional Characterization of a Novel Truncating Mutation in Lamin A/C Gene in a Family with a Severe Cardiomyopathy with Conduction Defects

    Directory of Open Access Journals (Sweden)

    Andrea Gerbino

    2017-12-01

    Full Text Available Background/Aims: Truncating LMNA gene mutations occur in many inherited cardiomyopathy cases, but the molecular mechanisms involved in the disease they cause have not yet been systematically investigated. Here, we studied a novel frameshift LMNA variant (p.D243Gfs*4 identified in three members of an Italian family co-segregating with a severe form of cardiomyopathy with conduction defects. Methods: HEK293 cells and HL-1 cardiomyocytes were transiently transfected with either Lamin A or D243Gfs*4 tagged with GFP (or mCherry. D243Gfs*4 expression, cellular localization and its effects on diverse cellular mechanisms were evaluated with western blotting, laser-scanning confocal microscopy and video-imaging analysis in single cells. Results: When expressed in HEK293 cells, GFP- (or mCherry-tagged LMNA D243Gfs*4 colocalized with calnexin within the ER. ER mislocalization of LMNA D243Gfs*4 did not significantly induce ER stress response, abnormal Ca2+ handling and apoptosis when compared with HEK293 cells expressing another truncated mutant of LMNA (R321X which similarly accumulates within the ER. Of note, HEK293-LMNA D243Gfs*4 cells showed a significant reduction of connexin 43 (CX43 expression level, which was completely rescued by activation of the WNT/β-catenin signaling pathway. When expressed in HL-1 cardiomyocytes, D243Gfs*4 significantly impaired the spontaneous Ca2+ oscillations recorded in these cells as result of propagation of the depolarizing waves through the gap junctions between non-transfected cells surrounding a cell harboring the mutation. Furthermore, mCh-D243Gfs*4 HL-1 cardiomyocytes showed reduced CX43-dependent Lucifer Yellow (LY loading and propagation. Of note, activation of β-catenin rescued both LY loading and LMNA D243Gfs*4 -HL-1 cells spontaneous activity propagation. Conclusion: Overall, the present results clearly indicate the involvement of the aberrant CX43 expression/activity as a pathogenic mechanism for the

  2. Mechanisms by which heme oxygenase rescue renal dysfunction in obesity

    Directory of Open Access Journals (Sweden)

    Joseph Fomusi Ndisang

    2014-01-01

    Collectively, these data suggest that hemin ameliorates nephropathy by potentiating the expression of proteins of repair/regeneration, abating oxidative/inflammatory mediators, reducing renal histo-pathological lesions, while enhancing nephrin, podocin, podocalyxin, CD2AP and creatinine clearance, with corresponding reduction of albuminuria/proteinuria suggesting improved renal function in hemin-treated ZFs. Importantly, the concomitant potentiation regeneration proteins and podocyte cytoskeletal proteins are novel mechanisms by which hemin rescue nephropathy in obesity.

  3. EUV actinic defect inspection and defect printability at the sub-32 nm half pitch

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Sungmin; Kearney, Patrick; Wurm, Stefan; Goodwin, Frank; Han, Hakseung; Goldberg, Kenneth; Mochi, Iacopp; Gullikson, Eric M.

    2009-08-01

    Extreme ultraviolet (EUV) mask blanks with embedded phase defects were inspected with a reticle actinic inspection tool (AIT) and the Lasertec M7360. The Lasertec M7360, operated at SEMA TECH's Mask Blank Development Center (MBDC) in Albany, NY, has a sensitivity to multilayer defects down to 40-45 nm, which is not likely sufficient for mask blank development below the 32 nm half-pitch node. Phase defect printability was simulated to calculate the required defect sensitivity for a next generation blank inspection tool to support reticle development for the sub-32 nm half-pitch technology node. Defect mitigation technology is proposed to take advantage of mask blanks with some defects. This technology will reduce the cost of ownership of EUV mask blanks. This paper will also discuss the kind of infrastructure that will be required for the development and mass production stages.

  4. 77 FR 2017 - Safety Zone; Ice Rescue Exercise; Green Bay, Dyckesville, WI

    Science.gov (United States)

    2012-01-13

    ... Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and does not concern an environmental risk to health or risk to safety that may disproportionately affect children... the Port Sector Lake has determined that this ice rescue exercise will pose hazards to the public...

  5. Accurate defect die placement and nuisance defect reduction for reticle die-to-die inspections

    Science.gov (United States)

    Wen, Vincent; Huang, L. R.; Lin, C. J.; Tseng, Y. N.; Huang, W. H.; Tuo, Laurent C.; Wylie, Mark; Chen, Ellison; Wang, Elvik; Glasser, Joshua; Kelkar, Amrish; Wu, David

    2015-10-01

    Die-to-die reticle inspections are among the simplest and most sensitive reticle inspections because of the use of an identical-design neighboring-die for the reference image. However, this inspection mode can have two key disadvantages: (1) The location of the defect is indeterminate because it is unclear to the inspector whether the test or reference image is defective; and (2) nuisance and false defects from mask manufacturing noise and tool optical variation can limit the usable sensitivity. The use of a new sequencing approach for a die-to-die inspection can resolve these issues without any additional scan time, without sacrifice in sensitivity requirement, and with a manageable increase in computation load. In this paper we explore another approach for die-to-die inspections using a new method of defect processing and sequencing. Utilizing die-to-die double arbitration during defect detection has been proven through extensive testing to generate accurate placement of the defect in the correct die to ensure efficient defect disposition at the AIMS step. The use of this method maintained the required inspection sensitivity for mask quality as verified with programmed-defectmask qualification and then further validated with production masks comparing the current inspection approach to the new method. Furthermore, this approach can significantly reduce the total number of defects that need to be reviewed by essentially eliminating the nuisance and false defects that can result from a die-to-die inspection. This "double-win" will significantly reduce the effort in classifying a die-to-die inspection result and will lead to improved cycle times.

  6. Multiscale crystal defect dynamics: A coarse-grained lattice defect model based on crystal microstructure

    Science.gov (United States)

    Lyu, Dandan; Li, Shaofan

    2017-10-01

    Crystal defects have microstructure, and this microstructure should be related to the microstructure of the original crystal. Hence each type of crystals may have similar defects due to the same failure mechanism originated from the same microstructure, if they are under the same loading conditions. In this work, we propose a multiscale crystal defect dynamics (MCDD) model that models defects by considering its intrinsic microstructure derived from the microstructure or material genome of the original perfect crystal. The main novelties of present work are: (1) the discrete exterior calculus and algebraic topology theory are used to construct a scale-up (coarse-grained) dual lattice model for crystal defects, which may represent all possible defect modes inside a crystal; (2) a higher order Cauchy-Born rule (up to the fourth order) is adopted to construct atomistic-informed constitutive relations for various defect process zones, and (3) an hierarchical strain gradient theory based finite element formulation is developed to support an hierarchical multiscale cohesive (process) zone model for various defects in a unified formulation. The efficiency of MCDD computational algorithm allows us to simulate dynamic defect evolution at large scale while taking into account atomistic interaction. The MCDD model has been validated by comparing of the results of MCDD simulations with that of molecular dynamics (MD) in the cases of nanoindentation and uniaxial tension. Numerical simulations have shown that MCDD model can predict dislocation nucleation induced instability and inelastic deformation, and thus it may provide an alternative solution to study crystal plasticity.

  7. Defective Proteasome Delivery of Polyubiquitinated Proteins by Ubiquilin-2 Proteins Containing ALS Mutations.

    Directory of Open Access Journals (Sweden)

    Lydia Chang

    Full Text Available Ubiquilin proteins facilitate delivery of ubiquitinated proteins to the proteasome for degradation. Interest in the proteins has been heightened by the discovery that gene mutations in UBQLN2 cause dominant inheritance of amyotrophic lateral sclerosis (ALS. However, the mechanisms by which the mutations cause ALS are not known. Here we report on the underlying defect of ubiquilin-2 proteins containing ALS-linked mutations in affecting proteasome-mediated degradation. We found that overexpression of ubiquilin-2 proteins containing any one of five different ALS mutations slow degradation of Myc, a prototypic proteasome substrate. Examination of coprecipitating proteins indicated that the mutant proteins are generally capable of binding polyubiquitinated proteins, but defective in binding the proteasome. GST-pulldown studies revealed that many of the mutants bind weaker to the S5a subunit of the proteasome, compared with wild type (WT ubiquilin-2 protein. The results suggest the mutant proteins are unable to deliver their captured cargo to the proteasome for degradation, which presumably leads to toxicity. Quantification of cell death is consistent with this idea. Measurement of protein turnover further indicated the mutant proteins have longer half-lives than WT ubiquilin-2. Our studies provide novel insight into the mechanism by which ALS-linked mutations in UBQLN2 interfere with protein degradation.

  8. Surface defects and chiral algebras

    Energy Technology Data Exchange (ETDEWEB)

    Córdova, Clay [School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, NJ 08540 (United States); Gaiotto, Davide [Perimeter Institute for Theoretical Physics,31 Caroline St N, Waterloo, ON N2L 2Y5 (Canada); Shao, Shu-Heng [School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, NJ 08540 (United States)

    2017-05-26

    We investigate superconformal surface defects in four-dimensional N=2 superconformal theories. Each such defect gives rise to a module of the associated chiral algebra and the surface defect Schur index is the character of this module. Various natural chiral algebra operations such as Drinfeld-Sokolov reduction and spectral flow can be interpreted as constructions involving four-dimensional surface defects. We compute the index of these defects in the free hypermultiplet theory and Argyres-Douglas theories, using both infrared techniques involving BPS states, as well as renormalization group flows onto Higgs branches. In each case we find perfect agreement with the predicted characters.

  9. Laterality defects in the national birth defects prevention study 1998-2007 birth prevalence and descriptive epidemiology

    Science.gov (United States)

    Little is known epidemiologically about laterality defects. Using data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007...

  10. [New possibilities in emergency medical transportation and emergency services of Polish Medical Air Rescue].

    Science.gov (United States)

    Gałazkowski, Robert

    2010-01-01

    In Poland, two types of medical services are accomplished by the Medical Air Rescue (MAR) operating all over the country: emergency transport from the incident scene to hospital and inter-hospital transport. Helicopters or planes are used for this purpose. In 2009, helicopters performed 4359 flights to incidents and 1537 inter-hospital transports whereas planes performed 589 inter-hospital ambulance and 196 rescue flights. MAR operates from 17 bases of the Helicopter Emergency Medical Service (HEMS) and one airbase. Helicopters are mainly used when medical transport is emergent, within the operational region of a given base whereas planes when the distance between the present and target airports exceeds 250 km. In 2008, new modern aircraft were introduced to HEMS-helicopters EC 135. They fulfil all requirements of air transport regulations and are adjusted to visual (VFR) and instrumental (IFR) flights rules, at day and night. The medical cabin of EC 135 is ergonomic and functional considering the majority of rescue activities under life-saving circumstances. It is equipped with ventilator, defibrillator, infusion pumps etc. Defibrillators have 12-lead ECG, E(T)CO2, SpO2, NIBP, and IBP modules. Transport ventilators can work in a variety of ventilation modes including CMV, SIMV, SVV, BILEVEL, PCV, ASB, PPV and CPAP. The purchase of helicopters with modern avionic and medical configuration ensures high quality services of MAR for many years to come.

  11. Inhibition of GSK3β rescues hippocampal development and learning in a mouse model of CDKL5 disorder.

    Science.gov (United States)

    Fuchs, Claudia; Rimondini, Roberto; Viggiano, Rocchina; Trazzi, Stefania; De Franceschi, Marianna; Bartesaghi, Renata; Ciani, Elisabetta

    2015-10-01

    Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in a rare neurodevelopmental disorder characterized by early-onset seizures, severe developmental delay, intellectual disability and Rett syndrome-like features. CDKL5 is highly expressed in the brain during early postnatal stages, suggesting its importance for brain maturation. Using a newly-generated Cdkl5 knockout (Cdkl5 -/Y) mouse, we recently found that loss of Cdkl5 impairs postnatal hippocampal development with a reduction in neuronal precursor survival and maturation. These defects were accompanied by increased activity of the glycogen synthase kinase 3β (GSK3β) a crucial inhibitory regulator of many neurodevelopmental processes. The goal of the current study was to establish whether inhibition of GSK3β corrects hippocampal developmental defects due to Cdkl5 loss. We found that treatment with the GSK3β inhibitor SB216763 restored neuronal precursor survival, dendritic maturation, connectivity and hippocampus-dependent learning and memory in the Cdkl5 -/Y mouse. Importantly, these effects were retained one month after treatment cessation. At present, there are no therapeutic strategies to improve the neurological defects of subjects with CDKL5 disorder. Current results point at GSK3β inhibitors as potential therapeutic tools for the improvement of abnormal brain development in CDKL5 disorder. Copyright © 2015. Published by Elsevier Inc.

  12. Neurospora crassa ASM-1 complements the conidiation defect in a stuA mutant of Aspergillus nidulans.

    Science.gov (United States)

    Chung, Dawoon; Upadhyay, Srijana; Bomer, Brigitte; Wilkinson, Heather H; Ebbole, Daniel J; Shaw, Brian D

    2015-01-01

    Aspergillus nidulans StuA and Neurospora crassa ASM-1 are orthologous APSES (ASM-1, PHD1, SOK2, Efg1, StuA) transcription factors conserved across a diverse group of fungi. StuA and ASM-1 have roles in asexual (conidiation) and sexual (ascospore formation) development in both organisms. To address the hypothesis that the last common ancestor of these diverse fungi regulated conidiation with similar genes, asm-1 was introduced into the stuA1 mutant of A. nidulans. Expression of asm-1 complemented defective conidiophore morphology and restored conidia production to wild type levels in stuA1. Expression of asm-1 in the stuA1 strain did not rescue the defect in sexual development. When the conidiation regulator AbaA was tagged at its C-terminus with GFP in A. nidulans, it localized to nuclei in phialides. When expressed in the stuA1 mutant, AbaA::GFP localized to nuclei in conidiophores but no longer was confined to phialides, suggesting that expression of AbaA in specific cell types of the conidiophore was conditioned by StuA. Our data suggest that the function in conidiation of StuA and ASM-1 is conserved and support the view that, despite the great morphological and ontogenic diversity of their condiphores, the last common ancestor of A. nidulans and N. crassa produced an ortholog of StuA that was involved in conidiophore development. © 2015 by The Mycological Society of America.

  13. Utopia documents: linking scholarly literature with research data.

    Science.gov (United States)

    Attwood, T K; Kell, D B; McDermott, P; Marsh, J; Pettifer, S R; Thorne, D

    2010-09-15

    In recent years, the gulf between the mass of accumulating-research data and the massive literature describing and analyzing those data has widened. The need for intelligent tools to bridge this gap, to rescue the knowledge being systematically isolated in literature and data silos, is now widely acknowledged. To this end, we have developed Utopia Documents, a novel PDF reader that semantically integrates visualization and data-analysis tools with published research articles. In a successful pilot with editors of the Biochemical Journal (BJ), the system has been used to transform static document features into objects that can be linked, annotated, visualized and analyzed interactively (http://www.biochemj.org/bj/424/3/). Utopia Documents is now used routinely by BJ editors to mark up article content prior to publication. Recent additions include integration of various text-mining and biodatabase plugins, demonstrating the system's ability to seamlessly integrate on-line content with PDF articles. http://getutopia.com.

  14. Exploring entrepreneurial learning during formal business rescue processes: Insights from the South African experience

    Directory of Open Access Journals (Sweden)

    Anéa Burke-le Roux

    2017-04-01

    Full Text Available Orientation: Currently, little is known about entrepreneurial learning under turnaround and rescue conditions. A better understanding of the content dimensions as well as the factors that drive or restrain entrepreneurial learning during business rescue (BR is relevant for theory and industry development. Research purpose: BR is a fairly new regime in South Africa that extends beyond turnaround practices. It is acknowledged that business failure can fuel cognitive processes and subsequently entrepreneurial learning but to what extent in the context of formal BR proceedings requires exploration. Practice suggests that the role of the business rescue practitioner (BRP as ‘disproportionate influencer’ can affect the learning of filing entrepreneurs. Motivation for the study: In the absence of guidelines, this study set out to explore and make sense of the specific content dimensions that entrepreneurs learn during such proceedings to assist role players. Research design, approach and method: The research question for this exploratory investigation obtained first-hand accounts from subjects that have been directly involved in BR proceedings. Semi-structured interviews were conducted. ‘Investigator triangulation’ was also used to extract as much richness and data as possible applying interpretative phenomenological analysis. Findings: We extracted three key content dimensions which entrepreneurs learned during BR: rescue process, business related and personal learnings. Entrepreneurs with ‘positive’ experiences of BR learned more than those with negative experiences. The key driving and restraining factors to entrepreneurial learning were both associated with the behaviour of the BRP. Practical/managerial implications: BR has introduced another dimension to learning from business failure. Understanding the content dimensions learned by entrepreneurs during BR broadens insights of the Regulator, BRPs and educators about the potential long

  15. Division of labor regulates precision rescue behavior in sand-dwelling Cataglyphis cursor ants: to give is to receive.

    Directory of Open Access Journals (Sweden)

    Elise Nowbahari

    Full Text Available Division of labor, an adaptation in which individuals specialize in performing tasks necessary to the colony, such as nest defense and foraging, is believed key to eusocial insects' remarkable ecological success. Here we report, for the first time, a completely novel specialization in a eusocial insect, namely the ability of Cataglyphis cursor ants to rescue a trapped nestmate using precisely targeted behavior. Labeled "precision rescue", this behavior involves the ability of rescuers not only to detect what, exactly, holds the victim in place, but also to direct specific actions to this obstacle. Individual ants, sampled from each of C. cursor's three castes, namely foragers, nurses and inactives, were experimentally ensnared (the "victim" and exposed to a caste-specific group of potential "rescuers." The data reveal that foragers were able to administer, and obtain, the most help while members of the youngest, inactive caste not only failed to respond to victims, but also received virtually no help from potential rescuers, regardless of caste. Nurses performed intermediate levels of aid, mirroring their intermediate caste status. Our results demonstrate that division of labor, which controls foraging, defense and brood care in C. cursor, also regulates a newly discovered behavior in this species, namely a sophisticated form of rescue, a highly adaptive specialization that is finely tuned to a caste member's probability of becoming, or encountering, a victim in need of rescue.

  16. Data Rescue in Collaboration with Federal Open Access Efforts

    Science.gov (United States)

    Avila, R.

    2017-12-01

    The recent calls to rescue scientific data is a real opportunity to collaborate with federal agencies which have been spending years managing research data and making it secure. The 2013 memos from the White House Office of Science and Technology Policy and Office of Management and Budget have spurred innovation across federal agencies to make publicly funded data accessible. Now is the time for stakeholders to take advantage of the groundwork laid by federal government, support the work to expand data sharing, thereby encouraging open science.

  17. Disruption of polyubiquitin gene Ubc leads to defective proliferation of hepatocytes and bipotent fetal liver epithelial progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyejin; Yoon, Min-Sik; Ryu, Kwon-Yul, E-mail: kyryu@uos.ac.kr

    2013-06-07

    Highlights: •Proliferation capacity of Ubc{sup −/−} FLCs was reduced during culture in vitro. •Ubc is required for proliferation of both hepatocytes and bipotent FLEPCs. •Bipotent FLEPCs exhibit highest Ubc transcription and proliferation capacity. •Cell types responsible for Ubc{sup −/−} fetal liver developmental defect were identified. -- Abstract: We have previously demonstrated that disruption of polyubiquitin gene Ubc leads to mid-gestation embryonic lethality most likely due to a defect in fetal liver development, which can be partially rescued by ectopic expression of Ub. In a previous study, we assessed the cause of embryonic lethality with respect to the fetal liver hematopoietic system. We confirmed that Ubc{sup −/−} embryonic lethality could not be attributed to impaired function of hematopoietic stem cells, which raises the question of whether or not FLECs such as hepatocytes and bile duct cells, the most abundant cell types in the liver, are affected by disruption of Ubc and contribute to embryonic lethality. To answer this, we isolated FLCs from E13.5 embryos and cultured them in vitro. We found that proliferation capacity of Ubc{sup −/−} cells was significantly reduced compared to that of control cells, especially during the early culture period, however we did not observe the increased number of apoptotic cells. Furthermore, levels of Ub conjugate, but not free Ub, decreased upon disruption of Ubc expression in FLCs, and this could not be compensated for by upregulation of other poly- or mono-ubiquitin genes. Intriguingly, the highest Ubc expression levels throughout the entire culture period were observed in bipotent FLEPCs. Hepatocytes and bipotent FLEPCs were most affected by disruption of Ubc, resulting in defective proliferation as well as reduced cell numbers in vitro. These results suggest that defective proliferation of these cell types may contribute to severe reduction of fetal liver size and potentially mid

  18. Defects at oxide surfaces

    CERN Document Server

    Thornton, Geoff

    2015-01-01

    This book presents the basics and characterization of defects at oxide surfaces. It provides a state-of-the-art review of the field, containing information to the various types of surface defects, describes analytical methods to study defects, their chemical activity and the catalytic reactivity of oxides. Numerical simulations of defective structures complete the picture developed. Defects on planar surfaces form the focus of much of the book, although the investigation of powder samples also form an important part. The experimental study of planar surfaces opens the possibility of applying the large armoury of techniques that have been developed over the last half-century to study surfaces in ultra-high vacuum. This enables the acquisition of atomic level data under well-controlled conditions, providing a stringent test of theoretical methods. The latter can then be more reliably applied to systems such as nanoparticles for which accurate methods of characterization of structure and electronic properties ha...

  19. Ribosomal protein gene knockdown causes developmental defects in zebrafish.

    Directory of Open Access Journals (Sweden)

    Tamayo Uechi

    Full Text Available The ribosomal proteins (RPs form the majority of cellular proteins and are mandatory for cellular growth. RP genes have been linked, either directly or indirectly, to various diseases in humans. Mutations in RP genes are also associated with tissue-specific phenotypes, suggesting a possible role in organ development during early embryogenesis. However, it is not yet known how mutations in a particular RP gene result in specific cellular changes, or how RP genes might contribute to human diseases. The development of animal models with defects in RP genes will be essential for studying these questions. In this study, we knocked down 21 RP genes in zebrafish by using morpholino antisense oligos to inhibit their translation. Of these 21, knockdown of 19 RPs resulted in the development of morphants with obvious deformities. Although mutations in RP genes, like other housekeeping genes, would be expected to result in nonspecific developmental defects with widespread phenotypes, we found that knockdown of some RP genes resulted in phenotypes specific to each gene, with varying degrees of abnormality in the brain, body trunk, eyes, and ears at about 25 hours post fertilization. We focused further on the organogenesis of the brain. Each knocked-down gene that affected the morphogenesis of the brain produced a different pattern of abnormality. Among the 7 RP genes whose knockdown produced severe brain phenotypes, 3 human orthologs are located within chromosomal regions that have been linked to brain-associated diseases, suggesting a possible involvement of RP genes in brain or neurological diseases. The RP gene knockdown system developed in this study could be a powerful tool for studying the roles of ribosomes in human diseases.

  20. Rescue of mitochondrial function in parkin-mutant fibroblasts using drug loaded PMPC-PDPA polymersomes and tubular polymersomes.

    Science.gov (United States)

    Yealland, G; Battaglia, G; Bandmann, O; Mortiboys, H

    2016-09-06

    Mutations in parkin cause autosomal recessive Parkinsonism and mitochondrial defects. A recent drug screen identified a class of steroid-like hydrophobic compounds able to rescue mitochondrial function in parkin-mutant fibroblasts. Whilst these possess therapeutic potential, the size and high hydrophobicity of some may limit their ability to penetrate the blood-brain barrier from systemic circulation, something that could be improved by novel drug formulations. In the present study, the steroid-like compounds Ursolic Acid (UA) and Ursocholanic Acid (UCA) were successfully encapsulated within nanoscopic polymersomes formed by poly(2-(methacryloyloxy)ethyl phosphorylcholine)-poly(2-di-isopropylamino)ethyl methacrylate) (PMPC-PDPA) and separated into spherical and tubular morphologies to assess the effects of nanoparticle mediated delivery on drug efficacy. Following incubation with either morphology, parkin-mutant fibroblasts demonstrated time and concentration dependent increases in intracellular ATP levels, resembling those resulting from treatment with nascent UA and UCA formulated in 0.1% DMSO, as used in the original drug screen. Empty PMPC-PDPA polymersomes did not alter physiological measures related to mitochondrial function or induce cytotoxicity. In combination with other techniques such as ligand functionalisation, PMPC-PDPA nanoparticles of well-defined morphology may prove a promising platform for tailoring the pharmacokinetic profile and organ specific bio-distribution of highly hydrophobic compounds. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.